FLMD26T • Florida Physicians 2025-2026

Table of Contents

FLMD26T • Florida Physicians 2025-2026

How to Receive Credit

NetCE 2 Hour Course #97923 • Domestic Violence: The Florida Requirement

97923 • Domestic Violence: The Florida Requirement

1. INTRODUCTION

2. DEFINING DOMESTIC VIOLENCE

3. NATIONAL AND STATE STATISTICS AND LEGISLATION

4. IDENTIFYING GROUPS AT RISK FOR DOMESTIC VIOLENCE

5. CHARACTERISTICS OF PERPETRATORS OF DOMESTIC VIOLENCE

6. SCREENING FOR DOMESTIC VIOLENCE AND ABUSE

7. ASSESSING DOMESTIC VIOLENCE AND ABUSE

8. INTERVENTIONS FOR DOMESTIC VIOLENCE AND ABUSE

9. DOCUMENTATION AND FOLLOW-UP

Works Cited

Evidence-Based Practice Recommendations Citations

NetCE 2 Hour Course #45122 • Strategies for Appropriate Opioid Prescribing: The Florida Requirement

45122 • Strategies for Appropriate Opioid Prescribing: The Florida Requirement

1. INTRODUCTION

2. DEFINITIONS

3. EPIDEMIOLOGY OF CHRONIC PAIN AND OPIOID MISUSE

4. INITIATION AND MANAGEMENT OF THE PATIENT WITH PAIN

5. CRISIS INTERVENTION: MANAGEMENT OF OVERDOSE

6. COMPLIANCE WITH STATE AND FEDERAL LAWS

7. IDENTIFICATION OF DRUG DIVERSION/SEEKING BEHAVIORS

8. INTERVENTIONS FOR SUSPECTED OR KNOWN DRUG DIVERSION

9. CASE STUDY

10. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

NetCE 2 Hour Course #90120 • Pulmonary Embolism

90120 • Pulmonary Embolism

1. INTRODUCTION

2. EPIDEMIOLOGY

3. PATHOPHYSIOLOGY

4. DIAGNOSIS

5. TREATMENT

6. PE IN THE OUTPATIENT SETTING

7. PE AND COVID-19

8. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

NetCE 2 Hour Course #91334 • Medical Error Prevention and Root Cause Analysis

91334 • Medical Error Prevention and Root Cause Analysis

1. INTRODUCTION

2. DEFINING "MEDICAL ERROR"

3. ROOT CAUSE ANALYSIS PROCESS

4. ERROR REDUCTION AND PREVENTION

5. OTHER CONSIDERATIONS FOR PATIENT SAFETY

6. CONCLUSION

Works Cited

NetCE 10 Hour Course #94820 • Chronic Cough in Adults

94820 • Chronic Cough in Adults

1. INTRODUCTION

2. BACKGROUND

3. COUGH SEVERITY MEASURES

4. EPIDEMIOLOGY

5. PATIENT IMPACT OF CHRONIC COUGH

6. NATURAL HISTORY AND DISEASE COURSE

7. PATHOPHYSIOLOGY OF CHRONIC COUGH

8. INITIAL EVALUATION OF CHRONIC COUGH

9. IDENTIFICATION AND MANAGEMENT OF UNDERLYING ETIOLOGIES

10. TREATMENT

11. TREATMENT OF REFRACTORY CHRONIC COUGH

12. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

NetCE 10 Hour Course #48854 • Pressure Injuries: Prevention and Management

48854 • Pressure Injuries: Prevention and Management

1. INTRODUCTION

2. EPIDEMIOLOGY

3. PATHOGENESIS

4. RISK FACTORS

5. STAGING OF PRESSURE INJURIES

6. PHASES OF WOUND HEALING: AN OVERVIEW

7. DIAGNOSIS

8. PREVENTION AND TREATMENT

9. WOUND MONITORING

10. COMPLICATIONS

11. TREATMENT OF COMORBIDITIES

12. ADVANCES IN PRESSURE INJURY CARE

13. MEDICO-LEGAL ASPECTS OF INJURY CARE

14. EDUCATING PATIENTS

15. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

FLMD26T • Florida Physicians 2025-2026

Marjorie Conner Allen, BSN, JD

Alice Yick Flanagan, PhD, MSW

Mark Rose, BS, MA, LP

Dalia Saha, MD

www.netce.com

Copyright © 2025 NetCE, All rights reserved.

FLMD26T • Florida Physicians 2025-2026

Expiration Date: 04/30/2026

How to Receive Credit

To complete this Special Offer for continuing education credit please go to http://www.netce.com/specials in your browser.

For assistance with receiving continuing education credit, please contact us at help@netce.com.

97923 • Domestic Violence: The Florida Requirement

Marjorie Conner Allen, BSN, JD

Alice Yick Flanagan, PhD, MSW

www.netce.com

Copyright © 2022 NetCE, All rights reserved.

Domestic violence continues to be a prevalent problem in the United States today. Because of the number of individuals affected, it is likely that most healthcare professionals will encounter patients in their practice who are victims. Accordingly, it is essential that healthcare professionals are taught to recognize and accurately interpret behaviors associated with domestic violence. It is incumbent upon the healthcare professional to establish and implement protocols for early identification of domestic violence victims and their abusers. In order to prevent domestic violence and promote the well-being of their patients, healthcare professionals in all settings must take the initiative to properly assess all women for abuse during each visit and, for those women who are or may be victims, to offer education, counseling, and referral information.

Table of Contents

97923 • Domestic Violence: The Florida Requirement

Course Overview

Audience

Accreditations & Approvals

Designations of Credit

Individual State Nursing Approvals

Individual State Behavioral Health Approvals

Special Approvals

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Division Planners

Division Planners Disclosure

Director of Development and Academic Affairs

Director Disclosure Statement

About the Sponsor

Disclosure Statement

Implicit Bias in Health Care

1. INTRODUCTION

2. DEFINING DOMESTIC VIOLENCE

3. NATIONAL AND STATE STATISTICS AND LEGISLATION

FLORIDA

4. IDENTIFYING GROUPS AT RISK FOR DOMESTIC VIOLENCE

PREGNANT WOMEN

CHILDREN

ELDERLY

MEN

LESBIAN, GAY, BISEXUAL, TRANSGENDER, AND QUEER/QUESTIONING VICTIMS

5. CHARACTERISTICS OF PERPETRATORS OF DOMESTIC VIOLENCE

6. SCREENING FOR DOMESTIC VIOLENCE AND ABUSE

7. ASSESSING DOMESTIC VIOLENCE AND ABUSE

CULTURALLY SENSITIVE ASSESSMENT

8. INTERVENTIONS FOR DOMESTIC VIOLENCE AND ABUSE

9. DOCUMENTATION AND FOLLOW-UP

Works Cited

Evidence-Based Practice Recommendations Citations

97923 • Domestic Violence: The Florida Requirement

Education Category. Ethics - Human Rights

Release Date. 08/01/2022

Review Date. 04/15/2025

Expiration Date. 07/31/2026

Course Overview

Domestic violence continues to be a prevalent problem in the United States today. Because of the number of individuals affected, it is likely that most healthcare professionals will encounter patients in their practice who are victims. Accordingly, it is essential that healthcare professionals are taught to recognize and accurately interpret behaviors associated with domestic violence. It is incumbent upon the healthcare professional to establish and implement protocols for early identification of domestic violence victims and their abusers. In order to prevent domestic violence and promote the well-being of their patients, healthcare professionals in all settings must take the initiative to properly assess all women for abuse during each visit and, for those women who are or may be victims, to offer education, counseling, and referral information.

Audience

This course is designed for all Florida healthcare professionals required to complete domestic violence education.

Accreditations & Approvals

In support of improving patient care, TRC Healthcare/NetCE is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. NetCE has been approved by NBCC as an Approved Continuing Education Provider, ACEP No. 6361. Programs that do not qualify for NBCC credit are clearly identified. NetCE is solely responsible for all aspects of the programs. As a Jointly Accredited Organization, NetCE is approved to offer social work continuing education by the Association of Social Work Boards (ASWB) Approved Continuing Education (ACE) program. Organizations, not individual courses, are approved under this program. Regulatory boards are the final authority on courses accepted for continuing education credit. NetCE is accredited by the International Accreditors for Continuing Education and Training (IACET). NetCE complies with the ANSI/IACET Standard, which is recognized internationally as a standard of excellence in instructional practices. As a result of this accreditation, NetCE is authorized to issue the IACET CEU. NetCE is recognized by the New York State Education Department's State Board for Social Work as an approved provider of continuing education for licensed social workers #SW-0033. This course is considered self-study, as defined by the New York State Board for Social Work. NetCE is recognized by the New York State Education Department's State Board for Mental Health Practitioners as an approved provider of continuing education for licensed mental health counselors #MHC-0021. This course is considered self-study by the New York State Board of Mental Health Counseling. NetCE is recognized by the New York State Education Department's State Board for Mental Health Practitioners as an approved provider of continuing education for licensed marriage and family therapists. #MFT-0015.This course is considered self-study by the New York State Board of Marriage and Family Therapy. Materials that are included in this course may include interventions and modalities that are beyond the authorized practice of licensed master social work and licensed clinical social work in New York. As a licensed professional, you are responsible for reviewing the scope of practice, including activities that are defined in law as beyond the boundaries of practice for an LMSW and LCSW. A licensee who practices beyond the authorized scope of practice could be charged with unprofessional conduct under the Education Law and Regents Rules.

Designations of Credit

This activity was planned by and for the healthcare team, and learners will receive 2 Interprofessional Continuing Education (IPCE) credit(s) for learning and change. NetCE designates this enduring material for a maximum of 2 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. NetCE designates this continuing education activity for 2 ANCC contact hour(s). NetCE designates this continuing education activity for 2.4 hours for Alabama nurses. NetCE designates this continuing education activity for 1 NBCC clock hour(s). Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 2 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Completion of this course constitutes permission to share the completion data with ACCME. Social workers participating in this intermediate to advanced course will receive 2 Clinical continuing education clock hours. This activity has been approved for the American Board of Anesthesiology’s® (ABA) requirements for Part II: Lifelong Learning and Self-Assessment of the American Board of Anesthesiology’s (ABA) redesigned Maintenance of Certification in Anesthesiology Program® (MOCA®), known as MOCA 2.0®. Please consult the ABA website, www.theABA.org, for a list of all MOCA 2.0 requirements. Maintenance of Certification in Anesthesiology Program® and MOCA® are registered certification marks of the American Board of Anesthesiology®. MOCA 2.0® is a trademark of the American Board of Anesthesiology®. Successful completion of this CME activity, which includes participation in the evaluation component, enables the learner to earn credit toward the CME and/or Self-Assessment requirements of the American Board of Surgery's Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit. Successful completion of this CME activity, which includes participation in the activity with individual assessments of the participant and feedback to the participant, enables the participant to earn 2 MOC points in the American Board of Pediatrics' (ABP) Maintenance of Certification (MOC) program. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABP MOC credit. This activity has been designated for 2 Lifelong Learning (Part II) credits for the American Board of Pathology Continuing Certification Program. Through an agreement between the Accreditation Council for Continuing Medical Education and the Royal College of Physicians and Surgeons of Canada, medical practitioners participating in the Royal College MOC Program may record completion of accredited activities registered under the ACCME's "CME in Support of MOC" program in Section 3 of the Royal College's MOC Program. NetCE is authorized by IACET to offer 0.2 CEU(s) for this program. AACN Synergy CERP Category B.

Individual State Nursing Approvals

In addition to states that accept ANCC, NetCE is approved as a provider of continuing education in nursing by: Arkansas, Provider #50-2405; California, BRN Provider #CEP9784; California, LVN Provider #V10662; California, PT Provider #V10842; District of Columbia, Provider #50-2405; Florida, Provider #50-2405; Georgia, Provider #50-2405; Kentucky, Provider #7-0054 through 12/31/2025; South Carolina, Provider #50-2405; West Virginia RN and APRN, Provider #50-2405.

Individual State Behavioral Health Approvals

In addition to states that accept ASWB, NetCE is approved as a provider of continuing education by the following state boards: Alabama State Board of Social Work Examiners, Provider #0515; Florida Board of Clinical Social Work, Marriage and Family Therapy and Mental Health Counseling, CE Broker Provider #50-2405; Illinois Division of Professional Regulation for Social Workers, License #159.001094; Illinois Division of Professional Regulation for Licensed Professional and Clinical Counselors, License #197.000185; Illinois Division of Professional Regulation for Marriage and Family Therapists, License #168.000190;

Special Approvals

This course fulfills the Florida requirement for 2 hours of Domestic Violence education every third renewal period. This activity is designed to comply with the requirements of California Assembly Bill 1195, Cultural and Linguistic Competency.

Course Objective

The purpose of this course is to enable healthcare professionals in all practice settings to define domestic violence and identify those who are affected by domestic violence in the United States. This course describes how a victim can be accurately diagnosed and identifies the community resources available in the state of Florida for domestic violence victims.

Learning Objectives

Upon completion of this course, you should be able to:

1. Define domestic violence and its impact on health care.

2. Cite the general prevalence of domestic violence on a national and state level and identify state laws pertaining to the issue.

3. Describe how to screen and assess individuals who may be victims or perpetrators of domestic violence, including the importance of conducting a culturally sensitive assessment.

4. Identify community resources presently available for domestic violence victims and their perpetrators throughout Florida concerning legal aid, shelter, victim and batterer counseling, and child protection services.

Faculty

Marjorie Conner Allen, BSN, JD, received her Bachelor of Science in Nursing degree from the University of Florida, Gainesville, in 1984. She began her nursing career at Shands Teaching Hospital and Clinics at the University of Florida, Gainesville. While practicing nursing at Shands, she gave continuing education seminars regarding the nursing implications for dealing with adolescents with terminal illness. In 1988, Ms. Allen moved to Atlanta, Georgia where she worked at Egleston Children’s Hospital at Emory University in the bone marrow transplant unit. In the fall of 1989, she began law school at Florida State University. After graduating from law school in 1992, Ms. Allen took a two-year job as law clerk to the Honorable William Terrell Hodges, United States District Judge for the Middle District of Florida. After completing her clerkship, Ms. Allen began her employment with the law firm of Smith, Hulsey & Busey in Jacksonville, Florida where she has worked in the litigation department defending hospitals and nurses in medical malpractice actions. Ms. Allen resides in Jacksonville and is currently in-house counsel to the Mayo Clinic Jacksonville.

Alice Yick Flanagan, PhD, MSW, received her Master’s in Social Work from Columbia University, School of Social Work. She has clinical experience in mental health in correctional settings, psychiatric hospitals, and community health centers. In 1997, she received her PhD from UCLA, School of Public Policy and Social Research. Dr. Yick Flanagan completed a year-long post-doctoral fellowship at Hunter College, School of Social Work in 1999. In that year she taught the course Research Methods and Violence Against Women to Masters degree students, as well as conducting qualitative research studies on death and dying in Chinese American families.

Previously acting as a faculty member at Capella University and Northcentral University, Dr. Yick Flanagan is currently a contributing faculty member at Walden University, School of Social Work, and a dissertation chair at Grand Canyon University, College of Doctoral Studies, working with Industrial Organizational Psychology doctoral students. She also serves as a consultant/subject matter expert for the New York City Board of Education and publishing companies for online curriculum development, developing practice MCAT questions in the area of psychology and sociology. Her research focus is on the area of culture and mental health in ethnic minority communities.

Faculty Disclosure

Contributing faculty, Marjorie Conner Allen, BSN, JD, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Contributing faculty, Alice Yick Flanagan, PhD, MSW, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Division Planners

John M. Leonard, MD

Jane C. Norman, RN, MSN, CNE, PhD

Division Planners Disclosure

The division planners have disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Director of Development and Academic Affairs

Sarah Campbell

Director Disclosure Statement

The Director of Development and Academic Affairs has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

About the Sponsor

The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.

Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.

Disclosure Statement

It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.

Implicit Bias in Health Care

The role of implicit biases on healthcare outcomes has become a concern, as there is some evidence that implicit biases contribute to health disparities, professionals' attitudes toward and interactions with patients, quality of care, diagnoses, and treatment decisions. This may produce differences in help-seeking, diagnoses, and ultimately treatments and interventions. Implicit biases may also unwittingly produce professional behaviors, attitudes, and interactions that reduce patients' trust and comfort with their provider, leading to earlier termination of visits and/or reduced adherence and follow-up. Disadvantaged groups are marginalized in the healthcare system and vulnerable on multiple levels; health professionals' implicit biases can further exacerbate these existing disadvantages.

Interventions or strategies designed to reduce implicit bias may be categorized as change-based or control-based. Change-based interventions focus on reducing or changing cognitive associations underlying implicit biases. These interventions might include challenging stereotypes. Conversely, control-based interventions involve reducing the effects of the implicit bias on the individual's behaviors. These strategies include increasing awareness of biased thoughts and responses. The two types of interventions are not mutually exclusive and may be used synergistically.

1. INTRODUCTION

Domestic violence continues to be a prevalent problem in the United States today. Because of the number of individuals affected, it is likely that most healthcare professionals will encounter patients in their practice who are victims. Accordingly, it is essential that healthcare professionals are taught to recognize and accurately interpret behaviors associated with domestic violence. It is incumbent upon the healthcare professional to establish and implement protocols for early identification of domestic violence victims and their abusers. In order to prevent domestic violence and promote the well-being of their patients, healthcare professionals in all settings should take the initiative to properly assess all women for abuse during each visit and, for those women who are or may be victims, to offer education, counseling, and referral information.

Victims of domestic violence suffer emotional, psychologic, and physical abuse, all of which can result in both acute and chronic signs and symptoms of physical and mental disease, illness, and injury. Frequently, the injuries sustained require abused victims to seek care from healthcare professionals immediately after their victimization. Subsequently, physicians and nurses are often the first healthcare providers that victims encounter and are in a critical position to identify domestic violence victims in a variety of clinical practice settings where victims receive care. Accordingly, each healthcare professional should educate himself or herself to enhance awareness of the presence of abuse victims in his or her particular practice or clinical setting.

Specifically, healthcare professionals should be aware of the signs and symptoms associated with domestic violence. In addition, when family violence cases are identified, there should be a plan of action that includes providing information on, and referral to, local community resources related to legal aid, sheltering, victim counseling, batterer counseling, advocacy groups, and child protection.

2. DEFINING DOMESTIC VIOLENCE

Domestic violence, which is sometimes also referred to as spousal abuse, battering, or intimate partner violence (IPV), refers to the victimization of an individual with whom the abuser has or has had an intimate or romantic relationship. Researchers in the field of domestic violence have not agreed on a uniform definition of what constitutes violence or an abusive relationship. The Centers for Disease Control and Prevention (CDC) defines IPV as, "violence or aggression that occurs in a romantic relationship" [1]. According to the Florida Department of Children and Families, domestic violence is "a pattern of abusive behaviors that adults use to maintain power and control over their intimate partners or former partners. People who abuse their partners use a variety of tactics to coerce, intimidate, threaten, and frighten their victims" [2]. Domestic violence may include physical violence, sexual violence, emotional abuse, economic abuse, isolation, pet abuse, threats relating to children, and a variety of other behaviors meant to increase fear, intimidation, and power over the victim [2]. Florida law defines domestic violence as "any assault, aggravated assault, battery, aggravated battery, sexual assault, sexual battery, stalking, aggravated stalking, kidnapping, false imprisonment, or any criminal offense resulting in physical injury or death of one family or household member by another family or household member" [3]. Family or household members, according to Florida definition, must "be currently residing or have in the past resided together in the same single dwelling unit" [3]. Domestic violence knows no boundaries. It occurs in intimate relationships regardless of race, religion, culture, or socioeconomic status [2].

Whatever the definition, it is important for healthcare professionals to understand that domestic violence, in the form of emotional and psychologic abuse, sexual abuse, and physical violence, is prevalent in our society. Because of the similar nature of the definitions, this course will use the terms "domestic violence" and "IPV" interchangeably.

3. NATIONAL AND STATE STATISTICS AND LEGISLATION

Domestic violence is one of the most serious public health problems in the United States [4]. More than 36.4% of women and 33.6% of men have a lifetime history of IPV [4]. In Florida, the weighted lifetime prevalence of IPV (including rape, physical violence, and/or stalking) is 37.4% among women and 29.3% among men [5]. Although many of these incidents are relatively minor and consist of pushing, grabbing, shoving, slapping, and hitting, IPV resulted in approximately 1,500 deaths in the United States in 2019, with 214 of those deaths occurring in Florida in the same year. Statistics indicate a slightly higher rate in 2020, with 217 deaths in Florida in 2020 [7,8]. One of the difficulties in addressing the problem is that abuse is prevalent in all demographics, regardless of age, ethnicity, race, religious denomination, education, or socioeconomic status [2].

Victims of abuse often suffer severe physical injuries and will likely seek care at a hospital or clinic. The health and economic consequences of domestic violence are significant. Statistics vary from report to report, and due to the lack of studies on the national cost of domestic violence, the U.S. Congress funded the CDC to conduct a study to determine the cost of domestic violence on the healthcare system [9]. The 2003 CDC report, which relied on data from the National Violence Against Women Survey conducted in 1995, estimated the costs of IPV by measuring how many female victims were nonfatally injured; how many women used medical and mental healthcare services; and how many women lost time from paid work and household chores. The estimated total annual cost of IPV against women in the 1995 survey was more than $5.8 billion [9]. When updated to 2017 dollars, the amount was more than $9.3 billion annually. The costs associated with IPV at this time would be considerably more, but no further studies have been conducted [10]. It should be noted that the costs of any one victimization may continue for years; therefore, these statistics most likely underestimate the actual cost of IPV [9].

The national rate of nonfatal domestic violence against women declined 72% between 1993 and 2011 [11]. The rate of overall violent crime fell by nearly 60% in this same time period [11]. Studies reveal that several factors may have contributed to the reduction in violence, including a decline in the marriage rate and decrease of domesticity, better access to federally funded domestic violence shelters, improvements in women's economic status, and demographic trends, such as the aging of the population [13,14]. Of note, declines in the economy and stress associated with financial hardship and unemployment are significant contributors to IPV in the United States. Following the economic downturn in late 2008, there was a significant increase in the use of the National Domestic Violence Hotline in 2009, with more than half of victims reporting a change in household financial situation in the last year [15]. This trend continued with the COVID-19 pandemic, with stressors from lockdown orders, unemployment, financial insecurity, childcare and homeschool responsibilities, and poor coping strategies (e.g., substance abuse) increasing the rate of domestic violence. Reports showed a 9.7% increase in domestic violence calls for service in the first two months state-mandated lockdowns were imposed; furthermore, the National Commission on COVID-19 and Criminal Justice reported an increase of 8.1% in domestic violence incidents within the first months of mandated stay-at-home orders [6].

FLORIDA

In response to troubling domestic violence statistics, Governor Lawton Chiles appointed a Task Force on Domestic Violence on September 28, 1993, to investigate the problems associated with domestic violence in Florida and to compile recommendations as to how the problems should be approached and ultimately resolved. On January 31, 1994, the Task Force issued its first report on domestic violence. This report recommended standards to accurately measure the extent of domestic violence and strategies for increasing public awareness and education. It identified programs and resources that are available to victims in Florida, made legislative and budgetary suggestions for needed changes, provided a methodology for implementing these changes, and identified areas of domestic violence that require further study.

As a result of this report, Florida enacted legislation during the 1995 session implementing various suggestions of the Task Force. Specifically, the Legislature amended Section 455.222 of the Florida Statutes to require that all physicians, osteopaths, nurses, dentists, dental hygienists, midwives, psychologists, and psychotherapists obtain, as part of their biennial continuing education requirements, a one-hour continuing education course on domestic violence [17]. In June of 2006, Governor Jeb Bush signed into law House Bill 699. The bill, which went into effect July 1, 2006, changed the domestic violence continuing education requirement from one hour every renewal period to two hours every third renewal period.

In 1997, at the request of the Governor's Task Force, a workgroup was established by the Florida Department of Law Enforcement (FDLE) to evaluate the feasibility of tracking incidents of domestic violence in the state [18]. This resulted in the creation of the Domestic Violence Data Resource Center (DVDRC). The original mission of the DVDRC was to collect information related to domestic violence and to report and maintain the information in a statewide tracking system [19]. Domestic Violence Fatality Review Teams were established to examine those cases of domestic violence that resulted in a fatality and identify potential changes in policy or procedure that might prevent future deaths. The teams were comprised of representatives from law enforcement, the courts, social services, state attorneys, domestic violence centers, and others who may come into contact with domestic violence victims and perpetrators [20]. In 2000, the creation of Florida Statute 741.316 required the FDLE to annually publish a report based on the data gathered by the Fatality Review Teams [19]. Due to budgetary constraints, responsibility of compiling this data transferred to the Department of Children and Families in 2008 [21].

As part of Governor Jeb Bush's initiative, the "Family Protection Act" was signed into law in 2001. The act requires a 5-day mandatory jail term for any crime of domestic battery in which the perpetrator deliberately injures the victim. The law also makes a second battery crime a felony offense, treating offenders as serious criminals. Additional legislation, signed into law in 2002, includes Senate Bills 716 and 1974. Senate Bill 716 protects domestic violence victims by including dating relationships of six months in the definition of domestic violence laws. Senate Bill 1974 requires judges to inform victims of their rights, including the right to appear, be notified, seek restitution, and make a victim-impact statement. Governor Bush also created the Violence Free Florida campaign to increase public awareness of domestic violence issues [22].

In 2003, Governor Bush signed House Bill 1099, which transferred funding authority of the Florida Domestic Violence Trust Fund from the Department of Children and Families to the Florida Coalition Against Domestic Violence. According to the Domestic Violence in Florida 2010–2011 Annual Report to the Legislature, this has strengthened domestic violence services provided by streamlining the process of allocating funds [23].

In 2007, the Domestic Violence Leave Act was signed into law by Governor Charlie Crist [21]. This law requires employers with 50 or more employees to provide guaranteed leave for domestic violence issues.

In 2020, the FDLE reported 106,736 domestic violence offenses [8]. In general, domestic violence rates have been declining since 1998. An estimated 19.5% of domestic violence incidents involved spouses and 27.8% involved cohabitants; 11.6% of the victims were parents of the offenders. Domestic violence offenses resulted in the death of 217 victims in Florida in 2020, a number that has been decreasing since 2014 [8]. Domestic violence accounted for 16.9% of the state's murders in 2020 [8].

In their 2019 Annual Report, Fatality Review Teams summarized 31 cases of domestic violence fatalities and near fatalities [49]. The most significant findings included the following observations [49]:

- The perpetrators were predominantly male (94%) with female victims (90%) and had prior criminal histories, non-domestic-violence-related (67%) and for domestic violence specifically (69%).

- In 31% of fatalities, the perpetrators had a known "do not contact" order filed against them, and 13% of perpetrators had a known permanent injunction for protection against them filed by someone other than the victim.

- Substance abuse histories by the perpetrator was identified in 77% of the cases and diagnosed mental health disorders in 45%.

- In most cases, neither the decedent nor perpetrator sought help from the various intervention programs available to them.

To obtain a copy of the most current Florida Statewide Domestic Violence Fatality Review report, please visit https://www.myflfamilies.com/service-programs/domestic-violence/publications.shtml.

4. IDENTIFYING GROUPS AT RISK FOR DOMESTIC VIOLENCE

Healthcare professionals are in a critical position to identify domestic violence victims in a variety of clinical practice settings. Nurses are often the first healthcare provider a victim of domestic violence will encounter in a healthcare setting and should therefore be prepared to provide care and support for these victims. Although women are most often the victims, domestic violence extends to others in the household as well. For example, domestic violence includes abused men, children abused by their parents or parents abused by their children, elder abuse, and abuse among siblings [3].

Many victims of abuse sustain injuries that lead them to present to hospital emergency departments. Research has found that 49.6% of women seen in emergency departments reported a history of abuse and 44% of women who were ultimately killed by their abuser had sought help in an emergency department in the two years prior to their death [25,50]. Another study of 993 police-identified female victims of IPV found that only 28% of the women were identified in the emergency department as being victims of IPV [26]. These alarming statistics demonstrate that healthcare professionals who work in acute care, such as hospital emergency rooms, should maintain a high index of suspicion for battering of the patients that they see. Healthcare professionals who work in these settings should work with hospital administrators to establish and institute assessment mechanisms to accurately detect these victims.

For every victim of abuse, there is also a perpetrator. Like their victims, perpetrators of domestic violence come from all socioeconomic backgrounds, races, religions, and walks of life [1,4]. Accordingly, healthcare professionals should likewise be aware that seemingly supportive family members may, in fact, be abusers.

PREGNANT WOMEN

Because a gynecologist or obstetrician is frequently a woman's primary care physician, the American College of Obstetricians and Gynecologists (ACOG) recommends that all women be routinely assessed for signs of IPV (i.e., physical and psychologic abuse, reproductive coercion, and progressive isolation), including during prenatal visits, and providers should offer support and referral information for those being abused [25]. According to the ACOG, IPV affects as many as 324,000 pregnant women each year [25]. A meta-analysis of 92 independent studies found that the average reported prevalence of emotional abuse during pregnancy was 28.4%, physical abuse was 13.8%, and sexual abuse was 8% [51]. As with all domestic violence statistics, these estimates are presumed to be lower than the actual incidence as a result of under-reporting and lack of data on women whose pregnancies ended in fetal or maternal death. This makes IPV more prevalent among pregnant women than some of the health conditions included in prenatal screenings, including pre-eclampsia and gestational diabetes [25]. Because 96% of pregnant women receive prenatal care, this is an optimal time to assess for domestic violence and develop trusting relationships with the women. Possible factors that may predispose pregnant women to IPV include being unmarried, lower socioeconomic status, young maternal age, unintended pregnancy, delayed prenatal care, lack of social support, and use of tobacco, alcohol, or illegal drugs [25,51].

The overarching problem of violence against pregnant women cannot be ignored, especially as both mother and fetus are at risk. At this particularly vulnerable time in a woman's life, an organized clinical construct leading to immediate diagnosis and medical intervention will ensure that therapeutic opportunities are available to the pregnant woman and will reduce the potential negative outcomes [29]. Healthcare professionals should also be aware of the possible psychologic consequences of abuse during pregnancy. There is a higher risk of stress, depression, and addiction to alcohol and drugs in abused women. These conditions may result in damage to the fetus from tobacco, drugs, and alcohol and a loss of interest on the part of the mother in her or her baby's health [16,30]. Possible direct injuries to the fetus may result from maternal trauma [25].

Control of reproductive or sexual health is also a recognized trend in IPV. This type of abuse includes trying to impregnate or become pregnant against a partner's wishes, refusal to use birth control (e.g., condoms, oral contraceptives), or stopping a partner from using birth control [4].

CHILDREN

Children exposed to family violence are at high risk for abuse and for emotional damage that may affect them as they grow older. The Department of Justice estimates that of the 76 million children in the United States, 46 million will be exposed to some type of violence during their childhood [52]. Results of the National Survey of Children's Exposure to Violence indicated that 11% of children were exposed to IPV at home within the last year, and as many as 26% of children were exposed to at least one form of family violence during their lifetimes [31]. Of those children exposed to IPV, 90% were direct eyewitnesses of the violence; the remaining children were exposed by either hearing the violence or seeing or being told about injuries [31]. Of note, according to Florida criminal law, witnessing domestic violence is defined as "violence in the presence of a child if an offender is convicted of a primary offense of domestic violence, and that offense was committed in the presence of a child under age 16 who is a family or household member with the victim or perpetrator" [32].

A number of studies indicate that child witnesses are at increased risk for post-traumatic stress disorder, impaired development, aggressive behavior, anxiety, difficulties with peers, substance abuse, and academic problems than the average child [33,54,55]. Children exposed to violence may also be more prone to dating violence (as a perpetrator or a victim), and the ability to effectively cope with partnerships and parenting later in life may be affected, continuing the cycle of violence into the next generation [34,56].

In addition to witnessing violence, various studies have shown that these children may also become direct victims of violence, and children who both witness and experience violence are at the greatest risk for adverse psychosocial outcomes [53]. Research indicates that between 30% and 65% of husbands who batter their wives also batter their children [27,35]. Moreover, victims of abuse will often turn on their children; statistics demonstrate that 85% of domestic violence victims abuse or neglect their children. The 2020 Crime in Florida report found that more than 13% of domestic homicide victims were children killed by a parent [8]. Teenage children are also victimized. According to the U.S. Department of Justice, between 1980 and 2008, 17.5% of all homicides against female adolescents 12 to 17 years of age were committed by an intimate partner [36]. Among young women (18 to 24 years of age), the rate is estimated to be 43% in the United States and 8% to 57% globally. Abused teens often do not report the abuse. Individuals 12 to 19 years of age report only 35.7% of crimes against them, compared with 54% in older age groups [28,37]. Accordingly, healthcare professionals who see young children and adolescents in their practice (e.g., pediatricians, family physicians, school nurses, pediatric nurse practitioners, community health nurses) should have the tools necessary to detect these "silent victims" of domestic violence and to intervene quickly to protect young children and adolescents from further abuse. Without such critical intervention, the cycle of violence will never end.

ELDERLY

Abused and neglected elders, who may be mistreated by their spouses, partners, children, or other relatives, are among the most isolated of all victims of family violence. In a national study conducted by the National Institute of Justice in 2010, 4.6% of participants (community dwelling adults 60 years of age or older) were victims of emotional abuse in the past year, 1.6% physical abuse, 0.6% sexual abuse, 5.1% potential neglect, and 5.2% current financial abuse by a family member [38]. A 2017 study found a self-reported incidence of 11.6% psychological abuse, 2.6% physical abuse, 6.8% financial abuse, 4.2% neglect, and 0.9% sexual abuse [59]. The estimated annual incidence of all elder abuse types is 2% to 10%, but it is believed to be severely under-measured. According to one study, only 1 in 24 cases of elder abuse are reported to the authorities [39].

The prevalence rate of elder abuse in institutional settings is not clear. However, in a 2019 review of nine studies, 64% of elder care facility staff disclosed to having perpetrated abuse against an elderly resident in the past year [40]. In a random sample survey, 24.3% of respondents reported at least one incident of elder physical abuse perpetrated by a nursing home staff member [57].

Evidence Based Practice Recommendation

The U.S. Preventive Services Task Force concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for abuse and neglect in all older or vulnerable adults.

https://jamanetwork.com/journals/jama/fullarticle/2708121

Last Accessed: July 26, 2022

Strength of Recommendation: I (Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.)

As healthcare professionals in Florida, which leads the nation in percentage of older residents, it is important to understand that the needs of older Floridians will increase as will the numbers of elder victims of domestic violence. Because elder abuse can occur in family homes, nursing homes, board and care facilities, and even medical facilities, healthcare professionals should remain keenly aware of the potential for abuse. When abuse occurs between elder partners, it is primarily manifested in one of two ways: either as a long-standing pattern of marital violence or as abuse originating in old age. In the latter case, abuse may be precipitated by issues related to advanced age, including the stress that accompanies disability and changing family relationships [39].

It is important to understand that the domestic violence dynamic involves not only a victim but a perpetrator as well. For example, an adult son or daughter who lives in the parents' home and depends on the parents for financial support may be in a position to inflict abuse. This abuse may not always manifest itself as violence but can lead to an environment in which the elder parent is controlled and isolated. The elder may be hesitant to seek help because the abuser's absence from the home may leave the elder without a caregiver [39]. Because these elderly victims are often isolated, dependent, infirm, or mentally impaired, it is easy for the abuse to remain undetected. Healthcare professionals in all settings should remain aware of the potential for abuse and keep a watchful eye on this particularly vulnerable group.

MEN

Statistics confirm that domestic violence is predominantly perpetrated by men against women; however, there is evidence that women also exhibit violent behavior against their male partners [4]. Studies demonstrate approximately 5% of homicides against men are perpetrated by intimate partners [36]. It is persuasively argued that the impact on the health of female victims of domestic violence is generally much more severe than the impact on the health of male victims [42]. Approximately 512,770 women were raped and/or physically assaulted by an intimate partner in 2008, compared to 101,050 men [58]. In addition, 1 in 4 women has been physically assaulted, raped, and/or stalked by an intimate partner, compared with 1 out of every 10 men [1]. Rape, non-contact unwanted sexual experiences, and stalking against men are primarily perpetrated by other men, while other forms of violence against men were perpetrated mostly by women [5]. Male victims of IPV experienced 3 victimizations per 1,000 boys and men 12 years of age or older in 1994, and this rate decreased by 64%, to 1.1 per 1,000, in 2010 [11]. Of all homicides committed against men between 1980 and 2008, 7.1% were committed by an intimate partner [36]. Although women are more often victims of IPV, healthcare professionals should always keep in mind that men can also be victimized and assess accordingly.

LESBIAN, GAY, BISEXUAL, TRANSGENDER, AND QUEER/QUESTIONING VICTIMS

Domestic violence exists in lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ+) communities, and the rates are thought to mirror those of heterosexual women—approximately 25% [43]. However, women living with female intimate partners experience less IPV than women living with men [8]. Conversely, men living with male intimate partners experience more IPV than do men who live with female intimate partners [8]. In addition, 78% of IPV homicide victims reported in 2017 were transgender women or cisgender men [24]. This supports other statistics indicating that IPV is perpetrated primarily by men. A form of abuse specific to the gay community is for an abuser to threaten or to proceed with "outing" a partner to others [41,43].

Transgender individuals appear to be at particular risk for violence. According to a large national report, transgender victims of IPV were 1.9 times more likely to experience physical violence and 3.9 times more likely to experience discrimination than other members of the LGBTQ+ community [24].

In 2017, an annual national report recorded 52 incidences of hate violence-related homicides of LGBTQ+ people, the highest incident number recorded in its 20-year history [24]. This increasing prevalence of anti-LGBTQ+ violence can exacerbate IPV in LGBTQ+ communities. For example, a person who loses their job because of anti-trans bias may be more financially reliant on an unhealthy relationship. An abusive partner may also use the violence that an LGBTQ+ person experiences from their family as a way of isolating that person further [24].

Because of the stigma of being LGBTQ+, victims may be reticent to report abuse and afraid that their sexual orientation or biologic sex will be revealed. In one study, the three major barriers to seeking help were a limited understanding of the problem of LGBTQ+ IPV, stigma, and systemic inequities [41]. Many in this community feel that support services (e.g., shelters, support groups, crisis hotlines) are not available to them due to homophobia of the service providers. Unfortunately, this results in the victim feeling isolated and unsupported. Healthcare professionals should strive to be sensitive and supportive when working with homosexual patients.

5. CHARACTERISTICS OF PERPETRATORS OF DOMESTIC VIOLENCE

Abuser characteristics have been studied far less frequently than victim characteristics. Some studies suggest a correlation between the occurrence of abuse and the consumption of alcohol. A man who abuses alcohol is also likely to abuse his mate, although the abuser may not necessarily be inebriated at the time the abuse is inflicted [44]. Domestic violence assessment questionnaires should include questions that explore social drinking habits of both victims and their mates.

Other studies demonstrate that abusive mates are generally possessive and jealous. Another characteristic related to the abuser's dependency and jealousy is extreme suspiciousness. This characteristic may be so extreme as to border on paranoia [12]. Domestic violence victims frequently report that abusers are extremely controlling of the everyday activities of the family. This domination is generally all encompassing and often includes maintaining complete control of finances and activities of the victim (e.g., work, school, social interactions) [12].

In addition, abusers often suffer from low self-esteem and their sense of self and identity is directly connected to their partner [12]. Extreme dependence is common in both abusers and those being abused. Due to low self-esteem and self-worth, emotional dependence often occurs in both partners, but even more so in the abuser. Emotional dependence in the victim stems from both physical and psychologic abuse, which results in a negative self-image and lack of self-worth. Financial dependence is also very common, as the abuser often withholds or controls financial resources to maintain power over the victim [1,4].

6. SCREENING FOR DOMESTIC VIOLENCE AND ABUSE

Evidence Based Practice Recommendation

The U.S. Preventive Services Task Force recommends that that clinicians screen for intimate partner violence (IPV) in women of reproductive age and provide or refer women who screen positive to ongoing support services.

https://jamanetwork.com/journals/jama/fullarticle/2708121

Last Accessed: July 26, 2022

Strength of Recommendation: B (There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.)

There is no universal guideline for identifying and responding to domestic violence, but it is universally accepted that a plan for screening, assessing, and referring patients of suspected abuse should be in place at every healthcare facility. Guidelines should review appropriate interview techniques for a given setting and should also include the utilization of assessment tools. Furthermore, protocols within each facility or healthcare setting should include referral, documentation, and follow-up. This section relies heavily on the guidelines outlined in the Family Violence Prevention Fund's National Consensus Guidelines on Identifying and Responding to Domestic Violence Victimization in Health Care Settings; however, protocols should be customized based on individual practice settings and resources available [35]. The CDC has provided a compilation of assessment tools for healthcare workers to assist in recognizing and accurately interpreting behaviors associated with domestic violence and abuse, which may be accessed at https://www.cdc.gov/violenceprevention/pdf/ipv/ipvandsvscreening.pdf [45].

Several barriers to screening for domestic violence have been noted, including a lack of knowledge and training, time constraints, lack of privacy for asking appropriate questions, and the sensitive nature of the subject [35]. Although awareness and assessment for IPV has increased among healthcare providers, many are still hesitant to inquire about abuse [46]. At a minimum, those exhibiting signs of domestic violence should be screened. Although victims of IPV may not display typical signs and symptoms when they present to healthcare providers, there are certain cues that may be attributed to abuse. The obvious cues are physical. Injuries range from bruises, cuts, black eyes, concussions, broken bones, and miscarriages to permanent injuries such as damage to joints, partial loss of hearing or vision, and scars from burns, bites, or knife wounds. Typical injury patterns include contusions or minor lacerations to the head, face, neck, breast, or abdomen and musculoskeletal injuries. These are often distinguishable from accidental injuries, which are more likely to involve the extremities of the body. Abuse victims are also more likely to have multiple injuries than accident victims. When this pattern of injuries is seen, particularly in combination with evidence of old injury, physical abuse should be suspected [44].

In addition to physical signs and symptoms, domestic violence victims also exhibit psychologic cues that resemble an agitated depression. As a result of prolonged stress, various psychosomatic symptoms that generally lack an organic basis often manifest. For example, complaints of backaches, headaches, and digestive problems are common. Often, there are reports of fatigue, restlessness, insomnia, or loss of appetite. Great amounts of anxiety, guilt, and depression or dysphoria are also typical. Women who experienced IPV are also more likely to report asthma, irritable bowel syndrome, and diabetes [4]. Healthcare professionals should look beyond the typical symptoms of a domestic violence victim and work within their respective practice settings to develop appropriate assessment mechanisms to detect victims who exhibit less obvious symptoms.

The unique relationship dynamics of the abuser and abused are not easily detected under the best of circumstances. They may be especially difficult to uncover in circumstances in which the parties are suspicious and frightened, as might be expected when a victim presents to the emergency department. The key to detection, however, is to establish a proper assessment tool that can be utilized in the particular setting and to maintain a keen awareness for the cues described in this course. Screening for IPV should be carried out at the entry points of contact between victims and medical care (e.g., primary care, emergency services, obstetric and gynecologic services, psychiatric services, and pediatric care) [35].

The key to an initial assessment is to obtain an adequate history. Establishing that a patient's injuries are secondary to abuse is the first task. Clearly, there will be times when a victim is injured so severely that treatment of these injuries becomes the first priority. After such treatment is rendered, however, it is important that healthcare professionals not ignore the reasons that brought the victim to the emergency department [35].

7. ASSESSING DOMESTIC VIOLENCE AND ABUSE

Healthcare providers have reported that even if routine screening and inquiry results in a positive identification of IPV, the next steps of assessing and referring are often difficult, and many feel that they are not adequately prepared [46]. According to the Family Violence Prevention Fund, the goals of the assessment are to create a supportive environment, gather information about health problems associated with the abuse, and assess the immediate and long-term health and safety needs for the patient to develop an intervention [35].

Assessment of domestic violence victims should occur immediately after disclosure of abuse and at any follow-up appointments. Assessing immediate safety is priority. Having a list of questions readily available and well-practiced can help alleviate the uncertainty of how to begin the assessment (Table 1). If the patient is in immediate danger, referral to an advocate, support system, hotline, or shelter is indicated [35].

Table 1: ASSESSMENT OF IMMEDIATE SAFETY FOR DOMESTIC VIOLENCE VICTIMS

Are you in immediate danger?

Is your partner at the health facility now?

Do you want to (or have to) go home with your partner?

Do you have somewhere safe to go?

Have there been threats or direct abuse of the child(ren) (if applicable)?

Are you afraid your life may be in danger?

Has the violence gotten worse or is it getting scarier? Is it happening more often?

Has your partner used weapons, alcohol, or drugs?

Has your partner ever held you or your child(ren) against your will?

Does your partner ever watch you closely, follow you or stalk you?

Has your partner ever threatened to kill you, him/herself or your child(ren)?

Source: [35]

If the patient is not in immediate danger, the assessment may continue with a focus on the impact of IPV on the patient's mental and physical health and the pattern of history and current abuse [35]. These responses will help formulate an appropriate intervention.

CULTURALLY SENSITIVE ASSESSMENT

During the assessment process, a practitioner should be open and sensitive to the patient's worldview, cultural belief systems and how he/she views the illness [47]. This may reduce the tendency to over-pathologize or minimize health concerns of ethnic minority patients.

Pachter proposed a dynamic model that involves several tiers and transactions [48]. The first component of Pachter's model calls for the practitioner to take responsibility for cultural awareness and knowledge. The professional should be willing to acknowledge that he/she does not possess enough or adequate knowledge in health beliefs and practices among the different ethnic and cultural groups he/she comes in contact with. Reading and becoming familiar with medical anthropology is a good first step.

The second component emphasizes the need for specifically tailored assessment [48]. Pachter advocates the notion that there is tremendous diversity within groups. For example, one cannot automatically assume that a Cuban immigrant adheres to traditional beliefs. Often, there are many variables, such as level of acculturation, age at immigration, educational level, and socioeconomic status, that influence health ideologies. Finally, the third component involves a negotiation process between the patient and the professional [48]. The negotiation consists of a dialogue that involves a genuine respect of beliefs. It is important to remember that these beliefs may affect symptoms or appropriate interventions in the case of domestic violence.

Culturally sensitive assessment involves a dynamic framework whereby the practitioner engages in a continual process of questioning. By incorporating cultural sensitivity into the assessment of individuals with a history of being victims or perpetrators of domestic violence, it may be possible to intervene and offer treatment more effectively.

8. INTERVENTIONS FOR DOMESTIC VIOLENCE AND ABUSE

After the assessment is complete, the patient may or may not want immediate assistance or referral. It is important for healthcare providers to assure patients in a nonjudgmental manner that the decision of what they would like in terms of assistance is their choice and that the provider will help regardless of the decisions they are currently ready to make [35].

If the patient would like to immediately implement a plan of action, information for referral to a local domestic violence shelter to assist the victim and the victim's family should be readily available. The acute situation should be referred immediately to local law enforcement officials. Other resources in an acute situation include crisis hotlines and rape relief centers. After a victim is introduced into the system, counseling and follow-up are generally available by individual counselors who specialize in the care of battered women and their spouses and children. These may include social workers, psychologists, psychiatrists, other mental health workers, and community mental health services. The goals are to make the resources accessible and safe and to enhance support for those who are unsure of their options [35].

In Florida, a 24-hour domestic violence hotline is available for toll-free counseling and information. The number is 800-500-1119. The counselors answering the toll-free line may refer the victim to her or his local domestic violence center. A list of Florida certified domestic violence centers organized by county may also be found on the Florida Department of Children and Families website at https://www.myflfamilies.com/service-programs/domestic-violence. Florida's domestic violence centers provide information and referral services, counseling and case management services, a 24-hour hotline, temporary emergency shelter for more than 24 hours, educational services for community awareness relative to domestic violence, assessment and appropriate referral of resident children, and training for law enforcement personnel.

9. DOCUMENTATION AND FOLLOW-UP

It is imperative that healthcare professionals document all findings and recommendations regarding domestic violence in the victim's medical record, including a patient's denial of abuse, if applicable. If domestic violence is disclosed, documentation should include relevant history, results of the physical examination, findings of laboratory and other diagnostic procedures, and results of the assessment, intervention, and referral. The medical record can be an invaluable document in establishing the credibility of the victim's story when seeking legal aid [35].

Healthcare professionals should offer a follow-up appointment if disclosure of past or current abuse is present. Reassurance that assistance is available to the patient at any time is critical in helping to break the cycle of abuse [35].

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54. Yount KM, DiGirolamo AM, Ramakrishnan U. Impacts of domestic violence on child growth and nutrition: a conceptual review of the pathways of influence. Soc Sci Med. 2011;72(9):1534-1554.

55. Schiff M, Plotnikova M, Dingle K, Williams GM, Najman J, Clavarino A. Does adolescent's exposure to parental intimate partner conflict and violence predict psychological distress and substance use in young adulthood? A longitudinal study. Child Abuse Neglect. 2014;38(12):1945-1954.

56. Narayan AJ, Englund MM, Carlson EA, Egeland B. Adolescent conflict as a developmental process in the prospective pathway from exposure to interparental violence to dating violence. J Abnorm Child Psychol. 2014;42(2):239-250.

57. Schiamberg LB, Oehmke J, Zhang Z, et al. Physical abuse of older adults in nursing homes: a random sample survey of adults with an elderly family member in a nursing home. J Elder Abuse Negl. 2012;24(1):65-83.

58. Catalano S, Smith E, Snyder H, Rand M. Female Victims of Violence. Available at https://www.bjs.gov/content/pub/pdf/fvv.pdf. Last accessed July 11, 2022.

59. Yon Y, Mikton CR, Gassoumis ZD, Wilber KH. Elder abuse prevalence in community settings: a systematic review and meta-analysis. Lancet Global Health. 2017;5(2):e147-e156.

Evidence-Based Practice Recommendations Citations

1. U.S. Preventive Services Task Force. Screening for intimate partner violence, elder abuse, and abuse of vulnerable adults: U.S. Preventive Services Task Force recommendation statement. JAMA. 2018;320(16):1678-1687. Available at https://jamanetwork.com/journals/jama/fullarticle/2708121. Last accessed July 26, 2022.

45122 • Strategies for Appropriate Opioid Prescribing: The Florida Requirement

Mark Rose, BS, MA, LP

www.netce.com

Copyright © 2024 NetCE, All rights reserved.

Opioid analgesic medications can bring substantial relief to patients suffering from pain. However, the inappropriate use, abuse, and diversion of prescription drugs in America, particularly prescription opioids, has increased dramatically in recent years and has been identified as a national public health epidemic. A set of clinical tools, guidelines, and recommendations are now available for prescribers who treat pain patients with opioids. By implementing these tools, clinicians can effectively address issues related to the clinical management of opioid prescribing, opioid risk management, regulations surrounding the prescribing of opioids, and problematic opioid use by patients. In doing so, healthcare professionals are more likely to achieve a balance between the benefits and risks of opioid prescribing, optimize patient attainment of therapeutic goals, and avoid the risk to patient outcome, public health, and viability of their own practice imposed by deficits in knowledge.

Table of Contents

45122 • Strategies for Appropriate Opioid Prescribing: The Florida Requirement

Course Overview

Audience

Accreditations & Approvals

Designations of Credit

Special Approvals

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Division Planner

Division Planner Disclosure

Director of Development and Academic Affairs

Director Disclosure Statement

About the Sponsor

Disclosure Statement

Implicit Bias in Health Care

1. INTRODUCTION

2. DEFINITIONS

3. EPIDEMIOLOGY OF CHRONIC PAIN AND OPIOID MISUSE

OPIOID MISUSE IN FLORIDA

4. INITIATION AND MANAGEMENT OF THE PATIENT WITH PAIN

ACUTE PAIN

PATIENT EVALUATION AND ASSESSMENT OF ADDICTION RISK

CREATING A TREATMENT PLAN

PERIODIC REVIEW AND MONITORING

CONCURRENT USE OF BENZODIAZEPINES

CONSULTATION AND REFERRAL

MEDICAL RECORDS

PATIENT EDUCATION ON THE USE AND DISPOSAL OF OPIOIDS

DISCONTINUING OPIOID THERAPY

CONSIDERATIONS FOR NON-ENGLISH-PROFICIENT PATIENTS

5. CRISIS INTERVENTION: MANAGEMENT OF OVERDOSE

OPIOID ANTAGONISTS

6. COMPLIANCE WITH STATE AND FEDERAL LAWS

CONTROLLED SUBSTANCES LAWS/RULES

THE ELECTRONIC FLORIDA ONLINE REPORTING OF CONTROLLED SUBSTANCES EVALUATION PROGRAM

7. IDENTIFICATION OF DRUG DIVERSION/SEEKING BEHAVIORS

8. INTERVENTIONS FOR SUSPECTED OR KNOWN DRUG DIVERSION

9. CASE STUDY

ASSESSMENT

FOLLOW-UP

10. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

45122 • Strategies for Appropriate Opioid Prescribing: The Florida Requirement

Education Category. Pharmacology

Release Date. 09/01/2024

Expiration Date. 08/31/2027

Course Overview

Opioid analgesic medications can bring substantial relief to patients suffering from pain. However, the inappropriate use, abuse, and diversion of prescription drugs in America, particularly prescription opioids, has increased dramatically in recent years and has been identified as a national public health epidemic. A set of clinical tools, guidelines, and recommendations are now available for prescribers who treat pain patients with opioids. By implementing these tools, clinicians can effectively address issues related to the clinical management of opioid prescribing, opioid risk management, regulations surrounding the prescribing of opioids, and problematic opioid use by patients. In doing so, healthcare professionals are more likely to achieve a balance between the benefits and risks of opioid prescribing, optimize patient attainment of therapeutic goals, and avoid the risk to patient outcome, public health, and viability of their own practice imposed by deficits in knowledge.

Audience

This course is designed for all physicians and osteopath physicians who may alter prescribing practices or intervene to prevent drug diversion and inappropriate opioid use.

Accreditations & Approvals

In support of improving patient care, TRC Healthcare/NetCE is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. NetCE is accredited by the International Accreditors for Continuing Education and Training (IACET). NetCE complies with the ANSI/IACET Standard, which is recognized internationally as a standard of excellence in instructional practices. As a result of this accreditation, NetCE is authorized to issue the IACET CEU.

Designations of Credit

NetCE designates this enduring material for a maximum of 2 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 2 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Completion of this course constitutes permission to share the completion data with ACCME. This activity has been approved for the American Board of Anesthesiology’s® (ABA) requirements for Part II: Lifelong Learning and Self-Assessment of the American Board of Anesthesiology’s (ABA) redesigned Maintenance of Certification in Anesthesiology Program® (MOCA®), known as MOCA 2.0®. Please consult the ABA website, www.theABA.org, for a list of all MOCA 2.0 requirements. Maintenance of Certification in Anesthesiology Program® and MOCA® are registered certification marks of the American Board of Anesthesiology®. MOCA 2.0® is a trademark of the American Board of Anesthesiology®. Successful completion of this CME activity, which includes participation in the evaluation component, enables the learner to earn credit toward the CME and/or Self-Assessment requirements of the American Board of Surgery's Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit. Successful completion of this CME activity, which includes participation in the activity with individual assessments of the participant and feedback to the participant, enables the participant to earn 2 MOC points in the American Board of Pediatrics' (ABP) Maintenance of Certification (MOC) program. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABP MOC credit. This activity has been designated for 2 Lifelong Learning (Part II) credits for the American Board of Pathology Continuing Certification Program. Through an agreement between the Accreditation Council for Continuing Medical Education and the Royal College of Physicians and Surgeons of Canada, medical practitioners participating in the Royal College MOC Program may record completion of accredited activities registered under the ACCME's "CME in Support of MOC" program in Section 3 of the Royal College's MOC Program. NetCE is authorized by IACET to offer 0.2 CEU(s) for this program.

Special Approvals

This course, offered by the NetCE Physicians Professional Association, is approved by the Florida Board of Medicine to fulfill the Florida requirement for 2 hours on the safe and effective prescribing of controlled substance medications. This activity is designed to comply with the requirements of California Assembly Bill 1195, Cultural and Linguistic Competency.

Course Objective

The purpose of this course is to provide clinicians who prescribe or distribute opioids with an appreciation for the complexities of opioid prescribing and the dual risks of litigation due to inadequate pain control and drug diversion or misuse in order to provide the best possible patient care and to prevent a growing social problem.

Learning Objectives

Upon completion of this course, you should be able to:

1. Define opioid prescribing and opioid misuse.

2. Apply epidemiologic trends in opioid use and misuse to current practice so at-risk patient populations can be more easily identified, assessed, and treated.

3. Create comprehensive treatment plans for patients with chronic pain that address patient needs as well as drug diversion prevention.

4. Identify state and federal laws governing the proper prescription and monitoring of controlled substances.

5. Evaluate behaviors that may indicate drug seeking or diverting as well as approaches for patients suspected of misusing opioids.

Faculty

Mark Rose, BS, MA, LP, is a licensed psychologist in the State of Minnesota with a private consulting practice and a medical research analyst with a biomedical communications firm. Earlier healthcare technology assessment work led to medical device and pharmaceutical sector experience in new product development involving cancer ablative devices and pain therapeutics. Along with substantial experience in addiction research, Mr. Rose has contributed to the authorship of numerous papers on CNS, oncology, and other medical disorders. He is the lead author of papers published in peer-reviewed addiction, psychiatry, and pain medicine journals and has written books on prescription opioids and alcoholism published by the Hazelden Foundation. He also serves as an Expert Advisor and Expert Witness to law firms that represent disability claimants or criminal defendants on cases related to chronic pain, psychiatric/substance use disorders, and acute pharmacologic/toxicologic effects. Mr. Rose is on the Board of Directors of the Minneapolis-based International Institute of Anti-Aging Medicine and is a member of several professional organizations.

Faculty Disclosure

Contributing faculty, Mark Rose, BS, MA, LP, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Division Planner

John M. Leonard, MD

Division Planner Disclosure

The division planner has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Director of Development and Academic Affairs

Sarah Campbell

Director Disclosure Statement

The Director of Development and Academic Affairs has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

About the Sponsor

The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.

Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.

Disclosure Statement

It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.

Implicit Bias in Health Care

The role of implicit biases on healthcare outcomes has become a concern, as there is some evidence that implicit biases contribute to health disparities, professionals' attitudes toward and interactions with patients, quality of care, diagnoses, and treatment decisions. This may produce differences in help-seeking, diagnoses, and ultimately treatments and interventions. Implicit biases may also unwittingly produce professional behaviors, attitudes, and interactions that reduce patients' trust and comfort with their provider, leading to earlier termination of visits and/or reduced adherence and follow-up. Disadvantaged groups are marginalized in the healthcare system and vulnerable on multiple levels; health professionals' implicit biases can further exacerbate these existing disadvantages.

Interventions or strategies designed to reduce implicit bias may be categorized as change-based or control-based. Change-based interventions focus on reducing or changing cognitive associations underlying implicit biases. These interventions might include challenging stereotypes. Conversely, control-based interventions involve reducing the effects of the implicit bias on the individual's behaviors. These strategies include increasing awareness of biased thoughts and responses. The two types of interventions are not mutually exclusive and may be used synergistically.

1. INTRODUCTION

Pain is the leading reason for seeking medical care, and pain management is a large part of many healthcare professionals' practice. Opioid analgesics are approved by the U.S. Food and Drug Administration (FDA) for moderate and severe pain and are broadly accepted in acute pain, cancer pain, and end-of-life care, but are controversial in chronic noncancer pain. In response to the long-standing neglect of severe pain, indications for opioid analgesic prescribing were expanded in the 1990s, followed by inappropriate prescribing and increasing abuse, addiction, diversion, and overdose through the 2000s. In tandem with the continued under-treatment of pain, these practice patterns led to needless suffering from uncontrolled pain, opioid analgesic addiction, and overdose. Opioid analgesic prescribing and associated overdose peaked in 2011 with both now in multi-year decline, but information on these important trends is largely absent in the medical literature and media reporting.

Patients show substantial opioid response variations in analgesia and tolerability and may exhibit a range of psychologic, emotional, and behavioral responses that reflect inadequate pain control, an emerging opioid use problem, or both. Clinician delivery of best possible care to patients with pain requires appreciation of the complexities of opioid prescribing and the dual risks of inadequate pain control and inappropriate use, drug diversion, or overdose. A foundation for appropriate opioid prescribing is the understanding of factual data that clarify the prevalence, causality, and prevention of serious safety concerns with opioid prescribing.

2. DEFINITIONS

Definitions and use of terms describing opioid analgesic misuse, abuse, and addiction have changed over time, and their current correct use is inconsistent not only among healthcare providers, but also by federal agencies reporting epidemiologic data, such as prevalence of opioid analgesic misuse, abuse, or addiction. Misuse and misunderstanding of these concepts and their correct definitions have resulted in misinformation and represent an impediment to proper patient care.

Inappropriate opioid analgesic prescribing for pain is defined as the non-prescribing, inadequate prescribing, excessive prescribing, or continued prescribing despite evidence of ineffectiveness of opioids[1]. Appropriate opioid prescribing is essential to achieve pain control; to minimize patient risk of abuse, addiction, and fatal toxicity; and to minimize societal harms from diversion. The foundation of appropriate opioid prescribing is thorough patient assessment, treatment planning, and follow-up and monitoring. Essential for proper patient assessment and treatment planning is comprehension of the clinical concepts of opioid abuse and addiction, their behavioral manifestations in patients with pain, and how these potentially problematic behavioral responses to opioids both resemble and differ from physical dependence and pseudo-addiction. Prescriber knowledge deficit has been identified as a key obstacle to appropriate opioid prescribing and, along with gaps in policy, treatment, attitudes, and research, contributes to widespread inadequate treatment of pain [2]. For example, a survey measuring 200 primary care physicians' understanding of opioids and addiction found that [3]:

- 35% admitted knowing little about opioid addiction.

- 66% and 57% viewed low levels of education and income, respectively, as causal or highly contributory to opioid addiction.

- 30% believed opioid addiction "is more of a psychologic problem," akin to poor lifestyle choices rather than a chronic illness or disease.

- 92% associated prescription analgesics with opioid addiction, but only 69% associated heroin with opioid addiction.

- 43% regarded opioid dependence and addiction as synonymous.

