FLDN18 • Florida Dentists 2018

Table of Contents

FLDN18 • Florida Dentists 2018

How to Receive Credit

NetCE 10 Hour Course #58882 • Sleep Disorders

58882 • Sleep Disorders

1. INTRODUCTION

2. THE PHYSIOLOGY OF SLEEP

3. OVERVIEW OF SLEEP DISORDERS

4. INSOMNIAS

5. SLEEP-RELATED BREATHING DISORDERS

6. CENTRAL DISORDERS OF HYPERSOMNOLENCE

7. CIRCADIAN RHYTHM SLEEP-WAKE DISORDERS

8. PARASOMNIAS

9. SLEEP-RELATED MOVEMENT DISORDERS

10. DIAGNOSING AND TREATING SLEEP DISORDERS WITH THE HELP OF AN INTERPRETER

11. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

NetCE 2 Hour Course #57922 • Domestic Violence: The Florida Requirement

57922 • Domestic Violence: The Florida Requirement

1. INTRODUCTION

2. DEFINING DOMESTIC VIOLENCE

3. NATIONAL AND STATE STATISTICS AND LEGISLATION

4. IDENTIFYING GROUPS AT RISK FOR DOMESTIC VIOLENCE

5. CHARACTERISTICS OF PERPETRATORS OF DOMESTIC VIOLENCE

6. SCREENING FOR DOMESTIC VIOLENCE AND ABUSE

7. ASSESSING DOMESTIC VIOLENCE AND ABUSE

8. INTERVENTIONS FOR DOMESTIC VIOLENCE AND ABUSE

9. DOCUMENTATION AND FOLLOW-UP

Works Cited

Evidence-Based Practice Recommendations Citations

NetCE 2 Hour Course #51333 • Medical Error Prevention and Root Cause Analysis

51333 • Medical Error Prevention and Root Cause Analysis

1. INTRODUCTION

2. DEFINING "MEDICAL ERROR"

3. ROOT CAUSE ANALYSIS PROCESS

4. ERROR REDUCTION AND PREVENTION

5. OTHER CONSIDERATIONS FOR PATIENT SAFETY

6. CONCLUSION

Works Cited

NetCE 5 Hour Course #54002 • A Review of Oral Histology and Physiology

54002 • A Review of Oral Histology and Physiology

1. INTRODUCTION

2. TEETH

3. THE PERIODONTIUM

4. THE ORAL MUCOSA

5. THE SALIVARY GLANDS

6. CONCLUSION

Works Cited

NetCE 5 Hour Course #55181 • Local Anesthetics in Dentistry

55181 • Local Anesthetics in Dentistry

1. INTRODUCTION

2. AN HISTORICAL PERSPECTIVE

3. CHEMICAL CLASSIFICATION OF LOCAL ANESTHETICS

4. THE PHYSIOLOGY OF LOCAL ANESTHETICS

5. LOCAL ANESTHETIC AGENTS

6. ADJUNCTIVE MEDICATIONS

7. BUFFERING LOCAL ANESTHETIC SOLUTIONS

8. TREATMENT OF LOCAL ANESTHETIC-INDUCED MEDICAL EMERGENCIES

9. CONCLUSION

Works Cited

FLDN18 • Florida Dentists 2018

Teisha Phillips, RN, BSN

Marjorie Conner Allen, BSN, JD

Alice Yick Flanagan, PhD, MSW

Mark J. Szarejko, DDS, FAGD

www.netce.com

Copyright © 2024 NetCE, All rights reserved.

FLDN18 • Florida Dentists 2018

Expiration Date: 12/31/2021

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.

58882 • Sleep Disorders

Teisha Phillips, RN, BSN

www.netce.com

Copyright © 2019 NetCE, All rights reserved.

Sleep is one of the most vital processes of life and serves many functions, including preservation, restoration, and memory processing. Repeated disruption of the natural sleep cycle or failure to initiate sleep (i.e., sleep disorder) can lead to a sleep deficit, which in turn causes physical, mental, and emotional fatigue. This is evidenced by the fact that many individuals with a sleep disorder express a reduction in quality of life. This course will provide information regarding the physiology of sleep; the causes, risk factors, epidemiology, and physiology of a variety of sleep disorders; diagnosis, including patient history, assessment of sleep habits, physical examination, laboratory tests, and sleep studies; and treatments to improve sleep patterns, including lifestyle/behavioral change (i.e., "sleep hygiene"), medication interventions, and other treatment options for patients.

Table of Contents

58882 • Sleep Disorders

Course Overview

Audience

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Division Planner

Division Planner Disclosure

About the Sponsor

Disclosure Statement

1. INTRODUCTION

2. THE PHYSIOLOGY OF SLEEP

CIRCADIAN RHYTHMS, HOMEOSTASIS, AND THE SLEEP-WAKE CYCLE

SLEEP STAGES

3. OVERVIEW OF SLEEP DISORDERS

DSM-5 CLASSIFICATION

SLEEP STUDY TESTS

4. INSOMNIAS

CHRONIC INSOMNIA DISORDER

SHORT-TERM INSOMNIA DISORDER

5. SLEEP-RELATED BREATHING DISORDERS

OBSTRUCTIVE SLEEP APNEA SYNDROME

6. CENTRAL DISORDERS OF HYPERSOMNOLENCE

NARCOLEPSY

IDIOPATHIC HYPERSOMNIA

OTHER HYPERSOMNIAS

7. CIRCADIAN RHYTHM SLEEP-WAKE DISORDERS

DELAYED SLEEP-WAKE PHASE DISORDER

8. PARASOMNIAS

SLEEPWALKING

9. SLEEP-RELATED MOVEMENT DISORDERS

RESTLESS LEGS SYNDROME AND PERIODIC LIMB MOVEMENT DISORDER

10. DIAGNOSING AND TREATING SLEEP DISORDERS WITH THE HELP OF AN INTERPRETER

11. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

58882 • Sleep Disorders

Education Category. Infection Control / Internal Medicine

Release Date. 01/01/2019

Expiration Date. 12/31/2021

Course Overview

Sleep is one of the most vital processes of life and serves many functions, including preservation, restoration, and memory processing. Repeated disruption of the natural sleep cycle or failure to initiate sleep (i.e., sleep disorder) can lead to a sleep deficit, which in turn causes physical, mental, and emotional fatigue. This is evidenced by the fact that many individuals with a sleep disorder express a reduction in quality of life. This course will provide information regarding the physiology of sleep; the causes, risk factors, epidemiology, and physiology of a variety of sleep disorders; diagnosis, including patient history, assessment of sleep habits, physical examination, laboratory tests, and sleep studies; and treatments to improve sleep patterns, including lifestyle/behavioral change (i.e., "sleep hygiene"), medication interventions, and other treatment options for patients.

Audience

This course is designed for all dental professionals who are involved in the care of patients experiencing a sleep-related disorder.

Course Objective

Many of the complications associated with sleep disorders are preventable, making early diagnosis and appropriate treatment vital. The purpose of this course is to provide dental professionals with the information necessary to identify and contribute to the treatment of sleep disorders, thereby improving patients' quality of life and preventing possible complications.

Learning Objectives

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

1. Discuss the physiology of normal sleep.

2. Describe the classification of sleep disorders.

3. Compare and contrast the types of insomnias and their associated diagnosis and treatment.

4. Evaluate the major types of sleep-related breathing disorders, particularly obstructive sleep apnea.

5. Identify the clinical signs and symptoms of narcolepsy.

6. Outline the characteristics of non-narcolepsy hypersomnias.

7. Analyze the complications and symptoms of circadian rhythm sleep disorders.

8. Describe the characteristics, diagnosis, and treatment of parasomnias.

9. Evaluate the presentation and treatment of sleep-related movement disorders.

10. Assess considerations for patients with sleep disorder who have low English literacy.

Faculty

Teisha Phillips, RN, BSN, received her Bachelor of Science in Nursing degree from Point Loma Nazarene University in 2005. She has nursing experience in a variety of clinical settings including multispecialty outpatient surgery, fertility, women's health, and cosmetic/aesthetic nursing. Her primary focus and passion is on direct patient care and patient education. She is presently employed as a perioperative nurse at an outpatient surgery center in the greater Sacramento area.

Faculty Disclosure

Contributing faculty, Teisha Phillips, RN, BSN, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Division Planner

William E. Frey, DDS, MS, FICD

Division Planner Disclosure

The division planner 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.

1. INTRODUCTION

Sleep is one of the most vital processes of life and serves many important functions, including preservation, restoration, and memory processing. Repeated disruption of the natural sleep cycle or failure to initiate sleep (i.e., sleep disorder) can lead to a sleep deficit, which in turn causes physical, mental, and emotional fatigue. Most individuals with a sleep disorder experience a myriad of symptoms and a reduction in quality of life [1].

The American Academy of Sleep Medicine (AASM) publication The International Classification of Sleep Disorders, Third Edition (ICSD-3) identifies more than 80 official sleep disorders [2]. Many are uncommon, but a handful (e.g., insomnias, obstructive sleep apnea, narcolepsy, restless legs syndrome) affect millions of Americans and are responsible for significant morbidity and mortality, including direct physiologic and/or psychologic complications and accidents associated with moderate or severe drowsiness.

It is estimated that 50 to 70 million adult Americans have a sleep or wakefulness disorder [1]. Some of the most serious long-term health consequences of sleep disorders (or sleep insufficiency/deficit) include glucose intolerance, increased blood pressure, increased inflammatory markers, higher evening cortisol levels, weight gain/obesity, and an increased risk of myocardial infarction, depression, and cancer [1,3,4]. Additionally, sleep apnea and narcolepsy are known to be responsible for some of the more than 800 fatalities and 44,000 nonfatal injuries caused by drowsy driving in the United States each year, adding to the considerable burden that untreated sleep disorders place on the healthcare system [5]. Other sleep disorders, including those that are transient, contribute to the remainder of the 72,000 annual crashes caused by excessive sleepiness while driving [5].

The economic cost of sleep disorders should not be underestimated. One study found that individual healthcare costs were approximately doubled for patients with undiagnosed obstructive sleep apnea [6]. Research commissioned by Congress in 1993 found that direct annual medical costs for insomnia were $15.2 billion (with the amount spent on over-the-counter products not included), and that the indirect and related annual costs (mostly costs arising from accidents) approached $56 billion [4,7,8,9]. In 2018 dollars, this translates to $26.6 billion and $98 billion, respectively, and these figures do not take into account population growth or today's increased healthcare costs.

A 2011 study found that annual workplace losses (including workplace accidents) due to insomnia and associated comorbidities totaled $91.7 billion per year [10]. The study, using extrapolated data from 7,428 U.S. workers enrolled in healthcare plans, found that presenteeism (i.e., attending work while drowsy) accounted for the majority of the losses (roughly two-thirds) and absenteeism accounted for the remainder. Comorbidity is a major factor, yet after 26 conditions were controlled for, the net annual costs of insomnia alone were $63.2 billion [10]. One limitation of the study was that only data from workers with healthcare insurance were sampled. Although the prevalence of insomnia may be similar among insured and uninsured populations, undiagnosed and untreated sleep disorders can amount to greater overall long-term cost. A 2015 study reiterated the negative impact on work performance (e.g., absenteeism, presenteeism, workplace injury, accidents driving to/from work) of one sleep disorder in particular, obstructive sleep apnea [11].

Sleep disorders have a clear impact on productivity and public health. The AASM and the Institute of Medicine emphasize that education on somnology and sleep medicine should be incorporated into continuing education programs [1]. Many of the complications associated with sleep disorders are preventable, making early diagnosis and appropriate treatment vital. Unfortunately, research indicates that sleep disorders continue to be underdiagnosed and undertreated [12,13,14,15]. One study of relatively healthy patients seeking preventive care found that 57% either reported a sleep complaint related to sleep apnea or were found to be at increased risk for the condition [13]. However, only 11% of individuals who reported sleep complaints underwent any subsequent diagnostic testing, indicating a gap in factual knowledge and appropriate clinical behaviors [13].

This course will provide information regarding the physiology of sleep; the causes, risk factors, epidemiology, and pathophysiology of various sleep disorders; diagnosis, including patient history, assessment of sleep habits, physical examination, laboratory tests, and sleep studies; and treatments to improve sleep patterns, including lifestyle/behavioral change (e.g., "sleep hygiene"), pharmacologic interventions, surgical interventions, and other treatment options for patients.

2. THE PHYSIOLOGY OF SLEEP

Sleep is an active body process marked by suspended consciousness, diminished sensory activity, relaxed musculature, reduced ability to react to stimuli, and other changes in brain activity that correspond with distinct sleep phases. Despite being necessary to humans, the basis for the need of sleep is still poorly understood. To date, the consequences of sleep deficit are the best indication of the functions sleep serves.

CIRCADIAN RHYTHMS, HOMEOSTASIS, AND THE SLEEP-WAKE CYCLE

The sleep-wake cycle consists of approximately 8 hours of sleep and 16 hours of wakefulness in healthy adults and is controlled by two internal factors: circadian rhythms and sleep homeostasis [16]. Circadian rhythms are "physical, mental, and behavioral changes that follow a roughly 24-hour cycle, responding primarily to light and darkness in an organism's environment" [17]. Biologic "clocks" located throughout the body manage circadian rhythms in individual body systems; these are all controlled and coordinated by the suprachiasmatic nucleus (SCN), or "master clock," located in the hypothalamus. The SCN's circadian rhythm has an endogenous component but is also driven by external cues from the environment, called zeitgebers [16]. The light-dark cycle is the overwhelmingly dominant zeitgeber for humans. Light acts on photosensitive ganglion cells in the retina that send signals directly to the SCN, providing synchronization with the particular environment. Thus, the body is able to adapt (in some cases with difficulty) and correct the sleep-wake cycle relative to differing light-dark conditions (e.g., when travelling to a different time zone).

Endogenous circadian rhythms, and therefore sleep needs, vary among individuals and age groups. Adolescents typically need 9.5 hours of sleep, and infants require 16 hours of sleep [16,18]. There are three chronotypes (identifiable using the Horne-Östberg questionnaire): morning type, an early circadian phase; evening type, a late circadian phase; and intermediate type. This is important because morning-type individuals typically sleep earlier and longer and are quicker to adjust to changes in sleep schedules than intermediate and evening types [18,19]. One study found that morning-type individuals are also less likely to deviate from their normal sleep schedule regardless of social cues (e.g., being on vacation) [18]. A 2012 study found that adolescents living in brightly lit, urban environs had a "stronger evening-type orientation than adolescents living in darker and more rural municipalities" [20]. The study also found that nighttime electronic-screen media use (i.e., a strong artificial light source) correlated with an evening-type rhythm in adolescents living in darker areas, but a morning rhythm could be established if limited and appropriate nighttime lighting (e.g., dimmer room lights, heavy curtains to block street lighting, no electronic-screen media use) was used.

Although the primary zeitgeber in humans is the light-dark cycle, there are other influential nonphotic cues, including exercise, temperature, and various social cues, that influence the regulation of various biologic processes (e.g., body temperature, hormone production) [18,21,22]. Researchers propose that sleep patterns may be influenced by other important zeitgebers, including sound, temperature, and the earth's magnetic field, that are as yet unproven or only considered weak factors [23,24]. Given that light is such a powerful influence and that humans are sensitive to very low levels of light, it is difficult to study the effects of these other possible cues. (Blind individuals typically have "free running" circadian rhythms ≥25 hours and are often the subject of zeitgeber investigations.) Some zeitgebers, such as aberrant work schedules, alarm clocks, artificial light, radio, television, and time-zone change, are known to cause disruptions to the natural sleep-wake cycle.

Homeostasis is the body process associated with maintaining a steady state of internal conditions (e.g., acid-base balance, blood pressure, body temperature). The sleep drive and amount of sleep are also under homeostatic control [16]. The neurochemistry of sleep is not fully understood, but the neurotransmitter adenosine is thought to have an important role as a homeostatic regulator of sleep [16,25]. Adenosine does not act as a classical neurotransmitter; it is neither stored nor released, but is instead thought to be formed inside or on the surface of cells [25]. The drive for sleep (and, alternately, wakefulness) has been found to be directly related to extracellular adenosine levels in the cerebral cortex and basal forebrain [25]. Concentrations of the chemical increase throughout the day and decrease during the sleep recovery period, and the feeling of intense sleepiness following prolonged wakefulness is thought to be caused by very high adenosine levels. Adenosine is a theoretical link between the humoral and neural mechanisms of sleep-wake regulation [25].

Produced in the pineal gland, melatonin is another key sleep hormone. It is regulated by darkness signals from the SCN and also provides feedback to that circadian oscillator [26]. Circulating melatonin levels increase in the hours following nightfall and drop significantly upon eye exposure to light. It is believed that this hormone supplements and reinforces the entraining effects of the light period [26]. Whereas the ganglion cells provide a light cue to the SCN, melatonin provides a darkness cue via receptors in and around the structure.

SLEEP STAGES

The sleep process consists of five stages of sleep, divided into two general categories: rapid eye movement (REM) sleep and non-REM sleep. Non-REM sleep consists of four distinct phases (or stages), each of which is defined by a set of unique electrophysiologic parameters, including electroencephalogram (EEG), electromyogram (EMG), eye movements, and respiration. When awake, EEG measurements of brainwave activity show frequencies of 8 Hz or greater. When a patient is awake but relaxed with eyes closed, EEG measurements fall in the alpha range (8 to 12 Hz) when measured at posterior head regions. In children, this basic rhythm is in the theta range (4 to 8 Hz), and in infants, it is in the delta range (slower than 4 Hz). A return to wakeful levels of brain activity (greater than 12 Hz) occurs if the subject opens his or her eyes or engages in mental activity. When awake or when relaxing with eyes closed, muscle tone is normal and individuals are fully aware of their surroundings.

Stage 1

During stage 1 sleep, individuals begin to feel drowsy but can be easily aroused. Relaxation of musculature begins, as does reduced environmental awareness. Slow and rolling lateral eye movements also may occur. EEG brain activity shows interruption of the posterior dominant rhythm (i.e., alpha dropout) and the onset of a low-voltage, intermixed pattern of frequencies [27,28]. Positive occipital sharp transients of sleep (POSTS) and very brief vertex sharp waves may occur in repetitive runs. (POSTS start around 4 years of age, are common by 15 years of age, and decline after 50 years of age.) Hypnagogic hypersynchrony, or bursts of high-amplitude, diffuse, rhythmic (sinusoidal) delta activity, can arise, especially among children 3 months to 13 years of age and is considered a normal variant of drowsiness in this age group.

Stage 2

Most time is spent in stage 2 sleep during an adult's normal night's sleep. Arousal is more difficult during this phase, and the low-voltage, intermixed pattern continues. Brainwave activity slows to the theta range (4 Hz to 7 Hz). Sleep spindles (and associated K-complexes) are the defining characteristic of stage 2 sleep. Spindles are short bursts of vertex rhythmic activity between 12 and 16 Hz (typically 14 Hz) lasting about 0.5 seconds. Sleep spindles begin at 6 to 8 weeks of age and continue throughout life [27,28].

Stages 3 and 4

Muscle tone continues to decrease progressively through stages 3 and 4. Arousal is most difficult during these stages, which are marked by slow-wave sleep consisting of progressively increasing high-voltage, delta-range brain activity. During stage 3, delta activity comprises 20% to 50% of brainwave activity, and during stage 4, it is in excess of 50% [27,28]. Sleep spindles may still occur in these stages but are not a major feature. Over a lifetime, the amount of time spent in slow-wave sleep decreases. For example, men 20 to 29 years of age spend 21% of total sleep time in slow-wave sleep; this decreases to 8% by 50 years of age and to 2% by 70 years of age. In elderly individuals, almost no time is spent in stage 4 sleep and little time is spent in stage 3.

REM Sleep

As the name suggests, the major feature of REM sleep is rapid eye movement, but this stage is also characterized by muscle atonia and EEG desynchronization. Brainwave activity returns to a low-voltage intermixed pattern and becomes faster (beta and theta range), almost resembling wakefulness. Dreaming is most likely to occur in this stage. Central activity in the theta range can produce waves with a "saw tooth" appearance on a polysomnogram display.

In healthy adults, about four or five sleep cycles, each about 90 minutes, occur in one night, each one progressing through the non-REM stages, followed by REM sleep. Slow-wave sleep is lessened and REM sleep becomes more predominant with each successive sleep cycle (Figure 1) [29].

Figure 1: NORMAL SLEEP STRUCTURE IN ADULTS

Source: Reprinted with permission from Kales A, Kales JD. Sleep disorders: recent findings in the diagnosis and treatment of disturbed sleep. N Engl J Med. 1974;290(9):487-499.

Some individuals enter REM sleep before descending through non-REM phases, which is referred to as sleep-onset REM periods (SOREMPs). This is considered an indicator of a sleep disorder, usually narcolepsy, but it may also occur in patients with obstructive sleep apnea [30]. SOREMPs are uncommon in the healthy adult population but are slightly more prevalent in individuals with excessive sleepiness (e.g., adolescents and young adults, shift workers) [31]. SOREMPs are also seen with other disorders, including Prader-Willi syndrome, Kleine-Levin syndrome, Parkinson disease, and periodic limb movement disorder (PLMD) [31].

3. OVERVIEW OF SLEEP DISORDERS

As discussed, there are more than 80 official sleep disorders defined in the current AASM diagnostic and coding manual, the ICSD-3 [2]. The ICSD-3 uses a pragmatic framework for categorizing sleep disorders based primarily on pathophysiology, if known, and also phenomenology and organ system methodology [2]. Unlike in original versions, disorders are no longer grouped into three major classes: dyssomnias, parasomnias, and sleep disturbances associated with mental, neurologic, or other medical disorders. Instead, the ICSD-3 contains seven major categories of sleep disorders [2]:

- Insomnia

- Sleep-related breathing disorders

- Central disorders of hypersomnolence

- Circadian rhythm sleep-wake disorders

- Parasomnias

- Sleep-related movement disorders

- Other sleep disorders

A goal of the ICSD-3 framework was to organize sleep disorders into an International Classification of Diseases (ICD-10)-compatible format [2]. Another goal was to describe in detail all currently recognized sleep and arousal disorders, which is a missing feature of other manuals, including the widely used Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), while still maintaining a good degree of concordance with the DSM-5.

DSM-5 CLASSIFICATION

The DSM-5 contains information for making a diagnosis of a sleep disorder; however, it has less detailed descriptions of certain sleep-wake disorders than the ICSD-3. For example, the DSM-5 section on insomnia disorders does not extensively describe each of the three forms of insomnia described in the ICSD-3. The DSM-5 takes what it refers to as a "lumping versus splitting" approach to classifying sleep-wake disorders. The insomnias identified in the ICSD-3 fall under the general category of insomnia disorder in the DSM-5, lumped together due to their similar presentations and impact on clinical care for nonspecialists. While this course incorporates information from both the DSM-5 and the ICSD-3, the organization structure of the latter will be used as an outline. The following sections will discuss the more common examples of each of the seven categories, and those with the greatest incidence will be discussed in more detail.

SLEEP STUDY TESTS

Many tests are available to assess the quality of an individual's sleep, and a discussion of each is beyond the scope of this course. However, the most commonly used tests are polysomnography and the multiple sleep latency test (MSLT), both of which are used in the evaluation of many sleep disorders.

Polysomnography is preferably conducted by a certified sleep technologist at an AASM-accredited facility. This test monitors many physiologic parameters, including electrocardiogram, EEG, eye movements (electrooculogram), chin EMG, airflow, oxygen saturation, respiratory effort, and heart rate [32]. A technician will note if snoring is present and, if so, the degree (i.e., mild, moderate, or severe). Body position and leg EMG derivations are also recommended.

One full-night study is typical, but split-night studies (i.e., polysomnography followed by continuous positive airway pressure [CPAP] titration) may be used when initial monitoring shows a high apnea-hypopnea index (AHI) score. This index will be discussed in detail later in this course. The AASM Manual for the Scoring of Sleep and Associated Events is used to set up and analyze the study, and the results are reported as an AHI score (or a respiratory disturbance index) for review by a qualified sleep physician. Polysomnography can help rule out the possibility of sleep disorders, and it will also show if the patient's sleep cycle is normal or if REM sleep occurs at unusual times.

Portable monitor testing has a known likelihood of producing false-negative results; therefore, it is considered inferior to overnight sleep lab polysomnography [32]. Airflow, blood oxygenation, and respiratory effort are the minimum test parameters needed for a complete at-home study. The sensors are similar or identical to those used for polysomnography and will either be placed by a sleep technologist, other trained professional, or the patient following detailed instruction. The AHI score is calculated per the AASM Manual using the truncated portable monitor test data. Tests of patients who have a high probability of obstructive sleep apnea and a low AHI should be considered inaccurate and should be repeated (in a sleep lab whenever possible) [32].

The MSLT is a daytime test that can determine if REM sleep patterns occur during wakefulness and monitor the amount of time it takes for the patient to fall asleep normally during the day. For example, sleep latency periods (i.e., the time it takes to fall asleep) are typically 8 minutes or less in narcoleptic patients, but healthy individuals usually take 12 or more minutes to fall asleep during the daytime [33].

4. INSOMNIAS

The term insomnia is defined generally as difficulty with initiation, duration, consolidation, or quality of sleep. It is commonly applied when three conditions are satisfied: ample time and opportunity for sleep, persistent sleep difficulty, and daytime dysfunction associated with sleep deficit [2].

Chronic or short-term insomnia is a problem for most people at some point in their lives. Patients will experience problems going to sleep or staying asleep and are distressed by the number of hours they are awake at night or by a quality of sleep perceived as poor [2]. However, if daytime function is unaffected, the complaint does not warrant treatment other than discussion and education, because by definition they do not have an insomnia disorder. Patients with clinically significant insomnia typically become fatigued, irritable, cognitively impaired, and/or depressed and some complain of headaches, muscle tension, palpitations, work impairment, and social withdrawal [2].

There are now three formal insomnia diagnoses listed in the ICSD-3: chronic insomnia disorder, short-term insomnia disorder, and other insomnia disorder [2]. This is a significant departure from the previous version of the ICSD, which included 11 diagnoses. Many sleep disorders diagnosed in the past have a complaint of insomnia in common. These included adjustment insomnia (acute insomnia); psychophysiologic insomnia; paradoxical insomnia; idiopathic insomnia; insomnia due to mental disorder; inadequate sleep hygiene; behavioral insomnia of childhood; insomnia due to drug or substance; insomnia due to medical condition; insomnia not due to a substance or known physiologic condition, unspecified (nonorganic insomnia, not otherwise specified [NOS]); physiologic (organic) insomnia, unspecified (organic insomnia, NOS).

Insomnia is no longer regarded as either being due only to a primary sleep disorder or because of an underlying medical or psychiatric condition (i.e., as a primary disorder or as a disorder secondary to another comorbid condition). For one, the symptoms and features of primary and secondary insomnia overlap considerably, and differentiation was often difficult or impossible. Additionally, patients usually met the criteria for more than one ICSD-2 insomnia subtype. Evidence has shown that when a patient's underlying medical condition causing insomnia is treated, the insomnia often persists, or when the insomnia was treated, both the comorbid medical condition and the sleep disorder improved [2]. The first two categories of insomnia—chronic insomnia disorder and short-term insomnia disorder—now reflect an all-encompassing view of disordered sleep and are based on various levels of sleep dysfunction. The third category—other insomnia—is included in the ICSD-3 to describe individuals with difficulty initiating and maintaining sleep, but who do not meet the criteria for the other two categories. The AASM does not foresee many individuals receiving this diagnosis, and it will not be discussed in this course.

CHRONIC INSOMNIA DISORDER

According to the ICSD-3, chronic insomnia disorder is defined as "chronic sleep onset and/or sleep maintenance complaints with associated daytime impairment, and is reserved for individuals whose sleep difficulties exceed minimal frequency and duration thresholds shown to be associated with clinically significant morbidity outcomes" [2]. This diagnosis encompasses many insomnia subtypes found in other texts, including primary insomnia, comorbid insomnia, chronic insomnia, secondary insomnia, sleep-onset association disorder, behavioral insomnia of childhood, disorder of initiating and maintaining sleep, and limit-setting sleep disorder. As discussed, this consolidation is not for the sake of simplicity, but reflects the actual state of current knowledge and evidence regarding chronic insomnia. The specific primary insomnia clinical/pathologic subtypes that are now considered part of this larger, global class in the ICSD-3 are shown in Table 1[2].

