GKY22 • Nurses 2022

Table of Contents

GKY22 • Nurses 2022

How to Receive Credit

NetCE 4 Hour Course #94343 • Sepsis: Diagnosis and Management

94343 • Sepsis: Diagnosis and Management

1. INTRODUCTION AND DEFINITIONS

2. EPIDEMIOLOGY AND BURDEN OF SEPSIS

3. RISK FACTORS AND PREVENTION

4. PATHOGENESIS OF SIRS

5. PATHOPHYSIOLOGY OF SEPSIS

6. MANIFESTATIONS OF SEPSIS

7. DIAGNOSIS AND MANAGEMENT

8. PEDIATRIC CONSIDERATIONS

9. RECOVERY FROM SEPSIS

10. CONCLUSION

11. CASE STUDY

Works Cited

Evidence-Based Practice Recommendations Citations

NetCE 3 Hour Course #97000 • Implicit Bias in Health Care

97000 • Implicit Bias in Health Care

1. INTRODUCTION

2. DEFINITIONS OF IMPLICIT BIAS AND OTHER TERMINOLOGIES

3. MEASUREMENT OF IMPLICIT BIAS: A FOCUS ON THE IAT

4. THEORETIC EXPLANATIONS AND CONTROVERSIES

5. CONSEQUENCES OF IMPLICIT BIASES

6. DEVELOPMENTAL MODEL TO RECOGNIZING AND REDUCING IMPLICIT BIAS

7. CREATING A SAFE ENVIRONMENT

8. STRATEGIES TO PROMOTE AWARENESS OF IMPLICIT BIAS

9. INTERVENTIONS TO REDUCE IMPLICIT BIASES

10. ROLE OF INTERPROFESSIONAL COLLABORATION AND PRACTICE AND IMPLICIT BIASES

11. CONCLUSION

12. RESOURCES

Works Cited

NetCE 2 Hour Course #96102 • Frontotemporal Dementia

96102 • Frontotemporal Dementia

1. INTRODUCTION

2. EPIDEMIOLOGY OF FTD

3. PATHOGENESIS AND PATHOPHYSIOLOGY OF FTD

4. CLINICAL PRESENTATION

5. GENETICS AND FTD

6. MANAGEMENT OF FTD

7. PROGRESSION OF FTD

8. RESEARCH RELATED TO FTD

9. CASE STUDY

10. CONCLUSION

11. RESOURCES

Works Cited

Evidence-Based Practice Recommendations Citations

NetCE 6 Hour Course #96442 • Suicide Assessment and Prevention

96442 • Suicide Assessment and Prevention

1. INTRODUCTION

2. EPIDEMIOLOGY OF SUICIDE

3. PATHOPHYSIOLOGY OF SUICIDAL BEHAVIOR

4. SUICIDE AND SPECIAL POPULATIONS

5. RISK AND PROTECTIVE FACTORS FOR SUICIDE

6. IMMINENT SUICIDE

7. SUICIDE ATTEMPTS

8. SCREENING AND ASSESSMENT OF SUICIDE RISK

9. MANAGEMENT OF SUICIDAL PATIENTS

10. SUICIDE PREVENTION

11. SUICIDE SURVIVORS: TREATMENT AND RESOURCES

12. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

GKY22 • Nurses 2022

Patricia Lea, RN, DNP, MSEd, CCRN

John M. Leonard, MD

Alice Yick Flanagan, PhD, MSW

Lauren E. Evans, MSW

Ellen Steinbart, RN, MA

www.netce.com

Copyright © 2024 NetCE, All rights reserved.

GKY22 • Nurses 2022

Expiration Date: 05/31/2024

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.

94343 • Sepsis: Diagnosis and Management

Patricia Lea, RN, DNP, MSEd, CCRN

John M. Leonard, MD

www.netce.com

Copyright © 2021 NetCE, All rights reserved.

Severe sepsis and septic shock present the clinician with a difficult management situation. The patients are usually unstable and may rapidly progress to ARDS, MODS, and death. There are evidence-based guidelines available to assist in the diagnosis and treatment of these disorders. This course outlines some of the current recommendations and suggestions by the Society of Critical Care Medicine and other experts experienced in treating patients with these disorders.

Table of Contents

94343 • Sepsis: Diagnosis and Management

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 AND DEFINITIONS

2. EPIDEMIOLOGY AND BURDEN OF SEPSIS

3. RISK FACTORS AND PREVENTION

4. PATHOGENESIS OF SIRS

FIRST PHASE: THE LOCAL RESPONSE

SECOND PHASE: THE EARLY SYSTEMIC RESPONSE

THIRD PHASE: PROINFLAMMATORY EXCESS

FOURTH PHASE: EXCESSIVE IMMUNOSUPPRESSIVE RESPONSE

FIFTH PHASE: TRANSITION TO MODS

5. PATHOPHYSIOLOGY OF SEPSIS

MICROBE RECOGNITION

ENDOTOXINS AND OTHER BACTERIAL TOXINS

COAGULATION SYSTEM

6. MANIFESTATIONS OF SEPSIS

CARDIOVASCULAR

PULMONARY

CENTRAL NERVOUS SYSTEM

RENAL

GASTROINTESTINAL

HEPATIC

HEMATOLOGIC

7. DIAGNOSIS AND MANAGEMENT

MANAGEMENT OF SEPSIS

SUPPORTIVE THERAPY FOR SEPSIS AND SEPTIC SHOCK

SEPSIS BUNDLE

MANAGEMENT OF SEVERE CORONAVIRUS DISEASE 2019 (COVID-19) IN THE ICU

8. PEDIATRIC CONSIDERATIONS

9. RECOVERY FROM SEPSIS

10. CONCLUSION

11. CASE STUDY

POST-OPERATIVE DAY 3

POST-OPERATIVE DAY 5

POST-OPERATIVE DAY 8

POST-OPERATIVE DAY 10

Works Cited

Evidence-Based Practice Recommendations Citations

94343 • Sepsis: Diagnosis and Management

Education Category. Infection Control / Internal Medicine

Release Date. 06/01/2021

Expiration Date. 05/31/2024

Course Overview

Severe sepsis and septic shock present the clinician with a difficult management situation. The patients are usually unstable and may rapidly progress to ARDS, MODS, and death. There are evidence-based guidelines available to assist in the diagnosis and treatment of these disorders. This course outlines some of the current recommendations and suggestions by the Society of Critical Care Medicine and other experts experienced in treating patients with these disorders.

Audience

This course is designed for all healthcare professionals who work with patients who present with sepsis, including nurses and physicians.

Accreditations & Approvals

In support of improving patient care, 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 by the California Nursing Home Administrator Program as a provider of continuing education. Provider number 1622. 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 4 Interprofessional Continuing Education (IPCE) credit(s) for learning and change. NetCE designates this enduring material for a maximum of 4 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 4 ANCC contact hour(s). NetCE designates this continuing education activity for 3 pharmacology hour(s) for physician assistants. NetCE designates this continuing education activity for 3 pharmacotherapeutic/pharmacology contact hour(s). NetCE designates this continuing education activity for 4.8 hours for Alabama nurses. Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 4 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 4 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 continuing education activity is approved for 5 CE credits by the Association, and Associate members of AST of Surgical Technologists, Inc., for continuing education for the Certified Surgical Technologist, Certified Surgical First Assistant, and Associate members of AST. This recognition does not imply that AST approves or endorses any product or products that are included in the enduring materials. 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 4 credit hour(s). This course is approved by the California Nursing Home Administrator Program for 4 hour(s) of continuing education credit - NHAP#1622015-9406/P. California NHAs may only obtain a maximum of 10 hours per course. AACN Synergy CERP Category A. NetCE is authorized by IACET to offer 0.4 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: Alabama, Provider #ABNP0353, (valid through July 29,2025); Alabama, Provider #ABNP0353, (valid through July 29, 2025); 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; 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

The purpose of this course is to provide healthcare professionals with a current review and updated, evidence-based guidance for the diagnosis and management of sepsis and septic shock. The objective is to address knowledge gaps, enhance clinical skill, and enable effective strategies of collaborative care to improve patient outcomes.

Learning Objectives

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

1. Define the various stages of sepsis, and describe the history and incidence of sepsis relative to mortality.

2. Identify risk factors associated with the development and progression of sepsis.

3. Describe the pathogenesis of SIRS, including the five phases of development, and the pathophysiology of sepsis.

4. Anticipate and assess emerging organ dysfunction associated with septic shock.

5. Recognize clinical and laboratory parameters of sepsis, and implement a strategy for antimicrobial therapy and incremental resuscitation that incorporates fluids, inotrope-vasopressors, and the selective use of corticosteroids.

6. List the diagnostic criteria of suspected SIRS in the pediatric patient.

Faculty

Patricia Lea, RN, DNP, MSEd, CCRN, received a Bachelor of Science degree in Nursing in 1973 from Houston Baptist University in Houston, Texas. She returned to graduate school to complete a Master’s degree in Education, specifically Health Education, in 1996 from Baylor University in Waco, Texas, and a Doctorate in Nursing Practice in Executive Leadership in 2014 from American Sentinel University in Aurora, Colorado. Dr. Lea specializes in critical care nursing, with an emphasis on heart failure and sepsis. She started her career at the Houston Methodist Hospital in the cardiovascular ICU and opened an acute dialysis unit at what is now Baylor St. Luke’s Medical Center in the Houston Medical Center. Dr. Lea was a Cardiovascular Clinical Coordinator and Director of the Heart Failure Clinic at Hillcrest Baptist Medical Center in Waco, Texas. In 2004, Dr. Lea returned to Houston and was employed as a Senior Research Clinical Nurse Specialist at the Texas Heart Institute coordinating stem cell and cardiac stent trials. She is currently Associate Professor and Baccalaureate Program Director at the University of Texas Medical Branch School of Nursing in Galveston, Texas.

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, Patricia Lea, RN, DNP, MSEd, CCRN, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

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

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

Shannon E. Smith, MHSC, CST, CSFA

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 AND DEFINITIONS

Sepsis is a systemic pathophysiologic and clinical syndrome caused by infection and manifest by signs of inflammation, host immune response, and organ dysfunction. The causes of sepsis are myriad, and the scope of illness is broad. Most cases of sepsis syndrome arise from bacterial infection, but certain viral (e.g., Ebola and other hemorrhagic fevers) and fungal (e.g., candidiasis, histoplasmosis) infections induce a sepsis syndrome as well.

Infection may be defined as invasion of normally sterile host tissue by a micro-organism. Clinically, infection is recognized by the constellation of symptoms and signs that result from the host's immune response to an invading micro-organism. Bacteremia is defined as demonstrable evidence (e.g., by culture) of viable bacteria within the general circulation.

Historically, there has been some confusion and a lack of consensus with respect to the various stages of systemic infection and how best to manage patients along the spectrum of illness and complications induced by sepsis. This lack of consensus prompted the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) to convene a conference for the purpose of agreeing on definitions for sepsis and its sequelae. The ACCP/SCCM published their definitions in 1992 [1].

A second task force, international in scope, was convened in 2001. The purpose of this conference (sponsored by the ACCP, SCCM, the European Society of Intensive Care Medicine, the American Thoracic Society, and the Surgical Infection Society) was to modify, where appropriate, the original ACCP/SCCM definitions to reflect current understanding of the pathophysiology of sepsis. Although the signs and symptoms of sepsis were expanded to reflect clinical bedside experience, the task force found insufficient evidence to support alternative definitions of sepsis [2]. This international effort spawned the global Surviving Sepsis Campaign, comprised of 29 sponsoring clinical specialty societies that convene at regular intervals to review the clinical literature and provide evidence-based guidelines for management of severe sepsis [62,65].

Task force guidelines redefined sepsis as a systemic inflammatory response arising from known or suspected infection, leading to widespread tissue injury and manifested by two or more of the following conditions [1,2]:

- Fever (temperature greater than 38.3°C [100.6°F])

- Hypothermia (core temperature less than 36°C [96.8°F])

- Tachycardia (heart rate greater than 90 beats per minute in adults)

- Tachypnea (respiratory rate greater than 20 breaths per minute)

- Altered mental status

- Hyperventilation (partial pressure of carbon dioxide [PaCO_2] less than 32 mm Hg)

- Leukocytosis (leukocyte count greater than 12,000 cells per mm^3)

- Leukopenia (leukocyte count less than 4,000 cells per mm^3)

This emphasis on the systemic signs of inflammation as the marker for sepsis requires the recognition that other, noninfectious, pathophysiologic conditions also cause tissue injury and inflammation with systemic ramifications. Systemic inflammatory response syndrome (SIRS) includes any serious, ongoing inflammatory process resulting in end-organ damage and multisystem failure. SIRS encompasses a continuum of escalating inflammatory responses to infectious or noninfectious stimuli; end-organ dysfunction and mortality increase with each stage of the advancing inflammatory process. While sepsis is a common and important form, SIRS may also develop in response to noninfectious insults, including trauma, burns, pancreatitis, anaphylaxis, adrenal insufficiency, pulmonary embolism, myocardial infarction, massive hemorrhage, and cardiopulmonary bypass [1,3,4].

Severe sepsis has been defined as sepsis associated with organ dysfunction and tissue hypoperfusion. Signs of tissue hypoperfusion are hypotension (systolic blood pressure <90 mm Hg or a drop in systolic pressure of >40 mm Hg), lactic acidosis, oliguria, and acute alteration in mental status. Organ dysfunction results from falling blood pressure and widespread microvascular injury caused by circulating toxic byproducts of infection and the inflammatory immune response. Common manifestations include acute lung injury, renal failure, disseminated intravascular coagulation (DIC), and laboratory signs of liver dysfunction. In clinical practice, "septic shock" (a subset of sepsis) is present when there is persistent hypotension requiring vasopressor therapy, after adequate fluid resuscitation has been administered [1,5].

In 2014, the European and American societies of critical care medicine convened a third task force (Sepsis 3) to re-examine current concepts and definitions of sepsis and septic shock based on current understanding of the pathobiology, epidemiology, and management of sepsis. After a synthesis of evidence, the task force determined that previous definitions (as presented by the previous task forces) lacked precision because of excessive focus on inflammation. The task force also concluded that the conceptual model of sepsis invariably following a continuum through severe sepsis to shock is misleading; that the SIRS criteria have inadequate specificity and sensitivity for defining sepsis; and that the term "severe sepsis" is redundant. The Sepsis 3 report, with new consensus definitions for sepsis and septic shock, was published in 2016 [6]. The Sepsis 3 definitions are intended to provide greater clarity and specificity while emphasizing the life-threatening nature of sepsis syndrome. The goal is to achieve greater clinical recognition and consistency in diagnosis, therapy, and clinical investigation of sepsis.

The Sepsis 3 task force emphasized that sepsis is the primary cause of death from infection and thus requires early recognition, urgent attention, and prompt treatment. Following infection, the clinical characteristics of sepsis may emerge gradually over time, shaped by the interplay of pathogen factors and host factors such as genetic determinants, age, comorbidities, and environment. Sepsis is differentiated from infection by the presence of an aberrant or dysregulated host response accompanied by organ dysfunction. Sepsis-induced organ dysfunction may be occult; therefore, its presence should be considered in any patient presenting with infection. Conversely, unrecognized infection may be the cause of new-onset organ dysfunction. Any unexplained acute-onset organ dysfunction should thus raise the possibility of underlying infection. Pre-existing illness, chronic comorbidities, medication, and medical interventions may modify signs and symptoms of sepsis. At times, systemic infection may disrupt critical organ function without generating signs of systemic inflammatory host response [6].

The definition of sepsis is a syndrome defined as life-threatening organ dysfunction caused by dysregulated host immune responses to infection [6]. This new definition emphasizes the loss of adaptive homeostasis in response to infection, the potential lethality of infection when any degree of organ dysfunction is present, and the importance of urgent assessment and prompt treatment. Because even modest organ dysfunction has been found to confer a mortality risk in excess of 10%, sepsis is inherently a serious condition and the term "severe sepsis" is no longer considered useful [6].

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 [6,7,62]:

- 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 cells/mcL

- Elevated bilirubin: >2 mg/dL

- Acute alteration in mental status

The scoring system currently used in most critical care units is the Sequential Organ Failure Assessment (SOFA) score, which grades abnormality by organ system and accounts for clinical interventions [7]. 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 [6].

Working from a model derived from a large data base, the 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, referred to as the quick SOFA (qSOFA). This measure consists of three elements:

- Respiratory rate ≥22 per minute

- Altered mentation

- Systolic blood pressure ≤100 mm Hg

Data analysis has demonstrated that patients with infection who are positive for two or more of these elements are likely to have a prolonged intensive care unit (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 hospital ward to quickly identify which patients with an infection 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 [6].

Sepsis 3 defines septic shock as 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:

- 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 [6].

2. EPIDEMIOLOGY AND BURDEN OF SEPSIS

The first description of multiple organ failure appeared in 1973 in a discussion of three patients who died of distal organ failure that followed ruptured aortic aneurysms. Multiple organ failure was subsequently described as multiple, progressive, or sequential systems organ failure. It was noted that shock or infection alone did not cause the distal organ dysfunction. Other severe insults could set in motion an underlying reaction that would lead to widespread endothelial damage, edema resulting from increased vascular permeability, and impaired availability of oxygen [8,9,10].

Sepsis, septic shock, and multiple organ failure are major causes of morbidity and mortality in the United States. The Centers for Disease Control and Prevention (CDC) estimates that each year 1.7 million adults develop sepsis, nearly 270,000 die as a result of sepsis, and 1 in 3 patients who dies in a hospital has sepsis [76]. Approximately 9.3% of all deaths in the United States can be attributed to sepsis, which equals the number of deaths resulting from myocardial infarction and far exceeds the mortality rates from acquired immune deficiency syndrome (AIDS) or breast cancer. The aggregate hospital cost of care for patients with septicemia totaled nearly $23.7 billion in 2013 [11,16,71].

A study of hospital emergency department visits between 1999 and 2005 found that of the 750,000 hospitalizations, more than two-thirds may have initially presented to an emergency department. Cases of suspected sepsis account for more than 570,000 emergency department visits annually. The average length of stay in the emergency department is 4.7 hours. However, more than 20% of patients with sepsis had a length of stay that exceeded six hours, resulting in a substantial burden on facilities nationwide in providing sepsis care [12,13].

The incidence of septicemia more than doubled between 1993 and 2009, increasing by an annual average of 6% [11]. Between 1993 and 2003, 8.4 million cases of sepsis and 2.4 million cases of severe sepsis were reported; the annual age-adjusted sepsis hospitalization and mortality rates increased from 5.6% to 8.2%, whereas the fatality rate decreased by 1.4% [15]. The percentage of severe sepsis cases among all sepsis cases increased from 25.6% to 43.8% during the same time period [15]. Sepsis is more common among men than women, and the fatality rate is greater in men and nonwhite populations [22].

Prior to 2017, national estimates of sepsis burden relied on the use of administrative codes, which demonstrated increasing incidence and decreasing mortality [77]. However, studies have demonstrated that coding for sepsis has steadily increased over the past decade, while coding for the most common underlying infections has been stable or decreasing. These analyses suggested that code-based case identification might be unreliable for surveillance purposes because of coding practice biases and changes in diagnosis over time [77]. In order to improve hospital surveillance of sepsis, the CDC developed a case definition based on objective clinical data elements conceptually analogous to Sepsis-3 and optimized for surveillance directly from electronic health records [77]. An analysis of data from 409 participating hospitals showed that sepsis was present in 6% of adult hospitalizations, and neither the incidence of sepsis nor the combined outcome of death or discharge to hospice changed significantly between 2009 and 2014 [78].

The reported incidence rates of sepsis increase with advanced age. Two-thirds of all sepsis cases occur in people 65 years of age and older, with case fatality rates as high as 40% [16]. In a study of the burden of sepsis among Medicare recipients for the period 2012 to 2018, six-month mortality rates remained high for septic shock (60%), severe sepsis (36%), sepsis attributed to a specific organism (31%), and unspecified sepsis (27%) [79]. In the same period, the estimated annual cost of sepsis care (inpatient and subsequent skilled nursing facility) for all Medicare patients increased from $27.7 to $41.5 billion.

Mortality from sepsis of gram-negative etiology is the cause of 20% to 50% of the overall total number of septic deaths. The figures are now similar for sepsis of gram-positive etiology [18]. Mortality has been reported as high as 60% in patients with underlying medical problems. Among patients who develop the complications of shock and organ failure, mortality can reach 90% [20]. Extent of organ failure contributes to the prognosis, with a greater survival rate in patients with fewer than three failing organs. The risk of death increases as each organ fails [20].

Sepsis is among the leading causes of hospitalization and ranks as the most expensive inpatient condition treated in U.S. hospitals [66]. Hospitalized patients with sepsis include those with community-onset infection/sepsis and those with hospital-onset sepsis. Data from the 2008 National Hospital Discharge Survey show that the rate of hospitalization for sepsis increased from 11.8 to 24 per 10,000 population during the period 2000 through 2008 [66]. Compared with other conditions, the hospital stay for sepsis was 75% longer and the likelihood of dying during hospitalization was eight times higher. In a large cohort study of 2.2 million adult patients hospitalized in 2009–2015, hospital-onset sepsis complicated 1 in 200 hospitalizations and accounted for 1 in 8 sepsis cases [80]. Patients with hospital-onset sepsis had more comorbidities, longer hospital length of stay, and higher risk of death (33% vs 17%) than patients with community-onset sepsis. Among patients admitted without sepsis, hospital-onset sepsis tripled the risk of dying in the hospital. The estimated annual cost of hospitalization for sepsis and septicemia in 2008 was $14.6 billion and increasing at the rate of 11.9% each year [66].

Despite immense clinical effort and high treatment expenditures, mortality rates remain high. Those who survive often sustain permanent organ damage, some degree of physical disability, and long-term cognitive impairment [67].

3. RISK FACTORS AND PREVENTION

The risk of sepsis complicating an infection is determined by virulence of the pathogen and host factors that increase susceptibility and/or impede host defense mechanisms. Factors considered important in the development of sepsis include: recent use of broad-spectrum antibiotics; immunosuppressive drugs, such as cancer chemotherapy; invasive procedures; organ transplantation; burns or other trauma; anatomic obstruction; intestinal ulceration; extremes of age; and progressive clinical conditions, such as malignancy, diabetes, or AIDS [24].

To the extent that a patient seeks medical care at an early stage of infection, risk factors for sepsis might also include how well the healthcare provider has recognized the nature of the clinical issue and taken into account the patient's vulnerabilities. In a retrospective cohort study involving 46,000 hospitalized patients with sepsis in two large healthcare delivery systems, half the patients had outpatient clinical encounters in the week prior to hospitalization and one-third were diagnosed with an acute infection [81]. Outpatient primary care and subspecialty providers play an important role in identifying patients who are at risk for sepsis and in need of close follow-up.

The majority of infections that progress to sepsis begin outside of hospitals; however, as noted, most patients with sepsis have had recent encounters with the healthcare system even before becoming ill. Using a data set from the CDC Emerging Infections Program, a retrospective cohort study was designed to identify patient characteristics and risk factors for sepsis. Among 1,078 adult patients hospitalized with sepsis across 10 states, the median age was 64 years and 973 (90%) were classified as community-onset sepsis [82]. Of the total, 654 patients (60.7%) had healthcare exposures before hospital admission for sepsis and 447 (41,5%) had received medical treatment (e.g., antimicrobial drugs, chemotherapy, wound care, dialysis, surgery) in the 30 days prior to admission. An etiologic diagnosis for sepsis was established in 57% of cases; the most common pathogens identified were Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae. Controlling for other factors, the 30-day mortality was significantly higher in patients with cirrhosis, immunosuppression, and vascular disease. These findings indicate that most adult patients with sepsis have health facility exposures or medical treatment in the weeks before hospital admission for sepsis, encounters that may offer opportunities to intervene in ways that alter the disease course for patients at risk of severe outcomes [82].

Healthcare-associated infections are a major cause of sepsis among severely ill patients. Increased risk of nosocomial infection is associated with the presence of underlying chronic disease, alteration in host defenses, prolonged hospital stay, and the presence of invasive catheters or monitoring devices [27]. Pulmonary, urinary tract, gastrointestinal, and wound infections predominate [28,29]. In hospitalized adult patients, the etiology of sepsis has shifted from being predominantly gram-negative nosocomial infections (Escherichia coli, Klebsiella spp., Enterobacter spp., and Pseudomonas aeruginosa) to gram-positive infections (Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes). The incidence of sepsis caused by gram-positive infections has increased by 26.3% per year over the last three decades [17]. Multidrug-resistant pathogens, such as S. aureus, now account for more than half of all sepsis cases. S. aureus is singly responsible for 40% of ventilator-associated pneumonia episodes and most cases of nosocomial pneumonia [17,25]. Group B streptococcus is a leading cause of neonatal sepsis in the United States [30].

Vascular and monitoring catheters and infusion sets may become contaminated and lead to the development of nosocomial infections and sepsis. The risk of catheter-related sepsis is increased when the IV catheter is placed in a central vein, particularly if the catheter remains in place longer than three to five days or if the catheter is used for blood sampling [31]. For this reason, consideration should be given to changing the catheter and possibly the insertion site after 72 hours. The risk of contamination of arterial catheters is higher than that observed with venous catheters. Contamination can occur if the system is entered frequently for blood sampling, if the infusate remains in place for more than 48 hours, or if inflammation develops near the catheterized artery [32]. Urinary catheters left in the bladder longer than two weeks often cause infection. Therefore, increased surveillance for signs of urinary tract infections when catheters remain in place beyond a few days is necessary [33].

Central venous catheters (CVCs) are increasingly used in the pediatric population, leading to an increase in CVC-related complications. Implanted ports may be the device of choice when long indwelling times are expected, with consideration given to the patient's age and need for sedation and analgesia during the insertion procedure. Radiograph following the insertion procedure is recommended to ensure correct catheter positioning. Full sterile barrier precautions, strict protocols for catheter care, and prompt removal of the catheter when it is no longer needed are recommended to prevent infectious complications [34].

Bacterial contamination of platelet units (estimated at 1 in 1,000–3,000) results in many occurrences of transfusion-associated sepsis in the United States each year. In 2004, the AABB (formerly the American Association of Blood Banks) adopted a standard requiring member blood banks and transfusion services to implement detection measures and limit bacterial contamination in all platelet components [35].

Patients who live with malignancy are commonly hospitalized due to infection. Immunosuppresive treatments (or the malignancy itself) can lead to severe infection, which is a frequent cause of death among cancer patients. One in six patients with sepsis has underlying disease [36].

4. PATHOGENESIS OF SIRS

The natural defense of the body to an infection, or other assault, involves a number of cellular and humoral factors. They include B and T lymphocytes, macrophages, neutrophils, platelets, tumor necrosis factor (TNF), interleukins, the coagulation factors, and probably several other products [26,37,38]. There are five rather distinct phases that describe how these biologic products work together to overcome the assault and, paradoxically, how they can interact to cause SIRS and potentially lead to critical organ failure [26,39].

FIRST PHASE: THE LOCAL RESPONSE

An infection, injury, burn, or similar process can initiate a response that causes the release of various proinflammatory mediators in the immediate area of involvement. Among others, these include the cytokines, eicosanoids, and platelet-activating factors. In an attempt to limit or ameliorate the local injury, these mediators act to remove damaged tissue, stimulate new tissue growth, and combat the spread of neoplastic cells, pathogenic organisms, and antigens. To counteract the effects of these mediators and prevent them from causing damage, the body soon produces a set of anti-inflammatory substances, such as interleukins and TNF receptors [26,39].

SECOND PHASE: THE EARLY SYSTEMIC RESPONSE

If the initial injury or insult is severe enough, the proinflammatory and anti-inflammatory mediators can appear in the systemic circulation. This may occur by direct entry into the bloodstream in the case of massive trauma, by spillover from the local site in the event of a severe infection, or by other means. The presence of these mediators in the general circulation is a sign that the local region is incapable of handling the situation and that assistance is needed. The proinflammatory response brings additional neutrophils, platelets, lymphocytes, coagulation factors, and other materials to the local site. This should eventually lead to a compensatory anti-inflammatory response that down regulates and controls the proinflammatory actions. In the typical situation, this will occur and no significant untoward effects are seen [26].

THIRD PHASE: PROINFLAMMATORY EXCESS

In some patients, control of the proinflammatory process fails to develop, resulting in a systemic reaction that produces tachycardia, abnormal body temperature, and, in time, hypotension. These are the early signs of SIRS and are thought to be due to: increased microvascular permeability with transudation into organs; platelet sludging, causing capillary blockage and ischemia; reperfusion injury; dysregulation of vasodilatory and vasoconstrictive mechanisms; and maldistribution of blood flow. Persistent hypotension and shock may supervene unless homeostasis is restored, leading to organ dysfunction or organ failure. In an acutely ill patient, altered function in more than one major organ constitutes multiple organ dysfunction syndrome (MODS). While emphasis has been placed on the role of the proinflammatory state in SIRS, an important alternative mechanism may involve an imbalance in the amount or effectiveness of proinflammatory and anti-inflammatory mediators [26].

FOURTH PHASE: EXCESSIVE IMMUNOSUPPRESSIVE RESPONSE

In some patients who survive an initial massive infection or other inflammatory process, there may be a compensatory, but excessive, anti-inflammatory response that results in immunosuppression [40]. This may explain the increased susceptibility to infection in patients with severe burns, trauma, hemorrhage, or pancreatitis. The process is thought to involve impaired monocyte function, altered T- and B-cell activity, diminished proinflammatory cytokines, and several other factors. This process can be self-limiting, and the immunosuppression can resolve without further consequences. If it does not resolve, patients may experience the final, life-threatening complication of MODS [26].

FIFTH PHASE: TRANSITION TO MODS

This phase indicates that there has been an overwhelming, dysregulated host response to the biologic insult. It can take varied forms, depending on the character and severity of critical organ failure. The progression to MODS is common in patients with late-stage SIRS and carries a high mortality risk. If the immune system cannot recover, organ failure and death may follow. In another group of patients, there may be an oscillating effect, with periods of severe inflammation, immunosuppression, and then another proinflammatory response, resulting in increased mortality rates. This has been seen in patients with severe burns, whose levels of cytokines fluctuate widely for several weeks after injury [26,38].

The nature of the insult can significantly affect the degree of local inflammation and tissue injury. The balance between the expression of pro- and anti-inflammatory mediators often determines the magnitude of early tissue injury and risk of subsequent infectious complications. High levels of the proinflammatory mediators can initiate remote organ injury as a result of organ cross talk. Organ failure and death will occur in patients in phase five unless homeostasis can be maintained and there is a balance between pro- and anti-inflammatory forces [26,41,42].

5. PATHOPHYSIOLOGY OF SEPSIS

A complex, dynamic, and bidirectional interaction occurs between pathogens and the body's immune defense mechanisms during the course of invasive infection. If the defenses are breached successfully, the result can be sepsis [20].

As noted, in the United States, the etiology of sepsis has shifted from a predominance of gram-negative bacteria to a predominance of gram-positive, drug-resistant bacteria [25]. This shift has led to a re-evaluation of basic assumptions about the pathogenesis of sepsis (e.g., there may or may not be differences in the host response to gram-negative organisms compared with the response to gram-positive organisms) [44,45]. It is important to note that discrimination between gram-negative and gram-positive organisms is based on the recovery of specific pathogens from blood or the presumed site of infection rather than from any specific immunologic criterion. In 30% to 50% of sepsis cases, the inciting organism is not identified [18,25].

MICROBE RECOGNITION

The innate immune system recognizes invading pathogens and initiates an inflammatory or septic response. Gram-positive and gram-negative bacteria activate the immune response through unique cellular constituents referred to as pattern-associated molecular patterns (PAMPs) or microbial-associated molecular patterns (because they are also common in nonpathogenic bacteria). PAMPs bind to immune system receptors called pattern recognition receptors (PRRs), which are expressed on the surface of host cells. PRRs are essential for initiating the host's immune response and regulating the adaptive immune response to infection or tissue injury, yet PRRs can also contribute to harmful systemic inflammation and tissue damage in organs [5,25].

Toll-like receptors (TLRs) are the most common class of PRRs. Each of the known TLRs has unique binding properties that allow for the differentiation between gram-negative and gram-positive bacteria. When the TLR system recognizes a pathogen, a response is generated that is both generalized (similar response to dissimilar stimuli) and specific (pathogen is recognized by multiple TLRs simultaneously). The result is an immune system response that is tailored to the pathogen [25,46]. The degree to which TLRs mediate the outcome of sepsis in individual patients is not yet fully understood [5].