This last point is very important because confusion and conflation of the clinical concepts of dependence and addiction has led to accusations of non-addicted patients with chronic pain of misusing or abusing their prescribed opioid and in the failure to detect treatment-emergent opioid problems. Knowledge gaps concerning opioid analgesics, addiction, and pain are related to attitude gaps, and negative attitudes may interfere with appropriate prescribing of opioid analgesics. For example, when 248 primary care physicians were asked of their prescribing approach in patients with headache pain with either a past or current history of substance abuse, 16% and 42%, respectively, would not prescribe opioids under any circumstance [5]. Possibly contributing to healthcare professionals' knowledge deficit in pain treatment is the extent of educational exposure in school. A 2011 study found that U.S. medical school students received a median 7 hours of pain education and Canadian medical students a median 14 hours, in contrast to the median 75 hours received by veterinarian school students in the United States [6].

In 2011, the American Society of Addiction Medicine (ASAM) published their latest revision in defining the disease of addiction. In 2018, ASAM's board recognized the need for an updated definition of addiction that would be more accessible to its stakeholder groups, including patients, the media, and policymakers. Accordingly, the Board appointed a Task Force that revised the definition of addiction for use in ASAM's policy statements. The revised definition states that [10]:

Addiction is a treatable, chronic medical disease involving complex interactions among brain circuits, genetics, the environment, and an individual's life experiences. People with addiction use substances or engage in behaviors that become compulsive and often continue despite harmful consequences. Prevention efforts and treatment approaches for addiction are generally as successful as those for other chronic diseases.

3. EPIDEMIOLOGY OF CHRONIC PAIN AND OPIOID MISUSE

Chronic pain affects about 100 million American adults—more than the total affected by heart disease, cancer, and diabetes combined [2]. It also costs the nation up to $635 billion each year in medical treatment and lost productivity and is the leading reason for receiving disability insurance [3,11]. The lifetime prevalence of chronic pain ranges from 54% to 80%, and among adults 21 years of age and older, 14% report pain lasting 3 to 12 months and 42% report pain that persists longer than one year [2]. While 5 to 8 million Americans receive long-term opioids for the management of chronic pain, an estimated 41% of patients with chronic pain report their pain is uncontrolled, and 10% of all adults with pain suffer from severe, disabling chronic pain [11].

The increasing prevalence of chronic pain is the result of multiple factors, including the aging population; rising rates of obesity and obesity-related pain conditions, such as joint deterioration; advances in life-saving trauma interventions; poorly managed post-surgical pain; and greater public awareness of pain as a condition warranting medical attention [2]. In addition, many armed forces veterans have been returning from military action in Afghanistan and Iraq with traumatic injuries and chronic pain, and veterans' care clinicians have been reporting the perception that long-term pain management is lacking support in the veteran healthcare infrastructure [12].

There is a widespread misperception that opioid analgesic prescribing and overdose continues to grow, fueling an opioid epidemic [13,14,15,16,17]. This is refuted by the following data showing that national opioid analgesic prescribing and overdose peaked in 2011 and are in multiyear decline.

According to a report from the National Forensic Laboratory Information System (NFLIS), prescription reports for hydrocodone increased dramatically from 2001 to 2010, but then steadily decreased through 2019. Oxycodone reports increased steadily from 2001 to 2004, and again from 2006 to 2010, and then steadily declined through 2019 [18]. Methadone prescribing data were not captured in the report.

Opioid analgesic-associated overdose fatalities have also decreased since 2011, despite published Centers for Disease Control and Prevention (CDC) data reporting a sharp rise in opioid analgesic fatalities in 2014 [19]. This increase was the result of the CDC adding clandestine fentanyl fatalities to figures for prescription opioids in 2014, a difference of more than 4,000 fatalities [20]. The CDC acknowledged this and presented revised 2014 figures with clandestine fentanyl overdoses removed, which supports the belief that opioid analgesic-associated overdose fatalities peaked in 2011 [21,22,23].

Opioid analgesic prescribing in the United States has declined from the 2011 peak but remains substantially higher than 1990. Before 1990, physicians seldom prescribed opioids for chronic noncancer pain. By the mid-2000s, 1 of 25 adults was prescribed an opioid for chronic pain, and annual opioid analgesic sales totaled more than $9 billion [25]. There is nearly universal agreement that opioid analgesics were injudiciously overprescribed during the 2000s. Interpretation of the broader trend of increased prescribing from 1990 might be viewed by public health professionals as entirely problematic and by pain medicine professionals as necessary in part, given the past neglect of patients in pain. This reflects the polarized nature of pain care and opioid analgesic prescribing in particular. Efforts to reduce opioid analgesic overprescribing and associated overdose have been successful but have come at a cost to patients who have faced increasing barriers to access, including stigma and abuse in a healthcare system, tapering of opioids without consideration for pain or functional improvements, and difficulty finding a physician [14,26].

Many prescribed opioid analgesic fatalities result from the co-ingestion central nervous system (CNS)/respiratory depressants (especially benzodiazepines) or prescribed methadone. According to the National Institute on Drug Abuse (NIDA), deaths involving benzodiazepines rose from 1,135 in 1999 to 11,537 in 2017. In 2021, nearly 14% of persons who died of an opioid overdose also tested positive for benzodiazepines [30,31]. A Canadian study evaluated 607,156 adults prescribed opioids for noncancer pain, and of those whose deaths were related to opioids, co-prescribed benzodiazepines were detected in 84.5% [32]. This is significant considering that dispensed benzodiazepine prescriptions increased more than 36% between 1996 and 2013 [34]. Additionally, many users obtain benzodiazepines by getting prescriptions from more than one doctor, forging prescriptions, or buying the drugs illicitly. Alprazolam and clonazepam are the two most frequently encountered benzodiazepines on the illicit market [18].

OPIOID MISUSE IN FLORIDA

In Florida, misuse of prescription opioids became a serious problem in the 1990s and 2000s, but efforts to stem the problem appear to be working. The rate of drug overdose deaths increased 58.9% during 2003–2010, and in 2009, one in eight deaths in Florida was attributable to drug overdose [35,36]. In 2022, opioids accounted for 79% of fatal drug overdoses in the state [35]. In 2015, Florida experienced an increase in oxycodone-caused deaths, the first in six years [27]. These trends resulted in the enactment of several measures to address prescribing that was inconsistent with best practices, and partnership with the U.S. Drug Enforcement Administration (DEA) to close and prevent "pill mills" from introducing millions of opioid dose units into illicit markets [37,38]. In May 2017, Governor Rick Scott signed an executive order declaring the opioid epidemic a public health emergency, providing additional funding and empowering state health professions to take steps to address this pressing issue [38]. As part of this order, the State Health Officer has issued a standing order for opioid antagonists to ensure emergency responders have access [38]. In 2022, the Florida Department of Health issued a statewide Standing Order for Naloxone, which authorizes pharmacists to dispense certain naloxone formulations to emergency responders for administration to persons exhibiting signs of opioid overdose [24].

An influx of clandestine fentanyl into Florida in early 2014, and several fentanyl analogs and other novel non-pharmaceutical opioids more recently, has largely driven the increases in opioid overdose fatalities. Analyses of data from 2013–2015 indicate sharp increases in overdose fatalities in Florida linked to counterfeit alprazolam, oxycodone, and hydrocodone tablets that contained fentanyl [39]. The decrease in prescription opioid fatalities, offset by increasing overdose fatalities from other opioid and non-opioid agents, reflects the intervention focus on the supply side ("pill mill laws") and neglect of treatment funding that would address the demand side of problematic drug use [40].

In Florida, fatalities with benzodiazepines present peaked in 2010 with 6,188, falling to 1,761 in 2023 (32% were alprazolam) [41]. Other primary contributors to opioid analgesic-related fatalities include alcohol and prescribed methadone [30,42].

In addition to the executive order issued in 2017, several new state laws were passed in 2018 to impose additional legal requirements on controlled substance prescribers [43]. These laws will be discussed in detail later in this course.

4. INITIATION AND MANAGEMENT OF THE PATIENT WITH PAIN

In 2016, the CDC issued updated opioid prescribing guidelines for chronic pain that address when to initiate or continue opioids for chronic pain; opioid selection, dosage, duration, follow-up, and discontinuation; and assessing risk and addressing harms of opioid use [44]. In addition, the CDC further updated guidance against the misapplication of this guideline in 2019, noting that some policies and practices attributed to the guideline were inconsistent with the recommendations [45]. In response to this and to the availability of new evidence, the CDC published an updated guideline in 2022 [4]. The updated clinical practice guideline is intended to achieve improved communication between clinicians and patients about the risks and benefits of pain treatment, including opioid therapy for pain; improved safety and effectiveness for pain treatment, resulting in improved function and quality of life for patients experiencing pain; and a reduction in the risks associated with long-term opioid therapy, including opioid use disorder, overdose, and death [4]. It is important to remember that inappropriately limiting necessary opioid medications to address patients' pain can be damaging and should be avoided. A central tenet of the updated 2022 guideline is that acute, subacute, and chronic pain needs to be appropriately and effectively treated regardless of whether opioids are part of a treatment regimen [4].

However, many guidelines do share common recommendations. These represent the current "conventional wisdom" in opioid analgesic prescribing and can inform healthcare professionals of the best clinical practices in opioid prescribing that include approaches to the assessment of pain and function and pain management modalities. Pharmacologic and nonpharmacologic approaches should be used on the basis of current evidence or best clinical practice. Patients with moderate-to-severe chronic pain without adequate pain relief from non-opioid or nonpharmacologic therapy can be considered for a trial of opioid therapy [44,52]. Initial treatment should always be considered individually determined and as a trial of therapy, not a definitive course of treatment [53].

ACUTE PAIN

Long-term opioid use often begins with treatment of acute pain. When opioids are used for acute pain, clinicians should prescribe the lowest effective dose of immediate-release opioids in a quantity no greater than that needed for the expected duration of severe pain. In most cases, three days or less will be sufficient; more than seven days will rarely be needed [44]. However, payers and health systems should not use the 2022 guideline to set rigid standards related to dosage or duration of opioid therapy. The guideline is not a replacement for clinical judgment or individualized, patient-centered care [5].

Florida law dictates that, for the treatment of acute pain, a prescription for an opioid drug may not exceed a three-day supply; an exception may be made for a seven-day supply if [54]:

- The prescriber, in his or her professional judgment, believes that more than a three-day supply of such an opioid is medically necessary to treat the patient's pain as an acute medical condition.

- The prescriber indicates "ACUTE PAIN EXCEPTION" on the prescription. (For the treatment of pain other than acute pain, a practitioner must indicate "NONACUTE PAIN" on a prescription.)

- The prescriber adequately documents in the patient's medical records the acute medical condition and lack of alternative treatment options that justify deviation from the three-day supply limit.

With postoperative, acute, or intermittent pain, analgesia often requires frequent titration, and the two- to four-hour analgesic duration with short-acting hydrocodone, morphine, and oxycodone is more effective than extended-release formulations. Short-acting opioids are also recommended in patients who are medically unstable or with highly variable pain intensity [55,56,57].

As part of House Bill 21, passed in 2018, the Florida Board of Medicine and the Board of Osteopathic Medicine are required to establish guidelines for prescribing controlled substances for acute pain; these guidelines are forthcoming [54].

PATIENT EVALUATION AND ASSESSMENT OF ADDICTION RISK

Information obtained by patient history, physical examination, and interview, from family members, a spouse, or state prescription drug monitoring program (PDMP), and from the use of screening and assessment tools can help the clinician to stratify the patient according to level of risk for developing problematic opioid behavioral responses (Table 1). Low-risk patients receive the standard level of monitoring, vigilance, and care. Moderate-risk patients should be considered for an additional level of monitoring and provider contact, and high-risk patients are likely to require intensive and structured monitoring and follow-up contact, additional consultation with psychiatric and addiction medicine specialists, and limited supplies of short-acting opioid formulations [44,58].

Table 1: RISK STRATIFICATION FOR PATIENTS PRESCRIBED OPIOIDS

Low Risk

No or well-defined and controlled personal or family history of alcohol/substance use disorder

No or minimal co-occurring psychiatric disorders or medical comorbidities

Age 45 years or older

High levels of pain acceptance and active coping strategies

High motivation and willingness to participate in multimodal therapy, attempting to function at normal levels

Medium Risk

Moderate concomitant psychiatric disorders, well controlled by therapy

Moderate coexisting medical disorders well-controlled by medical therapy and not affected by chronic opioid therapy (e.g., central sleep apnea)

History of personal or family alcoholism/substance abuse/addiction

Willing to participate in multimodal therapy, attempting to function in normal daily life

Pain involving more than three regions of the body

High Risk

Widespread pain without objective signs and symptoms

Pain involving more than three regions of the body

Aberrant drug-related behavior

History of alcoholism or drug misuse, abuse, addiction, diversion, dependency, tolerance, or hyperalgesia

Major psychologic disorders

Age younger than 45 years

Unwilling to participate in multimodal therapy, not functioning close to a near normal lifestyle

Source: [1,59,60,61]

Anxiety disorders, major depressive disorder, and intense emotional distress alter pain perception and response. Intensity and perception of reported pain is also influenced by factors such as mood, cultural background, social supports, and financial resources. A biopsychosocial model is required to inform pain assessment in order to address the biologic basis of pain and presence of social and psychologic contributors [51].

Before deciding to prescribe an opioid analgesic, clinicians should perform and document a detailed patient assessment that includes [1]:

- Pain indications for opioid therapy

- Nature and intensity of pain

- Past and current pain treatments and patient response

- Comorbid conditions

- Pain impact on physical and psychologic function

- Social support, housing, and employment

- Home environment (i.e., stressful or supportive)

- Pain impact on sleep, mood, work, relationships, leisure, and substance use

- Patient history of physical, emotional, or sexual abuse

Depression is perhaps the single most important comorbidity in patients with chronic pain and is vastly underdiagnosed and untreated. Patients with unrecognized and untreated depression are unlikely to respond to opioids and other pain therapies, but successful treatment of depression can promote analgesia [62].

If substance abuse is active, in remission, or in the patient's history, consult an addiction specialist before starting opioids [1]. In active substance abuse, do not prescribe opioids until the patient is engaged in a treatment/recovery program or other arrangements made, such as addiction professional co-management and additional monitoring. When considering an opioid analgesic (particularly those that are extended-release or long-acting), one must always weigh the benefits against the risks of overdose, abuse, addiction, physical dependence and tolerance, adverse drug interactions, and accidental exposure by children [44,63].

Screening and assessment tools can help guide patient stratification according to risk level and inform the appropriate degree of structure and monitoring in the treatment plan. It should be noted that despite widespread endorsement of screening tool use to help determine patient risk level, most tools have not been extensively evaluated, validated, or compared to each other, and evidence of their reliability is poor [64].

Opioid Risk Tool (ORT)

The Opioid Risk Tool (ORT) is a five-item assessment to help predict aberrant drug-related behavior. The ORT is also used to establish patient risk level through categorization into low, medium, or high levels of risk for aberrant drug-related behaviors based on responses to questions of previous alcohol/drug abuse, psychologic disorders, and other risk factors [65,66].

Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R)

The Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R) is a patient-administered, 24-item screen with questions addressing history of alcohol/substance use, psychologic status, mood, cravings, and stress. Like the ORT, the SOAPP-R helps assess risk level of aberrant drug-related behaviors and the appropriate extent of monitoring [67,68].

Screening Instrument or Substance Abuse Potential (SISAP)

The Screening Instrument or Substance Abuse Potential (SISAP) tool is a self-administered, five-item questionnaire addressing history developed to predict the risk of opioid misuse. The SISAP is used to identify patients with a history of alcohol/substance abuse and improve pain management by facilitating focus on the appropriate use of opioid analgesics and therapeutic outcomes in the majority of patients who are not at risk of opioid abuse, while carefully monitoring those who may be at greater risk [69].

CAGE and CAGE-AID

The original CAGE (Cut down, Annoyed, Guilty, and Eye-opener) Questionnaire consisted of four questions designed to help clinicians determine the likelihood that a patient was misusing or abusing alcohol. These same four questions were modified to create the CAGE-AID (adapted to include drugs), revised to assess the likelihood of current substance abuse [70].

Diagnosis, Intractability, Risk, and Efficacy (DIRE) Tool

The Diagnosis, Intractability, Risk, and Efficacy (DIRE) risk assessment tool is a clinician-rated questionnaire that is used to predict patient compliance with long-term opioid therapy [71]. Patients scoring lower on the DIRE tool are poor candidates for long-term opioid analgesia.

Mental Health Screening Tool

The Mental Health Screening Tool is a five-item screen that asks about a patient's feelings of happiness, calmness, peacefulness, nervousness, and depression in the past month [72]. A lower score on this tool is an indicator that the patient should be referred to a specialist for pain management.

CREATING A TREATMENT PLAN

Opioid therapy should be presented as a trial for a pre-defined period (e.g., ≤30 days). The goals of treatment should be established with all patients prior to the initiation of opioid therapy, including reasonable improvements in pain, function, depression, anxiety, and avoidance of unnecessary or excessive medication use [1,44]. The treatment plan should describe therapy selection, measures of progress, and other diagnostic evaluations, consultations, referrals, and therapies. All patients prescribed an opioid for pain related to a traumatic injury (severity score ≥9) should be concurrently prescribed an antagonist (e.g., naloxone) [54].

In opioid-naïve patients, start at the lowest possible dose and titrate to effect. Dosages for opioid-tolerant patients should always be individualized and titrated by efficacy and tolerability [1]. The need for frequent progress and benefit/risk assessments during the trial should be included in patient education. Patients should also have full knowledge of the warning signs and symptoms of respiratory depression.

Prescribers should be knowledgeable of federal and state opioid prescribing regulations. Issues of equianalgesic dosing, close patient monitoring during all dose changes, and incomplete cross-tolerance with opioid conversion should be considered. If necessary, treatment may be augmented, with preference for nonopioid and immediate-release opioids over long-acting/extended-release opioids. Taper opioid dose when no longer needed [63].

Non-Opioid Pain Management Options

Nonpharmacologic Approaches

Several nonpharmacologic approaches are therapeutic complements to pain-relieving medication, lessening the need for higher doses and perhaps minimizing side effects. These interventions can help decrease pain or distress that may be contributing to the pain sensation. Approaches include palliative radiotherapy, complementary/alternative methods, manipulative and body-based methods, and cognitive/behavioral techniques. The choice of a specific nonpharmacologic intervention is based on the patient's preference, which, in turn, is usually based on a successful experience in the past.

Methods to provide distraction from pain come in a wide variety of methods, including reciting poetry, meditating with a calm phrase, watching television or movies, playing cards, visiting with friends, or participating in crafts. Music therapy and art therapy are also becoming more widely used as nonpharmacologic options for pain management.

Non-Opioid Analgesics

Nonopioid analgesics, such as aspirin, acetaminophen (Tylenol), and nonsteroidal anti-inflammatory drugs (NSAIDs), are primarily used for mild pain and may also be helpful as coanalgesics for moderate and severe pain. Acetaminophen is among the safest of analgesic agents, but it has essentially no anti-inflammatory effect. Toxicity is a concern at high doses, and the maximum recommended dose is 3–4 g per day [73]. Acetaminophen should be avoided or given at lower doses in people with a history of alcohol abuse or renal or hepatic insufficiency [73].

NSAIDs are most effective for pain associated with inflammation. Among the commonly used NSAIDs are ibuprofen (Motrin, Advil), naproxen (Aleve, Naprosyn), and indomethacin (Indocin). There are several classes of NSAIDs, and the response differs among patients; trials of drugs for an individual patient may be necessary to determine which drug is most effective [74]. NSAIDs inhibit platelet aggregation, increasing the risk of bleeding, and also can damage the mucosal lining of the stomach, leading to gastrointestinal bleeding. There is a ceiling effect to the nonopioid analgesics; that is, there is a dose beyond which there is no further analgesic effect. In addition, many side effects of nonopioids can be severe and may limit their use or dosing.

Informed Consent and Treatment Agreements

The initial opioid prescription is preceded by a written informed consent or "treatment agreement" [1]. This agreement should address potential side effects, tolerance and/or physical dependence, drug interactions, motor skill impairment, limited evidence of long-term benefit, misuse, dependence, addiction, and overdose. Informed consent documents should include information regarding the risk/benefit profile for the drug(s) being prescribed. The prescribing policies should be clearly delineated, including the number/frequency of refills, early refills, and procedures for lost or stolen medications.

The treatment agreement also outlines joint physician and patient responsibilities. The patient agrees to using medications safely, refraining from "doctor shopping," and consenting to routine urine drug testing (UDT). The prescriber's responsibility is to address unforeseen problems and prescribe scheduled refills. Reasons for opioid therapy change or discontinuation should be listed. Agreements can also include sections related to follow-up visits, monitoring, and safe storage and disposal of unused drugs.

PERIODIC REVIEW AND MONITORING

Evidence Based Practice Recommendation

The CDC recommends that clinicians should evaluate benefits and risks with patients within one to four weeks of starting opioid therapy for subacute or chronic pain or of dosage escalation. Clinicians should regularly re-evaluate benefits and risks of continued opioid therapy with patients.

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm

Last Accessed: August 23, 2024

Strength of Recommendation/Level of Evidence: A4 (Most patients should receive based on clinical experience and observations, observational studies with important limitations, or randomized clinical trials with several major limitations)

When implementing a chronic pain treatment plan that involves the use of opioids, the patient should be frequently reassessed for changes in pain origin, health, and function [1]. This can include input from family members and/or the state PDMP. During the initiation phase and during any changes to the dosage or agent used, patient contact should be increased. At every visit, chronic opioid response may be monitored according to the "5 A's" [1,75]:

- Analgesia

- Activities of daily living

- Adverse or side effects

- Aberrant drug-related behaviors

- Affect (i.e., patient mood)

Signs and symptoms that, if present, may suggest a problematic response to the opioid and interference with the goal of functional improvement include [76]:

- Excessive sleeping or days and nights turned around

- Diminished appetite

- Short attention span or inability to concentrate

- Mood volatility, especially irritability

- Lack of involvement with others

- Impaired functioning due to drug effects

- Use of the opioid to regress instead of re-engaging in life

- Lack of attention to hygiene and appearance

The decision to continue, change, or terminate opioid therapy is based on progress toward treatment objectives and absence of concerning adverse effects and risks of overdose or diversion [1]. Satisfactory therapy is indicated by improvements in pain, function, and quality of life. It is important to remember that for some patients with severe chronic pain, improved function may take longer than pain control or either pain or function (not both) will improve. In some cases, preventing worsening pain/functional impairment is the best achievable outcome. Brief assessment tools to assess pain and function may be useful, as may UDTs. Treatment plans may include periodic pill counts to confirm adherence and minimize diversion.

Involvement of Family

Family members or the partner of the patient can provide the clinician with valuable information that better informs decision making regarding continuing opioid therapy. Family members can observe whether a patient is losing control of his or her life or becoming less functional or more depressed during the course of opioid therapy. They can also provide input regarding positive or negative changes in patient function, attitude, and level of comfort. The following questions can be asked of family members or a spouse to help clarify whether the patient's response to opioid therapy is favorable or unfavorable [76]:

- Is the person's day centered around taking the opioid medication? Response can help clarify long-term risks and benefits of the medication and identify other treatment options.

- Does the person take pain medication only on occasion, perhaps three or four times per week? If yes, the likelihood of addiction is low.

- Have there been any other substance (alcohol or drug) abuse problems in the person's life? An affirmative response should be taken into consideration when prescribing.

- Does the person in pain spend most of the day resting, avoiding activity, or feeling depressed? If so, this suggests the pain medication is failing to promote rehabilitation. Daily activity is essential, and the patient may be considered for enrollment in a graduated exercise program.

- Is the person in pain able to function (e.g., work, do household chores, play) with pain medication in a way that is clearly better than without? If yes, this suggests the pain medication is contributing to wellness.

Assessment Tools

VIGIL

VIGIL is the acronym for a five-step risk management strategy designed to empower clinicians to appropriately prescribe opioids for pain by reducing regulatory concerns and to give pharmacists a framework for resolving ambiguous opioid analgesic prescriptions in a manner that preserves legitimate patient need while potentially deterring diverters. The components of VIGIL are [77]:

- Verification: Is this a responsible opioid user?

- Identification: Is the identity of this patient verifiable?

- Generalization: Do we agree on mutual responsibilities and expectations?

- Interpretation: Do I feel comfortable allowing this person to have controlled substances?

- Legalization: Am I acting legally and responsibly?

The foundation of VIGIL is a collaborative physician/pharmacist relationship [77,78].

Current Opioid Misuse Measure (COMM)

The Current Opioid Misuse Measure (COMM) is a 17-item patient self-report assessment designed to help clinicians identify misuse or abuse in patients with chronic pain. Unlike the ORT and the SOAPP-R, the COMM identifies aberrant behaviors associated with opioid misuse in patients already receiving long-term opioid therapy [58]. Sample questions include: In the past 30 days, how often have you had to take more of your medication than prescribed? In the past 30 days, how much of your time was spent thinking about opioid medications (e.g., having enough, taking them, dosing schedule)?

Pain Assessment and Documentation Tool (PADT)

Guidelines by the CDC, the Federation of State Medical Boards (FSMB), and the Joint Commission stress the importance of documentation from both a healthcare quality and medicolegal perspective. Research has found widespread deficits in chart notes and progress documentation for patients with chronic pain who are receiving opioid therapy, and the Pain Assessment and Documentation Tool (PADT) was designed to address these shortcomings [79]. The PADT is a clinician-directed interview, with most sections (e.g., analgesia, activities of daily living, adverse events) consisting of questions asked of the patient. However, the potential aberrant drug-related behavior section must be completed by the physician based on his or her observations of the patient [80].

The Brief Intervention Tool

The Brief Intervention Tool is a 26-item, "yes-no," patient-administered questionnaire used to identify early signs of opioid abuse or addiction. The items assess the extent of problems related to drug use in several areas, including drug use-related functional impairment [72].

Urine Drug Tests

UDTs may be used to monitor adherence to the prescribed treatment plan and to detect unsanctioned drug use. They should be used more often in patients receiving addiction therapy, but clinical judgment is the ultimate guide to testing frequency (Table 2) [81]. The CDC 2016 guideline recommends clinicians should use UDT before starting opioid therapy and consider UDT at least annually to assess for prescribed medications as well as other controlled prescription drugs and illicit drugs [44]. However, this recommendation was based on low-quality evidence that indicates little confidence in the effect estimate, and it is not included in the 2022 updated guideline [4].

Table 2: PATIENT RISK LEVEL AND FREQUENCY OF MONITORING

Monitoring Tool

Patient Risk Level

Low

Medium

High

Urine drug test

Every one to two years

Every 6 to 12 months

Every three to six months

State prescription drug monitoring program

Twice per year

Three times per year

Four times per year

Source: [81]

CONCURRENT USE OF BENZODIAZEPINES

In 2021, nearly 14% of persons who died of an opioid overdose also tested positive for benzodiazepines, a class of sedative medication commonly prescribed for anxiety, insomnia, panic attack, and muscle spasm [8]. Benzodiazepines work by raising the level of the neurotransmitter gamma-aminobutyric acid (GABA) in the brain. Common formulations include diazepam, alprazolam, and clonazepam. Combining benzodiazepines with opioids is unsafe because both classes of drug cause central nervous system depression and sedation and can decrease respiratory drive—the usual cause of overdose fatality. Both classes have the potential for drug dependence and addiction.

The CDC recommends that healthcare providers use caution when prescribing benzodiazepines concurrently with opioids whenever possible [4]. If a benzodiazepine is to be discontinued, the clinician should taper the medication gradually, because abrupt withdrawal can lead to rebound anxiety and complications such as hallucinations, seizures, delirium tremens, and, in rare instances, death. The rate of tapering should be individualized [4].

CONSULTATION AND REFERRAL

It is important to seek consultation or patient referral when input or care from a pain, psychiatry, addiction, or mental health specialist is necessary. Clinicians who prescribe opioids should become familiar with opioid addiction treatment options (including licensed opioid treatment programs for methadone and office-based opioid treatment for buprenorphine) if referral is needed [1].

Ideally, providers should be able to refer patients with active substance abuse who require pain treatment to an addiction professional or specialized program. In reality, these specialized resources are scarce or non-existent in many areas [1]. Therefore, each provider will need to decide whether the risks of continuing opioid treatment while a patient is using illicit drugs outweigh the benefits to the patient in terms of pain control and improved function [82].

MEDICAL RECORDS

As noted, documentation is a necessary aspect of all patient care, but it is of particular importance when opioid prescribing is involved. All clinicians should maintain accurate, complete, and up-to-date medical records, including all written or telephoned prescription orders for opioid analgesics and other controlled substances, all written instructions to the patient for medication use, and the name, telephone number, and address of the patient's pharmacy [1]. Good medical records demonstrate that a service was provided to the patient and that the service was medically necessary. Regardless of the treatment outcome, thorough medical records protect the prescriber.

PATIENT EDUCATION ON THE USE AND DISPOSAL OF OPIOIDS

Patients and caregivers should be counseled regarding the safe use and disposal of opioids. As part of its mandatory Risk Evaluation and Mitigation Strategy (REMS) for extended-release/long-acting opioids, the FDA has developed a patient counseling guide with information on the patient's specific medications, instructions for emergency situations and incomplete pain control, and warnings not to share medications or take them unprescribed [63]. A copy of this form may be accessed online at https://www.accessdata.fda.gov/drugsatfda_docs/rems/ERLA_opioids_2016-04-26_Patient_Counseling_Document.pdf[83].

When prescribing opioids, clinicians should provide patients with the following information [63]:

- Product-specific information

- Taking the opioid as prescribed

- Importance of dosing regimen adherence, managing missed doses, and prescriber contact if pain is not controlled

- Warning and rationale to never break or chew/crush tablets or cut or tear patches prior to use

- Warning and rationale to avoid other central nervous system depressants, such as sedative-hypnotics, anxiolytics, alcohol, or illicit drugs

- Warning not to abruptly halt or reduce the opioid without physician oversight of safe tapering when discontinuing

- The potential of serious side effects or death

- Risk factors, signs, and symptoms of overdose and opioid-induced respiratory depression, gastrointestinal obstruction, and allergic reactions

- The risks of falls, using heavy machinery, and driving

- Warning and rationale to never share an opioid analgesic

- Rationale for secure opioid storage

- Warning to protect opioids from theft

- Instructions for disposal of unneeded opioids, based on product-specific disposal information

There are no universal recommendations for the proper disposal of unused opioids, and patients are rarely advised of what to do with unused or expired medications [84]. According to the Office of National Drug Control Policy, most medications that are no longer necessary or have expired should be removed from their containers, mixed with undesirable substances (e.g., cat litter, used coffee grounds), and put into an impermeable, nondescript container (e.g., disposable container with a lid or a sealed bag) before throwing in the trash [85]. Any personal information should be obscured or destroyed. The FDA recommends that certain medications, including oxycodone/acetaminophen (Percocet), oxycodone (OxyContin tablets), and transdermal fentanyl (Duragesic Transdermal System), be flushed down the toilet instead of thrown in the trash [85]. The FDA provides a free toolkit of materials (e.g., social media images, fact sheets, posters) to raise awareness of the serious dangers of keeping unused opioid pain medicines in the home and with information about safe disposal of these medicines. The Remove the Risk Outreach toolkit is updated regularly and can be found at https://www.fda.gov/drugs/ensuring-safe-use-medicine/safe-opioid-disposal-remove-risk-outreach-toolkit[86]. Patients should be advised to flush prescription drugs down the toilet only if the label or accompanying patient information specifically instructs doing so and no other disposal method is appropriate. In 2023, the FDA issued a letter requiring all manufacturers of opioid analgesics dispensed in outpatient settings to submit a proposed modification to the Opioid Analgesic REMS. The modification requires manufacturers to make available prepaid mail-back envelopes to outpatient pharmacies and other opioid dispensers as an opioid analgesic disposal option for patients [9].

The American College of Preventive Medicine has established best practices to avoid diversion of unused drugs and educate patients regarding drug disposal [84]:

- Consider writing prescriptions in smaller amounts.

- Educate patients about safe storing and disposal practices.

- Give drug-specific information to patients about the temperature at which they should store their medications. Generally, the bathroom is not the best storage place. It is damp and moist, potentially resulting in potency decrements, and accessible to many people, including children and teens, resulting in potential theft or safety issues.

- Ask patients not to advertise that they are taking these types of medications and to keep their medications secure.

- Refer patients to community "take back" services overseen by law enforcement that collect controlled substances, seal them in plastic bags, and store them in a secure location until they can be incinerated. Contact your state law enforcement agency or visit https://www.dea.gov to determine if a program is available in your area.

DISCONTINUING OPIOID THERAPY

The decision to continue or end opioid prescribing should be based on a physician-patient discussion of the anticipated benefits and risks. An opioid should be discontinued with resolution of the pain condition, intolerable side effects, inadequate analgesia, lack of improvement in quality of life despite dose titration, deteriorating function, or significant aberrant medication use [1,44].

Clinicians should provide physically dependent patients with a safely structured tapering protocol. Withdrawal is managed by the prescribing physician or referral to an addiction specialist. Patients should be reassured that opioid discontinuation is not the end of treatment; continuation of pain management will be undertaken with other modalities through direct care or referral.

As a side note, cannabis use by patients with chronic pain receiving opioid therapy has traditionally been viewed as a treatment agreement violation that is grounds for termination of opioid therapy. However, some now argue against cannabis use as a rationale for termination or substantial treatment and monitoring changes, especially considering the increasing legalization of medical use at the state level [82].

CONSIDERATIONS FOR NON-ENGLISH-PROFICIENT PATIENTS

For patients who are not proficient in English, it is important that information regarding the risks associated with the use of opioids and available resources be provided in their native language, if possible. When there is an obvious disconnect in the communication process between the practitioner and patient due to the patient's lack of proficiency in the English language, an interpreter is required. Interpreters can be a valuable resource to help bridge the communication and cultural gap between patients and practitioners. Interpreters are more than passive agents who translate and transmit information back and forth from party to party. When they are enlisted and treated as part of the interdisciplinary clinical team, they serve as cultural brokers who ultimately enhance the clinical encounter. In any case in which information regarding treatment options and medication/treatment measures are being provided, the use of an interpreter should be considered. Print materials are also available in many languages, and these should be offered whenever necessary.

5. CRISIS INTERVENTION: MANAGEMENT OF OVERDOSE

Individuals who have first contact with persons suspected of experiencing an opioid-related overdose are in the position to intervene to prevent the potentially devastating consequences. In these cases, care begins with crisis intervention directed at immediate survival by reversing the potentially lethal effects of overdose with an opioid antagonist.

Opioid antagonists have obvious therapeutic value in the treatment of opioid overdose. A 2012 study found that wider distribution of naloxone and training in its administration might have prevented numerous deaths from opioid overdoses in the United States [87]. Since the first community-based opioid overdose prevention program began distributing naloxone in 1996, more than 10,000 overdoses have been reversed [87].

In Florida, licensed healthcare providers may prescribe and pharmacists may dispense opioid antagonists (even as a standing order) for at-risk individuals, these individuals' relatives or other caregivers, and emergency responders to be used in their course of duties [88]. Emergency responders include (but are not limited to) law enforcement officers, paramedics, and emergency medical technicians [88]. As noted, there is a statewide standing order for naloxone for all emergency responders in Florida [38].

OPIOID ANTAGONISTS

Relatively minor changes in the structure of an opioid can convert an agonist drug into one with antagonistic actions at one or more opioid receptor types. Opioid antagonists include naloxone, naltrexone, and nalmefene. Interestingly, naloxone also appears to block the analgesic effects of placebo medications and acupuncture. These agents have no abuse potential [89].

In response to acute overdose, the short-acting opioid antagonist naloxone is considered the gold standard, and it remains the most widely used opioid antagonist for the reversal of overdose and opioid-related respiratory depression. It acts by competing with opioids at receptor sites in the brain stem, reversing desensitization to carbon dioxide, and reversing or preventing respiratory failure and coma. There is no evidence that subcutaneous or intramuscular use is inferior to intravenous naloxone. This has prompted some states to pass laws allowing opioid antagonists to be available to the general public for administration outside the healthcare setting to treat acute opioid overdose [90]. In 2014, the FDA approved naloxone as an autoinjector dosage form for home use by family members or caregivers, and in 2015, the agency approved intranasal naloxone after a fast-track designation and priority review. Intranasal naloxone is indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression [91,92].

When used for opioid overdose, a dose of 0.4–2 mg of naloxone is administered intravenously, intramuscularly, or subcutaneously [93]. If necessary, the dose may be repeated every two to three minutes for full reversal. For ease of use, naloxone is also available in a pre-filled auto-injection device. The intranasal formulation is available in doses of 2 mg, 4 mg, or 8 mg [93]. In 2023, the FDA approved Narcan, the first over-the-counter naloxone nasal spray [69]. Narcan is available as a 3-, 4-, or 8 -mg single dose, administered in one nostril [93]. It is important that standard Advanced Cardiac Life Support (ACLS) protocols be continued while naloxone is being administered and that medical treatment (at a healthcare facility) be given immediately.

6. COMPLIANCE WITH STATE AND FEDERAL LAWS

In response to the rising incidence in prescription opioid abuse, addiction, diversion, and overdose in the late 1990s and 2000s, the FDA has mandated opioid-specific REMS to reduce the potential negative patient and societal effects of prescribed opioids. Other elements of opioid risk mitigation include FDA partnering with other governmental agencies, state professional licensing boards, and societies of healthcare professionals to help improve prescriber knowledge of appropriate and safe opioid prescribing and safe home storage and disposal of unused medication [76].

Several regulations and programs at the state level have been enacted in an effort to reduce prescription opioid abuse, diversion, and overdose, including [94]:

- Physical examination required prior to prescribing

- Tamper-resistant prescription forms

- Pain clinic regulatory oversight

- Prescription limits

- Prohibition from obtaining controlled substance prescriptions from multiple providers

- Patient identification required before dispensing

- Immunity from prosecution or mitigation at sentencing for individuals seeking assistance during an overdose

CONTROLLED SUBSTANCES LAWS/RULES

The DEA is responsible for formulating federal standards for the handling of controlled substances. In 2011, the DEA began requiring every state to implement electronic databases that track prescribing habits, referred to as PDMPs. Specific policies regarding controlled substances are administered at the state level [95].

According to the DEA, drugs, substances, and certain chemicals used to make drugs are classified into five distinct categories or schedules depending upon the drug's acceptable medical use and the drug's abuse or dependency potential [96]. The abuse rate is a determinate factor in the scheduling of the drug; for example, Schedule I drugs are considered the most dangerous class of drugs with a high potential for abuse and potentially severe psychologic and/or physical dependence.

In Florida, the prescribing, dispensing, and consumption of certain controlled substances are governed by Chapter 893 of the Florida Statutes [97]. This law establishes the standards for controlled substance prescribing, including reporting system requirements, for prescribers and pharmacists in Florida. At the time of publication of this course, the Florida schedule of controlled substances aligns with the DEA schedule [43].

THE ELECTRONIC FLORIDA ONLINE REPORTING OF CONTROLLED SUBSTANCES EVALUATION PROGRAM

Emerging trends and patterns of prescription opioid abuse, addiction, and overdose are monitored by several industry and government agencies through data collection from a variety of sources. These include health insurance claims; the Automation of Reports and Consolidated Orders System, a DEA-run program that monitors the flow of controlled substances from manufacturing through distribution to retail sale or dispensing; the Treatment Episode Data Set, which monitors treatment admissions; the National Center for Health Statistics state mortality data; and the Researched Abuse, Diversion, and Addiction-Related Surveillance System, which monitors prescription drug abuse, misuse, and diversion [98].

Almost all states, including Florida, have enacted PDMPs to facilitate the collection, analysis, and reporting of information on controlled substances prescribing and dispensing [1]. All prescribers must consult the Electronic Florida Online Reporting of Controlled Substances Evaluation (E-FORCSE) to review a patient's controlled substance dispensing history before prescribing or dispensing a controlled substance to a patient 16 years of age or older [99]. This is mandated even for existing patients and should be done each time a controlled substance is prescribed or dispensed [43]. If the system is nonoperational or cannot be accessed due to a temporary technologic or electrical failure, the prescription may be issued (with documentation of the exception) for up to a maximum three-day supply.

All clinicians who dispense controlled substances are required to report the action to E-FORCSE as soon as possible, but no later than the close of the next business day [99]. This should be repeated each time the substance is dispensed. This reporting requirement is waived in certain circumstances, including for [99]:

- All acts of administration of a controlled substance

- The dispensing of a controlled substance in the healthcare system of the Department of Corrections

- The dispensing of a controlled substance to a person younger than 16 years of age

7. IDENTIFICATION OF DRUG DIVERSION/SEEKING BEHAVIORS

Research has more closely defined the location of prescribed opioid diversion into illicit use in the supply chain from the manufacturer to the distributor, retailer, and the end user (the patient with pain). This information carries with it substantial public policy and regulatory implications. The 2021 National Survey on Drug Use and Health asked non-medical users of prescription opioids how they obtained their most recently used drugs [100]. Among persons 12 years of age or older, 33.9% obtained their prescription opioids from a friend or relative for free, 39.3% got them through a prescription from one doctor (vs. 17.3% in 2009–2010), 7.3% bought them from a friend or relative, and 3.7% took them from a friend or relative without asking [100]. Other sources included a drug dealer or other stranger (7.9%); multiple doctors (3.2%); and theft from a doctor's office, clinic, hospital, or pharmacy (0.7%) [100].

As discussed, UDTs can give insight into patients who are misusing opioids. A random sample of UDT results from 800 patients with pain treated at a Veterans Affairs facility found that 25.2% were negative for the prescribed opioid while 19.5% were positive for an illicit drug/unreported opioid [50]. Negative UDT results for the prescribed opioid do not necessarily indicate diversion but may indicate the patient halted his/her use due to side effects, lack of efficacy, or pain remission. The concern arises over the increasingly stringent climate surrounding clinical decision-making regarding aberrant UDT results and that a negative result for the prescribed opioid or a positive UDT may serve as the pretense to terminate a patient rather than guide him/her into addiction treatment or an alternative pain management program [49].

In addition to aberrant urine screens, there are certain behaviors that are suggestive of an emerging opioid use disorder. The most suggestive behaviors are [47,48,82]:

- Selling medications

- Prescription forgery or alteration

- Injecting medications meant for oral use

- Obtaining medications from nonmedical sources

- Resisting medication change despite worsening function or significant negative effects

- Loss of control over alcohol use

- Using illegal drugs or non-prescribed controlled substances

- Recurrent episodes of:

- Prescription loss or theft

- Obtaining opioids from other providers in violation of a treatment agreement

- Unsanctioned dose escalation

- Running out of medication and requesting early refills

Behaviors with less association with opioid misuse include [47,48,82]:

- Aggressive demands for more drug

- Asking for specific medications

- Stockpiling medications during times when pain is less severe

- Using pain medications to treat other symptoms

- Reluctance to decrease opioid dosing once stable

- In the earlier stages of treatment:

- Increasing medication dosing without provider permission

- Obtaining prescriptions from sources other than the pain provider

- Sharing or borrowing similar medications from friends/family

8. INTERVENTIONS FOR SUSPECTED OR KNOWN DRUG DIVERSION

There are a number of actions that prescribers and dispensers can take to prevent or intervene in cases of drug diversion. These actions can be generally categorized based on the various mechanisms of drug diversion.

Prevention is the best approach to addressing drug diversion. As noted, the most common source of nonmedical use of prescribed opioids is from a family member or friend, through sharing, buying, or stealing. To avoid drug sharing among patients, healthcare professionals should educate patients on the dangers of sharing opioids and stress that "doing prescription drugs" is the same as "using street drugs" [84]. In addition, patients should be aware of the many options available to treat chronic pain aside from opioids. To prevent theft, patients should be advised to keep medications in a private place and to refrain from telling others about the medications being used.

Communication among providers and pharmacies can help to avoid inappropriate attainment of prescription drugs through "doctor shopping." Prescribers should keep complete and up-to-date records for all controlled substance prescribing. When possible, electronic medical records should be integrated between pharmacies, hospitals, and managed care organizations [84]. It is also best practice to periodically request a report from the E-FORCSE to evaluate the prescribing of opioids to your patients by other providers [84].

When dealing with patients suspected of drug seeking/diversion, first inquire about prescription, over-the-counter, and illicit drug use and perform a thorough examination [46,84]. Pill counting and/or UDT may be necessary to investigate possible drug misuse. Photo identification or other form of identification and social security number may be required prior to dispensing the drug, with proof of identity documented fully. If a patient is displaying suspicious behaviors, consider prescribing for limited quantities [46].

If a patient is found to be abusing prescribed opioids, this is considered a violation of the treatment agreement and the clinician must make the decision whether or not to continue the therapeutic relationship. If the relationship is terminated, it must be done ethically and legally. The most significant issue is the risk of patient abandonment, which is defined as ending a relationship with a patient without consideration of continuity of care and without providing notice to the patient. The American Medical Association Code of Ethics states, "Physicians have an obligation to support continuity of care for their patients. While physicians have the option of withdrawing from a case, they cannot do so without giving notice to the patient, the relatives, or responsible friends sufficiently long in advance of withdrawal to permit another medical attendant to be secured" [33]. The notice of termination should be sent in writing, should specifically note the causes for the termination, and should give a period of time prior to termination, usually 30 days [29]. Patients may also be given resources and/or recommendations to help them locate a new clinician.

Patients with chronic pain found to have an ongoing substance abuse problem or addiction should be referred to a pain specialist for continued treatment. Theft or loss of controlled substances is reported to the DEA. If drug diversion has occurred, the activity should be documented and a report to law enforcement should be made [28].

9. CASE STUDY

An unemployed man, 64 years of age, is brought to an emergency department by ambulance, after his wife returned from work to find him lying on the couch, difficult to arouse and incoherent. He has a past history of hypertension, diabetes (non-insulin dependent), mild chronic obstructive pulmonary disease, and chronic back and shoulder pain, for which he has been prescribed hydrocodone/acetaminophen for many years. His wife reports that while he seemed his usual self when she left for work that morning, he had, in recent weeks, been more withdrawn socially, less active, and complained of greater discomfort from the back and shoulder pain. She knows little about his actual medication usage and expresses concern that he may have been taking more than the prescribed amount of "pain medicine."

On evaluation, the patient is somnolent and arouses to stimulation but is non-communicative and unable to follow commands. His blood pressure is normal, he is afebrile, and there are no focal neurologic deficits. Oxygen saturation, serum glucose, and routine laboratory studies (blood counts and metabolic profile) are normal except for mild elevation in blood urea nitrogen (BUN) and creatinine; the urine drug screen is negative except for opioids. Additional history from the family indicates that the patient has been admitted to other hospitals twice in the past three years with a similar presentation and recovered rapidly each time "without anything being found."

Following admission, the patient remains stable-to-improved over the next 12 to 18 hours. By the following day, he is awake and conversant and looks comfortable. On direct questioning, he reports recent symptoms of depression but no suicidal ideation. The patient describes an increased preoccupation with his pain syndrome, difficulty sleeping at night, and little physical activity during the day, in part because of physical discomfort. He is vague about his medication regimen and admits to taking "occasional" extra doses of hydrocodone for pain relief.

The family is instructed to bring in all his pill bottles from home, which they do. In addition to the hydrocodone prescribed by his primary care physician, there is a recent refill of a prescription for the medication given to the patient at the time of his last hospital discharge six months earlier.

ASSESSMENT

A full evaluation, including radiographic studies and consultation with psychiatry and physical therapy, is completed. The working diagnosis for the patient's acute illness is toxic encephalopathy caused by the sedative side effects of opioid medication on the CNS. It is explained that the combination of his advancing age and diabetes likely reduced the efficiency of his kidneys in clearing the medication and its metabolites, making him more susceptible to CNS sedation. It is noted that the patient and his wife have little understanding of the rationale, proper use and safeguards, potential side effects, and limited effectiveness of opioid use for chronic pain.

In addition, the patient is diagnosed with poorly controlled chronic pain syndrome secondary to osteoarthritis and degenerative disc disease; exacerbating factors include deconditioning and reactive depression. The use of an opioid analgesic, at least for the near term, is considered appropriate, if dosed properly, monitored closely, and integrated into a comprehensive, multidisciplinary plan that includes treatment of depression and the use of adjunctive, nonpharmacologic modalities of care. In the setting of possible early diabetic nephropathy, the option of utilizing an NSAID, except for very brief periods of break-through pain, is not considered to be a safe option.

At discharge, and in consultation with his primary care physician, a written treatment and management plan addressing all aspects of the patient's care is presented to the patient and his wife for discussion and consent. Among the key issues addressed are:

- Goals: Improvement in subjective pain experience; improved function of daily living manifested by regular walking exercise and improved social interaction with family and friends; relief of depression; and in the long-term, anticipated withdrawal of opioid medication and resumption of part-time work and/or volunteer community activity

- Outpatient physical therapy and back exercise program to increase core muscular strength, improve flexibility, reduce pain, and increase exercise tolerance

- Patient and family counseling regarding the safe use, dosage regulation, side effects, and proper disposal of opioid medication

- Joint patient-physician responsibilities as regards to regular follow-up, monitoring of goals and treatment effectiveness, avoidance of "doctor-shopping," and assent to single provider for prescription medication

FOLLOW-UP

On follow-up six weeks after discharge, the patient is noticeably improved. He reports that he feels stronger and is sleeping better. His affect is brighter, and he is getting out more. He has maintained his physical therapy and exercise routine and is compliant with his medication. Though he still has pain, it is noticeably less and he is coping better. He and his wife are encouraged by his progress, particularly in regard to his improved functional status.

10. CONCLUSION

For patients suffering from pain, prescribed opioid analgesics may substantially lessen pain, distress, and impairment. Inappropriate overprescribing and overdose related to opioid analgesics increased dramatically in the 2000s. These trends are in multi-year reversal, but patient safety and risk mitigation remains no less important, and clinical tools, guidelines, and recommendations are available for use when prescribing opioids to patients with pain. By implementing these tools, the clinician can effectively address issues related to the clinical management of opioid prescribing, opioid risk management, regulations surrounding the prescribing of opioids, and problematic opioid use by patients. In doing so, healthcare professionals are more likely to achieve a balance between the benefits and risks of opioid prescribing, optimize patient attainment of therapeutic goals, and avoid the risk to patient outcome, public health, and viability of their own practice imposed by deficits in knowledge.

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Evidence-Based Practice Recommendations Citations

1. Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC Clinical practice guideline for prescribing opioids for pain—United States, 2022. MMWR. 2022;71(3):1-95. Available at https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm. Last accessed August 23, 2024.

90120 • Pulmonary Embolism

Dalia Saha, MD

www.netce.com

Copyright © 2023 NetCE, All rights reserved.

Pulmonary embolism (PE) is very common in both inpatient and outpatient settings. It should be one of the first considerations when a patient presents with acute chest pain and shortness of breath. There is typically a very high mortality and morbidity rate associated with PE. A variety of treatment options are at the forefront for ensuring that patients are given the best possible outcome.

Table of Contents

90120 • Pulmonary Embolism

Course Overview

Audience

Accreditations & Approvals

Designations of Credit

Individual State Nursing Approvals

Special Approvals

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Division Planners

Division Planners Disclosure

Director of Development and Academic Affairs

Director Disclosure Statement

About the Sponsor

Disclosure Statement

Implicit Bias in Health Care

1. INTRODUCTION

2. EPIDEMIOLOGY

3. PATHOPHYSIOLOGY

4. DIAGNOSIS

DIAGNOSTIC WORKUP

GENETIC TESTING

CLINICAL SCORING SYSTEMS

5. TREATMENT

INITIAL MANAGEMENT

PRIMARY PHARMACOTHERAPY

SURGICAL MANAGEMENT

SECONDARY PREVENTION

6. PE IN THE OUTPATIENT SETTING

7. PE AND COVID-19

8. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

90120 • Pulmonary Embolism

Education Category. Medical / Surgical

Release Date. 09/01/2023

Expiration Date. 08/31/2026

Course Overview

Pulmonary embolism (PE) is very common in both inpatient and outpatient settings. It should be one of the first considerations when a patient presents with acute chest pain and shortness of breath. There is typically a very high mortality and morbidity rate associated with PE. A variety of treatment options are at the forefront for ensuring that patients are given the best possible outcome.

Audience

This course is designed for physicians, PAs, and nurses involved in assessing, triaging, and managing patients with suspected pulmonary embolism.

Accreditations & Approvals

In support of improving patient care, TRC Healthcare/NetCE is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. NetCE is accredited by the International Accreditors for Continuing Education and Training (IACET). NetCE complies with the ANSI/IACET Standard, which is recognized internationally as a standard of excellence in instructional practices. As a result of this accreditation, NetCE is authorized to issue the IACET CEU.

Designations of Credit

This activity was planned by and for the healthcare team, and learners will receive 2 Interprofessional Continuing Education (IPCE) credit(s) for learning and change. NetCE designates this enduring material for a maximum of 2 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. NetCE designates this continuing education activity for 2 ANCC contact hour(s). NetCE designates this continuing education activity for 1 pharmacology hour(s) for physician assistants. NetCE designates this continuing education activity for 1 pharmacotherapeutic/pharmacology contact hour(s). NetCE designates this continuing education activity for 2.4 hours for Alabama nurses. Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 2 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Completion of this course constitutes permission to share the completion data with ACCME. Successful completion of this CME activity, which includes participation in the evaluation component, enables the learner to earn credit toward the CME and/or Self-Assessment requirements of the American Board of Surgery's Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit. This activity has been approved for the American Board of Anesthesiology’s® (ABA) requirements for Part II: Lifelong Learning and Self-Assessment of the American Board of Anesthesiology’s (ABA) redesigned Maintenance of Certification in Anesthesiology Program® (MOCA®), known as MOCA 2.0®. Please consult the ABA website, www.theABA.org, for a list of all MOCA 2.0 requirements. Maintenance of Certification in Anesthesiology Program® and MOCA® are registered certification marks of the American Board of Anesthesiology®. MOCA 2.0® is a trademark of the American Board of Anesthesiology®. This activity has been designated for 2 Lifelong Learning (Part II) credits for the American Board of Pathology Continuing Certification Program. Through an agreement between the Accreditation Council for Continuing Medical Education and the Royal College of Physicians and Surgeons of Canada, medical practitioners participating in the Royal College MOC Program may record completion of accredited activities registered under the ACCME's "CME in Support of MOC" program in Section 3 of the Royal College's MOC Program. NetCE is authorized by IACET to offer 0.2 CEU(s) for this program. AACN Synergy CERP Category A.

Individual State Nursing Approvals

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This activity is designed to comply with the requirements of California Assembly Bill 1195, Cultural and Linguistic Competency.

Course Objective

The purpose of this course is to provide healthcare professionals with the knowledge and clinical strategies necessary to optimally triage and treatment patients with pulmonary embolism.

Learning Objectives

Upon completion of this course, you should be able to:

1. Define a thromboembolic event.

2. Explain pathogenesis, risk factors, and demographics of pulmonary embolism (PE).

3. Review the diagnostic workup of PE.

4. Compare the different types of PE treatments in both inpatient and outpatient settings.

Faculty

Dalia Saha, MD, is a board-certified internal medicine physician with more than 15 years of clinical experience. With experience in both academic and private healthcare settings, Dr. Saha has vast exposure to many aspects of patient care and clinical medicine. Always interested in the didactic component of health care, Dr. Saha works on the education committee for the American College of Physicians and is an instructor and teaching staff for medical students and residents in George Washington University and Johns Hopkins Medical Schools. Lauded by her colleagues for her dedication and work ethic in the field of medicine, she has been awarded the Top Doctor Award in Washington, DC.

Faculty Disclosure

Contributing faculty, Dalia Saha, MD, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Division Planners

John M. Leonard, MD

Mary Franks, MSN, APRN, FNP-C

Division Planners Disclosure

The division planners have disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Director of Development and Academic Affairs

Sarah Campbell

Director Disclosure Statement

The Director of Development and Academic Affairs has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

About the Sponsor

The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.

Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.

Disclosure Statement

It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.

Implicit Bias in Health Care

The role of implicit biases on healthcare outcomes has become a concern, as there is some evidence that implicit biases contribute to health disparities, professionals' attitudes toward and interactions with patients, quality of care, diagnoses, and treatment decisions. This may produce differences in help-seeking, diagnoses, and ultimately treatments and interventions. Implicit biases may also unwittingly produce professional behaviors, attitudes, and interactions that reduce patients' trust and comfort with their provider, leading to earlier termination of visits and/or reduced adherence and follow-up. Disadvantaged groups are marginalized in the healthcare system and vulnerable on multiple levels; health professionals' implicit biases can further exacerbate these existing disadvantages.

Interventions or strategies designed to reduce implicit bias may be categorized as change-based or control-based. Change-based interventions focus on reducing or changing cognitive associations underlying implicit biases. These interventions might include challenging stereotypes. Conversely, control-based interventions involve reducing the effects of the implicit bias on the individual's behaviors. These strategies include increasing awareness of biased thoughts and responses. The two types of interventions are not mutually exclusive and may be used synergistically.

1. INTRODUCTION

Pulmonary embolism (PE) is very common in both inpatient and outpatient settings [1,2]. It should be one of the first considerations when a patient presents with acute-onset dyspnea, shortness of breath, and chest pain. Other common symptoms include cough, hemoptysis, diaphoresis, and feverishness.

A PE is an abrupt occlusion of the pulmonary artery and/or one of its branches. The occlusion may consist of blood clot/thrombus, air, fat, or malignancy/tumor originating in another part of the body, which dislodges and travels through the venous system to the right side of the heart and thence the pulmonary vasculature. In most cases, PE arises from deep vein thrombophlebitis in the lower legs or pelvis, following trauma, surgery, infection, or an acquired hypercoagulable state.

The natural history of PE is variable. PE may be single or multiple (pulmonary emboli), small and clinically silent, large or recurrent with progressive obliteration of the pulmonary vascular bed, causing cardiorespiratory failure. Symptomatic PE is commonly associated with significant morbidity and mortality risk; the challenge for clinical care providers is early recognition and prompt therapeutic intervention to relieve pulmonary artery obstruction and prevent additional pulmonary emboli, any one of which could prove fatal [1,2]. With modern technology, which can detect small embolic events, the condition is identified much earlier, making possible effective treatment prior to complete hemodynamic collapse [1,2,3]. Assessment and prevention in outpatient settings have also led to improvements in mortality. Research indicates that small, subclinical pulmonary emboli probably occur with some frequency but are transient in nature and go unnoticed; however,when there is predisposition to venous stasis (e.g., inflammation, injury, heart failure, coagulopathy), single large or recurrent PE becomes a challenging clinical illness requiring prompt diagnosis and treatment.

Classification of PE typically categorizes the disease as hemodynamically stable or unstable. The most common type is hemodynamically stable, which can range from small, mildly symptomatic or asymptomatic PE (previously referred to as low-risk PE or small PE) to those who present with right ventricular dysfunction but who are hemodynamically stable (previously referred to as submassive or intermediate-risk PE) [3,4]. While PE characterized by right ventricular dysfunction can be hemodynamically stable, more severe (unstable) disease is characterized by the presence of systemic arterial hypotension, which indicates at least half of the pulmonary vascular tree is affected [4,5]. Hemodynamically unstable PE (previously referred to as massive or high-risk PE) will result in significant hypotension. Hemodynamic instability is defined as the presence of cardiac arrest requiring resuscitation, or obstructive shock or persistent hypotension not caused by other pathologies [36].

2. EPIDEMIOLOGY

The annual incidence of PE is difficult to pinpoint but is estimated to be about 60 to 70 cases per 100,000 population [6]. General autopsy studies from all-cause mortality have found PE, variable in number and age, to be present in 30% to 45% of cases [6,7,8,9].

Behind only stroke and coronary artery disease, PE is one of the most common types of cardiovascular disease. It is more common in patients 60 to 70 years of age, with the highest incidence in patients 70 to 80 years of age. Although death following a diagnosis of PE is relatively common, as high as 30%, many of these patients have coexisting serious conditions, such as cancer, recent surgery, or sepsis. The direct mortality associated with undiagnosed/untreated PE during the course of diagnosis and treatment is about 5% to 8%. An estimated 10% of patients with acute PE die suddenly; approximately two-thirds of patients who die from PE do so within two hours of presentation. The mortality rate for those treated for hemodynamically unstable PE is about 20%, and those with cardiogenic shock have a mortality rate of 25% to 30%. Those with a hemodynamically stable PE have a mortality rate of 1% to 25%, depending on the degree of right ventricular dysfunction [2,4,5,10].

3. PATHOPHYSIOLOGY

Most commonly, a PE occurs when a deep vein thrombus detaches and migrates, or embolizes, into the pulmonary circulation. This can lead to blockage of the pulmonary vasculature, causing a ventilation-perfusion (VQ) mismatch and impairing gas exchange and circulation. PE is more common in the lower lung fields, compared with the upper ones, and both lungs are typically involved. Peripheral PE, as opposed to central PE, can lead to a pulmonary infarction coupled with alveolar hemorrhage. As further obstruction of the pulmonary artery occurs, there is an increase in dead space ventilation and elevation of pulmonary arterial pressure by increasing pulmonary vascular resistance. This further worsens VQ mismatch, with vascular occlusion of the arteries.

Various serum factors are released during a PE formation, including serotonin and thromboxane, which are produced from activated platelets [1,2,4]. This induces a cascade of hormonal triggers and related vasoconstriction. Pulmonary arterial pressure increases, which worsens right ventricular afterload and can lead to right ventricular failure and eventually left ventricular system failure. Further clinical progression will lead to a myocardial ischemia due to inadequate coronary circulatory flow, systemic hypotension, and eventual death [1,4,5].

4. DIAGNOSIS

A strict (confirmatory) diagnosis of PE would require direct anatomic evidence of pulmonary artery obstruction, which by modern imaging technique (e.g., computed tomography [CT] angiography) would involve invasive measures and exposure to radiation. As the size and distribution (severity) of PE are variable, the preferred strategy for selecting diagnostic testing relies on degree of clinical suspicion, clinical judgment, and assessment of pre-test probability. Selection of noninvasive testing to rule out the diagnosis, based on the assessed clinical probability of PE, has proved effective in reducing the use of CT imaging, thereby minimizing lung and breast-tissue exposure to irradiation [27]. The differential diagnosis includes heart failure, pneumothorax, pneumonia, sepsis, acute chest syndrome, chronic obstructive pulmonary disease (COPD) exacerbation, and anxiety or other psychotropic illnesses. A systematic review and meta-analysis found that a history of sudden dyspnea, syncope, thrombophlebitis, previous deep vein thrombosis, leg swelling, active cancer, or recent surgery was associated with an increased probability of PE [54]. An inability to increase alveolar oxygen pressure (PaO2) greater than 8.0 kPa (60 mm Hg) despite high-flow oxygen should also raise suspicion for PE.