Table 1: CLINICAL AND PATHOPHYSIOLOGIC SUBTYPES IN THE ICSD-3

Diagnosis

Features

Symptoms

Psychophysiologic insomnia

Elevated levels of somatic and cognitive arousal, especially when trying to sleep

Learned sleep-preventing associations

Excessive focus on sleep

Excessive worry about sleep

Difficulty sleeping in usual sleep setting (e.g., at home),but may fall asleep easily away from home or at home when not trying to sleep

Idiopathic insomnia

Early onset (i.e., infancy)

Genetic or congenital alterations in sleep-induction/arousal systems in the brain

No genetic markers are known

Gradual inability to sleep beginning at a very young age with no discernible cause

Paradoxical insomnia

Individuals underestimate the amount of sleep actually obtained

Complaint of wakefulness in spite of sleep studies showing normal amounts of sleep

Altered sleep/wake system

Extreme subjective sleep disturbance without objective corroboration

Inadequate sleep hygiene

Frequent napping/irregular sleep schedule

Regular use of caffeine, alcohol, tobacco, or other drugs close to bedtime

Regularly engaging in mentally, physically, or emotionally stressful activity before bedtime

Using the bed for activities other than sleep or sex (e.g., reading, television, video games)

Inappropriate pre-sleep and sleep environment (e.g., too hot, excessive light, too loud or quiet)

Inability to initiate sleep

Chronic sleep/wake difficulty

Behavioral insomnia of childhood (sleep-onset association type or limit-setting type)

Poor sleep training or limit setting by caretakers or parents

Some children are a mixed type

Child's dependence on specific objects, settings, or stimulation for initiating or returning to sleep (sleep-onset association type)

Bedtime stalling or refusal (limit-setting type)

Source: [2]

Although these subtypes are discussed in the ICSD-3, a diagnosis of chronic insomnia disorder should be made for all adult and pediatric patients who have a complaint of persistent and frequent insomnia, despite the absence or presence of a comorbid medical disorder, psychiatric disorder, or substance abuse [2]. Given the state of knowledge and evidence regarding insomnia, this has been deemed the most justifiable approach and is more compatible with the DSM-5.

Epidemiology

Approximately 10% of the adult population is affected by chronic insomnia disorder as defined by the ICSD-3 [2]. The disorder is more common in women than in men and affects a greater number of individuals with low socioeconomic status versus those who are economically and socially stable. Patients with medical, psychiatric, and/or substance abuse problems are disproportionately affected. Older individuals are more often diagnosed with chronic insomnia, likely due to medical conditions, medications used to treat them, and age-related sleep continuity decline [2]. Transient insomnia affects 30% to 35% of the adult population.

Prevalence of insomnia in children and adolescents is estimated at 10% to 30% and 3% to 12%, respectively, with wide variance due to definitions of insomnia used in research. It is more frequently diagnosed in adolescent girls than boys [2]. Although the specific ICSD-3 diagnosis has changed, the problems associated with childhood sleep disorders have not. Most chronic childhood insomnia cases are due to caregiver/parental behavior, bedtime interactions, and cultural influences, and the underlying difficulties are still primarily sleep-onset and/or limit-setting problems [2]. The need for and provision of nighttime contact varies among cultures, which should be taken into account. Infants do not establish a regular sleep pattern until approximately 3 to 6 months of age, and an insomnia diagnosis is typically not made before 6 months of age.

The evidence for familial occurrence of insomnia is weak, but there does appear to be some influence, particularly between mothers and daughters, monozygotic twins, and, to some extent, other first-degree relatives [2]. It is not known what the association(s) may be; theories range from learned behavior and a shared environment to genetic predisposition and the byproduct of a common psychopathology.

Diagnosis in Adults

A diagnosis of chronic insomnia disorder is based primarily on subjective reports from adult patients and objective and subjective reports for children and adolescents. The differential diagnosis of chronic insomnia may include a sleep study, if warranted, but typically is not needed for routine evaluation.

There are three features of chronic insomnia disorder [2]. The first is frequent and persistent difficulty initiating or maintaining sleep, and this is the intrinsic essential feature of chronic insomnia disorder [2]. This repetitive failure results in the patient's general dissatisfaction with sleep and quality of life. Insomnia, though chronic, does not necessarily occur every night. Some patients will have episodes of recurrent insomnia, while others constantly struggle with sleep insufficiency. It is common for individuals with persistent insomnia to have several bad nights of sleep with an occasional good sleep [2]. Other patients who are predisposed to insomnia may experience poor sleep in relation to stressful life events. An initial episode of acute insomnia related to a stressful event will typically resolve in most individuals as they adjust to their new reality; however, this episode has the potential to become a chronic problem for some patients. The remembrance and anticipation of insomnia following a stressful event, coupled with actual sleep difficulties and daytime impairment, can lead to a cycle of disordered sleep [2].

The second feature of chronic insomnia is worry about sleep difficulties and/or academic, family, social, vocational, or other functional impairment [2]. Patients with insomnia often display excessive preoccupation with sleep, which can be problematic. Worrying about not getting enough sleep and not being able to initiate sleep following an episode of insomnia can lead to a vicious cycle of becoming tense or agitated as bedtime approaches (with corresponding adrenaline release), trying too hard to sleep (e.g., lying in bed for extended periods of time), becoming increasingly distressed and agitated at the inability to sleep, and being further unable to initiate sleep [34].

Preoccupation with general health and wellness may predispose individuals to chronic insomnia, and repression and internalization of disturbing feelings may be a common trait [2]. It may appear that patients are overly anxious, and in fact, recurrent thoughts of poor sleep performance may trouble these individuals in the morning and afternoon and attain a peak at night. However, generalized anxiety is not the norm for chronic insomnia sufferers. Screening for comorbid general anxiety is recommended when symptoms seem to extend beyond an emphasis on disordered sleep [2]. Environmental and biologic sleep cues often become triggers for heightened sleep anxiety and arousal. For example, when the sun sets and darkness falls, thoughts of poor previous nights' sleep and sleep performance anxiety may begin. In healthy individuals, feelings of drowsiness lead to increased calm, but fatigue can cause panic and distress in those with chronic insomnia. Patients may think, "I feel tired, but I know that if I go to bed I will not be able to fall asleep," or, "I feel tired now, but I am going to feel even worse tomorrow morning when I am not able to sleep tonight." This may be, or become, true as the patient ruminates about sleep and stresses.

Subjective or objective deficits with daily functioning are noticed in individuals with chronic insomnia. These may manifest as depression, lethargy, or a desire to limit activities or work. Work productivity may suffer, as may academic performance.

Patients often readily express sleep anxiety and may acknowledge their ability to sleep normally in unfamiliar settings [2]. The lack of environmental triggers in unfamiliar environments can help prevent sleep performance worry.

The third essential feature of chronic insomnia disorder is inability to sleep and remain asleep despite plenty of time to sleep, no nighttime interruptions, an adequate sleep environment, and other sufficient circumstances [2]. Practicing sleep hygiene, or maintaining an ideal sleep environment and optimum mental/physical state to promote sleep, is discussed later in this course.

Diagnosis in Children

The diagnosis of chronic insomnia in children is somewhat different because of the strong influence of parental/caregiver and environmental factors on development. Parents should be questioned regarding their expectations for their child's sleep. Putting children to bed prematurely or allocating too much time in bed can cause sleep difficulties that may lead to chronic insomnia [2]. On the other hand, parents may not be implementing or enforcing regular bedtimes or may allow children to postpone bedtimes. As children develop greater language skills and seek individuality, limit setting becomes more important. Studies have also shown that parents of children who faced a life-threatening illness are less strict about enforcing bedtimes and allow their children greater leeway with sleeping (e.g., joining the adult bed upon waking) [2]. Abuse and unstable home environments are also known factors for insomnia in children and adults. Crowded homes (e.g., with extended family of many generations) are associated with poor limit setting and negative sleep-onset cues. Children should also be carefully screened for comorbid medical and psychiatric conditions that may have gone unnoticed. The diagnostic criteria for adults and children are shown in Table 2.

Table 2: THE ICSD-3 DIAGNOSTIC CRITERIA FOR CHRONIC INSOMNIA DISORDER

A. The patient reports, or the patient's parent or caregiver observes, one or more of the followinga:

1. Difficulty initiating sleep

2. Difficulty maintaining sleep

3. Waking up earlier than desired

4. Resistance to going to bed on appropriate schedule

5. Difficulty sleeping without parent or caregiver intervention

B. The patient reports, or the patient's parent or caregiver observes, one or more of the following related to the nighttime sleep difficulty:

1. Fatigue/malaise

2. Attention, concentration, or memory impairment

3. Impaired social, family, occupational, or academic performance

4. Mood disturbance/irritability

5. Daytime sleepiness

6. Behavioral problems (e.g., hyperactivity, impulsivity, aggression)

7. Reduced motivation/energy/initiative

8. Proneness for errors/accidents

9. Concerns about or dissatisfaction with sleep

C. The reported sleep/wake complaints cannot be explained purely by inadequate opportunity (e.g., enough time is allotted for sleep) or inadequate circumstances (e.g., the environment is safe, dark, quiet, and comfortable) for sleep.

D. The sleep disturbance and associated daytime symptoms occur at least three times per week.

E. The sleep disturbance and associated daytime symptoms have been present for at least three monthsb

F. The sleep/wake difficulty is not better explained by another sleep disorder.

aReports of difficulties initiating sleep, difficulties maintaining sleep, or waking up too early can be seen in all age groups. Resistance going to bed on an appropriate schedule and difficulty sleeping without parent or caregiver intervention is seen most commonly in children and older adults who require the supervision of a caretaker due to a significant level of functional impairment (e.g., those with dementia).

bSome patients with chronic insomnia may show recurrent episodes of sleep/wake difficulties lasting several weeks at a time over several years, yet not meet the three-month duration criterion for any single such episode. Nonetheless, these patients should be assigned a diagnosis of chronic insomnia disorder, given the persistence of their intermittent sleep difficulties over time.

Source: Reprinted with permission from American Academy of Sleep Medicine. The International Classification of Sleep Disorders-[3]Diagnostic and Coding Manual. [3]rd ed. Westchester, IL: American Academy of Sleep Medicine; 2014.

Subjective assessment with a sleepiness instrument, such as the Epworth Sleepiness Scale (Table 3), may be helpful to ascertain the patient's degree of impaired sleep, but laboratory testing to measure sleepiness (e.g., the Maintenance of Wakefulness Test) usually does not show greater sleepiness in this cohort compared with healthy individuals [35]. The Epworth Sleepiness Scale has been found to be particularly effective for identifying cases of insomnia and less useful for diagnosing other sleep disorders [36]. Sleep studies are not typically needed to make a diagnosis, but polysomnography may reveal poor sleep continuity (e.g., decreased sleep efficiency, intermittent wakefulness) and more stage 1 sleep and limited stage 3 and 4 sleep [35,37]. As noted, many persons with insomnia sleep better outside their own bed, and overnight laboratory testing may not provide significant data. Polysomnographic results also vary considerably from night to night in these patients [35]. Polysomnography is recommended for elderly individuals, as they are more prone to having identifiable etiologies of insomnia.

Table 3: THE EPWORTH SLEEPINESS SCALE

Situation

Scorea

Sitting and reading

0 = No chance of dozing

1 = Slight chance of dozing

2 = Moderate chance of dozing

3 = High chance of dozing

Watching television

0 = No chance of dozing

1 = Slight chance of dozing

2 = Moderate chance of dozing

3 = High chance of dozing

Sitting inactive in a public place (e.g., a theater or a meeting)

0 = No chance of dozing

1 = Slight chance of dozing

2 = Moderate chance of dozing

3 = High chance of dozing

As a passenger in a car for an hour without a break

0 = No chance of dozing

1 = Slight chance of dozing

2 = Moderate chance of dozing

3 = High chance of dozing

Lying down to rest in the afternoon when circumstances permit

0 = No chance of dozing

1 = Slight chance of dozing

2 = Moderate chance of dozing

3 = High chance of dozing

Sitting and talking to someone

0 = No chance of dozing

1 = Slight chance of dozing

2 = Moderate chance of dozing

3 = High chance of dozing

Sitting quietly after a lunch without alcohol

0 = No chance of dozing

1 = Slight chance of dozing

2 = Moderate chance of dozing

3 = High chance of dozing

In a car, while stopped for a few minutes in traffic

0 = No chance of dozing

1 = Slight chance of dozing

2 = Moderate chance of dozing

3 = High chance of dozing

aA total score of 10 or more from the eight criteria reflects above normal daytime sleepiness and need for further evaluation.

Source: [38]

Treatment

Approximately 7 of 10 individuals with persistent insomnia struggle with insomnia after one year of treatment, and half still have insomnia three years later [2]. Complications of chronic insomnia include increased risk of depression, hypertension, work disability, and protracted use of prescription or over-the-counter sleep aids. Therefore, effective professional therapies are needed to avoid dangerous comorbidities and adverse drug effects. Additionally, managing comorbid medical and psychologic conditions with sleep-disrupting effects is necessary for these patients.

Sleep Hygiene

Management of chronic insomnia centers on behavior and lifestyle modification combined with counseling and instruction in effective sleep hygiene practices. Some of the foremost behaviors patients should modify or adhere to include keeping a consistent sleep schedule (i.e., going to bed at the same time each night and waking up at the same time each morning), devoting at least seven to eight hours each night to sleep, and creating and maintaining a bedtime ritual. The optimum sleep time varies among individuals, but those with persistent excessive daytime sleepiness should sleep a minimum of six to eight hours [31].

Establishing a bedtime ritual involves deciding upon an activity or series of activities that provide conditioned sleep cues and consistently repeating those activities each night. The first part of the ritual should involve quitting challenging, engaging, or stressful tasks (e.g., paying bills, playing video games, watching television) and resolving any lingering worries (e.g., quarrels, dwelling problems). Some people find that if tasks are incomplete or issues are left unresolved, making a to-do list for the next day will help to clear their mind [31]. Next, patients should focus on relaxation for 20 or 30 minutes. During this time, they might read, listen to relaxing music, take a warm bath, or practice meditation and/or deep-breathing exercises. There are many other lifestyle modifications that can reduce the likelihood of developing a sleep disorder or can lead to a reduction of symptoms of an existing disorder. The following guidelines are all components of proper sleep hygiene and should be included as part of patient education for any sleep disorder [10,31]:

- Large, heavy meals should be avoided late in the day, as should spicy, new, or exotic foods.

- Alcohol, caffeine, and nicotine should be avoided for at least four to six hours before bedtime. Alcohol initially acts as a sedative, but as the effect wears off, it can cause individuals to wake during the night. Chocolate, coffee, tea, and many other beverages contain caffeine and should be avoided at night.

- Long naps should not be part of a normal day. Occasional, light (30-minute) naps are permissible, but regular naps interrupt the sleep-wake cycle and can make falling asleep difficult at night. Patients should be able to remain awake throughout the day, and if this is not possible, this indicates insufficient sleep and/or a sleep disorder.

- Upon waking in the morning, individuals should seek out sunlight. Exposure to bright sunlight helps regulate the sleep-wake cycle. This is especially important for older adults and those who do not leave the house regularly.

- Patients should be encouraged to engage in at least 20 minutes of moderate-intensity exercise per day, a minimum of two to three hours before bedtime. Vigorous exercise is best performed in the afternoon or earlier in the day, while relaxing exercises (e.g., deep breathing, light yoga, meditation) may be performed before bedtime. Exercise performed earlier in the day helps deepen sleep.

- The bed should be used only for sleep and sex. Patients who do not fall asleep within 15 to 20 minutes of being in bed should get out of bed and engage in an uncomplicated or relaxing activity in low-light conditions until they feel drowsy. Taking a bath, reading, or having a small snack is recommended; watching television, doing work, or engaging in other mentally engaging activities is not. One should not lie in bed trying to force sleep.

The following changes to the sleeping environment have also been shown to promote sleep [31]:

- Keep the bedroom at a cool, yet comfortable, temperature. Use blankets rather than a heater for warmth, as cooler room temperatures lead to better sleep.

- Remove the television from the bedroom. Television programs and commercials are designed to be engaging and/or provocative and can keep individuals awake for many hours. Additionally, darkness is necessary to stimulate melatonin production, and light from the television can be disruptive if left on all night.

- Keep the bedroom as dark, quiet, and relaxing as possible. Ensure that bedding is comfortable. Use an eye shade or thick curtains to block out early morning sunlight, streetlights, and headlights. Some people find earplugs useful, and others use white noise or other machines to block out aberrant sounds.

A sleep hygiene regimen is a universally applicable prevention and treatment strategy that can improve sleep quality for those with and without a specific sleep disorder. Most sleep experts recommend that sleep hygiene be used as an adjunct to treatment for sleep disorders [2]. Despite limited research supporting the role of proper sleep hygiene in patients with insomnia, many patients will find these suggestions helpful. It has been found that individuals with chronic insomnia who are highly aware of poor sleep hygiene practices may be the most indifferent toward making changes [2].

Cognitive-Behavioral Therapy and Other Modalities

Certain forms of chronic insomnia tend to be less amenable to control with simple nonpharmacologic and brief sedative-hypnotic modes of treatment. Some form of cognitive-behavioral therapy (CBT), utilizing stimulus control, relaxation training, and sleep restriction therapies, sequentially or in combination, achieves the best results [37,39]. Stimulus control therapy, which is akin to maintaining strict sleep hygiene, has been extensively studied and is the most recommended modality for initial insomnia treatment [34]. However, because sleep cues and other practices learned with sleep hygiene/stimulus control may become (or may already be) a cause of arousal, it is unlikely that all clinical subtypes will benefit significantly from this form of therapy.

The effectiveness of CBT for psychophysiologic insomnia has been demonstrated in several studies [34,39,40,41]. Patients also tend to prefer CBT over pharmacologic options and other forms of psychotherapy [41]. Relaxation techniques (e.g., biofeedback, breath counting/deep breathing, meditation, progressive relaxation) can be an effective adjunct to CBT [37,42]. Progressive relaxation can be particularly effective in patients who somatize stress into physical tension. This form of therapy involves tensing and relaxing individual muscle groups while breathing deeply, starting from the toes, working progressively through the calves, thighs, stomach, shoulders, hands, arms, and neck, and ending with the facial muscles. Deep breathing exercises use slow, controlled breaths (while counting) to "quiet" racing thoughts; if the mind wanders from counting breaths, patients should resume counting and eventually they should fall asleep [42].

Sleep restriction is also a useful form of therapy [42,43]. This technique is based on the observation of deeper, more consolidated sleep in sleep-deprived test subjects. Through this paradoxical approach, patients learn to associate time spent in bed with time spent sleeping [44]. The first step is for patients to keep a sleep log for two weeks to determine their average total sleep time (i.e., average amount of time asleep in bed); 30 minutes is added to this time to establish the time they will be allowed in bed [45]. For example, if the patient's average total sleep time is 5 hours, the allowed time in bed will be 5.5 hours. Next, a wake time is set based upon when the patient needs to start their day (e.g., 6:30 a.m.), and the bed time is set by counting backward based on the time in bed allowance (e.g., 1:00 a.m.). Regardless of how sleepy the patient feels, he or she must not nap or get into bed before the prescribed bedtime. Upon waking, the patient should expose his or her eyes to bright light (daylight whenever possible) to reinforce the sleep/wake cycle [45]. If after two weeks the patient feels tired during the day, they may add 15 minutes to the sleep allowance, and every successive week they may add an additional 15 minutes until they are able to get to sleep easily, are sleeping well throughout the night, and feel rested during the day [45]. The minimum amount of sleep needed to achieve these goals is recommended, and a consistent sleep and wake time must be maintained. This therapy should be discontinued if job performance or safety is compromised due to excessive daytime sleepiness.

Pharmacologic Options

For some patients, CBT in combination with a pharmacologic agent, administered over six to eight weeks, is an effective strategy. The primary pharmacologic option for patients with chronic insomnia disorders is the administration of sedative-hypnotic drugs at night (e.g., eszopiclone, ramelteon, triazolam, zaleplon, zolpidem). However, long-term treatment with sedative-hypnotics is associated with a high incidence of adverse effects, including cognitive impairment, constipation, dizziness, headache, heartburn, the development of parasomnias (e.g., sleepwalking, sleep driving), and reduced respiratory drive [40]. If used, the lowest effective dose is recommended to reduce the incidence of these effects [40]. Patients should be cautioned not to combine these medications with alcohol or other central nervous system (CNS) depressants, as their combination can cause increased liver toxicity and drastically reduced cognitive and psychomotor functioning [46].

Evidence Based Practice Recommendation

The American Academy of Sleep Medicine recommends the following agents be considered for the treatment of chronic sleep-onset insomnia:

- Eszopiclone

- Zaleplon

- Zolpidem

- Triazolam

- Temazepam

- Ramelteon

https://aasm.org/resources/clinicalguidelines/040515.pdf

Last Accessed: December 7, 2018

Strength of Recommendation: Weak (A lower degree of certainty in the outcome and appropriateness of the patient-care strategy for all patients)

Different sedative-hypnotics are indicated for various sleep difficulties. Zaleplon is fast acting, but has a short half-life; this drug may be best for patients who experience night awakenings with difficulty returning to sleep [47]. Zolpidem has a rapid onset and short-half life as well; patients with difficulty falling asleep may benefit from this drug. A controlled-release version is also available. Eszopiclone has a slow onset and long duration of action and is indicated for patients with difficulty staying asleep and with perception of poor sleep quality.

Hypnotic drugs are best utilized when nonpharmacologic measures do not achieve symptom reduction, when insomnia causes serious impairment, or when an immediate response is desired [44]. The following are best practice guidelines regarding the prescription and use of sedative-hypnotics [44,48]:

- Avoid these agents or exercise caution if patient has a history of substance abuse, acute cerebrovascular accident, myasthenia gravis, or respiratory impairment.

- Prescribe hypnotics only for short durations (one to two weeks) and intermittently (based on symptom resolution).

- Watch for requests for escalating doses or resistance to tapering/discontinuing hypnotic.

- Hypnotics should be discontinued gradually. Be alert for adverse effects (especially rebound insomnia) and withdrawal phenomena when titrating doses.

- The lowest effective dose should be prescribed.

Herbal and Hormonal Supplements

A variety of herbal, hormonal, and dietary supplements have been marketed as sleep aides, with scant evidence of significant benefit. Melatonin, a brain hormone produced by the pineal gland, does have some function in regulating the normal sleep cycle, and melatonin supplementation may be of benefit to a subset of patients with delayed sleep phase syndrome (a disturbance of the circadian rhythm). However, it does not appear to be helpful for most people who have insomnia. It is safe when used in modest dosage (2–3 mg per night) for short periods (three months or less) [49]. Melatonin is unregulated by the U.S. Food and Drug Administration (FDA); formulations vary in strength, and higher doses can lead to adverse side effects (e.g., disrupted sleep, fatigue, headache).

Valerian is a popular herbal product commonly used to self-treat insomnia. It causes CNS sedation by inhibiting the breakdown of certain chemical mediators within the brain. Clinical trials have shown minimal effectiveness at best [50]. This product is also unregulated by the FDA. Daytime drowsiness and rare instances of liver toxicity have been observed in association with its use.

SHORT-TERM INSOMNIA DISORDER

The essential features and diagnostic criteria of short-term insomnia disorder are similar to those of chronic insomnia disorder, minus the frequency and duration criteria. Insomnia is considered short-term if lasting fewer than three months [2,37]. The differential diagnosis should exclude circadian rhythm sleep-wake disorders caused by jet lag or rotating shift work. These are caused when the established circadian rhythm is decoupled from the normal sleep-wake schedule. Individuals with short-term insomnia experience sleep difficulties within their normal sleep-wake schedule.

Approximately 15% to 20% of individuals experience short-term insomnia each year [2]. The frequency is higher in women than in men and in older age groups. Although many cases of short-term insomnia resolve over time or when the stressor is removed, a significant number of cases progress to chronic insomnia, as discussed. Treatment of short-term insomnia should focus on good sleep hygiene, but CBT and pharmacotherapy may be warranted in order to ensure non-progression to chronic insomnia [37].

5. SLEEP-RELATED BREATHING DISORDERS

As the name suggests, the ICSD-3 category of sleep-related breathing disorders includes any respiratory disorders that occur during sleep. This category is further organized into the following subgroups and disorders [2]:

- Obstructive sleep apnea syndromes (adult and pediatric) caused by upper airway obstruction.

- Central sleep apnea syndromes, which are caused by cardiac or nervous system dysfunction. The eight disorders in this group are:

- Central sleep apnea with Cheyne-Stokes breathing

- Central apnea due to medical condition without Cheyne-Stokes breathing

- Central sleep apnea due to high altitude periodic breathing

- Central sleep apnea due to a medication or substance

- Primary central sleep apnea

- Primary central sleep apnea of infancy

- Primary central sleep apnea of prematurity

- Treatment-emergent central sleep apnea

- Sleep-related hypoventilation disorders, including obesity hypoventilation syndrome, congenital central alveolar hypoventilation syndrome, late-onset central hypoventilation with hypothalamic dysfunction, idiopathic central alveolar hypoventilation, sleep-related hypoventilation due to medication or substance, and sleep-related hypoventilation due to a medical disorder

- Sleep-related hypoxemia disorder, including sleep-related hypoxemia

- Isolated symptoms and normal variants

Only obstructive sleep apnea syndrome will be discussed in detail in this section, as the other sleep-related breathing disorders are comparatively rare and/or mainly associated with other medical conditions. For example, central sleep apnea due to Cheyne-Stokes breathing is primarily associated with congestive heart failure and stroke, and primary central sleep apneas of infancy or prematurity are associated with premature birth and low birth weight, occurring in 25% of infants weighing <2,500 g and 84% of infants weighing <1,000 g [2]. Others are extremely rare. It is estimated that there are perhaps a total of 200 congenital central alveolar hypoventilation syndrome cases worldwide [2].

OBSTRUCTIVE SLEEP APNEA SYNDROME

Obstructive sleep apnea syndrome is characterized by recurrent upper airway obstruction caused by repetitive narrowing or collapse of the pharyngeal airway during sleep, resulting in reductions (hypopneas) or pauses (apneas) in breathing, in spite of abdominal and chest movements; reduced blood oxygen saturation (less than 50% in some patients); and frequent arousals (potentially hundreds per night) [2,51]. Loud snoring coupled with periods of silence lasting at least 10 seconds, but often 20 to 30 seconds, are features of the syndrome. Gasping may occur instead of snoring, especially in children and adolescents; however, most patients with obstructive sleep apnea begin loud snoring in childhood. Patients may have grown accustomed to the excessive sleepiness, mental dullness, depression, frequent night awakenings, dry mouth, and morning headaches that accompany the disorder [2]. Alcohol use can increase snoring intensity, as can excess weight gain and obesity. Patients with obstructive sleep apnea often have nasopharyngeal abnormalities [2]. Adult patients typically have a generalized narrowing of the upper airway, and enlarged adenoids and/or tonsils are commonly seen in children.

Individuals may experience bouts of acute obstructive sleep apnea as the result of an inflammation-causing illness (e.g., Epstein-Barr virus, upper respiratory infection) or as a result of the ingestion of alcohol, drugs, or medications that cause relaxed muscle tone (especially in the genioglossus and geniohyoideus muscles). Individuals with occasional symptoms do not typically seek or need extensive evaluation or care for sleep apnea other than treatment for a primary condition or cessation of the substance causing airway restriction [2]. On the other hand, patients for whom the disorder is chronic (i.e., six months or longer) require careful evaluation and prompt initiation of treatment, as even mild cases of chronic obstructive sleep apnea have been consistently and independently linked to cardiac arrhythmias, cardiovascular disease, hypertension, stroke, motor vehicle accidents, and diminished quality of life [52,53].

If a patient presents with complaints of excessive daytime sleepiness or non-restful sleep and a history of snoring, obstructive sleep apnea should be suspected. A comprehensive medical history and physical evaluation should be obtained, and various objective sleep studies (e.g., polysomnography, portable monitors, MSLT) should be completed to confirm the diagnosis. The AHI scale has been developed to quantify and standardize the degree of obstructive sleep apnea severity. The score is determined by adding the number of apnea and hypopnea events during a patient's overnight sleep study, dividing the total number of events by the minutes of sleep, and finally multiplying the result by 60. For example, if a patient sleeps 8 hours (480 minutes) and has 120 apnea events and 80 hypopnea events (200 total events), the calculation for this patient would be 200 events ÷ 480 minutes × 60, for an AHI score of 25. The AASM Task Force has defined the following cut-points for obstructive sleep apnea [54]:

- Normal: Less than 5 AHI

- Mild: 5 to 15 AHI

- Moderate: 15 to 30 AHI

- Severe: More than 30 AHI

In the example, the patient has an AHI score of 25, or moderate obstructive sleep apnea.

Epidemiology

Obstructive sleep apnea is by far the most common sleep-related breathing disorder [51]. Using the AASM criteria, it is estimated that 1 in 5 American adults has at least mild obstructive sleep apnea and 1 in 15 has at least moderate obstructive sleep apnea [52]. The incidence of the disorder increases with age, and it is two to three times more common in men than in women [51,52,55]. The estimated incidence among various age-groups is [51,55]:

- Children: 2% to 8% among both sexes

- 30 to 65 years of age: 9% of women, 24% of men

- 65 to 99 years of age (with an AHI greater than 10): 56% of women, 70% of men

Differences in incidence among racial and ethnic groups have not been extensively studied. Although race is thought to be an important risk factor for sleep disordered breathing, at this time it is not certain what role race or ethnicity plays in the development of obstructive sleep apnea. Researchers have attempted to link occurrence of the disorder to racial craniofacial differences and variations in body mass trends or fat distribution, with little replicable data to support their hypotheses [55]. Again, this may be due to a lack of research that accounts for race in the United States and other Western countries and limited research of the disorder in Africa, Asia, and the Pacific Islands.

Risk Factors

Many risk factors have been theoretically linked to obstructive sleep apnea. The most widespread factors are alcohol consumption, smoking, overweight and obesity, and hormonal changes related to pregnancy, menopause, and polycystic ovary syndrome [52]. There are conflicting studies for each of these theories, and only overweight and obesity is considered a statistically significant risk factor.