TLRs can detect danger signals both inside and outside the cell [25]. TLRs induce the production of inflammasomes (multiprotein complexes) in response to the products of bacteria and damaged cells. This in turn activates caspase-1, which is important in the process of inflammation and apoptosis (a counter-regulator of the initial inflammatory response in sepsis). Caspase-1 activation is considered to be a prerequisite for an adequate immune response. Like other proinflammatory products, caspase-1 can have both positive and negative effects on the course and outcome of sepsis [5].

Nod-like receptors (NLRs) are a less well understood class of PRRs. NLRs can detect danger elements (e.g., microbial motifs, live bacteria, host-derived molecules) inside the cell [25].

ENDOTOXINS AND OTHER BACTERIAL TOXINS

Endotoxin was identified more than 100 years ago, but its potential role in the development of sepsis was not identified until 1951. Experimental studies using endotoxin reproduced some of the features of septic shock in animals, but they did not represent the features of septic shock characteristic to humans. Evidence that endotoxin might play a pathogenic role in humans was discovered accidentally in 1991, but its precise role in sepsis remains elusive. Endotoxin is often found in the blood of critically ill patients, making its measurement of limited diagnostic value. In addition, other bacterial toxins (e.g., gram-positive peptidoglycans) can induce the production of mediators associated with sepsis [18].

COAGULATION SYSTEM

The coagulation system plays an important role in the sepsis-induced inflammatory cascade. Coagulation is the inflammatory reaction to tissue injury and is activated independent of the type of microbe (e.g., gram-positive and gram-negative bacteria, viruses, fungi, or parasites). Coagulation contributes to the outcome in sepsis by down-regulating fibrinolysis and the anticoagulant systems. The collaboration between clotting and inflammation, which works to wall off damaged and infected tissues, is an important host survival strategy. Coagulation induced by inflammation can in turn contribute to further inflammation. A key to determining survival in sepsis is to limit the damage while retaining the benefits of localized clotting and controlled clearance of pathogens [5,14,47].

A continuum of coagulopathy in sepsis has been suggested, extending from the appearance of coagulation abnormalities prior to the onset of any clinical signs of sepsis to consumption of anticoagulant proteins and suppression of the fibrinolytic system. Depletion of anticoagulant and fibrinolytic factors contributes to the microvascular deposition of fibrin that is associated with organ dysfunction. Coagulation abnormalities in sepsis contribute significantly to organ dysfunction and death [5,14,48].

6. MANIFESTATIONS OF SEPSIS

Any patient with sepsis who has evidence of dysfunction in one organ in the absence of an obvious cause such as traumatic injury may have incipient dysfunction of other organs. The manifestations of sepsis may be seen in the cardiovascular, pulmonary, central nervous, renal, gastrointestinal, and hematologic systems of the body (most frequently in the lungs and circulatory system) [20].

The following signs and symptoms should not be thought of merely as the manifestations of sepsis but as clear evidence that MODS may be developing. The host response may be more important in the genesis of MODS than the specific bacterium, virus, or traumatic injury. In most patients, the extent of systemic changes corresponds to the extent of shock [19,20,49].

CARDIOVASCULAR

In addition to hypotension, a variety of other cardiovascular manifestations may be seen. Tachycardia is common. In addition, the left and right ventricles are dilated, ejection fractions are often depressed, and the Frank-Starling and diastolic pressure-volume relationships are altered [24].

Before the onset of shock, the patient's condition is usually hyperdynamic. The skin is warm and flushed, pulse volume is increased, and pulse pressure is wide. Cardiac output is typically elevated, and systemic vascular resistance (SVR) is usually decreased. Despite the increase in cardiac output, serum lactate levels are often elevated. Anaerobic metabolism occurs because of inadequate nutrient blood flow [24].

As shock sets in, SVR drops precipitously, although cardiac output continues to increase. In the later phases of shock cardiac output declines, which exacerbates the effects of hypoperfusion and allows lactate to accumulate. The decrease in cardiac output can result in a subsequent elevation of the SVR [24].

PULMONARY

Tachypnea, with a respiratory rate of more than 20 breaths per minute, is often the earliest pulmonary sign of sepsis, occurring before hypoxemia. Hypoxemia is usually present, although it may be masked by hyperventilation. The cause of hypoxemia is usually ventilation-perfusion mismatch.

As sepsis continues, marked respiratory alkalosis often ensues; PaCO_2 may be 30 mm Hg or less. The hypoxemia progresses rapidly. The result is often pulmonary edema and respiratory failure. Other pulmonary manifestations of sepsis include respiratory muscle dysfunction and bronchoconstriction. The onset of either acute respiratory distress syndrome (ARDS) or persistent pulmonary hypertension is an ominous sign [19,49,50].

CENTRAL NERVOUS SYSTEM

Altered mental status may be the most common and most overlooked manifestation of sepsis. This causes elderly patients to be at particularly high risk. Early changes include withdrawal, confusion, irritability, or agitation. In patients with severe infection, one may see disorientation, lethargy, seizures, or frank obtundation [21,50].

Eventually, symptoms and signs of encephalopathy, including nonfocal neurologic manifestations, may be seen, and some patients may become comatose. In addition, evidence of polyneuropathy, including impaired deep tendon reflexes, muscle weakness, and wasting, may be present [19,49,50].

Patients with sepsis and encephalopathy are more likely to be bacteremic and have concomitant renal and hepatic dysfunction than are patients with sepsis and normal mental status. Furthermore, the risk of death increases as the encephalopathy worsens [21].

RENAL

The renal manifestations of sepsis include oliguria and azotemia. Urinary sediment may contain red blood cells, casts, and protein. The urinary excretion of sodium may be markedly reduced (less than 20 mEq/L), and urinary osmolality may be increased (greater than 450 mOsm/kg). Protracted oliguria may reflect acute tubular necrosis, often reversible, or diffuse microvascular injury, often resulting in fixed renal failure [19,49].

GASTROINTESTINAL

Impaired motility is the most common gastrointestinal problem. Often, this manifests as abnormal gastric emptying or as a dynamic ileus. Stress ulceration is another common problem, although it may be seen less often now than in the past. There is some evidence that stress ulcers are less likely to develop when patients are given adequate fluid resuscitation, although this has not been proven conclusively [53].

HEPATIC

Large but transient elevations in serum transaminase levels may follow an episode of severe shock or hypoxemia. Less severe increases, often in association with mild-to-moderate hyperbilirubinemia, suggest focal hepatic necrosis. In the final states of sepsis, patients may have evidence of frank hepatic insufficiency, including hypoprothrombinemia, jaundice, lactic acidosis, and hypoglycemia [2,49,50].

HEMATOLOGIC

Leukocytosis, usually accompanied by a shift to the left (>10% immature cells), is the most common hematologic manifestation of sepsis. Multifactorial anemia is common in late-stage sepsis. Decreased maturity and/or survival of red blood cells may contribute to anemia. Thrombocytopenia and coagulation abnormalities (elevated prothrombin or partial thromboplastin times) are often seen in sepsis. Thrombocytopenia is more common than overt DIC in sepsis. DIC is a manifestation of advanced-stage sepsis and carries a poor prognosis [2,17,49,54,55].

7. DIAGNOSIS AND MANAGEMENT

Methods to identify critically ill patients who are likely to die as a result of sepsis have become clearer, and increased awareness that sepsis is more common and lethal than previously understood has helped to promote the development of an organized approach to care. While the early diagnosis of sepsis continues to be a challenge (primarily because a rapid, sensitive, and specific diagnostic test is lacking), research indicates that improvements in outcomes are possible when treatment protocols are applied in a timely manner [48].

As discussed, an international consortium of critical care specialty societies has worked to standardize the definition and clinical parameters of sepsis and to develop evidence-based guidelines for optimal management of sepsis and septic shock. This is an ongoing effort, the goal of which is to improve care and reduce mortality worldwide. Clinical care guidelines have been developed by the Surviving Sepsis Campaign and published by the Society of Critical Care Medicine (SCCM) in 2008, 2013, 2016, and 2021. Detailed management strategies are provided for rapid diagnostic evaluation and antimicrobial treatment, fluid resuscitation, and the use of vasopressors in septic shock [62,65,72]. Initial funding of the Surviving Sepsis Campaign was provided by the SCCM. The ongoing work and the campaign's guidelines have no direct or indirect connection to industry support. The 2021 international guideline for the management of sepsis and septic shock are available online at https://www.sccm.org/SurvivingSepsisCampaign/Home [72]. The 2021 guideline recommendations are graded for strength ("strong" or "weak") and for quality of evidence.

MANAGEMENT OF SEPSIS

Fluid Resuscitation and Diagnosis

The SCCM guideline emphasizes that sepsis and septic shock are medical emergencies; treatment and resuscitation should begin immediately upon recognition. Intravenous fluid resuscitation of a patient with sepsis-induced shock (defined as tissue hypoperfusion) should be initiated as soon as the hypoperfusion is recognized (i.e., not delayed pending admission to an ICU).

Evidence Based Practice Recommendation

The Society for Critical Care Medicine suggests that, in the resuscitation from sepsis-induced hypoperfusion, at least 30 mL/kg of IV crystalloid fluid be given within the first three hours.

https://journals.lww.com/ccmjournal/Fulltext/2021/11000/Surviving_Sepsis_Campaign__International.21.aspx

Last Accessed: June 2, 2022

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

The principal recommendations for fluid resuscitation are [72]:

- Crystalloids should be used as first-line fluid for resuscitation for adults with sepsis or septic shock (grade strong, moderate-quality evidence).

- In the setting of sepsis-induced hypoperfusion, at least 30 mL/kg of intravenous crystalloid fluid should be given within the first three hours (grade weak, low-quality evidence).

- It is suggested that albumin be added when patients require substantial amounts of crystalloids (grade weak, moderate-quality evidence).

- Fluid resuscitation should initially target a MAP of 65 mm Hg in patients with septic shock requiring vasopressors (grade strong, moderate-quality evidence).

It is recommended that, following initial fluid resuscitation, additional fluid administration be guided by frequent reassessment of hemodynamic status. A reasonable set of treatment goals suggested for the first six hours of resuscitation are [65,72]:

- Central venous pressure of at least 8 mm Hg (12 mm Hg in mechanically ventilated patients)

- MAP of 65 mm Hg or greater

- Urine output of 0.5 mL/kg/hour or greater

- Central venous or mixed venous oxygen saturation of at least 70% or 65%, respectively

Antibiotic Therapy and Source Control

Evidence Based Practice Recommendation

The Society for Critical Care Medicine recommends that appropriate routine microbiologic cultures (including blood) be obtained before starting antimicrobial therapy in patients with suspected sepsis or septic shock if doing so results in no substantial delay in the start of antimicrobials.

https://journals.lww.com/ccmjournal/Fulltext/2021/11000/Surviving_Sepsis_Campaign__International.21.aspx

Last Accessed: June 2, 2022

Strength of Recommendation/Level of Evidence: Best practice statement

The SCCM recommends obtaining appropriate cultures before beginning antimicrobial therapy, but the process of doing so should not delay antibiotic administration. At least two sets (aerobic and anaerobic) of blood cultures should be obtained, including one drawn through any indwelling vascular catheter or device in place prior to onset of infection. Cultures from other suspected sites should be obtained as well. The guideline committee also recommends that imaging studies be performed to confirm the source of infection, assuming the patient's condition allows it [62,65,72].

Intravenous antimicrobial therapy should be started as early as possible, ideally within the first hour of recognition of sepsis or septic shock (grade strong, moderate-quality evidence). Clinical studies have shown that delay in antimicrobial therapy for serious infection and sepsis prolongs morbidity, lengthens hospital stay, and increases mortality [68]. A retrospective cohort study involving 2,731 patients with sepsis showed that initiation of antimicrobial therapy within the first hour of documented hypotension was associated with increased survival to discharge. Moreover, each hour of delay conferred an approximately 12% decreased probability of survival [69].

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 hospitals. The clinician should assess risk factors for multidrug-resistant pathogens, including prior hospitalization, health facility residence, recent antimicrobial use, and evidence of prior infection with resistant organism. The anticipated susceptibility profile of prevalent local pathogens and the ability of the antibiotic to penetrate to the source of the infection must 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 [53,57]. It has been found that combining an extended-spectrum beta-lactam antibiotic (e.g., penicillins, cephalosporins) with an aminoglycoside (e.g., gentamicin) was no more effective in reducing mortality than using the beta-lactam agent alone. In addition, the combination carries an increased risk of renal damage [53,57]. 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 and Pseudomonas, often in combination with vancomycin to cover S. aureus pending culture results.

The empirical antimicrobial regimen should be narrowed as soon as the pathogen has been identified and sensitivities are known. The duration of therapy will depend on the nature of the infection and other considerations specific to a given case. As a general rule, a 5- to 8-day course of bactericidal antimicrobial therapy is considered adequate for most serious infections associated with sepsis [72]. In the event that the syndrome is due to something other than an infectious cause, such as trauma, antibiotics should be discontinued as soon as possible.

Source control requires that a specific anatomic diagnosis of infection (e.g., skin/soft tissue infection, pyelonephritis, cholangitis, peritonitis) be identified, or excluded, as soon as possible and preferably within the first six hours after presentation. Radiographic imaging is often necessary and should be undertaken promptly as soon as the patient's condition permits and antimicrobial therapy has been administered. Source control may be achieved by percutaneous drainage of an infected cyst or abscess, debridement of infected tissue, or removal of an infected device or catheter (removal should be prompt after other vascular access has been established) [53,72]. If necessary, surgical exploration and drainage should be undertaken within 12 hours of diagnosis (grade strong, low-quality evidence) [65].

Vasopressors and Inotropic Therapy

If hypotension persists after intravascular volume repletion, then vasopressors may be required to restore and maintain adequate blood pressure and tissue perfusion (goal MAP ≥65 mg Hg). Such patients are considered to have the combination of vasodilation and reduced cardiac contractility, a condition best managed with a combined inotrope-vasopressor agent. In order to monitor arterial pressure accurately, it is suggested that all patients requiring vasopressors have an arterial catheter placed as soon as practical, if resources are available [72].

Historically, norepinephrine, dopamine, and epinephrine were three inotrope-vasopressor used to correct hypotension in septic shock [53]. Based on comparison studies and a meta-analysis of six randomized trials, norepinephrine is considered superior to dopamine and is now the recommended first choice for vasopressor therapy in septic shock (grade strong, high-quality evidence) [65,70,72]. In settings where norepinephrine is not available, epinephrine or dopamine can be used as an alternative. Special attention should be given to patients at risk for arrhythmias when using dopamine and epinephrine [72]. For adults with septic shock on norepinephrine with inadequate MAP levels, vasopressin should be added instead of escalating the dose of norepinephrine (grade weak, moderate-quality evidence) [72]. If combination therapy is not effective, epinephrine may be added. For patient safety and effectiveness, intravenous vasopressor therapy should be administered via a central venous catheter.

As an alternative second drug, or to decrease the required effective dose of norepinephrine, vasopressin (up to 0.03 units/minute) may be added to norepinephrine [62,65,72]. Vasopressin should not be administered as the initial agent in septic shock.

Phenylephrine is a pure vasopressor that may be used in very select cases of septic shock [62,65]. It reduces cardiac stroke volume, which can have deleterious effects in the patient with low cardiac output, and thus is not recommended as initial or additive therapy. Phenylephrine is reserved for the unusual case in which tachyarrhythmia limits norepinephrine use or the patient has known high cardiac output. Intravenous phenylephrine should be administered only by properly trained individuals familiar with its use [53,56,60].

Inotropic therapy may involve the use of dobutamine if the cardiac output remains low. If dobutamine is used, it should be combined with the vasopressors. All patients requiring vasopressors should have an arterial line placed for monitoring blood pressure [53,56].

Monitoring Serum Lactate

If elevated, serum lactate provides a marker of tissue hypoperfusion, and serial measurements (of lactate clearance) can be used to monitor progress in resuscitation of the patient with sepsis or early septic shock. In cases in which elevated lactate levels are used as a marker of tissue hypoperfusion, it is recommended that resuscitation efforts target serum lactate with the goal to achieve normalization as rapidly as possible (grade weak) [62,65,72].

Corticosteroids

Prior to the 1990s, there was evidence that the overall 28-day mortality was not impacted by the use of corticosteroids; consequently, their use was not advised. A review of studies conducted between 1992 and 2003 concluded that corticosteroids did not change the 28-day mortality in patients with sepsis and septic shock, but that the use of low-dose corticosteroids did reduce the all-cause mortality [58]. According to the 2021 guideline, corticosteroids are not recommended in adult patients with sepsis if hemodynamic stability has been achieved with fluid resuscitation and vasopressor therapy.

The patient with persistent hypotension despite fluids and vasopressors should be assessed for adrenal responsiveness and may benefit from corticosteroid therapy. The 2021 SCCM guideline suggests using IV corticosteroids for adults with septic shock and an ongoing requirement for vasopressor therapy (grade weak, moderate-quality evidence) [72]. The typical corticosteroid used in adults with septic shock is IV hydrocortisone at a dose of 200 mg/day given as 50 mg intravenously every six hours or as a continuous infusion [72,73]. It is suggested that this is commenced at a dose of norepinephrine or epinephrine ≥0.25 mcg/kg/min at least four hours after initiation.

Recombinant Human Activated Protein C

Drotrecogin alpha (activated), or recombinant human activated protein C (rhAPC), has been studied in patients with sepsis due to its antithrombotic, anti-inflammatory, and profibrinolytic properties. It was voluntarily withdrawn from the market in 2011 due to studies showing no improvement in mortality with treatment [59].

Blood Product Administration

In some cases, blood product administration may be required. The 2021 guideline recommends RBC transfusion if the hemoglobin level falls below 7.0 g/L [72]. The routine use of erythropoietin is not recommended for treatment of anemia in patients with sepsis unless other conditions are present, such as the compromise of red blood cell production induced by renal failure. Prophylactic platelet transfusion is suggested when the platelet count is <10,000/mm^3 (10 × 10^9/L) in the absence of apparent bleeding and when counts are <20,000/mm^3 (20 × 10^9/L) if the patient has a significant risk of bleeding [72].

Patients who require invasive procedures or surgery typically require a platelet count that is in excess of 50,000/mm^3[53]. The routine use of fresh frozen plasma is not recommended unless there is active bleeding or planned surgery. Direct administration of antithrombin agents for the treatment of sepsis or septic shock is not advised [53].

SUPPORTIVE THERAPY FOR SEPSIS AND SEPTIC SHOCK

Mechanical Ventilation

Patients who develop sepsis-induced acute lung injury (ALI) or ARDS may require assisted ventilation. The routine use of pulmonary artery catheters for patients with ALI/ARDS is not recommended, and it is important to remember to avoid high pressures and volumes.

The SCCM guideline committee recommends a target goal for maximum end-inspiratory plateau pressures of 30 cm H_2O and a target tidal volume of 6 mL/kg predicted body weight in adult patients with sepsis-induced ARDS (grade strong, high-quality evidence). In addition, the use of lower tidal volumes over higher tidal volumes is suggested for adult patients with sepsis-induced respiratory failure without ARDS [72].

Unless contraindicated, it is recommended that mechanically ventilated patients be kept with the head of the bed elevated (30–45 degrees is suggested) to limit aspiration and prevent the development of ventilator-associated pneumonia. In hospitals with advanced experience and equipment, it may be advantageous to treat patients with ARDS in a prone position if higher pressures are required and the patient's condition allows for the positional change [53,72].

A protocol for weaning patients from the ventilator should be developed for use following a successful spontaneous breathing trial. Extubation should be considered if the breathing trial is successful. A successful breathing trial is characterized by the following criteria [53]:

- Patient is arousable.

- Patient is hemodynamically stable (without vasopressor agents).

- Patient has developed no new potentially serious conditions.

- Ventilatory and end-expiratory pressure requirements are low.

- Fraction of inspired oxygen requirements are able to be safely delivered with a face mask or nasal cannula.

The SCCM recommends a conservative fluid strategy for patients with established ARDS and no evidence of tissue hypoperfusion in order to minimize fluid retention and weight gain (which have been shown to prolong mechanical ventilation and lengthen ICU stay) [72].

Sedation, Analgesia, and Neuromuscular Blockade

Sedation, whether intermittent or by continuous infusion, may be required for patients who are mechanically ventilated. In such cases, the practice of daily interruption or lightening of the sedation, preferably by established protocol, will serve to maintain the minimum degree of necessary sedation.

Neuromuscular blockade agents are sometimes used in the ICU to improve chest compliance, reduce airway pressures, and facilitate mechanical ventilation. Neuromuscular blockade agents should be used with caution in the patient with sepsis and only for brief periods, so as to avoid the risk of prolonged blockade when the drug is discontinued. The SCCM 2021 guideline suggests using intermittent neuromuscular blockade agents (grade weak, moderate-quality evidence). If these agents are used, clinicians should ensure adequate patient sedation and analgesia [72].

Glucose Control

Glucose control includes a regimen of appropriate nutrition, beginning with IV glucose and advancing early to enteral feeding for the first seven days in critically ill patients with sepsis [72]. Following initial stabilization, patients with hyperglycemia should receive IV insulin therapy to reduce blood glucose levels. SCCM guidance strongly recommends that blood glucose management in ICU patients with sepsis be done by protocol [72]:

- Insulin dosing to commence when two consecutive blood glucose levels are greater than 180 mg/dL

- Target an upper blood glucose ≤180 mg/dL rather than an upper blood glucose ≤110 mg/dL (grade strong, high-quality evidence)

- Monitor blood glucose every one to two hours until glucose values and insulin infusion rates are stable, then every four hours while patients are receiving insulin infusions

Note: A 2009 study demonstrated more frequent episodes of hypoglycemia and higher mortality when tight glucose control was attempted in critically ill patients [63].

Bicarbonate Therapy and Deep Vein Thrombosis Prophylaxis

Bicarbonate therapy to improve hemodynamics or reduce vasopressor requirements in patients with sepsis-induced lactic acidemia is not recommended for those patients with a pH equal to or greater than 7.15 [72]. The use of bicarbonates in SIRS requires additional study.

The use of anticoagulants to prevent deep vein thrombosis (DVT) has been well studied. For patients with sepsis, the SCCM guideline committee recommends the administration of low-dose unfractionated heparin (UFH), two to three times per day, or low-molecular-weight heparin (LMWH), once daily, unless there are contraindications, such as active bleeding, thrombocytopenia, or severe coagulopathy. LMWH has been found to be superior to UFH and is preferred in high-risk patients if there are no contraindications [53,72].

When contraindications exist, other preventive measures, such as graduated compression stockings or an intermittent compression device, are recommended. In very high-risk patients, such as those who have sepsis and a history of DVT, trauma, or orthopedic surgery, a combination of both therapies is suggested [53,56].

Stress Ulcer Prophylaxis

The SCCM guideline recommends stress ulcer prophylaxis for patients with sepsis who have risk factors for gastrointestinal bleeding, using either a proton pump inhibitor or a histamine-2 antagonist. It is recommended that stress ulcer prophylaxis not be used for patients without risk factors for gastrointestinal bleeding [72].

Communication

Also included in the supportive therapy points of care is the SCCM recommendation that advance care planning, including the communication of likely outcomes and realistic goals of treatment, be discussed with patients and families [53,72]. 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 communication with patients and families is considered an essential aspect of care, it is each practitioner's responsibility to ensure that information regarding goals and potential outcomes 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.

SEPSIS BUNDLE

Reducing mortality due to sepsis requires an organized process that guarantees early recognition and consistent application of evidence-based practice. To this end, carefully designed protocols and measurable quality indicators should be incorporated into hospital practice. Beginning in 2005, the Surviving Sepsis Campaign converted its guideline into protocols, with sets of quality indicators that could be implemented by hospitals working to improve outcomes. The Sepsis Bundles are a series of therapies that, when implemented together, have been proven to achieve better outcomes than when implemented individually [62]. In conjunction with the 2013 guideline, two bundles (resuscitation and management) were released.

In order to reflect the changes in the 2016 guideline, in 2018 the Surviving Sepsis Campaign published the Hour-1 Bundle, taking the place of the previously separate resuscitation and management bundles [62]. This new bundle emphasizes the importance of beginning resuscitation and management immediately, then escalating care seamlessly (e.g., by adding vasopressor therapy) on the basis of ongoing clinical parameters rather than waiting or extending resuscitation measures over a longer period. The Hour-1 Bundle consists of five elements that are intended to be initiated within the first hour after the time of triage in the emergency department or, if referred from another care location, from the earliest chart annotation consistent with all elements of sepsis or septic shock. The five elements are [62]:

- Measure lactate level. Re-measure if initial lactate is >2 mmol/L.

- Obtain blood cultures prior to administration of antibiotics.

- Administer broad-spectrum antibiotics.

- Rapidly administer 30 mL/kg crystalloid for hypotension or lactate ≥4 mmol/L.

- Apply vasopressors if patient is hypotensive during or after fluid resuscitation to maintain MAP ≥65 mm Hg.

More than one hour may be required for resuscitation to be completed, but initiation of resuscitation and treatment should begin immediately [62]. The Hour-1 Bundle, based on the 2016 guideline, is evidence-based and intended for use by emergency department, hospital, and ICU staff as a tool for improving the care of patients with sepsis and septic shock. As of June 2022, the bundles have not been updated to reflect the 2021 guidelines.

MANAGEMENT OF SEVERE CORONAVIRUS DISEASE 2019 (COVID-19) IN THE ICU

Evidence Based Practice Recommendation

For adults with COVID-19 and shock, the Society for Critical Care Medicine suggests using norepinephrine as the first-line vasoactive agent over other agents.

https://journals.lww.com/ccmjournal/Fulltext/2021/03000/Surviving_Sepsis_Campaign_Guidelines_on_the.21.aspx

Last Accessed: May 17, 2021

Strength of Recommendation: Weak

In response to the ongoing COVID-19 pandemic, a Surviving Sepsis Campaign Coronavirus Disease 2019 panel of international experts was formed to provide guidance for managing patients with severe or critical COVID-19 [83]. The panel issues updated recommendations as new evidence becomes available. COVID-19 is defined as severe when the patient has clinical signs of pneumonia (e.g., fever, cough, dyspnea, tachypnea) combined with one or more of the following: respiratory rate >30 breaths/min, severe respiratory distress, or oxygen saturation <90% on room air [83]. COVID-19 is classified as critical when the patient has acute respiratory failure requiring ventilation and/or signs of sepsis or septic shock.

In March 2021, the Surviving Sepsis Campaign COVID-19 panel issued nine new or updated statements/recommendations for management of patients with COVID-19 in the ICU [83]. For severe or critical COVID-19, the panel recommends the use of systemic corticosteroids (preferably dexamethasone) and venous thromboprophylaxis but recommends against the use of hydroxychloroquine. In addition, the panel suggests against the use of convalescent plasma and therapeutic anticoagulation outside clinical trials. The use of remdesivir, an antiviral drug, is suggested for adults with severe COVID-19 who do not require mechanical ventilation; however, the panel suggests against starting remdesivir in patients with critical COVID-19 outside clinical trials. Because of insufficient evidence, no recommendation has been issued on the use of awake prone positioning [83].

8. PEDIATRIC CONSIDERATIONS

Sepsis is a common and frequently fatal condition affecting children worldwide. The global burden and mortality of sepsis in neonates and children was assessed in a systemic review and meta-analysis of epidemiologic studies published between 1979 and 2016 [84]. The analysis demonstrated an aggregate estimate of 48 cases of childhood sepsis and 22 cases of severe sepsis per 100,000 person-years. Childhood mortality ranged from 1% to 5% for sepsis and 9% to 20% for severe sepsis. The population-level estimate for neonatal sepsis was 2,202 per 100,000 live births, with mortality between 11% and 19%. Extrapolating data on a global scale yielded an estimated annual incidence of 3.0 million cases of sepsis in neonates and 1.2 million cases in children [84]. In the United States alone there are 72,000 children hospitalized for sepsis annually, with a reported mortality rate of 25% [75].

In 2002, an international panel of experts met to revise the definitions of sepsis and septic shock to include and reflect the developmental stages of children and age-specific norms of vital sign and laboratory data. The panel also modified the adult criteria for SIRS and proposed dividing the pediatric population into the following six distinct age groups to account for age-specific risks [51]:

- Newborn: 0 days to 1 week of age

- Neonate: 1 week to 1 month of age

- Infant: 1 month to 1 year of age

- Toddler and preschool: 2 to 5 years of age

- School-age child: 6 to 12 years of age

- Adolescent and young adult: 13 to 17 years of age

The panel's definition of SIRS for children includes the presence of at least two of the following criteria (one of which must be abnormal temperature or leukocyte count) [51]:

- Core temperature greater than 38.5°C or less than 36°C (measured by rectal, bladder, oral, or central catheter probe). Hypothermia may indicate serious infection (especially in infants).

- Tachycardia greater than two standard deviations above normal for the child's age in the absence of external stimulus; or unexplained persistent elevation over a four-hour time period; or, for children younger than 1 year of age, bradycardia (as defined by the panel); or unexplained persistent depression over a 30-minute time period. Bradycardia is not a sign of SIRS in older children but may be a sign in the newborn.

- Mean respiratory rate greater than two standard deviations above normal for the child's age or mechanical ventilation

- Leukocyte count that is either elevated or depressed for the child's age; or greater than 10% immature neutrophils

Because many pediatric disease processes present with symptoms of tachycardia and tachypnea, a diagnosis of SIRS should not be based solely on elevated heart and respiratory rates; abnormalities in temperature or leukocyte count must be present. Biomechanical markers of inflammation (e.g., elevated sedimentation rate, C-reactive protein, interleukin-6) have not been proven specific enough to be included in the diagnostic criteria [51].

The following definitions have also been proposed for use in the pediatric population [51]:

- Sepsis: SIRS in the presence of or as a result of suspected or proven infection

- Severe sepsis: Sepsis plus cardiovascular organ dysfunction, ARDS, or two or more other organ dysfunctions (as defined by specific criteria)

- Septic shock: Sepsis plus cardiovascular organ dysfunction

The diagnosis of sepsis and impending septic shock in neonates and children should be suspected when the usual inflammatory triad of fever, tachycardia, and vasodilation is accompanied by changes in mentation. Altered mentation may manifest as inability to be aroused, inconsolable irritability, or lack of interaction with parents. Children may present with hyper- or hypothermia, signs of decreased perfusion, and/or decreased urinary output. Because children often maintain their blood pressure until they are severely ill, hypotension is not necessary for the diagnosis (as in adults), but if present, it helps confirm a suspected case of septic shock. It is also important to note that shock in children may occur long before hypotension occurs [51].

Neonatal ICU (NICU) nurses play a key role in the early recognition and prompt treatment of infection/sepsis in the newborn. A published critical care nursing guide for understanding issues of sepsis in the NICU emphasizes the following goals [74]:

- A high index of suspicion for risk of infection

- An ability to recognize signs of infection and sepsis in infants

- A low threshold for reporting related concerns to the physician or advanced practice nurse

- Being an advocate on behalf of the infant to ensure a timely assessment and prompt therapeutic intervention

Prior to 2020, the most widely utilized guidance for management of sepsis in the pediatric age group was the Surviving Sepsis Campaign guidelines, reviewed and updated every four years [65,75]. Following the 2016 edition, SCCM formed a separate task force dedicated to developing guidelines for managing sepsis in children. Published in 2020, the objective of the SCCM Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children is to provide guidance for clinicians caring for infants, children, and adolescents with sepsis and septic shock [85]. Resources related to these guidelines can be found on the SCCM Surviving Sepsis Campaign website at https://www.sccm.org/SurvivingSepsisCampaign/Guidelines/Pediatric-Patients [86].

Systematic screening for sepsis is recommended in children who present as acutely unwell. Upon clinical suspicion of sepsis, an expedited diagnostic evaluation should be performed within three hours, including an assessment for sepsis-associated organ dysfunction and blood cultures [86]. If signs of shock develop, or clinical evaluation supports sepsis-associated organ dysfunction, management is escalated to a one-hour time frame with the following goals: obtain IV access, collect blood culture, start empiric broad-spectrum antibiotics, measure lactate, and administer fluid bolus(es) if the patient is hypotensive. Vasoactive agents should be added when hypotension persists despite completion of initial fluid resuscitation protocol. Continuous clinical reassessment is recommended for early recognition of ARDS, infectious source control, and titration of vasoactive drugs [86]. Patients refractory to hemodynamic support should be evaluated and treated for adrenal insufficiency. About 25% of children with septic shock have adrenal insufficiency and will benefit from corticosteroid therapy [75].