When a patient does not speak the same language as the clinician, a professional interpreter should be consulted to ensure accurate communication. A retrospective chart review found that, for non-English-speaking patients suspected of having sustained a PE, the positive diagnostic yield of pulmonary angiogram for those who requested an interpreter (7.37%) was nearly double that of those who did not request an interpreter (3.23%) [49].

DIAGNOSTIC WORKUP

Vital Signs

In initial evaluation, vital signs such as blood pressure, heart rate, and rapid estimation of oxygenation by pulse oximetry are critical to assessing severity of vascular compromise and the stability of the patient. Arterial blood gas (ABG) testing will confirm if a patient has hypoxemia and can be used to obtain the arterial-alveolar gradient to determine if there is a PE or other VQ mismatch [10,11,12,13].

D-dimer Level

Assessment of D-dimer levels can be used for screening purposes and to rule out PE if the pretest probability is intermediate or low. D-dimer is a byproduct of intrinsic fibrinolysis. It is considered to be a highly sensitive test for the absence of PE and has a very high negative predictive value. A normal D-dimer level effectively rules out PE or deep vein thromboembolism. In the event that the d-dimer is elevated, further testing (e.g., computed tomography [CT] angiography, planar VQ scanning) can be performed [10; 14; 15; 16]. Because the test is not specific, an elevated finding is not diagnostic. The specificity of D-dimer decreases with age, and the use of age-adjusted cut-offs is recommended for patients older than 50 years of age. The formula is age (years) x 10 mcg/L for patients older than 50 years of age.

Cardiac Biomarkers

Cardiac biomarker testing may also be useful, particularly as it can identify other diagnoses (e.g., myocardial infarction) [10,11,17]. It may help identify signs of right ventricular strain and/or ischemia. An elevated brain natriuretic peptide (BNP) level may indicate right ventricular dysfunction, and higher levels correlate with greater severity of dysfunction.

Various cardiac troponins have also been assessed for diagnostic significance in patients with PE. While these measurements are not diagnostic, elevated troponin is significantly associated with higher mortality in patients with PE [18].

Imaging

Diagnostic imaging is indicated for patients in whom PE cannot be ruled out based on clinical assessment and noninvasive testing. For these patients, CT pulmonary angiography is usually an easily accessible diagnostic imaging modality. It is fast, accurate, and both specific and sensitive. It is also useful for identifying other lung pathology, such as pneumonia and effusions [15,16]. However, it does require that the patient have good renal function due to the use of iodinated contrast, and it also entails lung and breast-tissue irradiation. Ventilation-perfusion single-photon-emission CT (VQ scan) is a low-radiation option to minimize radiation exposure in younger patients.

Chest x-ray is nonspecific but can help identify pleural effusions and diaphragmatic changes. The classic Westermark sign, which shows a clarified area (loss of vascular markings) distal to a large occluded vessel, and Hampton hump, a dome-shaped, pleural-based opacification, may be present on x-ray. These findings are strongly specific for PE (92% and 82%, respectively) but are not sensitive (14% and 22%, respectively). Chest x-ray can also assist in ruling out pneumonia as part of the differential.

VQ scans visualize areas that are ventilated but not perfused (i.e., VQ mismatch). This testing requires more time, is less specific than CT angiography, and should be done with clinical correlation. However, it is the imaging modality of choice for patients with suspected PE and normal chest x-ray for whom CT angiography is contraindicated, including those with impaired kidney function and pregnant patients. Normal ventilation is 4 L air/minute, and normal perfusion is 5 L blood/minute; thus, a normal VQ ratio is 0.8. A high VQ ratio (>0.8) indicates that the patient's ventilation is exceeding perfusion, while a low VQ ratio indicates a VQ mismatch caused by poor ventilation. When blood is diverted away from the occluded section, overperfusion can occur in the normally ventilated regions. The modified Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED-II) criteria score the probability of PE based on VQ scan findings (Table 1).

Table 1: MODIFIED PROSPECTIVE INVESTIGATION OF PULMONARY EMBOLISM DIAGNOSIS (PIOPED-II) CRITERIA

Probability of PE

Criteria

High probability

Two or more large mismatched segmental perfusion defects or the arithmetic equivalent of moderate and/or large defects

Normal perfusion or very low probability

No perfusion defects

Nonsegmental perfusion defects without other perfusion defects in either lung

Perfusion defects smaller than corresponding chest x-ray opacity

One to three small subsegmental perfusion defects

Two or more matched ventilation and perfusion defects with a regionally normal chest x-ray and some areas of normal perfusion elsewhere

Solitary triple-matched defect in a single segment in the middle or upper lung zone

Stripe sign

Large pleural effusion without other perfusion defects in either lung

Low or intermediate probability

All other findings

Source: [19]

Duplex ultrasonography for detection of lower extremity venous thrombi is a useful noninvasive test to assess risk and probability in a patient suspected of having PE. It has both high sensitivity and specificity for thrombus [14,20,21,22]. However, a negative test result does not rule out PE, as the thrombus may have dislodged and embolized prior to the testing.

Electrocardiogram

Electrocardiographic signs of right ventricle strain, such as T wave inversions in V1–V4, QR pattern in V1, the S1Q3T3 pattern, and incomplete or complete right bundle-branch block, are useful but insensitive for the assessment of right ventricle dysfunction in acute PE. However, the presence of right ventricular strain on electrocardiogram has been shown to correlate with the extent of pulmonary vascular obstruction and outcomes of acute PE [10,11,12,14,17,24].

Echocardiogram

Echocardiography can demonstrate if there was a clot in the right atrium or ventricle and can also be used to show if there are signs of right ventricular dilatation and hypokinesis [12]. When performed, echocardiography has been shown to reduce other testing and lead to more aggressive early therapy [12,22].

Pulmonary Arteriography

Pulmonary arteriography is a rare test typically performed only on patients with suspected PE for whom CT and chest x-ray are not feasible. It may also be used with cardiac catheterization to assess patients who have chronic thromboembolic pulmonary hypertension to determine if they are good candidates for pulmonary endarterectomy.

GENETIC TESTING

Factor V Leiden (FVL) and prothrombin (PT) genetic variants are associated with an increased risk of future venous thrombosis or PE. Genetic tests for FVL and PT variants are widely available and commonly used. One current use of these tests is to inform decisions regarding anticoagulant medication in order to decrease the risk of future clots (i.e., secondary prevention). The independent Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group found enough evidence to recommend against routine testing for FVL and PT gene variants in adults who have idiopathic venous thromboembolism, since longer term preventive treatment with anticoagulant medication offers similar benefits to patients whether or not they have these genetic variations. They also recommend against routine testing for adult family members who do not have a history or symptoms of venous thromboembolism, when the testing is conducted to help decide whether to treat them preventively with anticoagulant medication [50]. However, for patients with venous thromboembolism associated with commonly recognized modifiable risk factors (e.g., contraceptive use, estrogen replacement), genetic testing may help guide preventive treatment decisions.

CLINICAL SCORING SYSTEMS

The Wells criteria (Table 2) and the PE Rule-Out Criteria (PERC) assist clinicians with determining clinical probability for PE [14]. One of the important criteria in the determination of PE is if there is a more likely alternate diagnosis, and this is somewhat subjective. If the Wells criteria are used, a score greater than 6 is considered high probability of PE, 2–6 is moderate probability, and less than 2 is low probability. A modification of the Wells criteria simplifies scoring to either likely (>4) or unlikely (≤4).

Table 2: WELLS CRITERIA

Clinical Features

Points

Clinical symptoms of deep vein thromboembolism

3

Other diagnosis less likely than PE

3

Tachycardia (>100 beats per minute)

1.5

Immobilization for three or more days OR surgery in the past four weeks

1.5

Previous deep vein thromboembolism or PE

1.5

Hemoptysis

1

Malignancy

1

Source: [25]

The PERC rule was developed for use in emergency care to rule-out PE in patients whose likelihood of PE is low (<15%), so unnecessary diagnostic workups can be avoided. The PERC rule includes [26]:

- Age younger than 50 years

- Heart rate less than 100 beats per minute

- Oxygen saturation of at least 95%

- No prior deep vein thrombosis or PE

- No unilateral leg swelling

- No hormonal estrogen use

- No hemoptysis

- No history of surgery or trauma requiring prior hospitalization in the previous four weeks

If all eight criteria are fulfilled, the patient's risk for PE can be considered sufficiently low and further testing is not necessary [10,11,13,17]. In practice, clinicians tend to overestimate the probability of PE. In cases in which the clinician judges that the patient is very unlikely to have PE but is uncertain whether the estimated likelihood is <15%, the PERC rule or Wells score ≤4 in combination with a normal D-dimer level is reassuring and can be used to safely rule out PE.

5. TREATMENT

INITIAL MANAGEMENT

The mainstays of initial PE management focus on rapid assessment of clinical severity and stabilization of the patient. As noted, when a patient initially presents, the most critical pieces of information lie in their vital signs (e.g., heart rate, blood pressure, oxygenation). The initial goal for the patient with PE is to maintain oxygen levels. If mechanical circulatory support is required, cardiopulmonary bypass permits right ventricular recovery by decompressing the dilated and dysfunctional ventricle through diversion of the cardiac output to a pump and oxygenator [51]. Alternatively, venoarterial extracorporeal membrane oxygenation (VA-ECMO) functions similarly but is more mobile, allowing for support to be initiated and continued in more diverse settings.

For patients who are hemodynamically unstable, intravenous fluid should be given with caution, because this can lead to right ventricular overload. Hemodynamically stable, low-risk patients should receive anticoagulation alone; those who are at high risk and have hemodynamic compromise may require systemic thrombolysis or surgical- versus catheter-directed therapy. Those who are at intermediate risk have more complicated cases and can be treated with either anticoagulation alone or anticoagulation with potential procedures. As discussed, the risk level will depend on the severity of right ventricular dysfunction on echocardiography, the degree of troponin elevation, the amount of oxygen and vasopressor required, and clot burden and location [10,11,12,13]. The American Society of Hematology (ASH) recommends that patients with PE at low risk for complications be offered home treatment rather than hospital treatment [27].

The therapeutic treatment strategy for patients with a new diagnosis of PE, and venous thromboembolism in general, can be divided into three phases: initial treatment (the first three weeks after diagnosis), primary treatment (three to six months, or longer), and secondary prevention (beginning upon completion of primary therapy and continuing indefinitely) [27]. For primary treatment of patients with PE, whether unprovoked or provoked by a transient or chronic risk factor, the ASH suggests a shorter course of anticoagulation therapy (3 to 6 months) be preferred over a longer course (6 to 12 months). Anticoagulation therapy may be continued indefinitely in select patients for whom the risk for bleeding complications is less than the risk of recurrent PE.

PRIMARY PHARMACOTHERAPY

In selecting initial pharmacotherapy, European guidelines and a 2022 clinical practice review recommend that treatment be guided by risk stratification of PE as high, intermediate, or low based on the patient's clinical presentation [36,55]. Approximately 5% of patients present with signs of high-risk PE (e.g., shock, end-organ hypoperfusion/dysfunction, blood pressure <90 mm Hg) not caused by arrhythmia, hypovolemia, or intrinsic heart failure [55]. Intermediate-risk patients are those who present with echocardiographic evidence of right heart strain, elevated cardiac biomarkers, or both; those who are hemodynamically stable with normal cardiac biomarkers and no evidence of right ventricular strain are classified as having low-risk PE. Patients classified as having high-risk PE are candidates for initial reperfusion (thrombolytic) therapy; those with intermediate- and low-risk PE should receive immediate anticoagulation therapy [36,55]. Treatment should be started promptly whenever PE is strongly suspected and the patient's risk of serious bleeding complications is low. Pharmacotherapy options for initial anticoagulation include intravenous unfractionated heparin, subcutaneous low-molecular-weight heparin, subcutaneous fondaparinux, factor Xa inhibitors (e.g., apixaban, rivaroxaban), direct thrombin inhibitors (e.g., dabigatran), and intravenous argatroban for patients with heparin-induced thrombocytopenia.

Thrombolytic Therapy

Patients who present with high-risk PE warrant consideration for immediate reperfusion therapy, there being no contraindications (e.g., brain metastases, bleeding disorders, recent surgery) [36,55]. Intravenous systemic thrombolysis is a readily available option for reperfusion. Thrombolytic agents act to dissolve the thrombus by converting plasminogen into plasmin. With early thrombus resolution, the elevated pulmonary arterial pressure/resistance and accompanying right ventricular dysfunction improve rapidly. Thrombus resolution within the first 24 hours in particular is much faster in thrombolytic therapy than with heparin [52].

The first recombinant tissue plasminogen activator, and the most commonly used thrombolytic agent used in patients with PE, is alteplase (rtPA); other available agents include streptokinase, urokinase, reteplase, and tenecteplase. The main indication for thrombolysis is high-risk PE with thrombus and hemodynamic instability. rtPA is administered at a rate of 50 mg per hour for two hours; the dose should be reduced for patients with weight less than 65 kg. If streptokinase, is used, a loading dose of 250,000 IU is given, followed by and infusion of 100,000 IU per hour for 24 hours. Urokinase is started with a loading dose of 4,400 IU and an infusion of 4,400 IU/kg/hour for 12 hours [29,52].

According to the American College of Physicians, catheter-directed thrombolytic therapy can be considered if cardiopulmonary deterioration is imminent [53]. There is some evidence that ultrasound-assisted catheter-directed thrombolysis is superior to heparin anticoagulation alone in improving right ventricular dilatation within 24 hours without major bleeding complications or recurrent embolism. Absolute contraindications to thrombolytic therapy include history of intracranial hemorrhage, known structural cerebral vascular lesion, known malignant intracranial neoplasm, recent history (within past three months) ischemic stroke, active bleeding (excluding menses), and recent history (within past three months) significant closed-head trauma or facial trauma [52,53].

Oral Anticoagulants

Evidence Based Practice Recommendation

The European Society of Cardiology (ESC) and European Respiratory Society (ERS) recommends direct oral anticoagulants (DOACs) as first choice anticoagulants over warfarin even in those who are warfarin eligible.

https://academic.oup.com/eurheartj/article/41/4/543/5556136

Last Accessed: August 18, 2023

Level of Evidence: Expert Opinion/Consensus Statement

Direct oral anticoagulants (DOACs) (factor Xa inhibitors or direct thrombin inhibitors) are recommended over vitamin K antagonists (e.g., warfarin) for most patients; however, those with renal insufficiency (i.e., creatinine clearance <30 mL/min), moderate-to-severe liver disease, or antiphospholipid syndrome are not good candidates for DOAC therapy [27].

Factor Xa inhibitors such as apixaban and rivaroxaban have the advantage of fixed dosing and no need for monitoring laboratory values, both of which are required of vitamin K antagonists. Rivaroxaban and apixaban do not require any kind of overlap with an intravenous agent. Dose reductions are indicated for those with renal insufficiency. Apixaban can be used in patients with renal insufficiency and is safe for patients on dialysis [2,28]. Reversal agents are available: idarucizumab for reversal of dabigatran, and andexanet alfa apixaban and rivaroxaban.

The half-life of factor Xa inhibitors is much shorter than the half-life of warfarin. If bleeding develops and requires reversal, a four-factor prothrombin complex concentrate can be used. Direct thrombin inhibitors such as dabigatran can also be used for treatment for these patients. For those with heparin-induced thrombocytopenia, intravenous argatroban or subcutaneous fondaparinux can be used for anticoagulation. The dosage varies according to agent (Table 3).

Table 3: ORAL ANTICOAGULATION THERAPY

Agent

Dosage

Vitamin K Antagonist

Warfarin

5 mg once daily for most patientsa

Direct Thrombin Inhibitor

Dabigatran etexilate

After at least 5 days of initial therapy with a parenteral anticoagulant, transition to oral 150 mg twice daily.

Factor Xa Inhibitors

Apixaban

10 mg twice daily for 7 days, followed by 5 mg twice daily

Edoxaban

After at least 5 days of initial therapy with a parenteral anticoagulant, transition to once-daily oral 60 mg for patients >60 kg or 30 mg for patients ≤60 kg.

Rivaroxaban

15 mg twice daily with food for 21 days, followed by 20 mg once daily with food

aFor patients who are expected to be more sensitive to warfarin, a starting dose of 2.5 mg daily is recommended. After three days of treatment, dosage should be adjusted based on INR values.

Source: [29]

Drug-drug interactions with DOACs are common and may increase risk of bleeding or thrombosis. Important DOAC interactions are often due to medications that affect cytochrome P450 (CYP450) enzymes or transport proteins or increase bleeding propensity.

Warfarin, which used to be the mainstay of therapy, is no longer considered first choice, as the other DOACs have better safety profiles and patient satisfaction. Bleeding is common with warfarin usage and is more likely to be develop in patients who are older (65 years of age and older) and with comorbidities, such as diabetes, recent myocardial infarction, and other chronic conditions (e.g., kidney disease, stroke). If it develops, bleeding can be reversed with vitamin K at a dose of 2.5–10 mg intravenously or orally. Fresh frozen plasma can also be used with elevated prothrombin complex concentrates [5,30,31]. Drug interactions are also a concern with warfarin. Another potential complication is warfarin-induced necrosis, which is more likely to occur in patients with a history of heparin-induced thrombocytopenia. If warfarin is used, the dose should be adjusted to reach and maintain a target goal of an international normalized ratio (INR) of 2.5 (range: 2.0–3.0).

Heparin

Intravenous unfractionated heparin has a short half-life and can be reversed with protamine [28]. An initial bolus is given followed by an infusion, during which partial thromboplastin time (PTT) values are monitored. The dosage is based on a weight-based protocol. Although relatively safe to use, the pharmacokinetics of this drug are unpredictable, resulting in the need for close clinical monitoring. However, due to its short half-life, it can quickly be reversed, if needed.

Subcutaneous low-molecular-weight heparin has several advantages, including increased bioavailability and more predictable anticoagulation, as opposed to intravenous unfractionated heparin [28,32]. There is also decreased incidence of bleeding and potentially better outcomes. Low-molecular-weight heparin is given at a dosage of 1 mg/kg body weight. All heparin products include similar bleeding risk profiles as well as a risk for thrombocytopenia, urticaria, and anaphylaxis. For patients with breakthrough deep vein thrombosis and/or PE during therapeutic warfarin treatment, the ASH suggests using low-molecular-weight heparin over DOAC therapy [27].

Fondaparinux

Fondaparinux is a factor Xa antagonist given subcutaneously in the management of acute PE instead of heparin. Advantages include fixed-dose administration once or twice per day, lack of need for clinical monitoring, and lower risk of thrombocytopenia. The dose is 5 mg for patients who weigh less than 50 kg, 7.5 mg for patients weighing 50–100 kg, and 10 mg for those weighing more than 100 kg. The dose should be adjusted in persons with kidney disease. It is contraindicated for patients with a creatinine clearance less than 30 mL/minute. When used for thromboprophylaxis, some experts recommend a 50% dose reduction or use of low-dose heparin instead [29].

SURGICAL MANAGEMENT

Pulmonary embolectomy is indicated for patients that have high- or intermediate-risk PE with contraindications to thrombolysis; failed thrombolysis or catheter-assisted embolectomy; or hemodynamic shock that is likely to cause death before thrombolysis can take effect [52]. Surgical pulmonary embolectomy is a procedure performed on cardiopulmonary bypass through a midline sternotomy, involving either central or femoral vessel initiation. Management involves moderate hypothermia for better visualization and protection during moments of reduced cardiopulmonary bypass flows. Aortic cross-clamping and cardioplegic arrest are sometimes unnecessary to prevent negative effects on right ventricular recovery [51]. Dual incisions offer improved visualization and better clot extraction. Various methods, such as suction, retrograde perfusion, manual manipulation, or balloon-tipped catheters, can aid clot extraction, but balloon catheters may lead to increased postprocedural complications [51].

SECONDARY PREVENTION

Maintenance anticoagulation for secondary prevention is done for patients who have extensive clot burden or to reduce the risk of new clot formation. There are multiple pharmacotherapeutic options for this phase of treatment, including factor Xa inhibitors (e.g., apixaban), dabigatran, and aspirin. Warfarin and low-molecular-weight heparin are second-line options.

Factor Xa anticoagulants, such as apixaban and rivaroxaban, are the most common first-line option for secondary prevention. Though warfarin was previously used, research has shown a decreased risk for intracranial hemorrhage with factor Xa anticoagulants compared with warfarin. When used for maintenance therapy, the dosage of apixaban is 2.5 mg twice per day; the dosage of rivaroxaban is 10 mg once per day. Cessation of therapy should be considered again after 6 to 12 months [4,5].

Those with incidental PE, very small clot burdens, and minimal symptoms should likely be treated in an outpatient setting—unless other risk factors are present. However, patients with hemodynamically unstable PE (e.g., extensive clot burden, low blood pressure, abrupt clinical deterioration) often require an intensive care stay.

Aspirin has also been studied for long-term maintenance therapy and is more effective than placebo. However, anticoagulation is typically preferred over aspirin. When anticoagulation therapy is initiated in patients with PE with stable cardiovascular disease who were previously taking aspirin for cardiovascular risk modification, clinicians should consider suspending the aspirin during anticoagulation therapy. Enoxaparin sodium or low-molecular-weight heparin may be used in high-risk cancer patients with recurrent PE [2,28].

Duration of Pharmacotherapy for Secondary Prevention

As noted, the duration of anticoagulation therapy for secondary prevention is dependent on a variety of factors, such as bleeding risk and risk factors for PE, and can range from three months to lifelong therapy [3,28,32]. If the patient experienced PE following a transient risk factor (i.e., a provoked event), such as immobilization or recent surgery or trauma, at least three months of treatment is warranted, after which therapy should be reassessed. However, those who have chronic provoked factors for PE, such as active cancer, a hypercoagulable state, or chronic immobility, may benefit from long-term (indefinite) anticoagulation therapy. When creating the treatment plan, the goal is to weigh the benefits of PE and deep vein thrombosis prevention with the risk of anticoagulation events (e.g., bleeding). Risk factors for bleeding include age 65 years or older, frequent falls, alcohol abuse, renal failure, previous stroke, diabetes, and anemia.

For patients who develop PE provoked by a transient risk factor and who have a history of a previous thrombotic event also provoked by a transient risk factor, the ASH guideline panel suggests stopping anticoagulation after completion of the primary treatment phase of therapy [27].

6. PE IN THE OUTPATIENT SETTING

When possible, patients at assessed low risk for complications (i.e., minimal risk of PE-related death) should be discharged from the hospital and continue to receive treatment at home. Such patients are hemodynamically stable, with have no right heart strain and normal cardiac biomarkers. Most patients with low-risk PE can be treated with an oral anticoagulant or a brief period of low-molecular-weight heparin followed by oral therapy. The presence or absence of comorbidities and proper care and anticoagulation therapy, which can be provided on an outpatient basis, should be noted. Scoring systems have been developed to stratify these patients, including the HESTIA rule (Table 4), the PE Severity Index (PESI), and its simplified version (sPESI) (Table 5) [33,34,35].

Table 4: HESTIA EXCLUSION CRITERIA FOR OUTPATIENT TREATMENT

Criteria

Pointsa

Hemodynamically unstable

1

Thrombolysis or embolectomy needed

1

Active bleeding or high risk of bleeding

1

More than 24 hours on supplemental oxygen needed to maintain oxygen saturation >90%

1

PE diagnosed during anticoagulant treatment

1

Severe pain requiring IV pain medication for more than 24 hours

1

Medical or social reason for hospital treatment for more than 24 hours (e.g., infection, malignancy, no support system)

1

Creatinine clearance of <30 mL/min

1

Severe liver impairment

1

Pregnancy

1

History of heparin-induced thrombocytopenia

1

aA score of 1 or more is defined as high risk and rules out outpatient treatment.

Source: [36]

Table 5: THE ORIGINAL PULMONARY EMBOLISM SEVERITY INDEX (PESI) AND THE SIMPLIFIED PESI (sPESI) CLINICAL RISK SCORES

Parameter

PESI

sPESI

Age

Age in years

1 if older than 80 years

Male sex

10

—

Cancer diagnosis

30

1

Chronic heart failure

Chronic pulmonary disease

10

10

1

Pulse ≥110 beats per minute

20

1

Systolic blood pressure <100 mm Hg

30

1

Respiratory rate ≥30 breaths per minute

20

—

Temperature <36°C

20

—

Altered mental status

60

—

Arterial oxyhemoglobin saturation <90%

20

1

Risk Stratification (PESI)

Class I (≤65 points)

Very low 30-day mortality risk (0% to 1.5%)

Class II (66–85 points)

Low mortality risk (1.7% to 3.5%)

Class III (86–105 points)

Moderate mortality risk (3.2% to 7.1%)

Class IV (106–125 points)

High mortality risk (4% to 11.4%)

Class V (>125 points)

Very high mortality risk (10% to 24.5%)

sPESI Score

0 points

30-day mortality risk 1%

1 or more points

30-day mortality risk 10.9%

Source: [37,56,57]

The PESI scales identify those with a low risk of 30-day mortality [33]. The criteria used include age, sex, history of cancer, history of chronic pulmonary disease, heart rate, systolic blood pressure, and oxygen saturation [33]. The scales relate the risk stratification score to an associated 30-day mortality and risk of death and can assist in identifying patients who may appropriately be managed at home. The patient's social situation, access to supportive care, and ability to transfer to higher level care should all be considered before shifting to outpatient management.

Anticoagulation options to manage confirmed PE in an outpatient setting include subcutaneous low-molecular-weight heparin, fondaparinux, unfractionated heparin, or DOACs [28,32,38,39]. The treatment duration is generally three to six months [38,39]. Following the initial three-month period, the decision of whether or not to continue treatment will be made based on continued risk of recurrent thromboembolic balanced against the risks of continued anticoagulation [4,5,40].

7. PE AND COVID-19

Hospitalized patients with advanced COVID-19 may have laboratory signs of a coagulopathy and increased risk for arterial and venous thromboembolic complications, including PE [41,42,43]. The pathogenesis is unknown but likely involves some combination of systemic inflammation, endothelial dysfunction, platelet activation, immobility, and stasis of blood flow [43]. The earliest abnormalities are elevated D-dimer levels and mild thrombocytopenia; with disease progression, fibrin degradation products are elevated and prothrombin time becomes prolonged. Laboratory measure of coagulation factors in patients hospitalized with COVID-19 provides a way to track disease severity. The presence of an elevated D-dimer on admission carries a poor prognosis and has been associated with increased risk of requiring mechanical ventilation, intensive care unit admission, and mortality [43,44]. The most frequently reported complications of COVID-19 coagulopathy are deep venous thrombosis and PE. In a prospective study of 150 critically ill patients from two centers in France, 25 patients developed PE and 3 developed deep vein thrombosis, despite prophylactic anticoagulation [45]. In a report of 184 patients with severe COVID-19 from three centers in the Netherlands, the cumulative incidence of venous thromboembolism was 27%, including PE in 80% of the cases affected [46]. Other centers have reported lower rates. Among 393 patients from New York, venous thromboembolism was diagnosed in only 13 patients (3.3%), 10 of whom were on mechanical ventilation [47]. The National Institutes of Health recommends all hospitalized patients with COVID-19 who experience rapid deterioration of pulmonary, cardiac, or neurological function or sudden, localized loss of peripheral perfusion be evaluated for thromboembolic disease [48].

At present, there are limited data available to inform clinical management around prophylaxis or treatment of venous thromboembolic complications in patients with COVID-19 [41]. One source of interim guidance recommends regularly monitoring hemostatic markers—namely D-dimer, prothrombin time, and platelet count—in all patients presenting with COVID-19 and prophylactic use of low-molecular-weight heparin in all hospitalized patients, unless there are contraindications [43]. The National Institutes of Health recommends that hospitalized, nonpregnant adults with COVID-19 who do not require intensive-level care and have no evidence of venous thromboembolism receive a therapeutic dose of heparin if their D-dimer levels are above the upper normal limit and they require low-flow oxygen, as long as they do not have an increased risk of bleeding [48].

Contraindications for the use of therapeutic anticoagulation in patients with COVID-19 include [48]:

- Platelet count <50 x 10^9/L

- Hemoglobin <8 g/dL

- Need for dual antiplatelet therapy

- Bleeding within the past 30 days that required an emergency department visit or hospitalization

- History of a bleeding disorder or an inherited or active acquired bleeding disorder

Low-molecular-weight heparin is preferred over unfractionated heparin because of its ease of administration and because low-molecular-weight heparin was the predominant form of heparin used in the clinical trials for COVID-19 [48].

In patients without venous thromboembolism who have started treatment with therapeutic doses of heparin, treatment should continue for 14 days or until they are transferred to intensive care or discharged from the hospital, whichever comes first. A prophylactic dose of heparin is also recommended for patients who do not meet the criteria for receiving therapeutic heparin or are not receiving a therapeutic dose of heparin for other reasons, unless a contraindication exists [48].

For those patients who develop a PE in the setting of a COVID-19 infection, about 50% will report persistent fatigue, reduced exercise tolerance, and dyspnea [14,23]. Of these patients, one-half will also have signs of right ventricular dysfunction on echocardiogram after the diagnosis is made, referred to as post-PE syndrome. This further leads to dyspnea on exertion, damage to the venous valves in the leg, prolonged lower extremity swelling and aching, venous ulcers, and impaired quality of life.

8. CONCLUSION

PE is a common cause of acute-onset breathlessness and chest pain, often confused for many other diagnoses. It should remain on one's clinical differential due to the fact that it can be life-threatening and is treatable if caught and managed early. A variety of treatment options are at the forefront for ensuring that patients are given the best possible outcome.

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13. Panos RJ, Barish RA, Whye DW Jr, Groleau G. The electrocardiographic manifestations of pulmonary embolism. J Emerg Med. 1988;6:301-307.

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15. Ryu JH, Pellikka PA, Froehling DA, Peters SG, Aughenbaugh GL. Saddle pulmonary embolism diagnosed by CT angiography: frequency, clinical features and outcome. Respir Med. 2007;101:1537-1542.

16. Sista AK, Kuo WT, Schiebler M, Madoff DC. Stratification, imaging, and management of acute massive and submassive pulmonary embolism. Radiology. 2017;284:5-24.

17. Söhne M, Ten Wolde M, Boomsma F, Reitsma JB, Douketis JD, Büller HR. Brain natriuretic peptide in hemodynamically stable acute pulmonary embolism. J Thromb Haemost. 2006;4:552-556.

18. El-Menyar A, Sathian B, Al-Thani H. Elevated serum cardiac troponin and mortality in acute pulmonary embolism: systematic review and meta-analysis. Respir Med. 2019;157:26-35.

19. Derenoncourt P-R, Felder GJ, Royal HD, et al. Ventilation-perfusion scan: a primer for practicing radiologists. Radiographics. 2021;41(7):2047-2070.

20. Singh M, Guha D, Patterson B. Clot in transit: point-of-care ultrasound diagnosis of acute pulmonary embolism. J Emerg Med. 2021;60(5):659-660.

21. Le Gal G, Righini M, Roy PM, et al. Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med. 2006;144:165-171.

22. Joseph D, Lee E, Tabatabai R, Chilstrom M. Pulmonary embolism in transit: direct visualization of a PE passing through the heart using bedside ultrasonography. CJEM. 2016;18(4):313-314.

23. Torbicki A, Perrier A, Konstantidines S, et al. Guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2008;29:2276-2315.

24. Gerges C, Skoro-Sajer N, Lang IM. Right ventricle in acute and chronic pulmonary embolism (2013 Grover Conference series). Pulm Circ. 2014;4(3):378-386.

25. van Belle A, Buller HR, Huisman MV, et al. Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. JAMA. 2006;295:172.

26. Kline JA, Courtney DM, Kabrhel C, et al. Prospective multicenter evaluation of the pulmonary embolism rule-out criteria. J Thromb Haemost. 2008;6(5):772-780.

27. Ortel TL, Neumann I, Ageno W, et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism. Blood Adv. 2020;4(19):4693-4738.

28. Stevens SM, Woller SC, Kreuziger LB, et al. Antithrombotic therapy for VTE disease: second update of the chest guideline and expert panel report. Chest. 2021;160:e545-608.

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30. Klarin D, Busenkell E, Judy R, et al. Genome-wide association analysis of venous thromboembolism identifies new risk loci and genetic overlap with arterial vascular disease. Nat Genet. 2019;51:1574.

31. Lindström S, Wang L, Smith EN, et al. Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism. Blood. 2019;134:1645.

32. Hylek EM, Regan S, Henault LE, et al. Challenges to the effective use of unfractionated heparin in the hospitalized management of acute thrombosis. Arch Intern Med. 2003;163:621-627.

33. Yamashita Y, Morimoto T, Amano H, et al. Validation of simplified PESI score for identification of low-risk patients with pulmonary embolism: From the COMMAND VTE Registry. Eur Heart J Acute Cardiovasc Care. 2020;9(4):262-270.

34. Yamashita Y, Morimoto T, Amano H, et al. Usefulness of simplified pulmonary embolism severity index score for identification of patients with low-risk pulmonary embolism and active cancer: from the COMMAND VTE Registry. Chest. 2020;157(3):636-644.

35. Zhou XY, Ben SQ, Chen HL, Ni SS. The prognostic value of pulmonary embolism severity index in acute pulmonary embolism: a meta-analysis. Respir Res. 2012;13(1):111.

36. Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41(4):543-603.

37. Malik S, Bhardwaj A, Eisen M, Gandhi S. Advanced management options for massive and submassive pulmonary embolism.US Cardiology Review. 2016;10(1):30-35.

38. Baglin T, Bauer K, Douketis J, Buller H, Srivastava A, Johnson G. Duration of anticoagulant therapy after a first episode of an unprovoked pulmonary embolus or deep vein thrombosis: guidance from the SSC of the ISTH. J Thromb Haemost. 2012;10:698-702.

39. Cuculi F, Kobza R, Bergner M, Erne P. Usefulness of aspiration of pulmonary emboli and prolonged local thrombolysis to treat pulmonary embolism. Am J Cardiol. 2012;110:1841-1845.

40. Bellou E, Keramida E, Karampinis I, et al. Outpatient treatment of pulmonary embolism. Breathe (Sheff). 2020;16(3):200069.

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42. Cannegieter S, Klok FA. COVID-19-associated coagulopathy and thromboembolic disease: commentary on an interim expert guidance. Res Pract Thromb Haemost. 2020;4(4):439-445.

43. COVID-19 coagulopathy: an evolving story. Lancet. 2020;7(6):E425.

44. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18(4):844-847.

45. Helms J, Tacquard C, Severac F, et al. for the CRICS TRIGGERSEP Group. High risk of thrombosis in patients in severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020;46(6):1089-1098.

46. Klok FA, Kruip MJHA, van der Meer NJM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thrombosis Research. 2020;191:145-147.

47. Goyal P, Choi JJ, Pinheiro LC, et al. Clinical characteristics of COVID-19 in New York City. N Engl J Med. 2020;382:2372-2374.

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49. Stowell JR, Filler L, Sabir MS, Roh AT, Akhter M. Implications of language barrier on the diagnostic yield of computed tomography in pulmonary embolism. Am J Emerg Med. 2018;36(4):677-679.

50. Centers for Disease Control and Prevention. Genetic Tests for Idiopathic Venous Thromboembolism: EGAPP™ Recommendation. Available at https://www.cdc.gov/genomics/gtesting/egapp/recommend/fvl.htm. Last accessed August 13, 2023.

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52. Ucar EY. Update on thrombolytic therapy in acute pulmonary thromboembolism. Eurasian J Med. 2019;51(2):186-190.

53. Aggarwal V, Nicolais CD, Lee A, Bashir R. Acute Management of Pulmonary Embolism. Available at https://www.acc.org/latest-in-cardiology/articles/2017/10/23/12/12/acute-management-of-pulmonary-embolism. Last accessed August 23, 2023.

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Evidence-Based Practice Recommendations Citations

1. Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). Eur Heart J. 2020;41(4):543-603. Available at https://academic.oup.com/eurheartj/article/41/4/543/5556136. Last accessed August 18, 2023.

91334 • Medical Error Prevention and Root Cause Analysis

Marjorie Conner Allen, BSN, JD

www.netce.com

Copyright © 2022 NetCE, All rights reserved.

The Institute of Medicine's (IOM) 1999 publication To Err is Human: Building a Safer Health System, illuminated the unfortunate reality of medical errors in the healthcare industry. The report reviewed the prevalence of medical errors in the United States and highlighted measures that should be taken to prevent them. Specifically, the authors of the report noted that at least 44,000 and perhaps as many as 98,000 Americans were dying in hospitals each year as a result of medical errors. A 2016 report stated that the average number of annual in-hospital deaths attributable to medical error might actually be much higher, at around 400,000. Certainly, these numbers must be balanced against the millions of admissions to hospitals in the United States, which is in excess of 35 million annually. Healthcare professionals should commit to continuing to pay attention to evaluating current approaches for reducing errors and to building new systems to reduce the incidence of medical errors.

Table of Contents

91334 • Medical Error Prevention and Root Cause Analysis

Course Overview

Audience

Accreditations & Approvals

Designations of Credit

Individual State Nursing Approvals

Special Approvals

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Division Planners

Division Planners Disclosure

Director of Development and Academic Affairs

Director Disclosure Statement

About the Sponsor

Disclosure Statement

Implicit Bias in Health Care

1. INTRODUCTION

2. DEFINING "MEDICAL ERROR"

3. ROOT CAUSE ANALYSIS PROCESS

FLORIDA LAW

4. ERROR REDUCTION AND PREVENTION

PATIENT FALLS

DELAYS IN TREATMENT

UNINTENDED RETENTION OF A FOREIGN BODY

WRONG-SITE SURGERY

PATIENT SUICIDE

OPERATIVE AND POSTOPERATIVE COMPLICATIONS

MEDICATION ERRORS

COMMON MISDIAGNOSES

5. OTHER CONSIDERATIONS FOR PATIENT SAFETY

USE OF AN INTERPRETER

6. CONCLUSION

Works Cited

91334 • Medical Error Prevention and Root Cause Analysis

Education Category. Management

Release Date. 09/01/2022

Review Date. 04/15/2025

Expiration Date. 08/31/2026

Course Overview

The Institute of Medicine's (IOM) 1999 publication To Err is Human: Building a Safer Health System, illuminated the unfortunate reality of medical errors in the healthcare industry. The report reviewed the prevalence of medical errors in the United States and highlighted measures that should be taken to prevent them. Specifically, the authors of the report noted that at least 44,000 and perhaps as many as 98,000 Americans were dying in hospitals each year as a result of medical errors. A 2016 report stated that the average number of annual in-hospital deaths attributable to medical error might actually be much higher, at around 400,000. Certainly, these numbers must be balanced against the millions of admissions to hospitals in the United States, which is in excess of 35 million annually. Healthcare professionals should commit to continuing to pay attention to evaluating current approaches for reducing errors and to building new systems to reduce the incidence of medical errors.

Audience

This course is designed for all licensed healthcare professionals.

Accreditations & Approvals

In support of improving patient care, TRC Healthcare/NetCE is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. NetCE is approved to offer continuing education through the Florida Board of Nursing Home Administrators, Provider #50-2405. NetCE is accredited by the International Accreditors for Continuing Education and Training (IACET). NetCE complies with the ANSI/IACET Standard, which is recognized internationally as a standard of excellence in instructional practices. As a result of this accreditation, NetCE is authorized to issue the IACET CEU.

Designations of Credit

This activity was planned by and for the healthcare team, and learners will receive 2 Interprofessional Continuing Education (IPCE) credit(s) for learning and change. NetCE designates this enduring material for a maximum of 2 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. NetCE designates this continuing education activity for 2 ANCC contact hour(s). NetCE designates this continuing education activity for 2.4 hours for Alabama nurses. Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 2 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Completion of this course constitutes permission to share the completion data with ACCME. Through the American Board of Medical Specialties ("ABMS") ongoing commitment to increase access to practice relevant Continuing Certification Activities through the ABMS Continuing Certification Directory, Medical Error Prevention and Root Cause Analysis has met the requirements as a Lifelong Learning CME Activity (apply toward general CME requirement) for the following ABMS Member Boards: Allergy and Immunology; Anesthesiology; Colon and Rectal Surgery; Family Medicine; Medical Genetics and Genomics; Nuclear Medicine; Ophthalmology; Physical Medicine and Rehabilitation; Plastic Surgery; Preventive Medicine; Psychiatry and Neurology; Radiology; Thoracic Surgery; Urology. Completion of this course satisfies one Improvement in Medical Practice activity for the American Board of Ophthalmology (ABO). Successful completion of this CME activity, which includes participation in the evaluation component, enables the learner to earn credit toward the CME and/or Self-Assessment requirements of the American Board of Surgery's Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit. This activity has been approved for the American Board of Anesthesiology’s® (ABA) requirements for Part II: Lifelong Learning and Self-Assessment of the American Board of Anesthesiology’s (ABA) redesigned Maintenance of Certification in Anesthesiology Program® (MOCA®), known as MOCA 2.0®. Please consult the ABA website, www.theABA.org, for a list of all MOCA 2.0 requirements. Maintenance of Certification in Anesthesiology Program® and MOCA® are registered certification marks of the American Board of Anesthesiology®. MOCA 2.0® is a trademark of the American Board of Anesthesiology®. Successful completion of this CME activity, which includes participation in the activity with individual assessments of the participant and feedback to the participant, enables the participant to earn 2 MOC points in the American Board of Pediatrics' (ABP) Maintenance of Certification (MOC) program. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABP MOC credit. This activity has been designated for 2 Lifelong Learning (Part II) credits for the American Board of Pathology Continuing Certification Program. Through an agreement between the Accreditation Council for Continuing Medical Education and the Royal College of Physicians and Surgeons of Canada, medical practitioners participating in the Royal College MOC Program may record completion of accredited activities registered under the ACCME's "CME in Support of MOC" program in Section 3 of the Royal College's MOC Program. This home study course is approved by the Florida Board of Nursing Home Administrators for 2 credit hour(s). AACN Synergy CERP Category A. NetCE is authorized by IACET to offer 0.2 CEU(s) for this program.

Individual State Nursing Approvals

In addition to states that accept ANCC, NetCE is approved as a provider of continuing education in nursing by: Arkansas, Provider #50-2405; California, BRN Provider #CEP9784; California, LVN Provider #V10662; California, PT Provider #V10842; District of Columbia, Provider #50-2405; Florida, Provider #50-2405; Georgia, Provider #50-2405; Kentucky, Provider #7-0054 through 12/31/2025; South Carolina, Provider #50-2405; West Virginia RN and APRN, Provider #50-2405.

Special Approvals

This course fulfills the Florida requirement for 2 hours of education on the Prevention of Medical Errors. This activity is designed to comply with the requirements of California Assembly Bill 1195, Cultural and Linguistic Competency.

Course Objective

The purpose of this course is to satisfy the requirement of the Florida law and provide all licensed healthcare professionals with information regarding the root cause process, error reduction and prevention, and patient safety.

Learning Objectives

Upon completion of this course, you should be able to:

1. Describe how the Institute of Medicine defines "medical error."

2. Describe the types of sentinel events the Joint Commission has identified.

3. Discuss what factors must be included in a root cause analysis in order for the Joint Commission to consider it "thorough" and "credible."

4. Identify what types of adverse incidents must be reported to the Florida Agency for Healthcare Administration.

5. Identify the most common sentinel events reported to the Joint Commission.

6. Evaluate the most common misdiagnoses, as recognized by the Florida Board of Medicine, and outline the safety needs of special populations, including non-English-proficient patients.

Faculty

Marjorie Conner Allen, BSN, JD, received her Bachelor of Science in Nursing degree from the University of Florida, Gainesville, in 1984. She began her nursing career at Shands Teaching Hospital and Clinics at the University of Florida, Gainesville. While practicing nursing at Shands, she gave continuing education seminars regarding the nursing implications for dealing with adolescents with terminal illness. In 1988, Ms. Allen moved to Atlanta, Georgia where she worked at Egleston Children’s Hospital at Emory University in the bone marrow transplant unit. In the fall of 1989, she began law school at Florida State University. After graduating from law school in 1992, Ms. Allen took a two-year job as law clerk to the Honorable William Terrell Hodges, United States District Judge for the Middle District of Florida. After completing her clerkship, Ms. Allen began her employment with the law firm of Smith, Hulsey & Busey in Jacksonville, Florida where she has worked in the litigation department defending hospitals and nurses in medical malpractice actions. Ms. Allen resides in Jacksonville and is currently in-house counsel to the Mayo Clinic Jacksonville.

Faculty Disclosure

Contributing faculty, Marjorie Conner Allen, BSN, JD, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Division Planners

John M. Leonard, MD

Jane C. Norman, RN, MSN, CNE, PhD

Division Planners Disclosure

The division planners have disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Director of Development and Academic Affairs

Sarah Campbell

Director Disclosure Statement

The Director of Development and Academic Affairs has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

About the Sponsor

The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.

Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.

Disclosure Statement

It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.

Implicit Bias in Health Care

The role of implicit biases on healthcare outcomes has become a concern, as there is some evidence that implicit biases contribute to health disparities, professionals' attitudes toward and interactions with patients, quality of care, diagnoses, and treatment decisions. This may produce differences in help-seeking, diagnoses, and ultimately treatments and interventions. Implicit biases may also unwittingly produce professional behaviors, attitudes, and interactions that reduce patients' trust and comfort with their provider, leading to earlier termination of visits and/or reduced adherence and follow-up. Disadvantaged groups are marginalized in the healthcare system and vulnerable on multiple levels; health professionals' implicit biases can further exacerbate these existing disadvantages.

Interventions or strategies designed to reduce implicit bias may be categorized as change-based or control-based. Change-based interventions focus on reducing or changing cognitive associations underlying implicit biases. These interventions might include challenging stereotypes. Conversely, control-based interventions involve reducing the effects of the implicit bias on the individual's behaviors. These strategies include increasing awareness of biased thoughts and responses. The two types of interventions are not mutually exclusive and may be used synergistically.

1. INTRODUCTION

The Institute of Medicine's (IOM) 1999 publication To Err is Human: Building a Safer Health System, illuminated the unfortunate reality of medical errors in the healthcare industry. The report reviewed the prevalence of medical errors in the United States and highlighted measures that should be taken to prevent them. Specifically, the authors of the report noted that at least 44,000 and perhaps as many as 98,000 Americans were dying in hospitals each year as a result of medical errors and many more were being seriously injured [1]. They further noted that, even when using the lower estimate of 44,000, deaths in hospitals due to medical errors exceeded the annual deaths attributable to motor vehicle accidents (43,458), breast cancer (42,297), or AIDS (16,516) [1]. A 2016 report stated that the average number of annual in-hospital deaths attributable to medical error might actually be much higher, at around 400,000 [2]. This report places medical errors as the third leading cause of death in the United States. Certainly, these numbers must be balanced against the millions of admissions to hospitals in the United States, which is in excess of 33 million annually [1,3].

It does appear that some progress has been made in the past decade. The Agency for Healthcare Research and Quality found a 17% decline in hospital-acquired conditions between 2014 and 2017, or 910,000 fewer conditions and 20,500 fewer deaths than if the 2014 rate had remained steady [4]. Though the precise mechanism(s) responsible for this decline is not clear, it occurred following a concerted effort by federal agencies, organizations, and individual providers to curtail medical errors. However, the statistics indicate that medical errors continue to be an issue. Healthcare professionals should commit to continuing to pay greater attention to evaluating approaches for reducing errors and to building new systems to reduce the incidence of medical errors.

Spurred by a commitment to reducing medical error incidents, the Florida Legislature mandates that all healthcare professionals in Florida complete a two-hour course on the topic of prevention of medical errors [5]. This continuing education course is designed to satisfy the requirements of the Florida law and provide all licensed healthcare professionals with information regarding the root cause analysis process, error reduction and prevention, and patient safety, as well as information regarding the five most misdiagnosed conditions as determined by the Florida Board of Medicine.

2. DEFINING "MEDICAL ERROR"

The IOM Committee on Quality of Healthcare in America defines error as "the failure of a planned action to be completed as intended or the use of a wrong plan to achieve an aim" [1]. It is important to note that medical errors are not defined as intentional acts of wrongdoing and that not all medical errors rise to the level of medical malpractice or negligence. Errors depend on two kinds of failures: either the correct action does not proceed as intended, which is described as an "error of execution," or the original intended action is not correct, which is described as an "error of planning" [1]. A medical error can occur at any stage in the process of providing patient care, from diagnosis to treatment, and even while providing preventative care. Not all errors will result in harm to the patient. Medical errors that do result in injury are sometimes called preventable adverse events or sentinel events—sentinel because they signal the need for immediate investigation and response [6].

Preventable adverse events or sentinel events are defined as those events that cause an injury to a patient as a result of medical intervention or inaction on the part of the healthcare provider whereby the injury cannot reasonably be said to be related to the patient's underlying medical condition. Thus, for example, if a patient has a surgical procedure and dies postoperatively from pneumonia, the patient has suffered an adverse event. But was that adverse event preventable; was it caused by medical intervention or inaction? The specific facts of this case must be analyzed to determine whether the patient acquired the pneumonia as a result of poor handwashing techniques of the medical staff (i.e., an error of execution), which would indicate a preventable adverse event, or whether the patient acquired the pneumonia because of age and comorbidities, which would indicate a nonpreventable adverse event.

Healthcare professionals can learn much by closely scrutinizing and evaluating adverse events that lead to serious injury or death. The evaluation of such events would also enable healthcare professionals to improve the delivery of health care and reduce future mistakes. In addition, healthcare professionals should have a process in place to evaluate those instances in which a medical error occurred and did not cause harm to the patient. By reviewing these processes, healthcare professionals are afforded the unique opportunity to identify system improvements that have the potential to prevent future adverse events. The Joint Commission, recognizing the importance of analyzing both preventable adverse events and near-misses, has established guidelines for recognizing these events and requires healthcare facilities to conduct a root cause analysis to determine the underlying cause of the event [7].

3. ROOT CAUSE ANALYSIS PROCESS

The Joint Commission is a national organization with a mission to improve the quality of care provided at healthcare institutions in the United States. It accomplishes this mission by providing accredited status to healthcare facilities. Accreditors play an important role in encouraging and supporting actions within healthcare organizations by holding them accountable for ensuring a safe environment for patients. Healthcare organizations should actively engage in a cooperative relationship with the Joint Commission through this accreditation process and participate in the process to reduce risk and facilitate desired outcomes of care.

Root cause analysis, as defined by the Joint Commission, is "a process for identifying the basic or causal factors that underlie variation in performance, including the occurrence or possible occurrence of a sentinel event" [6]. In the 2022 update, the Joint Commission defines a sentinel event as a "patient safety event (not primarily related to the natural course of the illness or underlying condition) that reaches a patient and results in death, severe harm (regardless of duration of harm), or permanent harm (regardless of severity of harm)" [6,10]. Furthermore, the Joint Commission revision clarified the terms "severe" and "permanent" harm with regard to sentinel events. "Severe harm" is an event or condition that reaches the individual, resulting in life-threatening bodily injury (including pain or disfigurement) that interferes with or results in loss of functional ability or quality of life that requires continuous physiologic monitoring or a surgery, invasive procedure, or treatment to resolve the condition [6,10]."Permanent harm" is an event or condition that reaches the individual, resulting in any level of harm that permanently alters and/or affects an individual's baseline [6,10].

The following subsets of sentinel events are subject to review by the Joint Commission [6,11]:

- The event has resulted in an unanticipated death or major permanent loss of function, not related to the natural course of the patient's illness or underlying condition

or

- The event is one of the following (even if the outcome was not death or major permanent loss of function unrelated to the natural course of the patient's illness or underlying condition):

- Suicide of any patient receiving care, treatment, and services in a staffed around-the-clock care setting or within 72 hours of discharge

- Unanticipated death of a full-term infant

- Abduction of any patient receiving care, treatment, and services

- Any elopement (i.e., unauthorized departure) of a patient from a staffed around the-clock care setting (including the emergency department), leading to death, permanent harm, or severe temporary harm to the patient

- Discharge of an infant to the wrong family

- Rape, assault (leading to death or permanent loss of function), or homicide of any patient receiving care, treatment, and services

- Rape, assault (leading to death or permanent loss of function), or homicide of a staff member, licensed independent practitioner, visitor, or vendor while on site at the healthcare organization

- Hemolytic transfusion reaction involving administration of blood or blood products having major blood group incompatibilities (e.g., ABO, Rh, other blood groups)

- Invasive procedure, including surgery, on the wrong patient or wrong site

- Unintended retention of a foreign object in a patient after surgery or other invasive procedures

- Severe neonatal hyperbilirubinemia (bilirubin >30 mg/dL)

- Fluoroscopy resulting in permanent tissue injury when clinical and technical optimization were not implemented and/or recognized practice parameters were not followed

- Fire, flame, or unanticipated smoke, heat, or flashes occurring during an episode of patient care

- Any intrapartum (related to the birth process) maternal death

- Severe maternal morbidity

- Fall resulting in: any fracture; surgery, casting, or traction; required consult/management or comfort care for a neurological or internal injury; a patient with coagulopathy who receives blood products as a result of the fall; or death or permanent harm as a result of injuries sustained from the fall (not from physiologic events causing the fall)

Alternatively, the following examples are events that are NOT considered reviewable under the Joint Commission's sentinel event policy [6]:

- Any close call ("near miss")

- Full or expected return of limb or bodily function to the same level as prior to the adverse event by discharge or within two weeks of the initial loss of said function, whichever is the longer period

- Any sentinel event that has not affected a recipient of care (e.g., patient, individual, resident)

- Medication errors that do not result in death or major permanent loss of function

- Suicide other than in an around-the-clock care setting or following elopement from such a setting

- A death or loss of function following a discharge against medical advice

- Unsuccessful suicide attempts unless resulting in major permanent loss of function

- Minor degrees of hemolysis not caused by a major blood group incompatibility and with no clinical sequelae

For further definition of terms, please refer to the Joint Commission's Sentinel Event Policy and Procedures at https://www.jointcommission.org/resources/patient-safety-topics/sentinel-event/sentinel-event-policy-and-procedures.

As part of the accreditation requirement, the Joint Commission requires that healthcare organizations have a process in place to recognize these sentinel events, conduct thorough and credible root cause analyses that focus on process and system factors, and document a risk-reduction strategy and internal corrective action plan that includes measurement of the effectiveness of process and system improvements to reduce risk [6]. This process must be completed within 45 business days of the organization having become aware of the sentinel event.

The Joint Commission will consider a root cause analysis acceptable for accreditation purposes if it focuses primarily on systems and processes, not individual performance [6]. In other words, the healthcare organization should minimize the individual blame or retribution for involvement in a medical error. In addition, the root cause analysis should progress from special causes in clinical processes to common causes in organizational processes, and the analysis should repeatedly dig deeper by asking why, then, when answered, why again, and so on. The analysis should also identify changes that can be made in systems and processes, either through redesign or development of new systems or processes, which would reduce the risk of such events occurring in the future. The Joint Commission requires that the analysis be thorough and credible. To be considered thorough, the root cause analysis must include [6]:

- A determination of the human and other factors most directly associated with the sentinel event and the process(es) and systems related to its occurrence

- Analysis of the underlying systems and processes through a series of "why" questions to determine where redesign might reduce risk

- Inquiry into all areas appropriate to the specific type of event

- Identification of risk points and their potential contributions to this type of event

- A determination of potential improvement in processes or systems that would tend to decrease the likelihood of such events in the future, or a determination, after analysis, that no such improvement opportunities exist

To be considered credible, the root cause analysis must meet the following standards [6]:

- The organization's leadership and the individuals most closely involved in the process and systems under review must participate in the analysis.

- The analysis must be internally consistent; that is, it must not contradict itself or leave obvious questions unanswered.

- The analysis must provide an explanation for all findings of "not applicable" or "no problem."

- The analysis must include consideration of any relevant literature.

Finally, as previously discussed, after conducting this root cause analysis, the organization must prepare an internal corrective action plan. The Joint Commission will accept this action plan if it identifies changes that can be implemented to reduce risk or formulate a rationale for not undertaking such changes, and if, where improvement actions are planned, it identifies who is responsible for implementation, when the action will be implemented, and how the effectiveness of the actions will be evaluated [6].

FLORIDA LAW

Healthcare professionals have an obligation to report adverse events to leadership and ensure that organizations have processes in place to satisfy the Joint Commission requirement. In Florida, certain serious adverse incidents must also be reported to Florida's Agency for Health Care Administration (AHCA). Florida law requires that licensed facilities, such as hospitals, establish an internal risk management program. As part of that program, licensed facilities must develop and implement an incident reporting system, which requires the development of appropriate measures to minimize the risk of adverse incidents to patients, as well as imposes an affirmative duty on all healthcare providers and employees of the facility to report adverse incidents to the risk manager or to his or her designee. The risk manager must receive these incident reports within 3 business days of the incident, and depending on the type of incident, the risk manager may have to report the incident to AHCA within 15 days of receipt of the report.

Florida Statute 395.0197 specifically defines an adverse incident as [8]:

For purposes of reporting to the agency pursuant to this section, the term "adverse incident" means an event over which health care personnel could exercise control and which is associated in whole or in part with medical intervention, rather than the condition for which such intervention occurred, and which:

a) Results in one of the following injuries:

1. Death;

2. Brain or spinal damage;

3. Permanent disfigurement;

4. Fracture or dislocation of bones or joints;

5. A resulting limitation of neurological, physical, or sensory function which continues after discharge from the facility;

6. Any condition that required specialized medical attention or surgical intervention resulting from nonemergency medical intervention, other than an emergency medical condition, to which the patient has not given his or her informed consent; or

7. Any condition that required the transfer of the patient, within or outside the facility, to a unit providing a more acute level of care due to the adverse incident, rather than the patient's condition prior to the adverse incident

b) Was the performance of a surgical procedure on the wrong patient, a wrong surgical procedure, a wrong-site surgical procedure, or a surgical procedure otherwise unrelated to the patient's diagnosis or medical condition;

c) Required the surgical repair of damage resulting to a patient from a planned surgical procedure, where the damage was not a recognized specific risk, as disclosed to the patient and documented through informed-consent process; or

d) Was a procedure to remove unplanned foreign objects remaining from a surgical procedure.

In 2021, the Florida AHCA reported that a total of 184 deaths occurred as a result of hospital error, 21.4% of 859 adverse incidents reported for the year. The next most common incidents during this period were transfer of the patient to a unit providing a more acute level of care due to the adverse incident (18.7%), fracture or dislocation of bones or joints (17.0%), surgical procedures unrelated to the patient's diagnosis or medical needs (10.4%), surgical procedure to remove foreign object from a previous surgical procedure (10.2%), brain or spinal damage (5.0%), and surgical procedure performed on wrong site (4.3%) [9]. The following adverse incidents must be reported to the AHCA within 15 calendar days after their occurrence [8]:

- The death of a patient

- Brain or spinal damage to a patient

- The performance of a surgical procedure on the wrong patient

- The performance of a wrong-site surgical procedure

- The performance of a wrong surgical procedure

- The performance of a surgical procedure that is medically unnecessary or otherwise unrelated to the patient's diagnosis or medical condition

- The surgical repair of damage resulting to a patient from a planned surgical procedure, where the damage is not a recognized specific risk, as disclosed to the patient and documented through the informed-consent process

- The performance of procedures to remove unplanned foreign objects remaining from a surgical procedure

Each incident will be reviewed by the AHCA, who will then determine the penalty to be imposed upon the responsible party [8]. All Florida healthcare professionals who practice in licensed facilities should familiarize themselves with these requirements and ensure that the facility in which they practice has processes in place to ensure compliance.

Unlike Florida's mandatory reporting of serious adverse incidents, the Joint Commission recommends that healthcare organizations voluntarily report sentinel events, and it encourages the facilities to communicate the results of their root cause analyses and their corrective action plans. As a result of the sentinel events that have been reported, the Joint Commission has compiled Sentinel Event Alerts. These alerts are intended to provide healthcare organizations with important information regarding reported trends and, by doing so, highlight areas of potential concern so an organization may review its own internal processes to maximize error reduction and prevention with regard to a particular issue [7].

4. ERROR REDUCTION AND PREVENTION

Between 2005 and 2021, the Joint Commission reviewed 14,731 sentinel events [11]. Some events, such as fire, impacted multiple patients. Sentinel event reviews during this time period were frequently conducted for patient fall; delay in treatment; unintended retention of a foreign body; wrong-patient, wrong-site, wrong-procedure surgery; patient suicide; operative and postoperative complications; and medication error [11].

PATIENT FALLS

In 2021, the Joint Commission introduced a separate sentinel event line item for patient falls, making it the most frequently reported sentinel event that year. Patients who are at highest risk include the elderly, those who have an altered mental status due to chronic mental illness or acute intoxication, and those who have a history of prior falls. Additionally, the Joint Commission calls for an increased awareness to an under-recognized population at risk for falls. Newborns and infants are at risk for falls and/or drops, often due to maternal risk factors such as cesarean birth, use of pain medication within four hours, second or third postpartum night (specifically around midnight to early morning hours), and drowsiness associated with breastfeeding. It is obvious from these factors that a thorough and complete patient history may be the key to identifying those at risk.

The root causes of patient falls that healthcare facilities identified as sentinel events and reported to the Joint Commission included inadequate assessment; communication failures; lack of adherence to protocols and safety practices; inadequate staff orientation, supervision, staffing levels, or skill mix; deficiencies in the physical environment; and lack of leadership [19]. Risk reduction strategies to these root causes are fairly straightforward, although in practice, preventing falls is difficult. The most important are the use of a standardized assessment tool to identify fall and injury risk factors, assessing an individual patient's risks that may not have been captured through the tool, and interventions tailored to an individual patient's identified risks [19].

Because patient falls often result in morbidity, mortality, immobility, and early nursing home placement for patients, it is imperative that healthcare facilities initiate adequate fall prevention programs, which will ultimately reduce injuries. Failure to do so will result in a spiraling increase in the number of falls in healthcare facilities, particularly among the elderly who are at highest risk. As more Americans live beyond 65 years of age, the need to develop mobility protocols and programs to reduce the risk of falls and injuries for the older adult grows more urgent.