Excess body weight is the strongest risk factor for obstructive sleep apnea in the general population, and most (though not all) patients who present with the disorder are heavier than normal weight [2]. The overweight and obesity epidemic in the United States has caused a concurrent rise in the prevalence of sleep disordered breathing, but the mechanisms involved are still unclear [56]. Hypotheses for the pathophysiology of overweight and obesity in the disorder include distorted upper airway structure and function (caused by altered neck morphology), an altered relationship between respiratory drive and load compensation, and intensification of apnea/hypopnea events through obesity-related decreases in functional residual capacity and increased whole-body oxygen demand [52,57,58]. Other obesity-related conditions, including insulin resistance, generalized inflammation, hypoactive hypothalamic corticotropin-releasing hormone neurons, and visceral adiposity, have been suggested as factors in the development of obstructive sleep apnea following excessive weight gain [59]. Individuals with an "apple-shaped" body (i.e., central adiposity) or who have a greater neck circumference are thought to be more affected than those who are "pear shaped" (i.e., gynoid adiposity), but there is little concrete evidence to support this idea [56].

Obesity may also be a risk factor for obstructive sleep apnea in children and adolescents. One study found a relative risk 4.59 times higher in obese children 2 to 18 years of age compared with normal weight controls [60].

Despite the lack of consensus regarding the role of excess body weight in the pathogenesis of obstructive sleep apnea, studies have shown a strong positive correlation between body mass index (BMI) and AHI [52,57,61]. A decade-long Wisconsin study of 690 randomly selected participants (mean age: 46 years) found that a 10% weight gain yielded a six-fold increase in the odds of developing moderate-to-severe sleep disordered breathing compared with individuals who maintained a steady weight [56]. Those who lost 10% of their initial weight during the study period lowered their AHI score by an average of 26% (range: 18% to 34%). Several small-scale studies have shown improvements in obstructive sleep apnea symptoms following surgical weight-loss interventions. Body mass reduction following bariatric surgery can cause the most dramatic (though possibly short-term) decrease in AHI score [52,53,57,61].

Evaluation and Diagnosis

History and Physical Examination

The diagnosis of obstructive sleep apnea is usually made in one of three settings: a general, routine health evaluation, a screening of high-risk patients, or an evaluation suggestive of obstructive sleep apnea [32]. High-risk groups include individuals who are obese or are being evaluated for bariatric surgery; those with atrial fibrillation, congestive heart failure, treatment-refractory hypertension, nocturnal dysrhythmias, pulmonary hypertension, type 2 diabetes, and/or stroke; and high-risk driving populations (i.e., commercial truck drivers). During the initial evaluation, a history of snoring and daytime sleepiness should be taken, along with an assessment of BMI, blood pressure, maxillofacial irregularities (e.g., retrognathia), and upper airway restriction (e.g., large adenoids/tonsils).

A detailed sleep history should be obtained, including evaluation for [32]:

- Snoring

- Witnessed apneas

- Gasping/choking episodes

- Excessive sleepiness not explained by other factors, including assessment of sleepiness severity by the Epworth Sleepiness Scale

- Total sleep amount

- Nocturia

- Morning headaches

- Sleep fragmentation/sleep maintenance insomnia

- Decreased concentration and memory

Any of the previously discussed complications associated with obstructive sleep apnea (e.g., hypertension, stroke, motor vehicle accidents) should be documented. The physical examination may reveal common physical traits associated with obstructive sleep apnea, including [32]:

- Increased neck circumference (>17 inches in men, >16 inches in women)

- BMI ≥30

- Large tongue (modified Mallampati score of 3 or 4)

- Lateral peritonsillar narrowing

- Tonsillar hypertrophy

- Elongated/enlarged uvula

- High arched/narrow hard palate

- Nasal abnormalities (e.g., deviation, polyps, valve abnormalities, turbinate hypertrophy)

- Retrognathia

- Overjet (protrusion of the upper teeth)

The differential diagnosis of obstructive sleep apnea in adults includes nonpathologic snoring, panic attacks, laryngospasm related to gastroesophageal reflux, and dyspnea associated with pulmonary edema [2].

Testing

Evidence Based Practice Recommendation

The American College of Physicians recommends polysomnography for diagnostic testing in patients suspected of obstructive sleep apnea. Portable sleep monitors are recommended for patients without serious comorbidities as an alternative to polysomnography when it is not available for diagnostic testing.

http://annals.org/aim/fullarticle/1892620

Last Accessed: December 7, 2018

Level of Evidence: Moderate-quality evidence (Randomized, controlled trials with important limitations)

Objective testing with a standardized method follows suspicion of obstructive sleep apnea to confirm the diagnosis and guide the initiation of treatment. In-laboratory polysomnography is the preferred method of objective sleep testing and is recommended for most patients [32]. At-home testing with portable monitors may be used prior to laboratory testing or to confirm the efficacy of treatments, but it should not be used for individuals with a high degree of comorbidity unless in-laboratory monitoring is not feasible due to safety or mobility issues.

Diagnostic Criteria for Adult Patients

The AASM has established diagnostic criteria for adults suspected of having obstructive sleep apnea. In all cases, the disorder must not be better explained by another current sleep disorder, medical or neurologic disorder, medication use, or substance use disorder. In addition, patients must display the following signs and symptoms [2]:

- Polysomnographic recording or out of center sleep testing showing 15 or more predominantly obstructive respiratory events (i.e., apneas, hypopneas, or respiratory effort-related arousals) per hour of sleep

OR

- Polysomnographic recording or out of center sleep testing showing five or more predominantly obstructive respiratory events per hour of sleep

- At least one of the following:

- Complaints of daytime sleepiness, unrefreshing sleep, unintentional sleep episodes during wakefulness, fatigue, or insomnia

- Waking with breath holding, choking, or gasping

- Bed partner or observer reports loud snoring, breath interruptions, or both

- Diagnosis of hypertension, mood disorder, cognitive dysfunction, coronary artery disease, stroke, congestive heart failure, atrial fibrillation, or type 2 diabetes

Diagnostic Criteria for Pediatric Patients

The criteria established to diagnose obstructive sleep apnea in adults have been found to be insufficient to identify children with the disorder. For these patients, parents or caretakers must report a history of labored breathing, snoring, or both, and observation of at least one of the following must be made to diagnose pediatric obstructive sleep apnea [2]:

- Snoring

- Labored, paradoxical, or obstructed breathing during sleep

- Sleepiness

- Hyperactivity

- Behavioral problems

- Learning problems

Differentiating obstructive sleep apnea from primary snoring requires the use of polysomnography. Further, one (or more) scorable event per hour must be recorded during the sleep study. For diagnosis of obstructive sleep apnea in children, polysomnographic findings must include [2]:

- One or more obstructive apneas, mixed apneas, or hypopneas, per hour of sleep

OR

- A pattern of obstructive hypoventilation, defined as at least 25% of total sleep time with hypercapnia (PaCO_2 > 50 mm Hg) in association with one or more of:

- Snoring

- Flattening of the inspiratory nasal pressure waveform

- Paradoxical thoracoabdominal motion

The disorder must also not be better explained by any other medical condition, including another sleep disorder.

Treatment

Due to the chronic nature of the disorder, obstructive sleep apnea treatment is typically long-term and includes behavioral, medical, and surgical options. Patient education regarding the clinical consequences, natural history, pathophysiology, and risk factors of the disorder, and general information, such as alcohol avoidance, risk factor modification, medication effects, weight loss, sleep position, and drowsy driving, should be given upon diagnosis. The goals of treatment are to improve breathing during sleep, to lessen or prevent the sequelae associated with excessive daytime sleepiness and the disorder itself, and patient and partner satisfaction [32].

Positive Airway Pressure Therapy

According to the American College of Physicians (ACP) the principal initial treatment for obstructive sleep apnea is positive airway pressure (PAP) therapy, which uses forced air to maintain a patent pharyngeal airway [62]. This therapy may be provided in one of three modes: continuous (CPAP), bilevel (BPAP), or autotitrating (APAP), all with or without pressure relief (i.e., partial pressure reduction during expiration) [32,60]. CPAP is the standard mode of PAP therapy; BPAP and APAP are used when CPAP cannot be tolerated. CPAP therapy is also recommended for patients with mild obstructive sleep apnea who have failed to improve with behavior modification or who are unable to enact lifestyle changes and who have symptoms that affect their ability to perform daily tasks and impact their quality of life [60].

CPAP appliances consist of a mask or other device that fits over the nose or the nose and mouth, a tube that connects to the mask, and a motor that blows air into the tube [63]. A humidifier and/or heater can be used to condition the device air and lessen or prevent complications, such as throat irritation, nasal dryness, and nasal bleeding. Many patients have difficulty adjusting to wearing the mask and may feel confined during sleep. Periodically wearing the mask during the day, trying CPAP while awake, or using relaxation exercises should be recommended to help in getting comfortable with the device [63]. Newer machines have a "ramp" feature that slowly builds to the prescribed pressure level, which can help with adjusting to the unnatural feeling that CPAP can create.

The clinical effectiveness of CPAP therapy on measures of self-reported daytime sleepiness, fatigue, cognitive function, and depression is supported by evidence. However, the effect on other measures, such as hypertension and cardiovascular events, is unclear [63]. A 2012 clinical trial summary showed that 19% of patients in the CPAP study group developed hypertension, compared with 22% in the control group (dietary and sleep hygiene counseling), and 8% of patients using CPAP had a cardiovascular event, compared with 8% in the control [64]. Although the authors stated that CPAP therapy outcomes failed to reach statistical significance in reduction of these two measures, the small study size may have had limited power to detect a significant difference. A meta-analysis that included 3,780 patients found that, compared with medical therapy alone, CPAP was not associated with a reduced risk of major adverse cardiac events. Improved cardiac outcomes were observed only in a subgroup of patients who wore the CPAP mask for more than four hours at a time [65].

Oral Appliances

Evidence Based Practice Recommendation

The American Academy of Sleep Medicine recommends sleep physicians consider prescription of oral appliances, rather than no treatment, for adult patients with obstructive sleep apnea who are intolerant of CPAP therapy or prefer alternate therapy.

http://jcsm.aasm.org/ViewAbstract.aspx?pid=30098

Last Accessed: December 7, 2018

Level of Evidence: Moderate

An oral appliance is a custom-fit, molded mouthpiece that is fitted by a dental professional to enlarge the upper airway and/or decrease upper airway collapsibility. There are two types of oral appliances: mandibular advancement devices (MADs), which advance the mandible with respect to the resting position and cover the upper and lower teeth, and tongue-retaining devices, which do not reposition the mandible but hold the tongue forward relative to the resting position. The ACP recommends MADs as an alternative for patients who cannot tolerate or would prefer not to use PAP therapy [62]. A complete dental history and dental examination for appraisal of characteristic patterns of wear from nocturnal bruxism; soft tissue, periodontal, and temporomandibular joint (TMJ) assessment; evaluation of occlusion; and resolution of dental pathology precludes the fitting of the appliance. The type employed will be based on a patient's individual anatomy, preferences, and dental assessment. MADs require satisfactory jaw range of motion, no important TMJ disorder, and enough healthy teeth upon which to seat the oral appliance.

A 2006 Cochrane Database review found that oral appliances had similar effectiveness on self-reported outcome measures (e.g., subjective sleepiness, depression) as CPAP therapy but were inferior in reducing respiratory disturbances among most patients [66]. Patients expressed a strong preference for the oral appliances. However, participants were more likely to withdraw on oral appliances than on CPAP therapy. Oral appliance therapy is recommended for patients with mild obstructive sleep apnea who fail behavioral treatments or for patients with mild-to-moderate obstructive sleep apnea who prefer the option over CPAP, who are not candidates for CPAP, or who do not respond to CPAP, or for those carefully selected patients in whom they are as effective in reducing daytime symptoms and AHI score [32,66].

Behavior Modification

There have been no large-scale clinical trials of dietary, exercise, medication, or surgical weight-loss interventions on outcomes in patients with sleep disordered breathing. However, the ACP recommends that all overweight and obese patients diagnosed with obstructive sleep apnea be encouraged to lose weight [62]. Many small-scale studies have shown that BMI reduction (by any means) is effective at reducing the number and duration of apnea and hypopnea events [53]. Other behavioral options include positional therapy and avoidance of alcohol and sedative drugs.

A 10% weight loss can considerably reduce the total number of obstructive events per night, and all patients should be strongly encouraged to achieve a BMI ≤25 through a combination of diet and exercise to improve obstructive sleep apnea symptoms and lessen the risk of comorbidities [32,56]. Subsequent to body mass reduction, AHI should be reassessed using in-lab polysomnography to determine whether PAP adjustments are needed or if PAP therapy may be discontinued altogether. Because significant and lasting weight reduction is typically not achieved by most patients, especially with a dietary component alone, other treatment strategies should be employed simultaneously [32]. Even sustained weight loss does not often fully alleviate the disorder.

A supine sleep position is most likely to affect breathing, and maintaining a non-supine position throughout sleep helps to keep the airway patent in some patients [32]. Identification of individuals who have a low AHI in a non-supine position is necessary before positional therapy is initiated. If appropriate, a device (e.g., alarm, backpack, tennis ball, pillow) may be employed to keep the patient from sleeping on his or her back.

Surgical Treatment

Before the widespread use of PAP therapy, surgery was the primary treatment for obstructive sleep apnea, and it is still indicated for certain cases. Many surgical options involving reconstruction (or bypass) of the upper airway can be used to reduce the severity of obstructive sleep apnea symptoms and increase the effectiveness of behavioral and medical treatments (Table 4); however, it is beyond the scope of this course to cover the details of each procedure. Bariatric weight-loss surgery is also considered a treatment for obstructive sleep apnea and is indicated for patients with a BMI ≥40 or BMI ≥35 with significant comorbidities and failure to achieve weight loss with diet and exercise [32].

Table 4: COMMON SURGICAL PROCEDURES FOR OBSTRUCTIVE SLEEP APNEA BY SITE

Site

Procedure

Upper airway

Tracheotomy

Nasal

Septoplasty

Functional rhinoplasty

Nasal valve surgery

Turbinate reduction

Nasal polypectomy

Endoscopic procedures

Oral, oropharyngeal, and nasopharyngeal

Uvulopalatopharyngoplasty and variations

Palatal advancement pharyngoplasty

Tonsillectomy and/or adenoidectomy

Excision of tori mandibularis

Palatal implants

Hypopharyngeal

Tongue reduction

Partial glossectomy

Radiofrequency ablation

Lingual tonsillectomy

Tongue advancement/stabilization

Genioglossus advancement

Hyoid suspension

Mandibular advancement

Tongue suspension

Laryngeal

Epiglottoplasty

Hyoid suspension

Global airway

Maxillomandibular advancement

Bariatric surgery

Source: [32]

After a diagnosis of obstructive sleep apnea has been established, it should be determined if patients are appropriate candidates for surgery as a primary, secondary, or adjunct treatment [67]. Candidates should also be screened for comorbidities that would affect the outcome of surgery. This and individual anatomy will dictate which option is chosen. Patients with obstructive sleep apnea who have gross anatomic abnormalities that are correctable (e.g., tonsillar and/or adenoidal hypertrophy, collapse or narrowing of the retropalatal or retrolingual areas) should be considered for primary surgical treatment regardless of the severity of the disorder [32]. Surgery as secondary treatment should be considered for patients who have failed to improve with PAP therapy or with an oral appliance or who cannot tolerate either modality. Upon examination of the upper airway, a patient with a gross obstruction that is deemed likely to interfere with the placement, effectiveness, or tolerance of either oral appliances or PAP should be considered a candidate for surgery as an adjunct treatment [32].

The goals, benefits, risks, complications, and possible side effects of the chosen procedure(s) should be discussed, and the willingness to undergo surgical therapy should also be assessed. Although certain procedures (e.g., maxillomandibular advancement, radiofrequency ablation) seem to be effective in reducing AHI score, evidence for most procedures is of low quality and long-term data regarding effectiveness and sequelae is not available [67]. Patients should be informed that most surgeries will not cure obstructive sleep apnea but may improve clinical outcomes (e.g., cardiovascular risk, daytime sleepiness, mortality) [32]. The exception is tracheotomy, which can completely eliminate obstructive sleep apnea but not improve blood oxygen saturation or resolve other symptoms of hypoventilation syndrome. Tracheotomy for obstructive sleep apnea is typically only performed when all other options have been exhausted, when clinically urgent, or in special populations (e.g., patients with Alzheimer disease, Down syndrome, or mental and physical handicaps), as it is a radical procedure that requires a high level of care and lifestyle modification [67].

Pharmacologic and Oxygen Therapies

There are no effective pharmacotherapies for obstructive sleep apnea with the exception of medications used to treat conditions (e.g., hypothyroidism, acromegaly) that can precipitate obstructive sleep apnea or that worsen symptoms of the disorder (e.g., rhinitis) [32]. Patients with persistent daytime sleepiness (despite well-documented improvement in AHI score with PAP or other treatments) may benefit from use of the analeptic modafinil. All other causes of daytime sleepiness must be ruled out and PAP therapy should not be discontinued when taking modafinil. This drug is also used for the treatment of narcolepsy and will be discussed in detail later in this course.

Oxygen therapy is not considered a useful treatment for obstructive sleep apnea, as it has been found that it can lengthen the duration of apneas [32]. However, it is sometimes used to relieve hypoxemia. Resolution of hypoxemia must be documented to justify continued use, especially in patients with comorbid respiratory disease who are at an increased risk of hypercapnia with oxygen therapy.

6. CENTRAL DISORDERS OF HYPERSOMNOLENCE

The ICSD-3 category of central disorders of hypersomnolence includes those that cause excessive daytime sleepiness as the primary complaint; circadian-rhythm shifts and disturbed nocturnal sleep must not be the cause of the primary symptom [2]. The eight disorders in this group are narcolepsy type 1 (with cataplexy); narcolepsy type 2 (without cataplexy); idiopathic hypersomnia, Kleine-Levin syndrome, hypersomnia due to a medical disorder; hypersomnia due to a medication or substance; hypersomnia associated with a psychiatric disorder, and insufficient sleep syndrome [2]. For simplification, the two types of narcolepsy will be discussed as one in the following section, as will idiopathic hypersomnia, along with a brief section on other ICSD-3 hypersomnias.

NARCOLEPSY

Narcolepsy is a primary disorder of the CNS characterized by recurring episodes (every two to three hours) of extreme sleepiness, sudden and irresistible sleep attacks, disturbed nighttime sleep, and memory problems resulting from sleep deficit [2,68]. Sleep spells (or attacks) usually occur during activities or situations in which sleepiness is common (e.g., as a passenger, in a class with no participation, during movies) and last 10 to 20 minutes, on average. However, they may also occur at times when sleeping is not normal (e.g., while driving, eating, walking, or talking). Individuals will feel rested when they awake, but this sense of refreshment does not last long. Sleepiness soon returns, and the cycle repeats. The disorder strongly features SOREMPs and is associated with several pathologic REM sleep phenomena, including cataplexy, sleep paralysis, and hypnagogic/hypnopompic hallucinations.

Narcolepsy occurs in two basic subtypes: with cataplexy and without. Cataplexy is defined as a loss of bilateral muscle tone triggered by intense emotions with an exciting element (e.g., anger, elation, laughter, surprise, sexual arousal) [2,68]. All skeletal muscle groups may be involved, or the effects may be localized. Typical patterns include weakening of the eyelids, mouth, neck, waist, or upper or lower limbs. Smooth, cardiac, and oculomotor muscles are unaffected. The severity of cataplexy varies between individuals and can range from mild eye droop and slurred speech to buckling of the knees and complete postural collapse with fall. The episodes typically last from seconds to minutes. Recovery is usually immediate and complete, but episodes can be repetitive in some individuals if the emotional stimulus recurs, referred to as status cataplecticus, and in rare instances, recurrent attacks have been known to last for up to one hour [2]. Some patients experience cataplexy daily, while others may experience it less than monthly [68].

Most narcoleptic patients experience sleep paralysis, or an inability to speak or move for one to several minutes (up to one hour rarely) while transitioning into and out of sleep (hypnagogic and hypnopompic, respectively) [2]. Like cataplexy, sleep paralysis is a pathologic version of REM sleep atonia and does not affect smooth, cardiac, or oculomotor muscles; however, a sensation of being unable to breathe often accompanies the episode. In cataplexy and sleep paralysis, extensor and flexor reflexes are both lost, which typically only occurs in healthy individuals during REM sleep [33]. A 2011 meta-analysis of 35 studies found that sleep paralysis is experienced by approximately 7.6% of the U.S. general population at some point in their lives, but up to 60% of patients with narcolepsy regularly experience the phenomenon [69,70,71]. Sleep paralysis is typically accompanied by hallucinations.

The hypnagogic and hypnopompic experiences (HHEs) that accompany sleep paralysis appear in three generalized categories but are overwhelmingly of the first type of hallucination, dubbed "Intruder." These hallucinations are described as a sensed evil, malevolent, or threatening presence [72,73]. The second type, the "Incubus," is less common. Described as a demonic or alien being on/near the bed or on top of the body, it is associated with chest pressure, breathing difficulties, and/or pain. Pain is experienced by some individuals while attempting to move their limbs, and another subset may think their limbs are moving when they actually remain still (e.g., while fighting off a perceived threat) [72]. An extreme sense of dread or terror is usually felt during these two types of experiences. Individuals can misconstrue sounds and visions during HHEs (e.g., an object or a shadow may be seen as demon, but later they can reason the misinterpretation) or they may have full-blown, vivid hallucinations (e.g., interaction with beings they are convinced have an external source) [73]. Interestingly, descriptions of beings are consistent throughout history and across cultures, and it is thought that many alien, ghostly, and demonic assault, visitation, and possession incidents are derived from "Incubus"-type HHEs. The third type, "unusual bodily experiences," is infrequently encountered and is described as a flying/floating, out-of-body, or blissful experience without a frightening component [72].

Epidemiology

Narcolepsy is the second most common sleep-related disorder in the United States (after obstructive sleep apnea), affecting an estimated 1 in 2,000 individuals or an estimated 135,000 to 200,000 Americans [33]. Men and women are equally affected, but prevalence varies by race/ethnicity. For example, compared with the United States, narcolepsy is more common in Japan and less common in Israel. Narcolepsy with cataplexy is less common, estimated to affect 1 in 3,000 Americans [33]. The age of onset is typically between 7 and 25 years.

Risk Factors

The causes of narcolepsy are not well known, so it is difficult to determine the influencing factors. There is a heritable component that can predispose individuals to developing the disorder. Certain gene variants of the human leukocyte antigen (HLA) complex and its receptor, T-cell receptor alpha (TCRA), are strongly associated with narcolepsy [33]. Most (though not all) narcoleptic individuals possess the HLA-DR2 or HLA-DQB1*0602 phenotype, which are risk factors for autoimmune disease. However, inflammatory markers and signs/clinical features of inflammatory processes are typically not found in narcoleptics [74,75,76]. This suggests that if the disorder does have an autoimmune origin, the pathology is confined to the nervous system.

Researchers believe that individuals with the implicated subtypes of HLA and TCRA are more prone to an immune system attack on hypocretin-producing neurons in the hypothalamus [33]. The neurotransmitter protein hypocretin regulates appetite, feeding, and sleep patterns, including keeping brain systems from unexpectedly shutting off while awake. People with narcolepsy with cataplexy (and a certain subset of individuals without cataplexy) typically have very low levels of hypocretin, which could explain why they develop narcolepsy and also the higher rate of obesity in this population [33,77].

Though a genetic predisposition does exist, it does not fully explain development of the disorder, as most individuals with the HLA/TCRA variants do not develop narcolepsy and some narcoleptics do not possess these subtypes. In certain rare instances, tumor growth or head trauma have led to narcolepsy [33]. Other factors, including environmental toxins, stress, dietary factors, changes to the sleep schedule, and hormonal changes, likely contribute to the development of the disorder. Infectious agents have been identified as triggers for narcolepsy, particularly Streptococcus spp. and the H1N1 influenza virus, but it is not yet known if the infections are direct triggers or if they indirectly increase susceptibility (e.g., due to the relaxed blood-brain barrier during fever) [33].

Diagnosis

Evidence Based Practice Recommendation

According to the European Federation of Neurological Societies, a prerequisite before implementing a potentially lifelong treatment is to establish an accurate diagnosis of narcolepsy with or without cataplexy and to check for possible comorbidity. Following a complete interview, the patient should undergo an all-night polysomnography followed immediately by a multiple sleep latency test.

https://www.eaneurology.org/fileadmin/user_upload/guidline_papers/EFNS_guideline_2011_Management_of_narcolepsy_in_adults.pdf

Last Accessed: December 7, 2018

Level of Evidence: Expert Opinion/Consensus Statement

As discussed, the most common presentation for all sleep disorders, including narcolepsy, is excessive daytime sleepiness. Cataplexy is rare without narcolepsy and is considered a positive indicator of the disorder [33]. If cataplexy is not present, all other causes of excessive sleepiness must be ruled out by collecting a thorough medical history and conducting an exhaustive clinical examination. The Epworth Sleepiness Scale can be used to identify excessive daytime sleepiness. For the diagnosis of narcolepsy to be confirmed, polysomnography and an MSLT should be performed in a sleep clinic. A polysomnographic study for narcolepsy is similar to an obstructive sleep apnea study. The MSLT will indicate shorter sleep latency periods in patients with narcolepsy compared with healthy individuals [33].

Laboratory testing may include cerebrospinal fluid (CSF) hypocretin-1 levels, but the value of this test is debated [2,33,78]. CSF hypocretin sampling is generally not recommended unless MSLTs are inconclusive or unavailable. This is because reduced or absent levels are usually only found in patients with cataplexy [33,78]. Although most narcoleptic patients without cataplexy have normal hypocretin levels, there is a subset who is deficient, including individuals with the HLA-DR2 phenotype, those at a younger age at onset, and patients with shorter mean REM latency periods [77].

Treatment

Narcolepsy is incurable, and the loss of hypocretin in patients with cataplexy is believed to be irreversible [33]. However, there are several pharmacologic and behavioral treatment options that, when combined, can greatly reduce symptoms of the disorder and help improve patients' quality of life.

Pharmacologic Therapies

Traditional drug treatment options for narcolepsy have included CNS stimulants taken during the daytime to help patients remain alert, sedatives taken at night to help patients attain more restful sleep, and tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) to help control cataplexy, sleep paralysis, and HHEs [33,79,80]. Certain drugs have been found to exert multiple effects; for example, modafinil, a stimulant drug used to treat daytime sleepiness, may also exert antidepressant effects by modulating serotonin transmission [81]. These drug classes are still recommended for prescription today, but the use of a single drug, sodium oxybate, to control all symptoms of narcolepsy (including cataplexy) is gaining favor following a series of successful clinical trials [80,82,83,84,85,86]. However, due to abuse potential, access to the drug is tightly restricted [33,46].

If a CNS stimulant is prescribed in order to combat the effects of excessive daytime sleepiness, the most common are various amphetamines and methylphenidate [33,79]. These agents can be effective in reducing daytime sleepiness and the occurrence of sleep attacks. Amphetamines (e.g., amphetamine, dextroamphetamine, methamphetamine) have been prescribed for narcolepsy since the 1930s and, at lower dosages, act primarily by causing dopamine (and noradrenaline) release [87]. They may be prescribed at 10–60 mg/day. However, amphetamine use is associated with a number of adverse effects, including headache, insomnia, irritability, nervousness, and palpitations, and less frequently, anorexia, hyperhidrosis, nausea, orofacial dyskinesia, and psychosis [79]. Abuse of prescribed amphetamines is rare among narcoleptics, but tolerance develops in one-third of patients. Due to these risks and the proven efficacy of newer drugs, amphetamines are no longer recommended as first- or second-line therapy. Methylphenidate has similar, though milder, adverse effects and a much shorter half-life [80]. It is also prescribed at 10–60 mg/day, but it is recommended only when modafinil is insufficiently active, when modafinil must be supplemented at a specific time of the day, or in situations where maximum alertness is required [33,78].

Modafinil, a stimulant, was approved for use in the United States in 1998 and is the treatment of choice for narcolepsy when the most serious symptom is excessive daytime sleepiness due to its efficacy, limited adverse effects, and easiness of manipulation [33,78]. To date, researchers have been unable to determine the exact mechanism(s) of action, but modafinil is known to increase the release of monoamines (e.g., dopamine, norepinephrine, histamine) from synapses [79,88]. Therefore, the central histaminergic and dopaminergic systems are suspected to be involved. Unlike with classic CNS stimulants, the coadministration of a dopamine antagonist only partially weakens the effectiveness of modafinil, leading researchers to describe the drug as a wakefulness promoting agent [89]. The starting dose is 200 mg, and the usual effective dose is 200–400 mg taken as a single morning dose or as a split dose (first in the morning and then around noon). However, evidence of benefit with a dose greater than 200 mg/day is lacking [46]. There is a low prevalence of common side effects, including headache (13%), nervousness (8%), nausea (5%), and rhinitis, all of which are typically mild [78,80]. More serious side effects have been noted and are mainly allergic/inflammatory reactions, including hives, rash, and swelling. Other severe dermatologic reactions have occurred, such as drug rash with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome, and toxic epidermal necrolysis (TEN), prompting the FDA to issue a safety labeling change in 2007 [46]. There have been very few instances of DRESS, Stevens-Johnson syndrome, and TEN (less than 10 since 1998), and modafinil is considered a safe treatment for excessive daytime sleepiness.