Clinically, pediatric septic shock takes two forms. In hyperdynamic shock, the child has rapid capillary refill and bounding pulses. In hypodynamic shock, there is prolonged capillary refill, mottled cool extremities, and diminished pulses. In both types, immediate resuscitation involves maintaining necessary circulation with fluid replacement, assuring proper ventilation, and maintaining threshold heart rates. Suggested therapeutic end points include a capillary refill of less than two seconds, warm extremities, urine output greater than 1 mL/kg/hr, normal blood pressure, normal mental status, and normal pulses with no differential between peripheral and central pulses. Frequent monitoring is required as rapid changes may occur in the status of a child with sepsis [52,53].

The international consensus panel also developed criteria for MODS in the pediatric population based on scoring systems previously described in the literature. These systems include the Pediatric Logistic Organ Dysfunction score, Pediatric-MODS score, and Multiple Organ System Failure score. The panel also considered the criteria used in the open-label rhAPC study in their development of criteria for pediatric MODS [51].

The panel's goal was to identify criteria that would optimize the enrollment of children with severe sepsis in clinical studies. To that end, they specified the following [51]:

- Cardiovascular and respiratory organ dysfunction must be present (and mechanical ventilator support for respiratory failure, if used).

- Other organ dysfunctions should be monitored during clinical studies.

- The usefulness of organ dysfunction-free days as a primary end point should be confirmed.

- Documenting organ dysfunction should be achieved with a pediatric MODS scoring system.

Experts generally agree that additional evidence-based studies are needed to understand and accurately define pediatric sepsis by accounting for the physiologic variables, age-specific norms, and risk factors of this population [23,43,75].

9. RECOVERY FROM SEPSIS

There is limited information on the long-term complications of sepsis in those who survive. One systematic review of hospitalized patients who recover from sepsis found that about 40% are re-hospitalized within 90 days, one-third die within the following year, and one-sixth experience persistent physical or cognitive impairments [87]. The most prevalent of reported residual impairments are functional limitations (e.g., inability to bathe and dress independently), cognitive deficits, anxiety, depression, and post-traumatic stress disorder. Factors associated with late sequelae included poor pre-sepsis health status, severity of the acute sepsis episode, and timeliness and quality of initial sepsis care [87]. This review discusses inpatient practices for reducing long-term morbidity and provides a framework for evaluating and treating patients in the 90 days after hospitalization for sepsis [87].

A recommended hospital- and ICU-based approach to improving clinical outcomes centers on three strategies: attention to 2021 SCCM guidelines for sepsis care; protocol management of pain, agitation, and delirium; and early mobilization to prevent or minimize muscle atrophy [87]. Adherence to guidelines for the early identification and treatment of sepsis, including rapid administration of antibiotics, has been shown to decrease in-hospital mortality [88]. Critical care specialists have published the ABCDEF bundle, an evidence-based clinical care guide to optimize ICU patient recovery and outcomes [89]. This guide addresses issues such as pain prevention, spontaneous awakening and breathing trials, choice of sedation, management of delirium, early mobility, and family engagement and empowerment. The ABCDEF bundle helps assure more interactive ICU patients who can participate in higher-order physical and cognitive activities at the earliest in recovery from critical illness [89].

A recommended post-discharge management strategy for patients who recover from sepsis includes the following: identify new physical, mental, and cognitive problems that could benefit from appropriate treatment; review long-term medications and adjust dosage if indicated; and screen for treatable conditions that impact risk of rehospitalization, such as recurrent infection, heart failure, and aspiration [87].

10. CONCLUSION

Sepsis and septic shock present the clinician with a difficult management situation. Patients are usually unstable and may rapidly progress to ARDS, MODS, and death. There are several possible causes of sepsis, including traumatic injury, infections, and burns. Gram-negative and gram-positive organisms associated with nosocomial infections account for many cases. Other bacteria, viruses, fungi, and noninfectious etiologies account for the remaining [17,19]. The mortality rate from sepsis is approximately 30%, and it was the tenth leading cause of death in the United States in 2005 [22,61].

The pathophysiology of sepsis involves multiple organ systems and is often related to an abnormal proinflammatory and/or anti-inflammatory response to infection. Effective management requires early empiric antimicrobial therapy, hemodynamic monitoring, appropriate respiratory support, and maintenance of physiologic homeostasis.

Evidence-based practice guidelines are available to assist in the diagnosis and treatment of these disorders. This course outlines some of the current recommendations and suggestions provided by the SCCM and other experts experienced in treating patients with these disorders.

11. CASE STUDY

Patient A is a woman, 50 years of age, who was admitted to the emergency department after a motor vehicle accident. She incurred massive abdominal injuries and was transported to the emergency department unconscious and hypotensive upon arrival. She was receiving 35% O_2 via oxygen mask. Her respiratory rate was 28 breaths per minute, and lung sounds were clear bilaterally. She had a sinus tachycardia with a heart rate of 150 beats per minute. Her blood pressure was 80/45 mm Hg. The patient had a 40 pack-year history of cigarette smoking and had been taking medications to control hypertension.

She was transported via stretcher to radiology for a computed tomography scan, which revealed bleeding in the peritoneum. She was taken immediately to surgery. Following surgery, she was taken to the ICU. Three liters of lactated Ringer's solution had been infused in surgery. Estimated blood loss was 2,500 cc, and she received 6 units of whole blood in surgery. Despite fluid resuscitation, the patient was hypotensive during much of the surgical procedure. To assess fluid management, a pulmonary artery catheter was placed while in surgery. A variety of data was obtained upon arrival to the surgical ICU.

Table 0:

Vital Signs

Hemodynamic Parameters

Arterial Blood Gases (ABGs)

Laboratory Values

Ventilator Settings

BP: 100/50 mm Hg

Pulse: 120 beats per minute

Respirations: 14 breaths per minute on ventilator

Temperature: 96.5°F

CVP: 5 mm Hg

PAP: 25/15 mm Hg

PAWP: 13 mm Hg

CO: 3.2

SVR: 1,100

SvO_2: 72%

pH: 7.45

PaCO_2: 36

PO_2: 80

HCO_3: 28

SaO_2: 95%

Sodium: 130

Potassium: 4.5

Chloride: 95

Glucose: 140

Hemoglobin: 11.5

Hemocrit: 35

WBC: 11,000

Rate: 14 on assist control

FiO_2: 40%

Tidal Volume: 800

BP: blood pressure; CI: cardiac index; CO: cardiac output; CVP: central venous pressure; HCO_3: bicarbonate; FiO_2: fraction of inspired oxygen; PAP: pulmonary artery pressure; PAWP: pulmonary artery wedge pressure; PO_2: partial pressure of oxygen; SaO_2: oxygen saturation; SvO_2: venous oxygen saturation; SVR: systemic vascular resistance; WBC: white blood cells.

Patient A was hemodynamically stable following surgery. She awakened slowly and was able to be extubated and put on a 40% O_2 mask.

POST-OPERATIVE DAY 3

Three days after surgery, the patient's level of consciousness began to deteriorate. She was obtunded and only awoke when her name was called. Her skin was warm to touch and appeared flushed, and she had 4+ bounding pulses.

Table 0:

Vital Signs

Hemodynamic Parameters

ABGs on 40% O_2Mask

Laboratory Values

BP: 110/72 mm Hg

Pulse: 118 beats per minute

Respirations: 28 breaths per minute

Temperature: 104°F

CVP: 6 mm Hg

PAP: 20/12 mm Hg

PAWP: 10 mm Hg

CO: 6.0

CI: 4.2

SVR: 850

SvO_2: 85%

pH: 7.48

PaCO_2: 30

PO_2: 85

SvO_2: 85%

Hemoglobin: 9.8

Hemocrit: 28.8

WBC: 25,000

Platelets: 168,000

Urine output was 15 cc per hour for the last three hours. Cultures of sputum, urine, and blood were obtained. Antibiotic therapy was initiated.

Analysis

1. Identify the term that best describes Patient A's condition at the present moment.

Sepsis is caused by bacteria, viruses, or fungi in the blood. It is a clinical continuum ranging from bacteremia through septicemia to septic shock. Patient A is presently displaying signs of septicemia. Her blood pressure and cardiac output are within an acceptable range. Chemical mediators are being released and causing the physiologic changes.

POST-OPERATIVE DAY 5

On the 5th post-operative day, Patient A's blood pressure dropped to 84/58 mm Hg; her respirations were 32 breaths per minute, heart rate was 130 beats per minute, and temperature was 97°F. Despite 3000 cc fluid resuscitation, Patient A's condition continued to deteriorate. She was re-intubated and connected to a ventilator.

Table 0: Hemodynamic Parameters

CVP: 3 mm Hg

PAP: 15/7 mm Hg

PAWP: 5 mm Hg

CO: 3.0

CI: 1.6

SVR: 1,597

SvO_2: 68%

Analysis

1. List the risk factors applicable to Patient A's case.

Trauma

Cigarette smoking

Hypertension

Abdominal injuries

Multiple invasive lines

Surgery

2. Patient A is in what stage of septic shock? Describe the symptoms to support your answer.

Patient A is in the hypodynamic (cold) phase of septic shock. This phase is characterized by decreased cardiac output, increased SVR, hypotension, and inadequate tissue perfusion.

3. What are some of the causative organisms associated with sepsis in a post-operative, hospitalized patient?

Escherichia coli

Klebsiella

Enterobacter

Pseudomonas aeruginosa

Staphylococcus aureus

POST-OPERATIVE DAY 8

On post-operative day 8, Patient A's skin was cool and cyanotic, and mottling was noted in the extremities. She responded only to painful stimuli.

Table 0:

Vital Signs

Hemodynamic Parameters

ABGs

Laboratory Values

BP: 38/40 mm Hg

Pulse: 170 beats per minute

Respirations: 14 breaths per minute on ventilator. She is not assisting.

Temperature: 95.6°F

CVP: 6 mm Hg

PAP: 38/20 mm Hg

PAWP: 18 mm Hg

CO: 2.0

SVR: 1746

SvO_2: 48%

pH: 7.28

PaCO_2: 48

PO_2: 40

SvO_2: 52%

SaO_2: 80%

Sodium: 160

Potassium: 6.8

BUN: 48

Creatinine: 3.0

Platelets: 72,000

PT: 21

PTT: 100.5

BUN: blood urea nitrogen; PT: prothrombin time; PTT: partial thromboplastin time.

Analysis

1. Patient A's temperature is 95.6°F. Is this to be expected in the hypodynamic phase and why?

Yes. Hypothermia is common during the hypodynamic phase. Metabolic and myocardial activity are greatly reduced.

2. What is the physiologic cause of increased SVR in the hypodynamic phase?

In the hypodynamic phase, SVR is caused by decreased cardiac output and elevated serum lactate levels.

3. What management would be appropriate in this phase?

Afterload reduction and myocardial support are of great importance at this point. Before the use of vasodilators, cautious fluid administration with hemodynamic monitoring is essential to provide normovolemia as the vascular capacitance increases. If fluid resuscitation proves unsuccessful, the use of vasodilators in combination with a positive inotrope may be attempted.

POST-OPERATIVE DAY 10

Patient A died on the 10th post-operative day due to the complications of septic shock: renal failure and hepatic failure complicated by DIC and ARDS.

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55. Mammen EF. The haematological manifestations of sepsis. J Antimicrob Chemother. 1998;41(suppl A):17-24.

56. Hollenberg SM, Ahrens TS, Annane D, et al. Practice parameters for hemodynamic support of sepsis in adult patients: 2004 update. Crit Care Med. 2004;32(9):1928-1948.

57. Silbiger PM, Grozinsky S, Soares-Weiser K. Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic combination therapy for sepsis. Cochrane Database Syst Rev. 2006;1:CD003344.

58. Annane D, Bellissant E, Bollaert PE, Briegel J, Keh D, Kupfer Y. Corticosteroids for treating severe sepsis and septic shock. Cochrane Database Syst Rev. 2004;1:CD002243.

59. U.S. Food and Drug Administration. FDA Drug Safety Communication: Voluntary Market Withdrawal of Xigirs [Drotrecogin Alfa (Activated)] Due to Failure to Show a Survival Benefit. Available at https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-voluntary-market-withdrawal-xigris-drotrecogin-alfa-activated-due. Last accessed May 10, 2021.

60. LexiComp Online. Available at https://online.lexi.com. Last accessed May 10, 2021.

61. Institute for Healthcare Improvement. Defeating Sepsis: 25 Percent by 2009. Available at http://www.ihi.org/knowledge/Pages/ImprovementStories/DefeatingSepsis25Percentby2009.aspx. Last accessed May 10, 2021.

62. Society of Critical Care Medicine. SSC Hour-1 Bundle. Available at https://www.sccm.org/SurvivingSepsisCampaign/Guidelines/Adult-Patients. Last accessed April 30, 2021.

63. Finfer S, Chittock DR, Su SY, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360(13):1283-1297.

64. Flower O, Finfer S. Glucose control in ciritcally ill patients. Int Med J. 2012;42(1):4-6.

65. Dellinger RP, Levy MM, Rhodes A, et al.; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39:165-228.

66. Hall MJ, Williams SN, DeFrances CJ, Golosinskiy A. Inpatient Care for Septicemia or Sepsis: A Challenge for Patients and Hospitals. NCHS Data Brief, No. 62. Hyattsville, MD: National Center for Health Statistics; 2011.

67. Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010;304(16):1787-1794.

68. Ferrer R, Artigas A, Levy MM, et al. Improvement in process of care and outcome after a multicenter severe sepsis education program. JAMA. 2008;299(19):2294-2303.

69. Kumar A, Roberts D, Wood K, Light B, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34(6):1589-1596.

70. De Backer D, Aldecoa C, Mjimi H, Vincent JL. Dopamine versus norepinephrine in the treatment of septic shock: a meta-analysis. Crit Care Med. 2012;40:725-730.

71. Novosad SA, Sapiano MRP, Grigg C, et al. Epidemiology of sepsis: prevalence of health care factors and opportunities for prevention. MMWR. 2016;65(33);864-869.

72. Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2021. Crit Care Med. 2021;49(11):e1063-e1143.

73. Annane D, Pastores SM, Rochwerg B, et al. Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I). Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017. Crit Care Med. 2017;45(12):2078-2088.

74. Gardner SL. Sepsis in the neonate. Crit Care Nurs Clin North Am. 2009;21:121-141.

75. Mathias B, Mira JC, Larson, SD. Pediatric sepsis. Curr Opin Pediatr. 2016;28:380-387.

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77. Centers for Disease Control and Prevention. Hospital Toolkit for Adult Sepsis Surveillance. Available at https://www.cdc.gov/sepsis/pdfs/Sepsis-Surveillance-Toolkit-Aug-2018_508.pdf. Last accessed April 30, 2021.

78. Rhee C, Dantes R, Epstein L, et al. Incidence and trends in US hospitals using clinical vs claims data, 2009–2014. JAMA. 2017;318:1241-1249.

79. Buchman TG, Simpson SQ, Sciarretta KL, et al. Sepsis among Medicare beneficiaries: the burden of sepsis, 2012–2018. Crit Care Med. 2020;48:276-288.

80. Rhee C, Wang R, Zhang Z, et al. Epidemiology of hospital-onset versus community-onset sepsis in U.S. hospitals and association with mortality: a retrospective analysis using electronic clinical data. Crit Care Med. 2019;47:1169-1176.

81. Liu VX, Escobar GJ, Chaudhary R, et al. Healthcare utilization and infection in the week prior to sepsis hospitalization. Crit Care Med. 2018:46:513-516.

82. Fay K, Sapiano MRP, Gokhale R, et al. Assessment of health care exposures in adult patients with sepsis and septic shock. JAMA. 2020;3(7):e206004.

83. Athazzani W, Evans L, Alshamsi F, et al. Surviving Sepsis Campaign guidelines on the management of adults with coronavirus disease 2019 (COVID-19) in the ICU: first update. Crit Care Med. 2021;49(3):e219-e234.

84. Fleischmann-Struzek C, Goldfarb DM, Schlattmann P, et al. The global burden of pediatric and neonatal sepsis: a systematic review. Lancet Resp Med. 2018;6:223-230.

85. Surviving Sepsis Campaign. International guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Ped Crit Care Med. 2020;21:e52-e106.

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87. Prescott HC, Angus DC. Enhancing recovery from sepsis: a review. JAMA. 2018;319:62-78.

88. Seymour CW, Geston F, Prescott HC, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med. 2017;376:2235-2244.

89. Marra A, Ely EW, Pandharipande PP, et al. The ABCDEF bundle in critical care. Crit Care Clin. 2017;33:225-243.

Evidence-Based Practice Recommendations Citations

1. Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2021. Crit Care Med. 2021;49(11):e1063-e1143. Available at https://journals.lww.com/ccmjournal/Fulltext/2021/11000/Surviving_Sepsis_Campaign__International.21.aspx. Last accessed June 2, 2022.

2. Alhazzani W, Evans LE, Alshamsi F, et al. Surviving Sepsis Campaign guidelines on the management of adults with coronavirus disease 2019 (COVID-19) in the ICU: first update. Crit Care Med. 2021;49(3):e219-e234. Available at https://journals.lww.com/ccmjournal/Fulltext/2021/03000/Surviving_Sepsis_Campaign_Guidelines_on_the.21.aspx. Last accessed May 17, 2021.

97000 • Implicit Bias in Health Care

Alice Yick Flanagan, PhD, MSW

www.netce.com

Copyright © 2021 NetCE, All rights reserved.

The role of implicit biases on healthcare outcomes has become a concern as some cite that implicit biases contribute to health disparities, professionals' attitudes toward and interactions with patients, quality of care, diagnoses, and treatment decisions. This course will explore definitions of implicit and explicit bias, the nature and dynamics of implicit biases, and how they can affect health outcomes. Because implicit biases are unconscious, strategies will be reviewed to assist in raising professionals' awareness of and interventions to reduce them.

Table of Contents

97000 • Implicit Bias in Health Care

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. DEFINITIONS OF IMPLICIT BIAS AND OTHER TERMINOLOGIES

IMPLICIT VS. EXPLICIT BIAS

OTHER COMMON TERMINOLOGIES

3. MEASUREMENT OF IMPLICIT BIAS: A FOCUS ON THE IAT

EXTENT OF IMPLICIT BIASES AND RISK FACTORS

4. THEORETIC EXPLANATIONS AND CONTROVERSIES

SOCIAL PSYCHOLOGICAL AND COGNITIVE THEORETICAL FRAMEWORKS

BEHAVIORAL OR FUNCTIONAL PERSPECTIVES

NEUROSCIENTIFIC PERSPECTIVES

STRUCTURAL OR CRITICAL THEORY

5. CONSEQUENCES OF IMPLICIT BIASES

HEALTH DISPARITIES

CLINICAL DECISIONS AND PROVIDER-PATIENT INTERACTIONS

PATIENTS' PERCEPTIONS OF CARE

6. DEVELOPMENTAL MODEL TO RECOGNIZING AND REDUCING IMPLICIT BIAS

7. CREATING A SAFE ENVIRONMENT

8. STRATEGIES TO PROMOTE AWARENESS OF IMPLICIT BIAS

9. INTERVENTIONS TO REDUCE IMPLICIT BIASES

PERSPECTIVE TAKING

EMPATHY INTERVENTIONS

INDIVIDUATION

MINDFULNESS

COUNTER-STEREOTYPICAL IMAGING

EFFECTIVENESS OF IMPLICIT BIAS INTERVENTIONS

10. ROLE OF INTERPROFESSIONAL COLLABORATION AND PRACTICE AND IMPLICIT BIASES

11. CONCLUSION

12. RESOURCES

MINDFULNESS RESOURCES

Works Cited

97000 • Implicit Bias in Health Care

Education Category. Ethics - Human Rights

Release Date. 09/01/2021

Review Date. 01/15/2024

Expiration Date. 10/31/2024

Course Overview

The role of implicit biases on healthcare outcomes has become a concern as some cite that implicit biases contribute to health disparities, professionals' attitudes toward and interactions with patients, quality of care, diagnoses, and treatment decisions. This course will explore definitions of implicit and explicit bias, the nature and dynamics of implicit biases, and how they can affect health outcomes. Because implicit biases are unconscious, strategies will be reviewed to assist in raising professionals' awareness of and interventions to reduce them.

Audience

This course is designed for the interprofessional healthcare team and professions working in all practice settings.

Accreditations & Approvals

In support of improving patient care, 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. Continuing Education (CE) credits for psychologists are provided through the co-sponsorship of the American Psychological Association (APA) Office of Continuing Education in Psychology (CEP). The APA CEP Office maintains responsibility for the content of the programs. This course, Implicit Bias in Health Care, Approval #07152022-1236, provided by NetCE is approved for continuing education by the New Jersey Social Work Continuing Education Approval Collaborative, which is administered by NASW-NJ. CE Approval Collaborative Approval Period: Friday, July 15, 2022 through August 31, 2024. New Jersey social workers will receive 3 Clinical and Social & Cultural Competence CE credits for participating in this course. 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 approved as a provider of online continuing education for certified nursing assistants through the California Department of Public Health Licensing and Certification Division. Nurse Aide Certification (NAC) Provider #7005. 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. 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. 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.

Designations of Credit

This activity was planned by and for the healthcare team, and learners will receive 3 Interprofessional Continuing Education (IPCE) credit(s) for learning and change. NetCE designates this enduring material for a maximum of 3 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 3 ANCC contact hour(s). NetCE designates this continuing education activity for 3.6 hours for Alabama nurses. NetCE designates this continuing education activity for 1.5 NBCC clock hour(s). Social workers participating in this intermediate to advanced course will receive 3 Clinical continuing education clock hours. NetCE designates this activity for 3 ACPE credit(s). ACPE Universal Activity Number: JA4008164-0000-21-106-H04-P. Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 3 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 3 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 3 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 B. NetCE designates this continuing education activity for 3 credit(s). NetCE is authorized by IACET to offer 0.3 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: Alabama, Provider #ABNP0353, (valid through July 29,2025); Alabama, Provider #ABNP0353, (valid through July 29, 2025); 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; 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 has been approved by NetCE, as a NAADAC Approved Education Provider, for educational credits, NAADAC Provider #97847. NetCE is responsible for all aspects of their programming. NetCE is approved as a provider of continuing education by the California Consortium of Addiction Programs and Professionals. Provider Number 5-08-151-0624. NetCE is approved as a provider of continuing education by the California Association of DUI Treatment Programs (CADTP). Provider Number 185. NetCE is approved as a provider of continuing education by the California Association for Alcohol/Drug Educators. Provider Number CP40 889 H 0626. This activity is designed to comply with the requirements of California Assembly Bill 1195, Cultural and Linguistic Competency. NetCE designates this continuing education activity for 3 continuing education hours for addiction professionals.

Course Objective

The purpose of this course is to provide healthcare professionals with an overview of the impact of implicit biases on clinical interactions and decision making.

Learning Objectives

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

1. Define implicit and explicit biases and related terminology.

2. Evaluate the strengths and limitations of the Implicit Association Test.

3. Describe how different theories explain the nature of implicit biases, and outline the consequences of implicit biases.

4. Discuss strategies to raise awareness of and mitigate or eliminate one's implicit biases.

Faculty

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, 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

James Trent, PhD

Randall L. Allen, PharmD

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

In the 1990s, social psychologists Dr. Mahzarin Banaji and Dr. Tony Greenwald introduced the concept of implicit bias and developed the Implicit Association Test (IAT) as a measure. In 2003, the Institute of Medicine published the report Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care highlighting the role of health professionals' implicit biases in the development of health disparities [1]. The phenomenon of implicit bias is premised on the assumption that while well-meaning individuals may deny prejudicial beliefs, these implicit biases negatively affect their clinical communications, interactions, and diagnostic and treatment decision-making [2,3].

One explanation is that implicit biases are a heuristic, or a cognitive or mental shortcut. Heuristics offer individuals general rules to apply to situations in which there is limited, conflicting, or unclear information. Use of a heuristic results in a quick judgment based on fragments of memory and knowledge, and therefore, the decisions made may be erroneous. If the thinking patterns are flawed, negative attitudes can reinforce stereotypes [4]. In health contexts, this is problematic because clinical judgments can be biased and adversely affect health outcomes. The Joint Commission provides the following example [3]: A group of physicians congregate to examine a child's x-rays but has not been able to reach a diagnostic consensus. Another physician with no knowledge of the case is passing by, sees the x-rays, and says "Cystic fibrosis." The group of physicians was aware that the child is African American and had dismissed cystic fibrosis because it is less common among Black children than White children.

The purpose of this course is to provide health professionals an overview of implicit bias. This includes an exploration of definitions of implicit and explicit bias. The nature and dynamics of implicit biases and how they can affect health outcomes will be discussed. Finally, because implicit biases are unconscious, strategies will be reviewed to assist in raising professionals' awareness of and interventions to reduce them.

2. DEFINITIONS OF IMPLICIT BIAS AND OTHER TERMINOLOGIES

IMPLICIT VS. EXPLICIT BIAS

In a sociocultural context, biases are generally defined as negative evaluations of a particular social group relative to another group. Explicit biases are conscious, whereby an individual is fully aware of his/her attitudes and there may be intentional behaviors related to these attitudes [5]. For example, an individual may openly endorse a belief that women are weak and men are strong. This bias is fully conscious and is made explicitly known. The individual's ideas may then be reflected in his/her work as a manager.

FitzGerald and Hurst assert that there are cases in which implicit cognitive processes are involved in biases and conscious availability, controllability, and mental resources are not [6]. The term "implicit bias" refers to the unconscious attitudes and evaluations held by individuals. These individuals do not necessarily endorse the bias, but the embedded beliefs/attitudes can negatively affect their behaviors [2,7,8,9]. Some have asserted that the cognitive processes that dictate implicit and explicit biases are separate and independent [9].

Implicit biases can start as early as 3 years of age. As children age, they may begin to become more egalitarian in what they explicitly endorse, but their implicit biases may not necessarily change in accordance to these outward expressions [10]. Because implicit biases occur on the subconscious or unconscious level, particular social attributes (e.g., skin color) can quietly and insidiously affect perceptions and behaviors [11]. According to Georgetown University's National Center on Cultural Competency, social characteristics that can trigger implicit biases include [12]:

- Age

- Disability

- Education

- English language proficiency and fluency

- Ethnicity

- Health status

- Disease/diagnosis (e.g., HIV/AIDS)

- Insurance

- Obesity

- Race

- Socioeconomic status

- Sexual orientation, gender identity, or gender expression

- Skin tone

- Substance use

An alternative way of conceptualizing implicit bias is that an unconscious evaluation is only negative if it has further adverse consequences on a group that is already disadvantaged or produces inequities [6,13]. Disadvantaged groups are marginalized in the healthcare system and vulnerable on multiple levels; health professionals' implicit biases can further exacerbate these existing disadvantages [13].

When the concept of implicit bias was introduced in the 1990s, it was thought that implicit biases could be directly linked to behavior. Despite the decades of empirical research, many questions, controversies, and debates remain about the dynamics and pathways of implicit biases [2].

OTHER COMMON TERMINOLOGIES

In addition to understanding implicit and explicit bias, there is additional terminology related to these concepts that requires specific definition.

Cultural Competence

Cultural competence is broadly defined as practitioners' knowledge of and ability to apply cultural information and appreciation of a different group's cultural and belief systems to their work [14]. It is a dynamic process, meaning that there is no endpoint to the journey to becoming culturally aware, sensitive, and competent. Some have argued that cultural curiosity is a vital aspect of this approach.

Cultural Humility

Cultural humility refers to an attitude of humbleness, acknowledging one's limitations in the cultural knowledge of groups. Practitioners who apply cultural humility readily concede that they are not experts in others' cultures and that there are aspects of culture and social experiences that they do not know. From this perspective, patients are considered teachers of the cultural norms, beliefs, and value systems of their group, while practitioners are the learners [15]. Cultural humility is a lifelong process involving reflexivity, self-evaluation, and self-critique [16].

Discrimination

Discrimination has traditionally been viewed as the outcome of prejudice [17]. It encompasses overt or hidden actions, behaviors, or practices of members in a dominant group against members of a subordinate group [18]. Discrimination has also been further categorized as lifetime discrimination, which consists of major discreet discriminatory events, or everyday discrimination, which is subtle, continual, and part of day-to-day life and can have a cumulate effect on individuals [19].

Diversity

Diversity "encompasses differences in and among societal groups based on race, ethnicity, gender, age, physical/mental abilities, religion, sexual orientation, and other distinguishing characteristics" [20]. Diversity is often conceptualized into singular dimensions as opposed to multiple and intersecting diversity factors [21].

Intersectionality

Intersectionality is a term to describe the multiple facets of identity, including race, gender, sexual orientation, religion, sex, and age. These facets are not mutually exclusive, and the meanings that are ascribed to these identities are inter-related and interact to create a whole [22].

Prejudice

Prejudice is a generally negative feeling, attitude, or stereotype against members of a group [23]. It is important not to equate prejudice and racism, although the two concepts are related. All humans have prejudices, but not all individuals are racist. The popular definition is that "prejudice plus power equals racism" [23]. Prejudice stems from the process of ascribing every member of a group with the same attribute [24].

Race

Race is linked to biology. Race is partially defined by physical markers (e.g., skin or hair color) and is generally used as a mechanism for classification [25]. It does not refer to cultural institutions or patterns. In modern history, skin color has been used to classify people and to imply that there are distinct biologic differences within human populations [26]. Historically, the U.S. Census has defined race according to ancestry and blood quantum; today, it is based on self-classification [26].

There are scholars who assert that race is socially constructed without any biological component [27]. For example, racial characteristics are also assigned based on differential power and privilege, lending to different statuses among groups [28].

Racism

Racism is the "systematic subordination of members of targeted racial groups who have relatively little social power…by members of the agent racial group who have relatively more social power" [29]. Racism is perpetuated and reinforced by social values, norms, and institutions.

There is some controversy regarding whether unconscious (implicit) racism exists. Experts assert that images embedded in our unconscious are the result of socialization and personal observations, and negative attributes may be unconsciously applied to racial minority groups [30]. These implicit attributes affect individuals' thoughts and behaviors without a conscious awareness.

Structural racism refers to the laws, policies, and institutional norms and ideologies that systematically reinforce inequities resulting in differential access to services such as health care, education, employment, and housing for racial and ethnic minorities [31,32].

3. MEASUREMENT OF IMPLICIT BIAS: A FOCUS ON THE IAT

Project Implicit is a research project sponsored by Harvard University and devoted to the study and monitoring of implicit biases. It houses the Implicit Association Test (IAT), which is one of the most widely utilized standardized instruments to measure implicit biases. The IAT is based on the premise that implicit bias is an objective and discreet phenomenon that can be measured in a quantitative manner. Developed and first introduced in 1998, it is an online test that assesses implicit bias by measuring how quickly people make associations between targeted categories with a list of adjectives [33]. For example, research participants might be assessed for their implicit biases by seeing how rapidly they make evaluations among the two groups/categories career/family and male/female. Participants tend to more easily affiliate terms for which they hold implicit or explicit biases. So, unconscious biases are measured by how quickly research participants respond to stereotypical pairings (e.g., career/male and family/female). The larger the difference between the individual's performance between the two groups, the stronger the degree of bias [34,35]. Since 2006, more than 4.6 million individuals have taken the IAT, and results indicate that the general population holds implicit biases [3].

Interactive Activity

Visit https://implicit.harvard.edu/implicit and complete an assessment.

Measuring implicit bias is complex, because it requires an instrument that is able to access underlying unconscious processes. While many of the studies on implicit biases have employed the IAT, there are other measures available. They fall into three general categories: the IAT and its variants, priming methods, and miscellaneous measures, such as self-report, role-playing, and computer mouse movements [36]. This course will focus on the IAT, as it is the most commonly employed instrument.

The IAT is not without controversy. One of the debates involves whether IAT scores focus on a cognitive state or if they reflect a personality trait. If it is the latter, the IAT's value as a diagnostic screening tool is diminished [37]. There is also concern with its validity in specific arenas, including jury selection and hiring [37]. Some also maintain that the IAT is sensitive to social context and may not accurately predict behavior [37]. Essentially, a high IAT score reflecting implicit biases does not necessarily link to discriminating behaviors, and correlation should not imply causation. A meta-analysis involving 87,418 research participants found no evidence that changes in implicit biases affected explicit behaviors [38].

EXTENT OF IMPLICIT BIASES AND RISK FACTORS

Among the more than 4 million participants who have completed the IAT, individuals generally exhibited implicit preference for White faces over Black or Asian faces. They also held biases for light skin over dark skin, heterosexual over gender and sexual minorities (LGBTQ+), and young over old [39]. The Pew Research Center also conducted an exploratory study on implicit biases, focusing on the extent to which individuals adhered to implicit racial biases [40]. A total of 2,517 IATs were completed and used for the analysis. Almost 75% of the respondents exhibited some level of implicit racial biases. Only 20% to 30% did not exhibit or showed very little implicit bias against the minority racial groups tested. Approximately half of all single-race White individuals displayed an implicit preference for White faces over Black faces. For single-race Black individuals, 45% had implicit preference for their own group. For biracial White/Black adults, 23% were neutral. In addition, 22% of biracial White/Asian participants had no or minimal implicit racial biases. However, 42% of the White/Black biracial adults leaned toward a pro-White bias.