DELAYS IN TREATMENT

According to the Joint Commission, more than half of all reported delay in treatment sentinel events in 2010–2014 resulted in patient death [16]. It is important to keep in mind that delays in treatment can occur in any healthcare setting. The most common reason for a delay in treatment is misdiagnosis; however, delays can also result from delayed test results, lack of physician availability, delayed administration of ordered care, incomplete treatment, and even inability to get an initial appointment or follow-up appointment in a timely manner [16]. The main root causes contributing to delays in treatment are inadequate assessments, poor planning, communication failures, and human factors. Additionally, 48% of patients self-reported a delay in accessing healthcare during the COVID-19 pandemic. One study suggests that delays in treatment are likely due to widespread public health messages to avoid unnecessary visits, triage uncertainty, lack of providers, and lack of resources [36]. Recommendations from the Joint Commission include avoiding cognitive shortcuts, improving health information technology, incorporating diagnostic checklists into the electronic record, promoting provider-to-provider communication, engaging leadership in developing solutions, focusing organization attention on the scheduling process and on ordering tests and reporting test results, improving access to care, implementing a standardized communications method, maintaining adequate staffing levels, and increasing patient and family engagement/activation [16].

UNINTENDED RETENTION OF A FOREIGN BODY

In 2021, unintended retained foreign objects were the third most frequently reported sentinel event reported to the Joint Commission [11]. The prevalence of these events has remained relatively stable since 2009, indicating that preventing these errors remains difficult for practitioners and facilities. The most commonly retained items are sponges, followed by catheter guidewires and other (a broad category encompassing a wide variety of items) [11].

In addition to harming patients and contributing to distrust in the medical system, the unintended retention of foreign objects significantly contributes to patient care costs [13]. The average total cost of care related to unintended retained foreign objects is $166,000 to $200,000 [13].

According to the sentinel event data, the most common root causes of unintended retained foreign objects reported to the Joint Commission are [13]:

- The absence of policies and procedures

- Failure to comply with existing policies and procedures

- Problems with hierarchy and intimidation

- Failure in communication with physicians

- Failure of staff to communicate relevant patient information

- Inadequate or incomplete education of staff

WRONG-SITE SURGERY

Operating on the wrong part of a patient's body is an obvious sign that there is a problem in the operating room system. Interestingly, wrong-site surgery occurred more commonly in orthopedic procedures than in all other surgical specialties combined. The American Academy of Orthopaedic Surgeons takes this issue seriously, and it has taken special steps to eliminate the problem. For example, it recommends that a surgeon sign their initials at the correct site of surgery with an indelible pen. Unless the initials are visible, the surgeon should not make an incision [12]. Writing "NO" in large black letters on the side not to be operated on was suggested in the past, but this is discouraged due to possible confusion with the surgeon's initials. In spinal surgery, the Academy recommends that an intraoperative radiograph and radiopaque marker be used to determine the exact vertebral level of spinal surgery [12]. Whatever the mechanism used to prevent and reduce the incidence of this error, it is clear that this is not just the surgeon's problem. All operating room personnel, including physicians, nurses, technicians, anesthesiologists, and other preoperative allied health personnel, should monitor procedures to ensure verification procedures are followed, especially for high-risk procedures.

Due to the prevalence of wrong-site, wrong-procedure, and wrong-person surgeries, the Joint Commission, along with more than 50 professional healthcare organizations, convened two summits to help reduce the occurrence of these errors. The first summit, convened in 2003, developed a Universal Protocol that consisted of the following: a preprocedure verification process; marking the operative/procedure site with an indelible marker; taking a "time-out" with all team members immediately before starting the procedure; and adaptation of the requirements to all procedure settings, including bedside procedures. However, the incidence of wrong-site surgeries continued to increase, and in 2007 and 2010, additional summits were organized to pinpoint barriers in compliance and discover new strategies to eliminate these errors [14]. As of 2019, the Universal Protocol has been incorporated into the National Patient Safety Goal chapter of the Joint Commission accreditation manual [15].

PATIENT SUICIDE

It is estimated that between 48 and 65 hospital inpatient suicides occur per year in the United States. Most of these cases (31 to 52) occur in psychiatric units or involve psychiatric inpatients. The most common method is hanging [50]. Times of care transition are particularly risky, with a 200% increase in risk in the week after discharge from a psychiatric facility; the elevated risk continues for four years [18]. Other risk factors include previous suicide attempt or self-injury, mental or emotional disorders, history of trauma or loss, serious illness or chronic pain, substance use disorder, social isolation, and access to lethal means.

The most common root cause documented for patient suicide reported between 2010 and 2014 was shortcomings in assessment, most commonly psychiatric assessment [18]. In addition, nearly 25% of behavioral health facilities accredited by the Joint Commission were found noncompliant with the requirement to conduct an adequate suicide risk assessment in 2014.

The Joint Commission has recommended a number of suicide risk reduction strategies, including [18]:

- Review each patient's personal and family medical history for suicide risk factors.

- Screen all patients for suicide ideation, using a brief, standardized, evidence-based screening tool.

- Review screening questionnaires before the patient leaves the appointment or is discharged.

- Establish a collaborative, ongoing, and systematic assessment and treatment process with the patient involving the patient's other providers, family, and friends, as appropriate.

- To improve outcomes for at-risk patients, develop treatment and discharge plans that directly target suicidality.

- Educate all staff in patient care settings about how to identify and respond to patients with suicide ideation.

- Document decisions regarding the care and referral of patients with suicide risk.

A simple review of these measures demonstrates that healthcare providers can avoid the devastating impact of an inpatient suicide by implementing routine preventative strategies, such as removing harmful items and careful screening through the admission and discharge processes.

OPERATIVE AND POSTOPERATIVE COMPLICATIONS

Many of the sentinel events reported to the Joint Commission regarding operative and postoperative complications occurred in relation to nonemergent procedures, such as interventional imaging and/or endoscopy, tube or catheter insertion, open abdominal surgery, head and neck surgery, orthopedic surgery, and thoracic surgery [17]. The majority of the reporting healthcare facilities cited miscommunication as the primary root cause. Other identified causes include failure to follow established procedures, incomplete preoperative assessment, inconsistent postoperative monitoring procedures, and failure to question inappropriate orders. In order to reduce the risk, reporting facilities have identified a number of strategies, including improving staff orientation and training, increasing educational opportunities for physicians, clearly defining expected channels of communication, and monitoring consistency of compliance with procedures. Healthcare facilities should review postoperative patient monitoring procedures to ensure an adequate level appropriate to the needs of the patient, regardless of the setting (e.g., operating room, endoscopy suite, radiology department) [17]. Based upon these findings, it is clear that direct communication among healthcare providers is key to preventing operative and postoperative complications. Healthcare facilities should provide more staff education regarding preventative measures, and healthcare providers can do their part by engaging in a healthy and mutual respect for all of the members of the healthcare team [17].

MEDICATION ERRORS

Unquestionably, medication errors are one of the most common causes of avoidable harm to patients. These errors may occur at any of these critical points: when ordered or prescribed by a physician; during documentation; while transcribing; when dispensed by a pharmacist; when administered by a nurse; or during monitoring.

The National Coordinating Council for Medication Error Reporting and Prevention defines a medication error as [20]:

Any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the healthcare professional, patient or consumer. Such events may be related to professional practice, healthcare products, procedures, and systems, including prescribing: order communication; product labeling; packaging, and nomenclature; compounding; dispensing; distribution; administration; education; monitoring; and use.

It has been estimated that up to 50% of medication errors are caused by a provider writing the wrong medication, the wrong route or dose, or the wrong frequency, and nearly 75% of medication errors have been attributed to distraction of the care provider [24]. In addition, a number of medication errors can be linked to the prescriber who continually uses potentially dangerous abbreviations and dose expressions. Despite repeated warnings by the Institute for Safe Medication Practices about the dangers associated with using certain abbreviations when prescribing medications, this practice continues. To eliminate this factor, there are fairly simple steps that can eliminate much confusion. Prescribers should [21]:

- Avoid the use of the symbol "U" or "u" but rather spell "units" when ordering drugs, such as insulin.

- Spell out medication names completely rather than using abbreviations and acronyms.

- Avoid using abbreviations for "daily" (QD), "every other day" (QOD), or "four times daily" (QID), which are easily confused.

- Use leading zeros before a decimal point (e.g., 0.2 mg instead of .2 mg), and do not use trailing zeros (e.g., 2 mg instead of 2.0 mg).

- Write out "morphine sulfate" and "magnesium sulfate" instead of using the abbreviations (MS, MSO_4, MgSO_4).

The Institute for Safe Medication Practices publishes a list of error-prone abbreviations, symbols, and dose designations online at https://www.ismp.org/recommendations/error-prone-abbreviations-list.

Other factors contributing to prescriber errors are illegible or confusing handwriting and, a frequently cited cause of many adverse and sentinel events, the failure of healthcare providers to assess risk and prevent errors. Addressing illegibility may include developing appropriate policies and procedures, tracking and trending patterns, and evaluating results through peer review committees. Improving communication might include developing protocols for the use of verbal orders to assure that those from an onsite practitioner would be limited to an emergency situation only. No verbal orders should be taken for certain medications, such as for chemotherapy, and all verbal orders should be repeated for clarification and, whenever possible, reiterated to a third person. Another method of improving communication might involve reviewing the hospital formulary in collaboration with the Pharmacy and Therapeutics Committee of the medical staff to limit, where appropriate, the number of therapeutically and generically equivalent products [22].

It has been estimated that between 0.2% and 10% of prescriptions are dispensed incorrectly [23]. The three most common dispensing errors are: dispensing an incorrect medication, dosage strength, or dosage form; miscalculating a dose; and failing to identify drug interactions or contraindications [24]. Safe medication dispensing practices may include a number of risk reduction strategies to reduce the incidence of errors that may cause harm to patients [22,25,54,61]:

- Ensure that appropriate and current drug reference texts and/or online resources are immediately available to pharmacy personnel.

- Ensure that essential patient information, such as allergies, age, weight, current diagnoses, pertinent lab values, and current medication regimen, is available to the pharmacist prior to the dispensing of a new medication order.

- Require clarification of any order that is incomplete, illegible, or otherwise questionable using an established process for resolving questions.

- Whenever possible, dispense dosage units in a ready-to-administer form.

- Dispense single-dose vials and ampoules rather than multidose vials.

- Select oral rather than injectable routes, when possible.

- Require that a pharmacist double-check all mathematical calculations for neonatal and pediatric dilutions, parenteral nutrition solutions, and other compounded pharmaceutical products.

- Create an environment for the dispensing area that minimizes distractions and interruptions, provides appropriate lighting, air conditioning, and air flow, safe noise levels, and includes ergonomic consideration of equipment, fixtures, and technology.

- Require that a second pharmacist double-check the accuracy of order entry and dose calculations for all orders involving antineoplastic agents and other high-risk drugs dispensed by the pharmacy.

- Enhance the awareness of look-alike and sound-alike medications, and use warning signs to help differentiate medications from one another, especially when confusion exists between or among strengths, similar looking labels, or similar sounding names.

- Separate look-alike and sound-alike medications in pharmacy dispensing areas or consider repackaging or using different vendors.

- Follow-up and periodically evaluate the need for continued drug therapy for individual patients.

Once again, communication is likely the key to avoiding dispensing errors. Pharmacists should work closely with their staff to ensure that proper protocols are followed, and most importantly, when questions arise regarding a prescription, the pharmacist should take the time to contact the prescriber directly to obtain clarification.

The healthcare provider who has the responsibility to administer a medication has the final opportunity to avoid a mistake. In most cases, particularly in inpatient settings, this responsibility falls to the nurse. Nurses are often taught in nursing school to review the five "rights" prior to administering any medication: the right patient is given the right drug in the right dose by the right route at the right time [26]. Medication errors generally fall into four categories, which mimic these five "rights." The first is the failure to follow procedural safeguards, such as ensuring that essential patient information, including allergies, age, weight, and current medication regimen, is available. The second is unfamiliarity with a drug. In one case, a jury determined that a nurse was negligent for giving a drug without having reviewed the literature, which stated that the necessary precautions for the administration of the drug required the specialized skill of an anesthesiologist. The third category of drug administration is failure to use the correct mode of administration. A nurse in Delaware was held liable for administering a medication by injection after an order had been written to change the route to oral. The final category involves failure to obtain clarification if an order is incomplete, illegible, or otherwise questionable. In a case tried in Louisiana, a nurse was held liable for administering a medication that a physician ordered, notwithstanding that the dose was excessive. The nurse's administration of the drug led to the patient's death [27].

In addition, healthcare facilities should implement appropriate guidelines, policies, and procedures to ensure safe medication administration practice. These policies should require that staff members who administer medications [24,25,54,61]:

- Are knowledgeable about the drug's uses, precautions, contraindications, potential adverse reactions, interactions, and proper method of administration

- Resolve questions prior to medication administration

- Only administer medications that have been properly labeled with medication name, dose to be administered, dosage form, route, and expiration date

- Utilize a standard medication administration time schedule and receive education on how and when to incorporate newly started medication orders safely into the standardized schedule

- Have a second person verify a dosage calculation if a mathematical calculation of a dose is necessary

- Receive adequate education on the operation and use of devices and equipment used for medication administration (for example, patient-controlled anesthesia pumps and other types of infusion pumps)

- Have another person double-check infusion pump settings when critical, high-risk drugs are infused

- Document all medications immediately after administration

Finally, healthcare facilities should have proper quality assurance measures in place to monitor medication administration practices. Included among these would be protocols and guidelines for use with critical and problem-prone medications to help optimize therapies and minimize the possibility of adverse events and to integrate "triggers" to indicate the need for additional clinical monitoring [25].

It is important to note that the pediatric population is especially vulnerable to medication errors. When children are prescribed adult medications, care must be taken to adjust dosage according to weight, requiring the physician to use pediatric-specific calculations. Also, many healthcare settings are not trained to care for the pediatric patient. Intolerance due to physiologic immaturity is also a factor in adverse response to medications, and in many cases, this population cannot communicate their discomfort due to adverse reactions. Risk reduction strategies include standardizing and effectively identifying medications and processes for drug administration, ensuring pharmacy oversight, and using technology, such as medication dispensing programs, infusion pumps, and bar-coding, judiciously [28].

COMMON MISDIAGNOSES

As Florida healthcare professionals, it is important to be aware that in addition to wrong-site/wrong-procedure surgery, several medical conditions also continue to be misdiagnosed. As of 2024, the Florida Board of Medicine has determined the five most misdiagnosed conditions to be [29]:

- Oncology-related conditions

- Gastroenterology-related issues

- Cardiology-related issues

- Neurologic conditions

- Infectious disease-related conditions

It is important to be aware of the possibility of misdiagnosis and incorporate this knowledge into practice.

Oncology-Related Conditions

The early detection and diagnosis of cancers is crucial for selecting the appropriate treatment approach and to ensure an optimum outcome. However, an estimated 12% of cancer patients are initially misdiagnosed, and the missed or delayed diagnosis of cancers remains a significant cause of medical malpractice claims [30,31]. The causes of missed diagnoses vary widely among cancers in different parts of the body. In many cases, patients who do not fit the typical profile for a specific cancer (e.g., young age) may be underdiagnosed, and it is important that cancer is considered as part of the differential diagnosis in ambiguous cases [31,32,33]. In order to prevent missed or delayed cancer diagnosis, practitioners may take steps to ensure adherence to clinical guidelines for screening and diagnosis, use tools to facilitate communication, and engage strategies to ensure appropriate follow-up [55].

Gastroenterology-Related Conditions

Gasteroenterologic conditions may present with nonspecific complaints (e.g., abdominal pain, nausea) common to a variety of illnesses, complicating and delaying diagnosis. In one study of patients with pancreatic cancer, more than 30% were initially misdiagnosed, most commonly with gall bladder disease [58]. Diagnosis and screening for gastrointestinal disorders may be complicated by a lack of definitive test (e.g., irritable bowel syndrome) or by limits on screening recommendations (e.g., colorectal cancer). However, delayed diagnosis can lead to worsening conditions and poorer prognosis.

In general, gastrointestinal syndromes/symptoms may be classified into three general diagnostic categories: organic, motility, or functional disorders [59,60]. Functional GI disorders are idiopathic disorders of gut-brain interaction and, unlike organic and motility disorders, diagnosis involves identification of symptom clusters. As such, misdiagnosis is more common.

Another important consideration is GI symptom-specific anxiety, an important perpetuating factor that describes threatening interpretation and out-of-proportion behavioral response to GI sensations. This anxiety to real GI symptoms and the frequency of psychiatric comorbidity can lead to functional GI syndromes being dismissed as psychological or psychosomatic in nature.

Cardiology-Related Issues

The clinical presentation of chest pain has many possible etiologies, ranging from benign (e.g., panic/anxiety, pneumonia, peptic ulcer, gastroesophageal reflux disease, and pericarditis) to life-threatening (e.g., pulmonary embolism, acute coronary syndrome [ACS], aortic dissection, and pneumothorax). In many cases, it is best to rule out the more urgently threatening possibilities before testing for other causes.

Of the potentially life-threatening causes of chest pain, ACS is the most prevalent. Although a large percentage of individuals with suspected ACS will be seen initially in emergency departments, patients in any healthcare setting, regardless of other diagnoses, may abruptly develop chest pain suspicious for ACS. When a patient presents with clinical signs suspicious for myocardial infarction, immediate medical intervention is directed at confirming a diagnosis and stratifying the person's risk for adverse events such as cardiac arrest and severe/significant damage to the myocardium [41]. It is important to note that while some patients will present with classic ACS-related chest pain (tightness, sensation of pressure, heaviness, crushing, vise-like, aching pain in the substernal or upper left chest), many patients, particularly women and older patients, will present with "atypical" ACS-related chest pain [45,46]. Words commonly used to describe "atypical" chest pain associated with ACS include numbness, tingling, burning, stabbing, or pricking. Atypical chest pain location includes any area other than substernal or left sided, such as the back, area between shoulder blades, upper abdomen, shoulders, elbows, axillae, and ears [43,44,45,46]. Aside from atypical clinical presentation, other possible causes of missed ACS diagnosis include failure of interpretation of the history, failure to correctly interpret the electrocardiogram, failure to perform an electrocardiogram when necessary, and lack of proper use of cardiac enzyme test [47].

Neurologic-Related Conditions

Delayed or missed diagnoses of neurologic conditions may result in serious morbidity and mortality. Headaches are a common presenting condition in acute and primary care, and an estimated 5% of all patients admitted to emergency departments have neurologic symptoms [34]. Acute headache with neurologic symptoms may be misdiagnosed as stroke [35,64]. In addition, missed spinal fracture diagnoses are one of the leading causes of malpractice claims against radiologists [48].

One of the most common neurologic conditions is headache; however, it has been estimated that 50% of migraine patients remain undiagnosed or misdiagnosed, and only a small number (8% to 10%) of individuals with migraine take migraine-specific medications such as triptans or ergotamines [65,66]. Patients suffering from daily migraines may be misdiagnosed with chronic sinusitis or rhinitis and repeatedly and unsuccessfully treated with broad-spectrum antibiotics [62,63]. The diagnosis of migraine is based solely on a constellation of signs and symptoms, and a comprehensive medical and neurological examination is required to exclude secondary headache [56]. Useful evidence-based clinical guidelines for migraine screening have been developed and are summarized in the mnemonic POUND: pulsatile headache; one-day duration (4 to 72 hours); unilateral location; nausea or vomiting; and disabling intensity [57]. Competence of the clinician and effective communication with the patient play a crucial role in the diagnosis of migraine.

Infectious Disease-Related Conditions

Acute infection was the most commonly misdiagnosed disease in one study, with the potential adverse outcomes of sepsis, organ damage, and even death [37]. The presentation of infectious diseases may be atypical in certain populations (e.g., the elderly), making detection even more difficult. In one survey of physicians, delayed diagnoses were found to commonly occur with tuberculosis, nontuberculous mycobacterial infections, syphilis, epidural abscess, infective endocarditis, and endemic fungal infections (e.g., histoplasmosis, blastomycosis) [38]. Diseases with general symptoms and varied presentations (e.g., Lyme disease) also present complicated clinical pictures. Adherence to established guidelines for the diagnosis and treatment of specific infectious diseases and attentive patient assessment and history are recommended in order to improve diagnostic accuracy [39,40,42]. In addition, early consultation with an infectious disease specialist has been identified as potentially mitigating factor [38].

5. OTHER CONSIDERATIONS FOR PATIENT SAFETY

The most important issue to improving patient safety is being aware of the particular safety hazards that may exist for various patient populations and on particular specialty units. In addition, education of the patient and the family should be a priority.

Infants and young children are not developmentally or cognitively able to participate in care and decision making, thus putting them at higher risk, especially for medication errors. In addition, when a medication error occurs in this population, infants and young children are at higher risk because of their physical immaturity and increased sensitivity to the effects of drugs. The family or guardian of a pediatric patient should be encouraged to ask questions, especially if something seems wrong. In addition, a meta-analysis found that computerized provider order entry with clinical decision support reduced pediatric medication errors by 36% to 87% [51]. As such, the adoption of electronic support systems may help to reduce or eliminate these errors.

An estimated 30% of individuals 65 years of age or older who are living in the community fall each year [52]. Older patients may have poor vision, as a result of cataracts, glaucoma, and/or macular degeneration, and cardiovascular problems, which might result in syncope or postural hypotension. These conditions may affect patients' balance and stability. Bladder dysfunction, such as nocturia, may cause an elderly patient to have to ambulate more during the night in an unfamiliar environment, thereby increasing the risk of a fall. Lower extremity dysfunctions, such as arthritis, muscle weakness, or peripheral neuropathy, may make it more difficult to ambulate at any time. In addition to being at greater risk for falls, the elderly are also more prone to medication errors as their ability to understand instructions or to recognize an unfamiliar medication may be affected by dementia or other cognitive disorders. Interventions that can help prevent falls in the elderly include exercise programs, tai chi, vision improvement (e.g., first cataract surgery), and multifactorial assessment and intervention [52].

There are also unique factors that increase the risk of medical errors on specialty units. For instance, in critical care units, patients may be suffering from environmental psychosis, which could inhibit participation in their care. This is also true of lethargic and comatose patients. These patients are at particular risk because they cannot participate in the identification process. On psychiatric wards, patients may be suicidal or depressed, which may cause them to act out or attempt to harm themselves or others. Patients may also experience orthostatic side effects due to certain psychiatric medications, which may increase the incidence of falls. Obstetric patients are at higher risk for falls because they may have decreased sensation and mobility due to administration of epidural anesthesia, and they may also suffer from excessive blood loss, which could lead to postural hypotension [49]. Again, the key is identifying the unique needs of the particular population.

With regard to education, a number of organizations have developed guidelines to facilitate the role of patients as their own safety advocates. These guidelines are not intended to shift the burden of monitoring medical error to patients. Rather, they encourage patients to share responsibility for their own safety. As healthcare professionals, we should ensure that all of our patients are familiar with these guidelines. The Agency for Healthcare Research and Quality has developed a "Patient Fact Sheet" that outlines 20 tips for patients to help prevent medical errors [53]. Although some of these suggestions may seem extreme, many patients now desire to have a more active role in their care. Some of these items have become routine or are currently required, such as consultations by pharmacists when a patient picks up a prescribed medication.

USE OF AN INTERPRETER

As a result of the evolving racial and immigration demographics in the United States, interaction with patients for whom English is not a native language is inevitable. Because patient education is such a vital aspect of preventing medical errors, it is each practitioner's responsibility to ensure that information and instructions are explained in such a way that allows for patient understanding. When there is an obvious disconnect in the communication process between the practitioner and patient due to the patient's lack of proficiency in the English language, an interpreter is required.

Interpreters are more than passive agents who translate and transmit information back and forth from party to party. They should be professionally trained in ethics, accuracy, completeness, and impartiality. Furthermore, it is the interpreter's role to negotiate cultural differences and promote culturally responsive communication and practice. When they are enlisted and treated as part of the interdisciplinary clinical team, they serve as cultural brokers, who ultimately enhance the clinical encounter. In any case in which information regarding diagnostic procedures, treatment options, or medication/treatment measures is being provided, the use of an interpreter should be considered.

6. CONCLUSION

Although the United States has one of the top healthcare systems in the world, it is apparent that the numbers of medical errors are at unacceptably high levels. The consequences of medical errors are often more severe than the consequences of mistakes in other industries. They may lead to death or to serious and long-term disability, which underscores the need for aggressive action in this area. As a starting point, we should become an active part of the solution. This will only happen if all healthcare professionals voice their concerns when they identify problems in a system or process. In addition, we should actively participate in the root cause analysis process, understanding that the goal is not to assign blame, but rather to identify how we can improve the process to provide the best quality care to our patients. Medical errors are costly, not only because patients may lose their lives or livelihoods, but also because patients lose trust in the system and colleagues lose faith in each other. To preserve the integrity of our system, we must correct this problem, and the solution begins with each of us.

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94820 • Chronic Cough in Adults

Mark Rose, BS, MA, LP

www.netce.com

Copyright © 2024 NetCE, All rights reserved.

Chronic cough is common, debilitating, often treatment-refractory, and can persist for years or decades as patients cycle through repetitive clinical workups without effective treatment. Hypersensitivity of vagal afferent neurons in the airways and their central projections underlies chronic cough, regardless of inciting etiology or comorbid disease. Thorough assessment to identify and treat potential causes is required. Coughing that persists is considered refractory chronic cough; for these patients, the therapeutic focus shifts to downregulating the hypersensitive cough pathway. Chronic cough is now considered a distinct pathologic entity and not merely a symptom of another disease. This distinction is important for clinicians to make.

Table of Contents

94820 • Chronic Cough in Adults

Course Overview

Audience

Accreditations & Approvals

Designations of Credit

Individual State Nursing Approvals

Special Approvals

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Division Planners

Division Planners Disclosure

Director of Development and Academic Affairs

Director Disclosure Statement

About the Sponsor

Disclosure Statement

Implicit Bias in Health Care

1. INTRODUCTION

2. BACKGROUND

3. COUGH SEVERITY MEASURES

4. EPIDEMIOLOGY

PREVALENCE

REFRACTORY AND UNEXPLAINED CHRONIC COUGH

DISEASE BURDEN AND HEALTHCARE UTILIZATION

RISK FACTORS

5. PATIENT IMPACT OF CHRONIC COUGH

PHYSICAL IMPACT

PSYCHOSOCIAL AND QUALITY OF LIFE IMPACT

6. NATURAL HISTORY AND DISEASE COURSE

7. PATHOPHYSIOLOGY OF CHRONIC COUGH

NORMAL PHYSIOLOGY

PATHOPHYSIOLOGY OF CHRONIC COUGH AND COUGH REFLEX HYPERSENSITIVITY

SUMMARY

8. INITIAL EVALUATION OF CHRONIC COUGH

DEFINITIONS OF COUGH

PATIENT HISTORY

PHYSICAL EXAMINATION

MANDATORY INITIAL TESTS

"RED FLAG" ASSESSMENT OF SERIOUS UNDERLYING CAUSES OF COUGH

RECORDS REVIEW

THE ANATOMIC DIAGNOSTIC PROTOCOL (ADP)

DIAGNOSTIC TESTS

9. IDENTIFICATION AND MANAGEMENT OF UNDERLYING ETIOLOGIES

THE "TREATABLE TRAITS" APPROACH IN CHRONIC AIRWAY DISEASES

ENDOTYPES OF COUGH-RELATED CHRONIC INFLAMMATORY DISEASES

10. TREATMENT

CHRONIC AIRWAY INFLAMMATION

EMPIRIC TREATMENT APPROACH

BEHAVIORAL TREATABLE TRAITS

LOWER AIRWAY ETIOLOGIES OF CHRONIC COUGH AND MANAGEMENT

UPPER AIRWAY ETIOLOGIES OF CHRONIC COUGH AND THEIR MANAGEMENT

REFLUX DISORDER ETIOLOGIES OF CHRONIC COUGH AND THEIR MANAGEMENT

TREATABLE TRAITS AND THOROUGHNESS

11. TREATMENT OF REFRACTORY CHRONIC COUGH

PHARMACOTHERAPY

INVESTIGATIONAL PHARMACOTHERAPIES

NONPHARMACOLOGIC THERAPY

12. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

94820 • Chronic Cough in Adults

Education Category. Infection Control / Internal Medicine

Release Date. 08/01/2024

Expiration Date. 07/31/2027

Course Overview

Chronic cough is common, debilitating, often treatment-refractory, and can persist for years or decades as patients cycle through repetitive clinical workups without effective treatment. Hypersensitivity of vagal afferent neurons in the airways and their central projections underlies chronic cough, regardless of inciting etiology or comorbid disease. Thorough assessment to identify and treat potential causes is required. Coughing that persists is considered refractory chronic cough; for these patients, the therapeutic focus shifts to downregulating the hypersensitive cough pathway. Chronic cough is now considered a distinct pathologic entity and not merely a symptom of another disease. This distinction is important for clinicians to make.

Audience

This course is designed for physicians, physician assistants/associates, and nurses involved in the care of patients with chronic cough.

Accreditations & Approvals

In support of improving patient care, TRC Healthcare/NetCE is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. NetCE is accredited by the International Accreditors for Continuing Education and Training (IACET). NetCE complies with the ANSI/IACET Standard, which is recognized internationally as a standard of excellence in instructional practices. As a result of this accreditation, NetCE is authorized to issue the IACET CEU.

Designations of Credit

This activity was planned by and for the healthcare team, and learners will receive 10 Interprofessional Continuing Education (IPCE) credit(s) for learning and change. NetCE designates this enduring material for a maximum of 10 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. NetCE designates this continuing education activity for 10 ANCC contact hour(s). NetCE designates this continuing education activity for 5 pharmacology hour(s) for physician assistants. NetCE designates this continuing education activity for 5 pharmacotherapeutic/pharmacology contact hour(s). NetCE designates this continuing education activity for 12 hours for Alabama nurses. Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 10 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Completion of this course constitutes permission to share the completion data with ACCME. Successful completion of this CME activity, which includes participation in the evaluation component, enables the learner to earn credit toward the CME and/or Self-Assessment requirements of the American Board of Surgery's Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit. This activity has been approved for the American Board of Anesthesiology’s® (ABA) requirements for Part II: Lifelong Learning and Self-Assessment of the American Board of Anesthesiology’s (ABA) redesigned Maintenance of Certification in Anesthesiology Program® (MOCA®), known as MOCA 2.0®. Please consult the ABA website, www.theABA.org, for a list of all MOCA 2.0 requirements. Maintenance of Certification in Anesthesiology Program® and MOCA® are registered certification marks of the American Board of Anesthesiology®. MOCA 2.0® is a trademark of the American Board of Anesthesiology®. This activity has been designated for 10 Lifelong Learning (Part II) credits for the American Board of Pathology Continuing Certification Program. Through an agreement between the Accreditation Council for Continuing Medical Education and the Royal College of Physicians and Surgeons of Canada, medical practitioners participating in the Royal College MOC Program may record completion of accredited activities registered under the ACCME's "CME in Support of MOC" program in Section 3 of the Royal College's MOC Program. AACN Synergy CERP Category A. NetCE is authorized by IACET to offer 1 CEU(s) for this program.

Individual State Nursing Approvals

In addition to states that accept ANCC, NetCE is approved as a provider of continuing education in nursing by: Arkansas, Provider #50-2405; California, BRN Provider #CEP9784; California, LVN Provider #V10662; California, PT Provider #V10842; District of Columbia, Provider #50-2405; Florida, Provider #50-2405; Georgia, Provider #50-2405; Kentucky, Provider #7-0054 through 12/31/2025; South Carolina, Provider #50-2405; West Virginia RN and APRN, Provider #50-2405.

Special Approvals

This activity is designed to comply with the requirements of California Assembly Bill 1195, Cultural and Linguistic Competency.

Course Objective

Chronic cough is difficult to effectively assess and treat, leading to extended periods before diagnosis and significant negative impact on patients' quality of life. The purpose of this course is to provide clinicians with the knowledge and skills necessary to identify and treat patients with chronic cough, regardless of underlying etiology, in accordance with clinical guidelines.

Learning Objectives

Upon completion of this course, you should be able to:

1. Describe the background and terminology related to chronic cough.

2. Compare and contrast available cough severity measures.

3. Outline the epidemiology of chronic cough and underlying etiologies.

4. Evaluate the impact of chronic cough on various dimensions of patients' lives.

5. Discuss the natural history and course of chronic cough.

6. Describe the pathophysiology of chronic cough.

7. Outline components of the initial evaluation of patients with chronic cough.

8. Identify potential underlying etiologies of chronic cough as well as appropriate management approaches for these conditions.

9. Analyze available treatment modalities for chronic cough of various underlying causes, including upper respiratory, lower respiratory, and reflux-associated cough.

10. Identify appropriate modalities for the treatment of refractory chronic cough, including pharmacotherapy, nonpharmacologic approaches, and investigational agents.

Faculty

Mark Rose, BS, MA, LP, is a licensed psychologist in the State of Minnesota with a private consulting practice and a medical research analyst with a biomedical communications firm. Earlier healthcare technology assessment work led to medical device and pharmaceutical sector experience in new product development involving cancer ablative devices and pain therapeutics. Along with substantial experience in addiction research, Mr. Rose has contributed to the authorship of numerous papers on CNS, oncology, and other medical disorders. He is the lead author of papers published in peer-reviewed addiction, psychiatry, and pain medicine journals and has written books on prescription opioids and alcoholism published by the Hazelden Foundation. He also serves as an Expert Advisor and Expert Witness to law firms that represent disability claimants or criminal defendants on cases related to chronic pain, psychiatric/substance use disorders, and acute pharmacologic/toxicologic effects. Mr. Rose is on the Board of Directors of the Minneapolis-based International Institute of Anti-Aging Medicine and is a member of several professional organizations.

Faculty Disclosure

Contributing faculty, Mark Rose, BS, MA, LP, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Division Planners

John M. Leonard, MD

Mary Franks, MSN, APRN, FNP-C

Division Planners Disclosure

The division planners have disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Director of Development and Academic Affairs

Sarah Campbell

Director Disclosure Statement

The Director of Development and Academic Affairs has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

About the Sponsor

The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.

Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.

Disclosure Statement

It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.

Implicit Bias in Health Care

The role of implicit biases on healthcare outcomes has become a concern, as there is some evidence that implicit biases contribute to health disparities, professionals' attitudes toward and interactions with patients, quality of care, diagnoses, and treatment decisions. This may produce differences in help-seeking, diagnoses, and ultimately treatments and interventions. Implicit biases may also unwittingly produce professional behaviors, attitudes, and interactions that reduce patients' trust and comfort with their provider, leading to earlier termination of visits and/or reduced adherence and follow-up. Disadvantaged groups are marginalized in the healthcare system and vulnerable on multiple levels; health professionals' implicit biases can further exacerbate these existing disadvantages.

Interventions or strategies designed to reduce implicit bias may be categorized as change-based or control-based. Change-based interventions focus on reducing or changing cognitive associations underlying implicit biases. These interventions might include challenging stereotypes. Conversely, control-based interventions involve reducing the effects of the implicit bias on the individual's behaviors. These strategies include increasing awareness of biased thoughts and responses. The two types of interventions are not mutually exclusive and may be used synergistically.

1. INTRODUCTION

Chronic cough, or cough lasting longer than eight weeks, is a debilitating disease that can result in patients coughing hundreds to thousands of times every day. This physically exhausting and socially isolating condition can persist for years or decades, degrade the quality of life in nearly every domain, result in numerous medical and psychosocial consequences, yet its adverse impact on patients is often overlooked or underappreciated by clinicians. While acute cough is typically transient and self-limited, chronic cough often poses a diagnostic and therapeutic challenge; both non-treatment and over-treatment with ineffective medication are common [1,2]. Cough that persists despite investigation and treatment is especially vexing for patients and clinicians [3].

2. BACKGROUND

The anatomic, diagnostic protocol (ADP) established in the late 1970s that chronic cough in patients with negative chest x-ray findings is a symptom of asthma, postnasal drip, or acid reflux. Later refined to asthma, nonasthmatic eosinophilic bronchitis, upper airway cough syndrome, and GERD, it was believed that treating these underlying etiologies led to a favorable outcome in 90% of patients with chronic cough [4,5,6].

However, a large proportion of patients with these conditions do not have chronic cough [7]. Moreover, in many patients, cough persists despite treatment of its presumed cause (referred to as refractory chronic cough) or an underlying cause cannot be identified (referred to as unexplained chronic cough) [8]. This suggested that additional pathophysiological processes were involved [7].

In 2014, the European Respiratory Society (ERS) introduced cough hypersensitivity syndrome, defining chronic cough as a distinct clinical entity [9]. The 2020 ERS clinical practice guideline for chronic cough was pivotal in establishing cough hypersensitivity syndrome, influencing subsequent national and international chronic cough guidelines [10,11,12,13].

In 2016, the "treatable traits approach" was introduced to improve the outcomes of pulmonary patients with complex clinical syndromes (e.g., asthma and COPD) and variable treatment responses by moving beyond practice guidelines directed at diagnostic categories as a single disease entity, to identify and treat relevant phenotypic and endotypic "traits" instead [14,15,16]. The treatable traits approach gained rapid acceptance in pulmonary medicine and endorsement in chronic cough guidelines [5,17,18].

Cough performs an essential physiological function, mediated by cough reflex pathways in the airways and brain. In some individuals, irritation or inflammation of vagal afferent nerves in the airway leads to cough reflex hypersensitivity, the cardinal feature of cough hypersensitivity syndrome, peripheral and central sensitization, and clinical manifestations of allotussia, hypertussia, and/or laryngeal paresthesia (Table 1) [3,19,20]. The demographic, pathophysiological, and clinical similarities between cough hypersensitivity syndrome and chronic neuropathic pain are numerous. Chronic pain research has substantially informed how chronic cough and cough hypersensitivity syndrome are understood; both are disorders of sensory processing [4,21,22].

Table 1: CHRONIC COUGH TERMINOLOGY

Term

Definition

Acute cough

Cough lasting less than 3 weeks

Subacute cough

Cough lasting 3 to 8 weeks

Chronic cough

Cough lasting more than 8 weeks

Refractory chronic cough

Cough that persists despite guideline-based treatment of the presumed underlying cause(s)

Unexplained chronic cough

No diagnosable cause of cough is found despite extensive investigation for common and uncommon causes

Allotussia

Cough triggered by innocuous stimuli (e.g., laughing, talking, changes in ambient temperature)

Hypertussia

Exaggerated coughing triggered by mildly tussive stimuli (e.g., strong odors, second-hand cigarette smoke)

Urge to cough (laryngeal paresthesia)

A distinct, often debilitating sensation of irritation or "itch" in the throat or chest that precede cough and is not satiated by coughing

Cough reflex hypersensitivity

The cardinal feature of cough hypersensitivity syndrome

Cough hypersensitivity syndrome

Disorder characterized by cough triggered by mildly tussive or innocuous stimuli, with features of allotussia, hypertussia, and/or laryngeal paresthesia

Source: [5,9,26]

Sensitization of cough pathways may persist long after resolution of the inciting acute or subacute event. These chronic coughs will remain unexplained by diagnostic workups that do not consider cough hypersensitivity. Cough hypersensitivity syndrome may improve with the targeted intervention of other treatable traits. If chronic cough persists, the patient has refractory chronic cough [5].

Refractory and unexplained chronic cough are diagnoses of exclusion. A thorough, systematic clinical workup is required so that non-obvious and obvious causes of chronic coughing can be identified. The treatable traits approach may significantly expand clinically important intervention targets. After a diagnosis of refractory/unexplained chronic cough is made, therapeutic attention shifts to downregulating the hypersensitive cough reflex [5].

Maturation in research and practice has led to novel and emerging therapeutic options for patients with refractory chronic cough. Randomized controlled trials of existing centrally acting agents have identified the efficacy of low-dose morphine and gabapentin [10,23,24]. The development of P2X3 receptor antagonists, a novel peripherally acting drug class, has led to the approval of gefapixant for the treatment of refractory chronic cough in the European Union, Japan, and Switzerland, with U.S. Food and Drug Administration (FDA) advisory committee review believed imminent as of 2024 [25]. In a given patient, refractory/unexplained chronic cough may primarily involve peripheral mechanisms, central mechanisms, or both, and no tool is available for predicting therapeutic response to peripherally or centrally acting antitussive agents.

As of 2024, there are no FDA-approved treatments for chronic cough or for refractory chronic cough. When chronic cough persists after potential underlying causes are identified and treated according to current practice guidelines (e.g., for chronic cough related to nonasthmatic eosinophilic bronchitis or GERD), all therapeutic options for refractory chronic cough are prescribed off-label.

Important knowledge advances in this rapidly evolving field are not reaching healthcare professionals in the United States because chronic cough guidelines published for domestic consumption have become outdated. From this course, clinicians will gain current information on chronic cough and refractory/unexplained chronic cough, including the pathophysiology, differential diagnosis, and clinical management, essential for healthcare professionals in primary care, respiratory medicine, and ear/nose/throat (ENT) settings.

3. COUGH SEVERITY MEASURES

Patients with chronic cough experience cough-related physical, psychological, and social burdens, which can result from different aspects of cough severity, including cough frequency, cough intensity, disruption of daily activities due to cough, and cough-specific health-related quality of life. The severity and impact of chronic cough on physical, psychological, and social domains can be quantified through several validated objective and subjective measures [27].

Patient-reported outcome measures obtain a comprehensive understanding of the impact across these domains [27]. Patient-reported outcomes capture many issues that cannot be assessed effectively by objective measures and are also inexpensive, readily available, convenient, and easy to use for the patient [28]. A minimal clinically importance difference, the smallest change in an outcome that patients would perceive as important, is established for both objective and patient-reported outcome tools [29]. Cough measures mentioned throughout this course are summarized inTable 2. Cough frequencies of greater than 700 over an hour have been recorded [28].

Table 2: COUGH MEASURES

Name

Domains/Items, Rating and Minimal Clinically Importance Difference (MCID)

Comments

Health-related quality of life patient-reported outcome tools

Leicester Cough Questionnaire (LCQ)

Seven-point Likert scale (1=all of the time; 7=none of the time); 19 items in 3 domains: physical, psychological, and social. Total score range: 3 (maximal impairment) to 21 (no quality-of-life impairment).

MCID: 1.5 to 2.5 increase

The most widely used tool for assessing quality of life impact of chronic cough

Cough Quality of Life Questionnaire (CQLQ)

Four-point Likert scale (1=strongly disagree; 4=strongly agree); 28 items over 6 domains: physical and extreme physical complaints, psychosocial issues, emotional well-being, safety fears, and functional abilities. Total score range: 28 (no adverse effect of cough) to 112 (worst possible impact).

MCID: 10.6 to 21.9

Contains more items on physical impact of chronic cough (e.g., fractured ribs, headaches, immune deficiency, tuberculosis)

Hull Airway Reflux Questionnaire (HARQ)

Six-point scale (0=no symptoms; 5=most severe) of 14 items that measure airway hypersensitivity in chronic cough. Total score range: 0 to 70

Normal is <14

MCID: 16

Also used as a diagnostic tool for airway reflux, and to assess unexplained respiratory symptoms

Cough Severity Diary (CSD)

11-point scale (0=never; 10=constantly) of 7 items on frequency; intensity; disruptiveness

MCID ≥1.3 total score, −1.4 to −1.1 domain scores

Captures the severity and impact of chronic cough. Developed in response to patient feedback.

Objective assessment tools

VitaloJAK Cough Monitor

Electronic cough recording monitors worn by patients to measure cough frequency, typically as coughs per hour over 24 hours

MCID: ≥20% to 30% decrease

Does not capture the episodic nature of chronic cough, a primary factor in patients' disease burden

Leicester Cough Monitor (LCM)

Subjective tools

Visual Analogue Scale (VAS)

Score range 0 (no cough) to 100 mm (worst cough ever)

MCID: 30-mm reduction on the 100-mm cough severity VAS

—

Numerical Rating Scale (NRS)

Score range 0 (no cough) to 10 (worst cough ever)

Source: [28,29,30]

4. EPIDEMIOLOGY

PREVALENCE

Cough is a frequent reason for seeking outpatient medical attention in the United States, accounting for as many as 30 million clinical visits per year, up to 40% of which result in specialist referral [31].

Chronic cough has a prevalence among U.S. adults of roughly 10%, of whom 92% visited healthcare clinicians in the past six months [32]. Chronic cough is estimated to cost $6.8 billion annually in the United States, and an estimated $3.6 billion is spent annually on over-the-counter therapies [33]. The economic implications of chronic cough include the cost of outpatient visits, plus diagnostic workups, prescription medications to treat cough, and lost work and lost school productivity [1]. While inconsistent definitions prohibit direct comparisons of chronic cough prevalence between different countries or ethnicities, chronic cough appears to be more common in Europe, North America, and Australia than in Asian countries [32,34].

In KNHANES, a nationally representative study of the Korean adult population, the point prevalence of acute (<3 weeks), subacute (3 to 8 weeks), and chronic (>8 weeks) cough was 2.5%, 0.8% and 2.6%, respectively. The modal durations of current cough were less than one week (31.1%), and more than one year (27.7%); this bimodal distribution reflects the different pathophysiology of acute and chronic cough [35].

REFRACTORY AND UNEXPLAINED CHRONIC COUGH

Refractory chronic cough is seen in 20% to 59% of patients presenting to specialist cough clinics [36]. At Kaiser Permanente Southern California, 11,290 patients with specialist-diagnosed chronic cough were treated and followed for one year; 40.6% continued coughing despite etiological treatment by specialists (i.e., refractory chronic cough) [37].

Roughly 10% of patients with chronic cough lack an identifiable cause despite thorough evaluation (i.e., unexplained chronic cough), including 17% of patients with chronic cough in the Kaiser Permanente cohort [1,37]. Of 43,453 patients receiving primary care for chronic cough in the UK, 31% had ongoing chronic cough in the absence of associated comorbidities (i.e., no causal explanation or unexplained chronic cough) [4].

DISEASE BURDEN AND HEALTHCARE UTILIZATION

The Kaiser Permanente study examined the disease burden of chronic cough in comorbidities, medication use, and exacerbations [37]. Diagnoses included GERD (44%), hypertension (42%), allergic rhinitis (33%), chronic rhinitis (31.5%), asthma (31%), chronic sinusitis (24.4%), obesity (24%), upper airway cough syndrome (20.4%), depression (20%), and cough complications (19%). Nearly 40% of patients with unexplained chronic cough consulted at least two different specialist departments. In the previous three years, about half of the patients with emergency department visits (28.5%) or hospitalizations (10%) were for respiratory events [37]. Medications were respiratory: nasal corticosteroids (55%), short-acting b2-agonists (50.5%), inhaled corticosteroids/long-acting b2-agonist (27%), inhaled corticosteroid monotherapy (24%), and leukotriene modifiers (18.6%); non-respiratory: antitussive codeine (59%), proton pump inhibitors (PPIs) (45%), antidepressants (26%), anxiolytics (15.5%), and gabapentinoids (14%); and other: systemic antibiotics (72.4%) and oral corticosteroids (47%).

Over one year, patients with emergency department visits (26%) and hospitalizations (12%) remained high; more than 50% were respiratory-related. Antitussive and psychotherapeutic drugs were dispensed at a frequency similar to the baseline year. The clinical and economic burden was especially high in patients with both respiratory disease and GERD, but chronic cough persistence (40.6%) was similar between subgroups [37].

A subsequent Kaiser Permanente study of patient-level burden used patient-related outcomes (average chronic cough 8 years) [38]. Mean scores were 11 on LCQ (maximum: 21), 33 on HARQ (normal: ≤13), and 57 on CQLQ (maximum: 112). Correlations were high between LCQ and HARQ (–0.65), LCQ and CQLQ (–0.80), and HARQ and CQLQ (0.69). Patients with chronic cough-related respiratory and gastrointestinal disorders were generally similar. Treatment responses were suboptimal. Women (compared with men) and non-White individuals (compared with White individuals) reported significantly worse cough severity and poorer LCQ, HARQ, and CQLQ scores.

The patient-reported burden of chronic cough was substantial, with long duration, high severity, poor health status, high degree of cough hypersensitivity, low quality of life, multiple cough triggers, and frequent laboratory testing, specialist care, and medications. The study provides strong evidence that patients with chronic cough exhibit frequent poor responses to medications and overall control [38].

The objective and patient-reported burden of chronic cough is substantial, particularly in women and non-White minorities, which markedly affects daily living with inadequate response to treatments.

RISK FACTORS

Risk factors of chronic cough include smoking, female sex, older age, obesity, asthma, allergic rhinitis, rhinosinusitis, and angiotensin-converting enzyme (ACE) inhibitor use for hypertension treatment [34,39].

In the United States, 18% of adults who smoke cigarettes have chronic coughs [39]. Cigarette smokers are three times more likely to report chronic cough than never-smokers and ex-smokers, and the cough is usually due to chronic bronchitis. However, most patients in cough specialist clinics are nonsmokers [19]. Among 1,000 patients evaluated at a cough center in the Bronx, 2.7% were active smokers and 27% former smokers [40]. Of 11,290 Kaiser Permanente patients with chronic cough, 65% were never-smokers and 2.3% were current smokers [37].

Age and sex underlie the burden and prevalence of chronic cough; more than 67% of patients presenting with chronic cough to specialist clinics are female, likely due to gender differences in cough reflex sensitivity [1,19]. Cough reflex sensitivity was assessed in individuals from China, India, and northwest Europe. No differences between ethnic groups were found, suggesting that racial variation in chronic cough prevalence may not reflect differences in cough reflex sensitivity and may be influenced by asthma, allergy, or environmental factors [34,39,41]. Women in all three ethnic groups demonstrated lower cough thresholds [41].

While chronic cough can occur at any age, the rate rises substantially in women who are 40 years of age or older and is highest in the 60 to 69 age group. The highest rates in men occur between 50 and 69 years of age [1]. In KNHANES, chronic cough increased significantly with age. The odds ratio of 2.20 suggests a substantial increase in chronic cough likelihood for individuals 65 years of age or older (compared with those 18 to 39 years of age). The associations with older age were independent of current smoking and comorbidities [35].

In separate longitudinal European population studies, chronic cough was associated with low educational level and lower socioeconomic status [34]. A systematic review found a significant association between low education level and risk of chronic cough [42].

In South Korea and China, higher male prevalence of chronic cough was attributed to differences in smoking habits and air pollution exposures, respectively [28]. Occupational irritants, such as fumes, gases, cleaning products or dust, may cause cough by triggering cough reflex or by inducing oxidative stress and eosinophilic inflammation, but the effect of such factors on chronic cough remains elusive. Air pollution is an important risk factor for chronic cough. Levels of fine particulate matter ≤2.5 mcm in diameter (or PM2.5) are higher in East Asian than in European or North American countries but the prevalence of chronic cough is lower, suggesting potential host-environment interactions in developing chronic cough [19].

Persistent cough is a class-wide adverse effect of ACE inhibitors, and the 5% to 35% prevalence is much higher in East Asian than in other populations. In genotype studies, the genetic polymorphisms ACE I/D and SLCO1B1 were related to ACE inhibitor-induced cough and were more common in East Asian populations, which may account for the ethnic differences and possibly predict risk of ACE inhibitor-induced cough [43].

5. PATIENT IMPACT OF CHRONIC COUGH

Patients report numerous cough-related physical and psychosocial effects, most commonly fatigue, sleep disturbance, exhaustion, breathlessness, headache, dizziness, musculoskeletal pain, wheezing, impairment of speech, vomiting, excessive perspiration, self-consciousness, and interference with daily activities [28,44]. These effects have a significant impact on patients' quality of life.

PHYSICAL IMPACT

During vigorous coughing, intrathoracic pressures may reach 300 mm Hg and expiratory velocities approach 500 miles per hour (mph) (85% of the speed of sound). These physical forces cause many of the cardiovascular, gastrointestinal, genitourinary, quality of life, musculoskeletal, neurologic, ophthalmologic, psychosocial, and respiratory complications of chronic cough, ranging from the relatively minor to life-threatening or even fatal. Comorbid illnesses or older age can magnify these effects [44,45].

Surgical Complications and Hernia

Surgical complications from uncontrolled coughing include extrusion (i.e., expulsion) of ocular contents during eye surgery, and wound dehiscence (i.e., splitting or bursting open) following cardiac or abdominal surgery. Similarly, severe coughing can cause inguinal, femoral, umbilical, lumbar, or abdominal wall hernia [45].

Fracture

Cough-induced rib fractures, another painful and potentially serious complication of chronic cough, often involve multiple ribs, particularly ribs 5 through 7. The number of ribs fractured is associated with higher mortality rates, particularly in older patients who often have decreased bone density due to osteoporosis (also an adverse effect of long-term corticosteroid treatment). However, rib fractures can also occur in patients with normal bone density [44,46].

Stress Urinary Incontinence

Stress urinary incontinence, defined as the unintentional loss of urine during or following a bout of coughing or other physical activity, significantly contributes to quality-of-life disruption caused by chronic cough in women. Of 210 consecutive adult women evaluated at a cough center for chronic cough, 63.3% reported stress urinary incontinence induced by cough episodes; stress urinary incontinence developed after the onset of chronic cough and solely occurred during or after coughing in 92.5% and at least daily in 47.3%. For context, 3.5% of similarly aged women in the community experience stress urinary incontinence, while only 5% of men with chronic cough report stress urinary incontinence as an issue significantly impacting their quality of life [28,47].

Surveys have reported lower rates of urinary incontinence in women with chronic cough, but most women will not volunteer a history of cough-induced stress urinary incontinence unless specifically asked. This may explain the higher prevalence in this study, because the establishment of trust between patient and physician may have encouraged sharing such information. After discussion ensues, patients are often relieved to learn this is a common problem faced by women with chronic cough [47].

Cough Syncope

Cough-evoked syncope is a serious and potentially fatal consequence of coughing. Numerous reports of motor vehicle accidents resulting from cough syncope include the deaths of drivers and pedestrians. While the exact mechanism of remains debated, the required generation of very high intrathoracic pressures likely explains the nearly uniform profile of patients with cough syncope as large male subjects with obstructive airway disease [48]. Cough syncope is considered relatively uncommon, although 10% of subjects with chronic cough in a community sample reported experiencing cough syncope [5,49]. The mandatory loss of driver's license in some countries (e.g., the UK) has a major impact on employment prospects for these patients [28].

PSYCHOSOCIAL AND QUALITY OF LIFE IMPACT

Chronic cough can interfere with all aspects of patients' lives, including daily living activities, social interactions, home management, recreational activities, and employment. Importantly, when triggers of coughing bouts are very difficult to avoid, the psychosocial impact can be substantial. Chronic cough has a negative impact on relationships, with spouses not being able to tolerate the cough as a key reason for patients' health-related dysfunction [28]. In a multinational European survey of 1,120 persons with chronic cough, most reported that coughing affected their quality of life (96%), disturbed their family and friends (94%), and affected activities they enjoyed (81%) [51].

The psychological effects associated with chronic cough are highly prevalent, with an impact on mental health comparable to that of stroke or Parkinson disease. Studies of patients with chronic cough have reported high rates of anxiety (33% to 52%) and depression (16% to 91%) [28].

Patients may avoid or be uncomfortable in social situations due to the embarrassment of coughing, its effects (e.g., stress urinary incontinence, retching), and/or the perception by others that they have a contagious condition or are a heavy smoker [28]. The COVID-19 pandemic increased the social stigma of persistent coughing due to its association with contagious respiratory diseases [50].

6. NATURAL HISTORY AND DISEASE COURSE

Little is known about the natural history of cough hypersensitivity, but the available evidence suggests that patients often suffer from it for many years [4]. In a longitudinal study of patients with unexplained chronic cough, cough severity worsened (36%) or was unchanged (23%) over 7 to 10 years. Predictors of cough persistence or improvement could not be identified. Unexpectedly, longitudinal spirometry data showed declines in forced expiratory volumes over one second (FEV1) that were well above population norms for similarly aged nonsmokers. The striking magnitude of decline argued against a chance finding. Around 10% of patients developed spirometric features of COPD [52].

The abnormally rapid decline in FEV1 and a significant minority of patients developing COPD raise the possibility that unexplained chronic cough is associated with a persistent damaging airway process and could be a risk factor for COPD [52]. A 2023 study confirmed that chronic cough is highly associated with FEV1 decline, regardless of COPD presence, while chronic cough in patients suffering from COPD is associated with lower FEV1, more dyspnea, worse health status, and is an independent risk factor for exacerbations of COPD possibly linked to altered transient receptor potential (TRP) channel function [53].

Cough is often the most bothersome and intractable symptom reported by patients with asthma, and the significant disease burden of chronic cough was described in a prospective cohort of 323 consecutive adult participants with asthma who received optimized asthma therapy. After 12-month, those with chronic cough had more airflow obstruction; worse asthma control and quality of life; increased airway inflammation; upper respiratory tract infection as a trigger; more psychological, rhinitis, and COPD comorbidities; greater work productivity loss and daily activity impairment; and increased exacerbations. These findings call for more attention to chronic cough in asthma [54].

In summary, chronic cough is related to an accelerated FEV1 decline over time, regardless of smoking history or COPD diagnosis, but the relationship between chronic cough and worse clinical outcomes lacks a clear pathophysiological explanation [55].

7. PATHOPHYSIOLOGY OF CHRONIC COUGH

NORMAL PHYSIOLOGY

The Cough Reflex

Cough is an innate reflex that protects the airways from foreign objects, clears excess secretions, and preserves airway patency. The cough reflex consists of peripheral airway receptors of afferent nerves, cough control centers in the central nervous system (CNS), and efferent nerves.

Cough occurs in three phases [31,56]. The first is inspiratory, during which the glottis opens widely followed by rapid inhalation sufficient for generating enough air movement to be productive. The second phase is compression. This phase is characterized by the rapid closure of the glottic apparatus and contraction of abdominal and other respiratory muscles compresses the alveoli and bronchiole, increasing intrathoracic pressure to greater than 300 mm Hg. The final phase is expiration, or the sudden opening of the epiglottis and vocal cords results in rapid, high-volume expiratory airflow that may exceed 500 mph in velocity. The force of this process loosens and expels mucous secretions from the airway wall, while the rapid airflow vibrates the larynx and pharynx, inducing the characteristic sounds of cough.

Vagal Afferents

The cough reflex is activated by vagal afferent A-δ and C fibers, sensory neurons originating from brainstem vagal ganglia that innervate the larynx and proximal airways. A-δ fibers are mechanoreceptors, activated by airway mucus, inhaled foreign bodies, and low pH (i.e., acidity). C-fibers are nociceptive chemoreceptors, activated by signaling molecules and mediators of inflammation or tissue damage within the airway [19,25,57,58].

Neurobiological Processes

Complex neurobiological processes in the peripheral nervous system, brainstem, and higher cerebral cortex mediate coughing [59]. Receptors (e.g., P2X3 purinergic receptors, voltage-gated sodium channels [NaV], bradykinin receptors, and transient receptor potential [TRP] ion channels) and neuropeptides (e.g., substance P, calcitonin gene-related peptide [CGRP]) play important roles [60].

Noxious mechanochemical stimuli in the airways activate ligand-gated ion channels and G protein-coupled receptors on vagal nerve endings; NaV channels depolarize, propagating the signal up the vagus nerve to first-order synapses in brainstem nuclei. From there, the signal is relayed by second-order neurons to brainstem and spinal motor neurons to reflexively modify breathing; to third-order neurons of the primary somatosensory cortex where the unpleasant urge-to-cough sensation is mediated; and to higher-order cortical neurons that mediate conscious perception of cough [23,60].

These ascending third-order pathways enable perception of airway irritation, and regulatory control of descending motor pathways that terminate in the brainstem and in spinal respiratory circuits [22,61]. Under physiologic conditions, higher inhibitory brain processes permit the modification of coughing behavior, and the urge to cough may be suppressed [21].

Extrapulmonary airways (i.e., larynx, trachea, and mainstem bronchi) are also reflexogenic sites essential for preventing aspiration, inhalation of noxious chemicals, and accumulation of excessive mucus; all can induce reflex coughing with irritation of vagal afferent nerves [21].

Coughing is a reflex and a voluntary behavior with or without the sensation of an urge to cough. Reflex cough, behavioral cough, and the urge to cough (which precedes the motor act of coughing) are three separate entities, each dependent on their own neural processes [21,22]. The relevance of these neurophysiological processes is apparent when considering the development of cough hypersensitivity syndrome [21].

PATHOPHYSIOLOGY OF CHRONIC COUGH AND COUGH REFLEX HYPERSENSITIVITY

Chronic cough, unlike protective cough, is a pathologic state that no longer serves a physiologic role [60]. Excessive coughing is a consequence of increased activation of neuronal cough-mediating pathways due to [62,63]:

- Excessive activation of airway vagal afferent terminals by chemical or mechanical irritants

- Neuroplastic changes in vagal afferent fibers

- Neuroplastic changes in the CNS

Nervous system plasticity, or malleability, dictates that excessive stimulation of peripheral nerve fibers can reshape their excitability through changes in receptor expression; synaptic transmission in the CNS is subsequently altered, further increasing the gain within the system [62].

Chronic cough is most associated with and traditionally considered a symptomatic byproduct of asthma, nonasthmatic eosinophilic bronchitis, upper airway cough syndrome, and/or GERD, but most patients with these chronic inflammatory diseases do not have chronic cough. Further, cough severity correlates poorly with cough-associated disease severity, and chronic cough can occur in the absence of these conditions as unexplained chronic cough or unexplained chronic cough [19,20,64]. This implies individual differences in cough reflex sensitivity and that hypersensitivity of airway sensory nerves may underlie chronic cough [65].

Cough hypersensitivity, defined as repeated episodes of coughing often in response to minimal or no discernible triggers, is common to all persons with chronic cough [66]. Extracellular adenosine triphosphate (ATP) may play a prominent role in cough hypersensitivity. During cellular injury or inflammation, cells release ATP to alert neighboring cells to damage. In respiratory conditions associated with chronic cough and airway inflammation, such as COPD and asthma, extracellular ATP may be elevated and sensitivity to ATP is heightened [33]. The NK-1 receptor and its ligand, substance P, may also be involved in inducing and maintaining cough hypersensitivity, both peripherally and centrally, either indirectly through inflammatory mediators or directly by stimulating sensory nerve fibers [33].

Cough Hypersensitivity Syndrome

Cough hypersensitivity syndrome frames chronic cough as a hypersensitivity disorder, akin to chronic pain. Sensitization of vagal afferents by upper or lower airway inflammation leads to increased cough sensitivity to normally anodyne stimuli, the cardinal feature of cough hypersensitivity syndrome [22,58].