For patients with excessive daytime sleepiness with poor nighttime sleep and cataplexy, the first-line treatment is sodium oxybate [78]. This drug, also known as gamma hydroxybutyrate (GHB), is a powerful sedative that has been burdened by the stigma as a party or "date-rape" drug and a performance-enhancing drug [80]. Misuse of the drug can be life-threatening, and steps should be taken to ensure no other sedatives (including alcohol), muscle relaxants, or respiratory depressants are taken concurrently and that sleep disordered breathing is not present or does not develop. Sodium oxybate is restricted and can only be prescribed by those enrolled in the Xyrem Patient Success Program and dispensed by the designated centralized pharmacy [46]. The initial dose is 4.5 g/night in two equal doses [46]. The first dose is taken sitting upright in bed just before sleep; the patient should lie down immediately after dose one; the second dose is taken 2.5 to 4 hours later. (An alarm may be necessary.) The dose can be increased by 1.5 g at two-week intervals up to a maximum dose of 9 g/night [46,78]. Patients usually begin to improve after the first few nights, but the optimal response (even at the starting dose) can take up to 8 to 12 weeks. Adverse effects are common and include headache (9% to 37%), dizziness (8% to 37%), nausea (8% to 40%), vomiting (2% to 23%), pain (9% to 20%), confusion (3% to 17%), sleep disorder (6% to 14%), somnolence (1% to 14%), abdominal pain (3% to 11%), enuresis (3% to 17%), and urinary incontinence (<1% to 14%, usually nocturnal) [46].

Antidepressants are considered second-line agents for cataplexy and are also an effective treatment for sleep paralysis and HHEs [78]. The most potent anticataplectic drugs are tricyclic antidepressants, especially clomipramine (10–75 mg). However, these agents have the disadvantage of anticholinergic side effects. SSRIs have fewer side effects but are slightly less active [78]. Venlafaxine, a norepinephrine/serotonin reuptake inhibitor, is widely prescribed despite a lack of published clinical evidence to support its use. The same paucity of data exists for norepinephrine reuptake inhibitors (e.g., reboxetine, atomoxetine) [78]. Other pharmacologic agents are no longer recommended for use based on either a lack of clinical efficacy data or on their undesirable adverse effects and safety profiles [78].

Caution should be given when treating patients with comorbid psychiatric disorders. Sodium oxybate should not be used in patients with depression. Instead, antidepressants should be prescribed along with a referral to a psychiatrist or mental health provider [78].

Behavioral Therapies

There are several lifestyle and dietary changes that may help reduce the symptoms and risks of narcolepsy, although there are no accepted behavioral treatments for cataplexy [78]. Behavior modification is useful as medications cannot ensure a consistent state of alertness in individuals with the disorder. Practicing strict sleep hygiene is important, and engaging in relaxation exercises or taking a bath before bedtime may offer a benefit [33]. Daytime napping has been shown to improve alertness and shorten reaction times [33]. Regular exercise (20 minutes/day, four to five hours before bedtime) can lead to better sleep and help prevent or reduce narcolepsy-related weight gain. Alcohol and caffeine should be avoided, especially at night.

One of the major risks of narcolepsy is falling asleep while performing hazardous tasks (e.g., driving, operating machinery) or collapsing due to cataplexy at an ill-timed moment (e.g., while descending a stairway). Automobile accidents are 10 times more common in individuals with untreated narcoleptic symptoms, but when medication and behavioral therapies are being used, the accident rates are similar to healthy individuals [33]. Scheduled naps are recommended to reduce the likelihood of falling asleep unexpectedly. The Americans with Disabilities Act guarantees equal opportunity for narcoleptic students and workers, and reasonable adjustments to school and work schedules should be encouraged to accommodate periodic naps [33].

Support groups for narcolepsy are helpful for many patients. Overcoming feelings of isolation by connecting with other people with the disorder and lessening the sense of judgment by outsiders are important both for those who have just received a diagnosis and experienced patients alike. It may be difficult for individuals living in non-metropolitan areas to find a support group, and for these patients online groups can be useful. More information about narcolepsy support groups is available at https://www.narcolepsynetwork.org. The Narcolepsy Network offers meetings in several U.S. cities and hosts online support groups as well [90].

IDIOPATHIC HYPERSOMNIA

Idiopathic hypersomnia is a rare disorder, affecting approximately 50 people per million population [91]. However, there are many potential causes of daily, unrelenting hypersomnia, and the disorder is a consideration in the differential diagnosis of several other conditions and sleep disorders. Therefore, a brief discussion is warranted.

Idiopathic hypersomnia is characterized by excessive daytime sleepiness without cataplexy and is not better explained by another disorder [2]. Most hypersomniacs have extreme difficulty waking from sleep. If naps are taken, they are usually longer than those taken by individuals with narcolepsy, and many patients experience confusion or disorientation, called sleep drunkenness, upon waking [92]. Also unlike narcolepsy, most (though not all) patients wake from naps still feeling drowsy or unrefreshed. Irresistible urges to sleep (sleep attacks) are rare with this disorder, and cataplexy is not a feature [91,92]. Narcoleptics typically have disturbed nighttime sleep, whereas patients with this disorder do not. Unusual or inappropriate behaviors (e.g., staring, acting intoxicated) may occur in patients who do not take daytime naps.

Diagnosis

There are many medical conditions that can cause hypersomnia, including Kleine-Levin syndrome, Parkinson disease, dementia, and post-traumatic stress disorder, all of which should be ruled out with a complete medical history, physical examination, and diagnostic workup. Standard sleep studies are used to confirm the diagnosis of idiopathic hypersomnia, including MSLT and polysomnography. The absence of multiple SOREMPs (one or fewer) during MSLT and greater time spent in slow-wave sleep during polysomnography suggest idiopathic hypersomnia [91]. On the other hand, multiple SOREMPs (two or more) are indicative of narcolepsy.

Treatment

The same array of pharmacologic options used to treat excessive daytime sleepiness in narcolepsy may be prescribed for idiopathic hypersomnia, but the level of effectiveness is typically not replicated [91,92]. Only half of patients treated report any improvement of symptoms. Although sleep hygiene practices are usually not helpful for idiopathic hypersomnia patients, they should be discussed because there are virtually no risks or drawbacks [91]. Patients should be advised to avoid sedative drugs and alcohol.

OTHER HYPERSOMNIAS

Recurrent hypersomnia is characterized by periodic episodes of extreme somnolence accompanied by cognitive and behavioral disturbances lasting for days to weeks that punctuate an otherwise normal, healthy sleep pattern. During hypersomnia episodes, patients may sleep up to 20 hours per day (range: 10 hours to nearly 24 hours) [2,93]. The average number of episodes is 2 per year, but it can occur up to 12 times per year. The most commonly known form of this disorder is Kleine-Levin syndrome, but there are other forms of recurrent hypersomnia with incomplete features of the syndrome, which may be associated with a medical disorder, psychologic disorder, or medication/substance use [2]. Kleine-Levin syndrome is exceptionally rare in the United States, with fewer than 1 case per million population, although some believe this is an underestimate [93]. The prevalence is greater in individuals of Jewish descent compared with the overall population [94]. The onset of Kleine-Levin syndrome usually occurs in adolescence and follows an infection, such as a cold or influenza.

All patients with recurrent hypersomnia have various forms of cognitive impairment and altered perception during episodes [94]. Cognitive symptoms include impaired speech (94%), difficulty with concentration (91%), and memory impairment (66%). Altered perception symptoms include dream-like state (81%), derealization (66%), and hypnagogic hallucinations (42%). Many patients experience other psychologic symptoms, including eating behavior disorders (95%), hypersexuality and disinhibition (53%), and depressed mood (53%) [94].

Recurring excessive sleepiness can occur during the premenstrual period in adolescent girls, referred to as menstrual-related hypersomnia, and is often controlled with birth-control pills [95]. This and other disorders that cause bouts of excessive sleepiness (e.g., encephalopathy, depression) should be differentiated from hypersomnia disorders.

Treatments include various stimulants, lithium, carbamazepine, and the antiparkinsonian drug amantadine, all of which have marginal efficacy [94,95]. Hypersomnia episodes typically decrease in intensity and frequency within 8 to 12 years of onset, with eventual complete resolution common.

7. CIRCADIAN RHYTHM SLEEP-WAKE DISORDERS

Disorders that fall into the ICSD-3 category of circadian rhythm sleep-wake disorders are caused by alterations to the internal circadian timekeeping system or by environmental, physiologic, or behavioral factors that alter timing of sleep relative to an individual's circadian rhythm, leading to insomnia and/or excessive daytime sleepiness and impaired functioning [2]. Sleep timing that does not follow circadian rhythms will typically cause nonoptimal sleep. The ICSD-3 contains seven disorders of this type [2]:

- Delayed sleep-wake phase disorder

- Advanced sleep-wake phase disorder

- Irregular sleep-wake rhythm disorder

- Non-24-hour sleep-wake rhythm disorder

- Shift work disorder

- Jet lag disorder

- Circadian sleep-wake disorder not otherwise specified NOS

Most circadian rhythm sleep disorders are uncommon or occur overwhelmingly in specific populations (e.g., the non-24-hour sleep-wake rhythm type in blind individuals). Jet lag and shift work disorders are related to very specific sets of conditions. Medical conditions that may be responsible for circadian rhythm abnormalities include dementia, Parkinson disease, and hepatic encephalopathy [2]. Delayed sleep-wake phase disorder affects a significant number of adolescents and young adults.

DELAYED SLEEP-WAKE PHASE DISORDER

Delayed sleep-wake phase disorder is characterized by a habitually delayed sleep time (relative to socially acceptable or conventional sleep times) with difficulty falling asleep when others do [2]. The offset is usually more than two hours, but sleep is normal once initiated (though a late wake time is preferred if allowed). Daytime functioning is normal when individuals are allowed to sleep later, but dictated schedules cause deteriorated well-being. Depression or suicidal ideation may be the primary reason for adolescents' clinical presentation [2]. Patients with this disorder are definite "evening types."

The incidence of this disorder is unknown in the general population, but it is more common in adolescents and young adults (7% to 16%), with a mean onset of 20 years of age [2]. About 1 in 10 sleep clinic patients with chronic insomnia have a delayed sleep phase. Roughly 40% of patients with this disorder have a family member with the disorder [2].

Staying up late, with activity and indoor bright lights, can promote the disorder, as can a corresponding reduction in bright morning light [2]. Shift work, changes in schedules, and frequent travel across time zones can also precipitate the disorder. Attempts at retraining, using sleep hygiene and bright light therapy may work, but patients usually maintain a strong desire for "eveningness" despite intervention [2].

8. PARASOMNIAS

In the ICSD-3, parasomnias are divided into three categories: non-REM-related parasomnias (i.e., disorders of arousal from non-REM sleep), REM-related parasomnias, and other parasomnias [2]. Non-REM-related parasomnias consist of disorders of arousal, confusion arousals, sleepwalking, and sleep terrors, and sleep-related eating disorder; parasomnias usually associated with REM sleep consist of REM sleep behavior disorder, recurrent isolated sleep paralysis, and nightmare disorder. Other parasomnias consist of exploding head syndrome, sleep-related hallucinations, sleep enuresis, parasomnia due to a medical disorder, parasomnia due to a medication or substance, and parasomnia, unspecified [2].

SLEEPWALKING

Sleepwalking, or somnambulism, is a non-REM arousal disorder that causes individuals to walk or perform other activities while asleep. Activities may include sitting upright in bed, walking around inside/outside the house, moving furniture, getting dressed, preparing food, trying to "escape," jumping from windows, driving a car, and many others, though dangerous activities are rare [96,97]. It is fairly common for sleepwalking children to engage in inappropriate behaviors, such as urinating in a closet or waste basket [2]. Accidents and falls may also occur, and people have even committed homicide or pseudosuicide while asleep. Patients can become violent when others attempt to awaken them from the sleepwalking episode, and most will be extremely confused if awakened and will not recall the events of the episode [96,97].

It should be noted that sleep driving associated with z-drugs (e.g., zolpidem, zopiclone) and other psychiatric medications is unrelated to sleepwalking [98]. Sleep drivers will typically have some level of cognitive function (e.g., are responsive to police questioning) but will display poor balance and walking ability. Sleepwalkers, on the other hand, are perfectly able to balance while walking but have no ability to interact.

Sleepwalking typically occurs during non-REM sleep stages 3 and 4 (slow-wave sleep), which is more common early in the night (during the first-third of sleep) [96]. Episodes last an average of 10 minutes but range from a few minutes to more than 30 minutes. Patients usually return to bed before waking, but some may fall asleep in another location or awaken while sleepwalking [2]. Sleep talking may also be exhibited by these individuals, and sleep terrors may occur at other times. Sleepwalking episodes may occur frequently (several times per night, for several nights) or only rarely or when precipitating factors are present [2].

Epidemiology

The prevalence of sleepwalking ranges from 4% in adults to 17% in children [2]. The disorder may begin as soon as a child is able to walk, but the age of onset is usually between 4 and 8 years. The disorder is most common in children 5 to 12 years of age [2,96]. A 2004 National Sleep Foundation poll found that sleepwalking a few nights per week occurs in 1% of preschoolers and 2% of school-age children [99]. Sleepwalking is more common in children with sleep enuresis (chronic bedwetting). Symptoms of sleepwalking disappear after adolescence in most patients; however, the disorder can occur at any age [2,96]. Approximately one-third of cases develop after adolescence [2]. Girls and boys are affected equally in childhood, but the gender distribution in adults is not well defined [2]. One study of an adult population of sleepwalkers in Nigeria found prevalence roughly three times higher in men than in women [100].

Sleepwalking may occur in isolated cases, but there is a known genetic susceptibility and a familial pattern [2,101]. The incidence in children is 60% when both parents have the disorder and 45% when one parent is affected. The incidence is 22% if neither parent has the disorder but when sleepwalking is familial (i.e., occurs in more distant relatives) [2]. A 2012 Stanford School of Medicine study found that the self-reported yearly incidence of sleepwalking was 3.6%, equating to about 8.5 million Americans [102]. According to the study, the lifetime prevalence of a sleepwalking episode was estimated at 29.2%, with 30.5% of participants reporting a family history of the disorder. Twin studies support the role of genetic susceptibility in at least 65% of cases [2].

Risk Factors

Although there is a strong heritable factor for sleepwalking, the pathology of sleepwalking is not known [2,96]. Individuals who are predisposed to sleepwalking may become active sleepwalkers when priming factors exist and a precipitating factor triggers an episode [2,101]. Priming factors deepen and increase slow-wave sleep and include anxiety, fatigue, fever, the premenstrual period, sleep deprivation, and physical or emotional stress. Alcohol use and certain medications may also be priming factors, but it is unclear if the many case reports of "sleepwalking" under the influence of substances are due to extreme intoxication or complex medication interactions (or medication/psychopathologic interactions) [2,96,101]. Precipitating factors, or triggers, identified in primed individuals in sleep laboratories include light, noise, periodic leg movements, sleep disordered breathing, and touch.

Certain mental disorders (e.g., obsessive-compulsive disorder) and medical conditions (e.g., organic brain syndrome, partial complex seizures) are associated with sleepwalking, as is obstructive sleep apnea [2,96,102]. Medication-related sleepwalking may occur, most commonly in individuals with a complex medical and psychiatric history associated with multiple medications [101]. The 2012 study found a higher risk of frequent sleepwalking episodes (two or more times/month) with obstructive sleep apnea syndrome (odds ratio [OR]: 3.9), obsessive-compulsive disorder (OR: 3.9), alcohol abuse/dependence (OR: 3.5), major depressive disorder (OR: 3.5), circadian rhythm sleep disorder (OR: 3.4), SSRI antidepressant use (OR: 3.0), over-the-counter sleep aid use (OR: 2.5), and insomnia disorder (OR: 2.1) [102].

Diagnosis

Steps should be taken to ensure that sleepwalking is not the result of a medication side effect or an underlying medical or psychiatric condition. Specific medications and their dosages should be reviewed. In cases of pediatric sleepwalking, parents or caretakers will have witnessed one or more behaviors associated with the disorder, including [96,97]:

- Aggressive behavior when aroused (rare)

- The appearance of being awake while still asleep

- Open eyes during sleep, with a blank look on the face

- Confusion or disorientation when roused

- Performance of detailed activities during sleep

- No memory of the sleepwalking episode

- Sleep-talking and nonsensical verbalizations

Adult patients with no history of the disorder may similarly present with no recollection of any episode of sleepwalking or associated behaviors, which may have instead been witnessed by another person. Sleep studies and other tests and procedures are typically not needed to confirm a diagnosis in patients with known good health [2,96]. However, testing to rule out other medical conditions (e.g., partial complex seizures, obstructive sleep apnea) in patients with a limited medical history is recommended.

Treatment

There is no cure or specific treatment for sleepwalking [96,99]. As a first step in the management of sleepwalking, conditions or medications that may cause somnambulism should be identified and treated or discontinued, which may eliminate or greatly reduce sleepwalking episodes. For patients with sleepwalking as the primary diagnosis, identifying the priming and precipitating factor(s) is a cornerstone of management. Patients (or parents) should be instructed to keep a journal that includes daily activities, level of daytime sleepiness, total hours of sleep, and any illnesses or triggers of stress or anxiety to help to determine possible triggers, though dedication to observation and journaling lessens and more omissions occur over time [103].

Again, there is no high-quality evidence to support any specific sleepwalking treatment [99,104]. A tailored approach to therapy, including improvements in sleep hygiene, should be made on a patient-by-patient basis. Although medication is not usually required and is not recommended as a first-line therapy, sedative-hypnotics, tricyclic antidepressants, or SSRIs may be prescribed if sleepwalking interferes significantly with the patient's or the family's quality of life (e.g., excessive daytime sleepiness, high risk of injury, unusual symptoms, inappropriate behaviors causing family distress) [96,99]. However, the usefulness of these medications is not certain [105,106]. Care must be taken when prescribing tricyclic antidepressants, as they have many serious side effects (especially in children) and can exacerbate sleepwalking [107]. Benzodiazepines (e.g., clonazepam, diazepam) were initially prescribed for sleepwalking, with only limited benefit [105,106]. One study of individuals with either isolated sleepwalking or sleepwalking related to psychiatric conditions or obstructive sleep apnea found that benzodiazepines and psychiatric medications were not effective in reducing sleepwalking episodes. Nasal CPAP therapy for participants with obstructive sleep apnea eliminated sleepwalking in all individuals who remained compliant throughout each of the follow-up periods [106].

Hypnosis has been used as a low-cost, safe therapy for various parasomnias, including sleepwalking [99]. One small-scale study (27 participants) conducted by Hurwitz and colleagues showed a 74% success rate for long-term reduction of sleepwalking and night terror episodes ("much" or "very much" improvement on self-report) following one to six office visits and continued with at-home self-hypnotic exercises [108]. A five-year follow-up study of 36 parasomnia patients (modeled on the Hurwitz study) found a 45.4% success rate after 1 month (symptom free or "much improved"), which diminished slightly to 42.2% at 18 months and 40.5% at 5 years [109]. In this study, participants underwent one or two 50-minute hypnosis sessions, described as "deep physical relaxation but with retention of an active and focused mind, so possible new thoughts could be evaluated and incorporated into the hypnotized person's thinking" [109].

One behavioral approach, anticipatory awakenings, can be effective in reducing sleepwalking episodes. This method requires parents or caretakers to wake the patient three hours into the night and 15 minutes before the usual sleepwalking time. The patient is kept awake for 30 minutes and then may return to sleep. Anecdotal reports have found this intervention to be successful; however, it requires a significant commitment on the part of those involved [107,110].

Another key to treatment is the maintenance of a safe living environment. Patient/parent education should cover precautions to be taken, including [99,107]:

- Locking windows and doors in a way that allows for safe emergency exit

- Installing door alarms on all doors that lead outside or to a basement or attic

- Securing all potentially dangerous objects or items (e.g., tripping hazards, sharp objects, chemicals, medications, knives, guns)

- Moving the patient's bedroom to the ground floor (if possible)

- Covering windows to block out light

9. SLEEP-RELATED MOVEMENT DISORDERS

The ICSD-3 includes 10 sleep-related movement disorder diagnoses: restless legs syndrome; periodic limb movement disorder (PLMD); sleep-related leg cramps; sleep-related bruxism; sleep-related rhythmic movement disorder; benign sleep myoclonus of infancy; propriospinal myoclonus at sleep onset; sleep-related movement disorder due to a medical disorder; sleep-related movement disorder due to a drug or substance; and; sleep-related movement disorder, unspecified [2].

RESTLESS LEGS SYNDROME AND PERIODIC LIMB MOVEMENT DISORDER

Although restless legs syndrome and PLMD are two distinct disorders, they are often discussed together, as they have overlapping features. PLMD is also comorbid in most (85% to 90%) patients with restless legs syndrome [2,111].

Restless legs syndrome, also known as Willis-Ekbom disease, is a neurologic sleep disorder characterized by disagreeable leg sensations that worsen when individuals are at rest (e.g., when seated) and/or at night before bedtime [2]. There is an accompanying urge to move the legs to relieve the unpleasant sensations, which are described as aching, bubbling, creeping, crawling, pulling, searing, and/or tingling; walking, stretching, or shaking usually provides relief [112]. The area between the ankle and the knee is most often affected (usually bilaterally), but the thighs, feet, and to a lesser extent the arms may also be affected [2]. Pathologic changes in efficiency of central dopamine neurotransmission are thought to cause the disorder, based on the observation that restless legs syndrome symptoms are relieved by the use of dopaminergic drugs [111]. The secondary (non-idiopathic) form of restless legs syndrome can be caused by a variety of medical conditions. Iron deficiency and uremia are common causes; others include chronic kidney disease, cobalamin (vitamin B12) deficiency, folate deficiency, diabetes, fibromyalgia, Parkinson disease, peripheral neuropathy, pregnancy, radiculopathy, rheumatoid arthritis, Sjögren syndrome, use of certain drugs (e.g., caffeine, calcium channel blockers, lithium, neuroleptics), and withdrawal from sedatives [112,113].

Troubling and painful leg sensations that cause an irresistible urge to move initially keep patients from being able to sleep, and the discomfort is often so disrupting that patients awaken several hours after falling asleep. As such, restless legs syndrome is a significant cause of (secondary) insomnia. Periodic limb movements during sleep are very common in patients with restless legs syndrome, and involuntary limb movements occur in many patients with restless legs syndrome while awake [2]. Involuntary limb movements while awake are much less common among patients with PLMD alone.

PLMD is characterized by episodes of repetitive, stereotyped leg movements during stage 1 and stage 2 sleep, consisting of extension of the big toe in combination with partial flexion of the ankle, knee, and sometimes hip [2,111]. The legs typically remain still during non-REM stages 3 and 4 and during REM sleep. Episodes prevail during the first half of the night and diminish progressively [113]. Intermittent flexion at the elbow may also be seen in some patients.

Some patients may not be roused by the movement episodes and only complain of excessive daytime sleepiness. However, the typical presentation is with frequent awakenings and poor sleep quality (i.e., insomnia). Bed partners' sleep is often disturbed by the movements. As with restless legs syndrome, this disorder is also thought to be caused by altered dopamine neurotransmission (based on the efficacy data of dopaminergic drugs) but can also be caused by a medical condition [111]. Certain medications can cause periodic limb movements during sleep, including tricyclic antidepressants (e.g., amitriptyline), neuroleptics and other antidopaminergic agents (e.g., haloperidol), and dopaminergic agents (e.g., carbidopa, which may be used in the treatment of PLMD).

Epidemiology

Approximately 5% to 15% of the adult U.S. population is affected by restless legs syndrome, and women are affected twice as often as men [2,114]. The disorder is more common in certain groups, including pregnant women (11%), uremic patients (15% to 20%), and patients with rheumatoid arthritis (up to 30%). In general, restless legs syndrome is associated with advancing age; however, the age of onset is younger than 20 years in one-quarter of patients. Among children 8 to 11 years of age and adolescents 12 to 17 years of age, the prevalence is 1.9% and 2.0%, respectively [95]. Restless legs syndrome symptoms usually appear after the 20th week when associated with pregnancy [2].

The exact incidence of PLMD alone is unknown in adults [2]. However, it is very uncommon in children and is more prevalent after middle age, with approximately 44% of adults 65 years of age or older found to have symptoms of the disorder [2,113]. It is unclear if the prevalence among older adults differentiates symptoms indicative of idiopathic PLMD and limb movements related to other conditions, but some questions have been raised as to whether PLMD is a true sleep disorder based on the high prevalence in this population [113].

Risk Factors

There is a strong heritable risk factor for restless legs syndrome [112]. One study found that more than 70% of pediatric patients with restless legs syndrome had at least one parent with the disorder [95]. As noted, restless legs syndrome is more common in women, but race does not appear to be a factor [2]. Overall, prevalence and incidence have not been well defined [95,111].

Medical or psychiatric conditions and certain medications have been associated with an increased incidence of restless legs syndrome and/or PLMD. Children with attention deficit hyperactivity disorder are more likely to have both restless legs syndrome and PLMD. Uremia and other metabolic disorders are known to cause periodic limb movements during sleep [2]. Monoamine oxidase inhibitors and tricyclic antidepressants can cause or worsen the disorder, as can withdrawal from certain drugs, including anticonvulsants, benzodiazepines, barbiturates, and other hypnotic agents. PLMD may be associated with an underlying arousal disorder [111].

Diagnosis

The history and physical examination should focus on differentiating restless legs syndrome from other conditions with shared features, including akathisia, anxiety disorders, chronic myelopathy, erythromelalgia, leg compartment syndromes, muscular pain fasciculation syndromes, myokymia, and peripheral neuropathy [2]. Subclinical hypopneas can also trigger limb movements. Iron-deficiency anemia, caffeinism, and uremia should also be considered as possible causes of secondary restless legs syndrome. The use of and withdrawal from high-risk medications should also be identified from the medical history. All conditions known to cause the symptoms indicative of the disorder should be ruled out, and serology should be obtained (e.g., cobalamin, creatinine, ferritin, folate, iron, urea) [113]. Additional serology and electrodiagnostic testing may be considered if peripheral neuropathy is suspected. The presence of periodic limb movements during sleep is a strong indication of restless legs syndrome. Several instruments are available to measure restless legs syndrome severity, including the Johns Hopkins Restless Legs Syndrome Severity Scale (Table 5) and the Restless Legs Syndrome Quality of Life Instrument (RLS-QLI) [115]. The RLS-QLI consists of 17 items that assess the patient's social function, daily function, sleep quality, and emotional well-being, while the Johns Hopkins measure focuses on timing of symptoms [116,117].

Table 5: JOHNS HOPKINS RESTLESS LEGS SYNDROME SEVERITY SCALE

Timing of Symptoms

Score

No symptoms

0 (never)

Symptoms less than daily or almost daily

0.5 (infrequent)

At bedtime and/or during the sleep period.

Symptoms may occur within 60 minutes before the usual bedtime or simply at the time of going to bed or during the night after in bed.

1 (mild)

Evening, after 6 p.m.

Symptoms may occur anytime between 6 p.m. and the usual bedtime. (The definition of evening may need to be adjusted for patients who routinely have much later bedtimes.)

2 (moderate)

Afternoon, before 6 p.m.

Symptoms may start in the afternoon and persist into the evening or night.

3 (severe)

Before noon.

Symptoms may start in the morning or they may present virtually all day. There is usually a "protected period" in the mid-morning (8–10 a.m.) with few if any symptoms.

4 (very severe)

Source: Reprinted from Allen RP, Earley CJ. Validation of the Johns Hopkins restless legs severity scale. Sleep Med. 2001;2(3):239-242, with permission from Elsevier.

Sleep studies are not typically needed for a diagnosis of restless legs syndrome to be made; however, periodic limb movements during sleep may be confirmed using polysomnography, if necessary [2]. Polysomnographic features of PLMD are recorded using bilateral anterior tibialis EMG. Patterns of movement include repetitive contractions (four or more, with a duration of 0.5 to 5 seconds)—typically a leg jerk, followed by a short interval (milliseconds) and a tonic contraction—spaced apart by 20 to 40 seconds of relaxed muscle tone [2]. Both legs are involved in the majority of patients, but there may be inconsistent and random alternation between the left and right limbs or a unilateral, predominant pattern. The periodic limb movement arousal index measures the number of limb movements associated with EEG arousals per hour. Mild PLMD is defined as 5 to 25 movements per hour, moderate as 25 to 50 per hour, and severe as more than 50 movements per hour or more than 25 movements associated with arousals per hour [113].

Treatment

Anticonvulsants, dopamine agonists, tranquilizers, and opioid narcotics are used to manage symptoms of restless legs syndrome, and iron supplements are used when indicated [111,112]. Dopamine agonists considered effective for restless legs syndrome management include pramipexole and ropinirole, but rotigotine is recommended for long-term therapy [112,118]. These and other antiparkinsonian drugs are also first-line therapies for PLMD and may improve sleep in patients with both disorders. The anticonvulsants gabapentin and pregabalin reduce movement symptoms and neuropathic pain in patients with either restless legs syndrome or PLMD and may also help to improve sleep; however, use of these medications for restless legs syndrome and PLMD is off-label [46,112]. Gabapentin enacarbil is on-label and is preferred over gabapentin for long-term treatment [46,118]. Other treatments for these sleep disorders include stress management, muscle relaxation exercises, and sleep hygiene.