In another interesting field experiment, although not specifically examining implicit bias, resumes with names commonly associated with African American or White candidates were submitted to hiring officers [41]. Researchers found that resumes with White-sounding names were 50% more likely to receive callbacks than resumes with African American-sounding names [41]. The underlying causes of this gap were not explored.

Implicit bias related to sex and gender is also significant. A survey of emergency medicine and obstetrics/gynecology residency programs in the United States sought to examine the relationship between biases related to perceptions of leadership and gender [42]. In general, residents in both programs (regardless of gender) tended to favor men as leaders. Male residents had greater implicit biases compared with their female counterparts.

Other forms of implicit bias can affect the provision of health and mental health care. One online survey examining anti-fat biases was provided to 4,732 first-year medical students [43]. Respondents completed the IAT, two measures of explicit bias, and an anti-fat attitudes instrument. Nearly 75% of the respondents were found to hold implicit anti-fat biases. Interestingly, these biases were comparable to the scope of implicit racial biases. Male sex, non-Black race, and lower body mass index (BMI) predicted holding these implicit biases.

Certain conditions or environmental risk factors are associated with an increased risk for certain implicit biases, including [44,45]:

- Stressful emotional states (e.g., anger, frustration)

- Uncertainty

- Low-effort cognitive processing

- Time pressure

- Lack of feedback

- Feeling behind with work

- Lack of guidance

- Long hours

- Overcrowding

- High-crises environments

- Mentally taxing tasks

- Juggling competing tasks

4. THEORETIC EXPLANATIONS AND CONTROVERSIES

A variety of theoretical frameworks have been used to explore the causes, nature, and dynamics of implicit biases. Each of the theories is described in depth, with space given to explore controversies and debates about the etiology of implicit bias.

SOCIAL PSYCHOLOGICAL AND COGNITIVE THEORETICAL FRAMEWORKS

One of the main goals of social psychology is to understand how attitudes and belief structures influence behaviors. Based on frameworks from both social and cognitive psychology, many theoretical frameworks used to explain implicit bias revolve around the concept of social cognition. One branch of cognitive theory focuses on the role of implicit or nondeclarative memory. Experts believe that this type of memory allows certain behaviors to be performed with very little conscious awareness or active thought. Examples include tooth brushing, tying shoelaces, and even driving. To take this concept one step farther, implicit memories may also underlie social attitudes and stereotype attributions [46]. This is referred to as implicit social cognition. From this perspective, implicit biases are automatic expressions based on belonging to certain social groups [47]. The IAT is premised on the role of implicit memory and past experiences in predicting behavior without explicit memory triggering [48].

Another branch of cognitive theory used to describe implicit biases involves heuristics. When quick decisions are required under conditions of uncertainty or fatigue, and/or when there is a tremendous amount of information to assimilate without sufficient time to process, decision-makers resort to heuristics [49]. Heuristics are essentially mental short cuts that facilitate (usually unconscious) rules that promote automatic processing [50]. However, these rules can also be influenced by socialization factors, which could then affect any unconscious or latent cognitive associations about power, advantage, and privilege. Family, friends, media, school, religion, and other social institutions all play a role in developing and perpetuating implicit and explicit stereotypes, and cognitive evaluations can be primed or triggered by an environmental cue or experience [51]. When a heuristic is activated, an implicit memory or bias may be triggered simultaneously [47]. This is also known as the dual-process model of information processing [50].

BEHAVIORAL OR FUNCTIONAL PERSPECTIVES

Behavioral or functional theorists argue that implicit bias is not necessarily a latent or unconscious cognitive structure. Instead, this perspective recognizes implicit bias as a group-based behavior [52]. Behavior is biased if it is influenced by social cues indicating the social group to which someone belongs [52]. Social cues can occur rapidly and unintentionally, which ultimately leads to automatic or implicit effects on behavior. The appeal of a behavioral or functional approach to implicit bias is that it is amoral; that is, it is value- and judgment-free [52]. Rather than viewing implicit bias as an invisible force (i.e., unconscious cognitive structure), it is considered a normal behavior [53].

NEUROSCIENTIFIC PERSPECTIVES

Implicit bias has neuroscientific roots as well and has been linked to functions of the amygdala [2,54]. The amygdala is located in the temporal lobe of the brain, and it communicates with the hypothalamus and plays a large role in memory. When situations are emotionally charged, the amygdala is activated and connects the event to memory, which is why individuals tend to have better recall of emotional events. This area of the brain is also implicated in processing fear. Neuroscientific studies on implicit biases typically use functional magnetic resonance imaging (fMRI) to visualize amygdala activation during specific behaviors or events. In experimental studies, when White research subjects were shown photos of Black faces, their amygdala appeared to be more activated compared to when they viewed White faces [55]. This trend toward greater activation when exposed to view the faces of persons whose race differs from the viewer starts in adolescence and appears to increase with age [54]. This speaks to the role of socialization in the developmental process [54].

It may be that the activation of the amygdala is an evolutionary threat response to an outgroup [56]. Another potential explanation is that the activation of the amygdala is due to the fear of appearing prejudiced to others who will disapprove of the bias [56]. The neuroscientific perspective of implicit bias is controversial. While initial empirical studies appear to link implicit bias to amygdala activation, many researchers argue this relationship is too simplistic [2].

STRUCTURAL OR CRITICAL THEORY

Many scholars and policymakers are concerned about the narrow theoretical views that researchers of implicit bias have taken. By focusing on unconscious cognitive structures, social cognition and neuroscientific theories miss the opportunity to also address the role of macro or systemic factors in contributing to health inequities [9,57]. By focusing on the neurobiology of implicit bias, for example, racism and bias is attributed to central nervous system function, releasing the individual from any control or responsibility. However, the historical legacy of prejudice and bias has roots in economic and structural issues that produce inequities [58]. Larger organizational, institutional, societal, and cultural forces contribute, perpetuate, and reinforce implicit and explicit biases, racism, and discrimination. Psychological and neuroscientific approaches ultimately decontextualize racism [9,57].

In response to this conflict, a systems-based practice has been proposed [59]. This type of practice emphasizes the role of sociocultural determinants of health outcome and the fact that health inequities stem from larger systemic forces. As a result, medical and health education and training should focus on how patients' health and well-being may reflect structural vulnerabilities driven in large part by social, cultural, economic, and institutional forces. Health and mental health professionals also require social change and advocacy skills to ensure that they can effect change at the organizational and institutional levels [59].

Implicit bias is not a new topic; it has been discussed and studied for decades in the empirical literature. Because implicit bias is a complex and multifaceted phenomenon, it is important to recognize that there may be no one single theory that can fully explain its etiology.

5. CONSEQUENCES OF IMPLICIT BIASES

HEALTH DISPARITIES

Implicit bias has been linked to a variety of health disparities [1]. Health disparities are differences in health status or disease that systematically and adversely affect less advantaged groups [60]. These inequities are often linked to historical and current unequal distribution of resources due to poverty, structural inequities, insufficient access to health care, and/or environmental barriers and threats [61]. Healthy People 2030 defines a health disparity as [62]:

…a particular type of health difference that is closely linked with social, economic, and/or environmental disadvantage. Health disparities adversely affect groups of people who have systematically experienced greater obstacles to health based on their racial or ethnic group; religion; socioeconomic status; gender; age; mental health; cognitive, sensory, or physical disability; sexual orientation or gender identity; geographic location; or other characteristics historically linked to discrimination or exclusion.

As noted, in 2003, the Institute of Medicine implicated implicit bias in the development and continued health disparities in the United States [1]. Despite progress made to lessen the gaps among different groups, health disparities continue to exist. One example is racial disparities in life expectancy among Black and White individuals in the United States. Life expectancy for Black men is 4.4 years lower than White men; for Black women, it is 2.9 years lower compared with White women [63]. Hypertension, diabetes, and obesity are more prevalent in non-Hispanic Black populations compared with non-Hispanic White groups (25%, 49%, and 59% higher, respectively) [64]. In one study, African American and Latina women were more likely to experience cesarean deliveries than their White counterparts, even after controlling for medically necessary procedures [65]. This places African American and Latina women at greater risk of infection and maternal mortality.

Gender health disparities have also been demonstrated. Generally, self-rated physical health (considered one of the best proxies to health) is poorer among women than men. Depression is also more common among women than men [66]. Lesbian and bisexual women report higher rates of depression and are more likely than non-gay women to engage risk behaviors such as smoking and binge drinking, perhaps as a result of LGBTQ+-related stressors. They are also less likely to access healthcare services [67].

Socioeconomic status also affects health care engagement and quality. In a study of patients seeking treatment for thoracic trauma, those without insurance were 1.9 times more likely to die compared with those with private insurance [68].

CLINICAL DECISIONS AND PROVIDER-PATIENT INTERACTIONS

In an ideal situation, health professionals would be explicitly and implicitly objective and clinical decisions would be completely free of bias. However, healthcare providers have implicit (and explicit) biases at a rate comparable to that of the general population [6,69]. It is possible that these implicit biases shape healthcare professionals' behaviors, communications, and interactions, which may produce differences in help-seeking, diagnoses, and ultimately treatments and interventions [69]. They 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 [7].

In a landmark 2007 study, a total of 287 internal medicine physicians and medical residents were randomized to receive a case vignette of an either Black or White patient with coronary artery disease [70]. All participants were also administered the IAT. When asked about perceived level of cooperativeness of the White or Black patient from the vignette, there were no differences in their explicit statements regarding cooperativeness. Yet, the IAT scores did show differences, with scores showing that physicians and residents had implicit preferences for the White patients. Participants with greater implicit preference for White patients (as reflected by IAT score) were more likely to select thrombolysis to treat the White patient than the Black patient [70]. This led to the possible conclusion that implicit racial bias can influence clinical decisions regarding treatment and may contribute to racial health disparities. However, some argue that using vignettes depicting hypothetical situations does not accurately reflect real-life conditions that require rapid decision-making under stress and uncertainty.

PATIENTS' PERCEPTIONS OF CARE

It has been hypothesized that providers' levels of bias affect the ratings of patient-centered care [34]. Patient-centered care has been defined as patients' positive ratings in the areas of perception of provider concern, provider answering patients' questions, provider integrity, and provider knowledge of the patient. Using data from 134 health providers who completed the IAT, a total of 2,908 diverse racial and ethnic minority patients participated in a telephone survey. Researchers found that for providers who scored high on levels of implicit bias, African American patients' ratings for all dimensions of patient-centered care were low compared with their White patient counterparts. Latinx patient ratings were low regardless of level of implicit bias.

A 2013 study recorded clinical interactions between 112 low-income African American patients and their 14 non-African American physicians for approximately two years [71]. Providers' implicit biases were also assessed using the IAT. In general, the physicians talked more than the patients; however, physicians with higher implicit bias scores also had a higher ratio of physician-to-patient talk time. Patients with higher levels of perceived discrimination had a lower ratio of physician-to-patient talk time (i.e., spoke more than those with lower reported perceived discrimination). A lower ratio of physician-patient talk time correlated to decreased likelihood of adherence.

Another study assessed 40 primary care physicians and 269 patients [72]. The IAT was administered to both groups, and their interactions were recorded and observed for verbal dominance (defined as the time of physician participation relative to patient participation). When physicians scored higher on measures of implicit bias, there was 9% more verbal dominance on the part of the physicians in the visits with Black patients and 11% greater in interactions with White patients. Physicians with higher implicit bias scores and lower verbal dominance also received lower scores on patient ratings on interpersonal care, particularly from Black patients [72].

In focus groups with racially and ethnically diverse patients who sought medical care for themselves or their children in New York City, participants reported perceptions of discrimination in health care [73]. They reported that healthcare professionals often made them feel less than human, with varying amounts of respect and courtesy. Some observed differences in treatment compared with White patients. One Black woman reported [73]:

When the doctor came in [after a surgery], she proceeded to show me how I had to get up because I'm being released that day "whether I like it or not"…She yanked the first snap on the left leg…So I'm thinking, 'I'm human!' And she was courteous to the White lady [in the next bed], and I've got just as much age as her. I qualify on the level and scale of human being as her, but I didn't feel that from the doctor.

Another participant was a Latino physician who presented to the emergency department. He described the following [73]:

They put me sort of in the corner [in the emergency department] and I can't talk very well because I can't breathe so well. The nurse comes over to me and actually says, "Tu tiene tu Medicaid?" I whispered out, "I'm a doctor…and I have insurance." I said it in perfect English. Literally, the color on her face went completely white…Within two minutes there was an orthopedic team around me…I kept wondering about what if I hadn't been a doctor, you know? Pretty eye opening and very sad.

These reports are illustrative of many minority patients' experiences with implicit and explicit racial/ethnic biases. Not surprisingly, these biases adversely affect patients' views of their clinical interactions with providers and ultimately contribute to their mistrust of the healthcare system.

6. DEVELOPMENTAL MODEL TO RECOGNIZING AND REDUCING IMPLICIT BIAS

There are no easy answers to raising awareness and reducing health providers' implicit bias. Each provider may be in a different developmental stage in terms of awareness, understanding, acceptance, and application of implicit bias to their practice. A developmental model for intercultural sensitivity training has been established to help identify where individuals may be in this developmental journey [74,75]. It is important to recognize that the process of becoming more self-aware is fluid; reaching one stage does not necessarily mean that it is "conquered" or that there will not be additional work to do in that stage. As a dynamic process, it is possible to move back and forth as stress and uncertainty triggers implicit biases [74]. This developmental model includes six stages:

- Denial: In this stage, the individual has no awareness of the existence of cultural differences between oneself and members of other cultural groups and subgroups. Individuals in this stage have no awareness of implicit bias and cannot distinguish between explicit and implicit biases.

- Defense: In this stage, the person may accept that implicit biases exist but does not acknowledge that implicit biases exist within themselves.

- Minimization: An individual in this stage acknowledges that implicit biases may exist in their colleagues and possibly themselves. However, he or she is uncertain of their consequences and adverse effects. Furthermore, the person believes he or she is able to treat patients in an objective manner.

- Acceptance: In the acceptance stage, the individual recognizes and acknowledges the role of implicit biases and how implicit biases influence interactions with patients.

- Adaptation: Those in the adaptation stage self-reflect and acknowledge that they have unrecognized implicit biases. Not only is there an acknowledgement of the existence of implicit bias, these people begin to actively work to reduce the potential impact of implicit biases on interactions with patients.

- Integration: At this stage, the health professional works to incorporate change in their day-to-day practice in order to mitigate the effects of their implicit biases on various levels—from the patient level to the organization level.

7. CREATING A SAFE ENVIRONMENT

Creating a safe environment is the essential first step to exploring issues related to implicit bias. Discussions of race, stereotypes, privilege, and implicit bias, all of which are very complex, can be volatile or produce heightened emotions. When individuals do not feel their voices are heard and/or valued, negative emotions or a "fight-or-flight" response can be triggered [76]. This may manifest as yelling, demonstrations of anger, or crying or leaving the room or withdrawing and remaining silent [76].

Creating and fostering a sense of psychological safety in the learning environment is crucial. Psychological safety results when individuals feel that their opinions, views, thoughts, and contributions are valued despite tension, conflict, and discomfort. This allows the individual to feel that their identity is intact [76]. When psychological safety is threatened, individuals' energies are primarily expended on coping rather than learning [76]. As such, interventions should not seek to confront individuals or make them feel guilty and/or responsible [77].

When implicit bias interventions or assessments are planned, facilitators should be open, approachable, non-threatening, and knowledgeable; this will help create a safe and inclusive learning environment [77]. The principles of respect, integrity, and confidentiality should be communicated [77]. Facilitators who demonstrate attunement, authenticity, and power-sharing foster positive and productive dialogues about subjects such as race and identity [76]. Attunement is the capacity of an individual to tacitly comprehend the lived experiences of others, using their perspectives to provide an alternative viewpoint for others. Attunement does not involve requiring others to talk about their experiences if they are not emotionally ready [76]. Authenticity involves being honest and transparent with one's own position in a racialized social structure and sharing one's own experiences, feelings, and views. Being authentic also means being vulnerable [76]. Finally, power-sharing entails redistributing power in the learning environment. The education environment is typically hierarchical, with an expert holding more power than students or participants. Furthermore, other students may hold more power by virtue of being more comfortable speaking/interacting [76]. Ultimately, promoting a safe space lays a foundation for safely and effectively implementing implicit bias awareness and reduction interventions.

8. STRATEGIES TO PROMOTE AWARENESS OF IMPLICIT BIAS

As discussed, the IAT can be used as a metric to assess professionals' level of implicit bias on a variety of subjects, and this presupposes that implicit bias is a discrete phenomenon that can be measured quantitatively [79]. When providers are aware that implicit biases exist, discussion and education can be implemented to help reduce them and/or their impact.

Another way of facilitating awareness of providers' implicit bias is to ask self-reflective questions about each interaction with patients. Some have suggested using SOAP (subjective, objective, assessment, and plan) notes to assist practitioners in identifying implicit biases in day-to-day interactions with patients [80]. Integrating the following questions into charts and notes can stimulate reflection about implicit bias globally and for each specific patient interaction:

- Did I think about any socioeconomic and/or environmental factors that may contribute to the health and access of this patient?

- How was my communication and interaction with this patient? Did it change from my customary pattern?

- How could my implicit biases influence care for this patient?

When reviewing the SOAP notes, providers can look for recurring themes of stereotypical perceptions, biased communication patterns, and/or types of treatment/interventions proposed and assess whether these themes could be influenced by biases related to race, ethnicity, age, gender, sexuality, or other social characteristics.

A review of empirical studies conducted on the effectiveness of interventions promoting implicit bias awareness found mixed results. At times, after a peer discussion of IAT scores, participants appeared less interested in learning and employing implicit bias reduction interventions. However, other studies have found that receiving feedback along with IAT scores resulted in a reduction in implicit bias [81]. Any feedback, education, and discussions should be structured to minimize participant defensiveness [81].

9. INTERVENTIONS TO REDUCE IMPLICIT BIASES

Interventions or strategies designed to reduce implicit bias may be further categorized as change-based or control-based [58]. 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 [58]. These strategies include increasing awareness of biased thoughts and responses. The two types of interventions are not mutually exclusive and may be used synergistically.

PERSPECTIVE TAKING

Perspective taking is a strategy of taking on a first-person perspective of a person in order to control one's automatic response toward individuals with certain social characteristics that might trigger implicit biases [82]. The goal is to increase psychological closeness, empathy, and connection with members of the group [4]. Engaging with media that presents a perspective (e.g., watching documentaries, reading an autobiography) can help promote better understanding of the specific group's lives, experiences, and viewpoints. In one study, participants who adopted the first-person perspectives of African Americans had more positive automatic evaluations of the targeted group [83].

Interactive Activity

Consuming media that presents a viewpoint and life experience different from your own can help minimize implicit biases. Visit the following sites and consider how they might challenge or expand your perception of each group. Internet searches can help identify many more options for various social groups.

Think Out Loud Podcast

Young Black people share their experiences growing up in Portland, Oregon.

https://www.opb.org/article/2020/10/30/young-black-people-share-their-experiences-growing-up-in-portland

George Takei: Growing Up Asian-American

This PBS clip is a brief introduction, and the subject can be further explored in Takei's book They Called Us Enemy.

https://www.pbs.org/wnet/pioneers-of-television/video/george-takei-growing-up-asian-american

Seattle Public Library LGBTQ Staff Picks

A reading list including books and films focusing on LGBTQ+ life, culture, history, and politics.

https://www.spl.org/programs-and-services/social-justice/lgbtq/lgbt-staff-picks

EMPATHY INTERVENTIONS

Promoting positive emotions such as empathy and compassion can help reduce implicit biases. This can involve strategies like perspective taking and role playing [77]. In a study examining analgesic prescription disparities, nurses were shown photos of White or African American patients exhibiting pain and were asked to recommend how much pain medication was needed; a control group was not shown photos. Those who were shown images of patients in pain displayed no differences in recommended dosage along racial lines; however, those who did not see the images averaged higher recommended dosages for White patients compared with Black patients [84]. This suggests that professionals' level of empathy (enhanced by seeing the patient in pain) affected prescription recommendations.

In a study of healthcare professionals randomly assigned to an empathy-inducing group or a control group, participants were given the IAT to measure implicit bias prior to and following the intervention. Level of implicit bias among participants in the empathy-inducing group decreased significantly compared with their control group counterparts [85].

INDIVIDUATION

Individuation is an implicit bias reduction intervention that involves obtaining specific information about the individual and relying on personal characteristics instead of stereotypes of the group to which he or she belongs [4,82]. The key is to concentrate on the person's specific experiences, achievements, personality traits, qualifications, and other personal attributes rather than focusing on gender, race, ethnicity, age, ability, and other social attributes, all of which can activate implicit biases. When providers lack relevant information, they are more likely to fill in data with stereotypes, in some cases unconsciously. Time constraints and job stress increase the likelihood of this occurring [69].

MINDFULNESS

Mindfulness requires stopping oneself and deliberately emptying one's mind of distractions or allowing distractions to drift through one's mind unimpeded, focusing only on the moment; judgment and assumptions are set aside. This approach involves regulating one's emotions, responses, and attention to return to the present moment, which can reduce stress and anxiety [86]. There is evidence that mindfulness can help regulate biological and emotional responses and can have a positive effect on attention and habit formation [4]. A mindfulness activity assists individuals to be more aware of their thoughts and sensations. This focus on deliberation moves the practitioner away from a reliance on instincts, which is the foundation of implicit bias-affected practice [4,87].

Mindfulness approaches include yoga, meditation, and guided imagery. Additional resources to encourage a mindfulness practice are provided later in this course.

An approach to mindfulness using the acronym STOPP has been developed as a practical exercise to engage in mindfulness in any moment. STOPP is an acronym for [88]:

- Stop

- Take a breath

- Observe

- Pull back

- Practice

Interactive Activity

Visit the following website to view a short, animated video on the STOPP technique. After viewing the video, consider how you can incorporate the technique into your work.

https://www.youtube.com/watch?v=tStXi7f7Vgk

Mindfulness practice has been explored as a technique to reduce activation or triggering of implicit bias, enhance awareness of and ability to control implicit biases that arise, and increase capacity for compassion and empathy toward patients by reducing stress, exhaustion, and compassion fatigue [89]. One study examined the effectiveness of a loving-kindness meditation practice training in improving implicit bias toward African Americans and unhoused persons. One hundred one non-Black adults were randomized to one of three groups: a six-week loving-kindness mindfulness practice, a six-week loving-kindness discussion, or the waitlist control. The IAT was used to measure implicit biases, and the results showed that the loving-kindness meditation practice decreased levels of implicit biases toward both groups [90].

There is also some novel evidence that mindfulness may have neurologic implications. For example, one study showed decreased amygdala activation after a mindfulness meditation [91]. However, additional studies are required in this area before conclusions can be reached.

COUNTER-STEREOTYPICAL IMAGING

Counter-stereotypical imaging approaches involve presenting an image, idea, or construct that is counter to the oversimplified stereotypes typically held regarding members of a specific group. In one study, participants were asked to imagine either a strong woman (the experimental condition) or a gender-neutral event (the control condition) [92]. Researchers found that participants in the experimental condition exhibited lower levels of implicit gender bias. Similarly, exposure to female leaders was found to reduce implicit gender bias [93]. Whether via increased contact with stigmatized groups to contradict prevailing stereotypes or simply exposure to counter-stereotypical imaging, it is possible to unlearn associations underlying various implicit biases. If the social environment is important in priming positive evaluations, having more positive visual images of members in stigmatized groups can help reduce implicit biases [94]. Some have suggested that even just hanging photos and having computer screensavers reflecting positive images of various social groups could help to reduce negative associations [94].

EFFECTIVENESS OF IMPLICIT BIAS INTERVENTIONS

The effectiveness of implicit bias trainings and interventions has been scrutinized. In a 2019 systematic review, different types of implicit bias reduction interventions were evaluated. A meta-analysis of empirical studies published between May 2005 and April 2015 identified eight different classifications of interventions [13]:

- Engaging with others' perspectives, consciousness-raising, or imagining contact with outgroup: Participants either imagine how the outgroup thinks and feels, imagine having contact with the outgroup, or are made aware of the way the outgroup is marginalized or given new information about the outgroup.

- Identifying the self with the outgroup: Participants perform tasks that lessen barriers between themselves and the outgroup.

- Exposure to counter-stereotypical exemplars: Participants are exposed to exemplars that contradict negative stereotypes of the outgroup.

- Appeal to egalitarian values: Participants are encouraged to activate egalitarian goals or think about multiculturalism, cooperation, or tolerance.

- Evaluative conditioning: Participants perform tasks to strengthen counter-stereotypical associations.

- Inducing emotion: Emotions or moods are induced in participants.

- Intentional strategies to overcome biases: Participants are instructed to implement strategies to over-ride or suppress their biases.

- Pharmacotherapy

Interventions found to be the most effective were, in order from most to least, [13]:

- Intentional strategies to overcome biases

- Exposure to counter-stereotypical exemplars

- Identifying self with the outgroup

- Evaluative conditioning

- Inducing emotions

In general, the sample sizes were small. It is also unclear how generalizable the findings are, given many of the research participants were college psychology students. The 30 studies included in the meta-analysis were cross-sectional (not longitudinal) and only measured short-term outcomes, and there is some concern about "one shot" interventions, given the fact that implicit biases are deeply embedded. Would simply acknowledging the existence of implicit biases be sufficient to eliminate them [95,96]? Or would such a confession act as an illusion to having self-actualized and moved beyond the bias [95]?

Optimally, implicit bias interventions involve continual practice to address deeply habitual implicit biases or interventions that target structural factors [95,96].

10. ROLE OF INTERPROFESSIONAL COLLABORATION AND PRACTICE AND IMPLICIT BIASES

The study of implicit bias is appropriately interdisciplinary, representing social psychology, medicine, health psychology, neuroscience, counseling, mental health, gerontology, LGBTQ+ studies, religious studies, and disability studies [13]. Therefore, implicit bias empirical research and curricula training development lends itself well to interprofessional collaboration and practice (ICP).

One of the core features of ICP is sharing—professionals from different disciplines share their philosophies, values, perspectives, data, and strategies for planning of interventions [97]. ICP also involves the sharing of roles, responsibilities, decision making, and power [98]. Everyone on the team employs their expertise, knowledge, and skills, working collectively on a shared, patient-centered goal or outcome [98,99].

Another feature of ICP is interdependency. Instead of working in an autonomous manner, each team member's contributions are valued and maximized, which ultimately leads to synergy [97]. At the heart of this are two other key features: mutual trust/respect and communication [99]. In order to share responsibilities, the differing roles and expertise are respected.

Experts have recommended that a structural or critical theoretical perspective be integrated into core competencies in healthcare education to teach students about implicit bias, racism, and health disparities [100]. This includes [100]:

- Values/ethics: The ethical duty for health professionals to partner and collaborate to advocate for the elimination of policies that promote the perpetuation of implicit bias, racism, and health disparities among marginalized populations.

- Roles/responsibilities: One of the primary roles and responsibilities of health professionals is to analyze how institutional and organizational factors promote racism and implicit bias and how these factors contribute to health disparities. This analysis should extend to include one's own position in this structure.

- Interprofessional communication: Ongoing discussions of implicit bias, perspective taking, and counter-stereotypical dialogues should be woven into day-to-day practice with colleagues from diverse disciplines.

- Teams/teamwork: Health professionals should develop meaningful contacts with marginalized communities in order to better understand whom they are serving.

Adopting approaches from the fields of education, gender studies, sociology, psychology, and race/ethnic studies can help build curricula that represent a variety of disciplines [78]. Students can learn about and discuss implicit bias and its impact, not simply from a health outcomes perspective but holistically. Skills in problem-solving, communication, leadership, and teamwork should be included, so students can effect positive social change [78].

11. CONCLUSION

In the more than three decades since the introduction of the IAT, the implicit bias knowledge base has grown significantly. It is clear that most people in the general population hold implicit biases, and health professionals are no different. While there continue to be controversies regarding the nature, dynamics, and etiology of implicit biases, it should not be ignored as a contributor to health disparities, patient dissatisfaction, and suboptimal care. Given the complex and multifaceted nature of this phenomenon, the solutions to raise individuals' awareness and reduce implicit bias are diverse and evolving.

12. RESOURCES

American Bar Association Diversity and Inclusion Center

Toolkits and Projects

https://www.americanbar.org/groups/diversity/resources/toolkits

National Implicit Bias Network

https://implicitbias.net/resources/resources-by-category

The Ohio State University

The Women's Place: Implicit Bias Resources

https://womensplace.osu.edu/resources/implicit-bias-resources

The Ohio State University

Kirwan Institute for the Study of Race and Ethnicity

http://kirwaninstitute.osu.edu

University of California, Los Angeles

Equity, Diversity, and Inclusion: Implicit Bias

https://equity.ucla.edu/know/implicit-bias

University of California, San Francisco, Office of Diversity and Outreach

Unconscious Bias Resources

https://diversity.ucsf.edu/resources/unconscious-bias-resources

Unconscious Bias Project

https://unconsciousbiasproject.org

MINDFULNESS RESOURCES

University of California, San Diego Center for Mindfulness

https://cih.ucsd.edu/mindfulness

University of California, Los Angeles Guided Meditations

https://www.uclahealth.org/programs/marc/free-guided-meditations/guided-meditations

Mindful: Mindfulness for Healthcare Professionals

https://www.mindful.org/mindfulhome-mindfulness-for-healthcare-workers-during-covid

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96102 • Frontotemporal Dementia

Lauren E. Evans, MSW

Ellen Steinbart, RN, MA

www.netce.com

Copyright © 2021 NetCE, All rights reserved.

Frontotemporal dementia (FTD) is a group of degenerative brain disorders causing progressive deterioration in behavior, language, and/or movement. There are presently approximately 60,000 people with FTD in the United States. Onset generally occurs between 50 and 70 years of age, making FTD one of the most common presenile dementias. FTD affects the frontal and temporal lobes of the brain, which control emotions, judgment, personality, memory and language. The clinical diagnosis of FTD can be challenging, as some symptoms overlap with Alzheimer disease and other forms of dementia. FTD can be categorized based on its primary symptoms into three basic types: behavioral variant FTD, primary progressive aphasia, and progressive motor decline. Although most FTD does not appear to be inherited, genetics does play a role in a significant minority of cases. There is no effective treatment or cure for FTD, but there are strategies for management of symptoms. This course will discuss the possible causes and pathophysiology, diagnosis, and management strategies for FTD.

Table of Contents

96102 • Frontotemporal Dementia

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 OF FTD

3. PATHOGENESIS AND PATHOPHYSIOLOGY OF FTD

4. CLINICAL PRESENTATION

BEHAVIORAL PRESENTATION

LANGUAGE PRESENTATION

FTD OVERLAP WITH MOVEMENT DISORDERS

CLINICAL DIAGNOSIS OF FTD

5. GENETICS AND FTD

6. MANAGEMENT OF FTD

CAREGIVER SUPPORT

7. PROGRESSION OF FTD

8. RESEARCH RELATED TO FTD

9. CASE STUDY

10. CONCLUSION

11. RESOURCES

Works Cited

Evidence-Based Practice Recommendations Citations

96102 • Frontotemporal Dementia

Education Category. Psychiatric / Mental Health

Release Date. 11/01/2021

Expiration Date. 10/31/2024

Course Overview

Frontotemporal dementia (FTD) is a group of degenerative brain disorders causing progressive deterioration in behavior, language, and/or movement. There are presently approximately 60,000 people with FTD in the United States. Onset generally occurs between 50 and 70 years of age, making FTD one of the most common presenile dementias. FTD affects the frontal and temporal lobes of the brain, which control emotions, judgment, personality, memory and language. The clinical diagnosis of FTD can be challenging, as some symptoms overlap with Alzheimer disease and other forms of dementia. FTD can be categorized based on its primary symptoms into three basic types: behavioral variant FTD, primary progressive aphasia, and progressive motor decline. Although most FTD does not appear to be inherited, genetics does play a role in a significant minority of cases. There is no effective treatment or cure for FTD, but there are strategies for management of symptoms. This course will discuss the possible causes and pathophysiology, diagnosis, and management strategies for FTD.