In chronic cough, as in chronic pain, peripheral sensitization is necessary but probably insufficient without central sensitization, which alters the efficacy of neurotransmission in the brainstem and regulation of cough reflex-mediating brain pathways [21]. Patients with cough hypersensitivity or chronic pain have shown abnormal activity in the same midbrain areas that amplify incoming cough (or pain) signals [58,67,68].

Chronic pain research substantially informs the conceptual transformation in how chronic cough and refractory chronic cough are understood. Both disorders involve abnormal sensory processing. Taking inspiration from chronic pain, hypertussia describes abnormal excessive coughing in response to airway irritation. Allotussia describes coughing in response to innocuous stimuli. Laryngeal paresthesia describes noxious sensations in the throat or chest associated with an "urge to cough." Peripheral and central sensitization describe processes that alter cough pathway function [62,63].

Peripheral Sensitization

Dysregulation of airway innervation contributes to chronic coughing and is considered the main driver of cough in refractory chronic cough [63].

In airway inflammation, vagal neuron sensitization and plasticity is shown by increased production of neuropeptides, upregulation of glutamate receptors and nociceptive ion channels (e.g., TRPV1), and lower thresholds for activating sensory-evoked cough responses. Neuropeptide upregulation occurs in airway sensory neurons where they are not normally expressed. These effects underlie hypertussia by expanding the cough-evoking stimuli field [21].

For example, bronchoscopic biopsies of patients with chronic cough demonstrated increases in airway epithelial nerve length and branching. The remodeling of these vagal C fibers may contribute to airway hypersensitivity through increased density of fiber terminals and enlargement of their receptive fields. The shearing forces of chronically coughing and/or the resultant release of inflammatory mediators (e.g., ATP) may explain the increased density of epithelial innervation [69].

Whether the primary stimulus for peripheral sensitization is cellular damage, mechanical stress, or nociceptor stimulation is unclear, as all three can trigger ATP release, activating P2X3 receptors [59].

Central Mechanisms

While peripheral nervous system dysfunction is the most-described component of cough hypersensitivity, central dysfunction plays a fundamental role [70]. Patients with cough hypersensitivity attempting to voluntarily suppress coughing show reduced activity in dorsomedial prefrontal and anterior mid-cingulate cortices, suggesting diminished ability to inhibit cough reflex activation [66,67,71].

Patients with refractory chronic cough demonstrate structural and functional alterations in the left frontal brain regions, including lower gray matter volume and enhanced frontoparietal functional connectivity, which may underlie the higher cough scores, greater psychosocial impact, longer disease duration, and impaired cough inhibition in these patients [72].

Studies of chronic cough in asthma and nonasthmatic eosinophilic bronchitis identified increased neuronal sensitivity and subsequent central sensitization via mechanisms of inflammatory-mediated nociceptor sensitization and altered afferent nerve terminal excitability, phenotypic changes in vagal afferent neurons, and central neuroplasticity resulting from increased synaptic signaling from peripheral afferents [73].

The contribution of CNS mechanisms accounts for the efficacy of centrally acting medications (e.g., gabapentin and low-dose morphine) in patients with refractory chronic cough [58].

Laryngeal Hypersensitivity

A study of refractory/unexplained chronic cough patients with cough hypersensitivity referred to a cough clinic suggests highly prevalent laryngeal dysfunction. The 12-month cohort of all referred patients showed high rates of cough hypersensitivity (100%), multiple cough triggers (75%), laryngeal paresthesias (95%), voice abnormalities (50%), upper airway dyspnea (25%), and laryngeal functional abnormalities on nasoendoscopy (73%). Given the frequent constellation of symptoms typifying laryngeal dysfunction and cough hypersensitivity, the authors suggest designating laryngeal hypersensitivity as a specific cough phenotype [74].

Many refractory chronic cough cases have a sensory neuropathic etiology in the hypopharynx and larynx, with laryngeal hypersensitivity a key mechanism [75]. Pharyngeal/laryngeal sensations (e.g., irritation, tickle, throat-clearing), frequently associated with upper airway cough syndrome and reflux cough, may represent sensory neuron dysfunction of vagal afferents in the upper airways and a phenotype of cough hypersensitivity syndrome. Dysphonia, dysphagia, dyspnea, and abnormalities of vocal fold motion on laryngoscopy may present with chronic cough as part of the pharyngeal/laryngeal nerve dysfunction seen in cough hypersensitivity syndrome [76].

Autonomic Dysregulation

There is also evidence of broader autonomic nervous system dysregulation. Compared with healthy controls, patients with chronic cough report more frequent and severe autonomic symptoms in gastrointestinal, orthostatic intolerance, bladder, and pupillomotor domains, primarily in parasympathetically mediated systems, suggesting this population may suffer from dysautonomia. Whether this results from coughing, or if both the cough and dysfunction are part of wider vagal pathology, is unclear [70].

SUMMARY

Functional changes in TRPV1, TRPA1, and P2X3 nerve channels and the development of peripheral and central sensitization are thought to turn cough from a defensive reflex into a cough hypersensitivity syndrome [77]. Hypersensitivity of the cough reflex and deterioration in central inhibition of the cough explain cough persistence [78].

Evidence Based Practice Recommendation

According to the European Respiratory Society, cough hypersensitivity through cell damage and inflammation underlies much of the increased cough seen in other pathologies. The different pathological processes in individual conditions contribute to the disease-specific heterogeneous etiology of cough in other lung disease.

https://erj.ersjournals.com/content/55/1/1901136

Last Accessed: August 12, 2024

Level of Evidence: Expert Opinion/Consensus Statement

Cough hypersensitivity syndrome is identified by symptoms of allotussia, hypertussia, and/or laryngeal paresthesia and may improve with the treatment of other treatable traits. If the chronic cough persists, the patient has refractory chronic cough [5].

Owing to nervous system plasticity, sensitization of cough pathways may persist long after resolution of the inciting event, such as acute viral airway infection. These chronic coughs will remain unexplained by diagnostic workups that do not consider cough hypersensitivity [5].

Currently, there are no available methods to identify susceptibility to nervous system plasticity and sensitization, objectively diagnose cough hypersensitivity syndrome, or predict treatable versus refractory chronic cough.

8. INITIAL EVALUATION OF CHRONIC COUGH

When initially encountering a patient with chronic cough, the primary task is to perform a thorough evaluation that seeks potential underlying treatable causes of chronic cough and to treat the cause(s) according to current clinical practice guidelines [99]. These patients typically undergo extensive medical workup and treatment across multiple subspecialties without improvements in their symptoms, and clinicians should try to break the often-repetitive cycle of investigations, empirical treatment, and worry experienced by these patients [75]. The degree to which patients have been investigated varies, so basic tests may be required. Further investigations depend on the individual's presentation [5]. After a diagnosis of refractory chronic cough is made, the therapeutic focus shifts from identification and treatment of underlying causes to suppression of the hypersensitive cough reflex [99].

The initial evaluation (detailed history and physical examination) accomplishes the key tasks of identifying or ruling out a wide range of diseases underlying the chronic cough and identifying any danger signs that may indicate a diagnosis that needs urgent attention. Any positive findings should guide the initial management [8,44].

DEFINITIONS OF COUGH

To eliminate confusion on how to define cough, the ACCP and the ERS have standardized the definition of cough according to its duration [10,100]. Consistently applying these guideline-established definitions is crucial [2].

Thus, the first step in evaluating cough is to determine its duration. This also helps to narrow the differential diagnosis based on the most common underlying causes [10,100]:

- Acute (<3 weeks) cough:

- Infectious etiologies, especially with viral causes

- Exacerbations of chronic diseases (e.g., asthma, COPD)

- Pneumonia

- Environmental exposures

- Subacute (3 to 8 weeks) cough:

- Postinfectious cough

- Exacerbations of chronic diseases (e.g., asthma, COPD)

- Upper airway cough syndrome

- Chronic (>8 weeks) cough:

- Upper airway cough syndrome

- Asthma

- Nonasthmatic eosinophilic bronchitis

- GERD

In chronic cough, allergies are considered secondary to upper airway cough syndrome or asthma.

When cough has lasted three or more weeks and is not postinfectious, some experts recommend not waiting for eight weeks to begin a chronic cough workup [6].

PATIENT HISTORY

A detailed evaluation is performed and should include the following [2,5,6,8,10,100]:

- Presenting symptoms or cough characteristics:

- Duration

- Productive or nonproductive

- Associated symptoms (e.g., rhinorrhea, nasal congestion, sneeze, fever, sputum production, hemoptysis, dyspnea, weight loss, dysphonia, dysphagia, peripheral edema)

- Prior episodes

- Preceding illnesses (e.g., recent viral infection)

- Clarify whether the patient is coughing, throat-clearing, or both.

- Medical history, including pulmonary and extrapulmonary (e.g., GERD, hypertension, allergic, immune) conditions

- Surgical history, especially involving cardiac, pulmonary, gastrointestinal, and otolaryngological organ systems

- Family history of atopic disease

- Exposure history

- Tobacco and cannabis smoking or vaping (e.g., electronic cigarettes)

- Occupational and environmental exposures

- Recent travel

- Country of origin

- Potential sick contacts

- Review current medications for potential iatrogenic cause. Ask about current use of both prescribed and over-the-counter NSAIDs and aspirin.

It is important to always rule out culprit medications by assessing whether the patient is taking an ACE inhibitor antihypertensive, NSAID, sitagliptin, or any medication that may be suspected of inducing the cough. A dry persistent cough from ACE inhibitor use is caused by bradykinin, substance P, and prostaglandins that accumulate in the upper respiratory tract or lung when ACE is inhibited, enhancing the cough reflex. Stopping the drug typically resolves coughing within four weeks or improves it sufficiently for a diagnosis of iatrogenic cough. Switching to angiotensin II receptor blockers (ARBs) provides antihypertensive control without provoking coughing [6,101].

PHYSICAL EXAMINATION

The physical examination of a patient presenting with chronic should assess for nasal congestion, pharyngeal erythema, tonsillar swelling, hoarseness, stridor, wheeze (particularly focal wheeze), crackles, and other adventitious sounds.

MANDATORY INITIAL TESTS

Evidence Based Practice Recommendation

The European Respiratory Society suggests that clinicians do not routinely perform a chest CT scan in patients with chronic cough who have normal chest radiograph and physical examination.

https://erj.ersjournals.com/content/55/1/1901136

Last Accessed: August 12, 2024

Strength of Recommendation/Level of Evidence: Conditional recommendation, very low-quality evidence

Initial diagnostic testing should include chest radiography (usually x-ray). Spirometry testing of pulmonary function is recommended pre- and post-bronchodilator to evaluate possible asthma or COPD.

"RED FLAG" ASSESSMENT OF SERIOUS UNDERLYING CAUSES OF COUGH

In cough of any duration, the initial evaluation should identify any danger signs that may indicate a diagnosis requiring urgent attention. Important danger signs that will need further evaluation with chest x-ray and possibly laboratory testing and computed tomography (CT) include [44,100]:

- Systemic symptoms (raises suspicion for chronic infection or rheumatic disease):

- Fever

- Night sweats

- Weight loss

- Peripheral edema with weight gain

- Hemoptysis, an indicator of infection (e.g., bronchiectasis, lung abscess, tuberculosis), cancer (e.g., lung, bronchus, or larynx), rheumatologic diseases, heart failure, or foreign body inhalation

- Prominent dyspnea, especially at rest or at night, a possible clue to airway obstruction or lung parenchymal disease

- Possible foreign-body inhalation (requires urgent bronchoscopy)

- Smoker older than 45 years of age with a new cough, change in cough, or co-occurring voice disturbance

- Hoarseness

- Trouble swallowing when eating or drinking

- Vomiting

- Recurrent pneumonia

- Abnormal respiratory exam and/or abnormal chest radiograph coinciding with duration of cough

RECORDS REVIEW

If patients have undergone prior evaluations for upper airway cough syndrome, asthma, GERD, or nonasthmatic eosinophilic bronchitis, obtain and review these medical records, including laboratory values, diagnostic reports, and treatments prescribed, to determine if these etiologies have been accurately assessed, diagnosed, and treated. Patients may not have been completely evaluated for these conditions yet diagnosed based on their response (or lack thereof) to empiric trials, which is important to ascertain [2].

THE ANATOMIC DIAGNOSTIC PROTOCOL (ADP)

Even in current international guidelines that emphasize treatable traits, the anatomic diagnostic protocol (ADP) remains useful in the clinical workup of patients with chronic cough for identifying possible treatable conditions, while recognizing that treatment of the presumed cause(s) does not always improve the cough [19]. Consistent with the ADP, this section organizes chronic cough etiologies and management by their lower airway, upper airway, and gastroesophageal origin.

In nonsmoking, immunocompetent patients not taking an ACE inhibitor and with unremarkable chest radiography, cough lasting longer than eight weeks is considered a symptom of asthma, nonasthmatic eosinophilic bronchitis, upper airway cough syndrome, GERD, or any combination [6]. These four common causes to consider should be evaluated (Table 3).

Table 3: EVALUATION OF COMMON CAUSES OF CHRONIC COUGH

Evaluation

Common Causes

Asthma

NAEB

UACS

GERD

Spirometry

X

Bronchodilator reversibility

X

Bronchoprovocation challenge

X

Allergy evaluation

X

X

X

Sputum eosinophilia

X

Blood eosinophilia

X

Fractional exhaled nitric oxide (FeNO)

X

Sinus imaging

X

Nasopharyngoscopy

X

Empiric treatment trialsa

X

X

X

X

aDiagnostic-Therapeutic Trials

UACS

First-generation oral antihistamines

Inhaled corticosteroids

Inhaled ipratropium

Asthma or NAEB

Inhaled corticosteroids

Systemic (oral) corticosteroids

Leukotriene receptor antagonist

GERD

High-dose proton pump inhibitor (PPI) acid-suppression therapy

Anti-reflux lifestyle measures

Pro-kinetic agent: metoclopramide

GERD = gastroesophageal reflux disease; NAEB = nonasthmatic eosinophilic bronchitis; UACS = upper airway cough syndrome.

Source: [1,82,83,100]

The ADP has been modified to simplify the clinical workup by emphasizing empiric treatment trials for suspected, but not fully investigated or confirmed, disease [77]. According to the rationale, objective diagnostic methods for upper airway cough syndrome, asthma, nonasthmatic eosinophilic bronchitis, and GERD are technically demanding, sometimes difficult for patients, and require specialized instruments and personnel. Further, with GERD, discerning causal and temporal relationships between acid reflux and cough is difficult. Thus, sequential empirical therapy is frequently considered and is advised by some before embarking on extensive workup [39,102]. Because symptom reduction is said to confirm a diagnosis, empiric treatment has been called a diagnostic-therapeutic trial [1].

DIAGNOSTIC TESTS

If airway disease is suspected, the treatable traits approach is advocated to identify and optimize treatment of pulmonary, extrapulmonary, and behavioral traits (Table 4). Optimizing airway disease treatment is usually the key to managing cough in these patients. Cough hypersensitivity may be a trait in airway disease and require additional specific treatment [5].

Table 4: AIRWAY INVESTIGATIONS IN PATIENTS WITH CHRONIC COUGH

Investigation

Description

Utility

Lower Airway

Chest radiograph

Plain radiograph of the chest from anterior or posterior aspect (occasionally lateral view)

Mandatory. Abnormal findings should be pursued first as potential cause of chronic cough.

Spirometry

Maximal inhalation and exhalation into a spirometer measures forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)

Mandatory test for airflow obstruction. FEV1 ≤80% or FEV1/FVC ratio <70% predicted for age and sex prompts reversibility testing.

Bronchodilator reversibility test

Pre- and post-bronchodilator spirometry in patients with obstructive airflow to measure change 10 to 15 minutes after SABA (e.g., albuterol)

Increase in FEV1 ≥12%, or ≥200 mL, after SABA indicates reversibility. Ideally, perform before starting asthma therapy.

Fractional exhaled nitric oxide (FeNO)

Measurement of nitric oxide levels in exhaled breath to indicate eosinophilic airway inflammation

Increased FeNO levels correlate with type 2 airway inflammation in asthma or nonasthmatic eosinophilic bronchitis. High FeNO (>30 ppb) may predict corticosteroids response.

Induced airway sputum

Patient inhales nebulized hypertonic saline (3% to 5%), inducing sputum expectoration for differential cell count analysis.

The criterion standard assessment of eosinophilic airway, routinely used in cough clinics but not widely adopted

Bronchial challenge/provocation test

Patient inhales histamine or methacholine; a ≥20% drop in FEV1 confirms bronchial hyperresponsiveness (positive test).

Positive test with isolated cough and normal spirometry indicates an anti-asthma therapy trial. A negative test makes asthma improbable.

Chest computed tomography (CT)

Provides better resolution of lung parenchymal and mediastinal structures than chest x-ray

In productive cough, may identify early lung fibrosis or confirm bronchiectasis. Low utility in chronic cough with normal physical exam and chest x-ray.

Bronchoscopy (fiberoptic)

Allows direct visualization of the upper and lower airways and bronchoalveolar lavage to obtain specimens

Mandatory in all patients with suspected inhaled foreign body. Endobronchial appearance typically normal in chronic cough with normal chest x-ray.

Upper Airway

Laryngoscopy (fiberoptic)

Allows direct inspection of laryngopharyngeal area including epiglottis and vocal cords

Typically unremarkable, but may reveal laryngopharyngeal reflux. Suspected laryngeal dysfunction prompts challenge laryngoscopy.

Sinus CT imaging

Visualizes the frontal, ethmoid, and maxillary sinuses and nasal passages

May provide evidence of sinus opacification or mucosal thickening. Unclear role in patients with chronic cough without nasal symptoms.

Other

Peripheral blood eosinophil count

Measures absolute number or relative percentage of eosinophils in peripheral blood

May help predict corticosteroid response in respiratory diseases; utility in chronic cough not established.

ppb = parts per billion, SABA = short-acting beta-agonist.

Source: [10,19,103]

Classic asthma, cough-variant asthma, and nonasthmatic eosinophilic bronchitis are clinical diagnoses with no clear-cut, absolute diagnostic test available to either rule asthma in or out as the cause of a patient's chronic cough [10]. In a stepwise diagnostic approach, initial abnormal lung function testing suggests classic asthma or COPD; normal testing is inclusive of cough-variant asthma, nonasthmatic eosinophilic bronchitis, or chronic bronchitis. Absence of bronchial hyperreactivity to methacholine challenge in patients with normal physical exam and spirometry findings suggests nonasthmatic eosinophilic bronchitis. Negative airway responsiveness can exclude cough-variant asthma. Abnormal spirometry contraindicates bronchial challenge testing [104].

Lung Function Tests

Spirometry can reveal airflow obstruction, variability (>20%) in peak expiratory flow measurements, or an improvement in threshold testing (FEV1 >12%, improvement from baseline of >200 mL) in response to bronchodilators (b-2 agonists). Abnormal spirometry can be seen in patients with classic asthma and COPD, but not cough-variant asthma or nonasthmatic eosinophilic bronchitis [104].

Spirometry

An FEV1/forced vital capacity (FVC) ratio of <70% (or below the lower limit of normal, if available) is a positive test for obstructive airway disease (obstructive spirometry) [103].

Bronchodilator Reversibility Test

Bronchodilator reversibility testing is recommended in patients with obstructive spirometry (FEV1/FVC ratio <70%). Following short-acting beta-agonist bronchodilator administration, improvement in FEV1 of ≥12%, together with an increase in volume of ≥200 mL, is a positive test [103].

Airway Inflammation Measures

Asthma is often, but not always, mediated by eosinophilic inflammation, and measurement of airway inflammation has clinical utility because eosinophilic airway inflammation is associated with favorable inhaled corticosteroid response. Fractional exhaled nitric oxide (FeNO) levels and peripheral blood eosinophil count indirectly estimate airway eosinophilia [5,10,84]

Significant (>3%) sputum eosinophilia is the criterion standard for eosinophilic inflammation, but sputum eosinophilia may not be routinely available. Blood eosinophil count is simple and readily available but has diurnal and seasonal variability so multiple assessments should be performed. A blood eosinophil count >0.3 cells/mcL may indicate eosinophilic airway inflammation.

FeNO is a surrogate marker of eosinophilic airway inflammation and inhaled corticosteroid response in classic asthma. FeNO has a relatively high specificity in predicting asthma among patients with chronic cough, but a cut-off level for diagnosis lacks consensus. Elevated FeNO levels (>40 ppb) support a diagnosis of asthma with typical symptoms, but the usefulness in predicting inhaled corticosteroid response in chronic cough is uncertain [5].

A meta-analysis of studies in patients with chronic cough reported significantly higher inhaled corticosteroid response rates in high (>25 ppb) compared with low FeNO (87.4% vs. 46.3%) [105]. After three weeks of high-dose inhaled corticosteroids, the response rate (defined as a ≥1.3-point increase in LCQ) was 68% in patients with high FeNO and no other apparent etiology; LCQ scores and FeNO significantly improved. However, improvements in cough were unrelated to changes in FeNO levels, challenging their direct mechanistic link [106]. Thus, an inhaled corticosteroid trial should be prompted with FeNO >25 ppb but avoided with FeNO <25 ppb unless other factors suggest eosinophilic airway disease [5]. Treatment decisions should not solely hinge on FeNO values [6].

Airway Hyper-Reactivity Measures

In patients with negative physical examination and spirometry findings, bronchial challenge testing (e.g., methacholine) should be performed to confirm airway hyper-reactivity consistent with symptomatic asthma [84]. Bronchial challenge testing is recommended in patients with reactive airway diseases to help diagnosis of asthma and nonasthmatic eosinophilic bronchitis as a cause of chronic cough. A negative bronchial challenge test (defined as an FEV1 decrease of <20% at the highest methacholine challenge dose [10 mg/mL]) has a high negative predictive value of asthma as an etiological diagnosis in chronic cough [104].

Airway eosinophilic inflammation can be present in both asthma and nonasthmatic eosinophilic bronchitis but can be distinguished by a methacholine inhalational challenge (positive in asthma, negative in nonasthmatic eosinophilic bronchitis) because substantially more mast cells localize in the smooth muscle layer in asthma compared with nonasthmatic eosinophilic bronchitis [6].

9. IDENTIFICATION AND MANAGEMENT OF UNDERLYING ETIOLOGIES

The concept that chronic cough is a disease in its own right has only recently gained acceptance. Different phenotypes of this condition are recognized (e.g., asthmatic cough, reflux cough), but the underlying pathology involves hypersensitivity of the vagus nerve and its central projections. The paradigm of asthma, GERD, and postnasal drip causing the symptom of chronic cough was promulgated from the 1980s onwards. However, after it became apparent that many patients suffering from chronic cough with a particular disease label (e.g., asthma, GERD) failed to respond to treatments for that condition, clinical practice guidance changed [79].

Systematic evaluation and treatment guidelines for chronic cough, based on the anatomic locations of receptors and afferent pathways in the cough reflex, first appeared in 1977 [80]. Using such an approach was estimated to determine the cause of chronic cough in 100% of patients, and the subsequent cause-specific treatment was reportedly almost always successful. Termed the ADP, this stepwise diagnostic approach involves a targeted patient history and physical examination to investigate the possible cause/s of their cough. This information is then used to initiate a stepwise treatment approach until resolution of the cough symptoms [77].

The American College of Chest Physicians (ACCP) recommended the ADP in their comprehensive clinical practice guideline on cough in 1998 and in 2006 [81,82]. More recent ACCP guidelines evaluate ADP components and provide treatment recommendations on the major causes of cough, including chronic cough due to GERD in 2016, asthma and nonasthmatic eosinophilic bronchitis in 2020, stable chronic bronchitis in 2020, and unexplained/refractory chronic cough in 2016 [77,83,84,85,86].

However, the understanding of chronic cough has evolved beyond the ADP, especially since 2020 with incorporation of cough hypersensitivity and the treatable traits approach into clinical practice guidelines and endotyping of many cough-associated chronic inflammatory conditions. These knowledge advances are not efficiently reaching U.S. clinicians, because ACCP guidelines on chronic cough have not kept pace. While the ADP remains an important structure of the diagnostic workup for chronic cough patients, its assumptions have been supplanted in recent international chronic cough guidelines.

THE "TREATABLE TRAITS" APPROACH IN CHRONIC AIRWAY DISEASES

In the late 19th century, Sir William Osler established the modern approach to the diagnosis and treatment of disease, based on the principal organ system where symptoms and signs manifest, with some biological correlates. The Oslerian paradigm of disease classification using diagnostic categories has been in use for more than 100 years, with substantial merit, but limitations of the diagnostic label approach have become evident [16].

As noted, in 2016, the treatable traits approach was introduced to pulmonary medicine to overcome the shortcomings of the diagnostic label approach, which does not consider the biological complexity of airway diseases, the distinct endotypes present in each patient, or common patterns of disease such as chronic cough [14,17].

The treatable traits approach addresses the complexity of chronic airway diseases as heterogeneous, frequently overlapping, and often comorbid conditions. In clinical trials of patients with asthma and COPD, the treatable traits approach led to significantly greater improvements in health-related quality of life and biological outcomes and reductions in primary care visits (compared with usual care) [16].

A trait is defined as clinically relevant, measurable, and treatable. These traits can be identified by their phenotypes and/or endotypes in pulmonary, extrapulmonary, and behavioral/environmental domains, and can coexist, interact, and change over time in the same patient. The treatable traits approach is agnostic to the traditional diagnostic labels of asthma or COPD and can be used in any patient with airway disease. The treatable traits approach often extends beyond the diagnostic label itself to find more treatment targets, especially in complex patients with suboptimal response to conventional guideline-based treatment [87,88]. In other words, the treatable traits approach represents a transdiagnostic model.

In asthma, many extrapulmonary traits present as connected comorbidities, meaning they coexist with asthma and may share mechanisms. Extrapulmonary traits (e.g., chronic rhinosinusitis, GERD, anxiety, atopic dermatitis) are clinically relevant as they predict poor outcomes, confound the management of asthma, and are treatable themselves. Through multidimensional assessment of pulmonary, extrapulmonary, and behavioral/environmental domains, the treatable traits approach identifies and targets extrapulmonary traits with effective treatments, improving both asthma and the comorbidity [89].

In the 1970s, the ADP extended the Oslerian classification system to cough, addressing the three common causes (asthma, postnasal drip, reflux) arising from three different anatomical areas. Refined to four causes (asthma, nonasthmatic eosinophilic bronchitis, upper airway cough syndrome, and GERD), this approach benefitted many patients, but in 30% to 40% of these patients, the coughing continues or a presumed cause cannot be identified [16,90]. In 2023, COPD was added to become a fifth common potential underlying cause of chronic cough [24].

Chronic cough is associated with airway and reflux diseases that are heterogeneous, frequently overlapping, and often comorbid, the same characteristics the treatable traits approach addresses [14,17]. For instance, asthma is a clinical syndrome with varying phenotypes and endotypes, rather than a single disease entity. COPD is an umbrella term encompassing different respiratory conditions sharing airflow obstruction. Asthma is not always eosinophilic, and GERD is not necessarily acidic [15]. Despite its relatively recent appearance, the treatable traits paradigm is endorsed throughout pulmonary medicine and in post-2019 (international) clinical practice guidelines on chronic cough.

ENDOTYPES OF COUGH-RELATED CHRONIC INFLAMMATORY DISEASES

A phenotype is an observed characteristic resulting from interactions between genotype and environment. An endotype is a specific biological pathway that forms the basis of observable traits in the phenotype [56].

In the 2016 treatable traits paper, the authors broadly call for a shift away from the classical Oslerian top-to-bottom approach (i.e., from symptoms to mechanisms) to reclassifying airway diseases bottom-up, by linking causal molecular pathways (i.e., endotypes) to disease phenotypes (i.e., from molecules to symptoms) [14].

This has been unfolding in allergy and immunology, and these advances are highly relevant to pulmonary medicine and to chronic cough. For instance, the chronic inflammatory diseases of asthma, allergic rhinitis, chronic rhinosinusitis with or without nasal polyposis, eosinophilic esophagitis, and atopic dermatitis, are now defined by a constellation of symptoms that may result from different pathological mechanisms and not as homogeneous diseases [91].

The discovery of new endotypes in allergic and immune diseases has prompted the transition from symptom-focused disease descriptions to biomarkers and pathogenetic pathways—from phenotypes to endotypes [91]. The imperative for transitioning to endotypes is heightened by FDA approval of several biologicals that target specific inflammatory pathways important in disease pathophysiology [92]. These include the most common chronic cough-associated disorders.

Immune dysregulation has been endotyped as type 1, type 2, and type 3 responses. Asthma has been commonly dichotomized as type 2 and non-type 2. Type 2 inflammation is the best-characterized endotype [91,93,94,95].

Type 2 inflammation involves eosinophils as the key players, which contribute to chronic allergic inflammation by producing cytokines, or interleukins (IL), with specific roles in the inflammatory pathway. IL-5 promotes eosinophil recruitment to sites of inflammation. IL-4 and IL-13 promote immunoglobulin E (IgE) production and immune cell trafficking to tissue, driving and sustaining the type 2 response, tissue damage, and chronic inflammation. IL-31 activates binding sites on sensory neurons, which release CGRP and nerve growth factor, causing neurogenic inflammation. In non-type 2 asthma, Th2 cells migrate to asthmatic bronchi and change their phenotype to produce T1 effector cytokines, such as interferon-γ(IFN-γ) and tumor necrosis factor-α(TNF-α), inducing bronchial epithelial apoptosis and remodeling. TNF-αpromotes neutrophilic inflammation, which correlates with sputum TNF-αlevels in patients with severe asthma. In type 3 inflammation, innate lymphoid cells type 3 (ILC3), T helper lymphocyte type 17 (Th17), and Th22 cells produce cytokines IL-17, IL-22, and IL-23. This mechanism is particularly relevant in the pathogenesis of chronic rhinosinusitis with nasal polyps and neutrophilic asthma [91,93,94,95].

In 2023, the European Academy of Allergy and Clinical Immunology (EAACI) published an updated disease taxonomy with advances in biomarkers, pathogenetic and metabolic pathways, and pathogenic genetic variants. This expanded nomenclature characterizes the following types with relevance to chronic cough [91].

Type V: Epithelial Barrier Defect

The epithelial barrier defect and microbial dysbiosis lead to dysregulation of the immune response, including extensive activation and release of inflammatory cytokines, chemokines and inflammatory mediators (histamine, leukotrienes, reactive oxygen species). The sequence of events eventually leads to tissue damage in asthma, chronic allergic rhinitis, chronic rhinosinusitis, and chronic rhinosinusitis with nasal polyps.

Type VI: Metabolic-Induced Immune Dysregulation

Obesity is a distinguishing variable for clustering and classifying asthma subtypes, and the number of obese patients with asthma has risen dramatically with increasing obesity rates. The obese asthmatic, more likely to be female with adult-onset asthma and to become corticosteroid resistant, has a higher risk of being hospitalized and more frequently presents with severe disease. Higher body mass index (BMI) is associated with increased circulating inflammatory mediators, blood neutrophils, and eosinophils. An additive effect of asthma and obesity further increases inflammatory mediators and airway inflammation.

An asthma endotype introduced in 2020, IL-6-high asthma, is characterized by elevated plasma IL-6 levels, increased markers of systemic inflammation, metabolic dysfunction, and obesity [96].

Type VII: Inflammatory Drug Reactions

These idiosyncratic reactions include hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) and phenotypes such as NSAIDs-exacerbated respiratory disease in patients with asthma and/or chronic rhinosinusitis ± nasal polyposis. NSAIDs-exacerbated respiratory disease is a chronic inflammatory condition characterized by the triad of asthma, recurrent nasal polyps and hypersensitivity to NSAIDs/aspirin. In the underlying mechanism, cyclooxygenase (COX)-1 inhibition releases eicosanoid mediators, causing bronchoconstriction, increased vascular permeability, mucus production and recruitment of inflammatory cells.

These advances in endotyping chronic inflammatory diseases associated with chronic cough have not yet appeared in practice guidelines on chronic cough, with the exception of eosinophilic airway inflammation, but this science is being translated into practice. For example, cough is the most troublesome symptom for patients with asthma. Older patients with asthma and chronic cough show worse clinical outcomes in asthma control, quality of life, and airway obstruction, and more frequent moderate-to-severe exacerbations, partly explained by the interaction of chronic coughing with aging [97]. Non-type 2 inflammation (e.g., increased neutrophils) is associated with cough in older patients with asthma with chronic cough. Interferon-γis a non-type 2 biomarker that enhances cough reflex sensitivity by inducing calcium influx in vagal sensory neurons and is associated with increased cough in patients with refractory chronic cough. Older patients with asthma show increased levels of sputum IFN-γ. Non-type 2 inflammation (i.e., neutrophils and IFN-γ) is also associated with reduced inhaled corticosteroid response [54,97,98].

10. TREATMENT

CHRONIC AIRWAY INFLAMMATION

Treatment of chronic airway inflammation includes inhaled corticosteroids, long-acting beta-agonists, long-acting muscarinic antagonists, leukotriene receptor antagonists, systemic corticosteroids, and biologicals. Confirmation that chronic cough is due to asthma (or another chronic cough-associated condition) requires a beneficial response to therapy for asthma, as patients with asthma can also have chronic cough due to non-asthmatic causes [44].

For chronic cough due to cough-variant asthma or nonasthmatic eosinophilic bronchitis, the ACCP recommends inhaled corticosteroids as first-line treatment [84]. With incomplete response, the inhaled corticosteroid dose should be escalated and adding a leukotriene receptor antagonist should be considered. Other causes of cough should be reconsidered as well. For cough-variant asthma, adding beta-agonists should be considered.

Evidence Based Practice Recommendation

In adult and adolescent patients with chronic cough due to non-asthmatic eosinophilic bronchitis (NAEB), we suggest inhaled corticosteroids as first-choice treatment

https://journal.chestnet.org/article/S0012-3692(20)30045-3/fulltext

Last Accessed: August 12, 2024

Strength of Recommendation/Level of Evidence: 2B (Weak recommendation based on moderate-quality evidence)

In patients with chronic cough in asthma, the first-line treatment is inhaled corticosteroid with or without long-acting beta-agonist [6]. A leukotriene receptor antagonist or long-acting muscarinic antagonist may be added in for those who do not fully respond to initial treatment. Whether biologics can treat chronic cough related to asthma has not been studied.

When an offending allergen cannot be identified or avoided, chronic cough associated with nonasthmatic eosinophilic bronchitis should be treated with an inhaled corticosteroid. Second-line therapy calls for escalation of the inhaled corticosteroid dose; if response remains incomplete, the patient should be assessed for other causes of cough and a trial of leukotriene receptor antagonist initiated. Occasionally, systemic corticosteroids may needed.

Tiotropium may be another therapeutic option. In 17 patients with chronic asthmatic cough refractory to inhaled corticosteroid/long-acting beta-agonist, four to eight weeks of tiotropium (5 mcg/day) significantly improved cough reflex sensitivity and cough severity in a subgroup of 11 patients [107]. These results were replicated in a randomized comparison to theophylline 400 mg/day over four weeks. Both drugs improved cough severity and cough-specific quality of life. Tiotropium decreased cough reflex sensitivity, which correlated with changes in cough severity, and higher baseline cough reflex sensitivity predicted greater tiotropium response. The authors conclude that tiotropium may modulate cough reflex sensitivity to alleviate chronic cough in asthma refractory to inhaled corticosteroid/long-acting beta-agonist [108].

EMPIRIC TREATMENT APPROACH

Empiric treatment of chronic cough is systematically directed at the four most common causes of cough, starting with upper airway cough syndrome. In its 2006 guideline, the ACCP states that therapy should be given in sequential and additive steps, because more than one cause of cough may be present [82]. Initial empiric treatment should begin with an oral first-generation antihistamine/decongestant.

If chronic cough persists after treatment for upper airway cough syndrome, asthma as the possible cause should be worked up next. If spirometry does not indicate reversible airflow obstruction, bronchoprovocation testing is performed in the evaluation for asthma.

With the diagnoses of upper airway cough syndrome and asthma ruled out or treated without the elimination of cough, nonasthmatic eosinophilic bronchitis should be considered next, with a properly performed induced sputum test for eosinophils. In most patients with suspected cough due to asthma, a bronchoprovocation challenge should be performed and, if the result is positive, some combination of inhaled corticosteroids, inhaled beta-agonists, and/or oral leukotriene inhibitors should be administered.

In patients whose cough responds only partially or not at all to interventions for upper airway cough syndrome and asthma or nonasthmatic eosinophilic bronchitis, treatment for GERD should be instituted next. In patients with cough whose condition remains undiagnosed after all of these conditions has been worked up, referral to a cough specialist is indicated.

When the cause of chronic cough is identified or suspected, there are two options [26,44,57,109]. The first is to pursue one diagnostic and treatment path at a time; with incomplete response of the cough to one line of therapy, adding therapy for the next most likely diagnosis is reasonable. The second option in patients with more than one suspected cause and a cough that is especially disruptive is to empirically treat or evaluate the likely causes simultaneously. After the cough resolves, treatments can be stopped sequentially, starting with the least likely to have been helpful, observing the patient for any return of cough.

BEHAVIORAL TREATABLE TRAITS

Nonadherence and poor inhalation technique strongly influence outcomes in airway disease. Despite their critical importance, the proportion of patients with poor technique is high, unimproved over the past 40 years, and often unaddressed by clinicians. These behavioral treatable traits can be improved using strategies such as patient-centered communication, motivational interviewing, shared decision-making, and simplification of drug regimens; and should be assessed in every follow-up visit [110].

Smoking cessation improves cough by resolving chronic bronchitis. Nicotine suppresses the cough reflex, and nicotine withdrawal due to smoking cessation may enhancement cough hypersensitivity; hence, patients may experience more coughing for a period after quitting. This can be attenuated and quit rates improved by using nicotine replacement [5].

LOWER AIRWAY ETIOLOGIES OF CHRONIC COUGH AND MANAGEMENT

Lower airway diseases commonly associated with chronic cough are classic asthma, cough-variant asthma, nonasthmatic eosinophilic bronchitis, and COPD [20].

Chronic cough is a central feature that develops in diverse pulmonary pathologies, such as asthma (an inflammatory airway disease) and idiopathic pulmonary fibrosis (an alveolar fibrosing disease), highlighting the significant role of dysregulated cough pathways in lung disease phenotypes [60]. Chronic cough prevalences have been reported for asthma (8% to 58%), COPD (10% to 74%), bronchiectasis (82% to 98%), interstitial lung disease (50% to 89%) and sarcoidosis (3% to 64%); in all five diseases, patients demonstrate cough reflex hypersensitivity, a cardinal feature of cough hypersensitivity syndrome [111].

Presence of chronic cough generally predicts impaired health status and more severe respiratory disease and is associated with greater symptom burden and disease severity in asthma, COPD, bronchiectasis, and interstitial lung disease. It has also been linked to greater exacerbations in asthma and bronchiectasis and increased mortality and lung transplantation in idiopathic pulmonary fibrosis [111].

Asthma and Nonasthmatic Eosinophilic Bronchitis

Asthma is a complex, chronic airway inflammatory disease of bronchial hyper-responsiveness, intermittent airflow obstruction, and symptoms of wheeze and dyspnea that impacts 26 million people in the United States, results in approximately 10,000 deaths annually, incurs an estimated $56 billion annually in medical care and lost productivity costs, and accounts for cough in 24% to 32% of adult nonsmokers with chronic cough [84,112,113]. Asthma prevalence has increased with rising obesity rates. Obesity often precedes an asthma diagnosis, making it an important modifiable risk factor (or treatable trait) [5,113].

In atopic asthma, the most common type (affecting approximately 50% of adults with asthma), allergens trigger innate and adaptive immune activity, releasing inflammatory mediators such as histamine, prostaglandins, and leukotrienes that promote bronchoconstriction and cough [20,114]. Classic asthma describes symptoms of wheezing, chest tightness, and dyspnea. In these patients, immune response to allergen exposure results in airway inflammation, airflow obstruction, and characteristic symptoms. Increased mucous secretions in narrowing airways induce cough [31,112].

Cough-variant asthma, in contrast, presents with persistent cough as the primary or only symptom. Cough receptor density is highest in the proximal airways, decreasing as the airways get smaller. In cough-variant asthma, inflammation is primarily in the proximal airways, where cough is stimulated, and less so distally, where inflammation and narrowing cause wheezing and dyspnea in classic asthma [31,56]. Some have suggested that asthma-variant cough is a more appropriate term than cough-variant asthma, given that cough hypersensitivity symptoms are the chief complaints, while asthmatic features act as triggers and treatable traits of chronic cough in these patients [115].

Nonasthmatic eosinophilic bronchitis was first described in 1989 as corticosteroid-responsive chronic cough in nonsmokers with airway eosinophilia, but without variable airway obstruction or bronchial hyper-responsiveness [116]. Nonasthmatic eosinophilic bronchitis accounts for 10% to 30% of specialist referrals for chronic cough, but nonasthmatic eosinophilic bronchitis prevalence is uncertain, as its diagnosis requires assessment of eosinophilic airway inflammation [44,84,117]. In nonasthmatic eosinophilic bronchitis, patients have chronic cough, no symptoms or evidence of variable airflow obstruction, sputum eosinophilia, and normal bronchial provocation tests [56,117].

Chronic cough in asthma is mechanistically complex, involving IgE or non-IgE mediated eosinophilic airway (i.e., atopic or nonatopic) inflammation, abnormal neuromechanical properties of the lungs, and presence of cough reflex hypersensitivity independently of airway eosinophilia or bronchial hyper-responsiveness [20].

Nonasthmatic eosinophilic bronchitis and asthma share airway eosinophilia and similar basal membrane thickening, but inflammatory mast cells primarily infiltrate the superficial airway epithelium in nonasthmatic eosinophilic bronchitis versus airway smooth muscle in asthma. Along with lower IL-13 expression in nonasthmatic eosinophilic bronchitis, this partially explains bronchitis and cough with normal airway responsiveness in nonasthmatic eosinophilic bronchitis [116,118]. Nonasthmatic eosinophilic bronchitis lacks the airway hyper-responsiveness of cough-variant asthma, but both share atopic features of eosinophilia and airway inflammation [109].

Eosinophilic airway inflammation in cough-variant asthma is linked to more severe disease. Cough-variant asthma may be a precursor of classic asthma, and both cough phenotypes can manifest overlapping symptoms, airway inflammation, and bronchial hyper-responsiveness [20]. Chronic dry cough, eosinophilic inflammation, and chronic airflow obstruction can present in both cough-variant asthma and nonasthmatic eosinophilic bronchitis [56].

Chronic Obstructive Pulmonary Disease (COPD)

COPD comprises several lung diseases, including emphysema and chronic bronchitis, with persistent and usually progressive airflow limitation associated with an enhanced chronic inflammatory response in the airways and lungs. Exacerbations and comorbidities contribute to the overall severity, while airway and systemic inflammation in COPD is related to disease progression and mortality [119,120].

In the United States, 14.2 million adults had diagnosed COPD in 2021, of whom 25% were never-smokers, and COPD accounted for 354,000 deaths in 2020 [121,122]. Among patients with COPD, 70% experience persistent cough and many consider it extremely severe and impairing [64].

Chronic bronchitis describes productive cough on most days of the week for at least three months total duration in two successive years. Chronic obstructive bronchitis is chronic bronchitis with spirometric evidence of airflow obstruction. Chronic asthmatic bronchitis is a similar condition with chronic productive cough, wheezing, and partially reversible airflow obstruction mostly found in smokers with a history of asthma [123].

Emphysema is defined as the permanent enlargement and damage of the lung air sacs with destruction of the airspace walls, causing symptoms of breathlessness. Emphysema can exist without airflow obstruction but is more common in patients with moderate or severe airflow obstruction [119].

COPD manifests as productive cough with airflow limitation and occasional bronchial hyper-responsiveness [20]. COPD and asthma share symptoms of cough, wheeze, and difficulty breathing. The blurred distinction between chronic obstructive bronchitis and chronic asthmatic bronchitis is termed asthma-COPD overlap [123].

Cigarette smoking is the primary risk factor, but only 15% of smokers develop clinically apparent COPD. Smokers with pre-existing airway reactivity, even in the absence of clinical asthma, have greater risk of developing COPD. Inflammation in the large and small airways can persist after smoking cessation. The genetic disorder alpha-1 antitrypsin deficiency is an important cause of emphysema in nonsmokers and markedly increases susceptibility to COPD in smokers [120,123].

Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis is an interstitial lung disease, a group of pulmonary disorders characterized by inflammation and/or fibrosis of the lung parenchyma associated with progressive dyspnea frequently resulting in end-stage respiratory failure. Interstitial lung disease affects 650,000 people and causes 25,000 to 30,000 deaths per year in the United States [124].

Idiopathic pulmonary fibrosis, the most common interstitial lung disease accounting for 35% to 61% of all patients, is a chronic, progressive, invariably fatal fibrotic lung disease [111,124]. Despite approvals of two antifibrotic therapies, the five-year survival rate remains 25%, far worse than many common cancers. Pharmacotherapies slow the disease progression, but none address the significant symptoms of chronic cough, fatigue, and dyspnea suffered by 85% to 95% of patients with idiopathic pulmonary fibrosis [125].

Chronic cough in idiopathic pulmonary fibrosis predicts disease progression and mortality, is as distressing as breathlessness for patients, and remains one of the most difficult symptoms to control [64,125]. Among 1,447 patients with idiopathic pulmonary fibrosis cough, every 1-point decrease in LCQ score increased the risk of respiratory-related hospitalization by 6.5%, death by 7.4%, and lung transplantation by 8.7% over 12 months. Worse cough-specific quality of life independently associated with increased risk of respiratory hospitalization, death, and lung transplantation [126].

Two breakthrough studies demonstrated that low-dose morphine and nalbuphine can safely decrease coughing in idiopathic pulmonary fibrosis patients, as will be described later in this course.

Bronchiectasis

Bronchiectasis is a heterogenous disorder characterized by infection, airway inflammation, failure of mucociliary clearance, and airway structural damage. Absolute suppression of cough is not recommended because bronchiectasis is a suppurative condition with an increased risk of infection. However, much of the cough exceeds what is physiologically needed for sputum clearance and is thus maladaptive or pathological [111]. Cough is a central clinical feature of bronchiectasis that contributes to impaired health status and may be an early indicator of disease exacerbation, but it is almost never evaluated [64].

UPPER AIRWAY ETIOLOGIES OF CHRONIC COUGH AND THEIR MANAGEMENT

In upper airway cough syndrome, diverse chronic infectious, inflammatory, or neurogenic upper airway diseases induce chronic cough [20,127]. While upper airway cough syndrome lacks a uniform definition, its prevalence in chronic cough patients is probably comparable to other major causes like asthma and GERD; in some studies, it is the first or second leading cause [39,127].

Rhinitis, comprising most chronic upper airway diseases in upper airway cough syndrome, has a lifetime prevalence up to 33% in the United States [6]. Nasal mucosa inflammation due to allergic or non-allergic cause leads to mucus secretion, sneezing, nasal pruritus, and postnasal drip that irritates the airways and stimulates coughing [31]. In chronic rhinitis, these symptoms persist at least three months, inducing nasal obstruction and increased nasal discharge [119].

Rhinitis has numerous phenotypes and the nomenclature is not straightforward (Table 5). Allergic rhinitis requires immunoglobulin E (IgE)-mediated sensitization to an allergen exposure [6]. Chronic cough in patients with allergic rhinitis is often related to undiagnosed asthma or nonspecific bronchial hyperreactivity. Bronchial biopsy studies of patients with allergic rhinitis without asthma have shown inflammatory cell infiltration and active structural remodeling of the lower airways similar to that of patients with asthma, thereby potentially contributing to cough in these patients [128].

Table 5: DISTINGUISHING CHARACTERISTICS OF RHINITIS PHENOTYPES

Rhinitis Phenotype

Primary Symptoms

Associated Features

More Responsive to

Less Responsive to

Allergic

Sneezing, nasal pruritis, clear rhinitis

Ocular itching, wheezing, atopic dermatitis

INCS, INAH, FGAH, SGAH, SCS, AIT

Decongestants, ABX

Nonallergic noninfectious

Intermittent congestion, clear rhinitis

Physical triggers (temperature changes, food, irritants)

INCA, INAH, INAC

FGAH, SGAH, SCS, AIT, ABX

GERD-associated

Postnasal drip, throat clearing

Epigastric pain, heartburn, dysphagia

GERD diet and lifestyle changes, INAC

FGAH, SGAH, INCS, INAH, SCS, ABX, AIT

Chronic rhinosinusitis with or without nasal polyposis

Anosmia/hyposmia, unremitting congestion, facial pain/pressure

Wheezing, NSAID hypersensitivity

SCS, biologics, intermittent INCS

FGAH, SGAH, INAH

Infectious

Acute onset, sinus pressure, nasal congestion with purulent discharge

Viral prodrome, episodic nature lasting <2 weeks

Saline nasal lavage, INAH, decongestants, INAC

FGAH, SGAH, INCS, SCS, ABX, AIT

ABX = antibiotics; AIT = allergen immunotherapy; FGAH = first-generation oral antihistamines; GERD = gastroesophageal reflux disease; INAC = intranasal anticholinergics; INAH = intranasal antihistamines; INCS = intranasal corticosteroids, SCS = systemic corticosteroids; SGAH = second-generation oral antihistamines.

Source: [6]

Chronic nonallergic rhinitis syndromes include chronic nonallergic rhinitis, nonallergic rhinitis with eosinophilia syndrome (NARES), atrophic rhinitis, and drug-induced rhinitis; nonallergic rhinitis accounts for up to 80% of cases [129]. Nonallergic rhinitis phenotypes include [6]:

- Vasomotor

- Irritant

- Infectious

- GERD-associated

- Chronic rhinosinusitis with or without nasal polyposis

Rhinosinusitis is preferred to sinusitis because purulent sinus disease without similar rhinitis is rare [130].

Chronic rhinosinusitis is an inflammatory disease of the sinonasal mucosal lining secondary to infectious and allergic etiology, with symptoms of anosmia, nasal obstruction, thick nasal drainage, and facial pressure [92]. Retention of sinus secretions, the key event in chronic rhinosinusitis development, fosters infection and is caused by obstruction or narrowing of sinus ostia, mucociliary dysfunction, or altered mucus composition; 90% of sinus infections involve the maxillary sinus [119]. Cough, one of the important symptoms of chronic rhinosinusitis, occurs in 1% to 5% of U.S. adults [131].

Chronic rhinosinusitis with nasal polyposis, representing up to 20% of chronic rhinosinusitis cases, is more debilitating than the phenotype without nasal polyposis. Comorbidities in chronic rhinosinusitis with nasal polyps are asthma (55% to 56%), allergy (12% to 77%), and allergic rhinitis (17% to 76%). Asthma with nasal polyps is harder to control and more prone to severe exacerbations [92,93].

Chronic cough pathogenesis in upper airway cough syndrome was previously tied to postnasal drip, because the nose and sinuses lack vagal sensory innervation. However, only a minority of patients with postnasal drip have chronic cough, some patients with upper airway cough syndrome do not have postnasal drip, and the pathophysiology is more complex [11,127].

In chronic rhinitis and rhinosinusitis, inflammatory mediators are transmitted via glossopharyngeal and vagal receptors in the pharynx and larynx, and via afferent fibers of the trigeminal nerve, sensitizing the cough reflex centrally [11]. Direct irritation of nasolaryngeal mucosa and stimulation of vagal afferents by postnasal drip lead to hematogenous spread of inflammatory mediators and neurogenic or systemic communication between upper and lower airways, resulting in airway sensory nerve inflammation, cough reflex hypersensitivity, and chronic cough [10,39].

Convergence of trigeminal and vagal afferents in central cough pathways provides a mechanistic/neuronal link between upper airway disease and the development of cough hypersensitivity [5]. In general, upper airway diseases lead to chronic cough only if the cough reflex becomes hypersensitive; therefore, they are generally considered a trigger rather than a cause of chronic cough [11].

In 2024, nonallergic rhinopathy was introduced to replace vasomotor rhinitis as the term describing 80% of the larger nonallergic rhinitis category, prompted by evidence that neuroinflammation and TRPV1 receptor activation play important roles, rather than blood vessels. TRPV1 also contributes to nasal hyper-reactivity in allergic rhinitis, an entity called mixed rhinitis. The management of nonallergic rhinitis requires the correct diagnosis; rhinopathy draws attention to the underlying neuro-immune endotype [129,132].

Chronic cough is triggered in many patients with chronic upper airway disease (usually allergic rhinitis or chronic rhinosinusitis with or without nasal polyps) with common symptoms and signs of postnasal drip, compulsive throat-clearing, nasal stuffiness, globus feeling, headache/facial pain, loss of smell and taste, recurrent hoarseness, and cobblestone appearance of the pharyngeal mucosa on inspection [11]. The most commonly used tool is the SinoNasal Outcome Test (SNOT) [92].

With numerous symptoms and unclear diagnostic criteria, upper airway cough syndrome diagnosis has been based on first-generation oral antihistamine response, which may have central antitussive effects. Upper airway and other airway disease is frequent in patients with chronic cough, making it unclear whether coughing arises from upper or lower airways [5].

A large case series found allergic rhinitis, classic asthma, chronic rhinosinusitis, and nasal polyposis in 46%, 31%, 12%, and 9% of patients with chronic cough, respectively. The high predictive value for concomitant asthma in upper airway cough syndrome calls for investigating lower airway pathology in chronic cough of upper airway origin [20].

Rhinitis is a principal contributor to upper airway cough syndrome. The lengthy differential diagnosis of rhinitis in upper airway cough syndrome includes both allergic and nonallergic diseases; many patients have a combination of both or mixed rhinitis. Distinguishing these will increase treatment success and decrease the time before symptoms improve [6].

Radiological investigations may be useful and are guided by nasal symptoms. Incidental sinus changes may be present in up to 33% of CT and 67% of MRI scans. PPIs should not be used to treat upper airway symptoms [5].

Laryngeal dysfunction and hypersensitivity are common in chronic cough [5]. Consider treatment of laryngeal hypersensitivity as a symptom of cough hypersensitivity. Laryngitis often leads to chronic cough with voice changes (e.g., hoarseness, aphonia). Chronic cough is frequent in functional voice disorders, (e.g., muscle tension dysphonia) [11].

In vocal cord dysfunction, laryngeal hypersensitivity leads to persistent laryngospasm due to different triggering factors, manifesting as cough, wheeze, breathlessness, and voice disturbance. Coughing can be both a trigger and a symptom. Symptoms may be episodic. Diagnosis is based on findings in history, laryngoscopy, and, if possible, spirometry during an attack [5,11]. In a refractory chronic cough population, vocal cord dysfunction is a common finding and may be a manifestation of laryngeal hypersensitivity. Treatment is by speech and language therapy intervention [5].

REFLUX DISORDER ETIOLOGIES OF CHRONIC COUGH AND THEIR MANAGEMENT

In GERD, retrograde transit of gastric contents into the esophagus leads to troublesome symptoms of heartburn, esophageal chest pain, and regurgitation (i.e., "typical" esophageal symptoms) [133,134]. Cough is an extraesophageal symptom of reflux disease [11]. Chronic cough has a low, but potential, pathophysiological relationship to reflux disease [133]. Estimated chronic cough due to GERD vary widely (7% to 85%), with higher prevalence in Western than Asian countries [20]. Chronic cough and GERD are both very common conditions and can therefore co-appear without being causally related [99].

GERD was previously considered a leading chronic cough etiology directly caused by the acidity of proximal esophageal refluxate, but patients with chronic cough and healthy controls show similar proximal reflux events [58,135]. Many patients with chronic cough report GERD symptoms, but PPI therapy is ineffective in those without acidic reflux and only modestly benefit those with typical esophageal symptoms [109].

Reflux can be acidic or non-acidic, liquid or gaseous, and proximal or distal in location. Reflux can trigger cough, coughing can induce reflux, and chronic cough may also cause GERD or increase reflux episodes [20,134]. PPIs decrease reflux acidity but not reflux events and work poorly in patients with airway or extraesophageal reflux [136]. PPI failure in chronic cough treatment suggests the acidic component of reflux has little effect on chronic cough or its etiology [58].

In extraesophageal reflux, troublesome symptoms not normally considered esophageal manifest in the lower and upper airways as chronic cough, asthma, laryngitis, dysphonia, pulmonary fibrosis, sinus disease, ear disease, postnasal drip, throat clearing, non-cardiac chest pain, or dental erosion [20,134].

Laryngopharyngeal reflux is defined as the backflow of weakly or non-acidic "mist" or liquid above the upper esophageal sphincter into the upper airways. Due to weaker mucosal defenses in the upper respiratory tract, inflammation of the mucous membranes and epithelial tissue damage occur with exposure to fewer, and less acidic, reflux events. A significant negative effect from pepsin, a gastric enzyme, on oropharyngeal and respiratory tract tissues is also demonstrated [58,137].

Airway reflux is interchangeably used for laryngopharyngeal, non-acid esophageal, extraesophageal, and silent reflux. But it is important to remember that airway reflux is not GERD. Defined by the symptoms of heartburn and dyspepsia, and associated with esophagitis, GERD is a peptic condition predominantly of liquid acidic reflux [59]. The majority of patients with airway reflux/laryngopharyngeal reflux do not have esophagitis or heartburn [137].

Airway reflux shifts the paradigm from traditional GERD to cough hypersensitivity through sensitization of vagal afferents. Evidence that esophageal irritation by acid and non-acid reflux may directly initiate cough led to the concept of an esophagobronchial reflex based on crosstalk at the nucleus tractus solitarius between esophageal and airway sensory neurons converging in this brainstem area [58].

This led to gastroesophageal reflux-associated cough, a cough-predominant phenotype of GERD, as a chronic airway inflammatory disease. Epithelial damage and airway inflammation in gastroesophageal reflux-associated cough patients suggest micro-aspiration, and the esophagobronchial reflex mediated by distal esophageal vagal afferents [136].

Chronic cough may result from GERD/extraesophageal reflux-induced airway inflammation and supra-esophageal pathology. Whether refluxate causes damage leading to extraesophageal reflux, needs to be acidic or merely contain pepsin, or whether neurogenic signaling leads to inflammation and subsequent symptoms remains unclear [134,136].

In sum, GERD can directly affect the airways when gastric acid backflows into the esophagus, irritating the proximal esophagus and laryngopharyngeal areas, triggering the cough reflex to clear the airways. Gastric content can indirectly cause chronic cough by stimulating the distal esophagus, resulting in vagus nerve irritation and cough reflex sensitization. Airway reflux may comprise most cases of reflux-induced cough, its extraesophageal symptom hampering diagnosis based on symptoms alone [39].

Management

As discussed, the role of reflux, esophageal dysmotility, and aspiration in chronic cough is controversial. Studies suggest non-acidic reflux, both liquid and gaseous, may be an etiological factor. However, no tool reliably detects such reflux and diagnosis relies on clinical history supported by validated questionnaires (e.g., the HARQ). Moreover, the high prevalence of esophageal dysmotility in patients with chronic cough suggests esophagopharyngeal reflux rather than GERD may be the problem [10].

Many of the signs and symptoms associated with chronic cough are explicable by reflux and aspiration, including voice change, nasal symptoms, and dysgeusia. Frequent chest infection bronchitis, even frank bronchiectasis, may be the consequence rather than the cause of cough via repeated aspiration. Unsurprisingly, following aspiration of GI contents there is a neutrophilic or eosinophilic inflammatory response that might be giving rise to asthmatic cough and mucus hypersecretion [10].

The 2016 ACCP clinical practice guideline for reflux-associated chronic cough suggests that esophageal manometry and pH-metry be performed in patients with suspected reflux cough refractory to a three-month antireflux trial and being evaluated for surgical management (antireflux or bariatric); or with strong clinical suspicion warranting diagnostic testing for gastroesophageal reflux (Table 6). Esophageal manometry assesses for major motility disorder. It involves placing the pH electrode 5 cm above the lower esophageal sphincter in the pH monitoring study after the patient is off PPIs for seven days and histamine H2-receptor antagonists for three days [83].

Table 6: REFLUX INVESTIGATIONS IN PATIENTS WITH CHRONIC COUGH

Investigation

Description

Utility

24-hour esophageal pH testing

A catheter is inserted nasally into the esophagus with two pH sensors for 24-hour measurement of proximal and distal acid reflux

Does not reliably predict response to PPI therapy

Barium meal

Radiographic test that visualizes the movement of barium liquid. Can detect structural and motility abnormalities of the esophagus, stomach, and duodenum.

May demonstrate a hiatal hernia and document the extent of non-acid reflux not identified on 24-hour pH testing

Manometry

A catheter is inserted to assess motility patterns by measuring the amplitude of contractile events in the esophagus and its sphincters

Impaired peristalsis is more prevalent in patients with chronic cough, consistent with symptoms of esophageal dysmotility

Impedance testing

Intraesophageal probes measure impedance and pH to record acid, weakly acidic, and non-acid reflux events

Non-acid refluxate may be important in chronic cough etiology, but impedance testing is not validated to investigate chronic cough

Upper GI endoscopy

Allows direct inspection of the upper GI tract and biopsy of stomach and duodenum

Often unrevealing; endoscopic evidence of GERD less common with atypical (e.g., chronic cough) vs. typical symptoms

Source: [19]

For overweight and obese patients, treatment of suspected reflux-cough should include diet change to promote weight loss. In all patients, recommended diet and lifestyle modifications include [6]:

- Eliminate coffee, tea, soda, other carbonated beverages, fish oil supplements, chocolate, mints, alcohol, and energy drinks, sports, or other drinks containing citric acid

- Consume no more than 45 grams of fat daily

- Avoid smoking and vaping

- Avoid exercising that markedly increases intra-abdominal pressure

- Elevate the head of the bed and avoid meals within three hours of bedtime

In patients with heartburn and regurgitation, PPIs, histamine H2-receptor antagonists, alginate, or antacid therapy is often sufficient to control these symptoms. Gastrointestinal symptoms respond within 4 to 8 weeks, but cough may take 12 weeks to improve [83]. PPI monotherapy is not recommended for chronic cough with solely extraesophageal symptoms, as it is unlikely to resolve the cough.

The ACCP suggests against antireflux surgery for patients with chronic cough patients with a major motility disorder and/or normal acid exposure time in the distal esophagus, as the procedural risks and lack of supporting evidence make the risk-benefit ratio unacceptable [83]. However, surgery may be considered for presumed reflux-cough in patients with normal peristalsis, abnormal esophageal acid exposure on pH-metry, and refractory to medical therapy.