The initial dosage of pramipexole (immediate-release) is 0.125 mg once daily, two to three hours before bedtime, but higher doses (up to 0.5 mg) are typically required in order to be effective [46]. The maximum recommended dose is 0.5 mg, but doses up to 2 mg daily are occasionally used. The most frequent side effects are nausea (11% to 27%), particularly early in treatment, and headache (16%) [46]. There is no evidence that doses higher than 0.5 mg/day offer benefit [119].

Evidence Based Practice Recommendation

The American Academy of Sleep Medicine has identified pramipexole and ropinirole as the agents with the highest level of evidence supporting their use in the treatment of patients with restless legs syndrome.

https://aasm.org/resources/practiceparameters/updateto.pdf

Last Accessed: December 7, 2018

Strength of Recommendation/Level of Evidence: Standard (High or moderate evidence that benefits clearly outweigh harm/burden)

The initial dose of ropinirole (immediate-release) is 0.25 mg taken one to three hours before bedtime; the dose may be increased to 0.5 mg after two days, to 1 mg after one week, and to a maximum dose of 4 mg at week 7. Common adverse effects include dizziness (6% to 40%), fatigue (8% to 11%), nausea (40% to 60%), somnolence (11% to 40%), syncope (1% to 12%), and viral infection (11%) [46].

The rotigotine (transdermal patch) initial dose is 1 mg/24 hours (one patch per day). The daily dose may be increased by 1 mg/24 hours each week, to a maximum daily dose of 3 mg/24 hours [46]. Dose-related application site reactions are common (21% to 46%), as are gastrointestinal complications such as nausea (15% to 48%) and vomiting (2% to 20%), and CNS reactions (e.g., somnolence, dizziness, headache, fatigue, orthostatic hypotension, hallucinations) [46]. Therefore, an extended low-dose trial is recommended.

Higher doses of gabapentin (2,000–2,400 mg daily) have been found to be significantly more effective than placebo in reducing moderate-to-severe restless legs syndrome symptoms, but higher doses are also associated with a high prevalence of adverse effects (e.g., dizziness, fatigue, nausea, pain, weakness) [46,120]. The recommended initial dose for restless legs syndrome treatment (off-label) is 300 mg taken two hours before bedtime; the dose may be titrated every two weeks, until desired response is achieved, to a maximum dose of 1,800 mg [46]. (Dosages of up to 3,600 mg have been tolerated in short-term studies but are not recommended.) A combination of lower-dose gabapentin (300–1,000 mg daily) and ropinirole (0.25–1.5 mg daily) is also effective for treating restless legs syndrome and is associated with a lower incidence of adverse effects than high-dose gabapentin alone [120].

Gabapentin enacarbil is FDA-approved for the treatment of restless legs syndrome and is preferred over gabapentin due to longer duration of action and improved absorption [46,118,121]. The dosage is 600 mg once daily at approximately 5 p.m. Worsening side effects are seen at higher doses, and no benefit is reported at a dose of 1,200 mg compared with 600 mg [46]. Adverse effects (at a 600-mg daily dose) include dizziness (13% to 17%), headache (10% to 12%), and somnolence (20%), and a low rate of gastrointestinal effects are also observed (e.g., nausea, 6% to 8%) [46]. Pooled analysis of long-term use of gabapentin and other antiepileptic drugs has validated concerns regarding suicidal ideation and behavior (0.43%) compared with placebo (0.24%) [46]. Human data regarding pancreatic cancer risk have yet to be compiled, although gabapentin is associated with pancreatic adenocarcinoma in rats [46,121].

Multiple studies have shown that pregabalin is effective for managing sensory and motor symptoms of restless legs syndrome and has a low rate of mild adverse effects across a wide dosage range [122,123]. A reduction of periodic limb movements and sleep architecture improvements (e.g., increase in slow-wave sleep, decrease in waking after sleep onset and during sleep stages 1 and 2) were noted. In one study, the mean effective dose for pregabalin was approximately 350 mg/day, but in another study, a dose of 125 mg/day was shown to be effective in 90% of participants [122,123]. Pregabalin is usually taken in divided doses, either two or three times a day [46]. Dizziness (3% to 45%) and somnolence (17% to 26%) are the most frequent adverse effects [46,122].

Lifestyle Modifications and Alternative Therapies

Stress reduction, muscle relaxation techniques, and physical activity are important components of a restless legs syndrome management strategy, along with improved nutrition, proper sleep hygiene, and elimination of caffeine and alcohol intake [112,113,115]. Supplementation with specific vitamins and minerals known to support the nervous system and improve blood circulation (e.g., vitamins B12, C, D, and E; glucosamine; magnesium; zinc) may be considered for patients with inadequate nutritional intake, but little research exists apart from small studies showing some degree of symptom reduction with supplementation with vitamins B and E [115]. Other alternative therapies with little or no scientific support include acupuncture, meditation, and prayer.

Moderate aerobic exercise and lower-body resistance training are recommended to both assist in the relief of psychologic stress and lessen the severity of symptoms [112]. Endorphin release, dopamine production, and increased blood flow to leg muscles are believed to mediate symptoms [115]. Massage, warm baths, and heating pads may also be used to relieve and/or prevent restless legs syndrome symptoms, though there is a lack of strong efficacy data for these therapies. Case studies have shown a positive effect with massage (and a return of symptoms after cessation of massage therapy regimens), but the mechanisms involved are unclear [115]. Theories include improved blood circulation, dopamine release, counterstimulation of the cerebral cortex, and modulated thalamic neural activity as a response to tactile and temperature stimulus. Pulsed pneumatic compression devices have also been shown to reduce symptom severity; the proposed beneficial mechanisms are similar to those of massage [115]. Near-infrared light therapy has also successfully reduced restless legs syndrome symptom severity in small-scale studies [124].

There is a strong placebo effect in restless legs syndrome therapy [115]. A 2008 meta-analysis of 36 clinical trials found that one-third of patients had a significant improvement while receiving placebo medications [125]. In 24 of the trials, 40% of participants had a placebo response. However, this level of response was based on a reduction in the International Restless Legs Severity Scale score alone, and the placebo response was only moderate for other measures (e.g., daytime functioning, other restless legs syndrome measures). The placebo effect was found to be small for PLMD therapy [125].

In 2014, the FDA cleared the first device to improve sleep quality in patients with restless legs syndrome [126]. The device, marketed as Relaxis, consists of a vibrating pad that provides counterstimulation to a patient's legs as he or she sleeps. The manufacturer cautions that this device should not be used on patients who have had deep venous thrombosis in either leg in the six months prior to the initiation of therapy.

10. DIAGNOSING AND TREATING SLEEP DISORDERS WITH THE HELP OF AN INTERPRETER

As a result of the evolving racial and immigration demographics in the United States, interaction with patients for whom English is not a native language is inevitable. Because patient education is such a vital aspect of the treatment and management of sleep disorders, it is each practitioner's responsibility to ensure that information and instructions are explained in such a way that allows for patient understanding. When there is an obvious disconnect in the communication process between the practitioner and patient due to the patient's lack of proficiency in the English language, an interpreter is required. (In many cases, the terms "interpreting" and "translating" are used interchangeably, but interpreting is specifically associated with oral communication while translating refers to written text.) While this may be easier said than done, due to institutional and/or patient barriers, the U.S. Department of Health and Human Services Office for Civil Rights has stated that denying adequate interpreter services to patients with limited English proficiency is a form of discrimination and that insufficient use of professional interpreters and inappropriate reliance on ad hoc interpreters may compromise patient care [127].

Depending upon the patient's language, an interpreter may be difficult to locate. Or, an organization may not have the funds to bring in an interpreter. Many view interpreters merely as neutral individuals who communicate information back and forth. However, another perspective is that the interpreter is an active agent, negotiating between two cultures and assisting in promoting culturally competent communication and practice [128]. In this more active role, the interpreter's behavior also is influenced by a host of cultural variables, such as gender, class, religion, educational differences, and power/authority perceptions of the patient [128]. Consequently, an intricate, triangular relationship develops between all three parties. Another factor affecting the communication process is that many interpreters are not adequately trained in the art of interpretation in mental health and general health settings, as there are many technical and unfamiliar terms. An ideal interpreter goes beyond being merely proficient in the needed language/dialect [129]. Interpreters who are professionally trained have covered aspects of ethics, impartiality, accuracy, and completeness [130]. They also are well-versed in interpreting both the overt and latent content of information without changing any meanings and without interjecting their own biases and opinions [130]. Furthermore, knowledge about cross-cultural communication and all the subtle nuances of the dynamics of communicating in a mental health or general health setting is vital [129].

On the patients' side, they may be wary about using interpreters for a host of reasons. They may find it difficult to express themselves through an interpreter [131]. If an interpreter is from the same community as the patient, the client/patient may have concerns about sharing private information with an individual who is known in the community and the extent to which the information disclosed would remain confidential. In some cases, raising the issue of obtaining an interpreter causes the client/patient to feel insulted that their language proficiency has been questioned. Finally, if an interpreter is from a conflicting ethnic group, the patient may refuse having interpreter services. The ideal situation is to have a well-trained interpreter who is familiar with health and mental health concepts.

If an interpreter is required, the practitioner should acknowledge that he/she is more than a body serving as a vehicle to transmit information verbatim from one party to another [131]. Instead, the interpreter should be regarded as part of a collaborative team, bringing to the table a specific set of skills and expertise [131]. Several important guidelines should be adhered to in order to foster a beneficial working relationship and a positive atmosphere.

A briefing time between the practitioner and interpreter held prior to the meeting with the client/patient is crucial. The interpreter should understand the goal of the session, issues that will be discussed, specific terminology that may be used to allow for advance preparation, preferred translation formats, and sensitive topics that might arise [129,131,132]. It is important for the client/patient, interpreter, and practitioner to be seated in such a way that the practitioner can see both the interpreter and client/patient. Some experts recommend that the interpreter sit next to the client/patient, with both parties facing the practitioner [130].

The practitioner should always address the client/patient directly. For example, the practitioner should query the client/patient, "How do you feel?" versus asking the interpreter, "How does she feel?" [130]. The practitioner should also always refer to the client/patient as "Mr./Mrs. D," rather than "he" or "she" [131]. This avoids objectifying the client/patient.

At the start of the session, the practitioner should clearly identify his/her role and the interpreter's role [131]. This will prevent the client/patient from developing a primary relationship or alliance with the interpreter, turning to the interpreter as the one who sets the intervention [129]. The practitioner also should be attuned to the age, gender, class, and/or ethnic differences between the client/patient and the interpreter [131]. For example, if the client/patient is an older Asian male immigrant, and the interpreter is a young, Asian female, the practitioner should be sensitive to whether the client/patient is uncomfortable, given the fact he may be more accustomed to patriarchal authority structures. At the conclusion of the session, it is advisable to have a debriefing time between the practitioner and the interpreter to review the session [129,131,132].

In this multicultural landscape, interpreters are a valuable resource to help bridge the communication and cultural gap between clients/patients and practitioners. Interpreters are more than passive agents who translate and transmit information back and forth from party to party. When they are enlisted and treated as part of the interdisciplinary clinical team, they serve as cultural brokers, who ultimately enhance the clinical encounter. In any case in which information regarding diagnostic procedures, treatment options, and medication/treatment measures are being provided, the use of an interpreter should be considered.

11. CONCLUSION

Consistent and refreshing sleep is vital to health and an overall sense of wellness. However, nearly 25% of the U.S. population is troubled by a sleep disorder, many of which remain undiagnosed or undertreated, leading to a sleep deficit that can be difficult or impossible to repay. While most forms of disordered sleep are not immediately life-threatening, they can cause considerable distress, including accidental injury, depression, fatigue, and substance abuse. Most patients with a sleep disorder initially present to their primary care provider or other non-specialist, and appropriate identification and treatment or referral are important in this setting. This is especially true for the handful of sleep disorders that cause the majority of morbidity and mortality, including obstructive sleep apnea, narcolepsy, and insomnia. Increased understanding and adherence to best practices can improve patients' quality of life and help prevent associated complications.

Works Cited

1. Institute of Medicine Committee on Sleep Medicine and Research, Colten HR, Altevogt BM (eds). Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem. Washington, DC: National Academies Press; 2006.

2. American Academy of Sleep Medicine. The International Classification of Sleep Disorders-3: Diagnostic and Coding Manual. 3rd ed. Westchester, IL: American Academy of Sleep Medicine; 2014.

3. Skaer TL, Sclar DA. Economic implications of sleep disorders. Pharmacoeconomics. 2010;28(11):1015-1023.

4. National Commission of Sleep Disorders Research. Wake Up America: A National Sleep Alert: Report of the National Commission on Sleep Disorders Research. Washington, DC: The National Commission; 1993, 1994.

5. U.S. Department of Transportation, National Highway Traffic Safety Administration. Drowsy Driving. Available at https://www.nhtsa.gov/risky-driving/drowsy-driving. Last accessed December 3, 2018.

6. Wittmann V, Rodenstein DO. Health care costs and the sleep apnea syndrome. Sleep Med Rev. 2004;8(4):269-279.

7. Leger D. The cost of sleep-related accidents: a report for the National Commission on Sleep Disorders Research. Sleep. 1994;17(1):84-93.

8. Webb WB. The cost of sleep-related accidents: a reanalysis. Sleep. 1995;18(4):276-280.

9. Leger D. The cost of sleepiness: a response to comments. Sleep. 1995;18(4):281-284.

10. Kessler RC, Berglund PA, Coulouvrat C, et al. Insomnia and the performance of U.S. workers: results from the America Insomnia Survey. Sleep. 2011;34(9):1161-1171.

11. Hirsch Allen AJ, Bansback N, Ayas NT. The effect of OSA on work disability and work-related injuries. Chest. 2015;147(5): 1422-1428.

12. Ohayon MM, Schenck CH. Violent behavior during sleep: prevalence, comorbidity and consequences. Sleep Med. 2010;11(9): 941-946.

13. Grover M, Mookadam M, Armas D, et al. Identifying patients at risk for obstructive sleep apnea in a primary care practice.J Am Board Fam Med. 2011;24(2):152-160.

14. Roth T, Bogan RK, Culpepper L, et al. Excessive sleepiness: under-recognized and essential marker for sleep/wake disorder management. Curr Med Res Opin. 2010;26(Suppl 2):S3-S24.

15. Wang CL, Li XZ, Cai XL, Pan XL, Min J. Anesthesiologist's knowledge and attitudes about obstructive sleep apnea: a survey study. Sleep Breath. 2012;16(1):41-46.

16. National Sleep Foundation. Sleep-Wake Cycle: Its Physiology and Impact on Health. Available at http://www.sleepfoundation.org/sites/default/files/SleepWakeCycle.pdf. Last accessed December 3, 2018.

17. National Institute of General Medical Sciences. Circadian Rhythms. Available at https://www.nigms.nih.gov/education/pages/factsheet_circadianrhythms.aspx. Last accessed December 3, 2018.

18. Korczak AL, Martynhak BJ, Pedrazzoli M, Brito AF, Louzada FM. Influence of chronotype and social zeitgebers on sleep/wake patterns. Braz J Med Biol Res. 2008;41(10):914-919.

19. Zimmermann LK. Chronotype and the transition to college life. Chronobiol Int. 2011;28(10):904-910.

20. Vollmer C, Michel U, Randler C. Outdoor light at night (LAN) is correlated with eveningness in adolescents. Chronobiol Int. 2012;29(4):502-508.

21. Hughes AT, Piggins HD. Feedback actions of locomotor activity to the circadian clock. Prog Brain Res. 2012;199:305-336.

22. Santrock JW, Mitterer JO. Psychology. 3rd ed. Toronto: McGraw-Hill Ryerson; 2006.

23. Bodenstein C, Heiland I, Schuster S. Temperature compensation and entrainment in circadian rhythms. Phys Biol. 2012;9(3):036011.

24. Mistlberger RE, Skene DJ. Nonphotic entrainment in humans? J Biol Rhythms. 2005;20(4):339-352.

25. Huang ZL, Urade Y, Hayaishi O. The role of adenosine in the regulation of sleep. Curr Top Med Chem. 2011;11(8):1047-1057.

26. Brown GM. Light, melatonin and the sleep-wake cycle. J Psychiatry Neurosci. 1994;19(5):345-353.

27. Kaplan PW, Fisher RS (eds). Imitators of Epilepsy. 2nd ed. New York, NY: Demos Medical Publishing; 2005.

28. Williams RL, Karacan I, Hursch CJ. EEG of Human Sleep: Clinical Applications. New York, NY: John Wiley & Sons; 1974.

29. Kales A, Kales JD. Sleep disorders: recent findings in the diagnosis and treatment of disturbed sleep. N Engl J Med. 1974;290(9):487-499.

30. Chervin RD, Aldrich MS. Sleep onset REM periods during multiple sleep latency tests in patients evaluated for sleep apnea.Am J Respir Crit Care Med. 2000;161(2 Pt 1):426-431.

31. National Sleep Foundation. Sleep Hygiene. Available at https://www.sleepfoundation.org/sleep-topics/sleep-hygiene. Last accessed December 3, 2018.

32. Epstein LJ, Kristo D, Strollo PJ Jr, et al. Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med. 2009;5(3):263-276.

33. National Institute of Neurological Disorders and Stroke. Narcolepsy Fact Sheet. Available at https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Narcolepsy-Fact-Sheet. Last accessed December 3, 2018.

34. Espie CA. Insomnia: conceptual issues in the development, persistence, and treatment of sleep disorder in adults. Annu Rev Psychol. 2002;53:215-243.

35. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013.

36. Beaudreau SA, Spira AP, Stewart A, et al. Validation of the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale in older black and white women. Sleep Med. 2012;13(1):36-42.

37. American Academy of Sleep Medicine. Insomnia: Overview and Facts. Available at http://sleepeducation.org/essentials-in-sleep/insomnia/overview-facts. Last accessed December 3, 2018.

38. American Academy of Sleep Medicine. The Epworth Sleepiness Scale. Available at http://yoursleep.aasmnet.org/pdf/Epworth.pdf. Last accessed December 3, 2018.

39. Sato M, Yamadera W, Matsushima M, Itoh H, Nakayama K. Clinical efficacy of individual cognitive behavior therapy for psychophysiological insomnia in 20 outpatients. Psychiatry Clin Neurosci. 2010;64(2):187-195.

40. Conroy DA, Culebras A. Psychophysiological Insomnia. Available at http://www.medlink.com/article/psychophysiological_insomnia. Last accessed December 3, 2018.

41. Morgan K, Dixon S, Mathers N, Thompson J, Tomeny M. Psychological treatment for insomnia in the regulation of long-term hypnotic drug use. Health Technol Assess. 2004;8(8):1-68.

42. National Sleep Foundation. Relaxation Exercise. Available at https://www.sleepfoundation.org/insomnia/content/relaxation-exercise. Last accessed December 3, 2018.

43. Stanford Health Care. Sleep Restriction and CBTI. Available at https://stanfordhealthcare.org/medical-treatments/c/cognitive-behavioral-therapy-insomnia/procedures/sleep-restriction.html. Last accessed December 3, 2018.

44. Ramakrishnan K, Scheid DC. Treatment options for insomnia. Am Fam Physician. 2007;76(4):517-526.

45. Kaiser Permanente. Sleep Restriction Therapy. Available at https://thrive.kaiserpermanente.org/care-near-you/northern-california/sanjose/wp-content/uploads/sites/7/2015/10/sleep-restriction-rev2_tcm28-557887.pdf. Last accessed December 3, 2018.

46. LexiComp Online. Available at http://online.lexi.com. Last accessed December 3, 2018.

47. Harvard Medical School. Overcoming Insomnia. Available at https://www.health.harvard.edu/newsletter_article/overcoming-insomnia. Last accessed December 3, 2018.

48. Shahid A, Chung SA, Phillipson R, Shapiro CM. An approach to long-term sedative-hypnotic use. Nat Sci Sleep. 2012;4:53-61.

49. Cardinali DP, Srinivasan V, Brzezinski A, Brown GM. Melatonin and its analogs in insomnia and depression. J Pineal Res. 2012;52(4):365-375.

50. Fernández-San-Martín MI, Masa-Font R, Palacios-Soler L, Sancho-Gómez P, Calbó-Caldentey C, Flores-Mateo G. Effectiveness of Valerian on insomnia: a meta-analysis of randomized placebo-controlled trials. Sleep Med. 2010;11(6):505-511.

51. Schröder CM, O'Hara R. Depression and obstructive sleep apnea (OSA). Ann Gen Psychiatry. 2005;4:13.

52. Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med. 2002;165(9):1217-1239.

53. Leinum CJ, Dopp JM, Morgan BJ. Sleep-disordered breathing and obesity: pathophysiology, complications, and treatment.Nutr Clin Pract. 2009;24(6):675-687.

54. Meltzer LJ, Johnson C, Crosette J, Ramos M, Mindell JA. Prevalence of diagnosed sleep disorders in pediatric primary care practices. Pediatrics. 2010;125(6):e1410-e1418.

55. Downey Ralph III. Obstructive Sleep Apnea: Epidemiology. Available at https://emedicine.medscape.com/article/295807-overview#a5. Last accessed December 3, 2018.

56. Peppard PE, Young T, Palta M, Dempsey J, Skatrud J. Longitudinal study of moderate weight change and sleep-disordered breathing. JAMA. 2000;284(23):3015-3021.

57. Barvaux VA, Aubert G, Rodenstein DO. Weight loss as a treatment for obstructive sleep apnoea. Sleep Med Rev. 2000;4(5): 435-452.

58. Strobel RJ, Rosen RC. Obesity and weight loss in obstructive sleep apnea: a critical review. Sleep. 1996;19(2):104-115.

59. Vgontzas AN. Does obesity play a major role in the pathogenesis of sleep apnoea and its associated manifestations via inflammation, visceral adiposity, and insulin resistance? Arch Physiol Biochem. 2008;114(4):211-223.

60. National Institute for Health and Clinical Excellence. Continuous Positive Airway Pressure for the Treatment of Obstructive Sleep Apnoea/Hypopnoea Syndrome. London: National Institute for Health and Clinical Excellence; 2008.

61. Rajala R, Partinen M, Sane T, Pelkonen R, Huikuri K, Seppäläinen AM. Obstructive sleep apnoea syndrome in morbidly obese patients. J Intern Med. 1991;230(2):125-129.

62. Qaseem A, Holty J-EC, Owens DK, Dallas P, Starkey M, Shekelle P. Management of obstructive sleep apnea in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2013;159(7):471-483.

63. National Heart, Lung and Blood Institute. CPAP. Available at https://www.nhlbi.nih.gov/health-topics/cpap. Last accessed December 3, 2018.

64. Barbé F, Durán-Cantolla J, Sánchez-de-la-Torre M, et al. Effect of continuous positive airway pressure on the incidence of hypertension and cardiovascular events in nonsleepy patients with obstructive sleep apnea: a randomized controlled trial. JAMA. 2012;307(20):2161-2168.

65. Abuzaid AS, Al Ashry HS, Elbadawi A, et al. Meta-analysis of cardiovascular outcomes with continuous positive airway pressure therapy in patients with obstructive sleep apnea. Am J Cardiol. 2017;120(4):693-699.

66. Giles TL, Lasserson TJ, Smith BJ, White J, Wright J, Cates CJ. Continuous positive airways pressure for obstructive sleep apnoea in adults. Cochrane Database Syst Rev. 2006;(3):CD001106.

67. Aurora RN, Casey KR, Kristo D, et al. Practice parameters for the surgical modifications of the upper airway for obstructive sleep apnea in adults. Sleep. 2010;33(10):1408-1413.

68. American Academy of Sleep Medicine. Narcolepsy: Overview and Facts. Available at http://sleepeducation.org/essentials-in-sleep/narcolepsy. Last accessed December 3, 2018.

69. Sharpless BA, Barber JP. Lifetime prevalence rates of sleep paralysis: a systematic review. Sleep Med Rev. 2011;15(5):311-315.

70. Hishikawa Y. Sleep paralysis. In: Guilleminault C, Dement WC, Passouant P (eds.) Narcolepsy. New York, NY: Spectrum; 1976: 97-124.

71. Ohayon MM, Zulley J, Guilleminault C, Smirne S. Prevalence and pathologic associations of sleep paralysis in the general population. Neurology. 1999;52(6):1194-1200.

72. Cheyne JA. A Webpage About Sleep Paralysis and Associated Hypnagogic and Hypnopompic Experiences. Available at https://sleeptechnologists.org/article/view/389. Last accessed December 3, 2018.

73. Cheyne JA, Rueffer SD, Newby-Clark IR. Hypnagogic and hypnopompic hallucinations during sleep paralysis: neurological and cultural construction of the night-mare. Conscious Cogn. 1999;8(3):319-337.

74. Mitler MM, Hajdukovic R, Erman M, Koziol JA. Narcolepsy. J Clin Neurophysiol. 1990;7(1):93-118.

75. Rubin RL, Hajdukovich RM, Mitler MM. HLA-DR2 association with excessive somnolence in narcolepsy does not generalize to sleep apnea and is not accompanied by systemic autoimmune abnormalities. Clin Immunol Immunopathol. 1988;49(1):149-158.

76. Mignot E, Hayduk R, Black J, Grumet FC, Guilleminault C. HLA DQB1*0602 is associated with cataplexy in 509 narcoleptic patients. Sleep. 1997;20(11):1012-1020.

77. Oka Y, Inoue Y, Kanbayashi T, et al. Narcolepsy without cataplexy: 2 subtypes based on CSF hypocretin-1/orexin-A findings.Sleep. 2006;29(11):1439-1443.

78. Billiard M, Dauvilliers Y, Dolenc-Groselj L, Lammers GJ, Mayer G, Sonka K. Management of narcolepsy in adults. In: Gilhus NE, Barnes MP, Brainin M (eds). European Handbook of Neurological Management. 2nd ed. Vol. 1. Oxford: Wiley-Blackwell; 2011: 513-528.

79. Morgenthaler TI, Kapur VK, Brown T, et al. Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin. Sleep. 2007;30(12):1705-1711.

80. Billiard M. Narcolepsy: current treatment options and future approaches. Neuropsychiatr Dis Treat. 2008;4(3):557-566.

81. Ferraro L, Antonelli T, Beggiato S, Tomasini MC, Fuxe K, Tanganelli S. The vigilance promoting drug modafinil modulates serotonin transmission in the rat prefrontal cortex and dorsal raphe nucleus: possible relevance for its postulated antidepressant activity. Mini Rev Med Chem. 2013;13(4):478-492.

82. Mamelak M, Swick T, Emsellem H. 12-week open-label, multicenter study evaluating the safety and patient-reported efficacy of sodium oxybate in patients with narcolepsy and cataplexy. Sleep Med. 2015;16:52-58.

83. Xyrem International Study Group Sodium oxybate demonstrates long-term efficacy for the treatment of cataplexy in patients with narcolepsy. Sleep Med. 2004;5:119-123.

84. Black J, Swick T, Bogan R. Impact of sodium oxybate, modafinil, and combination treatment on excessive daytime sleepiness in patients who have narcolepsy with or without cataplexy. Sleep Med. 2016;24:57-62.

85. Black J, Pardi D, Hornfeldt CS. The nightly administration of sodium oxybate results in significant reduction in the nocturnal sleep disruption of patients with narcolepsy. Sleep Med. 2009;10:829-835.

86. Black J, Houghton WC. Sodium oxybate improves excessive daytime sleepiness in narcolepsy. Sleep. 2006;29:939-946.

87. Prinzmetal M, Bloomberg W. The use of benzedrine for treatment of narcolepsy. JAMA. 1935;105:2051-2054.

88. Ishizuka T, Murakami M, Yamatodani A. Involvement of central histaminergic systems in modafinil-induced but not methylphenidate-induced increases in locomotor activity in rats. Eur J Pharmacol. 2008;578(2-3):209-215.

89. Engber TM, Koury EJ, Dennis SA, Miller MS, Contreras PC, Bhat RV. Differential patterns of regional c-Fos induction in the rat brain by amphetamine and the novel wakefulness-promoting agent modafinil. Neurosci Lett. 1998;241(2-3):95-98.

90. Narcolepsy Network. Support Groups. Available at http://narcolepsynetwork.org/resources/support-groups. Last accessed December 3, 2018.

91. Kryger MH, Roth T, Dement WC. Principles and Practice of Sleep Medicine. 6th ed. Philadelphia, PA: Elsevier Saunders; 2015.

92. MedlinePlus. Idiopathic Hypersomnia. Available at https://www.nlm.nih.gov/medlineplus/ency/article/000803.htm. Last accessed December 3, 2018.

93. Kleine Levin Syndrome Foundation. What is KLS? Available at https://klsfoundation.org/what-is-kleine-levin-syndrome. Last accessed December 3, 2018.

94. Arnulf I, Lin L, Gadoth N, et al. Kleine-Levin syndrome: a systematic study of 108 patients. Ann Neurol. 2008;63(4):482-493.

95. Picchietti D, Allen RP, Walters AS, Davidson JE, Myers A, Ferini-Strambi L. Restless legs syndrome: prevalence and impact in children and adolescents—the Peds REST study. Pediatrics. 2007;120(2):253-266.

96. MedlinePlus. Sleepwalking. Available at https://www.nlm.nih.gov/medlineplus/ency/article/000808.htm. Last accessed December 3, 2018.