Audience

This course is designed for physicians, nurses, and allied health and mental health professionals who may intervene to support patients with frontotemporal dementia and their families.

Accreditations & Approvals

In support of improving patient care, 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 by the California Nursing Home Administrator Program as a provider of continuing education. Provider number 1622. 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 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. 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). This course is approved by the California Nursing Home Administrator Program for 2 hour(s) of continuing education credit - NHAP#1622002-9389/P. California NHAs may only obtain a maximum of 10 hours per course. NetCE is authorized by IACET to offer 0.2 CEU(s) for this program. AACN Synergy CERP Category A.

Individual State Nursing Approvals

In addition to states that accept ANCC, NetCE is approved as a provider of continuing education in nursing by: Alabama, Provider #ABNP0353, (valid through July 29,2025); Alabama, Provider #ABNP0353, (valid through July 29, 2025); 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; 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

The purpose of this course is to provide healthcare professionals with current information on frontotemporal dementia (FTD). Understanding the epidemiology, pathology, clinical features, diagnostic process, genetics, symptom treatment/management, role of brain autopsy, and current research provides a foundation for the care of patients with FTD and support for their families.

Learning Objectives

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

1. Describe the epidemiology of frontotemporal dementia (FTD) in the United States.

2. Explain the brain changes of FTD and their general clinical manifestations.

3. Identify the three general presentations of FTD.

4. Review how a clinical diagnosis of FTD is made, including differentiation from Alzheimer disease.

5. Summarize the role of genetics in FTD.

6. Discuss strategies for managing symptoms of FTD and providing support to family caregivers.

7. Identify goals of current research on FTD.

Faculty

Ellen Steinbart, RN, MA, received a Bachelor of Arts from Macalester College in 1972, a Bachelor of Science in Nursing from Cornell University-New York Hospital School of Nursing in 1974, and a Master of Arts from the University of Washington School of Nursing in 1979. She worked as a hospital medical-surgical nurse and an intensive-care burn unit nurse, and she taught medical-surgical nursing at the University of Washington School of Nursing. For 25 years, she was a research nurse at the University of Washington, coordinating research projects on the role of genetics in dementia, including frontotemporal degeneration. She is now retired.

Lauren E. Evans, MSW, received her Master’s degree in Social Work from California State University, Sacramento, in 2008. Her focus was on political and community social work. She has also been a Registered International Instructor of Therapeutic Horseback Riding through the Professional Association of Therapeutic Horsemanship International (PATH Intl.) since 2006. She currently works as a mental health practitioner with the homeless population.

Faculty Disclosure

Contributing faculty, Ellen Steinbart, RN, MA, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Contributing faculty, Lauren E. Evans, 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

Frontotemporal dementia (FTD) is a group of degenerative brain disorders characterized by behavior and language problems and also overlapping with some motor/movement diseases. FTD causes progressive deterioration in a person's ability to function as the result of damage to the frontal and temporal lobes of the brain. FTD is also referred to as frontotemporal degeneration, frontotemporal lobar degeneration, and Pick disease.

Dr. Arnold Pick, a Czech neurologist, psychiatrist, and neuropathologist, first described frontal and temporal lobe atrophy causing dementia and progressive aphasia in 1892 [1]. The clinical syndrome subsequently became known as "Pick disease." FTD is the third leading cause of dementia across all age groups, after Alzheimer disease (AD) and Lewy body dementia [2]. It is one of the most common causes of early-onset dementia, with onset typically between 45 and 64 years of age [2,3].

The clinical presentation of FTD can be complex, and obtaining an accurate diagnosis can be challenging. The unique clinical symptoms of FTD, neuropsychologic assessment, and brain imaging can help distinguish it from AD and other dementias. There is presently no effective treatment for FTD, and symptom management can be challenging for healthcare providers and family caregivers. Research is in progress to better understand FTD, hopefully leading to effective treatment, cure, and prevention of this devastating disease.

2. EPIDEMIOLOGY OF FTD

It is estimated that FTD affects approximately 60,000 people in the United States [3]. As noted, the age of onset for FTD is typically 45 to 64 years, with a mean of 58.5 years and a reported range between 21 and 80 years of age [2,3,4,5]. In the United States, the prevalence in people 45 to 64 years of age is estimated at 15 to 22 per 100,000 population; the incidence in this group is 2.7 to 4.1 per 100,000 [5]. It is estimated that 60% of those with FTD have onset between 45 and 64 years of age; 10% have onset before 45 years of age, and 30% have onset after 64 years of age [5]. FTD is now considered by some to be the most common form of pre-senile dementia in patients younger than age 60, even more common than AD in this group [6,7,8].

FTD affects both men and women. However, it is unclear if men and women are affected equally, or if some subtypes of FTD may be more common in one gender or the other [9]. Significant time (average: 3.6 years) often passes between symptom onset and actual clinical diagnosis [5].

The disease duration for FTD can range from 2 to 20 years from symptom onset to death, with a mean duration of 6 to 13 years [3,5]. Pneumonia is the most common cause of death [3].

3. PATHOGENESIS AND PATHOPHYSIOLOGY OF FTD

Patients with FTD experience a progressive loss of neurons in the frontal and anterior temporal lobes, resulting in atrophy in these areas of the brain. They may also develop gliosis in the frontal and temporal lobes where neurons have been lost or damaged.

In FTD, affected neurons have an abnormal accumulation of protein within the cell, called inclusions. Three types of intra-neuronal inclusions have been identified, based on the protein involved. In some cases, the inclusions are composed of an abnormal form of the protein tau. In other patients, the inclusions are composed of the transactive response DNA-binding protein 43 (TDP-43). In a smaller number of FTD cases, the inclusions are composed of fused in sarcoma (FUS) protein [10].

The frontal and anterior temporal lobes of the brain control executive functions (e.g., planning, organizing, abstract thinking, judgment, decision making), personality, social behavior, and language. The changes associated with FTD causes impairments in executive function, personality, behavior, and/or language. The location of the neurodegeneration correlates fairly well with the clinical presentation [10]. Changes in other areas of the brain may cause overlapping movement problems. While the cause of most cases of FTD is not known, some cases are now known to be caused by genetic mutations.

4. CLINICAL PRESENTATION

FTD causes a gradual, progressive decline in behavior and/or language; movement disorders may also be involved. Behavior or language problems are typically the first and most prominent symptoms of FTD, whereas memory problems are the first symptoms of AD [5]. Subtypes of FTD have been identified based on clinical presentation (Table 1). Behavioral variant FTD (bvFTD) is the most common form and involves changes in behavior, personality, and emotions. Language presentations are referred to as primary progressive aphasia (PPA) and can take one of three forms: nonfluent/agrammatic variant PPA (nfvPPA), semantic variant PPA (svPPA), or logopenic variant PPA (lvPPA) [11]. Nonfluent/agrammatic PPA begins with problems in speech production, while svPPA involves impaired word comprehension and object recognition and lvPPA involves word-finding problems. A movement presentation may appear as progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), or motor neuron disease (MND). Some patients may present with symptoms that overlap the different subtypes of FTD or may develop symptoms of other subtypes of FTD as the disease evolves. As more is learned about FTD, the terminology and classification of the subtypes may be revised.

Table 1: FORMS OF FRONTOTEMPORAL DEGENERATION

Behavioral presentation

- Behavioral variant FTD (bvFTD)

Language presentation, variants of primary progressive aphasia (PPA)

- Nonfluent/agrammatic PPA (nfvPPA), previously called progressive non-fluent aphasia (PNFA)

- Semantic variant PPA (svPPA), previously called semantic dementia (SD)

- Logopenic variant PPA (lvPPA) (often found to have Alzheimer disease pathology at autopsy)

Associated movement disorders (not classified as FTD, but have shared symptoms)

- Corticobasal syndrome (CBS)

- Progressive supranuclear palsy (PSP)

- Motor neuron disease, also called amyotrophic lateral sclerosis (FTD/MND or FTD/ALS)

Source: Compiled by Author

BEHAVIORAL PRESENTATION

Behavioral Variant FTD

As noted, bvFTD is the most common type of FTD, estimated to account for more than half of all cases [12]. The prominent features include disinhibition, apathy/inertia, loss of empathy, compulsive behaviors, hyper-orality, and impaired executive function (Table 2) [13]. People with FTD may become socially withdrawn, inflexible, and impulsive. They may have a shortened attention span and a tendency to be easily distracted. Behavior may become socially inappropriate. People with bvFTD are usually unaware of the changes in their personality and behavior and the impact these changes have on others. Memory and visual-spatial functioning are initially relatively spared in bvFTD. Some individuals with bvFTD may develop symptoms similar to Parkinson disease, such as bradykinesia, rigidity, postural instability, and masked face.

Table 2: BEHAVIORAL VARIANT FTD

Major Clinical Features

Examples

Disinhibition

Making inappropriate comments, taking food off someone else's table at a restaurant, telling sexual jokes, shoplifting, hitting

Apathy

Less involved in old hobbies or activities, deterioration in personal hygiene

Loss of empathy

Indifferent when a family member is hurt

Compulsive behaviors

Repeating the same phrase, clapping hands in the same pattern repeatedly, checking the time repeatedly

Hyper-oral behaviors

Overeating, eating one certain type of food, eating excessive sweets

Impaired executive function

Poor performance at work, poor financial decisions, difficulty planning and preparing a meal

Source: Compiled by Author

LANGUAGE PRESENTATION

Nonfluent/Agrammatic Variant PPA

Nonfluent/agrammatic variant PPA, also referred to as progressive non-fluent aphasia (PNFA), accounts for about 25% of all FTD cases and involves problems with language expression [12]. People with nfvPPA have difficulty producing speech but retain the meaning of words and know what they want to say. As a result, speech may become hesitant, slow, and labored. Speech patterns may be "agrammatic" or "telegraphic," meaning that only the most important content words are used, without connecting words. For example, a patient might say "Tuesday…hospital…sister." Patients with nfvPPA have difficulty talking on the telephone and tend to talk progressively less. Eventually, some may become mute. While in the early stages, these patients continue to understand the speech of others, but this comprehension is eventually lost also. Reading and writing skills are better preserved than speech, although these abilities are also eventually lost. As the disease progresses, patients may develop behavioral symptoms. Some individuals with nfvPPA may develop extrapyramidal symptoms of rigidity and tremors, as seen in CBS and PSP.

Semantic Variant PPA

Semantic variant PPA, also referred to as semantic dementia, represents about 20% of FTD cases [12]. Semantic variant PPA involves the loss of understanding of the meaning of words and objects. Speech is still fluent and grammatically correct, but people with svPPA have a declining ability to comprehend the meaning of words (especially nouns) or to recognize familiar objects or faces. For example, a person with svPPA who is very familiar with vegetables might read a menu and ask: "What is broccoli?" If shown a picture of a carrot, the patient may not be able to name it and may not recognize the word when told. There are progressive word-finding problems, reading and spelling skills decline, and retrieving names becomes difficult. Later in the disease, people with svPPA may develop behavioral changes similar to those seen in patients with bvFTD.

Logopenic Variant PPA

Logopenic variant PPA is characterized by difficulty retrieving words, resulting in slow speech with frequent pauses. These patients may also have trouble repeating long phrases and understanding complex sentences. Eventually, people with lvPPA may become mute. Reading and writing skills are initially preserved, but these decline as the disease progresses. People with lvPPA have word-finding problems similar to people with AD and are often found to have AD pathology at autopsy [8].

For all patients with suspected language presentations of FTD, it is important to consider the role of culture and preferred language.

FTD OVERLAP WITH MOVEMENT DISORDERS

Progressive Supranuclear Palsy

PSP is a neurodegenerative condition characterized by problems with gait and balance, causing postural instability, falls, and difficulty with eye movement coordination. The pathophysiology of PSP shows a loss of cells in the basal ganglia, substantia nigra, subthalamus, and brainstem, and affected neurons have inclusions composed of abnormal tau protein. There are similarities between PSP and Parkinson disease, including bradykinesia, rigidity, masked face, dysarthria, dysphagia, apathy, and depression. Some people with PSP develop behavioral problems, but these are often milder than those seen in other types of FTD. Some people with PSP may develop progressive memory and language problems, and there may be a decline in executive function.

Corticobasal Syndrome

CBS is a neurodegenerative condition that may initially present with movement problems, dementia, or both. In CBS, there is atrophy in multiple areas of the brain, including the frontoparietal regions, basal ganglia, and cerebral peduncles. Neuronal inclusions are usually composed of abnormal tau protein. Signs of CBS typically begin with decreased movement on one side of the body, muscle rigidity, and tremor. A hand, arm, or leg on the affected side may demonstrate apraxia (i.e., inability to make the limb follow commands). Patients may describe the affected limb as not feeling like a part of their body, a sensation referred to as "alien limb syndrome." Symptoms may become bilateral as the disease progresses. People with CBS may also experience personality changes, executive dysfunction, and language problems as the disease progresses.

FTD with Motor Neuron Disease

Approximately 15% of people with FTD also develop problems with motor neurons that control voluntary movement [10]. This is referred to as FTD with motor neuron disease (FTD/MND) or FTD with amyotrophic lateral sclerosis (FTD/ALS). Pathologically, in addition to frontal and temporal lobe atrophy, there is also atrophy in the motor regions of the cortex and loss of motor neurons in the brain stem and spinal cord. In FTD/MND, damaged neurons usually have abnormal inclusions composed of the protein TDP-43. Patients may present with behavior or language problems, but then additionally develop muscle problems, including weakness, stiffness, twitches, cramps, and/or atrophy. Muscle problems can affect arms, legs, face, mouth, and tongue, causing patients to experience clumsiness, dysphagia, dysarthria, and hyper-reflexia. An estimated 15% of patients with MND or ALS go on to develop behavioral and executive dysfunction symptoms of FTD as their disease progresses [10].

CLINICAL DIAGNOSIS OF FTD

The diagnosis of FTD can be challenging because of the wide range of symptoms, the relatively early age of onset, and the slow progression. There is no single test to diagnose FTD, and it may be initially misdiagnosed as a psychiatric disorder (e.g., depression, schizophrenia), AD, Parkinson disease, or vascular dementia. Accurate diagnosis of FTD is important because some of the medications used to treat these other diseases may be detrimental to patients with FTD. Patients with suspected FTD are often referred to neurologists or neuropsychologists with special expertise in FTD and related neurodegenerative disorders for a comprehensive evaluation.

The clinical diagnosis of FTD is based on the clinical history, family history, neurologic examination, neuropsychologic evaluation, and neuroimaging. Other tests may also be performed for differential diagnosis. The diagnostic process may take time, and the diagnosis may change as more tests are done or as new symptoms appear.

The clinical history is obtained from the patient and his/her family or friends. It is important that family or friends provide information regarding symptoms, as patients are often unaware of their behavior changes.

The family history should focus on whether any other relatives have had a neurodegenerative disease. Any cases of dementia, language problems, or movement disorders should be noted, along with specific information about symptoms, diagnosis, age of onset, course of disease, age at death, and autopsy findings. Such background information may be valuable for both diagnosis and understanding genetic risk.

The neurologic examination typically includes assessment of the patient's general appearance and speech, mental status, cranial nerves, motor system, sensation, reflexes, and cerebellar function (coordination and balance). Consulting a neurologist who has knowledge and experience in FTD can be valuable when reaching a definitive diagnosis.

The neuropsychologic examination assesses brain function and may identify areas of the brain that have been damaged. It typically involves an interview and the administration of written tests. These tests may focus on attention and concentration, memory, orientation, language, visual-spatial abilities, and/or executive functions (e.g., reasoning, planning, organizing, problem solving). Patients with FTD may show deterioration in the areas of attention and concentration, language, and executive function, but may do relatively well on memory and visual-spatial tests.

The Neuropsychiatric Inventory (NPI) may be administered to caregivers of patients with suspected FTD. This survey helps assess behavior and psychopathology by inquiring about the patient's delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability, unusual motor activity, nighttime behavioral problems, and eating abnormalities.

Brain scans are important tools in the diagnosis of FTD. Computed tomography (CT) may be done to determine if there is a tumor, hemorrhage, or other brain injury that could account for the symptoms. Magnetic resonance imaging (MRI) provides better visualization of the brain than CT and is often done to evaluate brain atrophy when FTD is suspected. Patients with FTD have progressive frontal and anterior temporal atrophy apparent on MRI. Typically, in bvFTD, there is atrophy of the frontal lobe (involved in personality, judgment, and executive function) and the anterior temporal lobe. In nfvPPA, there is left frontal lobe atrophy (involved in speech production). In svPPA, the atrophy is focused in the anterior temporal lobe (involved in language and face recognition). In specialty or research centers, positron emission tomography (PET), single photon emission computed tomography (SPECT), or functional MRI (fMRI) brain scans may be done to further evaluate brain functioning.

While there is no laboratory test that can diagnose FTD, some tests may be ordered to rule out other diseases with symptoms similar to those of FTD. Blood work may be ordered to identify dehydration, thyroid disease, vitamin B12 deficiency, or infections affecting the brain. An electroencephalogram (EEG) may be done if there is concern that seizures might be causing the patient's symptoms. In the early stages of FTD, EEG findings are usually normal or have non-specific findings. Lumbar puncture may be done to evaluate cerebral spinal fluid and rule out rare brain infections or cancer. Electromyography may be used to identify muscle weakness or myoclonus if MND (or ALS) is being considered as a possible diagnosis. In addition, language evaluation by a speech pathologist can be an important tool in diagnosing patients with nonfluent/agrammatic, semantic, or logopenic variant PPA.

It may be challenging to clinically differentiate FTD from early AD (Table 3). The only way to establish an unquestionable diagnosis of FTD is through a brain autopsy after a patient has died. Examination of the brain tissue will show the precise location and severity of the brain atrophy, and microscopic studies can determine the protein composition of the inclusions in affected neurons.

Table 3: EARLY SIGNS AND SYMPTOMS OF FTD VERSUS ALZHEIMER DISEASE

Clinical Features

FTD

Alzheimer Disease

Hallmark

Decline in behavior, language, and/or movement; memory is retained initially

Decline in memory; socially appropriate behavior is retained initially

Initial language problems

May involve speech production, understanding words and recognizing familiar objects, or retrieving words

Word-finding or name recall

Age at onset

Usually 45 to 64 years of age

Usually 65 years of age or older

Movement problems

May have early movement disorder, with gait and balance problems, rigidity, apraxia, or muscle weakness

Usually no movement problems early in disease

Source: [3,8,14]

For families, brain autopsy can confirm the diagnosis (or identify a different cause of the dementia) and bring a measure of closure. Accurate diagnosis may be especially important if there is concern about genetic risk to other family members.

Discussion about brain autopsy should be handled delicately and with compassion at a time that is appropriate for the family; the subject may be emotionally difficult for some families. Introducing the topic ahead of time allows families to consider their feelings about brain autopsy aside from the emotional crisis of the death of a loved one and the immediate time pressure of funeral arrangements. Families may then discuss the topic among themselves and come to a consensus.

Should a family wish to have a brain autopsy done when the patient dies, the physician can help identify a pathology service experienced in neurologic disorders and preliminary logistical planning can be done ahead of time. Arrangements may be coordinated with a research center that specializes in brain autopsy for FTD. The autopsy is done as soon as possible after death, often within 6 to 24 hours. The procedure is not disfiguring, so open-casket funerals may be planned if the family so chooses.

In addition to answering families' questions regarding diagnosis, brain autopsy can also aid researchers in better understanding the correlation between the clinical signs of FTD and the pathologic changes in the brain. This may benefit future generations by improving diagnosis and advancing research on therapies for FTD.

5. GENETICS AND FTD

Understanding of the role of genetics in FTD is still evolving. Presently, it appears that most cases of FTD (approximately 60%) are sporadic, meaning one person in a family has the disease, there is no family history of any relative with the disease, and the disease does not appear to be inherited.

However, approximately 40% of those with FTD report a family history of one or more relatives with a neurodegenerative disease [6,9,10]. This is referred to as familial FTD. In some cases of familial FTD, no specific genetic mutation can be identified as the cause. The risk to family members of a person with familial FTD without an identified genetic mutation is increased over the general population, but the specific increased risk is unclear.

An estimated 10% to 20% of all FTD cases are caused by an inherited genetic mutation [6,8]. Patients with a strong family history of multiple relatives with FTD and/or MND are more likely to have an inherited form of FTD caused by a genetic mutation. Genetic mutations causing FTD are inherited in an autosomal dominant inheritance pattern, meaning each child of an affected parent is born with a 50% chance of inheriting the genetic mutation.

Several specific genetic mutations have been identified as being implicated in inherited FTD. In 1998, the first gene associated with hereditary FTD—the microtubule-associated protein tau (MAPT) gene on chromosome 17—was discovered [15,16]. Mutations in this gene cause an abnormal accumulation of tau protein in affected neurons. MAPT mutations are thought to account for 2% to 11% of familial FTD cases [17]. These mutations most commonly cause bvFTD but may also cause svPPA, PSP, and/or CBS. FTD symptoms may vary widely, even within families.

In 2006, mutations in the progranulin (GRN) gene on chromosome 17 were discovered to cause FTD [18,19]. Mutations in the GRN gene cause abnormal accumulations of TDP-43 protein in affected neurons. GRN mutations are thought to represent about 5% to 10% of all inherited FTD cases [17]. They most commonly cause bvFTD, but are also associated with nfvPPA and CBS. GRN mutations appear to have decreased penetrance, meaning that, for unknown reasons, some people with the mutation may not develop symptoms of the disease.

In 2011, the genetic mutation C9orf72 was discovered on chromosome 9 [20,21]. Mutations in C9orf72 cause an abnormal accumulation of TDP-43 in affected neurons. To date, C9orf72 mutations are the most common genetic cause of FTD, found in about 25% of familial FTD and 6% of sporadic cases [22]. C9orf72 mutations appear to cause FTD (usually bvFTD or language presentation), MND, and a combination of FTD and MND.

Other very rare genetic mutations have also been associated with FTD. Mutations in the gene valosin-containing protein (VCP) on chromosome 9, charged multivesicular body protein 2B (CHMP2B) on chromosome 3, TAR DNA-binding protein (TARDBP), FUS, TBK1, EXT2, and SQSTM1 have been associated with FTD [29].

Clinical genetic testing is available for the MAPT, GRN, and C9orf72 genetic mutations causing hereditary FTD, as well as some of the other very rare genetic mutations. Genetic testing may be ordered after informed consent and clear discussion of the implications with the patient and his/her family. For patients with FTD, identification of a genetic mutation confirms the diagnosis of FTD and provides information about risk to other family members. Each of the patient's siblings and each of the patient's children would be at 50/50 risk for having inherited the genetic mutation causing FTD. If a genetic mutation causing FTD is identified, other at-risk family members may be tested.

If a genetic mutation causing FTD is identified in a patient with FTD, unaffected at-risk family members could choose to have pre-symptomatic (predictive) genetic testing done to determine if they have inherited the genetic mutation that would someday cause FTD. Individuals considering pre-symptomatic genetic testing are referred for formal professional genetic counseling to help them make the best decision regarding whether or not to learn their FTD genetic status.

6. MANAGEMENT OF FTD

There is presently no treatment to slow the progression of or cure FTD. No medication has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of FTD; however, medications used to treat other disorders may be prescribed off-label for the management of FTD symptoms. Their use may be limited by the potential adverse effects. Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), may be prescribed for behavioral symptoms of FTD, and low-dose trazodone has been used for agitation and aggression [9]. While the anticholinesterase inhibitors donepezil, galantamine, and rivastigmine are beneficial for some patients with AD, they generally have not been helpful for patients with FTD [9]. The glutamate NMDA receptor antagonist memantine, used for moderate-to-severe AD, has been used for patients with FTD as well, but a 2013 study showed that it provided no benefit to patients with FTD and that it may be harmful to cognition [23]. Antipsychotics are occasionally used to treat significant agitation and behavioral symptoms, but only with caution, as antipsychotics can have serious adverse effects such as extrapyramidal adverse effects (parkinsonism), depression, sedation, falls, incontinence, and disinhibition, and patients with FTD may have an increased susceptibility to the these effects [9]. Elderly patients with dementia who take antipsychotics have a 1.6- to 1.7-fold increase in mortality secondary to cardiac problems or infection, prompting the FDA to issue a warning about their use in older patients with behavioral disturbances [9]. L-DOPA has shown a minimal response for parkinsonism in patients with PSP and CBD [28]. Research is being done to further evaluate the use of available medications for the management of FTD and to find new, more effective treatments.

Evidence Based Practice Recommendation

According to the Royal Australian and New Zealand College of Psychiatrists, general principles of dementia care apply for the management of frontotemporal dementia, but specific issues relate to the early onset of the illness in middle life and that affected persons may lack insight into their deficits leading to occupational and social problems.

https://journals.sagepub.com/doi/abs/10.1177/1039856215582276

Last Accessed: October 15, 2021

Strength of Recommendation/Level of Evidence: Expert Opinion/Consensus Statement

Management of FTD includes providing care to patients with FTD and support to their families. Caring for a person with FTD involves managing the symptoms, keeping the patient safe, and providing help in activities of daily living.

Apathy is a common symptom in patients with bvFTD, often resulting in neglect of their personal hygiene and grooming. Supervision, encouragement, and help with bathing, dressing, and grooming may be needed. For behavioral problems, simple interventions like distraction (e.g., introducing a new activity) may help interrupt the troublesome behavior. For some patients, modification of the environment or behavior may help minimize the potential for harm. For example, if the patient is pacing, creating a safe route for him or her to walk can be helpful. Physical therapists may be able to help develop an exercise program to maintain mobility. Exercise has also been shown to improve mood and cognition and may improve behavior management in patients with dementia [24]. If behaviors such as agitation or aggression become severe, a medication may be prescribed off-label to control difficult or dangerous behaviors. Supervision may be necessary to ensure patients take medications as prescribed.

Some individuals with FTD have eating problems, such as overeating, eating just one type of food, or craving sweets. For these patients, it may be necessary to monitor weight and provide help with meal preparation to provide a balanced, nutritious diet. Access to additional foods, drinks, or sweets should be limited.

Speech pathologists or therapists may be helpful in diagnosing the specific language problems exhibited by patients with FTD, including nonfluent/agrammatic, semantic, or logopenic variant PPA. Speech therapy may also help patients to find new communication strategies, such as sign language, carrying cards with specific messages, or using a computer with pre-programmed words or phrases [25]. Such techniques may help those with language problems communicate with family and friends. Speech therapists may also be able to evaluate and address swallowing problems, if these arise.

Caring for a patient with FTD includes maintaining a safe environment for the patient and for those around him/her. A structured environment and keeping the daily routine the same is often helpful. In addition, persons with FTD should no longer drive, and safety measures should be taken at home, especially in the kitchen and bathroom. If a patient with FTD shows aggression, disinhibition, or poor judgment, close supervision is necessary when he/she is around others, especially children or the frail elderly, to prevent them from being inadvertently harmed.

It also may be necessary to monitor the patient's behavior in public places. If an individual displays inappropriate behavior, tense situations may be diffused by explaining that he or she has FTD and cannot control his/her behavior. Simple cards with this brief explanation can be made, carried, and shared with people who might be disturbed by a patient's inappropriate behavior.

If a patient with FTD has gait and balance problems, measures should be taken to prevent falls. This may include keeping the home environment free of obstacles and loose rugs and installing shower bars and a raised toilet seat. Mobility aids may be helpful. Occupational therapists should provide intervention to help patients with FTD complete activities of daily living as the disease progresses.

CAREGIVER SUPPORT

FTD places enormous burdens on the family. Most dementia care is provided at home by family caregivers, often spouses. Caregivers for those with FTD face physical, emotional, and financial challenges. FTD caregiver burden, stress, and depression are greater even than that seen with AD [26,27].

The first challenge that families of those with FTD may face is obtaining an accurate diagnosis. The process can involve years of uncertainty and stress before the correct clinical diagnosis of FTD is made. Even during the diagnosis process, support for families begins with information and education about FTD. Accurate information can lead to understanding and a greater sense of control over the stressful situation. It is important for families and caregivers to understand that the behavior changes they observe are the result of the disease. Their loved one may display behaviors that are embarrassing, offensive, self-centered, uncaring, and aggressive, with complete lack of insight about how the behavior affects others. The caregiver may feel like he/she is suddenly living with a stranger.

The aggression, disinhibition, and poor judgment associated with FTD can put family members at risk of harm. Because FTD affects people at a relatively young age, there may still be children in the home. Families should recognize the risk to others in the home and seek help creating strategies to keep themselves and other family members safe.

Language may be impaired in people with FTD, making communication difficult. This can interfere not only with communication between the patient and the caregiver, but it can also limit participation in larger social activities. Speech therapy can provide new approaches to communication, helping not only the patient but also the caregiver.

Because FTD usually begins at a relatively young age, it can cause a significant financial burden for families. There may be loss of income, and retirement benefits may be affected because the patient is unable to continue working. Financial and legal issues that should be addressed include insurance, social security disability, financial planning for the future (when additional care will be needed), power-of-attorney arrangements, and a living will. Social workers, financial advisors, and attorneys are resources available to families to help address these issues.

The demands on caregivers increase as FTD progresses. Caregivers will be required to provide more supervision and increasing assistance for activities of daily living. While providing care for an individual with FTD, the caregiver may also be grieving the loss of his or her previously healthy loved one. Family caregivers can become physically and emotionally exhausted, and they may feel isolated in their role as caregiver. Interventions to help reduce caregiver stress include an individualized patient management plan, environmental changes to promote safety and facilitate care, and strengthening caregiver coping strategies and skills. Family caregivers should be encouraged to ask for and accept help in caring for their loved one with FTD, allowing them to take time for themselves and address their own health needs. Connection with community resources may also be helpful. Community resources for FTD caregivers include national organizations such as the Association for Frontotemporal Degeneration, attorneys and financial planners, social service programs, adult day care programs, respite care, support groups, and individual or family counseling.

Family caregivers should look ahead and consider how they wish care to be provided to their loved one as FTD progresses. Patients with FTD will become more dependent and more difficult to safely manage at home by a family caregiver as the disease progresses. Social workers can be a good resource to caregivers as they consider options such as extra in-home nursing care, care communities, and long-term care facilities. Locating an appropriate care facility that accepts patients with FTD can be challenging. These patients are often younger, stronger, and more active than the typical residents of care facilities. Facility staff may need education and support to understand the unique features of FTD and to learn how to provide care to these patients while maintaining a safe environment for all residents in the facility.

Nurses play an important role in caring for those with FTD and providing support to their families. Nurses interact with patients with FTD and their families in the outpatient clinic setting, in-home care setting, and long-term care facility and may be involved in monitoring symptoms, developing and implementing individualized patient care plans, and providing direct patient care. It is important for all healthcare providers to coordinate care for the patient with FTD. All members of the interdisciplinary healthcare team can support families by listening to them, providing ongoing information and education about FTD, offering guidance to improve caregiving skills, and helping families connect to appropriate resources.

7. PROGRESSION OF FTD

The prognosis for people with FTD is poor. FTD worsens progressively, usually over several years, and patients require increasing behavioral supervision and personal care. Eventually, people with advanced FTD become mute and bedbound and require full care at home or in a care facility. As patients with FTD become more debilitated, they are vulnerable to complications such as infections and falls. The most common cause of death in people with FTD is infection (e.g., pneumonia) [3,8]. The average duration of the disease is 6 to 13 years, but it can range from 2 to 20 years [3,5].

8. RESEARCH RELATED TO FTD

The goals for research on FTD include gaining a better understanding of the pathology; identifying causes and risk factors (genetic and environmental); improving the diagnosis of FTD through enhanced neuroimaging, biomarkers, and characterization of clinical features; developing therapies to treat, cure, or prevent FTD; and exploring new ways to support family caregivers. However, research on FTD is challenging. It is an uncommon disease, so awareness is low, there are fewer potential subjects available for research studies, and there is a relatively small market for medications. FTD is a complicated disease with a wide variety of presentations (behavior, language, and movement problems) and underlying causes (sporadic and genetic). Pathologically, microscopic brain inclusions may consist of different abnormal proteins (e.g., tau, TDP-43, FUS), but there are no good biomarkers to diagnose FTD or to monitor the progression of the disease. Drug development faces the challenge of creating a medication to treat FTD that can cross the blood/brain barrier.

Despite these challenges, the pace of research on FTD has accelerated rapidly. There are an increasing number of studies and a better awareness of the varied symptoms of FTD. In the past few decades, there have been discoveries of the genetic mutations underlying some causes of FTD and a growing understanding of the changes that occur in the brain of those with FTD. Presently, there are clinical trials underway for potential medications to treat FTD. Information on clinical research studies, including participation in studies, can be found at the National Institutes of Health website https://clinicaltrials.gov.