TREATABLE TRAITS AND THOROUGHNESS

The variable success in managing chronic cough may be due, in part, to guidelines or protocols not being implemented as planned (Table 7) [6,80]. Failure to recognize the complexity of airway diseases can lead to suboptimal outcomes, as diseases with different endotypes can require different therapeutic strategies (precision medicine). Because the treatable traits approach is a label-free approach, it does not start on the assumption that the diagnosis (e.g., asthma, COPD) is well-established and clear, a situation that is not the case in many instances in clinical practice, particularly in primary care. This is a fundamental, but often overlooked, issue in the current guideline-directed management of airway diseases [14,16].

Table 7: PITFALLS IN THE MANAGEMENT OF CHRONIC COUGH

Upper Airway Cough Syndrome

Failing to recognize that upper airway cough syndrome (also asthma or GERD) can present as a cough-phlegm syndrome, misdiagnosed as chronic bronchitis.

Assuming that all histamine H1 receptor antagonists (H1RAs) are the same. H1RAs without anticholinergic activity do not help nonallergic rhinitis conditions. Further, anticholinergic H1RAs may adversely affect memory, glaucoma, and prostate problems. Instead, consider ipratropium bromide nasal therapy.

Failing to consider:

- "Silent" upper airway cough syndrome when a patient does not sense a postnasal drip or realize their frequent throat clearing

- Allergic rhinitis and recommend the avoidance of allergens because symptoms are perennial

- Sinusitis because it is nonobvious

- NSAID-exacerbated disease

- The potentially beneficial role of upper respiratory endoscopy

Asthma

Failing to recognize that:

Asthma can present as cough alone (i.e., cough-variant asthma)

Inhaled medications may exacerbate cough

Positive methacholine challenge alone is not diagnostic of asthma

Nonasthmatic Eosinophilic Bronchitis

Failing to consider the diagnosis, occupational/environmental causes, or order the correct test

GERD

Failing to recognize that:

- "Silent" reflux disease can be causal and that it may take two to three months of intensive treatment before cough starts to improve and five to six months to resolve

- GERD can be worsened by comorbidities (e.g., obstructive sleep apnea) or their treatment (e.g., nitrates or calcium channel blockers for coronary artery disease, progesterone for hormone replacement)

Assuming that:

- Cough cannot be due to GERD because cough remains unchanged when gastrointestinal symptoms improve

- Vocal cords' appearance can diagnose GERD, when inflammatory changes from coughing can mimic those of reflux

Being unaware that acid suppression alone will not improve cough

Failing to consider:

- Non-acid reflux disease

- The role of diet, intense exercise, and prokinetic therapy

- Adequately treat co-existing causes of cough that perpetuate the cycle of cough and reflux because cough can provoke reflux

Triad of Upper Airway Cough Syndrome, Asthma, and GERD

Failing to consider that more than one condition may be contributing simultaneously to cough, or failing to consider additional contributing conditions because of another "obvious" cause (e.g., COPD)

Failing to appreciate:

- These chronic disorders cannot be cured and will periodically flare, especially with viral illness

- When cough flares after a period of remission, re-evaluate as if a new problem

- Asthma may become a problem when it was not before

Unsuspected Airway Diseases

Failing to perform bronchoscopy when chest x-ray and CT are normal. Transnasal route allows inspection of both upper and lower respiratory tracts.

Failing to appreciate that prolonged IV therapy for suppurative airway disease may succeed when the same drug given orally failed

Source: [6,80]

Pulmonary and Extrapulmonary Traits as "Connected Comorbidities"

As discussed, the treatable traits approach encourages transdiagnostic thinking about chronic cough and associated diseases to identify distinct endotypes and phenotypes within traditional diagnostic categories, as well as shared mechanisms across diagnostic boundaries. For example, asthma and severe chronic rhinosinusitis with nasal polyposis are frequently associated with other, coexisting type 2 inflammatory diseases, such as NSAID-exacerbated respiratory disease, allergic rhinitis, eosinophilic esophagitis, atopic dermatitis, and type 2 eosinophilic COPD [114]. Chronic rhinosinusitis with nasal polyposis has a 7% prevalence in patients with asthma, increasing to 40% in NSAIDs-exacerbated respiratory disease [138]. In predisposed subjects, a dysregulated type-2 inflammation can develop in epithelial barriers (e.g., airways, intestine, skin) in response to various antigens, such as allergens, micro-organisms, and pollutants. This dysregulated epithelial response leads to diseases such as asthma, rhinitis/rhinosinusitis, eosinophilic gastrointestinal disorders, and atopic dermatitis [95].

Allergens are not the only antigens that trigger inflammation. Rather than allergic disorders, type 2 disorders would be a more appropriate definition, also including non-allergic eosinophilic diseases such as nonasthmatic eosinophilic bronchitis, chronic rhinosinusitis, and eosinophilic disorders of the gastrointestinal tract [95].

Targeted biological therapies can also address conditions with shared type 2 pathophysiology. Biologics with FDA approval targeting type 2 inflammatory disease pathophysiology include dupilumab (anti-IL-4 and IL-13), omalizumab (anti-IgE), mepolizumab (anti-IL-5), and benralizumab (anti-IL-5R) [92]. Mepolizumab has proven effective in chronic rhinosinusitis with nasal polyposis and asthma with high eosinophil levels in sputum. Dual targeting of IL-4 and IL-13 by dupilumab has shown efficacy across chronic rhinosinusitis with nasal polyposis, asthma, eosinophilic esophagitis, and atopic dermatitis, and in uncontrolled COPD with high eosinophil counts [93]. Chronic cough, it should be stressed, has not been examined in any study of biological therapies.

The Argument for Thoroughness

The optimal clinical approach in chronic cough and refractory chronic cough continues to evolve. The ERS guideline suggests simplifying the diagnostic process to shorten a patient's journey to a diagnosis of refractory/unexplained chronic cough and limiting sequential empiric trials to two to four weeks unless responses are observed [10]. However, the 2023 BTS guideline and others argue for a more assertive approach to identify all treatable traits and maximize therapy response before diagnosing refractory/unexplained chronic cough [5,78]. This would be the counterargument to the diagnostic-therapeutic empiric trials approach.

In a 2024 study, all 201 patients presenting to a cough center in 2018–2022 were prospectively studied. Refractory chronic cough (defined as persistent cough severity VAS ≥40 with little improvement after at least two treatment attempts) was diagnosed in 30.7% and unexplained chronic cough in 1.5% [78]. The authors suggest a thorough diagnostic algorithm, with frequent second-step investigations, enabled diagnoses of less common cough etiologies and the low (1.5%) unexplained chronic cough rate. As many therapeutic trials as necessary were engaged in order to target all identifiable treatable traits of chronic cough. Treatment followed a stepwise intensification of therapy and introduced add-on treatment of all cough causes, but this was time-consuming and related to difficulties in keeping patients' adherence. In routine practice, the authors usually recommend more than two therapeutic trials before diagnosing refractory chronic cough. When refractory/unexplained chronic cough is diagnosed, additional treatments should be initiated. These patients require nonpharmacologic and/or drug therapies with opioids, neuromodulators, or novel refractory chronic cough agents.

In a separate study conducted at a clinic in China, experts found that among 1,554 patients with chronic cough patients with negative chest x-rays, 58.8% were attributable to common causes, including nonasthmatic eosinophilic bronchitis (18.3%), cough-variant asthma (16.3%), gastroesophageal reflux-associated cough (13.2%), and upper airway cough syndrome (11.1%) [139]. In addition, 18.4% of cases were attributable to other causes: chronic bronchitis (6.1%), bronchiectasis (4.5%), atopic (4.4%), and postinfectious (3.5%) cough; 9.6% had chronic cough of unexplained etiology. Finally, 13.1% of cases were due to rare causes (e.g., bacterial bronchitis, somatic cough syndrome, diffuse panbronchiolitis, obstructive sleep apnea, and interstitial lung disease). These findings suggest that special examinations should be considered after excluding common causes of chronic cough.

It is important to remember that the workup to rule out refractory/unexplained chronic cough is not complete until bronchoscopy has been performed [6]. A study of bronchoscopy involving 54 patients with refractory/unexplained chronic cough with sputum production (more than 1 tbsp/day), atypical urge-to-cough sensations in chest, and unremarkable chest CT revealed bronchoalveolar neutrophilia in 84% and excessive dynamic airway collapse in 31% [140]. Bronchoscopy influenced or changed the management in 89% of patients. Bronchoscopy findings in this specific population have rarely been described, and treatment strategies in these patients differ from typical refractory/unexplained chronic cough. Bronchoscopy provides high diagnostic value in refractory/unexplained chronic cough with mucus production, identifying specific treatable traits of neutrophilic airway inflammation and excessive dynamic airway collapse [140].

Another argument for moving away from the routine use of empiric therapeutic-diagnostic trials is to spare patients with chronic cough from exposure to minimally helpful or unhelpful medications with potentially adverse effects. For example, PPIs are recommended against for chronic cough in patients who lack classic GERD symptoms. Cumulative doses of PPIs dose-dependently increase the risk of developing hypomagnesemia and other side effects. Both hypomagnesemia and its consequent decrease in melatonin production can decrease lower esophageal sphincter tone and trigger a paradoxical iatrogenic cough. Rather than PPI dose escalation for partial responders, magnesium and melatonin supplementation is recommended to curtail side effects of long-term PPIs [104].

Oral corticosteroids, due to their substantial cumulative side effects, are now recommended only as a last resort in the most recent asthma treatment guidelines [141,142]. Even occasional short courses of oral corticosteroids are associated with significant short-term and cumulative long-term adverse effects, with a pronounced dose-response. Short-term adverse effects of oral corticosteroids include sleep disturbance, increased appetite, reflux, mood changes, sepsis, pneumonia, and thromboembolism. As few as four to five lifetime courses of oral corticosteroids are associated with a significantly increased dose-dependent risk of diabetes, cataracts, heart failure, osteoporosis, and several other conditions [142].

11. TREATMENT OF REFRACTORY CHRONIC COUGH

Refractory and unexplained chronic cough are diagnoses of exclusion. For cases with no clear etiology after an extensive workup, or when guideline-based treatment improves the presumed underlying cause of coughing but not the chronic cough itself, cough hypersensitivity syndrome is the most likely explanation [39].

A variety of organizations have published guideline recommendations for the treatment of refractory and/or unexplained chronic cough (Table 8). The British Thoracic Society asserts that cough hypersensitivity is a treatable trait of many conditions and often the foremost problem in patients with chronic dry/unproductive cough [5]. However, there are currently no tools to positively identify cough hypersensitivity. If the condition does not improve with treatment of treatable traits, it is considered refractory chronic cough. In these patients, the most effective treatments are those addressing cough hypersensitivity and include low-dose morphine, gabapentin, and nonpharmacological therapy. In addition, novel therapies are in development, with P2X3 antagonists the most promising [5].

Table 8: GUIDELINE RECOMMENDATIONS FOR NEUROMODULATOR TREATMENT OF REFRACTORY/UNEXPLAINED CHRONIC COUGH

Drug

Guideline Organization (Year)

ACCP (2016)

ERS (2020)

GRS (2020)a

FRS (2023)

BTS (2023)

NEURO-COUGH (2023)

Low-dose morphine slow-release

Not reportedb

Strong recommendation

Strong recommendation

Recommended: Grade B

Recommended

Recommended, very high consensus

Codeine

Not reported

Not recommended

Not reported

Not reported

Recommended against

Not reported

Gabapentin

Recommended

Conditional recommendation

Can be used

Recommended: Grade B

Recommended

Recommended, high consensus

Pregabalin

Not reported

Conditional recommendation

Can be used

Recommended: Grade B

Recommended

Not reported

Amitriptyline

Not reported

Not reported

Can be used

Recommended: Grade C

Not reported

Recommended, high consensus

Baclofen

Not reported

Not reported

Not reported

Not reported

Not reported

Not reported

a"Can be used" is a weaker endorsement than "recommendation" (i.e., "should be used").

b75% of expert panelists endorsed a recommendation of morphine, falling short of 80% required for inclusion; thus, morphine is neither recommended for nor against.

ACCP = American College of Chest Physicians; BTS = British Thoracic Society; ERS = European Respiratory Society; FRS = French-Speaking Society of Respiratory Diseases; GRS = German Respiratory Society; NEURO-COUGH = New Understanding in the treatment Of COUGH Clinical Research Collaboration; SR = sustained-release.

Source: [5,10,11,12,18,86]

PHARMACOTHERAPY

Neuromodulators are centrally acting agents for refractory chronic cough that can downregulate the hypersensitive cough reflex to decrease coughing. Neuromodulators are first-line options for refractory chronic cough [39,57]. However, some of the literature on neuromodulator use in patients with refractory chronic cough might seem counterintuitive.

Clinical trials of P2X3 antagonists have shown efficacy in reducing cough frequency in many patients with refractory/unexplained chronic cough, but the exact mechanisms underlying refractory/unexplained chronic cough remain poorly understood. Although data also suggest central mechanisms may be a key component in the pathophysiology of refractory/unexplained chronic cough, antitussive drug development has focused on peripheral targets [143].

Among patients with unexplained chronic cough started on amitriptyline and contacted by mail two to three years later, 64% had stopped the medication due to no improvement (40%) and/or side effects (48%). The most common side effects triggering treatment nonadherence were sedation (18%), dry mouth (18%), anxiety (8%), difficulty sleeping (8%), and dizziness (5%). Combining patients who continued and stopped amitriptyline, 53% reported cough improvement of at least 50%. There is some evidence that as treatment duration increases, amitriptyline efficacy may decrease [144].

Opioid Medications

The concept of chronic cough as a neuropathic condition, treated with neuromodulators, is not new. In 1856, Edward Smith described chronic cough as a "disease in itself" due to "irritability of the nerves" that could be treated with "morphia," 164 years before expert consensus in the European Respiratory Society chronic cough guidelines concluded the same, albeit for refractory chronic cough [10,111]. Opioids are thought to exert antitussive effects through opioid receptors within inhibitory cortical descending pathways [59].

Codeine

Codeine is a weak opioid that is metabolized to morphine (5% to 10%) by the enzyme cytochrome P450 2D6 (CYP2D6) in the liver to produce its antitussive effects [145]. Codeine has long been used as an antitussive, but a minority of the population possess a genetic variation in CYP2D6 activity, with variable and unpredictable metabolism that increases unpleasant side effects and decreases efficacy. Codeine is now considered an unreliable antitussive and should not be used in chronic cough [5].

Low-Dose Morphine Slow-Release (SR)

Morphine is not affected by interindividual variability in CYP2D6 metabolism; thus, its biological effects are more predictable than codeine [146]. In the first positive results from a double-blind randomized controlled trial for any drug therapy of refractory chronic cough, morphine was selected to minimize the variability of codeine [25,147]. This study compared twice-daily slow-release morphine 5 mg with placebo for four weeks, followed by four weeks of crossover to the alternate treatment. A three-month open-labeled extension of the randomized controlled trial allowed dose escalation to 10 mg twice per day if patients thought their cough was inadequately controlled [147].

The mean LCQ score significantly improved on morphine but not placebo, with significant improvement in physical, psychological, and social subdomains. A 40% reduction in daily cough scores was noted with morphine; placebo had no discernable effect over baseline. Of patients entering the extension, 67% opted for dose escalation and, after three months, had cough outcome improvements similar to 5-mg full-responder patients. Side-effects of constipation (40%) and drowsiness (25%) were tolerable; no patient dropped out from adverse events. Sedation, previously believed to explain the antitussive action of morphine, was transient, but the antitussive effect continued throughout the core and extension study phases [147].

The authors of this study state that side effects and dependence are obvious concerns with opioid therapy for what is a disabling but non-life-threatening condition. However, they note that the risk-benefit ratio makes low-dose slow-release morphine a credible therapeutic option in patients with refractory chronic cough for whom other treatments have failed. Comparisons of similar therapeutic options were made with patients who require long-term oral corticosteroids for severe nonasthmatic eosinophilic bronchitis or cough-variant asthma with a consequently worse adverse event profile [147].

Another double-blind crossover study randomized previous morphine responders to slow-release morphine 5–10 mg twice daily or placebo. After five days, morphine reduced 24-hour cough frequency by 72% over placebo, including overnight (83%) and daytime (71%) cough frequency [148]. Morphine also significantly reduced noxious somatic sensations driving the urge to cough, suggesting this may be an important component of opioid modality in refractory chronic cough [149].

In a real-world effectiveness and tolerability study of long-term, low-dose opioids, 100 patients were prescribed twice daily slow-release morphine 5–10 mg (72%), oxycodone, or oxycodone/naloxone for a median 52 weeks for refractory/unexplained chronic cough. Median cough severity score (CSS, on a 0–10 scale) decreased from 8 pre-treatment to 4. In all, 60% had good-to-excellent response, while 25% had no response. Side effects (present in 38%) were most commonly constipation (25%), which was managed with dose reduction or constipation therapy; however, 15% stopped treatment due to side effect intolerance. Low-dose opioids improved long-term cough outcomes and were tolerated by most patients with refractory/unexplained chronic cough, but managing constipation allowed more patients to continue therapy [150].

Clinical experience with low-dose, slow-release morphine suggests that up to 50% to 60% of patients with refractory chronic cough obtain benefit [5,59,150]. Response dichotomizes into either a large effect on cough symptoms or no effect at all and is usually apparent within five days. The main side effect, constipation, can be managed with laxatives or adding oral low-dose naloxone. Once-daily dosing may be sufficient if cough symptoms are mainly troublesome during waking hours or overnight. Antitussive tolerance does not seem to develop. Unlike in severe chronic pain, there appears to be a dose ceiling for slow-release morphine of twice daily 10 mg, with no further antitussive effect beyond this. Concerns remain about misuse/addiction potential, and patients must be carefully monitored [5,59]. As noted in a 2024 review, it is unclear why such low doses, compared with those used for analgesia, are effective in some patients with refractory chronic cough [25].

Gabapentinoids

Gabapentin and pregabalin are synthetic analogs of gamma-aminobutyric acid (GABA) that bind theα2δsubunit of voltage-gated calcium channels to block excitatory neurotransmitter release. Both were developed originally for epilepsy treatment and subsequently found to ameliorate chronic neuropathic pain, which is associated with central sensitization. The similar pathophysiologic mechanisms of chronic neuropathic pain and chronic cough suggested that gabapentin and pregabalin may also be beneficial in patients with refractory chronic cough [151].

Evidence Based Practice Recommendation

The European Respiratory Society suggests a trial of gabapentin or pregabalin in adults with chronic refractory cough.

https://erj.ersjournals.com/content/55/1/1901136

Last Accessed: August 12, 2024

Strength of Recommendation/Level of Evidence: Conditional recommendation, low-quality evidence

Gabapentin (1,800 mg/day or the maximum tolerable dose) was compared with placebo for eight weeks in a double-blind randomized controlled trial of 62 patients with refractory chronic cough. Gabapentin significantly improved LCQ score over placebo by 1.8 points, and significantly reduced objective cough frequency and cough severity over placebo. Gabapentin response was greater in patients with symptoms of central sensitization (e.g., laryngeal paresthesia, allotussia, hypertussia). The onset of action of gabapentin took up to four weeks [152]. It was subsequently noted that cough frequency differed between gabapentin and placebo groups at baseline (45.3 vs. 68.8 coughs per hour) and was measured only for one hour at each assessment visit, making interpretation of cough frequency outcomes difficult [25,146].

An open-label randomized trial compared gabapentin (300 mg three times per day) to baclofen (20 mg three times per day), an antispasticity drug, in 234 patients with refractory gastroesophageal reflux-associated cough over nine weeks. Compared with baseline, gabapentin and baclofen similarly led to decreased cough symptom scores and patients with success for cough resolution (57.3% vs. 53.0%). Gabapentin led to lower side effect rates than baclofen of somnolence (20% vs. 35%) and dizziness (11% vs. 24%) [151]. In addition to other burdensome side effects, sudden discontinuation of baclofen can result in seizures [5].

In another study, twice daily pregabalin 75 mg was prescribed to 50 consecutive patients with refractory or unexplained chronic cough for three months. Pregabalin response, defined as LCQ total score improvement of ≥1.3, was attained by 56% of patients. Responders were more likely to have refractory (with underlying pulmonary disease) than unexplained chronic cough, and on average were more symptomatic at baseline. There was no information on side effects or dropout [153].

In another study, 40 patients with refractory chronic cough were randomized to speech pathology treatment plus pregabalin 300 mg/day or speech pathology treatment plus placebo for four weeks. Compared with the placebo group, those who received speech pathology treatment/pregabalin experienced a statistically significant improvement [154]. However, CNS adverse effects (e.g., dizziness, disorientation, confusion, fatigue, blurred vision) were common and sometimes intolerable. The effects of pregabalin on 24-hour cough frequency outcome were non-significant [146].

Because gabapentinoids have beneficial effects on anxiety, improvements in mood may contribute to the apparent benefit or changes in symptom perception or cough intensity. Side effects are common, wide ranging, and can be difficult for patients to tolerate. Slow dose escalation may help minimize this, and maximal doses may not be needed to afford some improvement in cough. Gabapentin and pregabalin may have abuse potential in susceptible patients [5].

Gabapentin should be started at a low dose (e.g., 100 mg three times per day) and titrated up to a maximum dose (600 mg three times per day), depending on clinical effects and tolerability. The usual starting dose of pregabalin for chronic cough is 25 mg twice daily, with increases in increments to a maximum 75 mg twice daily. Patients should be reassessed during dose titration and therapy stopped if there are significant side effects or inadequate response to treatment [5].

In clinical experience, the minority of patients who achieve cough suppression often do so at the expense of intolerable adverse effects, usually sedation [57]. Among 38 patients prescribed gabapentin (maximum: 1,800 mg per day) or pregabalin (maximum: 300 mg per day) for refractory chronic cough, 24% developed immediate intolerable side effects and 37% tolerated the drugs but had no response and stopped the medication. Among the 39% with an initial favorable response, 18% eventually developed intolerable side effects and 21% were able to continue with therapy long-term. The most common side effect was drowsiness/sedation. In real-world practice, gabapentinoids are effective in a subgroup of patients with refractory chronic cough, but side effects may outweigh their potential benefits, which were intolerable for 42% of patients [155].

Tricyclic Antidepressants

Amitriptyline and nortriptyline are tricyclic antidepressants with a broad range of pharmacologic actions effecting adrenergic, serotonergic, muscarinic, and histaminergic systems. Amitriptyline is also used in chronic neuropathic pain (e.g., migraine, postherpetic neuralgia, painful diabetic neuropathy) and has been suggested to be effective in the treatment of chronic cough, with anticholinergic properties thought to underlie the antitussive effect [57,156]. However, clinical experience with amitriptyline in refractory chronic cough suggests more limited value [5].

In a small randomized trial of patients attending an otolaryngology clinic with postviral refractory chronic cough, amitriptyline 10 mg per day was compared with codeine 10 mg/guaifenesin 100 mg combined in a syrup taken every six hours. The majority of patients reported a 75% to 100% improvement in cough with amitriptyline, while most reported no improvement with codeine/guaifenesin. Compared with the control arm, amitriptyline was significantly associated with a response greater than 50% [157]. In a randomized controlled trial of patients with chronic pharyngolaryngeal neuropathy, 67% had subjective improvement with amitriptyline (up to 50 mg/day), compared with 44% with placebo. The mean Voice Handicap Index-10 (VHI-10) score worsened with amitriptyline but was unchanged with placebo. Attrition over the eight-week trial was 40% [158].

Nortriptyline was studied in 42 patients with neurogenic chronic cough, of whom 45% discontinued nortriptyline due to side effect intolerance or lack of response. The average time to clinical response was 5.5 months. The average minimum effective dose was 21 mg per day in responders. Laryngeal asymmetry was present in 85.7% of all patients. Side effects included sedation, xerostomia, and anxiety. The intolerability was surprising, because nortriptyline is both a metabolite of amitriptyline and reported to be better tolerated [159].

Pharmacotherapy for Chronic Cough in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis is a chronic, progressive, and invariably fatal fibrotic lung disease, and 85% of patients with idiopathic pulmonary fibrosis experience cough, a distressing symptom associated with rapid disease progression. Available treatments for idiopathic pulmonary fibrosis slow disease progression but do not improve symptoms or quality of life. Thalidomide benefitted idiopathic pulmonary fibrosis cough in one randomized controlled trial, but its side effect profile renders it practically useless, as only 20% of patients were able to tolerate it [125]. Worse still, the potentially severe adverse effect of peripheral neuropathy suggests it may damage sensory nerves (vagal afferents). Thalidomide should not be considered even as second-line therapy for idiopathic pulmonary fibrosis cough until further evaluation of the benefit/risk ratio has been undertaken [160].

Although studies on refractory chronic cough can help inform the treatment of idiopathic pulmonary fibrosis cough, the biological mechanisms that contribute to cough probably differ in these conditions, as evidenced by the contrasting results with gefapixant, a P2X3 receptor antagonist, in refractory chronic cough (positive findings) and idiopathic pulmonary fibrosis cough (negative findings) [161].

Nalbuphine

Nalbuphine extended-release (ER) is an opioid agonist-antagonist. In a double-blind randomized controlled trial of patients with idiopathic pulmonary fibrosis and chronic cough, nalbuphine ER tablets (titrated up to 162 mg twice daily) led to 75.1% reduction in daytime objective cough frequency, compared with 22.6% with placebo, a 50.8% placebo-adjusted reduction in 24-hour cough frequency, and similar improvements in patient reported outcomes [162]. Nalbuphine ER was the first therapy to show robust effects on chronic cough in idiopathic pulmonary fibrosis [25]. However, nalbuphine side effects of nausea (42.1%), fatigue (31.6%), constipation (28.9%), and dizziness (26.3%) led to a 24% dropout during the drug initiation phase, partially attributed to the inflexible forced-titration study design [162].

Low-Dose Morphine SR

In a multicenter randomized controlled trial of patients with idiopathic pulmonary fibrosis and chronic cough, low-dose, slow-release morphine (5 mg twice daily) reduced objective awake cough frequency by 39.4% over placebo, and all cough-related patient-reported outcomes remained significantly improved when adjusted for placebo. Morphine side effects of nausea (14%) and constipation (21%) resulted in only one participant discontinuing morphine, indicating tolerability for these patients. The authors note that the safety assessments during study visits were reassuring and there appeared to be no changes in mood or excessive fatigue with morphine [161]. The authors advocate for rapid implementation in clinical practice due to the well-established safety profile and worldwide availability [163].

A 2024 study reported variable effectiveness of slow-release morphine (8–32 mg per day) in reducing breathlessness in patients with COPD. But, it provided reassuring safety data by observing no evidence of harm and no worsening of subjective daytime sleepiness, alertness, or sleep quality at one and four weeks in these severely ill patients [164].

INVESTIGATIONAL PHARMACOTHERAPIES

Low-dose, slow-release morphine has the strongest observational and empirical evidence of antitussive benefit in refractory chronic cough of any commercially available (although off-label) medication and may be used safely in this population when patients are carefully screened and monitored. Because as many as 50% of patients with refractory chronic cough have no response to low-dose morphine and with substantial restrictions on opioid prescribing in the United States, effective peripherally acting antitussives are an urgent priority for investigators.

P2X3 Receptor Antagonists

P2X3 receptors form ion channels containing ATP-binding sites. In the lungs and airway, ATP activates P2X3 receptors localized on vagal sensory nerve terminals, resulting in bronchoconstriction, cough, and localized release of inflammatory neuropeptides [165].

A breakthrough occurred when gefapixant, a P2X3 receptor antagonist, demonstrated a dramatic reduction in chronic cough. Other P2X3 antagonists confirmed the efficacy of this drug class in refractory chronic cough. The endogenous ligand for P2X3 is ATP. Epithelial damage is believed to release ATP. Evidence suggests that ATP largely mediates peripheral hypersensitivity; therefore, gefapixant is peripherally acting in refractory chronic cough [166].

P2X3 receptors are ion channels found on sensory afferent nerve fibers, activated by ATP. In preclinical studies, vagal C fibers, including those thought to be important in mediating cough, have been shown to express P2X3 and P2X2. At present, it is unclear whether ATP concentrations are elevated or P2X3 receptor expression increased in the airways of patients with refractory chronic cough, or how antagonism of P2X3 plays a role in reducing coughing to a range of chemical irritants, temperature changes, and mechanical stimuli. Nonetheless, in clinical trials, P2X3 receptor antagonism has provided robust reductions in cough frequency and patient-reported outcomes [25].

Gefapixant

The first novel therapy to have significant effects in patients with refractory chronic cough was gefapixant, a first-in-class P2X3 antagonist that was originally planned to be developed as an analgesic. Gefapixant has become the first therapeutic to undergo systematic development as a treatment for refractory chronic cough following unprecedented reductions in cough frequency.

In a landmark study, twice daily gefapixant 600 mg showed remarkable therapeutic effects in patients with refractory chronic cough [167]. Objective 24-hour cough frequency was reduced 74% compared with placebo, and daytime cough severity VAS score and CQLQ score reduced by −25.6 and −9.2, respectively. However, another important finding was that virtually all treated patients reported ageusia, or loss of taste, and 24% withdrew because of the adverse effect. These taste side effects are likely attributable to the inhibition of P2X2/3 channels on the nerve fibers innervating the taste buds by high-dose gefapixant [146].

Subsequent studies suggest that antitussive effects are retained at much lower doses (30–50 mg twice daily), at which taste was altered rather than lost and hence the therapy was better tolerated. Larger multi-center parallel group studies were performed in the UK and the United States followed by the first-ever global phase 3 trials of an antitussive treatment for refractory chronic cough, which reported positive findings over placebo for a 45-mg twice daily dose [25].

Eliapixant and Filapixant

Following the taste side effects reported for gefapixant, more selective P2X3 antagonists were evaluated for the treatment of refractory chronic cough; however, there was some uncertainty about whether effects at both P2X3 and P2X2/3 channels were both contributing to antitussive efficacy and hence whether more selective agents would have similar efficacy. Eliapixant and filapixant both demonstrated efficacy in dose-ranging studies, but eliapixant appeared to cause less taste disturbance (up to 21% of patients) and was therefore progressed to a phase 2b parallel trial. Although this trial reported positive findings, a small number of cases of liver toxicity prevented further development of this therapy for refractory chronic cough [25].

Sivopixant

Another more selective P2X3 antagonist, sivopixant, exhibited promising findings in a single-dose crossover study, very similar in design to the first gefapixant study. The reduction in daytime cough frequency of 32% over placebo (the primary endpoint) was not quite statistically significant, but taste adverse effects were only reported in 6.4% of patients. In a follow-up, multicenter parallel group study assessing a range of doses for four weeks, no dose of sivopixant could be discriminated from the very large placebo effect—there was 60% placebo reduction in cough frequency from baseline. The largest absolute change in cough frequency was observed for the highest dose (300 mg), but 30% of patients reported taste adverse effects. No further studies of sivopixant in refractory chronic cough have been planned [25].

Camlipixant

Finally, thought to be the most selective P2X3 antagonist, camlipixant is the second compound in this class to be evaluated in phase 3 trials. The first double-blind randomized controlled crossover trial of camlipixant studied escalating doses from 25 mg to 200 mg versus matched placebo. Although the primary endpoint of awake cough frequency did not reach statistical significance, preplanned subgroup analysis in patients with a cough frequency of at least 20 coughs per hour (80% of patients) and those with greater than the median cough frequency (≥32 coughs per hour, 50% of patients) exhibited significant improvements versus placebo for all doses tested. This preplanned analysis was based on observations from several of the gefapixant studies that suggested P2X3 antagonism was most efficacious in patients with the highest baseline cough frequency [25].

In post-hoc analysis of a phase 2a study, among patients who reported cough-related urinary incontinence at baseline, 11%, 15%, and 21% of those treated with 12.5 mg, 50 mg, and 200 mg camlipixant, respectively, reported no cough-related urinary incontinence at day 29 (compared with 3% with placebo) [168]. As of 2024, camlipixant is being evaluated in two large-scale phase 3 studies, again in patients selected for higher cough frequencies [25].

Other Novel Antitussives Under Investigation

The studies completed to date investigating P2X3 antagonists have typically found that between one-quarter and one-third of patients do not experience the 30% reduction in cough frequency thought to be the meaningful clinical threshold, suggesting some heterogeneity in the mechanisms underlying refractory chronic cough. Furthermore, patients with less frequent/severe coughing than those recruited to these trials may not benefit from treatments interrupting the ATP-P2X3 axis. Therefore, treatments with alternative modes of action are required to optimally manage patients with refractory chronic cough [25].

Sodium Channel Blockade

Lidocaine non-selectively blocks voltage-gated sodium channels important in the initiation of action potentials and their conduction and is a local anesthetic agent in routine topical use to reduce coughing during bronchoscopy. Case reports and case series have also described the use of nebulized lidocaine as an antitussive to treat refractory chronic cough [169].

In a three-way crossover study of single-dose lidocaine in refractory chronic cough, lidocaine throat spray reduced coughing by about 50% and was more effective than nebulized lidocaine, probably because nebulization into the lower airways has an irritant effect and evokes coughing initially [169]. The antitussive effects of lidocaine spray are relatively short lived and also associated with numbness in the mouth and lips, preventing patients from safely eating after treatment. Efforts have been made to develop similar therapies with a longer duration of action and without loss of sensation [25].

A novel approach to sodium channel blockade has been developed using a compound that is only active in blocking sodium channels after entering neurons via large-pore ion channels, such as P2X3 channels. As of 2024, a phase 2a clinical trial has been performed but the results are not yet published.

TRPM8 Agonism

Activation of TRPM8 ion channels produces cooling sensations. One new therapy has used an orally dissolving tablet containing a TRPM8 agonist (AX-8) placed on the back of the tongue to act as a counter irritant to the sensations of throat irritation reported by many patients with refractory chronic cough. In a randomized controlled trial, AX-8 reduced cough frequency, but not significantly over eight hours, the duration of action suggested by a previous open-label study. However, the effect was significant over four hours and exaggerated in those patients reporting greater throat discomfort, consistent with the proposed mechanism of action. Further studies in this subgroup of patients are hoped to confirm efficacy [25].

On day 1, AX-8 reduced cough frequency within 15 minutes and more than placebo over two and four hours, but not eight hours. In participants with baseline throat discomfort, reduction in cough frequency was significant over 24 hours, with a maximum reduction compared to placebo of 43% over two hours. Over 14 days, AX-8 significantly improved patient-reported outcomes and the safety profile was good with no serious adverse events. This suggests that TRPM8 agonism has potential for control of refractory/unexplained chronic cough as an alternative or adjunct to other therapies, especially in those patients complaining of cough driven by throat sensations [170].

NK-1 Antagonism

Following a positive study testing aprepitant as a cough treatment in patients with lung cancer, there has been interest in the potential antitussive effects of centrally acting neurokinin-1 (NK-1) antagonists. Following a negative trial in refractory chronic cough, a double-blind randomized controlled trial is in progress testing the effects of orvepitant in patients with cough associated with idiopathic pulmonary fibrosis [25].

NONPHARMACOLOGIC THERAPY

Speech and Language Therapy

Speech and language therapy techniques were first described as improving chronic cough in a randomized controlled trial in 87 patients with refractory chronic cough. The intervention appeared to have positive impact on cough, voice, throat symptoms, and symptom limitation after four therapy sessions over two months. Another study investigated a similar intervention delivered by speech and language therapists and physiotherapists. Compared with sham therapy, LCQ score improved by 1.5 points. Cough frequency improved by 40% more than in the sham-treated arm at four weeks and seemed to be maintained at three months. No larger-scale trials have been completed [25].

Evidence Based Practice Recommendation

The European Respiratory Society suggests a trial of cough control therapy (physiotherapy/speech and language therapy) in adult patients with chronic cough.

https://erj.ersjournals.com/content/55/1/1901136

Last Accessed: August 12, 2024

Strength of Recommendation/Level of Evidence: Conditional recommendation, moderate-quality evidence

Speech and language therapy is a complex intervention, comprising components of education, cough suppression techniques, vocal hygiene, and psychoeducational counseling. Thus, it is difficult to standardize the intervention, and it is not clear whether all or just some of the components are essential for efficacy. In practice, the therapy seems to be most effective when delivered by experienced therapists, who may not be widely available. There is also a question about the durability of the effects over longer timescales when patients may not continue to practice the techniques [25].

The speech and language therapy approach to the management of chronic cough involves four steps: education, vocal hygiene, cough control/suppression training, and psychoeducational counseling [19].

Education

Patients are provided education on the biology of coughing, chronic cough, and cough hypersensitivity. The negative effects of repeated coughing and throat clearing are explained [19].

Vocal Hygiene

Vocal and laryngeal hygiene and hydration are advised with a reduction in caffeine and alcohol intake. Nasal breathing with nasal douching may be recommended with nasal steam inhalation [19].

Cough Control/Suppression Training

Following identification of patient cough triggers, patients are taught a range of suppression strategies, including forced/dry swallow, sipping water, chewing gum, or sucking non-medicated sweets. Breathing pattern re-education is used to promote relaxed abdominal breathing while inhaling through the nose [19].

Psychoeducational Counseling

Behavior modification is used to reduce over-awareness of the need to cough and facilitate an individual's internalization of control over their cough and to help manage stress and anxiety [19].

Local Injection Therapies

The experience of superior laryngeal nerve block by the injection of local anesthetic agents and corticosteroids has been described retrospectively following implementation in several clinics. In 2024, a small single-blind placebo-controlled study was performed comparing this treatment in 10 patients injected with active treatment and 7 with placebo, finding improvements in cough VAS and LCQ scores. Transient sensations of globus (lump in the throat) and soreness at the site of inject were the main adverse effects. Laryngeal botulinum toxin injections have also been reported to produce improvements in series of patients in clinical care, but no controlled studies have been performed. The broad safety of these interventions and duration of any effect currently remains unclear [25].

12. CONCLUSION

Chronic cough affects roughly 10% of adults in the United States [32]. These individuals can cough hundreds to thousands of times every day, often with uncontrollable bouts of coughing triggered by laughing, speaking, or changes in ambient temperature. This can continue for many years or decades, leading to substantial physical and emotional symptoms, including fatigue, urinary incontinence, cough syncope, dysphonia, depression, anxiety, embarrassment, social isolation, and severely diminished quality of life [28,40,64].

In 20% to 59% of patients with chronic cough, coughing persists despite extensive guideline-recommended evaluation and treatment of comorbidities or an underlying cause of cough cannot be identified. In these cases, a diagnosis of refractory or unexplained chronic cough is rendered [7,36].

Chronic cough is a distinct pathologic entity (cough hypersensitivity syndrome) that develops when repetitive activation of airway cough receptors (typically by inflammatory mediators) induces neuroplastic changes, resulting in peripheral and central sensitization with symptoms of allotussia, hypertussia, and/or laryngeal paresthesia [3,19,20]. Hypersensitivity of vagal afferent neurons in the airways and their central projections, and deterioration in cortical inhibitory control of cough, explain the chronicity characteristics of this condition [33,78].

According to current best evidence, clinical management of patients with chronic cough requires that clinicians perform thorough history, physical examination, and diagnostic testing to identify any potential underlying causes, with asthma, COPD, nonasthmatic eosinophilic bronchitis, upper airway cough syndrome, and GERD the top diagnoses to consider. After assessment is complete, clinicians should treat any identified airway and esophageal conditions according to practice guidelines. As part of the treatment approach, behavioral treatable traits, including cigarette smoking, use of ACE inhibitors and NSAIDs, poor inhaler technique (when relevant), and treatment adherence in general should be identified and addressed [5,6,10,18,24,25,79,171].

It is important to recognize that cough hypersensitivity syndrome is present when cough persists despite etiologically based treatment or no etiology can be identified. Clinicians can make a diagnosis of refractory or unexplained chronic cough and refocus management to downregulating a hyper-reactive cough reflex using commercially available medication prescribed off-label and cough-specific speech and language therapy [5,6,10,18,24,25,79,171].

Despite showing the best effectiveness, safety, and tolerability of commercially available medications evaluated in patients with refractory/unexplained chronic cough patients and despite recommended by international clinical practice guidelines, use of low-dose, slow-release morphine may be untenable or unrealistic. In light of this fact, gabapentin, pregabalin, and amitriptyline remain options for effective pharmacotherapy. Clinicians should also stay informed about possible FDA approval of gafapixant, the first-ever drug approved for refractory/unexplained chronic cough in several other countries, and about phase 3 trials of campilixant. Approval of these agents could expand the treatment options for these patients and potentially improve patient quality of life.

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124. Maher TM. Interstitial lung disease: a review. JAMA. 2024;331(19):1655-1665.

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126. Lee J, White E, Freiheit E, et al. Cough-specific quality of life predicts disease progression among patients with interstitial lung disease: data from the Pulmonary Fibrosis Foundation patient registry. Chest. 2022;162(3):603-613.

127. Dąbrowska M, Arcimowicz M, Grabczak EM, et al. Chronic cough related to the upper airway cough syndrome: one entity but not always the same. Eur Arch Otorhinolaryngol. 2020;277(10):2753-2759.

128. Dykewicz MS, Wallace DV, Amrol DJ, et al. Rhinitis 2020: a practice parameter update. J Allergy Clin Immunol. 2020;146(4):721-767.

129. Baroody FM, Gevaert P, Smith PK, Ziaie N, Bernstein JA. Nonallergic rhinopathy: a comprehensive review of classification, diagnosis, and treatment. J Allergy Clin Immunol Pract. 2024:12(6):1436-1447.

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131. Zhao P, Kariya S, Higak T, et al. Chronic rhinosinusitis possibly associated with decreased lung function in chronic cough patients. Braz J Otorhinolaryngol. 2024;90(4):101424.

132. Naclerio RM, Bousquet J. Nose woes. J Allergy Clin Immunol Pract. 2024;12(6):P1493-P1494.

133. Gyawali CP, Yadlapati R, Fass R, et al. Updates to the modern diagnosis of GERD: Lyon consensus 2.0. Gut. 2024;73(2):361-371.

134. Chen JW, Vela MF, Peterson KA, Carlson DA. AGA clinical practice update on the diagnosis and management of extraesophageal gastroesophageal reflux disease: expert review. Clin Gastroenterol Hepatol. 2023;21(6):1414-1421.

135. 135. Decalmer S, Stovold R, Houghton LA, et al. Chronic cough: relationship between microaspiration, gastroesophageal reflux, and cough frequency. Chest. 2012;142(4):958-964.

136. Zhang L, Zhang M, Aierken A, Dong R, Chen Q, Qiu Z. Role of alveolar nitric oxide in gastroesophageal reflux-associated cough: prospective observational study. Ther Adv Respir Dis. 2024;18:1-16.

137. Hránková V, Balner T, Gubová P, Staníková L, Zeleník K, Komínek P. Narrative review of relationship between chronic cough and laryngopharyngeal reflux. Front Med (Lausanne). 2024:11:1348985.

138. Pérez-Pazos J, García-Sánchez A, Estravís M, et al. Beyond T2-asthma biomarkers: risk stratification for NSAID-exacerbated respiratory disease. ERJ Open Res. 2024;10(4).

139. Lai K, Tang J, Zhan W, et al. The spectrum, clinical features and diagnosis of chronic cough due to rare causes. J Thorac Dis. 2021;13(4):2575-2582.

140. 140. Wingfield Digby J, King J, Al-Sheklly B, Marsden P, Fowler S, Smith J. Bronchoscopy for refractory/unexplained cough with mucus. Respir Med. 2023;217:107335.

141. Levy ML, Bacharier LB, Bateman E, et al. Key recommendations for primary care from the 2022 Global Initiative for Asthma (GINA) update. NPJ Prim Care Respir Med. 2023;33(1):7.

142. Global Initiative for Asthma. 2024 GINA Main Report: Global Strategy for Asthma Management and Prevention. Available at https://ginasthma.org/2024-report/. Last accessed July 25, 2024.

143. King J, Al-Sheklly B, Wingfield Digby J, et al. Refractory chronic cough patients are indiscriminately hyper-responsive to inhaled tussive irritants/agents. Am J Respir Crit Care Med. 2022;205:A2809.

144. Ryan MA, Cohen SM. Long-term follow-up of amitriptyline treatment for idiopathic cough. Laryngoscope. 2016;126(12):2758-2763.

145. Peechakara BV, Tharp JG, Eriator II, Gupta M. Codeine. Treasure Island, FL: StatPearls Publishing; 2023.

146. Song W-J, Chung KF. Pharmacotherapeutic options for chronic refractory cough. Expert Opin Pharmacother. 2020;21(11):1345-1358.

147. Morice AH, Menon MS, Mulrennan SA, et al. Opiate therapy in chronic cough. Am J Respir Crit Care Med. 2007;175(4):312315.

148. Al-Sheklly B, Mitchell J, Issa B, et al. S35 Randomised control trial quantifying the efficacy of low dose morphine in a responder group of patients with refractory chronic cough. Thorax. 2017;72(Suppl 3):A24-A25.

149. Mitchell J, Al-Sheklly B, Issa B, et al. P104 Sensations associated with experimentally evoked cough: influence of low dose morphine sulphate in opioid responders. Thorax. 2017;72(Suppl 3):A139-A140.

150. King J, Wingfield-Digby J, Hennessey S, et al. Real world effectiveness and tolerability of low-dose opiates for refractory/unexplained chronic cough (RCC/UCC) in a tertiary clinic. Eur Respir J. 2022;60(Suppl 66):1159.

151. Zhang M, Zhu Y, Dong R, Qiu Z. Gabapentin versus baclofen for treatment of refractory gastroesophageal reflux-induced chronic cough. J Thorac Dis. 2020;12(9):5243-5250.

152. Ryan NM, Birring SS, Gibson PG. Gabapentin for refractory chronic cough: a randomised, double-blind, placebo-controlled trial. Lancet. 2012;380(9853):1583-1589.

153. Saint-Pierre MD. Predictors of treatment response to pregabalin in unexplained or refractory chronic cough. Respir Med. 2023:218:107396.

154. Vertigan AE, Kapela SL, Ryan NM, Birring SS, McElduff P, Gibson PG. Pregabalin and speech pathology combination therapy for refractory chronic cough: a randomized controlled trial. Chest. 2016;149(3):639-648.

155. Al-Sheklly B, Badri H, Satia I, Woodcock A, Smith JA. P106 The use of gabapentin and pregabalin for the management of chronic cough in a tertiary cough clinic. Thorax. 2017;72(Suppl 3):A140-A142.

156. Dicpinigaitis PV, Morice AH, Birring SS, et al. Antitussive drugs: past, present, and future. Pharmacol Rev. 2014;66(2):468-512.

157. Jeyakumar A, Brickman TM, Haben M. Effectiveness of amitriptyline versus cough suppressants in the treatment of chronic cough resulting from postviral vagal neuropathy. Laryngoscope. 2006;116(12):2108-2112.

158. Jang M, Rubin SJ, Stein DJ, Noordzij JP. Randomized double blind trial of amitriptyline versus placebo in treatment of chronic laryngopharyngeal neuropathy. Am J Otolaryngol. 2017;38(6):683-687.

159. Song SA, Choksawad K, Franco RA Jr. The effectiveness of nortriptyline and tolerability of side effects in neurogenic cough patients. Ann Otol Rhinol Laryngol. 2021;130(7):781-787.

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162. Maher TM, Avram C, Bortey E, et al. Nalbuphine tablets for cough in patients with idiopathic pulmonary fibrosis. NEJM Evid. 2023;2(8):EVIDoa2300083.

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171. Krüger K, Holzinger F, Trauth J, Koch M, Heintze C, Gehrke-Beck S. Chronic cough. Dtsch Arztebl Int. 2022;119(5):59-65.

Evidence-Based Practice Recommendations Citations

1. Alyn H Morice 1, Eva Millqvist 2, Kristina Bieksiene, et al. ERS guidelines on the diagnosis and treatment of chronic cough in adults and children. Eur Respir J. 2020;55(1):1901136. Available at https://erj.ersjournals.com/content/55/1/1901136. Last accessed August 12, 2024.

2. Côté A, Russell RJ, Boulet L-P, et al. Managing chronic cough due to asthma and NAEB in adults and adolescents: CHEST Guideline and Expert Panel report. Chest. 2020;158(1):68-96. Available at https://journal.chestnet.org/article/S0012-3692(20)30045-3/fulltext. Last accessed August 12, 2024.

48854 • Pressure Injuries: Prevention and Management

John M. Leonard, MD

www.netce.com

Copyright © 2025 NetCE, All rights reserved.

Pressure injuries are among the most common conditions encountered in patients who suffer prolonged hospitalization or require long-term institutional care. The prevalence varies widely by clinical setting, age, and geographical region. Although generally preventable, not all pressure injuries can be classified as preventable or potentially curable, due to impaired blood circulation, sensory loss, and immobility, causing some patients to become more vulnerable to them. Several dynamics give rise to the occurrence of pressure injuries, but compression leading to ischemia is the ultimate communal culprit. Furthermore, cognitive impairment of some patients has made some preventive measures extremely challenging to employ. This course will outline the etiology, pathogenesis, identification, prevention, and treatment of pressure injuries in any practice setting.

Table of Contents

48854 • Pressure Injuries: Prevention and Management

Course Overview

Audience

Accreditations & Approvals

Designations of Credit

Special Approvals

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Division Planners

Division Planners Disclosure

Director of Development and Academic Affairs

Director Disclosure Statement

About the Sponsor

Disclosure Statement

Implicit Bias in Health Care

1. INTRODUCTION

2. EPIDEMIOLOGY

3. PATHOGENESIS

4. RISK FACTORS

EXTRINSIC FACTORS

INTRINSIC RISK FACTORS

RISK ASSESSMENT

5. STAGING OF PRESSURE INJURIES

DEEP TISSUE PRESSURE INJURY

STAGE 1: NONBLANCHABLE ERYTHEMA

STAGE 2: PARTIAL-THICKNESS SKIN LOSS WITH EXPOSED DERMIS

STAGE 3: FULL-THICKNESS SKIN LOSS

STAGE 4: FULL-THICKNESS SKIN AND TISSUE LOSS WITH EXPOSED BONE, TENDON, OR MUSCLE

UNSTAGEABLE

MEDICAL DEVICE-RELATED PRESSURE INJURY

MUCOSAL MEMBRANE PRESSURE INJURY

6. PHASES OF WOUND HEALING: AN OVERVIEW

INFLAMMATORY PHASE

PROLIFERATION PHASE

MATURATION PHASE

7. DIAGNOSIS

8. PREVENTION AND TREATMENT

SKIN CARE AND PRESSURE-RELIEVING STRATEGIES

NUTRITIONAL SUPPORT

WOUND CLEANSING

DEBRIDEMENT

DRESSINGS

PAIN MANAGEMENT

SURGICAL CLOSURE

INFECTION MANAGEMENT

ADJUNCTIVE TREATMENTS

INDIVIDUAL STAGING TREATMENT PLANS

9. WOUND MONITORING

WOUND ASSESSMENT

WOUND EDGE AND SURROUNDING SKIN

PAIN

PRESENCE OF INFECTION

10. COMPLICATIONS

CELLULITIS

SEPSIS AND SEPTIC SHOCK

BONE AND JOINT INFECTIONS

MALIGNANCY

GAS GANGRENE

NECROTIZING FASCIITIS

RECURRENCE

11. TREATMENT OF COMORBIDITIES

DIABETES

URINARY AND FECAL INCONTINENCE

PERIPHERAL VASCULAR DISEASE

HYPOTENSION AND HYPOXIA

GASTROINTESTINAL DISORDERS AND MALABSORPTION

MALIGNANCY

END-STAGE RENAL DISEASE

DEPRESSION

COGNITIVE IMPAIRMENT

12. ADVANCES IN PRESSURE INJURY CARE

REPOSITIONING ALERTS

DETECTION

DOCUMENTATION

ULTRASOUND

SKIN SUBSTITUTES OR GRAFTS

GENE THERAPY

NEGATIVE PRESSURE WOUND DEVICES

GROWTH FACTORS AND BIOLOGIC WOUND PRODUCTS

OTHER TREATMENT MODALITIES

13. MEDICO-LEGAL ASPECTS OF INJURY CARE

AVOIDABLE VERSUS UNAVOIDABLE INJURIES

DETERMINATION OF NEGLECT

14. EDUCATING PATIENTS

PATHOGENESIS OF PRESSURE INJURIES

REDUCTION OF RISK

REDUCTION OF FRICTION AND SHEAR

SKIN INSPECTION AND PROTECTION

NUTRITION

PROCEDURE FOR RECURRENCES

MANAGEMENT OF PRESSURE INJURY

PROPER DRESSING CHANGE PROCEDURE

15. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

48854 • Pressure Injuries: Prevention and Management

Education Category. Infection Control / Internal Medicine

Release Date. 05/01/2025

Expiration Date. 04/30/2028

Course Overview

Pressure injuries are among the most common conditions encountered in patients who suffer prolonged hospitalization or require long-term institutional care. The prevalence varies widely by clinical setting, age, and geographical region. Although generally preventable, not all pressure injuries can be classified as preventable or potentially curable, due to impaired blood circulation, sensory loss, and immobility, causing some patients to become more vulnerable to them. Several dynamics give rise to the occurrence of pressure injuries, but compression leading to ischemia is the ultimate communal culprit. Furthermore, cognitive impairment of some patients has made some preventive measures extremely challenging to employ. This course will outline the etiology, pathogenesis, identification, prevention, and treatment of pressure injuries in any practice setting.

Audience

This course is designed for physicians, primary care providers, and physician assistants involved in the care of patients at risk for pressure injury development.

Accreditations & Approvals

In support of improving patient care, TRC Healthcare/NetCE is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. NetCE is accredited by the International Accreditors for Continuing Education and Training (IACET). NetCE complies with the ANSI/IACET Standard, which is recognized internationally as a standard of excellence in instructional practices. As a result of this accreditation, NetCE is authorized to issue the IACET CEU.

Designations of Credit

This activity was planned by and for the healthcare team, and learners will receive 10 Interprofessional Continuing Education (IPCE) credit(s) for learning and change. NetCE designates this enduring material for a maximum of 10 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 10 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Completion of this course constitutes permission to share the completion data with ACCME. Successful completion of this CME activity, which includes participation in the evaluation component, enables the learner to earn credit toward the CME and/or Self-Assessment requirements of the American Board of Surgery's Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit. This activity has been approved for the American Board of Anesthesiology’s® (ABA) requirements for Part II: Lifelong Learning and Self-Assessment of the American Board of Anesthesiology’s (ABA) redesigned Maintenance of Certification in Anesthesiology Program® (MOCA®), known as MOCA 2.0®. Please consult the ABA website, www.theABA.org, for a list of all MOCA 2.0 requirements. Maintenance of Certification in Anesthesiology Program® and MOCA® are registered certification marks of the American Board of Anesthesiology®. MOCA 2.0® is a trademark of the American Board of Anesthesiology®. Successful completion of this CME activity, which includes participation in the activity with individual assessments of the participant and feedback to the participant, enables the participant to earn 10 MOC points in the American Board of Pediatrics' (ABP) Maintenance of Certification (MOC) program. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABP MOC credit. This activity has been designated for 10 Lifelong Learning (Part II) credits for the American Board of Pathology Continuing Certification Program. Through an agreement between the Accreditation Council for Continuing Medical Education and the Royal College of Physicians and Surgeons of Canada, medical practitioners participating in the Royal College MOC Program may record completion of accredited activities registered under the ACCME's "CME in Support of MOC" program in Section 3 of the Royal College's MOC Program. NetCE is authorized by IACET to offer 1 CEU(s) for this program.

Special Approvals

This activity is designed to comply with the requirements of California Assembly Bill 1195, Cultural and Linguistic Competency.

Course Objective

The purpose of this course is to provide physicians, physician assistants, and nurse practitioners a current review of the pathogenesis, diagnosis, and treatment of pressure injuries, with an emphasis on clinical recognition and staging, risk factor assessment and prevention, and management strategies for collaborative care to improve patient outcomes.

Learning Objectives

Upon completion of this course, you should be able to:

1. Discuss the epidemiology, etiology, and pathogenesis of pressure injuries.

2. Identify patients at risk based on extrinsic and intrinsic factors important to pathogenesis.

3. Recognize and define the severity and progression of pressure injuries by stage.

4. Analyze techniques available for the diagnosis of pressure injuries.

5. Develop an effective strategy for skin care and prevention of pressure injuries.

6. Choose appropriate options for wound cleansing, debridement, and dressing based on wound types.

7. Manage other aspects of the care of patients with pressure injuries, including pain management and infectious complications.

8. Create individual treatment plans based on patient characteristics and pressure injury stage.

9. Identify the qualities of a pressure injury that should be monitored.

10. Outline possible complications and comorbidities of pressure injuries and their treatment.

11. Describe the medico-legal aspects of pressure injuries and the significance of correct documentation and patient education.

Faculty

John M. Leonard, MD, Professor of Medicine Emeritus, Vanderbilt University School of Medicine, completed his post-graduate clinical training at the Yale and Vanderbilt University Medical Centers before joining the Vanderbilt faculty in 1974. He is a clinician-educator and for many years served as director of residency training and student educational programs for the Vanderbilt University Department of Medicine. Over a career span of 40 years, Dr. Leonard conducted an active practice of general internal medicine and an inpatient consulting practice of infectious diseases.

Faculty Disclosure

Contributing faculty, John M. Leonard, MD, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Division Planners

John V. Jurica, MD, MPH

Ronald Runciman, MD

Division Planners Disclosure

The division planners have disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Director of Development and Academic Affairs

Sarah Campbell

Director Disclosure Statement

The Director of Development and Academic Affairs has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

About the Sponsor

The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.

Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.

Disclosure Statement

It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.

Implicit Bias in Health Care

The role of implicit biases on healthcare outcomes has become a concern, as there is some evidence that implicit biases contribute to health disparities, professionals' attitudes toward and interactions with patients, quality of care, diagnoses, and treatment decisions. This may produce differences in help-seeking, diagnoses, and ultimately treatments and interventions. Implicit biases may also unwittingly produce professional behaviors, attitudes, and interactions that reduce patients' trust and comfort with their provider, leading to earlier termination of visits and/or reduced adherence and follow-up. Disadvantaged groups are marginalized in the healthcare system and vulnerable on multiple levels; health professionals' implicit biases can further exacerbate these existing disadvantages.

Interventions or strategies designed to reduce implicit bias may be categorized as change-based or control-based. Change-based interventions focus on reducing or changing cognitive associations underlying implicit biases. These interventions might include challenging stereotypes. Conversely, control-based interventions involve reducing the effects of the implicit bias on the individual's behaviors. These strategies include increasing awareness of biased thoughts and responses. The two types of interventions are not mutually exclusive and may be used synergistically.

1. INTRODUCTION

A pressure injury is a localized skin erosion and subcutaneous crater, usually over a bony prominence, caused by the mechanical effect of unrelenting pressure [1,2]. The skin and soft tissues become vulnerable when extrinsic factors, such as prolonged pressure, shearing forces, friction, and moisture, coincide with intrinsic (host) factors, such as immobility, poor nutritional state, and incontinence. The most common areas where pressure injuries occur include the sacrum, coccyx or tailbone, hips, heels, and elbows. These injuries can range from superficial to deep and may even penetrate through deep muscle layers to bone. Without proper attention to risk factors, preventive measures, and early vigorous care and treatment, superficial areas of pressure injury to the skin can evolve into deep soft tissue necrosis and ulceration, from which life-threatening complications may ensue.

In 400 B.C.E., Hippocrates was the first physician to document a pressure injury, but it is assumed they have existed for all of human history. The problem is commonly associated with the frail elderly, those with neurologic injury or disease, and with prolonged hospitalization and nursing home care. In fact, anyone with limited mobility, confined to bed or chair, and unable to shift position with relative frequency is at risk.

2. EPIDEMIOLOGY

Pressure injuries are among the most common conditions encountered in patients who suffer prolonged hospitalization or require long-term institutional care. The prevalence varies widely by clinical setting, age, and geographical region. Between the years 2000 to 2010, the reported prevalence of pressure injuries in the United States ranged from 0.4% to 38% in acute care settings, 2.2% to 23.9% in long-term care facilities, and 0.1% to 17% in the course of home care [3,4,5]. In general, the rate of newly acquired pressure injury in patients hospitalized for acute illness is estimated to be 5.85%, and approximately 14% of intensive care unit (ICU) patients develop pressure injuries [2]. The annual rate of pressure injuries in persons with neurologic impairment, such as spinal cord injury, stroke, or dementia, is estimated to be 5% to 8%, and the lifetime risk is 25% to 85%. Pressure injuries are listed as a primary cause of death in 7% to 8% of patients with spinal cord injury, the population at greatest risk for pressure injury formation [6]. Unfortunately, in spite of modern advances in clinical care, the recurrence rate in patients with healed pressure injuries remains as high as 74% [6].

A large-scale nation-wide epidemiologic study of the incidence and clinical outcomes of hospital-acquired pressure injuries was conducted utilizing the Medicare Patient Safety Monitoring System (MPSMS) database [7]. The MPSMS is designed to monitor adverse events within the hospitalized Medicare population. The MPSMS pressure injury study analyzed 51,842 inpatient discharges across 50 states between 2006 and 2007. The prevalence rate of pressure injury on admission was 5.8%, and the incidence rate for hospital-acquired pressure injury was determined to be 4.5%. Of 2,999 patients who entered the hospital with a pressure injury, 16.7% developed at least one new injury at a different location during the inpatient stay. The majority of hospital-acquired pressure injuries were located on the coccyx or sacrum (41%), the hip and buttock region (23%), and the heels (23%). Underlying chronic disease, corticosteroid use, and obesity were identified as significant risk factors. In contrast to patients without pressure injuries, the development of hospital-acquired pressure injuries was significantly associated with longer length of stay (11.6 days vs. 4.9 days), higher in-hospital mortality (11.2% vs. 3.3%), and higher mortality within 30 days of discharge (15.3% vs. 4.4%) [7].

The incidence of pressure injuries acquired in the outpatient setting is derived primarily from clinical studies and surveys conducted by home health agencies. In one cohort study of 1,711 non-hospitalized patients older than 60 years of age who did not have a pressure injury at initiation of home care, 108 (6.3%) subsequently developed a stage 1 to 4 pressure injury during the period of active home care [8].

According to data compiled by the Agency for Healthcare Research and Quality, an estimated 2.5 million patients develop pressure injuries each year, and approximately 60,000 die as a direct result of this condition. The individual cost of care ranges from $20,000 to $150,000 per case; the total aggregate annual health care cost is estimated to be between $9.1 billion and $11.5 billion [9].