97. Mayo Clinic. Sleepwalking. Available at https://www.mayoclinic.org/diseases-conditions/sleepwalking/symptoms-causes/syc-20353506. Last accessed December 3, 2018.

98. Pressman MR. Sleep driving: sleepwalking variant or misuse of z-drugs? Sleep Med Rev. 2011;15(5):285-292.

99. National Sleep Foundation. Sleepwalking. Available at https://www.sleepfoundation.org/sleep-disorders-problems/abnormal-sleep-behaviors/sleepwalking. Last accessed December 3, 2018.

100. Mume CO. Prevalence of sleepwalking in an adult population. Libyan J Med. 2010;5:2143.

101. Pressman MR. Factors that predispose, prime and precipitate NREM parasomnias in adults: clinical and forensic implications.Sleep Med Rev. 2007;11(1):5-33.

102. Ohayon MM, Mahowald MW, Dauvilliers Y, Krystal AD, Léger D. Prevalence and comorbidity of nocturnal wandering in the U.S. adult general population. Neurology. 2012;78(20):1583-1589.

103. Sadeh A. Assessment of intervention for infant night waking: parental reports and activity-based home monitoring. J Consult Clin Psychol. 1994;62(1):63-68.

104. Harris M, Grunstein RR. Treatments for somnambulism in adults: assessing the evidence. Sleep Med Rev. 2009;13(4):295-297.

105. Howell MJ. Parasomnias: an updated review. Neurotherapeutics. 2012;9(4):753-775.

106. Guilleminault C, Kirisoglu C, Bao G, Arias V, Chan A, Li KK. Adult chronic sleepwalking and its treatment based on polysomnography. Brain. 2005;128(Pt 5):1062-1069.

107. BMJ Group. Parasomnias in Children. Available at https://bestpractice.bmj.com/topics/en-gb/1177. Last accessed December 3, 2018.

108. Hurwitz TD, Mahowald MW, Schenck CH, Schluter JL, Bundlie SR. A retrospective outcome study and review of hypnosis as treatment of adults with sleepwalking and sleep terror. J Nerv Ment Dis. 1991;179(4):228-233.

109. Hauri PJ, Silber MH, Boeve BF. The treatment of parasomnias with hypnosis: a 5-year follow-up study. J Clin Sleep Med. 2007;3(4):369-373.

110. Frank NC, Spirito A, Stark L, Owens-Stively J. The use of scheduled awakenings to eliminate childhood sleepwalking.J Pediatr Psychol. 1997;22(3):345-353.

111. Remedy's Health Communities. Restless Legs Syndrome/Periodic Limb Movement Disorder Overview. Available athttp://www.healthcommunities.com/rls-plmd/overview-restless-legs-syndrome-periodic-limb-movement-disorder.shtml. Last accessed December 3, 2018.

112. National Institute of Neurological Disorders and Stroke. Restless Legs Syndrome Fact Sheet. Available at https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Restless-Legs-Syndrome-Fact-Sheet. Last accessed December 3, 2018.

113. Rama AN, Kushida CA. Restless legs syndrome and periodic limb movement disorder. Med Clin North Am. 2004;88(3):653-667.

114. Bozorg AM. Restless Legs Syndrome. Available at https://emedicine.medscape.com/article/1188327-overview. Last accessed December 3, 2018.

115. Mitchell UH. Nondrug-related aspect of treating Ekbom disease, formerly known as restless legs syndrome. Neuropsychiatr Dis Treat. 2011;7:251-257.

116. Allen RP, Earley CJ. Validation of the Johns Hopkins restless legs severity scale. Sleep Med. 2001;2(3):239-242.

117. Atkinson MJ, Allen RP, DuChane J, Murray C, Kushida C, Roth T; RLS Quality of Life Consortium. Validation of the Restless Legs Syndrome Quality of Life Instrument (RLS-QLI): findings of a consortium of national experts and the RLS Foundation. Qual Life Res. 2004;13(3):679-693.

118. Garcia-Borreguero D, Ferini-Strambi L, Kohnen R, et al. European guidelines on management of restless legs syndrome: report of a joint task force by the European Federation of Neurological Societies, the European Neurological Society and the European Sleep Research Society. Eur J Neurol. 2012;19(11):1385-1396.

119. NPS Radar. Pramipexole (Sifrol) for Severe Primary Restless Legs Syndrome. Available at https://www.nps.org.au/radar/articles/pramipexole-sifrol-for-severe-primary-restless-legs-syndrome. Last accessed December 3, 2018.

120. Bandolier. Gabapentin for RLS. Available at http://www.bandolier.org.uk/booth/RLS/gabap.html. Last accessed December 3, 2018.

121. Hayes WJ, Lemon MD, Farver DK. Gabapentin enacarbil for treatment of restless legs syndrome in adults. Ann Pharmacother. 2012;46(2):229-239.

122. Allen R, Chen C, Soaita A, et al. A randomized, double-blind, 6-week, dose-ranging study of pregabalin in patients with restless legs syndrome. Sleep Med. 2010;11(6):512-519.

123. Garcia-Borreguero D, Larrosa O, et al. Treatment of restless legs syndrome with pregabalin: a double-blind, placebo-controlled study. Neurology. 2010;74(23):1897-1904.

124. Mitchell UH, Myrer JW, Johnson AW, Hilton SC. Restless legs syndrome and near-infrared light: an alternative treatment option. Physiother Theory Pract. 2011;27(5):345-351.

125. Fulda S, Wetter TC. Where dopamine meets opioids: a meta-analysis of the placebo effect in restless legs syndrome treatment studies. Brain. 2008;131(Pt 4):902-917.

126. Sensory Medical. Relaxis for Medical Professionals. Available at http://myrelaxis.com/relaxis-clinical-data. Last accessed December 3, 2018.

127. Lee KC, Winickoff JP, Kim MK, et al. Resident physicians' use of professional and nonprofessional interpreters: a national survey. JAMA. 2006;296(9):1050-1053.

128. Hwa-Froelich DA, Westby CE. Considerations when working with interpreters. Commun Disord Q. 2003;24(2):78-85.

129. Lynch EW. Developing cross-cultural competence. In: Lynch EW, Hanson MJ (eds). Developing Cross-Cultural Competence: A Guide for Working With Children and Their Families. 4th ed. Baltimore, MD: Brookes Publishing Company; 2011.

130. Herndon E, Joyce L. Getting the most from language interpreters. Fam Pract Manag. 2004;11(6):37-40.

131. Lee E. Cross-cultural communication: therapeutic use of interpreters. In: Lee E (ed). Working With Asian Americans: A Guide For Clinicians. New York, NY: The Guilford Press; 2000.

132. Raval H, Smith JA. Therapists' experiences of working with language interpreters. Int J Ment Health. 2003;32(2):6-31.

Evidence-Based Practice Recommendations Citations

1. Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017;13(2):307-349. Available at https://aasm.org/resources/clinicalguidelines/040515.pdf. Last accessed December 7, 2018.

2. Qaseem A, Dallas P, Owens DK, Starkey M, Holty JE, Shekelle P, Clinical Guidelines Committee of the American College of Physicians. Diagnosis of obstructive sleep apnea in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2014;161(3):210-220. Available at http://annals.org/aim/fullarticle/1892620. Last accessed December 7, 2018.

3. Ramar K, Dort LC, Katz SG, et al. Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015. J Clin Sleep Med. 2015;11(7):773-827. Available at http://jcsm.aasm.org/ViewAbstract.aspx?pid=30098. Last accessed December 7, 2018.

4. Billiard M, Dauvilliers Y, Dolenc-Groselj L, Lammers GJ, Mayer G, Sonka K. Management of narcolepsy in adults. In: Gilhus NE, Barnes MP, Brainin M (eds). European Handbook of Neurological Management. 2nd ed. Vol 1. Oxford: Wiley-Blackwell; 2011. Available at https://www.eaneurology.org/fileadmin/user_upload/guidline_papers/EFNS_guideline_2011_Management_of_narcolepsy_in_adults.pdf. Last accessed December 7, 2018.

5. Aurora RN, Kristo DA, Bista SR, et al. The treatment of restless legs syndrome and periodic limb movement disorder in adults—an update for 2012: practice parameters with an evidence-based systematic review and meta-analyses: an American Academy of Sleep Medicine clinical practice guideline. Sleep. 2012;35(8):1039-1062. Available at https://aasm.org/resources/practiceparameters/updateto.pdf. Last accessed December 7, 2018.

57922 • Domestic Violence: The Florida Requirement

Marjorie Conner Allen, BSN, JD

Alice Yick Flanagan, PhD, MSW

www.netce.com

Copyright © 2019 NetCE, All rights reserved.

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

Table of Contents

57922 • Domestic Violence: The Florida Requirement

Course Overview

Audience

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Division Planner

Division Planner Disclosure

Director of Development and Academic Affairs

Director Disclosure Statement

About the Sponsor

Disclosure Statement

1. INTRODUCTION

2. DEFINING DOMESTIC VIOLENCE

3. NATIONAL AND STATE STATISTICS AND LEGISLATION

FLORIDA

4. IDENTIFYING GROUPS AT RISK FOR DOMESTIC VIOLENCE

PREGNANT WOMEN

CHILDREN

ELDERLY

MEN

LESBIAN, GAY, BISEXUAL, AND TRANSGENDER VICTIMS

5. CHARACTERISTICS OF PERPETRATORS OF DOMESTIC VIOLENCE

6. SCREENING FOR DOMESTIC VIOLENCE AND ABUSE

7. ASSESSING DOMESTIC VIOLENCE AND ABUSE

CULTURALLY SENSITIVE ASSESSMENT

8. INTERVENTIONS FOR DOMESTIC VIOLENCE AND ABUSE

9. DOCUMENTATION AND FOLLOW-UP

Works Cited

Evidence-Based Practice Recommendations Citations

57922 • Domestic Violence: The Florida Requirement

Education Category. Ethics - Human Rights

Release Date. 08/01/2019

Expiration Date. 07/31/2022

Course Overview

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

Audience

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

Course Objective

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

Learning Objectives

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

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

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

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

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

Faculty

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

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

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

Faculty Disclosure

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

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

Division Planner

William E. Frey, DDS, MS, FICD

Division Planner Disclosure

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

Director of Development and Academic Affairs

Sarah Campbell

Director Disclosure Statement

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

About the Sponsor

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

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

Disclosure Statement

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

1. INTRODUCTION

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

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

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

2. DEFINING DOMESTIC VIOLENCE

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

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

3. NATIONAL AND STATE STATISTICS AND LEGISLATION

Domestic violence is one of the most serious public health problems in the United States [4]. More than 36.4% of women and 33.6% of men have a lifetime history of IPV [4]. In Florida, the weighted lifetime prevalence of IPV (including rape, physical violence, and/or stalking) is 37.3% among women and 30.9% among men [5]. Although many of these incidents are relatively minor and consist of pushing, grabbing, shoving, slapping, and hitting, IPV resulted in approximately 1,300 deaths in the United States in 2017, with 162 deaths reported in Florida [7,8]. One of the difficulties in addressing the problem is that abuse is prevalent in all demographics, regardless of age, ethnicity, race, religious denomination, education, or socioeconomic status [2].

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

The national rate of nonfatal domestic violence against women declined 72% between 1993 and 2011 [11]. The rate of overall violent crime fell by nearly 60% in this same time period [11]. Studies reveal that several factors may have contributed to the reduction in violence, including a decline in the marriage rate and decrease of domesticity, better access to federally funded domestic violence shelters, improvements in women's economic status, and demographic trends, such as the aging of the population [13,14]. Of note, declines in the economy and stress associated with financial hardship and unemployment are significant contributors to IPV in the United States. Following the economic downturn in late 2008, there was a significant increase in the use of the National Domestic Violence Hotline in 2009, with more than half of victims reporting a change in household financial situation in the last year [15].

FLORIDA

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

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

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

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

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

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

In 2017, the FDLE reported 106,979 domestic violence offenses [6]. In general, domestic violence rates have been declining since 1998. An estimated 20.2% of domestic violence incidents involved spouses and 28.4% involved cohabitants; 11.5% of the victims were parents of the offenders. Domestic violence offenses resulted in the death of 162 victims in Florida in 2017, a number that has been decreasing since 2014 [6]. Domestic violence accounted for more than 15% of the state's murders in 2017 [6].

In their 2018 Annual Report, Fatality Review Teams summarized 32 cases of domestic violence fatalities and near fatalities [49]. The most significant findings included the following observations [49]:

- The perpetrators were predominantly male (90%) with female victims (84%) and had prior criminal histories, generally (55%) and for domestic violence specifically (48%).

- In 32% of fatalities, the perpetrators had a known "do not contact" order filed against them, and 32% of perpetrators had a known permanent injunction for protection against them filed by someone other than the victim.

- Substance abuse histories by the perpetrator was identified in 62% of the cases and diagnosed mental health disorders in 30%.

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

To obtain a copy of the Executive Summary of the 2018 Florida Domestic Violence Fatality Review Team Annual Report, please visit https://www.fcadv.org/sites/default/files/FACES%20OF%20FATALITY%20VIII%20web.pdf.

4. IDENTIFYING GROUPS AT RISK FOR DOMESTIC VIOLENCE

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

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

For every victim of abuse, there is also a perpetrator. Like their victims, perpetrators of domestic violence come from all socioeconomic backgrounds, races, religions, and walks of life [27]. Accordingly, healthcare professionals should likewise be aware that seemingly supportive family members may, in fact, be abusers.

PREGNANT WOMEN

Because a gynecologist or obstetrician is frequently a woman's primary care physician, the American College of Obstetricians and Gynecologists (ACOG) recommends that all women be routinely assessed for signs of IPV (i.e., physical and psychologic abuse, reproductive coercion, and progressive isolation), including during prenatal visits, and providers should offer support and referral information for those being abused [28]. According to the ACOG, IPV affects as many as 324,000 pregnant women each year [25]. A meta-analysis of 92 independent studies found that the average reported prevalence of emotional abuse during pregnancy was 28.4%, physical abuse was 13.8%, and sexual abuse was 8% [51]. As with all domestic violence statistics, these estimates are presumed to be lower than the actual incidence as a result of under-reporting and lack of data on women whose pregnancies ended in fetal or maternal death. This makes IPV more prevalent among pregnant women than some of the health conditions included in prenatal screenings, including pre-eclampsia and gestational diabetes [25]. Because 96% of pregnant women receive prenatal care, this is an optimal time to assess for domestic violence and develop trusting relationships with the women. Possible factors that may predispose pregnant women to IPV include being unmarried, lower socioeconomic status, young maternal age, unintended pregnancy, delayed prenatal care, lack of social support, and use of tobacco, alcohol, or illegal drugs [25,51].

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

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

CHILDREN

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

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

In addition to witnessing violence, various studies have shown that these children may also become direct victims of violence, and children who both witness and experience violence are at the greatest risk for adverse psychosocial outcomes [53]. Research indicates that between 30% and 60% of husbands who batter their wives also batter their children [35]. Moreover, victims of abuse will often turn on their children; statistics demonstrate that 85% of domestic violence victims abuse or neglect their children. The 2017 Crime in Florida report found that more than 16% of domestic homicide victims were children killed by a parent [6]. Teenage children are also victimized. According to the U.S. Department of Justice, between 1980 and 2008, 17.5% of all homicides against female adolescents 12 to 17 years of age were committed by an intimate partner [36]. Among young women (18 to 24 years of age), the rate is 42.9%. Abused teens often do not report the abuse. Individuals 12 to 19 years of age report only 35.7% of crimes against them, compared with 54% in older age groups [37]. Accordingly, healthcare professionals who see young children and adolescents in their practice (e.g., pediatricians, family physicians, school nurses, pediatric nurse practitioners, community health nurses) should have the tools necessary to detect these "silent victims" of domestic violence and to intervene quickly to protect young children and adolescents from further abuse. Without such critical intervention, the cycle of violence will never end.

ELDERLY

Abused and neglected elders, who may be mistreated by their spouses, partners, children, or other relatives, are among the most isolated of all victims of family violence. In a national study conducted by the National Institute of Justice in 2010, 4.6% of participants (community dwelling adults 60 years of age or older) were victims of emotional abuse in the past year, 1.6% physical abuse, 0.6% sexual abuse, 5.1% potential neglect, and 5.2% current financial abuse by a family member [38]. The estimated annual incidence of all elder abuse types is 2% to 10%, but it is believed to be severely under-measured. According to one study, only 1 in 14 cases of elder abuse are reported to the authorities [39].

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

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

Evidence Based Practice Recommendation

The U.S. Preventive Services Task Force concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening all elderly or vulnerable adults (physically or mentally dysfunctional) for abuse and neglect.

https://annals.org/aim/fullarticle/1558517/screening-intimate-partner-violence-abuse-elderly-vulnerable-adults-u-s

Last Accessed: July 26, 2019

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

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

MEN

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

LESBIAN, GAY, BISEXUAL, AND TRANSGENDER VICTIMS

Domestic violence exists in lesbian, gay, bisexual, and transgender (LGBT) communities, and the rates are thought to mirror those of heterosexual women—approximately 25% [43]. However, women living with female intimate partners experience less IPV than women living with men [6]. Conversely, men living with male intimate partners experience more IPV than do men who live with female intimate partners [6]. In addition, 78% of IPV homicide victims reported in 2017 were transgender women or cisgender men [24]. This supports other statistics indicating that IPV is perpetrated primarily by men. A form of abuse specific to the gay community is for an abuser to threaten or to proceed with "outing" a partner to others [41,43].

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

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

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

5. CHARACTERISTICS OF PERPETRATORS OF DOMESTIC VIOLENCE

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

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

In addition, abusers often suffer from low self-esteem and their sense of self and identity is directly connected to their partner [12]. Extreme dependence is common in both abusers and those being abused. Due to low self-esteem and self-worth, emotional dependence often occurs in both partners, but even more so in the abuser. Emotional dependence in the victim stems from both physical and psychologic abuse, which results in a negative self-image and lack of self-worth. Financial dependence is also very common, as the abuser often withholds or controls financial resources to maintain power over the victim [27].

6. SCREENING FOR DOMESTIC VIOLENCE AND ABUSE

Evidence Based Practice Recommendation

The U.S. Preventive Services Task Force recommends that clinicians screen women of childbearing age for intimate partner violence, such as domestic violence, and provide or refer women who screen positive to intervention services. This recommendation applies to women who do not have signs or symptoms of abuse.

https://annals.org/aim/fullarticle/1558517/screening-intimate-partner-violence-abuse-elderly-vulnerable-adults-u-s

Last Accessed: July 26, 2019

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

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

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

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

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

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

7. ASSESSING DOMESTIC VIOLENCE AND ABUSE

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

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

Table 1: ASSESSMENT OF IMMEDIATE SAFETY FOR DOMESTIC VIOLENCE VICTIMS

Are you in immediate danger?

Is your partner at the health facility now?

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

Do you have somewhere safe to go?

Have there been threats or direct abuse of the children (if s/he has children)?

Are you afraid your life may be in danger?

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

Has your partner used weapons, alcohol or drugs?

Has your partner ever held you or your children against your will?

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

Has your partner ever threatened to kill you, him/herself or your children?

Source: [35]

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

CULTURALLY SENSITIVE ASSESSMENT

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

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

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

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

8. INTERVENTIONS FOR DOMESTIC VIOLENCE AND ABUSE

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

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

In Florida, a 24-hour domestic violence hotline is available for toll-free counseling and information. The number is 800-500-1119. The counselors answering the toll-free line may refer the victim to her or his local domestic violence center. A list of Florida certified domestic violence centers organized by county and city may also be found on the Florida Coalition Against Domestic Violence website at https://www.fcadv.org/local-center-services. As of 2018, Florida had 72 certified domestic violence centers that provide information and referral services, counseling and case management services, a 24-hour hotline, temporary emergency shelter for more than 24 hours, educational services for community awareness relative to domestic violence, assessment and appropriate referral of resident children, and training for law enforcement personnel.

9. DOCUMENTATION AND FOLLOW-UP

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

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

Works Cited

1. Centers for Disease Control and Prevention. Preventing Intimate Partner Violence. Available at https://www.cdc.gov/ViolencePrevention/intimatepartnerviolence/fastfact.html. Last accessed July 18, 2019.

2. Florida Department of Children and Families. What Is Domestic Violence? Available at https://www.myflfamilies.com/service-programs/domestic-violence/what-is-domestic-violence.shtml. Last accessed July 18, 2019.

3. Florida Statutes. Section 741.28 (2018): Domestic Violence; Definitions. Available at http://www.leg.state.fl.us/statutes/index.cfm?App_mode=Display_Statute&URL=0700-0799/0741/Sections/0741.28.html. Last accessed July 18, 2019.

4. Smith, SG, Zhang, X, Basile, KC, et al. The National Intimate Partner and Sexual Violence Survey (NISVS): 2015 Data Report: Updated Release. Atlanta, GA: National Center for Injury Prevention and Control, Centers for Disease Control and Prevention; 2015.

5. Smith, SG, Chen, J, Basile, KC, et al. The National Intimate Partner and Sexual Violence Survey (NISVS): 2010–2012 State Report. Atlanta, GA: National Center for Injury Prevention and Control, Centers for Disease Control and Prevention; 2014.

6. Florida Department of Law Enforcement. Crime in Florida, 2017: Florida Uniform Crime Report. Available at https://www.fdle.state.fl.us/FSAC/UCR/2017/CIFAnnual17.aspx. Last accessed July 18, 2019.

7. Federal Bureau of Investigation. Crime in the United States, 2017. Available at https://ucr.fbi.gov/crime-in-the-u.s/2017. Last accessed July 18, 2019.

8. Florida Department of Law Enforcement. Crime in Florida, 2017: Florida Uniform Crime Report. Available at https://www.fdle.state.fl.us/FSAC/UCR/2017/2017SA_CIF.aspx. Last accessed July 18, 2019.

9. National Center for Injury Prevention and Control. Costs of Intimate Partner Violence Against Women in the United States. Atlanta, GA: Centers for Disease Control and Prevention; 2003.

10. Institute for Women's Policy Research. The Economic Cost of Intimate Partner Violence, Sexual Assault, and Stalking. Available at https://iwpr.org/wp-content/uploads/2017/08/B367_Economic-Impacts-of-IPV-08.14.17.pdf. Last accessed July 18, 2019.

11. Catalano S. Intimate Partner Violence: Attributes of Victimization, 1993–2011. Washington, DC: Bureau of Justice Statistics, U.S. Department of Justice; 2013.

12. Capaldi DM, Knoble NB, Shortt JW, Kim HK. A systematic review of risk factors for intimate partner violence. Partner Abuse. 2012;3(2):231-280.

13. National Institute of Justice. The decline of intimate partner homicide. National Institute of Justice Journal. 2005;252.

14. Farmer A, Tiefenthaler J. Explaining the recent decline in domestic violence. Contemp Econ Policy. 2003;21(s):158-172.

15. National Domestic Violence Hotline. Increased Financial Stress Affects Domestic Violence Victims. Available at https://www.thehotline.org/2009/01/30/increased-financial-stress-affects-domestic-violence-victims-2. Last accessed July 18, 2019.

16. Crane CA, Hawes SW, Weinberger AH. Intimate partner violence victimization and cigarette smoking: a meta-analytic review. Trauma Violence Abuse. 2013;14(4):305-315.

17. 1995 Florida Session Law Service Chapter 95-187, Domestic Violence, General Provisions.

18. Florida Governor's Task Force on Domestic and Sexual Violence. Florida Mortality Review Project. Jacksonville, FL: Office of the Governor; 1997.

19. Florida Department of Law Enforcement. Florida Domestic Violence Fatality Review Team Annual Report, 2001. Available at https://www.dcf.state.fl.us/programs/domesticviolence/publications/docs/FatalityReview2001.pdf. Last accessed July 18, 2019.

20. Florida Department of Law Enforcement. Florida Domestic Violence Fatality Review Team Annual Report, 2002. Available at http://www.ndvfri.org/reports/florida/Florida_Statewide_AnnualReport_2002.pdf. Last accessed July 18, 2019.

21. Florida Department of Law Enforcement. Florida Domestic Violence Fatality Review Team 2008 Annual Report: Executive Summary. Available at http://www.dcf.state.fl.us/programs/domesticviolence/publications/docs%5CFatalityReview2008.pdf. Last accessed July 18, 2019.

22. Florida Department of Children and Families. Violence Free Florida! Ending Abuse—Improving Lives. Available at https://www.dcf.state.fl.us/programs/domesticviolence/publications/docs/DVAnnualReport0102.pdf. Last accessed July 18, 2019.

23. Florida Coalition against Domestic Violence. Domestic Violence in Florida: 2010–2011 Annual Report to the Legislature. Available at http://www.dcf.state.fl.us/programs/domesticviolence/publications/docs/DVAnnualReport1011.pdf. Last accessed November 21, 2017.

24. National Coalition of Anti-Violence Programs. Lesbian, Gay, Bisexual, Transgender, Queer, and HIV-Affected Intimate Partner Violence in 2015. Available at http://avp.org/wp-content/uploads/2019/01/NCAVP-HV-IPV-2017-report.pdf. Last accessed July 18, 2019.

25. American College of Obstetricians and Gynecologists. Committee Opinion: Intimate Partner Violence. Available at http://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-on-Health-Care-for-Underserved-Women/Intimate-Partner-Violence. Last accessed July 18, 2019.

26. Rhodes KV, Kothari CL, Dichter M, Cerulli C, Wiley J, Marcus S. Intimate partner violence identification and response: time for a change in strategy. J Gen Intern Med. 2011;26(8):894-899.

27. National Center for Victims of Crime. Intimate Partner Violence. Available at http://victimsofcrime.org/docs/default-source/ncvrw2015/2015ncvrw_stats_ipv.pdf?sfvrsn=2. Last accessed July 18, 2019.

28. American College of Obstetricians and Gynecologists. Committee Opinion: Intimate Partner Violence. Available at https://www.acog.org/-/media/Committee-Opinions/Committee-on-Health-Care-for-Underserved-Women/co518.pdf?dmc=1&ts=20190624T1711014545. Last accessed July 18, 2019.

29. Cook J, Bewley S. Acknowledging a persistent truth: domestic violence in pregnancy. J R Soc Med. 2008;101:358-363.

30. Newberger EH, Barkan SE, Lieberman ES, et al. Abuse of pregnant women and adverse birth outcome: current knowledge and implications for practice. JAMA. 1992;267(17):2370-2372.

31. Hamby S, Finkelhor D, Turner H, Ormrod R. Children's Exposure to Intimate Partner Violence and Other Family Violence. Rockville, MD: U.S. Department of Justice Office of Juvenile Justice and Delinquency Prevention; 2011.

32. Child Welfare Information Gateway. Child Witnesses to Domestic Violence. Available at https://www.childwelfare.gov/pubPDFs/witnessdv.pdf. Last accessed July 18, 2019.

33. Kitzman KM, Gaylord NK, Holt AR, Kenny ED. Child witnesses to domestic violence: a meta-analytic review. J Consult Clin Psychol. 2003;71(2):339-352.

34. Finkelhor D, Turner H, Ormrod R, Hamby S, Kracke K. Children's Exposure to Violence: A Comprehensive National Survey. Rockville, MD: U.S. Department of Justice Office of Juvenile Justice and Delinquency Prevention; 2009.

35. Family Violence Prevention Fund. National Consensus Guidelines on Identifying and Responding to Domestic Violence Victimization in Health Care Settings. San Francisco, CA: Family Violence Prevention Fund; 2007.

36. Cooper A, Smith EL. Homicide Trends in the United States, 1980–2008. Washington, DC: Bureau of Justice Statistics; 2011.

37. U.S. Bureau of Justice. Press Release: Violence Rates Among Intimate Partners Differ Greatly According to Age. Available at https://www.bjs.gov/content/pub/press/ipva99pr.cfm. Last accessed July 18, 2019.

38. Acierno R, Hernandez MA, Amstadter AB, et al. Prevalence and correlates of emotional, physical, sexual, and financial abuse and potential neglect in the United States: the National Elder Mistreatment Study. Am J Public Health. 2010;100(2):292-297.

39. National Council on Aging. Elder Abuse Facts. Available at https://www.ncoa.org/public-policy-action/elder-justice/elder-abuse-facts/. Last accessed July 18, 2019.

40. Yon Y, Ramiro-Gonzalez M, Mikton CR, et al. The prevalence of elder abuse in institutional settings: a systematic review and meta-analysis. Eur J Public Health. 2019;29(1):58-67.

41. Calton JM, Cattaneo LB, Gebhard KT. Barriers to help seeking for lesbian, gay, bisexual, transgender, and queer survivors of intimate partner violence. Trauma Violence Abuse. 2016;17(5):585-600.

42. Compton MT. Clinical Manual of Prevention in Mental Health. 5th ed. Washington, DC: American Psychiatric Publishing; 2010.

43. Ard KL, Makadon HJ. Addressing intimate partner violence in lesbian, gay, bisexual, and transgender patients. J Gen Intern Med. 2011;26(8):930-933.

44. Bhandari M, Dosanjh S, Tornetta P 3rd, Matthews D, Violence Against Women Health Research Collaborative. Musculoskeletal manifestations of physical abuse after intimate partner violence. J Trauma. 2006;61(6):1473-1479.

45. Basile KC, Hertz MF, Back SE. Intimate Partner Violence and Sexual Violence Victimization Assessment Instruments for Use in Healthcare Settings: Version 1. Atlanta, GA: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control; 2007.