9. CASE STUDY

Patient A was a high school homecoming queen who completed two years of college, worked in an office, then married and had three children. She was an energetic homemaker and an active community volunteer, serving as school parent-teacher association president for several years, and was fastidious about her appearance.

Patient A's mother, three maternal uncles, a maternal grandfather, and great-grandmother died with dementia; her brother and maternal aunt are living with the disease. The mean age of onset of dementia in the family is 51 years, and the mean age at death is 67 years.

When Patient A is 52 years of age, her husband notices changes in her behavior. She often appears distracted, and her impeccable grooming declines. She is less affectionate toward him and she stops participating in community activities. She has difficulty making arrangements for a planned vacation. Her previously gourmet meals become simple, functional meals. She becomes obsessed with repeatedly raking the lawn, eventually killing all the grass in the yard. When her grandchildren visit, Patient A alternates between ignoring them and playing too rough. Patient A begins to impulsively leave the house for fast-paced walks, but she always returns home and never gets lost. She frequently visits a local shopping mall, getting down on her hands and knees looking for dropped change near the cash registers. She is once stopped by mall security for shoplifting. When shopping with her husband, she approaches strangers, stands inappropriately close to them, and announces "We don't know you."

Patient A's husband brings her to a dementia clinic for evaluation. A neurologic examination and neuropsychologic testing are completed. Memory and visual-spatial performance are in the normal range, but personality, judgment, and executive function show significant decline. A brain MRI shows frontal and anterior temporal lobe atrophy, and the diagnosis of familial bvFTD is made. Clinical genetic testing identifies a mutation in the MAPT gene on chromosome 17, the believed cause of the dementia.

Patient A's husband stops working in order to care for her at home. As her disease progresses, Patient A requires increasing care and supervision. She spends much of her day watching television, writing numbers in a notebook, and pacing. She develops a craving for sweets and often rummages through kitchen cabinets looking for candy. At mealtime, Patient A stuffs her mouth with food before chewing and swallowing properly, precipitating episodes of choking. She also develops a pattern of hand-clapping that she repeats every few minutes, along with the phrase "We haven't had any phone calls lately."

Patient A's husband is encouraged to accept help from others (such as their adult children), consider local adult day care programs, and utilize respite care at a nearby nursing home. He is in monthly phone contact with nursing staff to review symptoms and develop strategies for managing symptoms. At different times during her illness, Patient A is prescribed an antidepressant and an antipsychotic medication (off label) to treat difficult behavioral symptoms, but both were eventually discontinued. The family faces financial difficulties as a result of the husband's loss of income, diminished retirement benefits, and the later cost of nursing home care. Social work support helps the family address issues such as insurance, social security benefits, adult day care programs, and selecting a nursing facility for eventual long-term care.

When Patient A is 60 years of age, her husband is no longer able to care for her at home and she is admitted to a skilled nursing facility. She is incontinent and requires full care for all activities of daily living. Her husband visits twice daily, and she always appears to recognize him. That same year, Patient A dies unexpectedly of a myocardial infarction. A brain autopsy is done and confirms the diagnosis of FTD.

Patient A's husband shares the results of her genetic testing and autopsy with their three adult children. Each of Patient A's three children is at a 50% risk for having inherited the MAPT genetic mutation. Two of the children request pre-symptomatic genetic testing. The two children who request pre-symptomatic genetic testing are referred to professional genetic counselors. After genetic counseling, they both choose to have pre-symptomatic genetic testing done. One defers getting the results for two years, underscoring the very difficult personal decision it can be to choose pre-symptomatic genetic testing.

Patient A demonstrated the typical symptoms of bvFTD and her evaluation was done at a dementia center by specialists with expertise in FTD, so her initial diagnosis was strong. The neurologic evaluation, blood tests, neuropsychologic testing, and neuroimaging together led to the clinical diagnosis of bvFTD. Patient A's family history showed a pattern of autosomal dominant inheritance. The genetic cause of her FTD was confirmed by clinical genetic testing, which documented a mutation in the MAPT gene.

10. CONCLUSION

FTD is now recognized as one of the most common causes of dementia in persons younger than 65 years of age. This course has provided an overview of FTD epidemiology, pathophysiology, clinical presentation, diagnosis, management, prognosis, and current research. Understanding FTD can help healthcare professionals provide better care to patients with FTD and support to their families.

11. RESOURCES

Association for Frontotemporal Degeneration

2700 Horizon Drive, Suite 120

King of Prussia, PA 19406

(866) 507-7222

https://www.theaftd.org

National Institute on Aging

Building 31, Room 5C27

31 Center Drive, MSC 2292

Bethesda, MD 20892-2292

(800) 222-2225

https://www.nia.nih.gov

National Institute of Neurological Disorders and Stroke

P.O. Box 5801

Bethesda, MD 20824

(800) 352-9424

https://www.ninds.nih.gov

Works Cited

1. Pick A. Ueber die Beziehungen der senile Hirnatrophie zur Aphasie. Prager Medicinische Wochenschrift. 1892;17(16):165-167.

2. Arvanitakis Z. Update on frontotemporal dementia. Neurologist. 2010;16(1):16-22.

3. Association for Frontotemporal Degeneration. Disease Overview. Available at https://www.theaftd.org/what-is-ftd/disease-overview. Last accessed September 22, 2021.

4. Hodges JR, Davies R, Xuereb J, Kril J, Halliday G. Survival in frontotemporal dementia. Neurology. 2003;61(3): 349-354.

5. Knopman DS, Roberts RO. Estimating the number of persons with frontotemporal lobar degeneration in the U.S. population.J Mol Neurosci. 2011;45(3):330-335.

6. Ghosh S, Lippa CF. Clinical subtypes of frontotemporal dementia. Am J Alzhiemers Dis Other Demen. 2015;30(7):653-661.

7. Wang X, Shen Y, Chen W. Progress in frontotemporal dementia research. Am J Alzheimers Dis Other Demen. 2013;28(1):15-23.

8. UCSF Memory and Aging Center. Frontotemporal Dementia. Available at https://memory.ucsf.edu/dementia/ftd. Last accessed September 22, 2021.

9. Seltman RE, Matthews BR. Frontotemporal lobar degeneration. CNS Drugs. 2012;26(10):841-870.

10. Sieben A, VanLangenhove T, Engelborghs S, et al. The genetics and neuropathology of frontotemporal lobar degeneration. Acta Neuropathol. 2012;124:353-372.

11. Gorno-Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its variants. Neurology. 2011;76:1006-1014.

12. Johnson JK, Diehl J, Mendez MF, et al. Frontotemporal lobar degeneration: demographic characteristics of 353 patients. Arch Neurol. 2005;62(6):925-930.

13. Rascovsky k, Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic criteria for the behavioral variant of frontotemporal dementia. Brain. 2011;134(Pt 9):2456-2477.

14. Alzheimer's Association. Frontotemporal Dementia (FTD). Available at https://www.alz.org/alzheimers-dementia/what-is-dementia/types-of-dementia/frontotemporal-dementia. Last accessed September 22, 2021.

15. Hutton M, Lendon CL, Rizzu P, et al. Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17. Nature. 1998;393(6686):702-705.

16. Poorkaj P, Bird TD, Wijsman E, et al. Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann Neurol. 1998;43(6):815-825.

17. Rohrer JD, Warren JD. Phenotypic signatures of genetic frontotemporal dementia. Curr Opin Neurol. 2011;24:542-549.

18. Baker M, Mackenzie IR, Pickering-Brown SM, et al. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature. 2006;442(7105):916-919.

19. Cruts M, Gijselinck I, van der Zee J, et al. Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature. 2006;442(7105):920-924.

20. DeJesus-Hernandez M, Mackinzie IR, Boeve BF, et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron. 2011;72:245-256.

21. Renton AE, Majounie E, Waite A, et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron. 2011;72:257-268.

22. Majounie E, Renton AE, Mok K, et al. Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study. Lancet Neurol. 2012;11:323-330.

23. Boxer AL, Knopman DS, Kaufer DI, et al. Memantine in patients with frontotemporal lobar degeneration: a multicentre, randomized, double-blind, placebo-controlled trial. Lancet Neurol. 2013;12(2):149-156.

24. Ahlskog JE, Geda YE, Graff-Radford NR, et al. Physical exercise as a preventive or disease-modifying treatment of dementia and brain aging. Mayo Clin Proc. 2011;86(9):876-884.

25. Mesulam M. Primary progressive aphasia: a dementia of the language network. Dement Neuropsychol. 2013;7(1):2-9.

26. Wong C, Merrilees J, Ketelle R. The experience of caregiving: differences between behavioral variant of frontotemporal dementia and Alzheimer disease. Am J Geriatr Psychiatry. 2012;20(8):724-728.

27. Mioshi E, Bristow M, Cook R, Hodges JR. Factors underlying caregiver stress in frontotemporal dementia and Alzheimer's disease. Dement Geriatr Cogn Disord. 2009;27(1):76-81.

28. Association for Frontotemporal Degeneration. Treating FTD. Available at https://www.theaftd.org/for-health-professionals/treating-ftd. Last accessed September 22, 2021.

29. Olney NT, Spina S, Miller BL. Frontotemporal dementia. Neuro Clin. 2017;35(2):339-374.

Evidence-Based Practice Recommendations Citations

1. Mocellin R, Scholes A, Walterfang M, Looi JCL, Velakoulis D. Clinical update on frontotemporal dementia: diagnosis and treatment. Australas Psychiatry. 2015;23(5):481-487. Available at https://journals.sagepub.com/doi/abs/10.1177/1039856215582276. Last accessed October 15, 2021.

96442 • Suicide Assessment and Prevention

Mark Rose, BS, MA, LP

www.netce.com

Copyright © 2023 NetCE, All rights reserved.

Suicide is a major preventable public health problem and cause of mortality. This course will review the major aspects of suicide assessment, management, and prevention, with a special focus on military veterans. Primary care contact may represent the last opportunity for intervention in the severely depressed suicidal patient, making the thorough comprehension of identification and treatment of depression and suicide risk imperative.

Table of Contents

96442 • Suicide Assessment and Prevention

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 OF SUICIDE

THE MISREPORTING OF DEATH BY SUICIDE

SUICIDE REPORTING IN THE MEDIA

3. PATHOPHYSIOLOGY OF SUICIDAL BEHAVIOR

4. SUICIDE AND SPECIAL POPULATIONS

WOMEN

YOUTH

OLDER ADULTS (65 YEARS OF AGE AND OLDER)

LESBIAN, GAY, BISEXUAL, AND TRANSGENDER (LGBT+) INDIVIDUALS

MILITARY SERVICE MEMBERS

HEALTHCARE PROFESSIONALS

5. RISK AND PROTECTIVE FACTORS FOR SUICIDE

PROTECTIVE FACTORS

RISK FACTORS

ACTIVE-DUTY MILITARY AND VETERANS

6. IMMINENT SUICIDE

WARNING SIGNS

7. SUICIDE ATTEMPTS

LETHAL MEANS

MOTIVES BEHIND SUICIDAL BEHAVIOR

8. SCREENING AND ASSESSMENT OF SUICIDE RISK

SCREENING IN THE PRIMARY CARE SETTING: EXPERT CONSENSUS

ASSESSMENT OF SUICIDE RISK

DETERMINING LEVEL OF RISK AND APPROPRIATE ACTIONS

DOCUMENTATION

9. MANAGEMENT OF SUICIDAL PATIENTS

PHARMACOTHERAPY TO REDUCE SUICIDE RISK

PSYCHOTHERAPY TO REDUCE SUICIDE RISK

MENTAL HEALTH REFERRAL

REFERRAL TO BE HOSPITALIZED

ADDITIONAL OPTIONS FOR CONTINUITY OF CARE

SAFETY PLANNING

CONSIDERATIONS FOR VETERANS

CONSIDERATIONS FOR HEALTHCARE PROFESSIONALS

10. SUICIDE PREVENTION

HISTORY OF SUICIDE PREVENTION IN THE UNITED STATES

SUICIDE PREVENTION THAT TARGETS AT-RISK POPULATIONS

STIGMA AND SUICIDE

11. SUICIDE SURVIVORS: TREATMENT AND RESOURCES

12. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

96442 • Suicide Assessment and Prevention

Education Category. Psychiatric / Mental Health

Release Date. 04/01/2023

Expiration Date. 03/31/2026

Course Overview

Suicide is a major preventable public health problem and cause of mortality. This course will review the major aspects of suicide assessment, management, and prevention, with a special focus on military veterans. Primary care contact may represent the last opportunity for intervention in the severely depressed suicidal patient, making the thorough comprehension of identification and treatment of depression and suicide risk imperative.

Audience

This course is designed for physicians, nurses, pharmacists, and other healthcare professionals who may identify persons at risk for suicide and intervene to prevent or manage suicidality.

Accreditations & Approvals

In support of improving patient care, 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 by the California Nursing Home Administrator Program as a provider of continuing education. Provider number 1622. 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 6 Interprofessional Continuing Education (IPCE) credit(s) for learning and change. NetCE designates this enduring material for a maximum of 6 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 6 ANCC contact hour(s). NetCE designates this continuing education activity for 7.2 hours for Alabama nurses. Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 6 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. NetCE designates this activity for 6 ACPE credit(s). ACPE Universal Activity Number: JA4008164-0000-23-007-H04-P. 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 6 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 6 Lifelong Learning (Part II) credits for the American Board of Pathology Continuing Certification Program. Successful completion of this CME activity, which includes participation in the evaluation component, enables the learner to satisfy the Lifelong Learning requirements for the American Board of Ophthalmology's Maintenance of Certification program. It is the CME activity provider's responsibility to submit learning completion information to ACCME for the purpose of granting MOC credit. 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 6 credit hour(s). This course is approved by the California Nursing Home Administrator Program for 6 hour(s) of continuing education credit - NHAP#1622015-9387/P. California NHAs may only obtain a maximum of 10 hours per course. AACN Synergy CERP Category A. NetCE is authorized by IACET to offer 0.6 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: Alabama, Provider #ABNP0353, (valid through July 29,2025); Alabama, Provider #ABNP0353, (valid through July 29, 2025); 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; South Carolina, Provider #50-2405. West Virginia RN and APRN, Provider #50-2405.

Special Approvals

This course is approved by the Nevada State Board of Medical Examiners to fulfill 2 hours of education on suicide prevention and awareness. 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 health and mental health professionals with an appreciation of the impact of depression and suicide on patient health as well as the skills necessary to identify and intervene for patients at risk for suicide.

Learning Objectives

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

1. Review the epidemiology of suicide.

2. Describe the impact of suicide in the treatment of special populations, including among military veterans.

3. Identify risk and protective factors for suicide.

4. Discuss warning signs of imminent suicide and the importance of lethal means.

5. Evaluate tools available for the assessment and evaluation of suicide risk.

6. Outline key components of an effective suicide prevention plan.

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

Margo A. Halm, RN, PhD, NEA-BC, FAAN

Randall L. Allen, PharmD

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

In 2019, there were 47,511 reported suicide deaths in the United States, making it the 10th leading overall cause of mortality [1]. Every day, approximately 130 Americans take their own life, and one person dies by suicide every 11.2 minutes. An estimated 90% of persons who die by suicide have a diagnosable psychiatric disorder at the time of death, although only 46% have a documented diagnosis [2,3].

For the approximately 48,000 suicide deaths each year, an estimated 200,000 additional individuals are affected by the loss of a loved one or acquaintance by suicide [5,46]. This translate to about six survivors intimately affected per suicide. However, a 2019 study estimated that the rate is much higher, projecting a rate of 135 individuals exposed to a single suicide in addition to those intimately affected (equaling more than 6.9 million individuals) [13,14]. Among these, 20% (or more than 1 million individuals) reported that the experience had a devastating impact or caused a major-life disruption [4]. These figures do not take into account the physical and emotional pain and trauma endured by persons who survive suicide attempts [5].

The total economic burden of suicide is estimated to be $69 billion annually, with the costs falling most heavily on adults of working age [2]. Depression causes an estimated 200 million lost workdays each year at a cost to employers of $17 to $44 billion [6]. However, the accuracy of attempts to quantify such costs on a national scale is hampered by incomplete data, such as the under-reporting of suicides and an absence of reliable data on suicide attempts [5].

Among persons with a mood disorder, 12% to 20% will ultimately die by suicide. The first three months after diagnosis is the period of highest risk for a first attempt, with the three months following the first attempt being the highest risk period for a second attempt [7].

Case Scenario: Patient A

Two case studies will be referenced throughout the text to illustrate the challenges of assessing and treating patients with possible suicide attempt.

Patient A, 19 years of age, is brought to the local emergency department by ambulance after being found unconscious on the floor of her mother's living room, an empty pill bottle nearby. She exhibits quiet, shallow breathing but otherwise no spontaneous movement; she does react to deep, noxious stimuli by opening her eyes and moving her extremities but does not speak or respond to questioning. Her neck is supple, and a screening cranial nerve and motor exam shows no focal neurologic deficits. Her blood pressure is 110/70 mm Hg, pulse is 114 beats per minute, respiration 12 breaths per minute, and temperature 98.8°F; the lungs are clear. The empty bottle is a prescription for a tricyclic antidepressant made out to Patient A's mother. The friend who found her has followed and provides some context: she is not working at present, lives with a boyfriend who recently left her ("they fight a lot"), and has been living at her mother's home for several days. She is admitted to the intensive care unit and intubated, primarily to protect her airway from aspiration should she vomit.

2. EPIDEMIOLOGY OF SUICIDE

Every year, more than 700,000 people around the world die by suicide, with 77% occurring in low- and middle-income countries. The suicide rate has increased by more than 60% in the past 45 years, with suicide rates among young people increasing at alarming rates in both developed and developing countries [8]. Suicide is the 4th leading cause of death for people 15 to 29 years of age. However, since 2000, the overall rate appears to have decreased slightly.

Suicide rates vary according to race, ethnicity, sex, and many other factors, including age [8]. In almost every country, suicide is predominated by male victims, with the exception of China, which is the only country in which the female suicide rate (14.8 per 100,000) exceeds the male rate (13 per 100,000) [9]. In the United States, the number of deaths by suicide is nearly four times greater among men (37,256) than among women (10,255). Overall, suicide accounts for 1.7% of all deaths in the United States and a death rate of 13.9 per 100,000 [1].

From the mid-1950s to the late 1970s in the United States, the suicide rate tripled among men 15 to 24 years of age and doubled among women 15 to 24 years of age. The suicide rate reached a plateau during the 1980s and early 1990s and began decreasing during the mid-1990s [10]. However, the age-adjusted suicide rate increased 35% between 1999 and 2018, with increases in most groups younger than 75 years of age [11]. The suicide rate is consistently highest among men 75 years of age and older (40 deaths per 100,000). Among the elderly, the suicide rate peaked in 1987, at 21.8 per 100,000 people, and has since declined nearly 13% (to 19.2 per 100,000 in 2018) [11,13]. Despite the growing recognition of suicide as a problem demanding public health attention, the overall rates of suicide in the United States have increased over the last half-century [13].

Although official national statistics are not compiled on attempted suicide (i.e., nonfatal actions), it is estimated that 1.2 million adults (18 years of age and older) attempt suicide each year [13]. Overall, there are roughly 25 attempts for every death by suicide; this ratio changes to 100 to 200:1 for the young and 4:1 for the elderly [13,16]. The risk of attempted (nonfatal) suicide is greatest among women and the young, and the ratio of female-to-male nonfatal suicide attempts is 2 to 3:1 [2,10,13].

THE MISREPORTING OF DEATH BY SUICIDE

There is broad agreement that not all suicide deaths are accurately recorded and reported. Reasons for under-reporting include [5,18,19,20,21]:

- Families or family physicians may hide evidence due to the stigma of suicide.

- The determination of death is judged by local standards, which can vary widely.

- Ambiguous cases involving suicide may end up classified as "accidental" or " undetermined."

- Compared with the "accidental" or " undetermined" motive categories, a larger number of deaths are officially classified as "ill-defined and unknown causes of mortality," in which even the actual cause of death is uncertain and some of which are undoubtedly suicides.

- The frequency of physician-assisted suicide for the terminally ill is unknown but is probably both substantial and increasing.

In contrast, some ambiguous cases are classified as suicides, often in institutions such as prisons, hospitals, religious orders, and the military, where the verdict of suicide is likely to be less embarrassing than homicide. Other motivations for declaring a death a suicide, despite much doubt surrounding a case, are that homicides must be investigated and a murderer sought and accidental death may be the basis of negligence lawsuits [5].

SUICIDE REPORTING IN THE MEDIA

Suicide rates may temporarily spike with intense media coverage of a suicide, especially among youth, and both news reports and fictional accounts of suicide in movies and television can produce this effect [22,23,24]. Imitation is often the key factor and is most powerful with the highly publicized suicides of entertainment celebrities [5,25].

Media coverage of suicide can lead to misinformation, as when suicide is attributed to a single event, such as the loss of a job or a relationship, without mention of a broader context involving ongoing problems with depression, substance abuse, or lack of access to treatment for these conditions. On the other hand, responsible coverage of suicide can educate audiences about the causes, warning signs, and treatment advances and prevention of suicide [5].

Thirty-six hours after admission, Patient A has been extubated and is awake, sitting up, and talking to a young man (the boyfriend) at her bedside. As you approach, she smiles sheepishly and asks, "Can I go home now?" Before answering, which of the following management options would you consider appropriate at this juncture?

- Have physical therapy assess strength and ambulation. If normal, discharge her home to the care of her family.

- Ask the young man to step out, then take a careful medical and social history, exploring in detail her mindset, actions, and intent in the period leading up to admission.

- Anticipate transfer out of the intensive care unit and the need for an around-the-clock "sitter" in her room as a suicide prevention precaution.

- Request social service consult to assess her resources and support system and a psychiatry consult to assess the need for further inpatient care and recommend a plan for outpatient follow-up.

3. PATHOPHYSIOLOGY OF SUICIDAL BEHAVIOR

Although suicide is a potential complication of all psychiatric disorders, serious suicidal actions have a neurobiologic basis that is distinct from the psychiatric illnesses with which they are associated [26].

Alterations in several neurobiologic systems are associated with suicidal behavior, most prominently hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, serotonergic system dysfunction, and excessive activity of the noradrenergic system. While the first and the last system appear to be involved in the response to stressful events, serotonergic dysfunction is thought to be trait-dependent and associated with disturbances in the regulation of anxiety, impulsivity, and aggression [27,28]. Altered functioning of these systems may stem from both genetic and developmental causes. Exposure to extreme or chronic stress during childhood has developmental consequences on these systems that persist into adulthood. Genetic differences may also contribute to alterations in the functioning of these neurobiologic systems, and the interactive effect of adverse childhood experiences, such as physical abuse, sexual abuse, or caregiver abandonment, with genetic vulnerability is increasingly believed to play a role in suicidal behavior [27,29].

Neurobiologic and psychologic perspectives have converged to identify the most prominent risk factors for suicidal behavior: dysregulated impulse control and a propensity to intense psychologic pain that includes hopelessness, often in the context of a mood disorder. These factors are believed to largely reflect serotonergic system dysregulation [30]. Investigation into the role played by serotonergic dysfunction in suicidal behavior has identified two prominent regions: the dorsal and median raphe nuclei in the midbrain, which host the main serotonergic cell bodies, and the prefrontal cortex, particularly the ventral prefrontal cortex, which is innervated by the serotonergic system. In vivo and postmortem examinations have revealed serotonergic hypofunction in these two brain systems in persons who have died by suicide or made serious suicide attempts. The deficient serotonergic input in the ventral prefrontal cortex stemming from this serotonin hypofunction can result in a breakdown in inhibitory function leading to a predisposition to impulsive and aggressive behavior. This vulnerability to deficient impulse control coupled with the development of psychiatric illness or other life stressors elevates the risk of acting on suicidal thoughts [31].

4. SUICIDE AND SPECIAL POPULATIONS

WOMEN

A woman takes her own life every 51.25 minutes in the United States [1]. Suicide is more common among women who are single, recently separated, divorced, or widowed, and the suicide rates for women peak between the ages of 45 to 64 years. Precipitating life events for women who attempt suicide often involve interpersonal losses or crises in significant social or family relationships. As noted, more women attempt suicide than men, and there is a 2 to 3:1 ratio of women versus men with a history of attempted suicide. The higher rates of attempted suicide among women are likely due to the higher rates of mood disorders such as major depression, persistent depressive disorder (dysthymia), and seasonal affective disorder. Factors that may contribute to the lower rates of suicide deaths in women relative to men include stronger social supports, feeling that their relationships are a deterrent to suicide, differences in preferred suicide method, and greater willingness to seek psychiatric and medical intervention [2,13].

YOUTH

In 2020, suicide was the third leading cause of death for young people 10 to 24 years of age, exceeded only by unintentional injury and homicide [32]. As noted, an estimated 100 to 200 attempts are made for every suicide completion in this age group. Between 2008 and 2015, encounters for suicide ideation and/or attempt at children's hospitals nearly doubled [51]. Risk factors for suicide among the young include suicidal thoughts, psychiatric disorders (e.g., depression, impulsive aggressive behavior, bipolar disorder, panic disorder), drug and/or alcohol abuse, and previous suicide attempts. The risk is further elevated with situational stress or access to firearms [2,13].

Children 10 to 14 Years of Age

In 2020, suicide was the second leading cause of death for children 10 to 14 years of age, with a rate of approximately 3 per 100,000 [11,32]. The rate of suicide and percentage of total deaths varies considerably by race (Table 1) [122].

Table 1: DEATHS BY SUICIDE AMONG U.S. CHILDREN 10 TO 14 YEARS OF AGE BY RACE IN 2020

Race

Rate Per 100,000 Population

Total Suicide Deaths

Percentage of Total Deaths

Alaska Native/Native American

6.3

21

35%

Asian

1.3

15

14.5%

Black/African American

3.0

93

11.5%

Multiracial

2.1

24

19.7%

White

2.8

424

18.4%

Source: [122]

College Students

More than 1,000 suicides occur each year on college campuses, and 1 in 10 college students have made a suicide plan [34]. A 2011 survey of 27,774 college students from 44 campuses found that 6.6% had seriously contemplated suicide and 1.1% had attempted suicide [16]. In the 12 months before the survey, 60.5% reported feeling very sad, 45.2% reported feeling hopeless, and 30.3% reported feeling so depressed they were unable to function [16]. More than 45% reported feelings of hopelessness; however, only 6.7% of men and 13.1% of women reported a diagnosis of depression, suggesting that many students are not receiving adequate diagnosis and/or treatment [16]. A 2015 follow-up survey including 93,034 college students from 108 campuses found a much higher rate of suicidality, with 24% of the survey population reporting seriously contemplating suicide, nearly 20% reporting self-injury, and 9% reporting a suicide attempt [33]. Rates of suicidality were highest among racial/ethnic, sexual, and gender minorities.

Students with a pre-existing mental health condition or who develop mental health conditions in college are at highest risk of suicide. In the 2015 study, 25% students were diagnosed with and/or received treatment for a mental health condition in the previous 12 months [33]. Risk factors for suicide among college students include depression, sadness, hopelessness, and stress [13].

Other Considerations in Youth Suicide

Most adolescent suicides occur at home after school hours. Adolescent nonfatal suicide attempters are typically girls who ingest pills, while those who die by suicide are typically boys who die from gunshot wounds. Intentional self-harm should be considered serious and in need of further evaluation because not all adolescent attempters admit their intent. Most adolescent suicide attempts are triggered by interpersonal conflicts and are motivated by the desire to change the behavior or attitude of others. Repeat attempters may use this behavior as a coping mechanism for stress and tend to exhibit more chronic symptomatology, worse coping histories, and higher rates of suicidal and substance abuse behaviors in their family histories [13]. The presence of multiple emotional, behavioral, and/or cognitive problems may be a more important predictor of suicide behavior risk than a specific type of problem (e.g., an addictive behavior or an emotional problem) [13,33]. The presence of acne is associated with social and psychologic problems, and certain acne medications have been linked with an increased risk of suicidal ideation [36].

OLDER ADULTS (65 YEARS OF AGE AND OLDER)

The elderly account for roughly 19.3% of suicides but only 16% of the population [13]. Suicide rates rise with age for men, especially after 65 years of age, and the suicide rate in elderly men is 5 times that of same-aged women; more than 85% of elderly suicides are among men [13,35]. The overall rate of elderly suicide is nearly 20 per 100,000. However, the rate is 40 per 100,000 among elderly White men and 51.8 per 100,000 among White men older than 85 years of age, a rate that is almost 2 times the rate for men of all ages. In contrast, the suicide rate of women declines after 60 years of age [13,35].

Although undiagnosed and/or untreated depression is the primary cause of suicide in the elderly, suicide completion is rarely preceded by only one factor. Risk factors for suicide in this population include a previous suicide attempt; mental illness; physical illness or uncontrollable pain; fear of a prolonged illness; major changes in social roles, such as retirement; loneliness and social isolation (especially in older men who have recently lost a loved one); and access to lethal means, such as firearms in the home [13].

LESBIAN, GAY, BISEXUAL, AND TRANSGENDER (LGBT+) INDIVIDUALS

The true incidence of suicide among lesbian, gay, bisexual, transgender, and other gender and sexual minority (LGBT+) youth is unknown, but research indicates higher rates of suicidal behavior among LGBT+ youth (15 to 24 years of age) compared with heterosexual youth [33,43]. Among adolescents and young adults, the lifetime prevalence of suicide attempts ranges from 20.5% to 52.4% among LGB individuals versus 4.2% to 24.8% among same-aged heterosexuals [39,40,42]. Among adolescents and young adults, past-year suicide attempts are more than 4.5 times higher among LGB youth than same-aged heterosexual youth [13,37,47].

Evidence Based Practice Recommendation

The American Academy of Child and Adolescent Psychiatry asserts that family connectedness, adult caring, and school safety are highly significant protective factors against suicidal ideation and attempts in gay, lesbian, and gender-variant youth.

https://jaacap.org/article/S0890-8567(12)00500-X/fulltext

Last Accessed: March 24, 2023

Level of Evidence: Expert Opinion/Consensus Statement

LGBT+ youth generally have more risk factors, more severe risk factors, and fewer protective factors, such as family support and safe schools, than heterosexual youth. There are also risks unique to this population related to sexual orientation, such as disclosure to family or friends [13]. The impact of stigma and discrimination against LGBT+ individuals is enormous and is directly tied to risk factors for suicide such as isolation, alienation and rejection from family, and lack of access to culturally competent care [43]. Family connectedness, perceived caring from other adults, and feeling safe at school were reported as significant protective factors in a survey of 6th-, 9th-, and 12th-grade LGBT+ students [37,38]. It has also been noted that LGBT+ adults have a two-fold excess risk of suicide than their heterosexual counterparts [37].

The effect of race/ethnicity and other demographic characteristics on suicidal behavior in the LGB population has also been studied little, but reports suggest high suicide attempt rates among African American gay/bisexual men, among gay/bisexual men of lower socioeconomic status, and among LGB Latinx [35].

Depression and suicide are also common among transgender individuals. One survey assessed transgender individuals' school experiences from kindergarten through grade 12. Of the individuals who were out as transgender during their school years, 77% reported at least one negative experience, including physical attacks, verbal abuse, and mistreatment by teachers and/or administrators. Among those with negative school experiences, 58% attempted suicide, compared with 37% of transgender individuals without negative school experiences. Among out transgender college students, 24% reported that they were physically, verbally, or sexually harassed. [38]. Across all age groups, 39% of transgender individuals reported experiencing serious psychologic distress in the past month, compared with 5% of the general U.S. population. Up to 82% of transgender persons have considered suicide in their lifetimes [124]. In addition, 40% of individuals reported attempting suicide, more than nine times the rate in the United States [38,47,124].

MILITARY SERVICE MEMBERS

Although the true incidence of suicide among military service members and veterans is difficult to estimate due to the lack of national suicide surveillance data, the U.S. Department of Veterans Affairs (VA) estimates that 18% of all deaths from suicide in the United States are in military war veterans [79]. Despite preventive measures taken by the military, the number of suicides in this population continues to increase [52,54,56,79]. Although the majority of military suicides occur among young men shortly after their discharge from military service, military women 18 to 35 years of age die by suicide nearly three times more frequently than civilian women of the same age group [57,58]. Servicewomen, in particular, experience high rates of interpersonal violence, including childhood abuse, intimate partner violence, and sexual trauma during adulthood (e.g., military sexual assault) [123].