3. PATHOGENESIS

In susceptible individuals, the combination of immobility and extended periods of pressure or friction over bony prominences leads to reduction in capillary blood flow, tissue hypoxia, and ischemic tissue injury. This in turn evokes an inflammatory response that further impairs perfusion and augments soft tissue and skin injury. Current understanding favors a "bottom-up" model of tissue damage beginning deep in the muscle layer [10]. Muscle is more sensitive to pressure injury than skin because it is the more metabolically active layer and thus more susceptible to ischemic injury.

The age and health of overlying skin determine the ease with which ulceration of the superficial layers occurs. In the elderly, skin and subcutaneous tissue gradually lose regenerative, protective, and sensory functions. Chronic conditions or intercurrent illness such as diabetes, arthritis, incontinence, neurologic impairment, cigarette use, and hypotension are all associated with increased susceptibility and prevalence of pressure injuries [6]. As noted, pressure injuries develop most commonly over the sacrum and coccyx, hips and buttocks, and heels [7].

4. RISK FACTORS

The development of pressure-induced skin injury and subsequent ulceration usually arises in the setting of failing health and loss of independent mobility. In a community-based study of 12,650 patients older than 60 years of age enrolled in a primary care panel, 366 (2.9%) subsequently developed a pressure injury during the 40-month surveillance period [11]. The two most prominent risk factors were prior history of pressure injury and placement in a long-term care facility, followed by comorbid conditions such as diabetes, falls, cataracts, renal insufficiency, and cardiovascular disease. In a national study of 1,524 adults residing in 95 long-term care facilities, 443 (29%) developed a new pressure injury during the 12-week observational period; factors associated with increased risk included higher initial severity of illness, history of previous pressure injury, weight loss, feeding difficulty, use of catheters, and use of positioning devices [12].

For a given patient, immobility that leads to unrelieved pressure to the skin over a boney prominence is the most important factor in the development of pressure injuries [5,10]. Individual risk factors for pressure injuries may be categorized as extrinsic or intrinsic. Extrinsic factors are external conditions in the immediate environment that place a vulnerable individual at risk (e.g., moisture, compression from an applied device). Intrinsic factors are conditions and comorbidities peculiar to the individual that confer risk (e.g., advanced age, poor nutrition, smoking history).

EXTRINSIC FACTORS

Pressure and Shear

Pressure that results in injury and subsequent skin breakdown is defined as compression of soft tissues between two rigid surfaces. For example, skin, muscle, subcutaneous fat, and vasculature may be compressed between an underlying boney prominence and a rigid external surface, such as a bed or chair. All the tissues between the two points of pressure are affected, but the tissue closest to the bony prominence suffers the greatest damage. It is important to note that low-intensity pressure over a long period of time can create tissue damage, just as high-intensity pressure over a short period of time can result in damage [10].

The capillary level is the end point of circulation. From the capillaries, oxygen and nutrients diffuse into the tissues, and carbon dioxide and waste products are removed. A collapsed capillary bed is nonfunctioning and useless to the tissues. The minimal amount of pressure required to collapse a capillary is referred to as the capillary closing pressure [13]. Studies have shown that an average of 32 mm Hg will collapse the arterial side of the capillary circulation, and 18 mm Hg of pressure will collapse the venous end. However, these values cannot be accepted as universal; capillary pressures vary among persons, sites, and times [10]. Furthermore, the studies that elicited these values were done on healthy adult males, not debilitated or elderly patients. Other studies have shown that the functional capillary pressure in the peripheral tissues is around 17 mm Hg [14]. Extended pressure resulting in capillary collapse will cause tissue damage.

Shear is the result of gravity pushing down on the body and resistance (friction) between the patient and a surface, such as the bed or the chair, holding the skin in place [10]. For example, when the head of the bed is raised (e.g., high Fowler's position), gravity facilitates forward slide, pulling the body down toward the foot of the bed. The skin on the patient's lower back and gluteal area resists the motion and is held in place by the bed's surface while the bones and tissues beneath the area begin to slide. This causes puckering of the skin, stretching and angulation of small vessels, impedance of blood flow, and traction on subcutaneous tissue and muscle. Left unchecked, the net effect may result in ischemic injury to tissues at the fascia layer. When the head of the bed is elevated more than 30 degrees, shear force occurs over the sacrum and coccyx. Shear injury is not usually visible at the skin level, but shear is responsible for much of the damage associated with initiation of pressure injuries [15]. The areas of the body most vulnerable to shearing forces are shoulder blades, elbows, sacrum, ischial tuberosities, and heels. Signs of shear injury include irregular deep lesions, undermining, and tunneling.

Friction

As noted, friction occurs when one surface moves across another surface, such as when a patient's skin slides across a bed sheet. This can result in the "sanding away" of the epidermal layer and upper part of the dermis, causing abrasions [10]. Friction injuries often present as erythema and tenderness followed by skin loss and usually appear under restraints, braces, and on the elbows, or with repetitive rubbing or repetitive cleansing. Patients with uncontrollable movements or spasticity are also at high risk for friction injury, often referred to as "sheet burn." Friction injury occurs more frequently when the skin is fragile or macerated, and tissues subjected to friction are more susceptible to pressure injury damage [15].

Moisture

Moisture weakens the resilience of the epidermis to external forces. Maceration causes softening of the connective tissue, and a macerated epidermis erodes more easily, as overhydrated skin has decreased tensile strength. Skin can appear "water-logged," with areas of denuded skin and fissure formation. Shear and friction damage is increased when there is a moderate amount of moisture present, but it has been reported that shear and friction decrease in the presence of high levels of moisture. The role moisture plays in pressure injury development is an area of ongoing research [16,17,18].

Major sources of moisture are incontinence, wound drainage, tube leakage, and sweating. Urinary and fecal incontinence expose the skin to excessive amounts of moisture and chemical irritation. There is a higher risk for skin breakdown and infection with fecal incontinence than urinary incontinence because of the pathogens in stool.

INTRINSIC RISK FACTORS

Age

Patients older than 65 years of age experience pressure injuries most frequently [13]. With aging, the skin becomes more fragile; the skin layers adhere less securely to each other and can appear paper thin and almost transparent. There is also evidence of increased dryness, decreased vascularization, and increased vascular fragility.

In elderly individuals, there is a decrease in surface barrier function. The ability of the soft tissue to evenly distribute the mechanical load without compromising blood flow is impaired. There is less subcutaneous tissue to cushion boney prominences. This, in addition to decreased sensory perception, makes elderly skin more vulnerable to pressure, shear, and friction [10]. Research has shown that, in the geriatric population, blood flow in the area of the ischial tuberosity while sitting on an unpadded surface is lower than in younger adults [15].

Although much less common, children can also develop pressure injuries. These injuries usually develop in the occipital region in infants and toddlers and on the sacrum in young children [13].

Immobility

Immobile individuals carry the greatest risk of developing pressure injuries. While sleeping, a healthy individual changes body position approximately once every 10 to 12 minutes. This constant change of position maintains healthy blood circulation, stimulates body organs, and ensures movement of body fluids. However, when an individual is immobile, decreased vascularization and prolonged pressure pair with possible loss of sensation to make the patient extremely vulnerable to pressure injuries. Immobility may be the result of multiple traumas or injuries, spinal cord injuries, stroke, prolonged hospitalization, coma, recovery after surgery, or cognitive deficits [15].

Sensory Loss

Patients with spinal cord injury, neurologic disease, or even advanced diabetes carry an increased risk of developing pressure injuries as a result of loss of protective sensation. Patients with sensory loss may not feel discomfort or the need to be repositioned.

Poor Nutrition and/or Volume Depletion

Poor nutrition, intravascular volume depletion, and peripheral vascular disease can each lead to unhealthy skin and impaired wound healing, which in turn increases the risk of developing pressure injuries. Low body weight is also a concern. Weight less than 119 pounds or a body mass index (BMI) less than 20 indicates increased risk for pressure injury development [19].

Recent weight loss, decreased nutritional intake, inadequate dietary protein, and impaired ability to feed oneself have been identified as risk factors for pressure injury development. An estimated 50% of elderly patients admitted to hospitals have suboptimal protein nutrition [19]. When there is a sustained deficit of protein as an energy source, skin and soft tissues become more vulnerable to injury. In managing patients with pressure injury, or those at risk, the amount of protein in the diet appears to influence prognosis for recovery and prevention. In one study, patients who received a 24% increase in protein intake had significant improvements in pressure injury healing and prevention of new skin injury compared to those who received a 14% increase [20]. The potential role of nutritional supplementation on pressure injury management and prevention is an area of ongoing research [21,22].

Vitamin A, C, and E deficiencies have been associated with pressure injury formation. Vitamin A works in the body to maintain epithelial integrity and is involved in collagen synthesis. It also plays a role in protection against infection. A deficiency of vitamin A can inhibit collagen synthesis, delay re-epithelialization, and decrease cellular cohesion. Vitamin C is also involved in collagen synthesis, immune function, and wound repair. A deficiency of vitamin C can result in capillary fragility. Vitamin E deficiency often decreases the immune function of the skin.

Incontinence

Both urinary incontinence and bowel incontinence can result in excessive moisture on the skin, which decreases the tensile strength and increases skin breakdown. In addition, infection may occur more frequently.

Skin Perfusion Status

Maintenance of tissue health requires an adequate perfusion pressure in the systemic circulation for delivery of oxygen and nutrients to the cells and removal of waste products. Healthy tissue (in persons with normal sensation and movement) is able to tolerate brief, intermittent periods of inadequate perfusion; however, sustained ischemia leads to tissue damage and, with regard to skin, potentiates the development of pressure injuries.

Low arterial blood pressure (hypotension), defined as systolic blood pressure less than 100 mm Hg and diastolic pressure less than 60 mm Hg, has been linked to increased risk for pressure injury development. In response to hypotension, the body redirects blood flow to the vital internal organs at the expense of the peripheral vascular system, which serves the skin. As the perfusion level drops, so does the skin's ability to tolerate external pressure. Capillaries subsequently close at lower levels of interface pressure, and there is an increased risk of damage due to ischemia [13].

Smoking

Nicotine impedes blood flow to the tissues in two ways: it is a potent vasoconstrictor, and it increases the adhesiveness of platelets, resulting in clot formation. Carbon monoxide contained in cigarette smoke prevents oxygen from attaching to the hemoglobin molecule. This significantly reduces the amount of oxygen circulating in the blood stream. The same reaction occurs to some extent in people exposed to secondhand smoke. Studies have shown that cigarette smoking is associated with a higher incidence of pressure injury development, and patients who smoke also have a higher rate of recurrence of pressure injuries [15,23].

Stress

Stress is a primitive response to injury or anticipated injury. Research has shown that during periods of stress, blood vessels in the peripheral tissues constrict. In a study designed to mimic the body's response to stress, healthy subjects were given an infusion of exogenous epinephrine [13]. The increased levels of epinephrine decreased the levels of subcutaneous tissue oxygen by 45%. Other studies have shown that psychologic stress has a negative impact on healing [13].

Obesity

Obesity, or a BMI of 30 or greater, is common (more than 40%) in the United States; morbid ("severe") obesity, defined as a BMI greater than 40, is prevalent but less common [24,25]. Factors that contribute to pressure injury development in obese individuals include decreased blood supply in adipose tissue, difficulty in turning and repositioning, moisture within skin folds, incontinence, skin-to-skin friction, immobility, and poor nutrition. Obese patients are particularly at risk for "unusual" pressure injuries resulting from pressure within skin folds. Obese patients may have large panniculi ("aprons") weighing up to 50 pounds, and the abdominal panniculus must be regularly repositioned in order to prevent pressure injury. This can be accomplished by placing the patient on his or her side and lifting the panniculus away from the underlying skin surface in order to simultaneously relieve pressure and allow air to reach the area.

Comorbidities

People with severe mental health conditions, such as uncontrolled schizophrenia or severe depression, have an increased risk of pressure injuries. This is thought to be related to these patients having little interest in self-care and nutrition. In addition, patients may have comorbid health conditions, such as diabetes or incontinence, that compound the risk of pressure injury development.

Chronic disease often confers multiple risk factors for developing a pressure injury and for prolonging injury healing as well. Conditions that lead to low tissue perfusion, reduced sensation, poor cognition, and altered posture predispose a patient to the development and/or recurrence of injuries. Common medical conditions associated with an increased risk for pressure injury include:

- Diabetes

- End-stage renal disease (ESRD)

- Thyroid disease

- Congestive heart failure

- Peripheral vascular disease

- Collagen vascular disorders and vasculitis

- Immune deficiency states

- Malignancies

- Chronic obstructive pulmonary disease

- Depression and psychosis

- Drugs that delay healing

- Joint contractures

Tubes or catheters can also cause pressure by burrowing into skin folds. Poorly fitting bed, chairs, or wheelchairs may also be a source of friction, shear, and sustained pressure [26].

RISK ASSESSMENT

Evidence Based Practice Recommendation

When conducting a pressure injury risk assessment, the National Pressure Ulcer Advisory Panel, the European Pressure Ulcer Advisory Panel, and the Pan Pacific Pressure Injury Alliance recommend using a structured approach, including a comprehensive skin assessment, supplementing use of a risk assessment tool with assessment of additional risk factors, and interpreting the assessment outcomes using clinical judgment.

https://static1.squarespace.com/static/6479484083027f25a6246fcb/t/6553d3440e18d57a550c4e7e/1699992399539/CPG2019edition-digital-Nov2023version.pdf

Last Accessed: April 28, 2025

Level of Evidence: Good Practice Statement (The recommendation is not supported by a body of evidence but considered to be significant for clinical practice.)

No step is more important in preventing pressure injuries than understanding a patient's risk. Risk assessment is used to identify:

- Populations at risk

- Level of risk

- Type of risk

An informal risk assessment cannot take the place of a formal risk assessment, such as the one conducted using the Braden Scale. Research shows that without formal risk assessment, clinicians tend to intervene consistently only at the highest levels of risk [27]. In some studies, repositioning or turning, an important part of pressure injury prevention, was prescribed for fewer than 50% of the patients at mild-to-moderate risk for pressure injury development [15]. Although several scales/tools have been developed to assess pressure injury risk, the Braden Scale is probably the most widely used.

The Braden Scale

The Braden Scale was developed in 1987 by Barbara Braden and Nancy Bergstrom [27]. Since then, it has undergone testing in several clinical settings, and its validity has been established by expert opinion. It is considered one of the most reliable tools for identifying patients at risk for pressure injury development. The Braden Scale scores factors that contribute to prolonged pressure and factors that result in diminished tissue tolerance for pressure (Table 1) [27]. There are six items scored in the assessment [27]:

- Sensory perception

- Moisture

- Activity

- Mobility

- Nutrition

- Friction and shear

Table 1: THE BRADEN SCALE FOR PREDICTING PRESSURE ULCER RISK

Domain

Scorea

1

2

3

4

Sensory perception: The ability to respond meaningfully to pressure-related discomfort

Completely limited: Unresponsive (does not moan, flinch, or grasp) to painful stimuli due to diminished level of consciousness or sedation OR limited ability to feel pain over most of body surface.

Very limited: Responds only to painful stimuli and cannot communicate discomfort except by moaning or restlessness OR has a sensory impairment that limits the ability to feel pain or discomfort over half of body.

Slightly limited: Responds to verbal commands, but cannot always communicate discomfort or need to be turned OR has some sensory impairment that limits ability to feel pain or discomfort in one or two extremities.

No impairment: Responds to verbal commands and has no sensory deficit that would limit ability to feel or voice pain or discomfort.

Moisture: Degree to which skin is exposed to moisture

Constantly moist: Skin is kept moist almost constantly by perspiration, urine, etc. Dampness is detected every time patient is moved or turned.

Very moist: Skin is often, but not always, moist. Linen must be changed at least once a shift.

Occasionally moist: Skin is occasionally moist, requiring an extra linen change approximately once a day.

Rarely moist: Skin is usually dry. Linen only requires changing at routine intervals.

Activity: Degree of physical activity

Bedfast: Confined to bed

Chairfast: Ability to walk severely limited or non-existent. Cannot bear own weight and/or must be assisted into chair or wheelchair.

Walks occasionally: Walks occasionally during day, but for very short distances, with or without assistance. Spends majority of each shift in bed or chair.

Walks frequently: Walks outside the room at least twice a day and inside the room every two hours during waking hours.

Mobility: Ability to change and control body position

Completely immobile: Does not make even slight changes in body or extremity position without assistance.

Very limited: Makes occasional slight changes in body or extremity position but unable to make frequent or significant changes independently.

Slightly limited: Makes frequent though slight changes in body or extremity position independently.

No limitations: Makes major and frequent changes in position without assistance.

Nutrition: Usual food intake pattern

Very poor: Never eats a complete meal. Rarely eats more than one-third of any food offered. Eats two servings or less of protein per day. Takes fluids poorly. Does not take a liquid dietary supplement. OR is nothing by mouth and/or maintained on clear liquids or intravenous for more than five days.

Probably inadequate: Rarely eats a complete meal and generally eats only about half of any food offered. Protein intake includes only three servings of meat or dairy products per day. Occasionally will take a dietary supplement. OR receives less than optimum amount of liquid diet or tube feeding.

Adequate: Eats more than half of most meals. Eats a total of four servings of protein each day. Occasionally will refuse a meal but will usually take a supplement if offered. OR is on a tube feeding or total parental nutrition regimen that probably meets most of nutritional needs.

Excellent: Eats most of every meal. Never refuses a meal. Usually eats a total of four or more servings of protein. Occasionally eats between meals. Does not require supplementation.

Friction and shear

Problem: Requires moderate-to-maximum assistance in moving.

Potential problem: Moves feebly or requires minimum assistance. During a move, skin probably slides to some extent against sheets, chair restraints, or other devices. Maintains relatively good position in chair or bed most of the time, but occasionally slides down.

No apparent problem: Moves in bed and in chair independently and has sufficient muscle strength to lift up completely during move. Maintains good position in bed or chair at all times.

—

aA lower Braden Scale Score indicates a lower level of functioning and, therefore, a higher level of risk for pressure ulcer development. Risk levels assigned to each score range: ≤9 is very high risk, 10–12 is high risk, 13–14 is moderate risk, and 15–18 is mild risk. Scores of 19 or greater are considered very low or no risk.

Source: Copyright Barbara Braden and Nancy Bergstrom, 1988. Reprinted with permission. All Rights Reserved.

Each item is scored on a scale between 1 and 4, with the exception of friction and shear, which is scored between 1 and 3. The lower the score, the more severe the impairment or problem in that area. Therefore, the lower the overall score, the higher the patient's risk for pressure injury development. Various studies have shown cut-off scores from 15 to 18 as being at risk [10]. Although cut-off scores vary, usually a score of 13–14 is considered moderate risk, 10–12 indicates high risk, and 9 or less is very high risk.

The Braden Scale should be used for assessment on admission to a care facility or after return from a hospital. Research shows that a repeat assessment done 48 hours to 72 hours after admission further defines pressure injury risk. In nursing home populations, the majority of pressure injuries develop during the first two weeks following admission [13]. Most facilities set their own policies regarding reassessment frequency (e.g., quarterly). However, it is important to note that any change in a patient's condition warrants reassessment.

Braden Scale assessment is completed by licensed personnel familiar with the patient and is shared with all staff caring for the patient; good communication is essential to ensure a meaningful assessment [15]. Licensed and unlicensed staff must have a basic knowledge of Braden scores and how it directs patient care. Accuracy of scoring is very important to determining the appropriate intervention.

The Norton Scale

The Norton Scale was developed in the 1960s and also is used to assess the risk for pressure injury in adults (Table 2). The five items in the assessment are scored from 1 to 4, with 1 indicating a low level of functioning and 4 indicating the highest level of functioning. A score of 14 or less generally indicates the patient is at risk [28]. The Norton Scale should be used in conjunction with the clinical assessment [28].

Table 2: THE NORTON SCALE FOR PREDICTING PRESSURE ULCER RISK

Score

Physical condition

Mental condition

Activity

Mobility

Incontinent

4

Good

Alert

Ambulant

Full

Not

3

Fair

Apathetic

Walk-help

Slightly limited

Occasional

2

Poor

Confused

Chair-bound

Very limited

Usually (urine)

1

Very bad

Stupor

Stupor

Immobile

Doubly

Source: [28]

5. STAGING OF PRESSURE INJURIES

The National Pressure Ulcer Advisory Panel (NPUAP), in conjunction with a consensus conference format involving 400 health professionals, redefined the definition of pressure injuries in 2016 and provided an illustrated staging scheme that classifies pressure injuries by the depth and extent of tissue injury into six stages [29,30]. The NPUAP announced that it was changing its preferred terminology from pressure ulcer to pressure injury on the grounds that the latter term better described this injury process in both intact and ulcerated skin [31]. The term "pressure injury" will be used throughout this course as appropriate.

In November 2019, the NPUAP changed its name to the National Pressure Injury Advisory Panel (NPIAP) [31]. The NPIAP defines pressure injury as [30]:

... localized damage to the skin and underlying soft tissue usually over a bony prominence or related to a medical or other device. The injury can present as intact skin or an open ulcer and may be painful. The injury occurs as a result of intense and/or prolonged pressure or pressure in combination with shear. The tolerance of soft tissue for pressure and shear may also be affected by microclimate, nutrition, perfusion, comorbidities, and condition of the soft tissue.

In addition to redefining the definition of pressure injuries, the NPUAP added two additional pressure injury types [30]:

- Medical device-related pressure injury

- Mucosal membrane pressure injury

DEEP TISSUE PRESSURE INJURY

Deep tissue injury is described as a purple or maroon localized area of discolored, intact or non-intact skin or a blood-filled blister caused by damage of underlying soft tissue from pressure and/or shear (Image 1). The area may be preceded by tissue that is painful, firm, mushy, boggy, warmer, or cooler as compared to adjacent tissue.

Image 1: ILLUSTRATIONS OF DEEP TISSUE PRESSURE INJURY

Source: Used with permission of the National Pressure Ulcer Advisory Panel, 2016.

Deep tissue injury may be difficult to detect in individuals with dark skin tones. The injury may also present as a thin blister over a dark wound bed. The wound may further evolve and become covered by thin eschar. Evolution may be rapid, exposing additional layers of tissue even with optimal treatment. If necrotic tissue, subcutaneous tissue, granulation tissue, fascia, muscle, or other underlying structures are visible, this indicates a full thickness pressure injury.

STAGE 1: NONBLANCHABLE ERYTHEMA

Stage 1 is characterized by intact skin with nonblanchable redness of a localized area, usually over a bony prominence (Image 2). Darkly pigmented skin may not have visible blanching, making detection difficult, but its color may differ from the surrounding area. The area may be painful, firm, soft, warmer, or cooler as compared to adjacent tissue.

Image 2: ILLUSTRATION OF A STAGE 1 PRESSURE INJURY

Source: Used with permission of the National Pressure Ulcer Advisory Panel, 2016.

Stage 1 lesions may indicate "at risk" persons (a heralding sign of risk). No tissue destruction occurs, and it is a reversible condition.

STAGE 2: PARTIAL-THICKNESS SKIN LOSS WITH EXPOSED DERMIS

Stage 2 injuries present with partial-thickness skin loss into the dermis, presenting as a shallow, open injury with a red-pink wound bed, without slough (Image 3). This stage of injury may also present as an intact or open/ruptured, serum-filled or serosanguineous-filled blister.

Image 3: ILLUSTRATION OF A STAGE 2 PRESSURE INJURY

Source: Used with permission of the National Pressure Ulcer Advisory Panel, 2016.

Stage 2 injuries present as shiny or dry, shallow injuries without slough or bruising; bruising indicates suspected deep tissue injury. This stage should not be used to describe skin tears, tape burns, perineal dermatitis, maceration, or excoriation. Patients with stage 2 injuries now have an entry point for pathogens; therefore, cleaning the wound and providing some type of dressing is of utmost importance.

STAGE 3: FULL-THICKNESS SKIN LOSS

In the stage 3 injury, there is penetration into subcutaneous tissue but not through fascia; fat tissue may be visible, but bone, tendon, and muscle are neither exposed nor directly palpable (Image 4). Slough and/or eschar may be present but does not obscure the depth of tissue loss. These wounds may include undermining and tunneling. The depth of a stage 3 injury varies by anatomical location. The bridge of the nose, ear, occiput, and malleolus do not have subcutaneous tissue, and stage 3 injuries in these areas can be shallow. In contrast, areas of significant adiposity can develop extremely deep stage 3 injuries. Because infection is a very strong risk at this stage, irrigation of the wound is done each time the dressing is changed. Wound debridement may be necessary for healing.

Image 4: ILLUSTRATION OF A STAGE 3 PRESSURE INJURY

Source: Used with permission of the National Pressure Ulcer Advisory Panel, 2016.

STAGE 4: FULL-THICKNESS SKIN AND TISSUE LOSS WITH EXPOSED BONE, TENDON, OR MUSCLE

In stage 4 pressure injuries, slough or eschar may be present on some parts of the wound bed (Image 5). Undermining and tunneling are often present. The depth of a stage 4 injury varies by anatomical location. As with stage 3 injuries, wounds on the bridge of the nose, ear, occiput, and malleolus may be shallow. Stage 4 injuries can extend into muscle and/or supporting structures (e.g., fascia, tendon, or joint capsule), making osteomyelitis possible. Exposed bone/tendon is visible or directly palpable. At this stage, the pressure injury is often infected, with deep ulceration and tissue loss; therefore, the patient may need repair with myocutaneous flaps to close the defect. If slough or eschar obscures the extent of tissue loss, this is an unstageable pressure injury.

Image 5: ILLUSTRATION OF A STAGE 4 PRESSURE INJURY

Source: Used with permission of the National Pressure Ulcer Advisory Panel, 2016.

UNSTAGEABLE

Unstageable pressure injuries are defined as full-thickness skin and tissue loss in which the base of the injury is covered by slough (yellow, tan, gray, green, or brown) and/or eschar (tan, brown, or black), obscuring the wound bed (Image 6). Until enough slough and/or eschar is removed to expose the base of the wound, the true depth, and therefore stage, cannot be determined.

Image 6: ILLUSTRATION OF AN UNSTAGEABLE PRESSURE INJURY

Source: Used with permission of the National Pressure Ulcer Advisory Panel, 2016.

MEDICAL DEVICE-RELATED PRESSURE INJURY

Medical device-related pressure injuries describe injuries or ulcers that result from the use of devices designed and applied for diagnostic or therapeutic purposes. The injury is generally in the shape or pattern of the device and should be staged using the staging system.

MUCOSAL MEMBRANE PRESSURE INJURY

Mucosal membrane pressure injury is found on the mucous membranes and is typically attributed to use of a medical device. Due to the nature of this type of tissue, these injuries cannot be staged.

6. PHASES OF WOUND HEALING: AN OVERVIEW

There are three phases of wound healing: inflammation, proliferation, and maturation. Wounds heal by two possible mechanisms: regeneration or scar tissue formation. The depth of the wound (i.e., the number of tissue layers involved) will determine the mechanism by which the wound will heal. Partial-thickness wounds and stage 1 and 2 injuries usually heal by tissue regeneration. Stage 3 and 4 injuries and full-thickness wounds heal by scar formation and contraction. In one study, 20% shrinkage in wound size in a period of two weeks was a reliable predictive indicator of healing [32].

Pressure injuries are notoriously difficult to heal. Only 75% of stage 2 injuries and 17% of stage 3 or 4 injuries heal in eight weeks [33]. Up to 23% of stage 2 pressure injuries and 48% of stage 4 injuries remain unhealed after one year [34].

INFLAMMATORY PHASE

The standard signs and symptoms of inflammation are erythema, swelling, increased temperature, and pain. In normal healing, these signs are only minimally noticeable, and during the inflammatory phase of wound healing, they are considered a normal response [35]. In general, this phase occurs in the first 0 to 3 days after injury development but may last longer if healing is impaired.

The first part of inflammation is hemostasis, which begins soon after the wound develops. During the inflammatory phase, vasoconstriction results in platelets adhering to damaged endothelium, causing clumping of the thrombocytes and stopping bleeding. Polymorphonuclear leukocytes engorge the wound and clear the debris. Macrophages continue the cleansing process and stimulate growth factors, including cytokines, interleukin-1 (IL-1), tumor growth factor, tumor necrosis factor, and platelet-derived growth factor.

PROLIFERATION PHASE

The proliferation phase lasts approximately 3 to 12 days. During this phase, angiogenesis results in a new network of blood vessels in the wound. Production of epithelial cells starts. Collagen synthesis and improved vascularity ensure healthy granulation tissue. Wounds in the proliferation phase are usually pink in color and do not bleed easily.

In full-thickness wounds, the process of re-epithelialization occurs only from the wound edges [10]. Margin basal cells attached to the dermis eventually loosen and start migrating across the wound. The horizontal movement comes to a halt when the cells meet, which is referred to as contact inhibition. Wound contraction is the final part of the proliferative phase. Fibers in the wound contract to bring the wound edges closer together.

MATURATION PHASE

Maturation and remodeling of the wound involves rearranging collagen fibers from type III to type I, and increasing the tensile strength of scar tissue. The number of blood vessels in the wound regresses and cellular activity is reduced. Scar tissue regains about 80% of normal tissue strength within three months, but it never achieves the full strength of the original tissue [10]. Therefore, the healed site of an old wound is vulnerable to further breakdown.

7. DIAGNOSIS

Diagnosis of pressure injuries involves careful assessment of symptoms, medical history, physical examination, and certain medical tests. Usually, individuals will have a history of decreased mobility. Patients may complain about the appearance of a wound that may or may not be painful. In cases of infected wounds, fever may be present.

Careful examination in patients with pressure injuries reveals skin ulceration surrounded by erythema. The size and depth of the injury should be determined and documented at this point. Bleeding, malodor, and fluids or debris in the wound indicate severe infection.

Blood tests may be ordered to assess nutritional status and overall health status. No laboratory study of nutritional status can absolutely predict pressure injuries; however, monitoring a patient's protein status is of value. There are many serologic markers used to assess a patient's nutritional status; prealbumin level is one of the most sensitive. Prealbumin is a protein with a much shorter half-life than the other serologic markers; therefore, its level gives a more accurate picture of current conditions.

If infection is suspected, culture of the pressure injury is important to determine the pathogen. In some cases, a wound biopsy is performed to rule out vasculitis and skin cancers. An x-ray is done if bone infection is suspected and to rule out osteomyelitis. A bone scan is carried out when x-ray findings are equivocal.

8. PREVENTION AND TREATMENT

The principles and management strategies discussed in this section are applicable to prevention in high-risk patients, control of early stage injury, and treatment of established pressure injuries. The NPIAP, in conjunction with two international agencies, published evidence-based guidelines for risk assessment, prevention, and management of pressure injuries in 2014 and released an update to this guideline in 2019 [29,36]. The fourth edition, released in 2025, was developed as a living document that will be continuously updated. This guideline is available online at https://internationalguideline.com/the-international-guideline.

The primary objectives for prevention and arrest of progression are:

- Preventive skin care

- Pressure reduction, minimizing or eliminating friction and shear forces

- Adequate nutrition

- Exudate management

- Prevention of wound infection

- Managing moist wound environments

- Decreasing the frequency of dressing changes

The general treatment of established injuries involves:

- Pressure-relieving strategies

- Optimal nutritional support, including protein and micronutrient supplementation

- Intense injury care

- Pain management

- Prevention/eradication of infection

- Adjunctive treatment or surgery

The actual treatment plan is individualized based on the injury stage, patient health, and short- and long-term goals.

SKIN CARE AND PRESSURE-RELIEVING STRATEGIES

The principles of preventive skin care include [29,36]:

- Avoid positioning the patient over an area of erythema.

- Keep the skin clean and dry.

- Do not massage or vigorously rub skin that is at risk for pressure injury.

- Develop an individualized continence plan.

- Protect the skin from exposure to excessive moisture and friction.

For the at-risk patient, a strategy to avoid or relieve pressure is essential for the prevention and treatment of pressure injuries [37]. This is best accomplished by a three-pronged approach of:

- Careful patient positioning

- Use of protective devices

- Judicious use of support surfaces

Positioning

Bedbound Patients

Bedbound patients should be properly positioned and frequently repositioned, at least every two hours. When in lateral decubitus position, patients' heads should be maintained at an angle of 30 degrees in order to mitigate pressure in the trochanteric region. Pillows or foam wedges should be placed between the legs, at the knees and ankles, to prevent pressure at these sites when patients have little or no ability to move legs and feet.

To the extent the patient is able, regular physical activity should be encouraged and assisted. Even a few steps done frequently will help maintain current activity level, mobility, and range of motion. Lifting devices, such as an overhead trapeze or bed linen, are helpful when moving patients. It is important to avoid or minimize dragging the patient during transfers and position changes. Patients require protection from environmental factors leading to skin drying, such as low humidity (less than 40%) and exposure to cold [15]. Posting an individualized turning schedule in patient rooms can be helpful to healthcare professionals and families.

The heels are especially vulnerable, and pressure injuries at this location are very painful, difficult to heal, and prone to infection with easy access to adjacent bone. Heel pressure injuries can develop infection, and advanced cases may lead to amputation of the foot. To protect the heels, place a pillow under the calf to float the heels off the bed. There are also devices available that eliminate pressure on heels and prevent foot drop (e.g., suspension boots). Current guidelines state that heels are to be kept off the bed [10,36].

Chairbound Patients

Evidence Based Practice Recommendation

The National Pressure Ulcer Advisory Panel, the European Pressure Ulcer Advisory Panel, and the Pan Pacific Pressure Injury Alliance recommend using a seating support surface with pressure redistribution properties for individuals at risk of pressure injuries when in a seated position.

https://internationalguideline.com/the-international-guideline

Last Accessed: April 28, 2025

Strength of Recommendation/Level of Evidence: Strong recommendation based on moderate-quality evidence (The recommendation is supported by level 1,2, and 3 studies of moderate or low quality providing direct evidence.)

Chairbound patients require special attention to positioning as well. The risk of pressure injuries from prolonged sitting is greater than that from reclining in bed, as sitting puts the patient's weight on the relatively small surface areas of the buttocks, thighs, and soles of the feet. Much of this weight is centered over the small area of tissue covering the ischial tuberosities. It is important for patients who sit in a chair to regularly change position. A dependent patient must have his/her position changed in a chair at least every hour. Patients who are able to move themselves should shift their weight (even slightly) every 15 minutes.

A patient should be properly positioned in a chair for postural alignment, distribution of weight, balance, and stability. Patients should sit with their back erect and against the back of the chair, thighs parallel to the floor, knees comfortably parted, and arms horizontal and supported by the arms of the chair. This position distributes weight evenly over the available body surface area. Slouching can cause shearing and friction and places undue pressure on the sacrum and coccyx. Feet should be kept flat on the floor to protect the heels from pressure and distribute the weight of the legs over the largest available surface area. The thighs and arms should remain parallel to ensure that weight is evenly distributed instead of being focused on the ischial tuberosities and elbows. Parting the knees will prevent the knees and ankles from rubbing together. If a patient uses a footstool, it is vital that his or her knees are not above hip level, because this shifts the weight from the back of the thighs to the ischial tuberosities. This same problem can occur if the chair is too short for the patient.

Protective Devices

Protective padding and pillows should be utilized for pressure reduction whenever possible. Heel protectors, foam, and pillows can be helpful for patients in supine positions. Cutting a window through the cast can greatly reduce pressure at certain sites in patients immobilized by fractures. Patients should be provided soft seat cushions when sitting in a chair. Sheepskin and donut-shaped devices should not be used for treating pressure injuries; ring cushions can reduce blood flow to an even wider area of tissue.

Support Surfaces

Support surfaces are indicated when patients are not able to reposition themselves or when periodic repositioning care is not available. In a comprehensive literature review researchers founds good evidence that specially designed support surfaces effectively prevent pressure injuries [38].

An ideal support surface will manage microclimate, tissue loads, and other curative functions. Seat cushions, overlays, mattresses, and integrated bed systems are commonly used to prevent pressure injuries. The type of device or surface selected is based on level of risk as well as degree of assistance necessary for repositioning or mobility (Table 3).

Table 3: THERAPEUTIC SUPPORT SURFACE SELECTION TOOL

Validated Risk Assessment Category or Pressure Ulcer Description

At risk

OR

Redness present that fades quickly when pressure is removed

Moderate risk

OR

One pressure ulcer (excluding the heels) where the patient can be positioned off the ulcer

High risk

OR

One pressure ulcer (excluding the heels) and redness over another area

Very high risk

OR

Multiple pressure ulcers (excluding the heels) or the patient cannot be positioned off of an ulcerated area

Ability to change position in bed (e.g., bed mobility)

Total assist to change position in bed.

Reactive support surface (non-powered) (e.g., air/gel/foam overlay)

Reactive support surface (non-powered) (e.g., air/gel/foam overlay)

Active support surface:

Multi-zoned surface (e.g., alternating pressure mattress, rotational surface), or powered reactive support surface (e.g., low air loss)

Active support surface:

Multi-zoned surface (e.g., alternating pressure mattress, rotational surface) or powered reactive support surface (e.g., low air loss)

Moderate assistance with bed mobility required.

Reactive support surface (non-powered) (e.g., air/gel/foam overlay or high-density foam mattress)

Reactive support surface (non-powered) (e.g., foam overlay with air section inset in the area of the wound)

Reactive support surface (non-powered) (e.g., foam overlay with air section inset in the area of the wound)

Active support surface:

Multi-zoned surface (e.g., alternating pressure mattress, rotational surface) or powered reactive support surface (e.g., low air loss)

Patient independent with or without a device with bed positioning. (Light assist may be required.)

Reactive support surface (non-powered) (e.g., high-density foam mattress)

Reactive support surface (non-powered) (e.g., foam overlay with air section insert)

Reactive support surface (non-powered) (e.g., air/gel/foam overlay)

Reactive support surface (powered if the control is within the patient's reach)

Instructions for use of this clinical tool: Determine the patient's level of risk and level of mobility in bed and follow the column-and-row intersection to determine the appropriate reactive or active support system.

Source: Reprinted from Norton L, Coutts P, Sibbald RG. A model for support surface selection as a part of pressure ulcer prevention and management: a preliminary study. WCET Journal. 2008;28(3):25-29.

Types of Support Surfaces

Overlays are filled with water, air, gel, or foam (or a combination of these products) and are applied to the top of a mattress. Foam overlays should be a minimum of 3 inches thick. If a patient's weight completely compresses an overlay, it is not effective.

Pressure relief mattresses are made of a combination of foam, water, or gel or layers of varying foam densities. They are usually indicated in place of standard mattresses used in hospitals and at home. Studies have shown that people at high risk of developing pressure injuries should use higher-specification foam mattresses instead of standard hospital foam mattresses [39].

Air-fluidized beds are embedded with tiny, silicone-coated beads suspended by pressurized, temperature-controlled air. They are recommended for immobile patients who carry higher risk for posterior pressure injuries. These beds reduce pressure against the patient's skin surface, resulting in increased capillary blood flow to the skin. This greatly increases granulation and healing of injuries. These beds are beneficial in patients with multiple large injuries; however, they are unsuitable for patients who are ambulatory, have pulmonary disease, or have spinal instability. They are usually used as an adjunct to comprehensive care.

Low-air-loss beds are made of numerous interconnected air-filled pillows designed to lose air through the cushions at a controlled rate. These beds distribute the patient's weight evenly, which in turn reduces friction, provides pressure relief, and increases capillary blood flow. They are indicated in patients with stage 3 or 4 injuries or stage 1 injuries with hyperemia.

Combination air-fluidized/low-air-loss beds combine the benefits of both types of beds. The low-air-loss component is placed on the upper half of the bed, while the air-fluidized component is placed on the lower half of the bed.

The most important consideration when choosing a support surface is ease of use. Patient goals and overall care plan are also considerations when selecting a support surface. Pressure injury risk, bed mobility, transfer, posture and positioning, financial resources, and advantages and disadvantages of the support surfaces should all be taken into account prior to coming to a decision.

NUTRITIONAL SUPPORT

The role of nutrition, including evidence-based strategies for management, has recently been reviewed in connection with the NPIAP 2019 practice guideline for prevention and treatment of pressure injury [36]. Consultation with a nutritionist should be considered for every patient with, or at high risk for, a pressure injury.

Malnutrition has been shown to increase the risk of developing a pressure injury and to delay wound healing [40,41]. For this reason, nutritional assessment, including food intake and recent weight loss, is an essential component of effective prevention and care. The goal of the assessment is to identify the patient's current nutritional status and any changes that have occurred in recent months or weeks, including the patient's overall level of functioning. The patient's state of hydration should also be assessed, as blood volume depletion impairs circulation and the delivery of oxygen and nutrients to healing wounds [35,36].

A number of clinical and laboratory parameters have been used to screen for poor nutritional status and increased risk of pressure injuries, particularly in elderly patients admitted to a hospital and nursing home. These include serum albumin, prealbumin, and weight less than 80% of ideal. Other signs of malnutrition thought to be useful are:

- Loss of subcutaneous tissue

- Muscle wasting

- Generalized edema

- Dry, pluckable hair

- Dry, flaky, itchy skin

- Cracks in the mucous membranes

- Delayed wound healing/failure to granulate

The provision of an optimal diet (e.g., 30–35 kcalories/kg body weight for adults who are at risk for malnutrition), including the addition of supplemental protein, amino acids, zinc, and vitamins, has been shown to reduce risk of pressure-induced skin injury and to speed wound healing. The recommended daily protein intake for healthy adults (0.8 g/kg of body weight) may not be adequate in the frail elderly or under conditions of chronic inflammation and loss of lean body mass. For dietetic management of adults at high risk of pressure injury or delayed wound healing, the recommended intake is 1.25–1.5 g protein/kg body weight daily [29,42].

Protein is synthesized from amino acids, and specific amino acids (e.g., arginine and glutamine) become essential during periods of protracted metabolic stress (e.g., recovery from trauma, sepsis, pressure injuries). A deficiency in micronutrients, specifically vitamin A, vitamin C, zinc, and copper, is thought to impede injury healing. Zinc is important for the synthesis of protein and nucleic acid, for epithelial cell proliferation, and, along with copper, is essential for healthy collagen formation [42].

The benefit of a high-protein, arginine- and micronutrient-rich diet was evaluated in a prospective study among institutionalized, older adults with pressure injuries. Patients were randomized to receive either a standard diet with 16% energy from protein (control group) or a standard diet plus a 500-calorie supplement with 34 g protein, 6 g arginine, 500 mg vitamin C, and 18 mg zinc (treatment group). A standard protocol to measure rate of wound healing and reduction in injury size was used to monitor the progress of patients in each group. A significant difference in injury area (favoring the treatment group) was evident at week 8; an improved rate of healing, as evidenced by a difference in wound healing score (favoring treatment), reached significance at week 12 [43].

Interventions to Promote Nutrition

For patients with inadequate nutrition, strategies should be employed to increase oral intake. The preferred route of nutritional support is oral; whenever possible, the gastrointestinal tract should be used for feeding. It is the easiest and most comfortable way to provide supplementation, and it is also the least expensive and most convenient way. Patients should have diets prescribed with protein and caloric content sufficient to meet metabolic needs, with consideration of the patient's preferences and special needs (e.g., mechanical soft diets) [15]. Daily multivitamin supplementation may be implemented. Mouth care should be performed prior to eating. Additionally, toileting and hand washing should be offered prior to meals.

It is important to provide an environment conducive to eating. Position the patient properly; an upright position is preferred. Make sure the food is at the right temperature for the patient. Do not rush eating, particularly if the patient is elderly and requires more time to be oriented. Many patients benefit from the inclusion of snacks high in calories and protein in the diet (e.g., a peanut butter sandwich with milk). Consider adding powdered milk to yogurt and puddings to maximize caloric intake and protein levels. Commercial nutritional supplements, such as breakfast shakes, are also a common adjunct.

It is vital to maintain patient control as far as medically feasible. Some patients may not like ice in their water; others may prefer soup lukewarm. Patient preferences should be accommodated as much as possible.

Remind the patient to chew food thoroughly. If necessary, liquids may be offered between bites; some patients require this to help swallow their food.

Assuring adequate fluids and the maintenance of intravascular volume homeostasis are equally important. Vigilance is required to detect early signs of volume depletion or dehydration (e.g., change in weight, loss of skin turgor, falling urine output, hypernatremia); patients identified to be at risk should be listed on assignment/report sheets as a reminder to monitor these patients closely. Fluids should be scheduled between meals at least three times a day. Patient preferences for fluids (e.g., straws, temperature, ice, etc.) should be observed and noted. Refill water pitchers frequently and keep them within reach of patients, especially those with restricted mobility. Patients should be offered something to drink at every interaction. Ambulatory patients should be provided with a water bottle. As with nutrition and positioning, it is necessary to educate patients/families about the importance of regular fluid intake. When, despite these measures, patients are unable to consume adequate levels of water or nutrients, tube feeding or parenteral feeding should be considered. Patient and family preferences and the overall goals of treatment guide these decisions [19].

WOUND CLEANSING

Careful, regular wound cleansing and meticulous skin care is essential. Cleaning and gentle debridement are necessary to remove necrotic debris, contaminants, bacteria, and remnants of previous dressings from the wound surface and adjacent area, usually with the help of fluids (irrigation). This process helps accelerate the healing process and decreases the likelihood of infection [31,44]. One must remember that cleansing is "clearing" a wound, not sterilizing it. Minimal mechanical force is used while cleansing the wound in order to minimize trauma to the wound bed and surrounding healthy tissue. Irrigation at a pressure in the 4 to 5 pounds per square inch range should be used.

The injury and surrounding skin should be cleansed at least daily. If the dressing is being changed more than once daily, wound cleansing should be done during each dressing change.

Generally, normal saline is used for cleansing pressure injuries. In injuries with necrotic tissue, debris, or confirmed or suspected infection, antimicrobials or surfactants should be considered. For infected wounds, diluted povidone-iodine may be used as the irrigation fluid. However, it should not be used during the granulation phase of healing. Acetic acid (0.5%) is highly effective in fungating lesions, especially against Pseudomonas aeruginosa. There are various cleansing agents available in the market, but normal saline is usually the best option [31,45]. Normal saline also should be used as a rinse after other solutions are used to irrigate the wound and minimize fluid shifts within newly forming tissue. Normal saline solution can reduce the drying effects that some irrigants may have on tissue [31].

DEBRIDEMENT

Debridement has been shown to accelerate the healing process in some patients with advanced injuries. In addition to helping move the wound through the stages of healing, debridement is often necessary to visualize the wound bed and to stage the wound; a wound covered with necrotic tissue cannot be staged [15,31]. An exception is eschar on the heels, which acts as a natural biologic cover and should not be removed unless infection is present.

The method of debridement used depends on the amount of necrotic tissue present, the location of the wound, and the patient's overall condition [35]. Patients with stage 3 or 4 pressure injuries who have undermining and/or tunneling or extensive necrotic tissue should have a surgical evaluation for possible surgical debridement of the wound, if this is consistent with their condition and goals of care [29]. Infected wounds may require systemic antibiotic treatment and immediate surgical debridement [15]. Maintenance debridement should be continued until there is a covering of granulation tissue in the wound bed and the wound is free of necrotic tissue [29]. Debridement is contraindicated if there is inadequate blood supply to support wound healing.

Autolytic Debridement

Autolytic debridement uses the body's own enzymes and moisture to heal the injury. To be successful, there must be sufficient white blood cells available to the wound and a moist environment [13]. A layer of wound exudate should be kept in contact with the surface of the wound, usually using a moisture-retaining dressing [10,15,35]. This allows fluid to accumulate in the wound, rehydrating necrotic tissue and making it possible for enzymes in the wound to digest the dead tissue [35]. For a wound covered with dry eschar, it is appropriate to crosshatch the eschar, as this allows a faster build-up of moisture in the wound [35]. In their clinical practice guidelines for pressure injury treatment, the Agency for Healthcare Research and Quality recommends autolytic and enzymatic debridement as the preferred approach for patients in long-term care or home care and for patients who cannot tolerate other methods of debridement [35,46]. In general, this type of debridement is ideal for patients with stage 3 or 4 injuries with light-to-moderate exudates.

Autolytic debridement is highly selective; healthy tissue is spared and only necrotic tissue is liquefied. It is considered very safe, as it uses the patient's own immune system to promote healing and clean the wound of necrotic tissue. Autolytic debridement is easy to perform, very effective, and can be combined with other approaches. It is almost painless for the patient, making it a very attractive option.

However, there are disadvantages as well. It is comparatively slow in efficacy compared to surgical debridement, with progress usually seen in about one week [35]. Close monitoring of the injury is necessary to detect signs of infection. There is a risk of anaerobic growth when an occlusive hydrocolloid dressing is used, and this approach should not be used in infected injuries.

Mechanical Debridement

Mechanical debridement is a nonselective type of debridement that loosens and removes devitalized tissue and debris as well as viable tissue. This method is usually accomplished by means of mechanical force, such as wet-to-dry dressings, pulsatile lavage, or wound irrigation [31]. Pulse lavage may require special knowledge or training on equipment. Although it is a low-cost procedure, mechanical debridement is time consuming and can be painful.

Mechanical debridement is indicated for both acute and chronic wounds with moderate-to-large amounts of necrotic tissue, regardless of the presence of an active infection [47]. Depending on the modality used, the contraindications to mechanical debridement include the presence of granulation tissue in a higher amount than the devitalized tissue, inability to control pain, patients with poor perfusion, and an intact eschar with no gross clinical evidence of an underlying infection [47]. Mechanical debridement also is not indicated for clean wounds.

Surgical Debridement

Surgical debridement is indicated for wounds with thick exudate and necrotic tissue. Approaches include hydrotherapy, laser, maggot debridement therapy (MDT), ultrasound, whirlpool, or excision (with a scalpel or scissors). Extensive or deep injuries should be debrided in operating rooms, although a moderate amount of necrotic tissue can be debrided at the bedside. Newer approaches, such as laser debridement, limit collateral damage, but these approaches can be prohibitively expensive [48]. Hydrotherapy can result in tissue maceration, and there is a risk of infection. Therefore, it is considered a less attractive option. The use of ultrasound waves to debride wounds also has been explored. With this technique, low-frequency ultrasound creates small bubbles in the wound that implode, causing the necrotic tissue to liquefy [49]. This method is generally less painful and less traumatic than traditional methods, with faster healing rates compared with other types of mechanical debridement [50]. However, further comparative evidence is necessary before it can be recommended as a replacement for established treatment modalities. Sharp surgical debridement is contraindicated in patients with intact eschar and no clinical evidence of an underlying infection [47]. The decision to attempt inpatient surgical debridement should take into account the patient's surgical risk stratification [47].

Maggot Debridement Therapy

Debridement with maggots, an approach popular at the early 20th century, is finding a new place in wound care debridement [15]. MDT is an efficient, simple, cost-effective and reliable biosurgery method that uses mostly larvae of the Lucilia sericata species of the green bottle fly [51]. The larvae stimulate wound healing by activating molecular processes in the wound area through proteolytic enzymes, including collagenase, in their excretions/secretions that break down the necrotic tissue, ingest and digest micro-organisms, and inhibit bacterial growth by releasing ammonia into the would bed, which increases the wound pH [13,47]. Studies have shown that the excretions/secretions have antibacterial, antifungal, anti-inflammatory, and tissue-regenerating effects; the enzymes are still mostly unidentified [51]. Maggots have the ability to access moist tissue throughout the wound bed and clean small areas without harming healthy tissue [52]. MDT involves the application of sterilized larvae to the wound bed every two to three days [15]. The maggots can be applied to the wound directly or in a containment pouch [15]. The most appropriate dressing for wounds treated with maggots is one that keeps the larvae in place, allows for a flow of oxygen, and is suitable for the characteristics of the wound [35].

MDT is indicated for pressure injuries with necrotic tissue with or without infection [52]. Maggots work well in wounds in which moisture and oxygen are readily available and the pH is fairly stable [35]. The therapy is considered mainly for the treatment of wounds for which other forms of treatment are either not appropriate or not successful, and it is contraindicated in patients who have bleeding abnormalities or deep tunneled wounds [10,15,47].

Precautions should be taken to prevent the larvae from coming in contact with healthy skin, as there is a possibility of enzymatic damage [13]. Otherwise, there are no reported side effects from MDT [13]. However, some patients complain of a crawling or tingling feeling [13]. MDT also may cause psychologic distress for many patients, and its use should be discussed thoroughly with the patient and/or family prior to commencing therapy [15]. This therapy should only be used with appropriately informed consent.

Enzymatic Debridement

Enzymatic debridement is a selective method of debridement in which concentrated enzymes (e.g., collagenase, papain, becaplermin, trypsin) attack collagen and liquefy necrotic wound debris without damaging viable tissue. Enzymatic debridement is used either alone or in combination with other techniques to remove necrotic tissue and promote wound healing [53,54]. For instance, collagenase and moisture retentive dressings can work in synergy, thereby enhancing debridement [47].

Usually, stage 3 or 4 injuries are considered candidates for enzymatic debridement. Application of the enzyme should be discontinued when the wound is free of necrotic tissue. If eschar is present, it should be crosshatched prior to introduction of the enzyme to improve efficacy, as enzymes are not active on a dry surface.

Enzymatic debridement is relatively fast acting, with progress evident in 48 to 72 hours. However, complete debridement may be a long process, so other methods (e.g., surgical removal of loosely adherent necrotic tissue) are often used in conjunction.

Enzymatic debridement should not be used for heavily infected wounds or in conjunction with silver-based products or Dakin solution [47].

DRESSINGS

Wound dressings are a cardinal component in the treatment of pressure injuries. There is a variety of available dressings, each with its own benefits and drawbacks (Table 4) [55]. The selection of dressing for an injury is determined by several parameters. These include:

- Condition of the injury and wound bed

- Size and depth

- Necrosis/slough

- Dry/exudating

- Epithelializing

- Presence of tunneling

- Infection

- Over-granulating

- Malodorous

- Malignant

- Pain

- Aim of treatment

- Facilitate healing

- Promote debridement

- Combat infection

- Relieve pain

- Absorb exudates or add moisture

- Prevent or treat scarring

- Combat odor

- Cosmetic/provide concealment

- Condition of surrounding skin

- Fragile

- Macerated

- Anatomical location

- Difficult to dress

- Dressing affects use of normal clothing or shoes

- Etiology

- External compression

- Prospect of healing

- Palliation

- Indication of specific topical therapies (e.g., enzymatic debridement, antibiotics)

- Economics/cost

- Availability (reimbursement issues)

Table 4: OVERVIEW OF DIFFERENT DRESSINGS FOR PRESSURE ULCERS

Dressing Type

Description

Indication

Advantages

Disadvantages

Transparent film

Adhesive, semipermeable, polyurethane membrane that allows water to vaporize and cross the barrier

Management of stage 1 and 2 pressure ulcers with light or no exudates; may be used with hydrogel or hydrocolloid dressings for full-thickness wounds

Retains moisture

Impermeable to bacteria and other contaminants

Facilitates autolytic debridement

Allows for wound observation

Does not require secondary dressing (e.g., tape, wrap)

Not recommended for infected wounds or wounds with drainage

Requires border of intact skin for adhesion

May dislodge in high-friction areas

Not recommended on fragile skin

Hydrogel

Water- or glycerin-based amorphous gels, impregnated gauze, or sheet dressings; amorphous and impregnated gauze fill the dead tissue space and can be used for deep wounds

Management of stage 2, 3, and 4 ulcers; deep wounds; and wounds with necrosis or slough

Soothing, reduces pain

Rehydrates wound bed

Facilitates autolytic debridement

Fills dead tissue space

Easy to apply and remove

Can be used in infected wounds or to pack deep wounds

Not recommended for wounds with heavy exudate

Dehydrates easily if not covered

Difficult to secure (amorphous and impregnated gauze need secondary dressing)

May cause maceration

Alginate

Derived from brown seaweed; composed of soft, nonwoven fibers shaped into ropes or pads

May be used as primary dressing for stages 3 and 4 ulcers, wounds with moderate-to-heavy exudate or tunneling, and infected or noninfected wounds

Absorbs up to 20 times its weight

Forms a gel within the wound

Conforms to the shape of the wound

Facilitates autolytic debridement

Fills in dead tissue space

Easy to apply and remove

Not recommended with light exudate or dry scarring or for superficial wounds

May dehydrate the wound bed

Requires secondary dressing

Foam

Provides a moist environment and thermal insulation; available as pads, sheets, and pillow dressings

May be used as primary dressing (to provide absorption and insulation) or as secondary dressing (for wounds with packing) for stage 2 to 4 ulcers with variable drainage

Nonadherent, although some have adherent borders

Repels contaminants

Easy to apply and remove

Absorbs light-to-heavy exudate

May be used under compression

Recommended for fragile skin

Not effective for wounds with dry eschar

May require a secondary dressing

Hydrocolloid

Occlusive or semiocclusive dressings composed of materials such as gelatin and pectin; available in various forms (e.g., wafers, pastes, powders)

May be used as primary or secondary dressing for stage 2 to 4 ulcers, wounds with slough and necrosis, or wounds with light to moderate exudates; some may be used for stage 1 ulcers

Impermeable to bacteria and other contaminants

Facilitates autolytic debridement

Self-adherent, molds well

Allows observation, if transparent

May be used under compression products (compression stockings, wraps, Unna boot)

May be applied over alginate dressing to control drainage

Not recommended for wounds with heavy exudate, sinus tracts, or infection

May curl at edges

May injure fragile skin upon removal

Contraindicated for wounds with packing

Moistened gauze

2×2- or 4×4-inch square of gauze soaked in saline for packing

May be used for stage 3 and 4 ulcers and for deep wounds, especially those with tunneling or undermining

Accessible

Must be remoistened often

Time-consuming to apply

Source: Reprinted with permission from Bluestein D, Javaheri A. Pressure ulcers: prevention, evaluation, and management. Am Fam Physician. 2008;78(10):1186-1194.

One of the most important factors in the selection of a dressing is moisture maintenance in and around the injury. A dressing that absorbs but does not dry out the wound is needed for injuries with excessive exudates. For injuries with minimal drainage, a dressing that restores moisture and prevents drying is needed. Frequency of dressing change also depends on the quantity of drainage.

Transparent Films

For injuries with limited exudates, transparent films should be used; however, their use over cavities is contraindicated. These dressings should be changed every three to seven days, and application of triple antibiotic ointment is also recommended by some experts [55].

Hydrogels

Hydrogel dressings are useful for patients with very shallow, dry, or minimally exuding injuries and for painful pressure injuries [29]. These gels, sheets, sprays, or ribbons of cross-linked polymers require a secondary dressing to affix them to the patient. Hydrogels not only rehydrate the wound bed but also aid autolytic debridement and reduce pain. These dressings can be used in infected injuries and are easily applied and removed from the wound. However, they are not recommended for pressure injuries with heavy exudation. They also dehydrate easily and can cause maceration.

Hydrocolloids

Hydrocolloid dressings contain a gel that promotes the growth of new skin and are indicated for clean, uninfected stage 2 and shallow stage 3 injuries in body areas where they will not roll or melt [29]. They are available as pastes, powders, or wafers composed of gelatin, pectin, and carboxymethylcellulose. These dressings promote angiogenesis, autolysis, and granulation. Some hydrocolloids are self-adhering, but secondary dressings are required when powders and pastes are used. These dressings are especially beneficial on heels and sacral injuries that require contouring. They are recommended for partial and full-thickness injuries with or without necrotic tissue.

Hydrocolloid dressings can produce an odor upon removal [15]. In the absence of other signs of clinical infection, this is not an abnormal finding and should be explained to concerned patients and staff [15]. Hydrocolloids may also leave a residue in the wound bed, which should be gently irrigated out at dressing change [13]. These dressings lose their effectiveness if they are changed too frequently and should not be used for wounds that must be monitored daily [13].

Calcium Alginates

Calcium alginate dressings, or alginates, are polysaccharide seaweed derivatives containing alginic acid. Alginate dressings either form a moist gel when they come in contact with exudates or retain their original shape while absorbing exudates. They are hemostatic, protect surrounding skin from maceration, promote healing, and may reduce risk of infection. These dressings are available in the form of ribbons, pads, and ropes.

Alginate dressings should be considered for the treatment of moderately and heavily exuding pressure injuries and for clinically infected injuries when there is concurrent antimicrobial therapy [29]. They may also be used to control bleeding after surgical debridement. A secondary dressing is necessary to secure these dressings, and they should be changed every 12 hours to four days. Wounds treated with alginate dressings may smell fishy or like "low tide" [15].

Foam Dressings

Foam dressings are protective and absorbent and potentiate wound healing by providing a moist environment. They are also permeable to gas and provide good insulation. These dressings are a good choice for stage 2 and shallow stage 3 injuries with drainage and for painful injuries.

In patients with incontinence, waterproof versions of foam dressings are prescribed in order to protect the skin. They can also be used under compression to prevent damage from shear. However, foam dressings are not effective in removing necrotic tissue, and after the dressing becomes saturated, maceration of skin around the wound can develop quickly. Therefore, these dressings should be paired with alginates for wounds with a high level of exudate.

Silver-Impregnated Dressings

Silver-impregnated dressings are a treatment option for infected or heavily colonized wounds or wounds that are at increased risk for infection [29]. Silver has an antimicrobial effect on a broad spectrum of organisms and has been shown to reduce the bacterial count in wounds [13]. Sustained-release sliver dressings are toxic to bacteria and fungi but do not adversely affect healthy wound tissue [10]. However, silver-resistant organisms do exist, and the judicious use of silver is advised, similar to the approach adopted with antibiotics [13]. It is recommended that the use of silver dressings be limited to a two- to four-week period [13]. As stated, silver-based products should not be used for enzymatic debridement [47].

Cadexomer Iodine Dressings

Cadexomer iodine dressings are used for wounds with moderate-to-high amounts of drainage. They should not be used for patients who are sensitive to iodine or individuals with thyroid disease [29]. Cadexomer iodine dressings are antimicrobial and maintain a moist environment for wound healing [15]. Although these dressings are capable of reducing bacteria counts in wounds, they do not replace the need for systemic antibiotic therapy and are regarded as an adjunct in the treatment of wound infections [15].

Gauze

Gauze packing was used frequently in the past, but it is now regarded as less effective in coping with wound drainage than calcium alginate or hydrocolloid fiber dressings [10]. Gauze dressings do not provide a barrier against bacteria, lower wound temperature, and can pull healthy granulating tissue out of the wound on removal [10]. When other forms of moisture-retentive dressings are not available, continually moist gauze is preferable to dry gauze, and one should avoid the use of wet-to-dry gauze dressings [29]. Gauze dressings are also labor intensive, requiring several dressing changes daily, which adds to the cost of the overall care [15].