46. Sprague S, Madden K, Simunovic N, et al. Barriers to screening for intimate partner violence. Women Health. 2012;52(6):587-605.

47. Panos PT, Panos AJ. A model for a culture-sensitive assessment of patients in health care settings. Soc Work Health Care. 2000;31(1):49-62.

48. Pachter LM. Culture and clinical care: folk illness beliefs and behaviors and their implications for health care delivery. JAMA. 1994;271(9):690-695.

49. Florida Domestic Violence Fatality Review Team. Faces of Fatality, 2018. Available at https://www.fcadv.org/sites/default/files/FACES%20OF%20FATALITY%20VIII%20web.pdf Last accessed July 18, 2019.

50. de Boinville M. Screening for Domestic Violence in Health Care Settings. Available at https://aspe.hhs.gov/report/screening-domestic-violence-health-care-settings. Last accessed July 18, 2019.

51. James L, Brody D, Hamilton Z. Risk factors for domestic violence during pregnancy: a meta-analytic review. Violence Vict. 2013;28(3):359-380.

52. U.S. Department of Justice. Report of the Attorney General's National Task Force on Children Exposed to Violence. Available at https://www.justice.gov/defendingchildhood/cev-rpt-full.pdf. Last accessed July 18, 2019.

53. Ellonen N, Piispa M, Peltonen K, Oranen M. Exposure to parental violence and outcomes of child psychosocial adjustment. Violence Vict. 2013;28(1):3-15.

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

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

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

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

58. Catalano S, Smith E, Snyder H, Rand M. Female Victims of Violence. Available at https://www.bjs.gov/content/pub/pdf/fvv.pdf. Last accessed July 18, 2019.

Evidence-Based Practice Recommendations Citations

1. U.S. Preventive Services Task Force. Screening for intimate partner violence and abuse of elderly and vulnerable adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013;158(6):478-486. Available at http://annals.org/aim/fullarticle/1558517/screening-intimate-partner-violence-abuse-elderly-vulnerable-adults-u-s. Last accessed July 26, 2019.

51333 • Medical Error Prevention and Root Cause Analysis

Marjorie Conner Allen, BSN, JD

www.netce.com

Copyright © 2019 NetCE, All rights reserved.

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

Table of Contents

51333 • Medical Error Prevention and Root Cause Analysis

Course Overview

Audience

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Division Planner

Division Planner Disclosure

Director of Development and Academic Affairs

Director Disclosure Statement

About the Sponsor

Disclosure Statement

1. INTRODUCTION

2. DEFINING "MEDICAL ERROR"

3. ROOT CAUSE ANALYSIS PROCESS

FLORIDA LAW

4. ERROR REDUCTION AND PREVENTION

UNINTENDED RETENTION OF A FOREIGN BODY

WRONG-SITE SURGERY

DELAYS IN TREATMENT

OPERATIVE AND POSTOPERATIVE COMPLICATIONS

PATIENT SUICIDE

PATIENT FALLS

MEDICATION ERRORS

COMMON MISDIAGNOSES

5. OTHER CONSIDERATIONS FOR PATIENT SAFETY

USE OF AN INTERPRETER

6. CONCLUSION

Works Cited

51333 • Medical Error Prevention and Root Cause Analysis

Education Category. Management

Release Date. 09/01/2019

Expiration Date. 08/31/2022

Course Overview

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

Audience

This course is designed for all licensed dental professionals.

Course Objective

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

Learning Objectives

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

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

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

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

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

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

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

Faculty

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

Faculty Disclosure

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

Division Planner

William E. Frey, DDS, MS, FICD

Division Planner Disclosure

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

Director of Development and Academic Affairs

Sarah Campbell

Director Disclosure Statement

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

About the Sponsor

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

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

Disclosure Statement

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

1. INTRODUCTION

The Institute of Medicine's (IOM) 1999 publicationTo Err is Human: Building a Safer Health System, illuminated the unfortunate reality of medical errors in the healthcare industry. The report reviewed the prevalence of medical errors in the United States and highlighted measures that should be taken to prevent them. Specifically, the authors of the report noted that at least 44,000 and perhaps as many as 98,000 Americans were dying in hospitals each year as a result of medical errors and many more were being seriously injured [1]. They further noted that, even when using the lower estimate of 44,000, deaths in hospitals due to medical errors exceeded the annual deaths attributable to motor vehicle accidents (43,458), breast cancer (42,297), or AIDS (16,516) [1]. A 2016 report stated that the average number of annual in-hospital deaths attributable to medical error might actually be much higher, at around 400,000 [2]. This report places medical errors as the third leading cause of death in the United States. Certainly, these numbers must be balanced against the millions of admissions to hospitals in the United States, which is in excess of 35 million annually [1,3].

It does appear that some progress has been made in the past decade. The Agency for Healthcare Research and Quality found a 17% decline in hospital-acquired conditions between 2010 and 2013, or 1.3 million fewer conditions and 50,000 fewer deaths than if the 2010 rate had remained steady [4]. Though the precise mechanism(s) responsible for this decline is not clear, it occurred following a concerted effort by federal agencies, organizations, and individual providers to curtail medical errors. However, the statistics indicate that medical errors continue to be an issue. Healthcare professionals should commit to continuing to pay greater attention to evaluating approaches for reducing errors and to building new systems to reduce the incidence of medical errors.

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

2. DEFINING "MEDICAL ERROR"

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

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

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

3. ROOT CAUSE ANALYSIS PROCESS

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

The Joint Commission defines a sentinel event as "an unexpected occurrence involving the death or serious physical or psychological injury, or the risk thereof. Serious injury specifically includes loss of limb or function. The phrase 'or the risk thereof' includes any process variation for which a recurrence would carry a significant chance of a serious adverse outcome" [6]. Root cause analysis, as defined by the Joint Commission, is "a process for identifying the basic or causal factors that underlie variation in performance, including the occurrence or possible occurrence of a sentinel event" [6].

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

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

or

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

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

- Unanticipated death of a full-term infant

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

- Discharge of an infant to the wrong family

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

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

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

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

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

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

- Prolonged fluoroscopy with cumulative dose >1,500 rads to a single field or any delivery of radiotherapy to the wrong body region or >25% above the planned radiotherapy dose

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

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

- Severe maternal morbidity

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

- Any close call ("near miss")

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

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

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

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

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

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

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

(For further definition of terms, please refer to the Joint Commission's Sentinel Event Policy and Procedures at https://www.jointcommission.org/sentinel_event_policy_and_procedures.)

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

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

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

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

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

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

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

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

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

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

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

- The analysis must include consideration of any relevant literature.

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

FLORIDA LAW

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

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

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

1. Results in one of the following injuries:

1. Death;

2. Brain or spinal damage;

3. Permanent disfigurement;

4. Fracture or dislocation of bones or joints;

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

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

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

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

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

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

In 2018, the Florida AHCA reported that a total of 131 deaths occurred as a result of hospital error, 20.6% of 636 adverse incidents reported for the year. The next most common incidents during this period were surgical procedure to remove foreign object from a previous surgical procedure (16.5%), transfer of the patient to a unit providing a more acute level of care due to the adverse incident (14.2%), surgical procedures unrelated to the patient's diagnosis or medical needs (10%), and surgical procedure performed on the wrong site (5.3%) [9]. The following adverse incidents must be reported to the AHCA within 15 calendar days after their occurrence [8]:

- The death of a patient

- Brain or spinal damage to a patient

- The performance of a surgical procedure on the wrong patient

- The performance of a wrong-site surgical procedure

- The performance of a wrong surgical procedure

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

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

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

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

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

4. ERROR REDUCTION AND PREVENTION

Between 2005 and 2018, the Joint Commission reviewed 11,622 sentinel events [11]. Some events, such as fire, impacted multiple patients. Sentinel event reviews during this time period were frequently conducted for unintended retention of a foreign body; wrong-patient, wrong-site, wrong-procedure surgery; delay in treatment; operative and postoperative complications; patient suicide; patient fall; and medication error [11].

UNINTENDED RETENTION OF A FOREIGN BODY

In 2017–2018, the most frequently reported sentinel event reported to the Joint Commission was unintended retained foreign objects [11]. The prevalence of these events has remained relatively stable since 2009, indicating that preventing these errors remains difficult for practitioners and facilities. The most commonly retained items are sponges, followed by catheter guidewires and other (a broad category encompassing a wide variety of items) [10].

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

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

- The absence of policies and procedures

- Failure to comply with existing policies and procedures

- Problems with hierarchy and intimidation

- Failure in communication with physicians

- Failure of staff to communicate relevant patient information

- Inadequate or incomplete education of staff

WRONG-SITE SURGERY

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

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

DELAYS IN TREATMENT

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

OPERATIVE AND POSTOPERATIVE COMPLICATIONS

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

PATIENT SUICIDE

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

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

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

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

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

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

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

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

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

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

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

PATIENT FALLS

Patient falls are a constant challenge in healthcare facilities. Patients who are at highest risk include the elderly, those who have an altered mental status due to chronic mental illness or acute intoxication, and those who have a history of prior falls. It is obvious from these factors that a thorough and complete patient history may be the key to identifying those at risk. The root causes of those patient falls that healthcare facilities identified as sentinel events and reported to the Joint Commission included inadequate assessment, communication failures, lack of adherence to protocols and safety practices, inadequate staff orientation, supervision, staffing levels or skill mix, deficiencies in the physical environment, and lack of leadership [19]. Risk reduction strategies to these root causes are fairly straightforward, although in practice, preventing falls is difficult. The most important are the use of a standardized assessment tool to identify fall and injury risk factors, assessing an individual patient's risks that may not have been captured through the tool, and interventions tailored to an individual patient's identified risks [19].

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

MEDICATION ERRORS

Unquestionably, medication errors are one of the most common causes of avoidable harm to patients. These errors may occur at three critical points: when ordered by a physician, dispensed by a pharmacist, or administered by a nurse.

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

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

A number of medication errors can be linked to the prescriber who continually uses potentially dangerous abbreviations and dose expressions. Despite repeated warnings by the Institute for Safe Medication Practices about the dangers associated with using certain abbreviations when prescribing medications, this practice continues. To eliminate this factor, there are fairly simple steps that can eliminate much confusion. Prescribers should [21]:

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

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

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

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

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

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

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

It has been estimated that between 0.2% and 10% of prescriptions are dispensed incorrectly [23]. The most common type of medication error is wrong drug (43.8%), followed by wrong dose (31.5%), failure to consult with prescriber (4.9%), and compounding error (3.7%) [24]. Safe medication dispensing practices may include a number of risk reduction strategies to reduce the incidence of errors that may cause harm to patients [22,25,54]:

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

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

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

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

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

- Select oral rather than injectable routes, when possible.

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

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

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

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

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

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

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

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

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

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

- Resolve questions prior to medication administration

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

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

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

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

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

- Document all medications immediately after administration

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

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

COMMON MISDIAGNOSES

As Florida healthcare professionals, it is important to be aware that in addition to wrong-site/wrong-procedure surgery, several medical conditions also continue to be misdiagnosed. As of 2022, the Florida Board of Medicine has determined the five most misdiagnosed conditions to be [29]:

- Cancer-related conditions

- Neurologic conditions

- Cardiac-related issues

- Missed spinal cord compression

- Gastroenterology-related issues

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

Cancer

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

Neurologic/Spinal Cord-Related Conditions

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

One of the most common neurologic conditions is headache; however, it has been estimated that 50% of migraine patients remain undiagnosed or misdiagnosed, and only a small number (8% to 10%) of individuals with migraine take migraine-specific medications such as triptans or ergotamines [65,66]. Patients suffering from daily migraines may be misdiagnosed with chronic sinusitis or rhinitis and repeatedly and unsuccessfully treated with broad-spectrum antibiotics [67,68]. The diagnosis of migraine is based solely on a constellation of signs and symptoms, and a comprehensive medical and neurological examination is required to exclude secondary headache [69]. Useful evidence-based clinical guidelines for migraine screening have been developed and are summarized in the mnemonic POUND: pulsatile headache; one-day duration (4 to 72 hours); unilateral location; nausea or vomiting; and disabling intensity [70]. Competence of the clinician and effective communication with the patient play a crucial role in the diagnosis of migraine.

Cardiac-Related Issues

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

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

Missed Spinal Cord Compression

Epidural compression syndrome is an umbrella term that encompasses spinal cord compression, cauda equina syndrome, and conus medullaris syndrome. While these conditions differ in the level of neurologic deficit at presentation, they are otherwise similar in symptoms, evaluation, and management. Massive herniation of a midline disk, typically at the L4 to L5 disk level, is the most common cause of epidural compression syndrome. Tumor, epidural abscess, spinal canal hematoma, or lumbar spine spondylosis represent other causes [37].

Spinal cord compression is often secondary to herniated disk, vertebral fracture, or space-occupying lesion. Missing this diagnosis, typically by attributing the associated pain to muscle or nerve causes, will miss potentially catastrophic conditions [38,39,40,41]. In a study of 3,786 individuals, the estimated prevalence of asymptomatic spinal cord compression in a healthy population was 24.2%, with a significantly higher prevalence in older populations compared with younger populations and American/European populations compared with Asian populations [42].

In patients with spinal cord compression, neurologic status at diagnosis is the greatest predictor of ultimate neurologic outcome and underscores the importance of early accurate diagnosis. The dominant symptom is back pain with accelerating pain severity. Pain from epidural spinal cord compression is made worse with recumbent positioning, and unilateral or bilateral radiculopathy may develop over time. For many patients, leg pain or neurologic symptoms are more dominant than back pain. Also common at diagnosis is symmetrical lower extremity weakness that may have progressed to gait disturbance or paralysis. Decreased lower extremity reflexes are associated with cauda equina syndrome [37].

Gastroenterology-Related Conditions

Gasteroenterologic conditions may present with nonspecific complaints (e.g., abdominal pain, nausea) common to a variety of illnesses, complicating and delaying diagnosis. In one study of patients with pancreatic cancer, more than 30% were initially misdiagnosed, most commonly with gall bladder disease [71]. Diagnosis and screening for GI disorders may be complicated by a lack of definitive test (e.g., irritable bowel syndrome) or by limits on screening recommendations (e.g., colorectal cancer). However, delayed diagnosis can lead to worsening conditions and poorer prognosis.

In general, gastrointestinal syndromes/symptoms may be classified into three general diagnostic categories: organic, motility, or functional disorders [72,73]. Functional GI disorders are idiopathic disorders of gut-brain interaction and, unlike organic and motility disorders, diagnosis involves identification of symptom clusters. As such, misdiagnosis is more common.

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

5. OTHER CONSIDERATIONS FOR PATIENT SAFETY

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

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

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

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

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

USE OF AN INTERPRETER

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

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

6. CONCLUSION

Although the United States has one of the top 40 healthcare systems in the world, it is apparent that the numbers of medical errors are at unacceptably high levels. The consequences of medical errors are often more severe than the consequences of mistakes in other industries. They may lead to death or to serious and long-term disability, which underscores the need for aggressive action in this area. As a starting point, we should become an active part of the solution. This will only happen if all healthcare professionals voice their concerns when they identify problems in a system or process. In addition, we should actively participate in the root cause analysis process, understanding that the goal is not to assign blame, but rather to identify how we can improve the process to provide the best quality care to our patients. Medical errors are costly, not only because patients may lose their lives or livelihoods, but also because patients lose trust in the system and colleagues lose faith in each other. To preserve the integrity of our system, we must correct this problem, and the solution begins with each of us.

Works Cited

1. Committee on Quality of Health Care in American. To Err is Human: Building a Safer Health System. Washington, DC: National Academy Press; 1999.

2. Makary MA, Daniel M. Medical error: the third leading cause of death in the U.S. BMJ. 2016;353:i2139.

3. Centers for Disease Control and Prevention. Hospital Utilization (in Non-Federal Short-Stay Hospitals). Available at https://www.cdc.gov/nchs/fastats/hospital.htm. Last accessed August 1, 2019.

4. Agency for Healthcare Research and Quality. Efforts To Improve Patient Safety Result in 1.3 Million Fewer Patient Harms: Interim Update on 2013 Annual Hospital-Acquired Condition Rate and Estimates of Cost Savings and Deaths Averted From 2010 to 2013. Available at https://www.ahrq.gov/professionals/quality-patient-safety/pfp/interimhacrate2013.html. Last accessed August 1, 2019.

5. Florida Statutes. 456.013 Department; General Licensing Provisions. Available at http://www.leg.state.fl.us/Statutes/index.cfm?App_mode=Display_Statute&Search_String=&URL=0400-0499/0456/Sections/0456.013.html. Last accessed August 1, 2019.

6. The Joint Commission. Sentinel Events. Available at https://www.jointcommission.org/assets/1/6/CAMH_2012_Update2_24_SE.pdf. Last accessed August 1, 2019.

7. The Joint Commission. Sentinel Event Policy and Procedures. Available at https://www.jointcommission.org/sentinel_event_policy_and_procedures. Last accessed August 1, 2019.

8. Florida Legislature. The 2018 Florida Statutes: 395.0197 Internal Risk Management Program. Available at http://www.leg.state. fl.us/Statutes/index.cfm?App_mode=Display_Statute&Search_String=&URL=0300-0399/0395/Sections/0395.0197.html. Last accessed June 25, 2019.

9. Florida Agency for Health Care Administration. AHCA Incident Reporting System: Quarterly Report—Detail Data. Available at https://bi.ahca.myflorida.com/t/ABICC/views/QuarterlyReport_ASC-HOSP-HMO/DetailData?:embed=y&:showAppBanner=false&:showShareOptions=true&:display_count=no&:showVizHome=no. Last accessed August 6, 2019.

10. The Joint Commission. Most Commonly Reviewed Sentinel Event Types. Available at https://www.jointcommission.org/assets/1/18/Event_type_2Q_2016.pdf. Last accessed August 9, 2019.

11. The Joint Commission. Sentinel Event Data: General Information. Available at https://www.jointcommission.org/sentinel_ event_data_general. Last accessed August 9, 2019.

12. American Academy of Orthopedic Surgeons. Information Statement: Surgical Site and Procedure Confirmation. Available athttps://aaos.org/uploadedFiles/PreProduction/About/Opinion_Statements/advistmt/1043%20Surgical%20Site%20and%20Procedure%20Confirmation.pdf. Last accessed August 9, 2019.

13. The Joint Commission. Preventing unintended retained foreign objects. Sentinel Event Alert. 2013;51:1-5.

14. The Joint Commission. Performance of the Correct Procedure at the Correct Body Site. Available at https://www.who.int/patientsafety/solutions/patientsafety/PS-Solution4.pdf. Last accessed August 9, 2019.

15. The Joint Commission. Universal Protocol. Available at https://www.jointcommission.org/standards_information/up.aspx. Last accessed August 9, 2019.

16. The Joint Commission. Quick Safety: Preventing Delays in Treatment. Available athttps://www.jointcommission.org/assets/1/23/Quick_Safety_Issue_Nine_Jan_2015_FINAL.pdf. Last accessed August 9, 2019.

17. AHC Media. JCAHO Data Show Surgical Complications, Causes. Available at https://www.reliasmedia.com/articles/45354-jcaho-data-show-surgical-complications-causes. Last accessed August 9, 2019.

18. The Joint Commission. Detecting and treating suicide ideation in all settings. Sentinel Event Alert. 2016;56:1-7.

19. The Joint Commission. Preventing falls and fall-related injuries in health care facilities. Sentinel Event Alert. 2015;55:1-5.

20. National Coordinating Council for Medication Error Reporting and Prevention. About Medication Errors. Available at https://www.nccmerp.org/about-medication-errors. Last accessed August 9, 2019.

21. The Joint Commission. Facts About the Official "Do Not Use" List of Abbreviations. Available at https://www.jointcommission.org/facts_about_do_not_use_list/. Last accessed August 9, 2019.

22. Cohen MR (ed). Medication Errors. 2nd ed. Washington, DC: American Pharmacists Association; 2007.

23. Flynn EA, Barker KN, Carnahan BJ. National observational study of prescription dispensing accuracy and safety in 50 pharmacies.J Am Pharm Assoc (Wash). 2003;43(2):191-200.

24. O'Donnell J, Vogenberg FR. Legal risk management opportunities, pharmacy practice, and P&T committees. Part 1: deconstructing dispensing errors. P T. 2014;39(8):559-562, 579.

25. Breland BD. Strategies for the prevention of medication errors. Hospital Pharmacy Report. 2000;14(8):56-65.

26. Federico F. The Five Rights of Medication Administration. Available at http://www.ihi.org/resources/pages/improvementstories/fiverightsofmedicationadministration.aspx. Last accessed August 9, 2019.

27. Pozgar GD. Legal Aspects of Health Care Administration. 13th ed. Sudbury, MA: Jones & Bartlett Learning; 2018.

28. The Joint Commission. Sentinel Event Alert, Issue 39: Preventing Pediatric Medication Errors. Available at https://www.jointcommission.org/assets/1/18/SEA_39.pdf. Last accessed August 9, 2019.

29. Florida Administrative Code. 64B8-13.005. Continuing Education for Biennial Renewal. Available at https://www.flrules.org/gateway/ruleno.asp?id=64B8-13.005. Last accessed March 15, 2022.

30. Zarick AL. Leadership in Legal Education Symposium X. Damage deferred: determining when a cause of action begins to accrue for a cancer misdiagnosis claim. Univ Toledo Law Rev. 2010;41:445.

31. Lyratzopoulos G, Vedsted P, Singh H. Understanding missed opportunities for more timely diagnosis of cancer in symptomatic patients after presentation. Br J Cancer. 2015;112(Suppl 1):S84-S91.

32. Lydiatt DD. Medical malpractice and cancer of the larynx. Laryngoscope. 2010;112(3):445-448.

33. Lydiatt DD. Cancer of the oral cavity and medical malpractice. Laryngoscope. 2010;112(5):816-819.

34. Pope JV, Edlow JA. Avoiding misdiagnosis in patients with neurological emergencies. Emergency Medicine International. 2012;(2012):949275.

35. Kamalian S, Kamalian S, Boulter DJ, Lev MH, Gonzalez RG, Schaefer PW. Stroke differential diagnosis and mimics: part 1. Applied Radiology. 2015;44(11):26-39.

36. Kahn RL, Stanton MA, Tong-Ngork S, Liguori GA, Edmonds CR, Levine DS. One-year experience with day-of-surgery pregnancy testing before elective orthopedic procedures. Anesth Analg. 2006;106(4):1127-1131.

37. Corwell BN. The emergency department evaluation, management, and treatment of back pain. Emerg Med Clin North Am. 2010;28(4):811-839.

38. Ruckdeschel JC. Early detection and treatment of spinal cord compression. Oncology (Williston Park). 2005;19(1):81-86, 89-92.

39. Arce D, Sass P, Abul-Khoudoud H. Recognizing spinal cord emergencies. Am Fam Physician. 2001;64(4):631-638.

40. Lawton AJ, Lee KA, Cheville AL, et al. Assessment and management of patients with metastatic spinal cord compression: a multidisciplinary review. J Clin Oncol. 2018;37(1):61-71.

41. Boussios S, Cooke D, Hayward C, et al. Metastatic spinal cord compression: unraveling the diagnostic and therapeutic challenges. Anticancer Res. 2018;38(9):4987-4997.

42. Smith SS, Stewart ME, Davies BM, Kotter MRN. The prevalence of asymptomatic and symptomatic spinal cord compression on magnetic resonance imaging: a systematic review and meta-analysis. Global Spine J. 2021;11(4):597-607.

43. Roffi M, Patrono C, Collet JP, et al. 2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016;37(3):267-315.

44. Mosca L, Benjamin EJ, Berra K, et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women—2011 update: a guideline from the American Heart Association. Circulation. 2011;123(11):1243-1262.

45. El-Menyar A, Zubaid M, Sulaiman K, et al. Atypical presentation of acute coronary syndrome: a significant independent predictor of in-hospital mortality. J Cardiol. 2011;57(2):165-171.

46. Khan NA, Daskalopoulou SS, Karp I, et al. Sex differences in acute coronary syndrome symptom presentation in young patients. JAMA Intern Med. 2013;173(20):1863-1871.

47. Darawshe A, Rabkin Y, Batsheva Z, Abdelhadi F, Feldman A, Rosenfeld R. Misdiagnosed acute coronary syndrome: characteristics of patients with acute coronary syndrome discharged home from the emergency department. Israeli Journal of Emergency Medicine. 2007;7(3):3-10.

48. Whang JS, Baker SR, Patel R, Luk L, Castro A 3rd. The causes of medical malpractice suits against radiologists in the United States. Radiology. 2013;266(2):548-554.

49. Cooke LJ, Becker WJ. Migraine prevalence, treatment and impact: the Canadian Women Migraine Study. Can J Neurol Sci. 2010;37(5):580-587.

50. Williams SC, Schmaltz SP, Castro GM, Baker DW. Incidence and method of suicide in hospitals in the United States. Jt Comm J Qual Patient Saf. 2018;44(11):643-650.

51. Rinke ML, Bundy DG, Velasquez CA, et al. Interventions to reduce pediatric medication errors: a systematic review. Pediatrics. 2014;134(2):338-360.

52. Gillespie LD, Robertson MC, Gillespie WJ, et al. Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev. 2012;(9):CD007146.

53. Agency for Healthcare Research and Quality. 20 Tips to Help Prevent Medical Errors: Patient Fact Sheet. Available at https://www.ahrq.gov/patients-consumers/care-planning/errors/20tips/index.html. Last accessed August 9, 2019.

54. Lupoli TA, Lockey RF, Temporomandibular dysfunction: an often overlooked cause of chronic headaches. Ann Allergy Asthma Immunol. 2007;99(4):314-318.

55. Cady RK, Farmer K. Migraine. In: Jay GW (ed). Clinician's Guide to Chronic Headache and Facial Pain. New York, NY: Informa Healthcare USA; 2010: 1-15.

56. Beithon J, Gallenberg M, Johnson K, et al. Diagnosis and Treatment of Headache. Bloomington, MN: Institute for Clinical Systems Improvement; 2013.

57. McDonald C, Hernandez M, Gofman Y, Suchecki S, Schreier W. The five most common misdiagnoses: a meta-analysis of autopsy and malpractice data. Internet J Fam Pract. 2008;7(2).

58. Deaño RC, Glassner-Kolmin C, Rubenfire M, et al. Referral of patients with pulmonary hypertension diagnoses to tertiary pulmonary hypertension centers: the multicenter RePHerral study. JAMA Intern Med. 2013;173(10):887-893.

59. Lahey MB; Graul A, Meyers S, Ferrarello D, Oxford CM. Keeping our newborns safe: effectively decreasing the rate of neonatal falls during the postpartum period. Obstetrics & Gynecology. 2015;125(Suppl 1):108S-109S.

60. Jabbarpour YM, Jayaram G. Suicide risk: navigating the failure modes. Quality and Professionalism in Psychiatry. 2011;9(2):186-193.

61. American Society of Health-System Pharmacists. ASHP Guidelines on Preventing Medication Errors in Hospitals. Available at https://www.ashp.org/-/media/assets/policy-guidelines/docs/guidelines/preventing-medication-errors-hospitals.ashx?la=en&hash=CFDD375E109297517C3CB96BDADE7B0D59E2560A. Last accessed August 9, 2019.

62. Poon EG, Kachalia A, Puopolo AL, Gandhi TK, Studdert DM. Cognitive errors and logistical breakdowns contributing to missed and delayed diagnoses of breast and colorectal cancers: a process analysis of closed malpractice claims. J Gen Intern Med. 2012;27(11):1416-1423.

63. Pope JV, Edlow JA. Avoiding misdiagnosis in patients with neurological emergencies. Emergency Medicine International. 2012;(2012):949275.

64. Newman-Toker DE, Moy E, Valente E, Coffey R, Hines AL. Missed diagnosis of stroke in the emergency department: a cross-sectional analysis of a large population-based sample. Diagnosis. 2014;1(2):155-166.

65. Dahlf C, Maassen Van Den Brink A. Dihydroergotamine, ergotamine, methysergide and sumatriptan: basic science in relation to migraine treatment. Headache. 2012;52(4):707-714.

66. Cooke LJ, Becker WJ. Migraine prevalence, treatment and impact: the Canadian Women Migraine Study. Can J Neurol Sci. 2010;37(5):580-587.

67. Graff-Radford SB. Facial pain, cervical pain, and headache. Continuum (Minneap Minn). 2012;18(4):869-882.

68. Lupoli TA, Lockey RF, Temporomandibular dysfunction: an often overlooked cause of chronic headaches. Ann Allergy Asthma Immunol. 2007;99(4):314-318.

69. Cady RK, Farmer K. Migraine. In: Jay GW (ed). Clinicians Guide to Chronic Headache and Facial Pain. New York, NY: Informa Healthcare USA; 2010: 1-15.

70. Beithon J, Gallenberg M, Johnson K, et al. Diagnosis and Treatment of Headache. Bloomington, MN: Institute for Clinical Systems Improvement; 2013.

71. Mechcatie E. DDW: Study Finds Pancreatic Cancer Misdiagnosis Rate at 31%. Available at https://www.mdedge.com/gihepnews/article/101026/gastroenterology/ddw-study-finds-pancreatic-cancer-misdiagnosis-rate-31. Last accessed February 27, 2020.

72. Drossman DA. Functional gastrointestinal disorders: history, pathophysiology, clinical features, and Rome IV. Gastroenterology. 2016;150:1262-1279.