Patient A is transferred to a regular floor and a sitter is assigned to her room. With the aid of additional clinical observation and consultations, a clearer picture emerges. In the presence of staff, Patient A appears open and optimistic and takes initiative; when her boyfriend or family are present, she becomes passive, more withdrawn, and demanding, expecting others to attend to her needs. Patient A's parents divorced when she was 11 years of age, and two years later, she came under psychiatric care, followed by counseling, because of depression and a brief period of suicide ideation. She had attended college but dropped out after two years. In recent months, her life had become more chaotic. She was unhappy in her job and subject to fits of anger and despondency. She was often at odds with her live-in boyfriend, who, on occasion, threatened to leave her and in fact did so four days prior to her admission. The decision to take an overdose of her mother's medication was judged to have been abrupt and impulsive, perhaps a "suicide gesture"—partly misdirected anger and partly designed to win back the attention of her boyfriend. Nevertheless, she almost succeeded in taking her life. The consultant's diagnosis is borderline personality disorder and likely major depression. She is transferred to the inpatient psychiatry service for further evaluation and care. Some days later, she is discharged to a mental health clinic for psychiatric and social service follow-up combined with ongoing counseling.

HEALTHCARE PROFESSIONALS

Some occupations are known to have higher rates of suicide than others. Job factors, including chronic stress, vicarious trauma, low job security, and low pay, can contribute to risk of suicide, as can easy access to lethal means (e.g., medications, firearms) among people at risk. Other factors that can influence the link between occupation and suicide include gender, socioeconomic status, economic environment, cultural factors, and stigma [115].

Healthcare workers have historically been at disproportionate risk of suicide, due to a variety of factors, including difficult working conditions, such as [115]:

- Long work hours

- Irregular shifts

- Emotionally difficult situations

- Risk for exposure to infectious diseases and other hazards on the job, including workplace violence

- Routine exposure to human suffering and death (vicarious or secondary trauma)

- Access to lethal means (e.g., medications) and knowledge about using them

In 2019, a large review of more than 60 scientific studies was conducted to address conflicting data on the nature of suicide among healthcare workers. The researchers found that physicians were at a significant and increased risk for suicide, with female physicians at particularly high risk [116]. A cross-sectional survey involving 7,378 nurses found that nurses were at increased risk for past-year suicidal ideation (5.5%) [117]. In addition, nurses with suicidal ideation were less likely to be willing to seek help (72.6%) than nurses without suicidal ideation (85%). Burnout was strongly associated with suicidal ideation, even after controlling for other personal and professional characteristics [117].

5. RISK AND PROTECTIVE FACTORS FOR SUICIDE

Suicide is now understood to be a multidimensional disorder stemming from a complex interaction of biologic, genetic, psychologic, sociologic, and environmental factors [59,60]. One of the first social scientists to empirically investigate contributing factors to suicide was Émile Durkheim. Instead of focusing only on shared traits among persons who had died by suicide, Durkheim compared one group with another and originated the scientific study of suicide risk factors [5,61]. Protective factors reduce suicide risk by enhancing resilience and counterbalancing risk factors, while risk factors increase the potential for suicidal behavior. Protective and risk factors may be biopsychosocial, environmental, or sociocultural in nature [5].

PROTECTIVE FACTORS

Several protective factors against suicide behavior have been identified [5,62]. These include:

- Access to effective clinical care for mental, physical, and substance use disorders, and support for help-seeking

- Restricted access to highly lethal means of suicide

- Strong connections to family and community support

- Emotionally supportive connections with medical and mental health providers

- Effective problem-solving and conflict-resolution skills

- Cultural and religious beliefs that discourage suicide and support self-preservation

- Reality testing ability

- Pregnancy, children in the home, or sense of family responsibility

- Life satisfaction

RISK FACTORS

Evidence Based Practice Recommendation

According to the American Psychiatric Association, the assessment and treatment of major depressive disorder should consider the impact of language barriers, as well as cultural variables that may influence symptom presentation, treatment preferences, and the degree to which psychiatric illness is stigmatized.

https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf

Last Accessed: March 24, 2023

Strength of Recommendation: I (Recommended with substantial clinical confidence)

In addition to risk factors specific to special populations, there are many general risk factors common among most populations. General biopsychosocial risk factors include [2,5,62]:

- Psychiatric disorders

- Alcohol and other substance use disorders

- Hopelessness

- Impulsive and/or aggressive tendencies

- History of physical or sexual trauma or abuse, especially in childhood

- Medical illness involving the brain or central nervous system (CNS)

- Family history of suicide

- Suicidal ideas, plans, or attempts (current or previous)

- Lethality of suicidal plans or attempts

In addition, environmental factors can impact an individual's suicide risk. Attention to the presence of job or financial loss, relationship or social loss, easy access to lethal means, and local clusters of suicide (due to contagious influence) is necessary.

Lack of social support and sense of isolation are risk factors for suicide, along with cultural factors. Some cultural practices and/or beliefs can predispose an individual to suicide, such as stigma associated with help-seeking behavior; barriers to accessing mental health care and substance abuse treatment; certain cultural and religious beliefs (e.g., suicide as an honorable act); and media exposure to and the influence of others who have died by suicide [2,5,62].

Psychiatric Disorders

At least 90% of people who die by suicide have diagnosable psychiatric illness [2,3]. The psychiatric conditions with the greatest association with suicidal behavior are depression, bipolar disorder, substance abuse, schizophrenia, and personality disorders.

Depression

Major depression is the psychiatric diagnosis most commonly associated with suicide. The risk of suicide in persons with major depression is roughly 20 times that of the general population [13]. About 30% of all patients with major depression attempt suicide, half of whom ultimately take their own lives [63]. More than 60% of persons who die by suicide are clinically depressed at the time of their deaths, although this climbs to 75% when patients with comorbid depression and alcohol use disorder are added. Seven of every 100 men and 1 of every 100 women diagnosed with depression will die by suicide [13].

In one survey of adults who experienced depression in the previous year, 56.3% thought it would be better if they were dead during their worst or most recent episode, 40.3% contemplated suicide, 14.5% made a suicide plan, and 10.4% attempted suicide [65]. Among persons with depression, those with a history of multiple episodes of depression and those with an alcohol or other substance use disorder are at greatest risk [2]. Persons with depression who exhibit the following symptoms are at heightened risk for suicide [2,13]:

- Extreme hopelessness or desperation

- A lack of interest in previously pleasurable activities

- Intense anxiety and/or panic attacks

- Insomnia

- Talk of suicide or history of attempts

- Irritability, agitation, or enraged behavior

- Isolation

Feelings of hopelessness (e.g., belief that there is no solution) are more predictive of suicide risk than a diagnosis of depression per se. It is also important to remember that patients who desire an early death during a serious or terminal illness are usually experiencing a treatable depressive illness [2].

Bipolar Disorder

Between 5 and 10 million Americans currently have bipolar disorder. Of these, as many as 1 in 5 will die by suicide [67]. Like depression, bipolar disorder is treatable, and effective treatment decreases the risk of suicide.

Alcohol and Substance Abuse

Alcohol and drug abuse are second only to depression and other mood disorders as conditions most associated with suicide. Substance use disorders and disordered mood are often comorbid. The suicide risk among patients with alcohol use disorder is 50% to 70% higher than the general population. Alcohol abuse is a factor in roughly 30% of suicides, and about 7% of persons with alcohol dependence die by suicide [2,13,68].

In 2011, an estimated 228,366 emergency department admissions were made for alcohol- or drug-related suicide attempts. Almost all (94.7%) involved either a prescription drug or an over-the-counter medication [69]. Approximately 64.4% involved multiple drugs, and 29% involved alcohol [69].

As mentioned, comorbid psychiatric and substance use disorders substantially increase the risk of suicide behavior. Combined data from 2004 and 2005 indicated that 16.4 million adults 18 years of age and older experienced a major depressive episode in the previous year. Of these persons, more than 10% attempted suicide. But when alcohol abuse or illicit drug use occurred with major depression, the proportion of suicide attempts rose to nearly 14% for alcohol abuse and close to 20% for illicit drug use [65]. A 2017 study conducted among more than 10,000 individuals in a prison population showed that those with a documented substance abuse disorder or other psychiatric disorder had a higher rate of attempted suicide (2.0 and 9.2 greater odds, respectively) than those without a diagnosis [41].

There are several possible explanations for the association between alcohol/drug use and suicide. Alcoholism can cause loss of friends, family, or job, leading to social isolation; however, the reverse is equally plausible. Alcohol abuse and suicide may also both represent attempts to deal with depression and misery. Alcohol increases the sedating effects of some drugs that are frequently used in suicide attempts and may increase impulsive actions, making suicide attempts and completions more common [18,70]. To claim that alcoholism "causes" suicide is simplistic; while the association of alcohol and suicide is clear, a causal relationship is not. Both alcoholism and suicide may be responses to the same pain [18].

Schizophrenia

Suicide is the largest cause of premature death among individuals with schizophrenia, and young, unemployed men are at highest risk. Other risk factors include recurrent relapses; fear of deterioration, especially among persons with high intellectual ability; positive symptoms of suspiciousness and delusions; and depressive symptoms [59,60]. The suicide risk is highest during early stages of the illness, early relapse, and early recovery. The risk decreases with prolonging illness duration [59,60].

Personality Disorders

An estimated 20% to 50% of young people who die by suicide have a diagnosable personality disorder, with borderline personality and antisocial personality disorders being most frequently associated with suicide. Histrionic and narcissistic personality disorders and certain psychologic traits, such as impulsivity and aggression, are also associated with suicide [59,60].

Medical Disorders

Illnesses affecting the brain and CNS have a greater effect on suicide risk compared with other medical conditions. These conditions include epilepsy, AIDS, Huntington disease, traumatic head injury, and cerebrovascular accidents. In contrast, cancer and other potentially fatal conditions carry a more modest suicide risk [71].

Sociodemographic Factors

Suicide is an individual act that also occurs in the context of a broader culture, and specific sociodemographic factors are associated with suicide risk, including marital status, occupation, and previous suicide attempt(s) [59,60].

Marital Status

Divorced, widowed, and single people have a higher suicide risk. Marriage appears to be protective for men, but not so for women. Marital separation also increases the risk of suicide [59,60].

Occupation

Certain occupational groups, such as veterinary surgeons, pharmacists, dentists, farmers, and medical practitioners, have higher rates of suicide. Although obvious explanations are lacking, access to lethal means, work pressure, social isolation, and financial difficulties may account for the heightened risk [59,60].

Unemployment and suicide are also correlated, although the nature of the association is complex. Poverty, social deprivation, domestic difficulties, and hopelessness likely mediate the effect of unemployment, but persons with psychiatric illness and personality disorders are also more likely to be unemployed. Recent job loss is a greater risk factor than long-term unemployment.

Previous Suicide Attempt

Approximately 20% of people who kill themselves had made a previous attempt, making previous serious suicide attempts a very high risk factor for future attempts [2].

Incarceration

Suicide is the single most common cause of death in correctional settings, and collectively, inmates have higher suicide rates than their community counterparts. One study found that the rate of suicide among male prisoners is 5 to 6 times higher than in the general population and as much as 20 times higher among women prisoners. Also, for every suicide death there are many more suicide attempts [44,72].

Inmates at highest risk of suicide include young men, the mentally ill, the socially disenfranchised and socially isolated, substance abusers, previous suicide attempters, and juveniles placed in adult correctional facilities. Factors that increase the likelihood of suicidal behavior include the psychologic impact of arrest and incarceration; the stresses of prison life, including physical and sexual predation and assault from other inmates; and the absence of formal policies regarding managing suicidal patients, staff training, or access to mental health care [44,72].

Vicarious Trauma and Burnout

Compassion fatigue is comprised of two components: burnout and vicarious traumatic stress [118]. The first component consists of characteristic negative feelings such as frustration, anger, exhaustion, and depression. The second component, vicarious traumatic stress, may result when the professional is negatively affected through vicarious or indirect exposure to trauma material through their work. Compassion fatigue is associated with a variety of negative mental health repercussions, including increased risk for depression and suicidal ideation.

Being aware of the factors that increase a professional's risk of burnout is very valuable in contributing to a prevention strategy. Contributing factors may be individual/personal, systemic, or frequently a combination of both. It is important to know what does not work (or what makes a toxic environment) first in order to prevent exposure and the associated fallout from such exposure.

Creative Personalities

Anecdotes of famous painters, writers, and musicians who were depressed and died by suicide have occurred for centuries, but only recently has science been able to identify the underlying basis of vulnerability to depression and suicide among creative people. Treatment of major depressive or bipolar illness in artists presents unique problems, one of which is the concern that creativity and the disorder are so intertwined that treatment might suppress the artist's unique talent [73,74,76].

Holiday Suicide Myth

The idea that suicide occurs more frequently during the holiday season is a myth perpetuated in part by the media and has been debunked [2]. The National Center for Health Statistics of the Centers for Disease Control and Prevention (CDC) reports that the suicide rate is actually lowest in December, with peak rates in the spring and the fall. This pattern has remained constant for many years [77]. The holiday suicide myth has been considered important to counter because it provides misinformation about suicide that might ultimately hamper prevention efforts [78].

ACTIVE-DUTY MILITARY AND VETERANS

Protective Factors

Several general protective factors may be more prevalent among military service members and veterans, including strong interpersonal bonds, responsibilities/duties to others, steady employment, sense of belonging/identity, and access to health care [79]. Historically, the selection bias for healthy recruits, employment, purposefulness, access to health care and a strong sense of belonging were believed to be protective against suicide, but increasing rates have challenged this assumption [79]. In one study, having a service-connected disability was associated with a lower risk of suicide in veterans, likely due to greater access to VA health care and regular compensation payments [52]. It is interesting to note that many of these protective factors do not apply to discharged or retired veterans. Other potentially protective factors include older age, African American/Black race, and admission to a nursing home [79].

Risk Factors

Veterans and military members often possess many risk factors for attempting or completing suicide. This includes combat exposure (particularly deployment to a combat theater and/or adverse deployment experiences), combat wounds, post-traumatic stress disorder (PTSD) and other mental health problems, comorbid major depression, traumatic brain injury, poor social support, feelings of not belonging or of being a burden to others or society, acquired ability to inflict lethal self-injury, and access to lethal means [52,58,81,82,83]. There is conflicting evidence of the role of PTSD in suicide risk, with some studies finding PTSD diagnosis to be protective while others indicated it increased risk. Other possible risk factors include [79,123]:

- Disciplinary actions

- Reduction in rank

- Career threatening change in fitness for duty

- Perceived sense of injustice or betrayal (unit/command)

- Command/leadership stress, isolation from unit

- Transferring duty station

- Administrative separation from service/unit

- Military sexual trauma

Case Scenario: Patient B

Patient B is 56 years of age, married with one grown daughter. She consults a primary care physician because of a gradual decline in health over the past 12 to 18 months. She has come at the insistence of her daughter, who accompanies her. Her given purpose is vague: a "check-up" and perhaps laboratory work. Her daughter tells the nurse, "My mother's not well. She's home alone, doesn't get enough sleep, and won't eat right. She complains about her stomach and thinks she has food allergies; she has tried special diets, supplements, and herbal remedies and claims she's getting better, but she's not." The patient is petite, well-groomed, and smiles readily. She tells the physician, "I'll be okay, but I do want to be sure I'm not anemic or have a thyroid problem." She gives a history of chronic, recurrent abdominal discomfort, bloating, periodic constipation, and intolerance to many foods. As a young woman, she was told she has irritable bowel syndrome and was given trials of medication, but she reports being unable to take these medications and being "very sensitive to any prescription medication." She thinks she has lost maybe 5 pounds in the past year. Her examination is unrevealing, except she is thin and there is a hint of generalized muscle atrophy. Over the course of the interview, she appears tired and to have a slightly blunt affect. The following laboratory tests are ordered: complete blood count, chemistry profile, vitamin D and B12 levels, and thyroid function tests. She is given an appointment to return in five days to discuss the results and plan a course of treatment.

6. IMMINENT SUICIDE

While risk factors for suicide represent broader, durable, and ongoing factors, a suicide crisis is a time-limited event that signals an immediate danger of suicide. A suicide crisis can be triggered by a particularly distressing event, such as loss of a loved one or career failure, and involve an intense emotional state in addition to depression, such as desperation (anguish plus urgent need for relief), rage, psychic pain or inner tension, anxiety, guilt, hopelessness, or acute sense of abandonment. Changes in behavior or speech can suggest that suicide is imminent; speech may be indirect, with statements such as, "My family would be better off without me." Persons contemplating suicide may also talk as if they are saying goodbye or going away, exhibit actions ranging from buying a gun to suddenly putting one's affairs in order, or deterioration in social or occupational functioning, increasing use of alcohol, other self-destructive behavior, loss of control, or rage explosions [2].

WARNING SIGNS

Most people who are suicidal exhibit warning signs, whether or not they are in an acute suicide crisis. These warning signs should be taken seriously and include observable signs of serious depression, such as unrelenting low mood, pessimism, hopelessness, desperation, anxiety, psychic pain, and inner tension; withdrawal from friends and/or social activities; sleep problems; and loss of interest in personal appearance, hobbies, work, and/or school [2,13]. Other signs include:

- Increased alcohol and/or other drug use

- Recent impulsiveness and taking unnecessary risks

- Talk about suicide, death, and/or no reason to live

- Making a plan (e.g., giving away prized possessions, sudden or impulsive purchase of a firearm, or obtaining other means of killing oneself, such as poisons or medications)

- Unexpected rage, anger, or other drastic behavior change

- Recent humiliation, failure, or severe loss (especially a relationship)

- Unwillingness to "connect" with potential helpers.

The following expressions of thoughts, feelings, or behaviors may also be warning signs of suicidal behavior [13]:

- Can't stop the pain

- Can't think clearly

- Can't make decisions

- Can't see any way out

- Can't sleep, eat, or work

- Can't get out of the depression

- Can't make the sadness go away

- Can't see the possibility of change

- Can't see themselves as worthwhile

- Can't get someone's attention

- Can't seem to get control

A mnemonic device, IS PATH WARM, has been developed for use in identifying suicide risk [84]. This mnemonic device was derived from the consensus of internationally renowned clinical researchers held under the auspices of the American Association of Suicidology. It consists of the following [84]:

- Ideation

- Substance abuse

- Purposelessness

- Anxiety

- Trapped

- Hopelessness

- Withdrawal

- Anger

- Recklessness

- Mood change

Intentional Self-Harm

Intentional self-harm is behavior related to, but distinct from, suicide behavior and includes suicide attempts and nonsuicidal self-injurious behaviors, such as burning, cutting, and hair pulling, that does not have fatal intent [85]. Self-injurious behavior falls into three categories [85]:

- Major self-injury: Infrequent, usually associated with psychosis or intoxication

- Stereotypic self-injury: Repetitive and reflects a biologic drive of self-harm

- Superficial-to-moderate self-injury: The most common form and is used by self-mutilators to relieve tension, release anger, regain self-control, escape from misery, or terminate a state of depersonalization

Patients with a history of intentional and repetitive self-harm are likely to be highly impulsive with a diagnosis of borderline personality disorder, and distress over their inability to curtail the behavior may heighten suicide risk [85,86,87]. It is essential to recognize that previous nonlethal self-harm does not preclude the development of suicidal ideation or plans with serious intent and lethality [62]. It is important to assess the intent of self-harm behaviors during the risk assessment.

Five days after the initial visit, in anticipation of follow-up later that day, the physician reviews Patient B's laboratory results, all of which are normal. That afternoon, the patient is a "no-show," and no further action is taken. Some time the following week, the office nurse asks her colleague about Patient B, stating "Something about her really bothered me." She recommends that the physician call the patient to follow-up, which he does. The daughter answers with a mix of concern and relief. She states, "I'm really worried about my mother. She's not making sense at times, seems really down, and says we'd all be better off if she just went to sleep and didn't wake up…I didn't mention it last week, but she and my dad are not doing well. He's busy, on the road a lot, and I get the feeling she thinks he's unfaithful to her." At this juncture what do you do?

- Ask the daughter to bring her mother to the office today, along with all supplements and herbal medicines she may have been taking.

- Consider the key issue(s) and give some thought to your clinical approach (e.g., sequencing the encounter and useful tools that will help to identify major depression and assess suicide risk).

- Anticipate logistical barriers in relation to time of day and the possible need for immediate psychiatric consultation and/or hospitalization.

7. SUICIDE ATTEMPTS

LETHAL MEANS

In the United States in 2019, use of a firearm was the cause of death in 50.4% of suicides and is the number one means among all individuals 15 years of age and older. Gun use accounts for 47% of all suicide deaths in individuals 15 to 24 years of age, reaching a low of 42.1% in those 35 to 44 years of age, and increasing to 51.8% in those 55 to 64 years of age. Firearm use for suicide completion is extremely high among the elderly, with individuals 75 to 84 and 85 years of age and older having the highest rates, at 75.4% and 76.6%, respectively. Gun use is also the most common suicide method among youth, accounting for 31.5% of all suicide deaths [1,78].

Although most gun owners report keeping a firearm in their home for the purpose of protection or self-defense, 83% of gun-related deaths in these homes are the result of a suicide, usually by someone other than the gun owner. Guns are involved in more deaths by suicide than by homicide, and overall, death by firearm is the most common suicide method [12].

The suicide rates among youths 15 to 24 years of age by firearm increased from 5.3 per 100,000 in 2001 to 6.6 per 100,000 in 2019, while the suicide rates by suffocation (e.g., hanging) increased from 3.1 per 100,000 in 2001 to 5.0 per 100,000 in 2019. These trends among teens and young adults have been mirrored by children 5 to 14 years of age, in whom deaths by firearms and suffocation have been increasing since at least 2001 [1,78].

The most common method of suicide death among women in all age groups from 2001 to 2019 was poisoning (35.5%); however, in 2018, firearms surpassed poisoning for the first time since 2000 among female victims [15,78]. Although intentional overdose is the most common method for suicide attempts in women, it is much less likely to result in death. Many over-the-counter medications, prescription drugs, dietary supplements/herbal medications, or illicit drugs may be used to attempt suicide. Ibuprofen is a popular over-the-counter analgesic and a common drug of choice in intentional overdoses. There were more than 12,490 intentional overdose ingestions of ibuprofen reported by U.S. poison control centers in 2018, resulting in one death [89]. Opioid analgesics result in many deaths due to intentional overdose. In one study, researchers found that the percentage of individuals who died by suicide and had opioids in their system more than doubled, from 8.8% to 17.7%, between 2006 and 2017 [45].

Ingestion of other toxic substances (including bleach, poisons, and agricultural chemicals), jumps from tall heights, and exsanguination are also relatively common methods of suicide attempt and completion. When assessing risk, it is important to consider the patient's level of impulsivity and the potential lethality of available means (particularly firearms).

MOTIVES BEHIND SUICIDAL BEHAVIOR

Although thousands of books have explored the question of why people kill themselves, in most cases the answer can be summed up in three words: to stop pain. The pain may be physical, as in chronic or terminal illness, but is usually emotional. However, Stone has delineated a more elaborate description of the motivations for suicide, including [18]:

- Altruistic/heroic suicide: Occurs when someone (more or less) voluntarily dies for the benefit of the group. Examples include the Japanese kamikaze pilots in WWII and the Buddhist monks who burned themselves to death protesting the Vietnam war.

- Philosophical suicide: Various philosophical schools, such as the stoics and existentialists, have advocated suicide under some circumstances.

- Religious suicide: Often as martyrdom, this type of suicide has a long history that spans from early Christianity to the Branch Davidians in Waco, Texas, and some members at Jonestown, Guyana.

- Escape: This type of suicide represents an escape from an unbearable situation, such as persecution, a terminal illness, or chronic misery.

- Excess alcohol and other drug use

- Romantic suicide: This includes suicide pacts (dual suicide), which constitute about 1% of suicides in Western Europe. Participants are usually older than 51 years of age, except in Japan, where 75% of dual suicides are "lovers' pacts."

- "Anniversary" suicide: Suicide involving the same method or date as a deceased loved one.

- "Contagion" suicide: Occurs when one suicide appears to trigger others (e.g., "cluster" and "copycat" suicides), most often among adolescents.

- Manipulation: Usually involving the theme "If you don't do what I want, I'll kill myself." The word "manipulative" does not imply a lack of seriousness, as fatal suicide attempts can be made by people hoping to influence or manipulate the feelings of others even though they will not be around to witness the outcome. However, the intent of manipulative attempts is to produce guilt in the other person, and a nonfatal result is usually intended.

- Call for help: An expression of unbearable pain and misery that is more frequent in the young.

- "Magical thinking" and vengeance: Associated with a feeling of power and complete control. This motivation to attempt suicide is driven by a "you'll be really sorry when I'm dead" fantasy. A fatal outcome is intended, and this is sometimes called "aggressive suicide."

- Cultural approval: In some cultures, such as Japanese culture, society has traditionally accepted or encouraged suicide when matters of honor were concerned.

- Lack of an outside source to blame for one's misery: Evidence exists that rage and homicide is the extreme response when an external cause of one's unhappiness can be identified, and depression and suicide is the extreme response in the absence of a perceived or identifiable external source.

8. SCREENING AND ASSESSMENT OF SUICIDE RISK

Many persons who die by suicide have contact with healthcare providers in the time preceding their deaths. Roughly 45% of all persons who die by suicide had contact with a mental health professional in the year before their deaths, and 75% of elderly persons who die by suicide had visited their physician in the month before their death [2,5]. Although close to 90% of these cases had diagnosable psychiatric illness at the time of death, only 30% reported suicidal ideation or intent to a health professional before their suicide attempt [2]. These figures suggest a widespread inadequacy in identifying and assessing at-risk persons by healthcare professionals, and numerous studies have concluded that health professionals often lack sufficient training in the proper assessment, treatment, management, or referral of suicidal patients [2,5]. Many health professionals also lack training in identifying grieving family members of loved ones who have died by suicide [5]. Primary care providers occupy a niche in the healthcare system and have perhaps the greatest opportunity to impact suicidal persons through educational means [5,46,59,60,91].

SCREENING IN THE PRIMARY CARE SETTING: EXPERT CONSENSUS

Many organizations have issued consensus statements regarding screening for suicide risk in the primary care setting. The U.S. Preventive Services Task Force (USPSTF) states that although suicide screening is of high national importance, it is very difficult to predict who will die from suicide and has found insufficient evidence for routine screening by primary care clinicians to detect suicide risk and limited evidence of the accuracy of screening tools to identify suicide risk in the primary care setting[92,96]. The USPSTF recommends physicians screen all adolescents 12 to 18 years of age for major depressive disorder. The Canadian Task Force on Preventive Health Care found insufficient evidence for routine screening by primary care clinicians to detect depression and suicide risk[93].

However, the American Academy of Pediatrics (AAP) recommends universal screening for suicide risk throughout adolescence (12 years of age and older) and clinically indicated screening for children 8 to 11 years of age[94]. Screening should be performed in a developmentally and medically appropriate manner. The AAP notes that screening for depression is not the same as screening for suicide risk and that screening for depression alone misses 36% of patients at-risk for dying by suicide [94]. Screening children younger than 8 years of age is not recommended, but warning signs or parental reports of self-harm or suicidal behaviors should be assessed further; these may include [94]:

- Talking about wanting to die or wanting to kill oneself

- Grabbing their throat in a "choking" motion, or placing their hand in the shape of a gun pointed toward their head

- Acting with impulsive aggression

- Giving away their treasured toys or possessions

The American Academy of Child and Adolescent Psychiatry recommends clinician awareness of patients at high risk for suicide (i.e., older male adolescents and all adolescents with current psychiatric illness or disordered mental state, particularly major depressive disorder), especially when complicated by comorbid substance abuse, irritability, agitation, psychosis, or previous suicide attempt[95,125]. Suicide risk should be assessed at each visit in patients with long-term SSRI use.

ASSESSMENT OF SUICIDE RISK

Initial Inquiry

Healthcare providers may encounter a patient they suspect is suicidal. This suspicion may be prompted by the presence of one or more of the risk factors for suicide described previously, patient history, a statement expressed by the patient, or by their intuition. This scenario may present a dilemma of how to proceed. Although some healthcare professionals are uncomfortable with suicidal patients, it is essential not to ignore or deny the suspicion of suicide risk. The first and most immediate step is to allocate adequate time to the patient, even though many others may be scheduled. Showing a willingness to help begins the process of establishing a positive rapport with the patient. Closed-ended and direct questions at the beginning of the interview are not very helpful; instead, use open-ended questions such as, "You look very upset; tell me more about it." Listening with empathy is in itself a major step in reducing the level of suicidal despair and overall distress [59,60]. It is helpful to lead into the topic gradually with a sequence of useful questions, such as [59,60]:

- Do you feel unhappy and helpless?

- Do you feel desperate?

- Do you feel unable to face each day?

- Do you feel life is a burden?

- Do you feel life is not worth living?

- Have you had thoughts of ending your own life?

It is important to ask these questions after rapport has been established, when the patient feels comfortable expressing his or her feelings, and when the patient is in the process of expressing negative feelings [59,60].

After the patient confirms an initial suspicion of suicidal ideation, the next step is to assess the frequency and severity of the ideation and the possibility of suicide. It is important to ask the patient about whether a method has been developed and planned, the accessibility to the means to attempt suicide, and the magnitude of lethal intent in a manner that is not demanding or coercive, but is asked in a warm and caring way that demonstrates empathy with the patient. Such general questions might include [59,60]:

- Have you made any plans for ending your life?

- How are you planning to do it?

- Do you have in your possession [pills/guns/other means]?

- Have you considered when to do it?

In general, the more an individual has thought about suicide, made specific plans, and intends to act on those plans, the greater the suicide risk. Thus, as part of the assessment of suicide risk it is essential to inquire specifically about the patient's suicidal thoughts, plans, behaviors, and intent. Such questions may often flow naturally from discussion of the patient's current situation, but in other cases they should be explicitly asked [62].

Other questions may help further elucidate suicidal thoughts, plans, or behaviors, including [62]:

Patient's Feelings about Living

- Have you ever felt that life was not worth living?

- Did you ever wish you could go to sleep and just not wake up?

Thoughts of Death, Self-Harm, or Suicide

- Is death something you've thought about recently?

- Have things ever reached the point that you've thought of harming yourself?

Follow-Up Questions

- When did you first notice such thoughts?

- What led up to the thoughts (e.g., interpersonal and psychosocial precipitants, including real or imagined losses; specific symptoms such as mood changes, anhedonia, hopelessness, anxiety, agitation, psychosis)?

- How often have those thoughts occurred (including frequency, obsessional quality, controllability)?

- How close have you come to acting on those thoughts?

- How likely do you think it is that you will act on them in the future?

- Have you ever started to harm (or kill) yourself but stopped before doing something (e.g., holding knife or gun to your body but stopping before acting, going to edge of bridge but not jumping)?

- What do you envision happening if you actually killed yourself (e.g., escape, reunion with significant other, rebirth, reactions of others)?

- Have you made a specific plan to harm or kill yourself? If so, what does the plan include?

- Do you have guns or other weapons available to you?

- Have you made any particular preparations (e.g., purchasing specific items, writing a note or a will, making financial arrangements, taking steps to avoid discovery, rehearsing the plan)?

- Have you spoken to anyone about your plans?

- How does the future look to you?

- What things would lead you to feel more (or less) hopeful about the future (e.g., treatment, reconciliation of relationship, resolution of stressors)?

- What things would make it more (or less) likely that you would try to kill yourself?

- What things in your life would lead you to want to escape from life or be dead?

- What things in your life make you want to go on living?

- If you began to have thoughts of harming or killing yourself again, what would you do?

For persons with previous suicidal or self-harm behavior, the following questions address the antecedents, methods, and aftermath [62]:

- Can you describe what happened (e.g., circumstances, precipitants, view of future, use of alcohol or other substances, method, intent, seriousness of injury)?

- What thoughts were you having beforehand that led up to the attempt?

- What did you think would happen (e.g., going to sleep versus injury versus dying, getting a reaction out of a particular person)?

- Were other people present at the time?

- Did you seek help afterward yourself, or did someone get help for you?

- Had you planned to be discovered, or were you found accidentally?

- How did you feel afterward (e.g., relief versus regret at being alive)?

- Did you receive treatment afterward (e.g., medical versus psychiatric, emergency department, inpatient versus outpatient)?

- Has your view of things changed, or is anything different for you since the attempt?

- Are there other times in the past when you've tried to harm (or kill) yourself?

Repeated Suicidal Thoughts or Attempts

- About how often have you tried to harm (or kill) yourself?

- When was the most recent time?

- Can you describe your thoughts at the time that you were thinking most seriously about suicide?

- When was your most serious attempt at harming or killing yourself?

- What led up to it, and what happened afterward?