Composite Dressings

Composite dressings are a combination of more than one material used to fulfill several important functions in the wound [15]. They provide an effective barrier to bacterial contamination of the wound and include an absorptive layer and either foam, hydrocolloid, or hydrogel [15]. Composite dressings can have either a semi-adherent or non-adherent surface placed in contact with the wound bed [15]. Composite dressings are comfortable and are available in various shapes and sizes [13]. These dressings should not be cut, as this compromises the structure of the dressing [15].

Collagen Dressings

Some dressings incorporate collagen, which is an important protein involved in wound healing and repair [13]. The dressings can be 100% collagen or combined with other products, such as alginates [15]. They provide a high level of absorption while keeping the wound bed moist and are easily removed [15]. For wounds with very little drainage, collagen gel can be applied in a layer one-quarter inch thick [13]. Collagen used in most wound dressings is derived from cowhide [15]. Therefore, it should not be used in patients who are allergic to bovine products [15].

PAIN MANAGEMENT

A research study concluded that severity of pain was correlated to pressure injury stage, and patients with later-staged pressure injuries may experience excruciating pain [56]. The goal of pain management in the pressure injury patient is to eliminate the cause of pain and to provide analgesia. There are several interventions and practice modifications that can prevent or manage wound-associated pain.

Skin care and assessments should be performed at a time of day when the patient is less fatigued [2]. All procedures should be thoroughly explained before they are performed. If a patient has questions, this should be addressed, and healthcare professionals should be encouraging and provide positive reinforcement. It is important to avoid trauma (shearing and tear injuries) to fragile skin during transferring, positioning, or holding a patient. If necessary, adjunctive medications may be administered to improve sleep and reduce anxiety, which can contribute to experiences of pain.

Dressing changes are often very painful. An analgesic may be administered 30 minutes before dressing changes, and if possible, the number of daily changes should be kept to a minimum. Tape should always be avoided on fragile skin. If patients are able, they should be allowed to remove their own dressings or set the pace of dressing changes. All patients should be assessed for pain before, during, and after dressing changes, and these findings must be documented [2].

Evidence Based Practice Recommendation

The National Pressure Ulcer Advisory Panel, the European Pressure Ulcer Advisory Panel, and the Pan Pacific Pressure Injury Alliance recommend clinicians consider applying a topical opioid to manage acute pressure injury pain, if required and when there are no contraindications.

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Level of Evidence: B1 (The recommendation is supported by level 1 studies of moderate or low quality providing direct evidence or level 2 studies of high or moderate quality providing direct evidence)

Physical therapy and occupational therapy may be helpful to decrease contractures and muscle spasm. Of course, ensuring proper seating and positioning can improve pain scores and decrease the risk for further pressure injuries.

For mild-to-moderate pain, nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen may be used. Opioids should be avoided as much as possible, as the sedative effects boost immobility; however, they may be necessary during dressing changes and/or debridement.

SURGICAL CLOSURE

Surgical closure is required for large defects, particularly when musculoskeletal structures are exposed. In case of large but shallow defects, skin grafts may be beneficial. The most widely used reconstructions performed for pressure injuries are local flaps. In this reconstruction, well-vascularized skin is transferred with underlying structures (such as subcutaneous tissue, fascia, and muscle) to the wound area. These procedures are classified as [57]:

- Simple cutaneous: Includes skin and subcutaneous tissue only

- Fasciocutaneous: Includes skin, subcutaneous tissue, and fascia

- Myocutaneous: Includes all soft tissue layers from skin to muscle

There are benefits of surgical closure of pressure injuries, including more rapid healing of the wound and short-term resolution of complications [58]. Flaps containing muscle provide a physiologic barrier to infection, eliminate dead space in the wound, and improve vascularity [31]. Surgery may be difficult for some patients, however, particularly elderly and frail persons. The patient should be medically stable, of good nutritional status, and able to benefit from the procedure [31]. Complications as a result of surgical closure are considerable and include hematoma, seroma, wound dehiscence, and wound infection [31]. In addition, injuries frequently recur, even in younger patients.

INFECTION MANAGEMENT

Continuous assessment of pressure injuries for infection is vital. Signs of infection include erythema, fever, increased drainage, and increased leukocyte count, and these parameters should be monitored periodically. Topical treatment with silver sulfadiazine, triple antibiotic, or metronidazole is recommended for patients with infected injuries or who are at risk for infection. In general, noninfected wounds produce little or no odor.

Systemic antibiotic therapy is indicated when there are signs of cellulitis, purulent wound drainage, fever, or osteomyelitis. The choice of systemic agent should be supported by clinical assessment, imaging studies, and deep tissue culture.

Prophylaxis of infection is also important, as infected wounds are associated with pain, longer healing times, and greater impairments in patient functioning. Topical application of silver sulfadiazine and oral antibiotics are effective in infection prevention in pressure injuries [59,60].

ADJUNCTIVE TREATMENTS

There are many adjunctive treatments used in wound management. They include electrical stimulation, growth factors, hyperbaric oxygen, normothermic infrared and temperature therapy, and negative pressure wound therapy.

Electrical Stimulation

Electrical stimulation is effective in increasing the healing rate of chronic pressure injuries [61]. It is generally indicated for persons with spinal cord instability and difficult-to-heal injuries. In one study of individuals with spinal cord injury and pressure injuries, low-frequency pulsed current (i.e., alternating current) was compared to direct current and control groups [62,63]. Researchers found that injuries treated with electrical stimulation healed faster compared to controls and to standard treatment. Electrical stimulation is recommended by the ACP as adjunctive therapy in patients with pressure injuries to accelerate wound healing [64,65].

This therapy consists of the placement of a high-voltage, pulsed electrical current onto the wound bed (direct) or near the wound (induced), usually once daily for several weeks. The electrical settings (e.g., the polarity, amplitude and voltage, amperage) are established according to wound and patient characteristics. The Institute for Clinical Systems Improvement 2012 guideline recommends considering the use of direct contact electrical stimulation in the management of recalcitrant stage 2 as well as stage 3 and 4 pressure injuries to facilitate wound healing [61]. Although electrical stimulation is used for the treatment of pressure ulcers, a 2020 Cochrane review found that available evidence is insufficient to support its widespread use apart from its use in research [66].

Growth Factors

Fluids taken from chronic pressure injuries have a significant degradation of growth factor activity compared to acute wounds [67,68,69]. The application of topical gels containing platelet-derived growth factor can increase fibroblast activity and accelerate healing for chronic wounds [68,70]. The application of 100 mcg/g becaplermin gel once daily has been found to increase the incidence of complete healing compared to placebo [71].

Hyperbaric Oxygen

The use of hyperbaric oxygen in the treatment of pressure injuries is controversial. Hyperbaric oxygen therapy consists of 100% oxygen administered at a pressure of 2 to 3 atmosphere for a duration of one to two hours daily. This results in hemoglobin becoming saturated and oxygen spilling into the blood plasma. The vasoconstrictive effects result in reduction of edema in compromised flaps, pressure injuries, burns, and crush injuries. Improved oxygenation causes increased fibroblast activity and antimicrobial activity, with the stimulation of the phagocytic activity of the white blood cells [72]. It has been hypothesized that hyperbaric oxygen therapy could promote healing of pressure injuries; however, more research is necessary to evaluate the risks, benefits, and associated costs [73].

Normothermic Infrared and Temperature Therapy

Studies have shown that pressure injuries treated with radiant heat heal faster and result in shrinking of the injury [74]. Because this requires special equipment and trained clinicians, however, it is not yet widely used.

Therapeutic Ultrasound

Theoretically, therapeutic ultrasound can be beneficial in healing pressure injuries based on both thermal and non-thermal effects (Table 5). The NPIAP recommends that high-frequency ultrasound be considered as an adjunct for the treatment of infected pressure injuries. However, both a meta-analysis and a comprehensive review of available data on the efficacy of ultrasound in the treatment of pressure injuries were inconclusive [75,76].

Table 5: THERMAL AND NON-THERMAL EFFECTS OF THERAPEUTIC ULTRASOUND

Thermal

Non-Thermal

Increased collagen elasticity

Decreased muscle and joint stiffness

Decreased pain

Decreased muscle spasm

Increased oxygen transport

Hyperemia

Speeds up inflammatory process

Increases release of growth factors

Fibroblast and endothelial cell proliferation

Increased collagen production

Accelerated angiogenesis

Better organization of collagen matrix

Source: Reprinted from Lin VW, Cardenas DD, Cutter NC, et al. (eds). Spinal Cord Medicine: Principles and Practice. New York, NY: Demos Medical Publishing; 2003.

Pulsed Electromagnetic Field Energy

Pulsed electromagnetic field therapy can be an alternative treatment when pressure injuries are resistant to conventional therapies. This technique has been found to increase synthesis of DNA, improve revascularization, reduce bacterial growth, and increase neurotransmitter receptor and hormone receptor activity [77,78,79]. Researchers have demonstrated complete healing within a few weeks of initiating this treatment in patients with stage 3 and 4 injuries [80,81].

Negative Pressure Wound Therapy (Vacuum-Assisted Closure)

Negative pressure wound therapy is useful for advanced (stage 3 or 4) pressure injuries and poorly healing wounds with copious drainage. In general, it consists of a foam sponge dressing placed into the injury and connected by a drainage tube to a pump that exerts intermittent or continuous negative pressure on the wound bed. The negative pressure reduces edema and facilitates removal of excessive fluid and infectious debris from the bed of the injury. The effect is to increase local blood flow, promote granulation tissue, and speed wound healing

Negative pressure wound therapy has cost-saving advantages. It reduces the frequency of dressing change to three or less times a week, decreases nursing time and cost, and often permits earlier discharge and follow-up care in the ambulatory setting. Patients experience less of the pain associated with manipulation of the wound.

When considering negative pressure therapy for wound management, patient selection and plan of care should be made with caution and always in consultation with wound care specialists and/or experienced surgeons. Adverse events, such as serious bleeding and unrecognized deep infection, have been reported [82]. Moreover, this modality is not effective for injuries and wounds with necrotic tissue or malignancy in the margins.

INDIVIDUAL STAGING TREATMENT PLANS

An individualized treatment plan for the patient with a pressure injury is based on the stage of the injury, the patient's physical and psychosocial status, and whether infection is present (Figure 1) [83]. The following sections outline the general goals of treatment based on the stage of the wound, but it is important to individualize treatment as well.

Figure 1: ALGORITHM FOR THE TREATMENT OF PRESSURE ULCERS

Source: Reprinted with permission from Hess CT. Clinical Guide to Skin and Wound Care. Philadelphia, PA: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2008 © Wolters Kluwer.

Suspected Deep Tissue Pressure Injury

At this stage, injuries often heal with proper care and treatment, but some will deteriorate further. The aim is to quantify the extent of the wound, increase blood circulation, and prevent further breakdown of skin. Treatment should focus on:

- Pressure redistribution

- Prevention of shear and friction

- Moisture maintenance

- Physical therapy and nutritional support

- Periodic assessment of the patient

- Pain management

- Prevention and treatment of infection

Stage 1

The aim for patients with stage 1 pressure injuries is to prevent further deterioration of the injury and improve circulation. The same treatment plan implemented for suspected deep tissue injury should be the starting point. Skin should be cleansed and lightly moisturized. Massage on the affected area is contraindicated as it can lead to further tissue injury. If indicated, hydrocolloid dressings and transparent film dressings should be used. Surgical treatment and debridement are not indicated.

Stage 2

Promoting healing is the main goal for stage 2 injuries, with a focus on prevention of progression to full-thickness injury. Beginning with the same treatment plan implemented for previous stages, steps should be added to protect against infection. An appropriate dressing should be applied to promote healing and keep the wound bed clean. The skin is fragile at this stage, so adhesives should be avoided. Nutritional status should be re-evaluated, and supplements added, if necessary. Surgical treatment is not indicated, and debridement is rarely necessary.

Stage 3

Maintenance of a clean, moist wound bed to prevent infection and promote healthy granulation tissue is the prime goal in the treatment of stage 3 injuries. Infection impedes healing and may lead to complications such as sepsis and osteomyelitis. Careful assessment and follow-up are important at this stage; at the first clinical sign of infection, deep wound cultures should be obtained and appropriate antimicrobial therapy initiated promptly.

Along with the measures described for the previous stages, debridement should be carried out if indicated. Autolytic or enzymatic debridement is recommended for stage 3 injuries with light-to-moderate exudate; surgical debridement is necessary if there is necrotic tissue and infection [83].

Wound gels may be used if the injury is partially or completely covered with necrotic tissue. Foam dressings and cavity fillers are indicated if the injury bed is free of necrotic tissue and debris. Alginate dressings can also be applied if the wound has excessive exudates.

Stage 3 injuries usually heal spontaneously with appropriate cleaning and dressing. However, when treated conservatively, they have a recurrence rate of between 32% and 77% [84]. Surgical management can reduce the rate of recurrence in some patients [84]. However, according to a Cochrane review, randomized evidence neither supports nor refutes the role of surgery in the management of stage 2 or above pressure injuries [85].

Stage 4

For patients with stage 4 injuries, the focus of treatment is to provide an environment for new tissue growth. This can also involve removal of necrotic tissue and drainage reduction.

First, the injury should be assessed for bone involvement and signs of infection. If indicated, antibiotics should be started. Surgical management is often indicated in stage 4 injuries to address or prevent complications due to the large size of the wound. Debridement is often necessary to remove necrotic tissue.

Unstageable

When treating patients with unstageable pressure injury, practitioners should focus on providing a moist environment and preventing further deterioration. Injury stage should be reassessed when the base is visible and the treatment plan adjusted accordingly. The wound should be assessed for signs of infection, and antibiotics may be indicated. As with all stages, pain management and patient comfort should be ensured.

The wound should be debrided of nonviable tissue in the wound bed. One exception is the eschar on the heels, which should never be debrided unless infected.

9. WOUND MONITORING

During the treatment of pressure injuries, routine evaluation of improvement or wound progression is essential and wounds should be assessed at each dressing change. In addition, a holistic patient assessment is indicated, which encompasses systemic factors, psychosocial factors, and local factors. Systemic factors include assessment of etiology, duration, and blood flow to the injury; infection; medications; and comorbidities. Determination of the patient's knowledge, beliefs, social support, and financial health (psychosocial factors) is also important. Finally, factors specific to the wound itself, such as amount of exudate, recurrent injury, and tissue necrosis, must be evaluated and documented.

WOUND ASSESSMENT

When evaluating the wound, the most important factor to consider is whether the wound is progressing toward the goals established at the onset of treatment [13]. Clinical signs of improvement are expected to appear within two to four weeks [10]. If the wound is not progressing, further assessment and adjustment of the treatment approach are warranted [13].

For nonhealing wounds, the first factor to evaluate is the quality of wound care. This includes determining if dressing changes are being carried out at the recommended intervals, if the dressings are applied appropriately, and if the manufacturer's instructions for product use are being followed [13]. Factors affecting the patient's condition should be taken into consideration and addressed appropriately [10]. Failure of a wound to improve is often due to systemic factors, such as ischemia, infection, or malnutrition, or continuation of the causative factors [10]. These issues must be addressed first to achieve optimum wound healing. A change in the dressing treatment is indicated if any of the following problems occur [10]:

- Maceration of the surrounding skin

- Inadequate control of wound drainage

- A change in the amount of drainage or the depth of the wound

Reverse staging of pressure injuries is not an acceptable approach to gauging the level of wound healing. Healed pressure injuries do not replace lost muscle, subcutaneous fat, or dermis [29]. Tools that appropriately measure degrees of healing include the Bates-Jensen Wound Assessment Tool and the Pressure Ulcer Scale for Healing (PUSH) tool [15,86]. The Bates-Jensen Wound Assessment Tool has thirteen variables that provide a composite picture of the status of the wound [15]. The PUSH tool uses scores in three domains (i.e., size, exudate amount, and tissue type) to indicate improvement or deterioration of the injury (Table 6) [87]. When using this tool, surface area is calculated by multiplying the greatest length (head to toe) by the greatest width (side to side) in centimeters. After removal of the dressing and before applying any topical agent to the injury, the amount of exudate is estimated as none, light, moderate, or heavy. Finally, the type(s) of tissue present in the wound bed is evaluated (i.e., necrotic, slough, granulation, epithelial, or closed). A score of 0 on the PUSH tool indicates the wound has healed, whereas the highest score of 17 indicates wound degeneration [15]. Results of the assessment should be recorded; a decrease in score over time indicates improvement.

Table 6: THE PRESSURE ULCER SCALE FOR HEALING (PUSH) TOOL

Factor

Points

Size (surface area)

0 cm^2

0

<0.3 cm^2 (but more than 0 cm^2)

1

0.3–0.6 cm^2

2

0.7–1.0 cm^2

3

1.1–2.0 cm^2

4

2.1–3.0 cm^2

5

3.1–4.0 cm^2

6

4.1–8.0 cm^2

7

8.1–12.0 cm^2

8

12.1–24.0 cm^2

9

>24.0 cm^2

10

Exudate amount

None

0

Light

1

Moderate

2

Heavy

3

Tissue in wound bed

Closed wound

0

Epithelial tissue

1

Granulation tissue

2

Slough

3

Necrotic tissue

4

Source: [87]

Wound assessment also includes wound location, size and depth, signs of infection, and exudates. The wound is examined for presence of tissue debris, base tissues, quality and amount of exudate, odor, and pain.

Location

Documentation of location is paramount for proper monitoring of pressure injuries. Placement can affect healing and treatment decisions. Wounds that may be exposed to urine or feces should be provided special attention and care, and peripheral wounds may require more time to resolve.

The location of the wound should be stated in a manner that is clearly understood, such as the sacrum or right or left ischium [49]. Anatomical markings should be used when possible.

Size and Depth

Accurate measurement of the wound is probably the most important feature of wound assessment [35]. It provides information on the initial size and progression or non-progression of healing, allowing for valuable feedback on the effectiveness of clinical interventions [15]. Decreasing wound size is generally regarded as a sign of wound healing, but an increase in wound area is not necessarily indicative of deterioration [15].

Wounds should always be measured in centimeters, using a plastic or paper ruler. Wound length is measured from head to toe; width is measured from hip to hip [13]. The depth of the wound can be obtained by gently inserting a sterile cotton-tipped applicator into the wound bed and marking it at skin level. The applicator is then measured using a metric ruler [13].

Undermining/Tunneling

Sinus tracts and undermining impair healing, and it is important to immediately identify their presence. A sinus tract is a tunnel that extends from any part of the wound and can bore through subcutaneous tissue and muscle. This tunnel creates dead space, which can result in abscess formation and further impede the healing process. A sinus tract can be measured using a sterile cotton swab.

Undermining is defined as destruction of the tissue under the skin around the edges of the wound. This frequently occurs in pressure injuries that have been subjected to shear force as well as pressure. It is important to document the location and extent of undermining.

The easiest way to measure and describe undermining is by using the face of the clock [15]. With the patient's head representing 12 o'clock, sweep the area of undermining or probe the tunneling to ascertain the depth. For example, undermining along the right border would be recorded as extending from 1 o'clock to 5 o'clock with a depth of 4 cm. It is important to check around the entire perimeter of the wound, as undermining can occur in more than one location.

Wound Bed

It is also vital to assess and document the appearance of the wound bed (Table 7). If the wound bed has a mixture of tissue in it, this should be documented by an approximate percentage (e.g., 75% granulation tissue and 25% slough). Granulation results in "beefy" red tissue consisting of new capillaries, fibroblasts, and collagen fibers with a shiny, moist granular appearance. Grey or purple granulation is a sign of poor vascularization. Granulation present in the wound denotes healing.

Table 7: WOUND BASE COLOR DESCRIPTIONS

Color

Description and Clinical Implications

Red

Clean and uniformly pink to red in color.

Usually heals by secondary intention.

Dressings need to be changed less often, but the wound should be moist at all times.

Yellow

Varies from ivory to canary yellow or even green in color, depending on whether or not infection is present.

Caution: Tendon may appear as yellow or white.

The goal of care is to manage exudate and remove slough through surgical, sharp, mechanical, enzymatic, or autolytic debridement.

Not all yellow is detrimental to healing; granulation grows through yellow fibrin.

Black or brown

Ranges in color from dark brown and gray to black.

The goal for most individuals is to remove the necrotic tissue by surgical, sharp, enzymatic, or autolytic debridement.

Where there is no drainage or there is boggy surrounding tissue, leave the hard, dry eschar or black scab intact on the lower legs, feet, or heels of individuals whose healing potential is compromised by inadequate circulation. It provides a protective covering for the wound.

Source: [13]

Necrosis is gray, brown, or black unviable tissue that usually must be removed in order for healing to take place. Eschars are typically gray to black and dry or leathery in appearance. Slough tissue is yellow/white to gray in color. It may be stringy or thick and appear as a layer over the wound bed. Epithelial tissue will often begin to grow in from the edges over the wound surface. This tissue is generally pink and shiny. As a quick reference color guide, red is associated with normal healing, yellow indicates slough or dead tissue, and black is necrosis.

Exudates

Exudates are an indication of inflammation in the wound. The presence of large amount of exudate can delay healing and increase the risk of infection. As such, this factor has a significant impact on treatment decisions, particularly dressing type. The amount and quality of any exudates should be noted. Amount may be denoted as:

- Large/copious: Extends beyond dressing

- Moderate: Contained within the dressing

- Small/slight: Small amount of exudate in the center of dressing

- None: Absence of exudate

The quality of the exudates may be described as [88]:

- Purulent: Thick exudate that may be malodorous and tan, yellow, green, or opaque in appearance and denotes presence of infection

- Serosanguineous: Thin and pink or light red in color

- Serous: Thin/watery and clear or straw colored, with no blood or debris

- Hemorrhagic: Red and thick, consisting mainly of blood

- Fibrinous: Cloudy and thin with strands of fibrin

Odor

Malodor with purulent exudates suggests mixed infection often combined with ischemic necrosis. However, the majority of wounds (even those free of infection) do have some odor. As previously discussed, gram-negative and gram-positive infections have distinct odors. If present, an injury's odor (quality and strength) should be documented.

WOUND EDGE AND SURROUNDING SKIN

Wound edges are open and closed. Healthy wound edges are open and allow cell migration. Closed wound edges prevent cell migration and may delay healing. These edges may be described as calloused, approximated, or rolled. The presence or absence of erosion, papules, excoriation, denudement, pustules, or other lesions should be noted.

The condition of the surrounding skin surface up to 4 cm from the edge of the wound circumferentially must also be assessed and documented. Its characteristics should be noted, particularly color and integrity [10]. Maceration from excessive drainage may indicate that the dressing used is not appropriate and a different product is needed. Circumferential erythema and/or induration up to 2 cm from the wound are indicative of cellulitis.

PAIN

Pressure injuries cause considerable pain and suffering, ranging from sore to excruciating [30]. In one study, 75% of patients rated their pain as mild, discomforting, or distressing; 18% rated their pain as horrible or excruciating [89]. Pain and odor control are a major concern for patients, and studies have shown that patients rank pain control as more important than healing [15]. The level of pressure injury pain depends both on the stage of the injury and on manipulation of the area (e.g., if a dressing change is done at the time of assessment), although the majority of patients report pressure injury pain at rest as well as with dressing changes. Pressure injury pain may be due to tissue trauma, inflammation, damaged nerve endings, infection, and procedures such as debridement and dressing changes [90].

The gold standard for assessing pain intensity is self-reporting using standard pain intensity instruments. Two of the most widely used pain assessment scales are the numeric pain intensity scale and the Wong-Baker Faces Pain Rating Scale [91]. The numeric pain intensity scale consists of ratings from 0 (no pain) to 10 (worst possible pain). This scale can be used for pain assessment with adults and children older than 7 years of age [92]. Visual presentation of the numeric pain intensity scale is helpful with hearing impaired patients, and the scale has been translated into many languages.

The Wong-Baker Faces Pain Rating Scale consists of six faces ranging from a happy smiling face (no pain), to a crying, frowning face (worst pain). The patient is asked to choose the face that best reflects his or her pain. The Faces Pain Rating Scale is the preferred scale for use with children and may also be used with the geriatric population, cognitively impaired patients, and those for whom English is a second language.

After the initial pain assessment has been completed, reassessment should be done at regular intervals. As noted, pain intensity should be rated by the patient, not a healthcare professional. The following questions may be used to help determine patients' pain levels:

- What kind of pain are you experiencing?

- What word(s) would you use to best describe it (e.g., burning, aching, shooting)?

- What makes the pain better?

- What makes it worse?

- Where is the pain located?

- Does the pain radiate?

- Would you describe your pain as none, mild, moderate, severe, or excruciating?

- How would you rate your pain on a scale of 0 to 10, with 0 representing no pain and 10 being the worst imaginable pain?

- What is the pain intensity at its worst, best, and now?

- Is the pain better or worse at any particular time of the day or night?

- When does it start and when does it stop?

PRESENCE OF INFECTION

Infections remain a significant cause of both pain and poor outcomes in patients with pressure injuries. At each wound assessment, the patient should be evaluated for signs of local or systemic infection. Common signs and symptoms include:

- Systemic signs (e.g., fever, chills, sweats)

- Local signs (e.g., rubor, calor, color of adjacent tissues)

- Unusual odor

- Friable or dysmorphic granulation

- Purulent exudates

If any of these are present, infection should be suspected and treated. Culturing the wound may also be helpful, particularly for patients with refractory or recurring wound infections. Obtaining a good culture requires that a semi-quantitative swab collection also be taken. The gold standard is quantitative biopsy, but this procedure is invasive and expensive.

10. COMPLICATIONS

The prevention of complications in pressure injuries begins with injury recognition. As soon as an injury is diagnosed, pressure relief and prevention and control of infection begin. Without proper care and treatment, a superficial stage 1 or 2 injury can evolve to a more serious and severe stage 3 or 4 injury. The near-term complications of pressure injuries include cellulitis, abscess, sepsis, and osteomyelitis. Indolent, non-healing deep injuries may eventually lead to malignancy.

CELLULITIS

Cellulitis can occur when infection spreads from the site of the injury to a deeper layer of skin, causing acute infection of connective tissue and possibly leading to sepsis. Staphylococci and streptococci are the most common causative agents of cellulitis.

Physical exam may reveal signs of infection, including erythema, edema, warmth, and possibly increased drainage. Lymphadenopathy may be present near the area of cellulitis. Diagnosis may be confirmed by blood culture, complete blood count (CBC), or fluid or exudate culture from the affected area.

Treatment usually involves a course of antibiotics. Analgesics may be necessary if the area is painful.

SEPSIS AND SEPTIC SHOCK

Sepsis is one of the most serious complications of a pressure injury that has become secondarily infected. Sepsis occurs when bacteria or the products of bacterial infection in the wound enter the bloodstream, producing a systemic inflammatory response syndrome (SIRS) marked by fever, hemodynamic changes, and organ dysfunction. The SIRS designation is not specific to infection and may be used in reference to any serious, ongoing inflammatory process resulting in end-organ damage and multisystem failure. While sepsis is a common and important cause, SIRS may be encountered in association with noninfectious insults such as trauma, burns, pancreatitis, anaphylaxis, adrenal insufficiency, and pulmonary embolism.

In 2014, a task force of the European and American societies of critical care medicine was convened to reexamine current concepts and definitions of sepsis and septic shock in light of improved understanding of the pathophysiology and management of sepsis. The task force concluded that previous definitions are limited by excessive focus on inflammation, and that the SIRS criteria have inadequate specificity and sensitivity for defining sepsis. The task force report and new, consensus definitions for sepsis and septic shock were published in 2016 [93].

Sepsis is now defined as life-threatening organ dysfunction caused by a dysregulated host response to infection [93]. This definition emphasizes the loss of adaptive homeostasis in response to infection and the potential lethality of infection when any degree of organ dysfunction is present. Even modest organ dysfunction has been found to confer a mortality risk in excess of 10%, hence the importance of urgent assessment and prompt treatment [7]. The presence and extent of organ dysfunction can be assessed with various scoring systems that rely on clinical and laboratory parameters, such as the following [7,94,95]:

- Acute lung injury: a ratio of arterial oxygen tension to fraction of inspired oxygen of 280 or less

- The presence of a metabolic acidosis, e.g. lactate >2 mmol/L

- Oliguria (urinary output of less than 0.5 mL/kg body weight/hour for at least two hours in a patient with a urinary catheter in place)

- Coagulation abnormalities (international normalized ratio [INR] >1.5)

- Thrombocytopenia (platelet count <100,000/mcL)

- Bilirubin >2 mg/dL

- An acute alteration in mental status

The scoring system currently utilized in most critical care units is the Sequential Organ Failure Assessment (SOFA) score, which grades abnormality by organ system and accounts for clinical interventions [95]. A higher SOFA score is associated with an increased probability of mortality. Organ dysfunction can be identified by an acute change in SOFA score ≥2 points consequent to the infection. This score reflects an overall mortality risk of approximately 10% in a general hospital population with suspected infection [7].

Working from a model derived from a large inpatient data base, the sepsis task force was able to identify, and validate, a simple "bedside" clinical measure that can be used to identify which patients with suspected infection are at risk for developing sepsis. Designated the qSOFA (for quick SOFA), this measure consists of three elements [93,96]:

- Respiratory rate ≥22/min

- Altered mentation (Glasgow Coma Scale <15)

- Systolic blood pressure ≤100 mm Hg

The data analysis demonstrated that patients with infection who are positive for two or more of these elements are likely to have a prolonged ICU stay (i.e., three or more days) or die in the hospital.

Physicians and nurses can employ the qSOFA in the office, emergency department, or inpatient facility to quickly identify which patients with an infection (e.g., pressure injury) are on the clinical threshold of sepsis and thus at risk of further clinical deterioration. The task force suggests that positive qSOFA criteria be used to prompt clinicians to further investigate for organ dysfunction, to initiate or escalate therapy as appropriate, and to consider referral to critical care [7].

Septic shock is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality. Within the clinical construct of sepsis, the patient with septic shock can be identified by the presence of the following two criteria [93]:

- Persisting hypotension requiring vasopressors to maintain mean arterial blood pressure (MAP) ≥65 mm Hg

- Blood lactate >2 mmol/L despite adequate volume resuscitation

The hospital mortality rate for patients meeting these criteria is in excess of 40%, or four times greater than for patients with sepsis [7].

For patients with an infected pressure injury, the confirmation and etiology of sepsis is determined by blood cultures, wound culture and Gram staining of exudate and/or tissue obtained from the base of the injury, and/or by selective application of the polymerase chain reaction.

Antimicrobial Therapy

In addition to fluid and metabolic resuscitation, treatment of sepsis requires parenteral antibiotics and, when necessary, surgical debridement and/or drainage of deep tissue suppurative fluid collections. Vasopressors and inotropic therapy may be necessary to restore adequate blood pressure and perfusion. The initial choice of antibiotics will depend on the most likely pathogens associated with the source of infection as well as the prevalent micro-organisms in the local community and health facility. The anticipated susceptibility profile of prevalent local pathogens and the ability of the antibiotic to penetrate to the source of the infection should also be considered. A combination of drugs with activity against all likely pathogens should be administered initially, but the regimen should be reassessed in light of culture results, the goal being to identify a single, narrow-spectrum antibiotic that will best control the infection [97]. A common approach is to initiate empiric therapy with a carbapenem or extended-spectrum penicillin/beta-lactamase inhibitor (e.g., ticarcillin/tazobactam) to cover gram-negative enteric bacilli, anaerobes, and Pseudomonas, often in combination with vancomycin to cover Staphylococcus aureus pending culture results.

Proper support for organ failure is indicated for patients with severe sepsis, and sedation, mechanical ventilation, and analgesia are often required in late-stage disease. Adequate nutrition (usually administered parenterally) and glucose control are necessary. The patient should be stabilized prior to restarting injury treatments.

BONE AND JOINT INFECTIONS

When the infection from a full-thickness tissue injury, generally stage IV, spreads to bone and joints, periosteitis, septic or infectious arthritis, or osteomyelitis can result. If the injury crater can be probed to bone (i.e., one can see or palpate bone at the base of the crater), then the likelihood of bone infection approaches 80%. Confirmation of the diagnosis relies on imaging studies and needle aspiration or bone biopsy for histopathology and culture.

Plain bone radiographs are useful for diagnosing chronic osteomyelitis when infection has been present for many weeks; however, false-positive or false-negative results are common. Computed tomography scans are helpful for demonstrating fluid collections, bony erosion, and joint involvement. Radionuclide bone scanning (with technetium methylene-99m diphosphate) can be diagnostic, but it only has a moderate degree of sensitivity and specificity. Magnetic resonance imaging is the most sensitive and specific imaging modality for identifying the presence of osteomyelitis.

Bone biopsy is the definitive diagnostic test. Bone biopsy for histologic examination and culture not only verifies bone involvement but also helps to establish the bacterial etiology and antibiotic sensitivities upon which optimal treatment depends.

Treatment

In the presence of underlying osteomyelitis, satisfactory healing of the pressure injury is usually not possible unless the bone infection is eradicated. This requires parenteral followed by oral antimicrobial therapy for a minimum of six to eight weeks, combined, if necessary, with surgical debridement of necrotic bone. Any surgical approach to (presumed) infected bone, whether needle aspiration, biopsy, or debridement, should include submission of bone specimens for culture.

In the surgical management of stage 4 injury cases with little or no overt clinical or radiographic sign of bone infection, submission of bone specimens for culture is useful for identifying early, limited osteomyelitis and thus the need for post-operative antimicrobial treatment. Examples are cases requiring partial ostectomy or ablative surgery of stage 4 injuries with resection of bone from the base of the injury crater.

MALIGNANCY

Long-standing pressure injuries can develop into malignant tumors called Marjolin ulcers. These tumors were named for surgeon Jean-Nicolas Marjolin, who first described the condition in 1820 [98,99]. They are very aggressive ulcerating squamous cell carcinoma found in the area of injuries and other long-standing indolent wounds. It can develop many years after the initial trauma.

The first sign of Marjolin ulcer is a change in the character of the wound. Drainage increases, and the odor of the drainage becomes putrid. In some cases, there is frank bleeding. Diagnosis is made after histologic examination of a specimen removed from the injury, usually at the time of a flap closure. Confirmation of the diagnosis requires a preoperative tissue biopsy; wedge biopsy is the method of choice.

Excision of the lesion with 1-cm margin is required. Oncologic assistance is also necessary in the management of this condition, and extensive treatment is often necessary.

GAS GANGRENE

Gas gangrene is a rare but serious form of Clostridium perfringens infection. These obligate anaerobes release gas and harmful toxins that can result in gas gangrene, sepsis, and septic shock. The most common symptoms are severe pain and rapid swelling of the skin around or near the injury.

Surgical debridement is usually necessary [100]. In very serious cases, excision with amputation is required to prevent spread of the infection [101]. Penicillin is administered as adjuvant therapy. Hyperbaric oxygen therapy is effective in growth inhibition and killing C. perfringens [102,103]. However, results of a Cochrane review could not determine the efficacy and safety of hyperbaric oxygen therapy for the treatment of gas gangrene [101].

NECROTIZING FASCIITIS

People with stage 3 and 4 injuries are at a risk for contracting the rapidly progressive infection necrotizing fasciitis. Necrotizing fasciitis is defined as a group A streptococcal infection of the fascia with accompanying necrosis of the subcutaneous tissues. It is an uncommon consequence of pressure ulceration [104,105].

Initial signs of this condition are fever, pain, and massive swelling. Visual and microscopic evaluation of the tissues confirms the diagnosis. Emergency treatment is required, and aggressive surgical debridement is vital to prevent spreading [106]. In some cases, early amputation of affected tissues and maximum intensive care treatment (e.g., in case of sepsis) are required [106].

As soon as necrotizing fasciitis is suspected, antibiotics should be started. A combination of intravenous antibiotics, usually clindamycin, vancomycin, and penicillin, is administered. One review recommended aminopenicillin plus sulbactam in combination with clindamycin and/or metronidazole as initial treatment [106]. Hyperbaric oxygen therapy can also be effective.

RECURRENCE

Recurrence of a pressure injury is a common complication of treatment. As noted, as many as 90% of patients with a healed wound will experience a recurrence [6,9]. Compared to normal tissue, scar tissue has lower tensile strength, poor blood supply, and poor ability to withstand trauma, making it vulnerable to recurrent episodes. If an injury recurs at the same site within four months of the initial injury, it is likely due to incomplete healing rather than a true recurrence [107]. Risk factors for recurrence include male sex, younger age, African/black race, lower socioeconomic status, nursing home residence, and previous pressure injury surgery [107].

11. TREATMENT OF COMORBIDITIES

Comorbid conditions both increase susceptibility to pressure injuries and impair the healing process. Therefore, comorbid conditions should be addressed as part of the overall treatment plan. Common comorbid conditions in patients with pressure injuries include:

- Diabetes

- Incontinence

- Peripheral vascular disease (PVD)

- Hypotension and hypoxia

- Dehydration, poor nutritional status, or malnutrition

- Cancers

- ESRD

- Depression and cognitive impairment

Even with the best medical care and preventive measures, pressure injuries can occur [108]. It is unclear which combination of comorbid conditions can lead to injury formation, but changes in skin with comorbidities are believed to result in injuries. Recent acute illnesses or acute exacerbation of comorbid conditions may cause lethargy and reduced mobility, increasing the risk of pressure injuries. In patients with comorbid conditions, special attention to the drugs being used is necessary. Chemotherapeutic agents, systemic corticosteroids, and NSAIDs can impair healing.

DIABETES

In patients with long-standing diabetes, both macro- and microvasculature can be severely damaged, particularly if the disease is poorly controlled. Diabetes also causes neuropathy, and the resultant loss of sensation and protective reflexes is a risk factor for pressure injury progression. Patients with diabetes have elevated glucose levels that result in rigid blood cell walls and decreased blood flow through microvasculature. The disease also impairs oxygen release by the hemoglobin, resulting in hypoxia. Leukocytes have less effective chemotaxis and phagocytosis, which makes the patient susceptible to infection. Diabetics are prone to fungal rashes that can result in perineal irritation and skin breakdown. Impaired granulocyte function inhibits wound healing. All of these factors contribute to the increased risk of pressure injury development in a patient with diabetes.

The aim of diabetes management is to keep blood glucose levels close to normal (i.e., glycosylated hemoglobin less than 7%). Usually, pharmacotherapy and/or insulin therapy is necessary for optimum disease control. In addition, eating habits should be modified and physical activity should be increased.

URINARY AND FECAL INCONTINENCE

Approximately 10 to 13 million Americans have transient or chronic urinary incontinence [109]. It is also estimated that 50% to 70% of patients with urinary incontinence fail to seek medical intervention or treatment [109]. The high prevalence of incontinence among certain populations (e.g., nursing home residents) makes this an important factor in pressure injury development and healing.

Extended exposure of skin to urine and feces can result in breakdown, making the patient more susceptible to injuries [110]. Urinary incontinence results in maceration, which causes increased skin irritation and fragility. Coliform bacteria and C. difficile contamination of existing wounds can lead to severe infections.

The treatment of these patients is dependent on determining the incontinence etiology. General approaches include regular assessment of skin; hydration and infection should not be ignored. Patients should be checked for incontinence every two hours. For patients who are cooperative and aware of bladder filling, a toilet program should be instituted, including planned voiding every two hours. For patients who are uncooperative or unaware of bladder filling, consider the use of absorptive products or condom catheters for men. It is important to use diapers and underpads that wick moisture away from patients' skin. Incontinent patients should be cleaned as soon as possible after soiling using specialized incontinence skin cleansers or soaps.

For patients with severe diarrhea, all potential causative factors should be explored and addressed. A rectal pouch may be useful for these patients. In cases of chronic incontinence, an every other day suppository or enema may be considered. In addition, barrier ointments help protect the skin from incontinent episodes. If used, apply a thick coat of ointment, wipe off the soiled top layer, and apply another layer. Do not clean off the paste to skin level when bathing or cleaning.

PERIPHERAL VASCULAR DISEASE

PVD is an important contributory factor in the development of vascular injuries, particularly diabetic foot ulcerations (as the cause of 10% to 30% of all cases) [111]. The wounds of patients with severe PVD heal poorly as a result of inadequate blood supply, and minor trauma or pressure often leads to ulceration.

When conducting a thorough physical examination, signs and symptoms consistent with PVD should be documented and ankle-brachial index or pulse volume recordings should be recorded. The ankle-brachial index is not specific in patients with advanced calcific atherosclerotic disease, and for patients with this condition, photoplethysmography or magnetic resonance angiogram is more accurate [112,113].

Treatment of PVD first relies on assessment and management of modifiable risk factors (e.g., smoking, physical activity). Pharmacologic management with antiplatelets is the gold standard for patients whose disease is not well controlled with lifestyle changes [114]. In addition, comorbidities should be treated aggressively.

HYPOTENSION AND HYPOXIA

Prolonged hypotension and hypoxia can cause tissue hypoperfusion, especially in anatomical locations already at risk for developing injuries. Patients with septic shock have microvascular endothelial dysfunction, which results in tissue hypoxia despite adequate oxygenation [115,116]. Tissue hypoxia and hypoperfusion may also be caused by hemorrhagic shock. Anemia and low cardiac output limit the blood's oxygen-carrying capacity and perpetuate tissue hypoperfusion. It is necessary to check vital signs, CBC, blood gas, and echocardiogram and manage accordingly.

GASTROINTESTINAL DISORDERS AND MALABSORPTION

As discussed, optimal nutrition is important for the prevention and treatment of pressure injuries. Therefore, intestinal diseases and acquired disorders that adversely affect nutrient absorption should be identified and treated as part of a management plan. Conditions like celiac disease, Crohn disease, and gastrointestinal malignancy often lead to malabsorption and micronutrient deficiencies. C. difficile colitis can cause severe diarrhea and hypoalbuminemia, making patients nutritionally and hemodynamically compromised. Patients who have undergone surgical bowel resections and fecal diversion are also at risk for malabsorption, fluid depletion, and electrolyte deficiency.

In addition to correction of nutritional deficiencies, the primary cause of malabsorption should be identified and treated. The plan of care will include interventions to increase nutritional intake, keeping in mind that the patient's and family's preferences play an important role in establishing a diet plan.

MALIGNANCY

Malignancy often leads to cachexia, a syndrome characterized by weight loss, malnutrition, weakness, and anemia. However, there is limited research exploring the link between pressure injuries and cancer [117]. Radiation therapy can cause dermatitis and desquamation and increase the risk for skin breakdown. Both the malignancy and associated treatments may cause immunosuppression and increase the likelihood and severity of infections.

Patients with cancer who are also experiencing skin breakdown should be assessed for nutritional status, and medications may be prescribed to combat the anorexia associated with chemotherapy. Optimum skin care, particularly in areas affected by radiation therapy, is a necessity.

END-STAGE RENAL DISEASE

Severe uremia associated with ESRD necessitates the use of dialysis to remove uremic toxins and prevent or control complications, and pruritus and xerosis are common in these patients. Malnutrition and dehydration are also risks. Dietary management of patients with ESRD should be aimed at control of electrolytes (including calcium, phosphorus, and potassium), prevention of malnutrition, and maintenance of acceptable fluid volume status.

DEPRESSION

The National Institute of Mental Health estimates that 8.4% of adults in the United States are suffering from depression, and major depression is the leading cause of disability worldwide [118]. Depressed patients often have little interest in self-care and nutrition, both of which may predispose an individual to pressure injuries [15]. Pressure injuries have also been found to contribute to depressive symptoms [119]. Patients should be regularly assessed for depression or other psychologic illnesses and referred to mental health care.

COGNITIVE IMPAIRMENT

Loss of cognition is associated with increased risk for pressure injuries, and impaired mental status leads to a lack of awareness of discomfort or pressure and may be associated with incontinence. The ability to respond appropriately or to inform others of the need for assistance may be lost completely. As such, these patients often require intensive care.

12. ADVANCES IN PRESSURE INJURY CARE

Research and technical innovations are producing sophisticated technology and analytic devices to diagnose, prevent, and treat pressure injuries. These new innovations are changing the way injuries are cared for and prevented in a variety of settings.

REPOSITIONING ALERTS

Studies have shown that patients with less nocturnal periodic movements are at risk for pressure injuries, but sleeping patients may be unaware of their lack of movement [120]. Alert systems have been implemented to remind staff to reposition the patient every two hours. Because repositioning is one of the basic hallmarks of pressure injury prevention, alerts may help address this risk factor better.

DETECTION

Early detection is of utmost importance in pressure injury management. Advanced technology and devices can be used to achieve better sensitivity and specificity in the diagnosis of injuries. These techniques include laser Doppler, visible and near-infrared spectroscopy, ultrasound, and pulse oximetry [121]. Each of these approaches ascertains clinical parameters associated with blood flow and hemoglobin concentration, and combining such measures with clinical information allows for a high degree of sensitivity and specificity in identifying impending chronic wounds in patients with any skin color [121].

DOCUMENTATION

New methodologies for documenting and measuring wounds can help both with monitoring treatment and preventing legal complications. Highly advanced computerized documentation is being used by many organizations. Techniques are now available to thoroughly assess the geometric, physiologic (i.e., pressure and degree of wound perfusion), and biochemical (i.e., concentrations of various enzymes involved in tissue degradation and healing) aspects of the wound.

Electronic records and images are preferred by many institutions. The role of wound photography is growing and is a vital aspect of monitoring response to treatment and in defending against possible future litigation. Most home health agencies in the United States include wound photography as part of the patient's medical record [35].

ULTRASOUND

Ultrasound has been explored as a diagnostic and monitoring tool. High-frequency ultrasound provides greater resolution than other ultrasound techniques, but the depth of penetration of the sound waves is less. Therefore, it is ideal for imaging near-surface pathology. High-resolution ultrasound can easily detect the fluid content of tissue and measure skin thickness. More research is necessary to determine the efficacy and cost effectiveness of ultrasound for the routine care of pressure injuries.

SKIN SUBSTITUTES OR GRAFTS

Although the available skin substitutes are not perfect, they do offer benefits when treating pressure injuries, particularly those resistant to healing. Research in the field of skin tissue engineering focuses on improving the skin barrier properties and the structural interaction of the epidermal and dermal equivalent of composite grafts. There are two types of bioengineered skin replacements available: biosynthetic skin substitutes and skin grafts.

Biosynthetic skin substitutes are developed without allogenic cells and consist of a mesh coated with a dermal analogue (bilayer) or an acellular dressing (monolayer). They act as starting points to promote ingrowth of tissue in the wound. The bilayer options also include a removable silicone layer that functions as a protective dressing.

Skin grafts may be categorized as xenografts, autografts, or allografts. A xenograft is derived from a non-human source, usually porcine skin. An autograft is a graft taken from the patient, while an allograft is transplanted from a genetically non-identical individual, often from a cadaver donor. Grafts may be further identified as dermal or epithelial/epidermal (or both) and as cultured or processed. Within these categories, there are several specific options, each with their own benefits and drawbacks [122]. It has been suggested that the properties inherent to skin grafts, such as the presence of hair follicles, may make them a good option to accelerate wound healing [123]. Selection of the best option is dependent on the features of the wound, the goals of treatment, and patient preferences.

GENE THERAPY

Gene therapy has a tremendous potential, but use of the technology in the treatment of pressure injuries is still in its infancy. Gene therapy has been proposed to accelerate wound healing and also to reduce healing complications such as keloid formation or chronic ulceration.

Genetically modified skin grafts have a potential use for treatment of large wounds. Smaller wounds may be amenable to in vivo delivery of genetic material using a variety of approaches including gene injection, gene gun, microseeding, and liposomal gene delivery. The preclinical studies of genetically modified skin grafts are promising, but more tests are necessary to determine the effectiveness of this treatment option [124,125].

NEGATIVE PRESSURE WOUND DEVICES

Negative pressure wound devices provide an environment that resolves edema and hematoma and results in increased local perfusion. Newer negative pressure wound devices are smaller and more portable than earlier devices, and some deliver continuous subatmospheric pressure to the wound bed to promote healing. It should be noted that these devices have been associated with extensive bleeding, particularly in patients with blood vessel grafts in the leg, with breastbone or groin wounds, or who are receiving anticoagulant therapy [126]. Hemorrhage may also occur when dressings attached to the tissues are removed.

GROWTH FACTORS AND BIOLOGIC WOUND PRODUCTS

Biologic wound products accelerate healing by augmentation or modulation of inflammatory mediators. Growth factors that hold great promise in wound healing include eicosanoids, prostaglandin E1, cytokines, and interleukin-1.

OTHER TREATMENT MODALITIES

Lasers may also accelerate the process of tissue repairing [127]. The lasers appear to simulate fibroblastic activity, although the mechanism is not yet fully understood.

Nanoparticles containing chitosan have been shown to have effective antimicrobial activity against Staphylococcus saprophyticus and Escherichia coli [127]. These materials could be used to prevent infection and facilitate wound healing.

Researchers have shown that a novel peptide (UN3) created by the combination of two naturally occurring peptides found in platelet-rich plasma stimulates wound vascularization and promotes epithelial proliferation. This could lead to new treatments for pressure injuries [128]. The use of novel peptides derived from platelet-derived growth factor (PDGF-BB) also shows promise for wound healing and treatment [129]. PDGF stimulates bone cell replication and DNA synthesis.

Electrical stimulation may also accelerate healing in pressure injuries, but its effect on time to complete healing is uncertain compared with no electrical stimulation [130,131]. Free radical scavengers and special drug delivery systems can also be effective in prevention of injuries [132,133,134].

13. MEDICO-LEGAL ASPECTS OF INJURY CARE

Pressure injuries are the second most common medicolegal claim after wrongful death, resulting in more than 17,000 lawsuits annually in the United States [135]. Results of a retrospective study published in 2019 examined 141 cases related to pressure injuries over a 32-year period from 1987 to 2019 [136]. Of the 141 cases, 75.9% were for negligence and 22.7% were for malpractice. Hospitals were listed as the defendant 61.7% of the time, nursing homes 31.2% of the time, and individual providers 7.1% of the time. Hospitals lost 63% of the cases brought against them, nursing homes lost 75%, and individual providers lost 20%. Hospitals paid out approximately $1.6 million to plaintiffs, nursing homes $4 million, and individual providers an average of $400,000 [136].

As litigation is becoming more common, adherence to established standards of care is very important and has legal implications [137]. Some experts have suggested that if institutional neglect is responsible for development of pressure injuries, caregivers could be liable to criminal prosecution.

AVOIDABLE VERSUS UNAVOIDABLE INJURIES

Federal law establishes standards for long-term care facilities [138]. Based on the comprehensive assessment of a resident, the facility must ensure that 1) a resident who enters the facility without pressure sores does not develop pressure sores unless the individual's clinical condition demonstrates that they were unavoidable; and 2) a resident having pressure sores receives necessary treatment and services to promote healing, prevent infection, and prevent new sores from developing.

As noted, despite best patient care and treatment, not all pressure injuries are avoidable [139]. In long-term care, the NPIAP defines an unavoidable injury as one that occurs even though "the facility had evaluated the individual's clinical condition and pressure injury risk factors; defined and implemented interventions that are consistent with individual needs, goals, and recognized standards of practice; monitored and evaluated the impact of the interventions; and revised the approaches as appropriate" [140]. In addition to establishing the definition for long-term care facilities, in 2014 the NPIAP sought to establish consensus (80% agreement among conference delegates) on whether pressure injury development may be unavoidable in some individuals and whether there is a difference between pressure injuries and end-of-life skin changes. Unanimous consensus was reached for the following statements [141]:

- Most (but not all) pressure injuries are avoidable.

- Comorbid conditions can contribute to unavoidable pressure injuries.

- Some situations render pressure injury development unavoidable, including:

- Hemodynamic instability worsened by physical movement

- Poor nutrition/hydration status and/or advanced directive that prohibits artificial nutrition/hydration

- Pressure redistribution surfaces cannot replace turning/repositioning

- Skin cannot always survive even when pressure from external body skin is alleviated

In light of the significant changes to pressure injury prevention in acute care hospitals brought about by the COVID-19 pandemic, the NPIAP additionally published position statements on pressure injuries that develop during COVID-19 crisis situations in these healthcare settings [141].

Facilities should institute adequate measures to prevent wounds, and in the case an injury develops, staff should respond appropriately to prevent worsening of the wound. Wounds detected in the early stages have a greater chance of cure than later stage wounds that are infected or necrotic. Therefore, regular assessment and early intervention are required for all injuries, avoidable or not. The presence of risk factors, including comorbidities, inability to maintain adequate nutrition and hydration status (e.g., if an advance directive prohibits artificial feeding), certain drugs, and immobility, is an indicator of avoidability. After assessment of risk factors, the next step is to ascertain if the response was timely according to documentation of all interventions. If any skin ulceration develops in spite of timely, appropriate interventions, the injury may be considered unavoidable.

DETERMINATION OF NEGLECT

Suspicion that improper medical care resulting in the development and/or worsening of a pressure injury requires a full, document-intensive investigation. Because many factors can be indicative of medical neglect, each domain of care should be assessed (Table 8). Furthermore, the best defense against a claim of neglect is complete documentation of appropriate care.

Table 8: FACTORS LEADING TO A DETERMINATION OF NEGLECT

Inadequate prevention

Poor documentation

Inadequate nutrition

Inadequate medical care

No family notification

Poor care planning

Wound severity and outcome

Source: Compiled by Author

New or worsening pressure injuries are generally due to poor administrative organization, understaffing, and poor training. The medico-legal implications of proper care cannot be overlooked, as those injuries are responsible for a significant proportion of healthcare litigation.

Medical Record

The medical chart should be examined to determine the level of care planning, assessment, and interventions. Wound neglect is usually associated with improper treatment, inadequate nutrition, and/or poor survey results.

Family diaries, stage surveys, in-service records, complaint files, minutes of quality assurance meetings, and photographs can also be helpful for identification of deviations from standard injury care.

Wound Documentation

Documentation of pressure injury care must be timely and detailed. Regular and consistent descriptions of the injury should be documented, as should responses to treatment. Improper, irregular, or "late entries" are absolutely impermissible and unacceptable.

In patients with multiple injuries, progression of each wound should be documented and tracked. With the growing awareness of the possibility of litigation in wound care, many facilities have instigated a policy of photo documentation. Wounds present on admission are photographed, and some facilities require serial photographs to track wound progress and status at the time of discharge. Signed consent is required before wound photographs can be taken, and in most instances, the photographs become a permanent part of the patient's medical record.

Nutritional Assessments

It has been found that 30% to 85% of nursing home residents are malnourished and 30% to 50% are considered underweight [112]. Pressure injury treatment requires proper nutritional assessment and intervention during every stage. Weight loss, lab results, protein consumption, and vitamin levels should be documented, as should attempts to address abnormalities. If tube feeding is indicated, it should be discussed with the family prior to initiation.

Treatment Records

Treatment administration records should be examined to ensure that treatments were carried out per orders. Documentation should also include staffing records and time-sheets. Dates and times should always be included.

Minimum Data Sets and Care Plans

Minimum data sets are required for all residents of skilled nursing facilities. Improper and inaccurate entries in the minimum data sets indicate a facility with under-staffing and disorganized structure providing poor treatment to the resident. Scrutiny of this document can lead to litigation.

14. EDUCATING PATIENTS

A vital component of any pressure injury program is patient/family education, with an overall goal of decreasing the incidence of injury development or recurrence. If possible, pressure injury prevention should not be a passive process for the patient and his/her family members. Rather, it should be a dialogue in which the patient and family feel comfortable asking questions and discussing problems. Patients should have as much control as possible in the plan of care. Empowerment is very important in maintaining the patient's physical and emotional well-being, and the plan of care should be explained thoroughly to cognitively aware patients and/or their family. It is important for everyone involved to appreciate that the prevention of pressure injury formation is a lifelong process [142].

At the same time, it is necessary to evaluate the patient's/family's existing knowledge regarding pressure and pressure injuries. Healthcare professionals should show patients what they can do to facilitate pressure relief (e.g., how to make small position changes while in the chair). If possible, teach patients how to do simple range-of-motion exercises. Take time to train the patient as often as is appropriate; not everyone will absorb the information the first time they hear it [4]. It is important not to let noncompliance or a bad attitude from the patient or family discourage the teaching process. The subject should be approached as often as is reasonable. Include the family members and caregivers in the instructions; as well as assisting with care, they can encourage compliance. All efforts at patient and family/caregiver education should be documented, along with the patient's response (both verbal and behavioral).

Different methods of teaching, such as photographs, videos, charts, diagrams, and written materials in the patient's native language, should be used. Education should be reinforced regularly and consistently [143]. The information provided to patients and/or their families should be specific to the individual treatment plan and goals.

Patient education programs should include all of the following areas:

- Etiology of pressure injuries

- Reduction of risk

- Reduction of friction and shear

- Skin protection and inspection

- Importance of nutrition

- Proper and safe cleansing procedures and agents

- Procedure for recurrence(s)

- Management approaches

- Proper dressing change procedure

PATHOGENESIS OF PRESSURE INJURIES

Patients should be provided information about factors involved in pressure injury development. The role of pressure, friction, shear, and moisture in the development of injuries should be explained. Other conditions that can impact pressure injury development should be outlined, including:

- Immobility (partial or total)

- Excessive moisture and/or incontinence

- Poor local or systemic circulation

- Uncontrolled diabetes

- Severe trauma

- Dehydration

- Hypoxia

- Malnutrition

- Sepsis

- Previous history of pressure injury

REDUCTION OF RISK

Pressure reduction techniques should be thoroughly explained. Proper use of mattresses, cushions, and overlays and the placement of pillows, heel protectors, and wedges are essential. The role of repositioning and turning of the patient should be stressed. If the patient will be sitting in a chair for a long period of time, pressure release tactics should be included. Repositioning should be done every one to two hours, depending on the patient's condition [49].

REDUCTION OF FRICTION AND SHEAR

Patients and/or caregivers should have a clear understanding of measures to decrease friction and shear. Education should include the proper body alignments that should be maintained when sitting in a chair or lying on a bed. The importance of using lifting devices for repositioning or transferring should be stressed.

SKIN INSPECTION AND PROTECTION

Careful skin inspection is paramount in the care of pressure injuries. The patient or caregiver should carefully inspect the skin for new openings or breaks in the skin at every repositioning. Any discoloration or redness of the skin that does not resolve within 30 minutes after changing position should be reported.

Maintaining skin cleanliness and moisturizing frequently can protect skin integrity. The skin should be cleaned with water and a gentle soap, preferably a pH-balanced cleanser. Alkaline products remove skin lipids, which increases water loss and weakens the barrier function of the skin [2]. Avoid hot water for bathing and scrubbing or using harsh cleaning agents. A soft cloth should be used to pat rather than rub the skin dry. Thromboembolic deterrent hose should be removed when bathing, and the nurse or physician should be notified of any redness, discoloration, or skin breakdown.

It is important to individualize the frequency of skin cleansing based on the patient's age, skin texture, and dryness or excessive oiliness of the skin. A daily bath may not be needed for all patients.

The epidermis is about 30% water, but through a process called trans-epidermal water loss, skin can lose its natural moisture. Without sufficient moisture, skin can become dry, brittle, and vulnerable to breakdown [10]. Therefore, products should be used to keep the skin supple. Emollients, such as mineral oil, petrolatum, and lanolin, penetrate into the stratum corneum to increase the lipid component and add softness to the skin. The oil film on the skin surface also prevents water loss and helps to rehydrate the stratum corneum [10]. Moisture barriers such as dimethicone can prevent water loss and help to retain lipids and water within the skin cells [10].

Humectants, such as glycerin, urea, and lactic acid, increase the water content of the stratum corneum by pulling water from the environment. All moisturizers should be applied to clean, slightly moist skin. Special attention should be paid to bony prominences, heels, ears, and the back of the head.

NUTRITION

Adequate nutrition is an essential area of patient education, as malnutrition makes individuals susceptible to the development of pressure injuries and at increased risk for infections, including sepsis, necrotizing fasciitis, and gangrene. Patients must also understand that adequate hydration is essential to improve tissue perfusion and excreting waste products. Patients/caregivers should make sure they comply with dietitian recommendations for diet, adequate fluid intake, and nutritional supplements.

PROCEDURE FOR RECURRENCES

Patients should be advised to take the following actions should a pressure injury develop:

- Increase the frequency of repositioning and turning.

- Note the size, location, odor, color, and drainage of the wound and adjacent tissue.

- Notify the physician immediately about this new development.

- If the patient is receiving home care services, the home health nurse should be notified immediately.

MANAGEMENT OF PRESSURE INJURY

After a treatment plan is set, all aspects should be explained to the patient or caregiver again. Key education points include:

- Products being used for wound prevention or healing

- Where to procure dressings and pressure redistribution surfaces

- Signs and symptoms of pressure injury deterioration

- The importance of compliance to the established plan

Patients should be advised to look for new necrotic tissue in the wound bed, wound drainage with odor, and erythema and induration around the injury. If a clean wound enlarges or becomes deeper, the patient should be instructed to contact his or her physician immediately.

PROPER DRESSING CHANGE PROCEDURE

Proper dressing change technique should be demonstrated. The patient/caregiver should be able to change the dressing without any assistance from the supporting staff, and clean technique should be used. Hand washing, use of gloves, and infection prevention should all be a part of basic patient education.

15. CONCLUSION

Pressure injuries are a common but preventable condition frequently seen in elderly individuals and those with comorbid conditions. In the United States, the incidence of pressure injuries in critical care patients ranges from 12% to 33%, depending on treatment setting [2].

Pressure injuries are a major psychologic, physical, and social burden to patients and often result in significantly decreased quality of life. In addition, they are a major source of healthcare expenditures. The healthcare costs related to the care of patients with pressure injuries exceeds $11 billion annually in the United States [9].

Evolution of pressure injuries is multifactorial, and individuals with specific risk factors are more susceptible to injury development. Without proper care and treatment, superficial injuries progress to more serious deep tissue wounds, often with life-threatening complications. Satisfactory resolution of a well-established pressure injury is difficult, time-consuming, and costly; it is far better to prevent the injury in the first place. An interdisciplinary approach of creating a care plan that includes steps for the prevention of injuries is the best practice.

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Evidence-Based Practice Recommendations Citations

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2. National Pressure Ulcer Advisory Panel, European Pressure Ulcer Advisory Panel, Pan Pacific Pressure Injury Alliance. Prevention and Treatment of Pressure Ulcers: Clinical Practice Guideline. 4th ed. Washington, DC: National Pressure Ulcer Advisory Panel; 2025. Available at https://internationalguideline.com/the-international-guideline. Last accessed April 28, 2025.