Persons with Psychosis, Hallucinations, and Delusions

- Can you describe the voices (e.g., single versus multiple, male versus female, internal versus external, recognizable versus unrecognizable)?

- What do the voices say (e.g., positive remarks, negative remarks, threats)? If the remarks are commands, determine if they are for harmless versus harmful acts; ask for examples.

- How do you cope with (or respond to) the voices?

- Have you ever done what the voices ask you to do? What led you to obey the voices? If you tried to resist them, what made it difficult?

- Have there been times when the voices told you to hurt or kill yourself? How often? What happened?

- Are you worried about having a serious illness or that your body is rotting?

- Are you concerned about your financial situation even when others tell you there is nothing to worry about?

- Are there things that you have been feeling guilty about or blaming yourself for?

Potential to Harm Others

- Are there others who you think may be responsible for what you are experiencing (e.g., persecutory ideas, passivity experiences)? Are you having any thoughts of harming them?

- Are there other people you would want to die with you?

- Are there others who you think would be unable to go on without you?

When assessing for suicide, it is important to be cautious of misleading information or false improvement [59,60]. When an agitated patient suddenly appears calm, he or she may have made the decision to attempt suicide and feels calm after making the decision. Denial is another important consideration. Patients may deny harboring very serious intentions of killing themselves.

All patients at acute risk for suicide who are under the influence (intoxicated by drugs or alcohol) should be evaluated in an urgent care setting and be kept under observation until they are sober. If the patient is intoxicated when the initial assessment is completed, it should be repeated after he or she is sober [79].

Lethal Means

All persons at risk for suicide should be assessed for availability or intent to acquire lethal means, including firearms and ammunition, drugs, poisons, and other means in the patient's home [79].

Clinicians should always inquire about access to firearms and ammunition and how they are stored. For military members and veterans, this includes assessing privately owned firearms. In addition, medication reconciliation should be performed for all patients. For any current and/or proposed medications, consider the risk/benefit of any medications that could be used as a lethal agent to facilitate suicide. Consider prescribing limited supplies for those at elevated risk for suicide or with histories of overdose or the availability of a caregiver to oversee the administration of the medications. In addition to medications, the availability of chemical poisons, especially agricultural and household chemicals, should be assessed, as many of these are highly toxic [79].

DETERMINING LEVEL OF RISK AND APPROPRIATE ACTIONS

The formulation of the level of risk for suicide guides the most appropriate care environment in which to address the risk and provide safety and care needs. The first priority is safety. Patients assessed as having a clear intention of taking their lives will require higher levels of safety protection than those with less inclination toward dying. Patients who are at high risk for suicide may require inpatient care to provide for increased level of supervision and higher intensity of care. Those at intermediate and low acute risk may be referred to an outpatient care setting and, with appropriate supports and safety plans, may be able to be followed-up in the community (Table 2) [79].

Table 2: DETERMINE LEVEL OF RISK FOR SUICIDE AND APPROPRIATE ACTION

Risk of Suicide Attempt

Indicators of Suicide Risk

Contributing Factorsa

Initial Action Based on Level of Risk

High acute risk

Persistent suicidal ideation or thoughts

Strong intention to act or plan

Not able to control impulse

Recent suicide attempt or preparatory behaviorb

Acute state of mental disorder or acute psychiatric symptoms

Acute precipitating event(s)

Inadequate protective factors

Maintain direct observational control of the patient

Limit access to lethal means

Immediate transfer with escort to urgent/emergency care setting for hospitalization

Intermediate acute risk

Current suicidal ideation or thoughts

No intention to act

Able to control the impulse

No recent attempt or preparatory behavior or rehearsal of act

Existence of warning signs or risk factorsb and limited protective factors

Refer to behavioral health provider for complete evaluation and interventions

Contact behavioral health provider to determine acuity of referral

Limit access to lethal means

Low acute risk

Recent suicidal ideation or thoughts

No intention to act or plan

Able to control the impulse

No planning or rehearsing a suicide act

No previous attempt

Existence of protective factors and limited risk factors

Consider consultation with behavioral health to determine need for referral and treatment

Treat presenting problems

Address safety issues

Document care and rationale for action

aModifiers that increase the level of risk for suicide of any defined level include acute state of substance use, access to means (e.g., firearms, medications), and existence of multiple risk factors or warning signs or lack of protective factors.

bEvidence of suicidal behavior warning signs in the context of denial of ideation should call for concern (e.g., contemplation of plan with denial of thoughts or ideation).

Source: U.S. Department of Veterans Affairs. VA/DoD Clinical Practice Guideline for Assessment and Management of Patients at Risk for Suicide. Available at http://www.healthquality.va.gov/guidelines/MH/srb.

Risk Assessment Tools

Rating scales can be helpful in the assessment process. However, a clinical assessment by a trained professional is required to assess suicide risk. This professional should have the skills to engage patients in crisis and to elicit candid disclosures of suicide risk in a non-threatening environment. The assessment should comprise a physical and psychiatric examination, including a comprehensive history (with information from patient, parents, and significant others whenever possible) to obtain information about acute psychosocial stressors, psychiatric diagnoses, current mental status, and circumstances of prior suicide attempts. Assessment tools may be used to evaluate risk factors, in addition to the clinical interview, although there is insufficient evidence to recommend one tool over another.

High Acute Risk

Considering all the information gathered in the assessment, the clinician will formulate the level of risk in one of the following categories: high acute risk, intermediate acute risk, low acute risk, not at elevated risk [79].

High acute risk patients include those with warning signs, serious thoughts of suicide, a plan and/or intent to engage in lethal self-directed violence, a recent suicide attempt, and/or those with prominent agitation, impulsivity, and/or psychosis. In such cases, clinicians should ensure constant observation and monitoring before arranging for immediate transfer for psychiatric evaluation or hospitalization [79]. Patients at high acute risk should be immediately referred for a specialty evaluation with particular concern for ensuring the patient's safety and consideration for hospitalization.

Intermediate Acute Risk

Intermediate acute risk patients include those with suicidal ideation and a plan but with no intent or preparatory behavior. Combination of warning signs and risk factors to include history of self-directed violence (suicide attempt) increases a person's risk for suicide. Patients at intermediate risk should be evaluated by a behavioral health provider. The decision whether to urgently refer a patient to a mental health professional or emergency department depends on that patient's presentation. The patient who is referred may be hospitalized if further evaluation reveals that the level of illness or other clinical findings warrant it. The patient may be managed in outpatient care if patient and provider collectively determine that the individual is capable of maintaining safety by utilizing non-injurious coping methods and utilize a safety plan [79].

Low Acute Risk

Low acute risk patients include those with recent suicidal ideation who have no specific plans or intent to engage in lethal self-directed violence and have no history of active suicidal behavior. Consider consultation with behavioral health to determine need for referral to treatment addressing symptoms and safety issues. These patients should be followed up for reassessment. Patients at low acute risk should be considered for consultation with or referral to a behavioral health practitioner [79].

Not at Elevated Acute Risk or Risk Unknown

Persons with a mental disorder who are managed appropriately according to evidence-based guidelines and do not report suicidal thoughts are outside the scope of the classification of risk for suicide. Patients who at some point in the past have reported thoughts about death or suicide but currently do not have any of these symptoms are not considered to be at acute risk of suicide. There is no indication to consult with behavioral health specialty in these cases, and the patients should be followed in routine care, continue to receive treatment for their disorder, and be re-evaluated periodically for thoughts and ideation. Patients at no elevated acute risk should be followed in routine care with treatment of their underlying condition and evaluated periodically for ideation or suicidal thoughts. Patients for whom the risk remains undetermined (i.e., no collaboration of the patient or provider concerns about the patients despite denial of risk) should be evaluated by a behavioral health practitioner [79].

DOCUMENTATION

In order to ensure optimal patient care and to prevent miscommunication and litigation, the results of any suicide risk assessment should be fully documented. At a minimum, documentation should include the following points, noted by the mnemonic SUICIDE [17]:

- Suicide assessment: The results of suicide screening or assessment, including any relevant history (personal or family), access to lethal means, suicide plans, recent history of stressful events, and protective factors, should be noted.

- Unpredictable: Family members and/or other supportive third parties should be alerted that suicide can be unpreventable, even given the best efforts and plans.

- Interventions: All interventions planned and undertaken should be included in the patient's record.

- Clear and comprehensive: It is important to ensure that all documentation is clear and comprehensive, with specific notes regarding the patient's own words.

- Intent: The intentions of any suicide attempt(s) or intentional self-harm should be noted.

- Discussions with family members and/or other supportive third parties: Supportive third parties can be invaluable to the treatment process, and their inclusion in risk assessments and treatment planning should be documented.

- Educate, engage, empathize: Documentation should include notes regarding the patient's involvement in treatment planning and the creation of a safety plan.

Patient B arrives at the office with her daughter. She appears withdrawn and preoccupied, having a look of resignation and despair. Seated together, you begin the interview in a positive, affirming manner: "I'm pleased that all your laboratory work, including your thyroid tests, is normal. You know you told me you would be okay, and I believe if we work together, so as to know and understand better what you are going through, we can relieve many of your symptoms and get you to a much better place." She is receptive, and after further discussions, the following picture emerges: Patient B has been unhappy for "a very long time." There is little to add to the somatic complaints related on the first visit. She sleeps poorly and is tired all the time; she has lost interest in what was previously an active social life and rarely "goes out." There is a good deal of psychic stress and pain attached to the relationship with her husband, and a sense of hopelessness has been building for months. In recent days, she has not slept and has periods of confusion. She wishes not to be a burden to those closest to her and has thought often of ending her life. Recently she has been thinking about just how to do this, the options available to her, and how it might be done so as to mask her intent. At the conclusion of the interview, you glance at the nurse with an expression of appreciation, and shudder to think how easily you might have missed all this.

- Recall the mnemonic device IS PATH WARM. How many of the elements are positive for Patient B? Which ones?

- Would you rate Patient B's suicide risk as low? Intermediate? High?

- Which of the following management options is the LEAST appropriate at this juncture?

- Send the patient home with a prescription for an antidepressant and a plan for regular return psychotherapy sessions in your office.

- Refer her to a psychiatrist (appointment in 48 to 72 hours) and negotiate a "contract" with the patient that she is not to take matters into her own hands but will call you immediately if she has thoughts of doing so.

- Arrange admission to the hospital medical service with a "sitter" and place an urgent psychiatry consultation.

- Call your psychiatry consultant to summarize the case and request immediate consultation or admission to the inpatient psychiatry service.

9. MANAGEMENT OF SUICIDAL PATIENTS

The opportunity for an emotionally disturbed patient with vague suicidal ideation to vent his or her thoughts and feelings to an understanding health or mental health provider may bring a degree of relief such that no further intervention is needed. However, in all cases the encouragement of further contact and follow-up should be conveyed to the patient, especially when inadequate social support is present. Independent of the actual catalyst, most suicidal persons possess feelings of helplessness, hopelessness, and despair and a triad of three cognitive/emotional conditions [59,60]:

- Ambivalence: Most suicidal patients are ambivalent, with alternating wishes to die and to live. The healthcare provider can use patient ambivalence to increase the wish to live, thus reducing suicide risk.

- Impulsivity: Suicide is usually an impulsive act, and impulse, by its nature, is transient. A suicide crisis can be defused if support is provided at the moment of impulse.

- Rigidity: Suicidal people experience constricted thinking, mood, and action and dichotomized black-and-white reasoning to their problems. The provider can help the patient understand alternative options to death through gentle reasoning.

Healthcare professionals should assess the strength and availability of emotional support to the patient, help the patient identify a relative, friend, acquaintance, or other person who can provide emotional support, and solicit the person's help [59,60]. The engagement of supportive third parties in the patient's life can be a useful tool in preventing suicide completion.

Adherence to established best practices general assures that assessment and care will be ethical and legal. It is important to consider and document informed consent. Underlying key ethical principles include respect for persons, autonomy, and beneficence [121].

PHARMACOTHERAPY TO REDUCE SUICIDE RISK

Abundant evidence has demonstrated that lithium reduces the rate of suicidal behavior in patients with bipolar disorder and recurrent major depression and that clozapine reduces suicidal behavior in schizophrenia [97,98,99,100,101,102]. Both drugs reduce suicide risk independently of their effect on the primary psychiatric disorder. Although the exact anti-suicide mechanism of both drugs has yet to be identified, lithium enhances serotonergic activity and clozapine is a potent 5-HT2A antagonist. Serotonergic modulation is a likely explanation of the suicide-reducing effects of both medications, because aggression levels and suicide are correlated with prefrontal cortical 5-HT2A binding [71,104,105].

PSYCHOTHERAPY TO REDUCE SUICIDE RISK

In addition to pharmacotherapy, various psychotherapy approaches have been shown to decrease suicide risk in patients at low or intermediate risk for suicide [55]. Post-admission cognitive therapy is a cognitive-behavioral therapy approach designed to help patients who have suicide-related thoughts and/or behaviors. It consists of three phases of therapy for outpatients or inpatients [55]:

- The patient is asked to tell a story associated with her or his most recent episode of suicidal thoughts, behavior, or both.

- The patient is assisted with modifying underdeveloped or overdeveloped skills that are most closely associated with the risk of triggering a suicidal crisis.

- The patient is guided through a relapse-prevention task.

Another cognitive-behavioral approach is cognitive-behavioral psychotherapy for suicide prevention, which involves "acute and continuation phases, each lasting about 12 sessions, and includes a chain analysis of the suicidal event, safety plan development, skill building, psychoeducation, family intervention, and relapse prevention" [53].

Dialectical behavior therapy was originally designed to address the self-harm impulses of patients with borderline personality disorder, but it has good evidence for use in most suicidal individuals. Dialectical behavioral therapy is an adaptation of cognitive-behavioral therapy and is based on the theoretical principle that maladaptive behaviors, including self-injury, are attempts to manage intense overwhelming affect of biosocial origin. It consists of the two key elements of a behavioral, problem-solving approach blended with acceptance-based strategies and an emphasis on dialectical processes. Dialectical behavioral therapy emphasizes balancing behavioral change, problem-solving, and emotional regulation with validation, mindfulness, and acceptance of patients. Therapeutic targets are ranked in hierarchical order, with life-threatening behaviors addressed first, followed by therapy-interfering behaviors, and then behaviors that interfere with quality of life.

MENTAL HEALTH REFERRAL

Depending on the level of suicide risk, referral to a mental health professional (e.g., psychologist, counselor, therapist), psychiatrist, or hospitalization may be warranted. Long-term treatment and follow-up will be required for many patients, and appropriate referral to outpatient facilities is often necessary. If the person is currently in therapy, the therapist should be called and involved in the management decision. If the patient does not have a therapeutic relationship with a mental health professional, referral to one should be made. Suicidal patients should be referred to a psychiatrist when any of the following are present: psychiatric illness; previous suicide attempt; family history of suicide, alcoholism, and/or psychiatric disorder; physical illness; or absence of social support [59,60]. After deciding to refer a patient to a mental health professional, the clinician should explain to the patient the reason for the referral and help alleviate patient anxiety over stigma and psychotropic medications. It is also important to help the patient understand that pharmacologic and psychologic therapies are both effective and to emphasize to the patient that referral does not mean "abandonment." The referring clinician should also arrange an appointment with the mental health professional, allocate time for the patient following the initial appointment with the therapist or psychiatrist, and ensure the ongoing relationship with the patient [59,60].

REFERRAL TO BE HOSPITALIZED

Evidence Based Practice Recommendation

The Department of Veterans Affairs recommends choosing the appropriate care setting that provides the patient at risk of suicide maximal safety in the least restrictive environment. Despite insufficient evidence to demonstrate the effectiveness of acute hospitalization in the prevention of suicide, hospitalization is indicated in suicidal patients who cannot be maintained in less restrictive care settings.

https://www.healthquality.va.gov/guidelines/MH/srb

Last Accessed: March 24, 2023

Level of Evidence: Expert Opinion/Consensus Statement

Some indications for immediate hospitalization include recurrent suicidal thoughts, high levels of intent of dying in the immediate future (the next few hours or days), the presence of agitation or panic, or the existence of a plan to use a violent and immediate suicide method [59,60]. When hospitalizing a patient, she or he should not be left alone; the hospitalization and transfer of the patient by ambulance or police should be arranged and the family, and any appropriate authorities should be informed [59,60].

A patient may be discharged to a less restrictive level of care from an acute setting (emergency department/hospital/acute specialty care) after a behavioral health clinician evaluated the patient, or a behavioral health clinician was consulted, and all three of the following conditions have been met [79]:

- Clinician assessment indicates that the patient has no current suicidal intent.

- The patient's active psychiatric symptoms are assessed to be stable enough to allow for reduction of level of care.

- The patient has the capacity and willingness to follow the personalized safety plan (including having available support system resources).

ADDITIONAL OPTIONS FOR CONTINUITY OF CARE

It is important to ensure that the patient has follow-up contact even after discharge to another provider. At the point of discharge, information should be provided on crisis options (referred to as "crisis cards") and free, universally available help, such as hotlines. There is evidence that follow-up outreach in the form of letters or postcards expressing care and concern and continuing for up to three years may be helpful in suicide prevention [75]. These letters should generally be non-demanding, allowing the opportunity but not the requirement for patients to respond.

Alternatively, patients may be followed-up with phone calls from a mental health professional or suicide crisis volunteer [75]. If phone follow-up is preferred, calls should be made weekly or biweekly, in some cases supplemented with a home visit, and should continue for a period of three to six months.

In many cases, partnering with a community crisis center can be helpful [66]. Crisis call centers are a crucial resource in linking patients to services and providing emotional support. According to the Suicide Prevention Lifeline, crisis center follow-up before a service appointment is associated with improved motivation, a reduction in barriers to accessing services, improved adherence to medication, reduced symptoms of depression, and higher attendance rates [64].

SAFETY PLANNING

The VA recommends establishing an individualized safety plan for all persons who are at high acute risk for suicide as part of discharge planning, regardless of inpatient or outpatient status [79]. The safety plan is designed to empower the patient, manage the suicidal crisis, and engage other resources. Safety should also be discussed with patients at intermediate and low risk, with appropriate patient education and a copy of a safety plan handout [79].

Stressful events, challenging life situations, mental/substance use disorders, and other factors can precipitate a crisis of suicidal thoughts and behaviors leading directly to self-injury. Advance anticipation of challenging situations and envisioning how one can identify and break a cycle of suicidal crises can reduce risk of self-injury and enhance a patient's sense of self-efficacy. Open dialogue between patients and clinicians to establish a therapeutic alliance and develop strategies and skills supporting the patient's ability to avoid acting on thoughts of suicide (including minimizing access to lethal means) is an essential component of suicide prevention in clinical settings. Putting this thinking-through process in writing for the anticipation of a suicidal crisis and how to manage it constitutes a patient's safety (action) plan [79].

Safety planning is a provider-patient collaborative process—not a "no harm" contract. The safety planning process results in a written plan that assists the patient with restricting access to means for completing suicide, problem-solving and coping strategies, enhancing social supports and identifying a network of emergency contacts including family members and friends, and ways to enhance motivation. These plans are tailored to the patient by assisting with identifying his or her specific warning signs and past effective coping strategies [79].

The safety plan should include the following elements, as appropriate:

- Early identification of warning signs or stressors

- Enhancing coping strategies (e.g., to distract and support)

- Utilizing social support contacts (discuss with whom to share the plan)

- Contact information about access to professional help

- Minimizing access to lethal means (e.g., weapons and ammunition or large quantities of medication)

The safety plan should be reviewed and updated by the healthcare team working with the patient as needed and shared with family and other supportive third parties if the patient consents. Safety plans should be updated to remain relevant during changes in clinical state and transitions of care [79].

Providers should document the safety plan or reasons for not completing such a plan in the medical record. In addition, patients should receive a copy of the plan [79].

Limiting Access to Lethal Means

Restricting at-risk patients from access to lethal means is considered an essential part of suicide prevention and safety planning. Methods of ensuring persons with suicidal intent do not have access to lethal means include restriction of access to firearms and ammunition, safer prescribing and dispensing of medications to prevent intentional overdoses, and modifying the environment of care in clinical settings to prevent fatal hangings [79]. For military service members, concerns about firearms should include privately owned guns and ammunition. It is also important to educate caregivers, family members, and/or other supportive third parties regarding the potential dangers of lethal means and how to keep these items or substances from the patient.

Storing firearms away from suicidal individuals can reduce gun deaths [79]. It must be stressed that the firearms are still the property of the individual, and they are not "giving them away." Options for safe storage of firearms include removing ammunition from an individual's possession, asking a friend or relative to take possession of firearms, disassembling firearms and storing various parts in different locations, storing firearms at a storage unit or gun locker at a shooting range, storing firearms at a gun shop or pawn shop, asking law enforcement to take possession of firearms, or storing personal firearms at military unit arms rooms [79]. The least restrictive and most acceptable means of removing easy accesses to lethal means should be employed in order to assure an individual welcomes the intervention. It is important to avoid implying that an individual is incapable of firearm possession or that they are unfit in a legal sense.

CONSIDERATIONS FOR VETERANS

With military service members, the command element should also be involved in education, safety planning, treatment planning, and implementation of duty limitations. Additional areas to address are the patient's medical and other specific needs. These may be psychosocial, socioeconomic, or spiritual in nature [79].

The VA/DoD has made the following recommendations when creating a treatment plan for veterans and active service members [79]:

- Providers should take reasonable steps to limit the disclosure of protected health information to the minimum necessary to accomplish the intended purpose.

- Providers should involve command in the treatment plan of service members at high acute risk for suicide to assist in the recovery and the reintegration of the patient to the unit. For service members at other risk levels, the provider should evaluate the risk and benefit of involving command and follow service department policies, procedures, and local regulations.

- When performing a medical profile, the provider should discuss with command the medical recommendation and the impact on the service member's limitations to duty and fitness for continued service.

- Providers should discuss with service members the benefit of having command involved in their plan and assure them their rights to protected health information, with some exceptions, regarding to the risk for suicide.

- As required by pertinent military regulations, communicate to the service member's chain of command regarding suicidal ideation along with any recommended restrictions to duty, health and welfare inspection, security clearance, deployment, and firearms access. Consider redeployment to home station any service member deployed to a hazardous or isolated area.

- Service members at high acute risk for suicide who meet criteria for hospitalization and require continuous (24-hour) direct supervision should be hospitalized in almost all instances. If not, the rationale should specifically state why this was not the preferred action, with appropriate documentation.

- During operational deployment conditions or other extreme situations during which hospitalization or evacuation is not possible, "unit watch" may be considered as appropriate in lieu of a high level care setting (hospitalization), and service department policies, procedures, and local regulations should be followed.

- Because of the high risk of suicide during the period of transition, providers should pay particular attention to ensure follow-up, referral, and continuity of care during the transition of service members at risk for suicide to a new duty station or after separation from a unit or from military service.

CONSIDERATIONS FOR HEALTHCARE PROFESSIONALS

Although confidentiality is crucial when caring for any patient, this is heightened for healthcare providers who would potentially be seeking assessment and treatment in their workplace. All healthcare providers should be offered the opportunity for anonymous screening for depression and suicide. The healer education assessment and referral (HEAR) screening program is a sustainable suicide prevention program that uses an anonymous method to provide screening for untreated depression or suicide [119,121]. The American Foundation for Suicide Prevention also provides services specifically for healthcare providers, accessible at https://afsp.org/suicide-prevention-for-healthcare-professionals.

10. SUICIDE PREVENTION

Understanding the interactive relationship between risk and protective factors in suicidal behavior and how this interaction can be modified forms the basis of suicide prevention [5,106]. The characteristics shared by effective suicide prevention programs include clear identification of the intended population, definition of desired outcomes, use of interventions known to effect a particular outcome, and use of community coordination and organization to achieve an objective. Prevention efforts are based on a clear plan with goals, objectives, and implementation steps [5,45].

HISTORY OF SUICIDE PREVENTION IN THE UNITED STATES

In the United States, large-scale suicide prevention efforts began in 1958. Funding from the U.S. Public Health Service established the first suicide prevention center in Los Angeles, and other crisis intervention centers replicating this model were opened across the country [5]. The risk factor approach to suicide prevention was first implemented in 1966, and the American Association of Suicidology and the American Foundation for Suicide Prevention were established over the next two decades. Their activities included increasing the scientific understanding of suicide as the basis for effective prevention activities [5]. In 1983, the CDC established a violence prevention division that alerted the public to the disturbing increase in youth suicide rates.

In 1996, survivors of suicide loss mobilized to form the Suicide Prevention Advocacy Network USA (SPAN USA) and launched a campaign to advocate for the development of a national suicide prevention strategy [107]. In 2009, SPAN USA merged with the American Foundation for Suicide Prevention to raise awareness, fund research, and provide resources and aid to those affected by suicide [48].

The National Strategy for Suicide Prevention (NSSP) was released by the Surgeon General of the United States in 2001 and updated in 2012. The NSSP describes a series of goals and objectives designed to reduce the incidence of suicide behaviors in the United States [46]. Although activity in the field of suicide prevention has increased exponentially since publication of the NSSP, the overall rate of suicide since 2000 continues to increase [1].

SUICIDE PREVENTION THAT TARGETS AT-RISK POPULATIONS

College Students

Colleges and universities are increasingly challenged to identify and manage mental health and substance use problems in students. Because the risk and protective factors for suicide among young adults include substance abuse and interpersonal violence, suicide prevention may best be integrated within broader prevention efforts [5,108,109].

Inmates in Jails and Correctional Settings

As discussed, jails and juvenile justice facilities have exceptionally high suicide rates. The highest rates of jail suicide occur within the first 24 to 48 hours of arrest, suggesting an important role of medical assessment of substance abuse and suicide proneness at intake. Comprehensive prevention programs targeting inmate suicide include training, screening, effective communication methods, intervention, use of reporting protocols, and mortality review [5,110].

Elderly Persons

Almost 70% of elderly patients who take their own lives see their primary care physician within a few months of their death [111,112]. This represents an absolutely vital, yet narrow, window for accurate screening and assessment of suicide risk [2]. Unfortunately, healthcare and mental health professionals are not immune from harboring the stereotypes of the elderly often found among society in general. These can include attitudes that a depressive response to interpersonal loss, physical limitation, or changing societal role is an inevitable and even normal aspect of aging [111,113,114]. Suicidal thoughts may even be considered age-appropriate in the elderly [112]. When held by patients and family members, these erroneous beliefs can lead to under-reporting of symptoms and lack of effort on the part of family members to seek care for patients [114]. When held by clinicians, these beliefs can result in delayed or missed diagnoses, less effective treatment, or suicide in the elderly patient.

Because the elderly have the highest overall suicide rate of all age groups, organizations with special access to older persons have an important role in suicide prevention. State aging networks exist in every state, and these networks develop and fund a variety of in-home and community-based services. States organize the provision of such services through area agencies on aging, which coordinate a broad range of services for older people [5].

Patients with Bipolar Disorder

Although 20% of patients with bipolar disorder have their first episode during adolescence, diagnosis is often delayed for years, which can result in problems such as substance abuse and suicidal behaviors. Thus, early recognition and aggressive treatment may prevent years of needless suffering and death by suicide. In particular, lithium is effective in preventing suicidal behavior in patients with bipolar disorder. Maintaining treatment is essential in preventing suicide, and the suicide rate in the first year of discontinuation of lithium treatment is 20 times higher than during lithium treatment [103].

Patients with Schizophrenia

Approximately 0.9% of people in the United States are living with schizophrenia or a related disorder [49]. One study of patients with schizophrenia showed a lifetime prevalence of suicide attempt of 39.2%, versus 2.8% of nonafflicted individuals; furthermore, about 5% of patients with schizophrenia will eventually die by suicide [50,90]. Depression is the most important risk factor for suicide in patients with schizophrenia; only 4% of patients with schizophrenia who exhibit suicidal behavior do so in response to instructions from "command" voices. Clozapine is effective in reducing suicide and attempted suicide in patients with schizophrenia, and effective suicide prevention involves the early recognition and prompt treatment of schizophrenia and all comorbid conditions [2].

Military Veterans

Assessment of suicide risk and protective factors in military personnel is vital, particularly at times of transition (e.g., deployment, separation from service/unit). It is important to include life planning, referral information, and resources for patients who experience suicidal ideation, and there are military-specific resources available for current or former members of the military. The Veterans Crisis Line, https://www.veteranscrisisline.net or 988, is free to all active service members, including members of the National Guard and Reserve, and veterans, even if they are not registered with the VA or enrolled in VA health care [81].

STIGMA AND SUICIDE

The stigma of mental illness and substance abuse, both of which are closely linked to suicide, prevents many persons from seeking help out of a fear of prejudice and discrimination [88]. People who have a substance use disorder face additional stigma because many people believe that abuse and addiction are moral failings and that individuals are fully capable of controlling these behaviors if they want to [5,80]. The stigma of suicide, while deterring some from attempting suicide, is also a barrier to treatment for many persons who have suicidal thoughts or have attempted suicide. Family members of suicide attempters often hide the behavior from friends and relatives, because they may believe that it reflects badly on their own relationship with the suicide attempter or that suicidal behavior itself is shameful or sinful. Persons who attempt suicide may have many of these same feelings [5].

On a systems level, the stigma surrounding mental illness, substance use disorders, and suicide has contributed to inadequate funding for preventive services and inadequate insurance reimbursement for treatments. Substance use and mental health conditions, including those associated with suicide, will remain undertreated and services tailored to persons in crisis will remain limited as long as stigma persists, resulting in an unnecessarily high rate of suicidal behavior and suicide [5]. Additionally, the stigma associated with mental illness and substance abuse has led to separate systems for physical health and mental health care, a consequence being that preventive and treatment services for mental illness and substance abuse are much less available than for other health problems. This separation has also led to bureaucratic and institutional barriers between the two systems that impede and complicate access to care and service implementation [5].

11. SUICIDE SURVIVORS: TREATMENT AND RESOURCES

Family members and friends affected by the death of a loved one through suicide are referred to as "suicide survivors." Conservative estimates suggesting a ratio of six survivors for every suicide deaths indicate that an estimated 6 million Americans became suicide survivors in the past 25 years; however, as noted, many more individuals are affected by a single suicide [4,13,14].

The death of a loved one by suicide can be shocking, painful, and unexpected for survivors. The ensuing grief can be intense, complex, chronic, and nonlinear. Working through grief is a highly individual and unique process that survivors experience in their own way and at their own pace. Grief does not always move in a forward direction, and there is no timeframe for grief. Survivors should not expect their lives to return to their previous state and should strive to adjust to life without their loved one. The initial emotional response may be overwhelming, and crying is a natural reaction and an expression of sadness following the loss of a loved one [13].

Survivors often struggle with trying to comprehend why the suicide occurred and how they could have intervened. Feelings of guilt are likely when the survivor believes he or she could have prevented the suicide. The survivor may even experience relief at times, especially if the loved one had a psychiatric illness. The stigma and shame that surround suicide may cause difficulty among the family members and friends of survivors in knowing what to say and how to support the survivor and might prevent the survivor from reaching out for help. Ongoing support remains important to maintain family and other relationships during the grieving process [13].

Many survivors find that the best help comes from attending a support group for survivors of suicide in which they can openly share their own story and their feelings with fellow survivors without pressure or fear of judgment and shame. Support groups can be a helpful source of guidance, understanding, and support through the healing process [13]. The American Foundation for Suicide Prevention maintains an international directory of suicide bereavement support groups on their website, https://afsp.org.

12. CONCLUSION

Suicide is a major preventable public health problem and a significant cause of mortality. This course has reviewed the major aspects of suicide assessment, management, and prevention, with a special focus on military veterans. Primary care contact may represent the last opportunity for intervention in the severely depressed suicidal patient, making the thorough comprehension of identification and treatment of depression and suicide risk imperative.

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Evidence-Based Practice Recommendations Citations

1. Adelson SL, American Academy of Child and Adolescent Psychiatry Committee on Quality Issues. Practice parameter on gay, lesbian, or bisexual sexual orientation, gender nonconformity, and gender discordance in children and adolescents. J Am Acad Child Adolesc Psychiatry. 2012;51(9):957-974. Available at https://jaacap.org/article/S0890-8567(12)00500-X/fulltext. Last accessed March 24, 2023.

2. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major Depressive Disorder. 3rd ed. Arlington, VA: American Psychiatric Association; 2010. Available at https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf. Last accessed March 24, 2023.

3. Assessment and Management of Risk for Suicide Working Group. VA/DoD Clinical Practice Guideline for Assessment and Management of Patients at Risk for Suicide. Washington, DC: Department of Veterans Affairs, Department of Defense; 2019. Available at https://www.healthquality.va.gov/guidelines/MH/srb/. Last accessed March 24, 2023.