73. Drossman DA, Hasler WL. Rome IVfunctional GI disorders: disorders of gut-brain interaction. Gastroenterology. 2016;150(6):1257-1261.

54002 • A Review of Oral Histology and Physiology

Mark J. Szarejko, DDS, FAGD

www.netce.com

Copyright © 2020 NetCE, All rights reserved.

Members of the dental profession restore and extract teeth, manipulate gingival tissues, and retract mucosal tissues bathed in saliva every day. However, an appreciation of the cells that comprise these structures and tissues and their individual and collective functions, all of which contribute to oral health and general health, may be lacking. The healing properties of tissues, the compatibility or lack thereof for a plethora of restorative dental materials, the impact of systemic and oral diseases, and the beneficial or detrimental effect of medications all originate from a cellular basis. This course will review the basic cellular composition of the teeth, the components of the periodontal apparatus, the varied components of the oral mucosa, and the histology and function of the salivary glands. The cellular composition as it relates to structure, physiology, oral health, and clinical significance will be discussed.

Table of Contents

54002 • A Review of Oral Histology and Physiology

Course Overview

Audience

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Division Planner

Division Planner Disclosure

Director of Development and Academic Affairs

Director Disclosure Statement

About the Sponsor

Disclosure Statement

Implicit Bias in Health Care

1. INTRODUCTION

2. TEETH

ENAMEL

DENTIN

THE DENTAL PULP

3. THE PERIODONTIUM

GINGIVAL TISSUES

CEMENTUM

THE PERIODONTAL LIGAMENT

ALVEOLAR BONE

4. THE ORAL MUCOSA

KERATINIZED (MASTICATORY) MUCOSA

LINING MUCOSA

SPECIALIZED MUCOSA OF THE TONGUE

THE VERMILION ZONE OF THE LIPS

5. THE SALIVARY GLANDS

THE PAROTID GLAND

THE SUBMANDIBULAR GLAND

THE SUBLINGUAL GLAND

MINOR SALIVARY GLANDS

SALIVARY GLAND PATHOLOGY

6. CONCLUSION

Works Cited

54002 • A Review of Oral Histology and Physiology

Education Category. Infection Control / Internal Medicine

Release Date. 02/01/2020

Expiration Date. 01/31/2023

Course Overview

Members of the dental profession restore and extract teeth, manipulate gingival tissues, and retract mucosal tissues bathed in saliva every day. However, an appreciation of the cells that comprise these structures and tissues and their individual and collective functions, all of which contribute to oral health and general health, may be lacking. The healing properties of tissues, the compatibility or lack thereof for a plethora of restorative dental materials, the impact of systemic and oral diseases, and the beneficial or detrimental effect of medications all originate from a cellular basis. This course will review the basic cellular composition of the teeth, the components of the periodontal apparatus, the varied components of the oral mucosa, and the histology and function of the salivary glands. The cellular composition as it relates to structure, physiology, oral health, and clinical significance will be discussed.

Audience

This course is designed for all dental professionals.

Course Objective

The purpose of this course is to provide clinicians with a better understanding of the cellular components of the oral hard and soft tissues, supplying a scientific basis upon which clinical decisions for dental treatment can be made.

Learning Objectives

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

1. Outline the basic components of the enamel, dentine, and pulp.

2. Review the histology of the constituents of the periodontium.

3. Identify the varying divisions and functions of the oral mucosa.

4. Differentiate between the histology and salivary composition of the major and minor salivary glands.

5. Describe the manner by which disease and radiation therapy affect salivary glands.

Faculty

Mark J. Szarejko, DDS, FAGD, received his dental degree from the State University of New York at Buffalo in 1985. He received fellowship from the Academy of General Dentistry in 1994.

Faculty Disclosure

Contributing faculty, Mark J. Szarejko, DDS, FAGD, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Division Planner

William E. Frey, DDS, MS, FICD

Division Planner Disclosure

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

Director of Development and Academic Affairs

Sarah Campbell

Director Disclosure Statement

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

About the Sponsor

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

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

Disclosure Statement

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

Implicit Bias in Health Care

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

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

1. INTRODUCTION

General dentists and dental specialists, dental hygienists, and dental assistants all treat patients with dental caries, periodontal disease, edentulism, odontogenic infections, and oral and maxillofacial trauma. The unique oral environment is comprised of vastly different hard and soft tissues, with each component an essential link to appropriate oral and systemic health. The cellular constitution or histology of these structures is the basis from which the morphology originates and from which all physiologic actions commence. Form and function are inseparable.

This course will discuss the basic histologic components of the teeth, oral mucosa, salivary glands, and periodontium. The manner in which these structures are affected by varied oral pathologic processes, systemic diseases, and medications will be highlighted as related to their histologic origins and macroscopic appearance. The relationship between the normal histologic manifestations of these structures and their responses to inflammation, diseases, infection, and dental treatment will be outlined. An appreciation for the complexity of these tissues and their interrelationships with each other will instill dental clinicians with a renewed sense of respect for the teeth, bone, mucosa, and gingival tissues upon which they perform treatment on a daily basis.

2. TEETH

In the wild, most animals require their teeth for survival. Humans will suffer a decreased quality of life if natural teeth are not replaced by dentures, but edentulism alone is not a terminal condition. Beyond occlusion, teeth are critical to appropriate facial form and cosmetics, phonation and speech, and social acceptance. While some animals (e.g., sharks) regenerate new teeth to replace worn or fractured teeth, humans receive one set of deciduous (baby) teeth and one set of permanent teeth. (Rarely, supernumerary teeth may occur.) Teeth that are lost to caries, periodontal disease, or trauma can only be replaced by prosthetic means. Teeth are considered a triumph of engineering, as years of occlusion and masticatory forces, an oral environment that teams with complex microbial organisms, and parafunctional habits all contribute to challenge the integrity of teeth. This section will discuss the basic components of teeth, their response to common pathologic processes, and unique aspects of their clinical relevance.

ENAMEL

Enamel is the external layer of the tooth and is composed of 96% mineral deposits, with water and organic substances completing the remaining matrix [1]. It surpasses bone as the hardest and most mineralized substance in the body. A crystallized form of calcium phosphate known as hydroxylapatite is the main mineral component of enamel [2]. This compound accounts for the strength of enamel but also for its brittleness. Unlike the underlying dentin, enamel is without collagen. Enamel can exceed a thickness of 2 millimeters on the cusps of posterior teeth, but it exists as a thin veneer at the dentinoenamel junction.

Density and hardness are also highest where the enamel is thickest, such as the cusps of molars and the incisal edges of anterior teeth. These physical properties allow attrition to progress gradually on the surfaces of teeth that are subject to the repetitious forces of occlusion and mastication. Surface enamel is harder, denser, and less porous then the underlying layers of enamel. Enamel has a low tensile strength, which accounts for its brittle nature. However, its high modulus of elasticity, combined with support from the underlying dentin, decrease the incidence of enamel fracture [3].

Ameloblasts are the cells from which enamel is formed. The primary organizational units of enamel are the enamel rods (prisms) and interrod enamel (interprismatic substance). Enamel prisms originate at the dentinoenamel junction and extend to the surface of the enamel. Each enamel rod is approximately 5–6 micrometers in diameter and is as long as the enamel is thick [4]. Enamel is without a neural or vascular supply; therefore, teeth fractures strictly limited to enamel are painless and bloodless.

Although enamel is the hardest substance in the body, its lifelong exposure to the oral environment presents numerous challenges to its integrity and maintenance. When enamel is lost, there is no capacity for the production of new enamel. The loss of enamel through tooth-to-tooth contact is known as attrition. This is a gradual process that occurs throughout life but can be accelerated when parafunctional habits such as bruxing or clenching occur. The functional aspects of the teeth, such as the incisal edges of anterior teeth and the occlusal surfaces of posterior teeth, are most frequently involved, although the interproximal surfaces of teeth may also be affected. This loss of enamel can dull the incisal edges and flatten the occlusal surfaces of teeth, causing a decrease in the vertical dimension of occlusion and decreasing the penetrating ability of the involved surfaces during mastication. Sensitivity usually does not occur until the enamel has worn away to the point of exposing the underlying dentin. The loss of enamel supporting dental restorations can undermine their support and cause the loss of the restoration.

Abrasion involves the loss of tooth structure secondary to an external source of friction, such as excessive and overly aggressive tooth brushing. It is not limited to enamel, as root surface exposure via gingival recession can subject the cementum and underlying dentin to abrasive forces. Toothbrush abrasion usually occurs in the cervical area of the labial surfaces of anterior teeth and the buccal surfaces of posterior teeth. Sensitivity to thermal stimuli and sweets can occur upon exposure of the underlying dentin. The use of a soft-bristled toothbrush and a thorough, but gentle, cleaning motion during tooth brushing will decrease the incidence and severity of abrasion. In one study, loss of enamel was influenced mainly by the abrasivity of the toothpaste slurry, although this was modified by toothbrush filament stiffness [32]. So, type of toothpaste selected is also a consideration when attempting to limit erosion.

Erosion refers to the loss of tooth structures such as enamel via acidic substances, often extrinsic sources such as carbonated beverages or citrus fruits/juices. The primary intrinsic source of erosion is gastric acid introduced into the oral cavity during repeated episodes of regurgitation or vomiting. Patients who suffer from bulimia, anorexia, alcoholism, and gastroesophageal reflux disease are most frequently affected. Pregnant patients who experience prolonged bouts of morning sickness can also develop erosive defects that characteristically occur on the lingual surfaces of the maxillary anterior teeth and the occlusal surfaces of posterior teeth. Exposure of the underlying dentin can eventually occur and cause increased sensitivity and increased risk of caries and damage to existing restorations. Restorative efforts may be futile if the underlying cause of erosion is not diagnosed and treated.

Dental caries are the most frequent pathologic entity to adversely affect teeth. Despite advances in prevention and in oral hygiene, dental caries remain the most common chronic disease among children in the United States, with a prevalence five times greater than childhood asthma [5]. Two species of cariogenic bacteria, Streptococcus mutans and Lactobacillus, have been implicated in the initiation of the carious process [1]. Initial demineralization of the enamel left unchecked can extend to the underlying dentin and dental pulp to cause pain, abscesses, local and regional infections, and even sepsis.

An end-product of the fermentation of carbohydrates (e.g., glucose, sucrose, fructose) by these cariogenic bacteria is acid, which causes demineralization of the enamel [7]. However, enamel is the only component of the tooth with the capacity for remineralization via externally supplied calcium and phosphate ions. These minerals are deposited into the crystal voids of demineralized enamel and can replace the mineral content lost in incipient carious lesions [8]. When this equilibrium between demineralization and remineralization favors the former, the carious process progresses through the enamel, into the dentin, and ultimately the pulp. Carious lesions may be asymptomatic until advanced stages, at which time the extent and cost of treatment are greater. Any factor that increases the amount and duration of dental plaque on the teeth will increase the risk of caries. This includes decreased salivary flow, which is a side effect of many medications, radiation therapy for head and neck cancer, and autoimmune diseases such as Sjögren syndrome.

Prevention of dental caries has been associated with excellent oral hygiene and the use of fluoride-containing toothpastes, gels, mouth rinses, and supplements. Fluoride makes enamel more resistant to dental caries by encouraging remineralization and by decreasing the production of acid by cariogenic bacteria [10]. According to the Centers for Disease Control and Prevention, laboratory and epidemiologic research indicates that fluoride acts directly as a result of topical application on the enamel after eruption of the tooth [9]. This is in contrast to the long-held belief that ingested fluoride was the primary means by which enamel was strengthened.

DENTIN

Dentin is the substance that underlies the enamel of the clinical crown of the tooth and the cementum of the root. Its composition differs from enamel, consisting of 70% inorganic components, 20% organic components, and 10% water [1]. The significantly lower mineral content makes dentin softer than enamel and permits a more rapid progression of decay. It is formed by cells called odontoblasts and comprises the bulk of the tooth structure supporting the enamel.

Most of the organic matrix of dentin is type I collagen, which confers a property of resiliency such that dentin can deform under the forces of occlusion and support the more brittle layer of enamel [12]. Dentin is avascular, like enamel, and the substructure of dentin is a series of minute channels called dentinal tubules that contain cytoplasmic extensions of the progenitor odontoblasts and traverse much of the thickness of dentin. These odontoblastic processes are the main component within the dentinal tubules, and some may extend to the dentinoenamel junction. Cellular organelles such as mitochondria and secretory granules are associated with the cell bodies of the odontoblastic processes. Enamel is completely devoid of these live cellular elements.

The dentinal tubules are usually covered by enamel or cementum and do not make direct contact with the external oral environment. However, pathologic events such as attrition, abrasion, and erosion can deplete the surface layer of enamel and cause exposure of the underlying dentin. Gingival recession causes exposure of the tooth root and its protective cementum layer, the abrasion of which will also cause exposure of the supportive dentin. Thermal stimuli can cause changes in the hydraulic pressure within the exposed dentinal tubules and exert a force upon the odontoblastic processes, which is painful. Desensitizing toothpastes, gels, and mouth rinses contain ingredients that occlude the open and exposed dentinal tubules and can alleviate the pain. Components of other pastes have a direct effect on the odontoblastic processes.

Bacterial egress into exposed dentinal tubules can extend toward the pulp and stimulate an inflammatory response and even cause pulpal necrosis, which would require endodontic therapy, although this risk is remote. Gram-positive bacteria are the predominant micro-organisms found in the dentinal tubules and can be associated with carious and non-carious dentin [13].

After a tooth erupts, the enamel-forming ameloblast cells are lost and with them the capacity to produce any more enamel. However, dentin is capable of growth and repair and exists in several forms. Primary dentin is present at the time of the eruption of the tooth and is the predominant form of dentin. It is located between the enamel and the pulp chamber with the layer adjacent to the enamel known as mantle dentin, a less mineralized type than the remaining dentin. Secondary dentin develops after the root formation is complete and surrounds the pulp. All dentin develops from the dentinoenamel junction and progresses inwards toward the pulp. This progressive layering decreases the size of the pulp chamber and manifests as a clinical entity known as pulpal recession. This is clinically significant in the restoration of carious teeth. Younger patients with less secondary dentin and a subsequently large dental pulp will have a higher risk of pulpal involvement from dental caries than older patients with more secondary dentin and a receded pulp. Tertiary dentin, also called reparative or sclerotic dentin, forms in response to a stimulus such as dental caries, restorative procedures, or leakage around deficient restorations. It is deposited adjacent to the pulpal surface and is formed in response to these varied stimuli by previously inactive odontoblastic cells; it is not merely the formation of more secondary dentin.

Because dentin is less mineralized and softer than enamel, the occlusal surfaces of posterior teeth and the incisal edges of anterior teeth, where exposure is more likely, are more subject to attrition, fracture, and caries. Such deficiencies should be treated promptly to prevent the progressive destruction of tooth structure.

THE DENTAL PULP

Commonly called the "nerve" of the tooth, the dental pulp is a complex configuration of tissues. Blood vessels, nerve fibers, fibroblasts, macrophages, lymph vessels, lymph cells, and T-lymphocytes are all contained within this soft tissue matrix. The outer layer of the pulp consists of the cell bodies of the odontoblasts, cells that produce dentin. The tissue in the clinical crown of the tooth is the coronal pulp and is contained within the pulp chamber. Pulp within the tooth root is the radicular pulp or root canal, which ends at the apical foramen of the root and is continuous with the periodontal ligament. Nerve fibers (myelinated and unmyelinated) and blood vessels enter through the apical foramen and are closely associated throughout the entire pulp. The main sensory neurons within the dental pulp are pain fibers, some of which may extend into the dentinal tubules and may account for the sharp pain felt when thermal stimuli or acidic substances contact exposed dentin.

Pulpal tissues that are irreversibly inflamed or necrotic due to caries, trauma, or large restorations in close proximity to the pulp can be treated by endodontic (root canal) therapy. Occasionally, odontoblasts detach from the pulp chamber walls and cause the development of small conglomerations of dentin within the pulp, called pulp stones or denticles. These can be an obstruction to root canal therapy.

3. THE PERIODONTIUM

The structures that support, protect, and nourish the teeth externally are collectively referred to as the periodontium. This includes the free and attached gingiva, the cementum, the alveolar bone (process) of the maxilla and mandible, and the periodontal ligament. Each structure plays an important role in maintaining the health and stability of the teeth.

GINGIVAL TISSUES

The gingival tissues begin at the cervical area of the tooth, extend apically to cover the alveolar bone, and end at the intersection of the attached gingiva and the alveolar mucosa, referred to as the mucogingival junction. In health, the gingiva is coral pink in color and does not bleed upon periodontal probing. It can be divided into three zones: the free or marginal gingiva, the attached gingiva, and the interdental gingiva.

Free (Marginal) Gingiva

The free gingiva is composed of stratified squamous epithelial tissue supported by a matrix of dense connective tissue. This tissue surrounds the tooth in a collar-like fashion and is not attached to the underlying alveolar bone. In some patients, there is a minute linear demarcation, called the free gingival groove, between the free and attached gingiva. The space between the tooth and inner aspect of the free gingiva is the gingival sulcus. Bacteria and plaque that are deposited on and not removed from the gingival sulcus initiate an inflammatory response known as gingivitis. There is no loss of alveolar bone at this point, but the continued assault of bacterial toxins and the host inflammatory response may cause a progressive deepening of the sulcus beyond the 3 mm or less depth associated with ideal gingival health. The development of a periodontal pocket indicates progressive inflammation that will continue to deepen without treatment and will eventually cause resorption of the alveolar bone supporting the tooth and tooth loss. The epithelium of the free gingiva facing the gingival sulcus is called the sulcular epithelium. These cells are generally not keratinized (although some keratinization may extend into the sulcus) and are thinner than the external epithelial surface of the free gingiva (which is keratinized). At the depth of the gingival sulcus, the attachment between the tooth and the gingiva is known as the junctional epithelium. Important in this attachment is the presence of the basal lamina, a noncellular adhesive supporting sheet comprised of glycoproteins secreted by epithelial cells [14]. The epithelial attachment is the part of the junctional epithelium where the epithelial cells adhere to the tooth surface. The gingival sulcus contains gingival (crevicular) fluid that originates from the adjacent gingival connective tissue. This fluid contains substances with antimicrobial properties, antibodies, and plasma proteins that may improve the adhesion of the epithelial attachment [15]. The amount of this filtration product from the adjacent and highly vascular gingival connective tissue increases during gingival inflammation.

Two basal laminas are involved with the connection of the gingiva to the tooth. An internal basal lamina approximates the surface of the tooth, while an external basal lamina approximates the connective tissue. Most new cells of the junctional epithelium are derived from the germinating cell layer near the external basal lamina. When the lesions of periodontal disease become established, the connective tissue adjacent to the junctional epithelium is damaged. Inflammation associated with periodontal disease also increases the rate of epithelial turnover, which in turn inhibits the development of a healthy stratum of cells and induces migration of cells, resulting in thinned tissue. The damaged proximate connective tissue cannot properly support the junction epithelium against the tooth surface. The unsupported junctional epithelium proliferates in an apical direction, with a consequent deepening of the periodontal pocket [16]. Without the appropriate therapy, this process will involve and destroy the alveolar bone with a consequent loss of teeth.

Attached Gingiva

The keratinized attached gingiva is continuous with the free gingiva and extends to the facial alveolar mucosa of both the mandibular and maxillary arches. Lingually, it is continuous with the loose alveolar mucosa of the mandibular arch and blends imperceptibly with the firmly bound palatal mucosa of the maxillary arch. Its width can vary from 1–9 mm [17]. Unlike the free gingiva, the attached gingiva is tightly bound to the underlying alveolar bone by periosteal gingival fibers [18]. The exterior layer of the attached gingiva is composed of stratified squamous epithelium supported by a connective tissue matrix. There are few elastic fibers in its connective tissue matrix, as the attached gingiva is designed for minimal movement. This histologic consideration allows the attached gingiva to afford the periodontium protection against external injury, stabilize the gingival margin, and absorb the forces of the alveolar mucosa and the frenal attachments [1]. The surface of the attached gingiva has a stippled, "orange peel" texture that is absent from the gingival margin. The microscopic basis for stippling is alternating protuberances and depressions in the underlying tissue. Inflammation and edema from periodontal disease or odontogenic infections that extend into the attached gingiva will reduce or eliminate the stippling; the texture will return after the restoration of tissue health.

A decreasing width of attached gingiva can compromise both periodontal health and the ability to achieve favorable restorative outcomes for fixed prosthetics and implants. Periodontal surgical procedures, such as a free gingival graft or a subepithelial connective tissue graft, are used to restore deficiencies in the zone of attached gingiva.

Interdental Gingiva

The gingival tissues that occupy the gingival embrasure, the interproximal space beneath the contact area of the adjacent teeth, are referred to as the interdental gingiva. It is composed of both free and attached gingiva, and its shape reflects the anatomy of the bordering teeth. In the anterior teeth, for which the interproximal space is narrow and slit-like, the buccal and lingual gingival tissues (known as a gingival papilla) meet in a pinpoint fashion. In the posterior teeth, for which the contact area is much broader, a slight depression exists between the buccal and lingual papillae; this is known as the interdental col. Removing debris from this area requires floss, as tight contact between adjacent teeth usually precludes access to the bristles of a toothbrush. Conditions such as interproximal decay, lost or deficient restorations, and drifted teeth with poor interproximal contacts can cause the impaction of food and complicate oral hygiene, causing inflammation in the interdental gingiva.

CEMENTUM

The calcified tissue covering the roots of the teeth is known as cementum, and it is formed by cells called cementoblasts. By weight, its composition is about 50% inorganic material and 50% organic material and water. Cementum is thinnest at the cementoenamel junction (CEJ), the point of union of the coronal enamel and the cementum of the root [1]. At the CEJ and for the coronal two-thirds of the root, the cementum lacks cellular components and is known as acellular cementum. The more permeable cellular cementum is present in the apical one-third of the tooth [1].

The primary function of the cementum is to provide a surface into which the periodontal ligaments can insert and anchor the tooth to the alveolar bone. There are no blood vessels or nerves within the cementum, and it is not seen intra-orally unless gingival recession and periodontal disease occurs. In periodontal disease, the apical migration of the gingival tissue due to alveolar bone loss exposes the previously protected cementum, which is then susceptible to abrasion and caries. Root planing and scaling procedures upon cementum will not illicit a painful response, as this substance is without innervation. However, sensitivity can occur if exposed cementum is abraded and the previously protected dentinal tubules are subjected to thermal stimuli, acidic substances, or sweets. Likewise, if the cementum is removed during planing, exposure of the underlying dentin may result in pain. Unlike enamel, cementum is formed throughout life, which allows for the continuous reattachment of the fibers of the periodontal ligament.

In response to orthodontic forces, cementum has less of a tendency to be resorbed compared to the alveolar bone. However, small areas of cementum resorption can occur, the deficiencies of which are repaired with material similar to cellular cementum. Stimuli such as chronic periapical inflammation can cause the excessive production of cementum, known as hypercementosis, which is a generalized thickening of the cementum especially prevalent at the root apices. This is a benign condition, but globular masses at the root apex can complicate the ability to extract affected teeth.

Cementomas are benign cementum-producing tumors usually discovered upon routine radiographic examination. These lesions have a predilection for the mandibular incisor region but can involve any tooth. They are generally asymptomatic but can increase in size to a degree at which they are clinically palpable. While cementomas appear in the apical region, they may or may not be attached to the apex of the tooth.

The early development of these lesions features a fibrous composition that is radiolucent (dark) in radiographic appearance. As cementum deposition increases, a progressively more radiopaque (light) appearance will develop. Early lesions can present similar in radiographic appearance to the apical lesions associated with pulpal necrosis. The presence of pulpal caries or deep restorations and vitality testing allow for distinguishing between the lesions. Early radiolucent cementomas may be indistinguishable from initial malignancies of the mandible or maxilla. Referral to an oral surgeon should be considered so a differential diagnosis can be made and an appropriate treatment plan developed.

THE PERIODONTAL LIGAMENT

Ligaments are usually associated with connecting bones together at the joints. The periodontal ligament (PDL) connects the cementum of the tooth to the alveolar bone and has width ranging from 0.15–0.38 mm [22]. Radiographically, it is seen as a narrow black line surrounding the tooth. When widening of the PDL is seen on conventional periapical films, pulpal pathology or systemic medical conditions are usually the etiologic factor. Beyond its support and attachment of the tooth to the bone, it protects the underlying tissue from bacterial invasion. The PDL also has neural input that responds to the sensations of pain, touch, and pressure.

The PDL is composed of an interconnecting meshwork of fibers between the alveolar bone and cementum. Type I collagen fibrils are the principal constituent of the periodontal ligament [23]. Collagen-producing fibroblasts are bountiful in the periodontal ligament, with other cells such as macrophages, osteoblasts, and cementoblasts also present [24].

Individual fibers do not traverse this span in a cable-like fashion [25]. There is diversity among the fibers of the periodontal ligament, and the groups of fibers are classified according to their anatomic location. Beginning in the apical region of the tooth are the apical fibers, which extend from the cementum to the bone at the base of the socket and resist vertical force. Moving in a coronal direction, oblique fibers, the largest fiber group of the PDL, extend from the cementum to the alveolar bone in the apical one-third of the tooth. These fibers transmit much of the vertical masticatory stress to the alveolar bone. Horizontal fibers extend at right angles to the long axis of the tooth between the cementum and alveolar bone. These fibers resist lateral movement and primarily function to retain the tooth within the socket. The alveolar crest fibers extend from the cementum just below the junctional epithelium to the alveolar crest of bone and function in a manner similar to the horizontal fibers. Inter-radicular fibers, which are only present on multi-rooted teeth, extend perpendicularly from the root surface to the alveolar bone, acting to resist vertical and lateral movement [12]. These five fiber groups comprise the principal dentoalveolar fibers, the function of which is to attach the tooth to the alveolar bone. The ends of these fibers, referred to as Sharpey's fibers, terminate in either cementum or alveolar bone. The matrix of the PDL also contains capillaries, which are essential for the metabolic needs of the PDL and lymph cells and vessels, which are important to the immunocompetence of the PDL. The resilience of the PDL is afforded by the elastic fibers present throughout the matrix. Oxytalan fibers within the PDL span the long axis of the tooth and provide structural support [1].

Collagen is an essential component of the PDL and requires vitamin C, which the human body cannot synthesize, for its production. A sustained deficiency of vitamin C, resulting in scurvy, adversely affects collagen synthesis and therefore oral health. Without the replenishment of this essential nutrient, the support of the tooth provided by the PDL decreases and tooth loss can occur.

Poorly controlled type 1 or type 2 diabetes can impair the ability of the immune system to provide an adequate defense against pathogenic bacteria, and patients with diabetes are at an increased risk for periodontal disease. In these patients, the direct effect of bacterial toxins and the host inflammatory response can cause realignment and the destruction of the principal fibers of the PDL, the progression of which will lead to the loss of teeth.

ALVEOLAR BONE

The portion of the maxillary or mandibular arch that supports and protects the teeth is known as the alveolar bone. A boundary at the level of the root apices separates the alveolar process from the basal bone of the mandible or the maxilla. The terms alveolar bone and alveolar process are often used interchangeably; for the purpose of this course, the bone that surrounds and supports the teeth in either the mandibular or maxillary arch is considered the alveolar process. Anatomically, the alveolar process can be divided into separate areas, but in support and retention of the teeth, it is one functional unit. It is composed of a thin inner socket wall of compact (cortical) bone called the alveolar bone proper and the supporting alveolar bone, which consists of facial (outer) and lingual (inner) plates of compact bone, interior to which is the spongy cancellous bone. Radiographically, the alveolar bone proper is known as the lamina dura and appears as a radiopaque band that surrounds the tooth root. It is the alveolar bone proper to which the fibers of the periodontal ligament attach. When radiographs reveal loss of density in the lamina dura, it can indicate resorption of this bone as a symptom of inflammation or infection of the periodontal tissues.

When teeth are extracted, the resorption of the alveolar process can significantly decrease the height of the residual ridge, and when all teeth have been extracted, the cumulative shrinkage can present a challenge for the placement of implants or the use of complete dentures. The combined loss of teeth and the alveolar process will decrease the support of the soft tissues of the face and detract from the cosmetic appearance.

The functional unit of compact bone is the osteon, also called the Haversian system, in the center of which is a Haversian canal. This canal provides the neural and vascular supply to the surrounding concentric lamellae in which mature bone-producing cells, osteocytes, reside in lacunae. Microscopic canals called canaliculi interconnect the osteocytes with the neural and vascular supply of the Haversian canal. The lattice-like structures or trabeculae that compose the spongy bone are nourished by diffusion through the canaliculi from capillaries of the endosteum that surround the trabeculae. Interspersed within the trabeculae are deposits of red and yellow bone marrow, with the latter predominating.

The thickness of the outer cortical plates of bone is variable. It is the thinnest in the maxillary arch and the thickest over the mandibular molars and premolars. This is evident in the manner in which local anesthesia of the teeth is obtained. Teeth of the maxillary arch can be anesthetized by the infiltration and subsequent diffusion of a local anesthetic over the bone and roots of the desired teeth. This technique will be unsuccessful for mandibular molars, over which the outer plate of cortical bone is much thicker. In these cases, anesthetizing the inferior alveolar nerve by a regional block technique is required.

Alveolar bone may appear to be a static tissue, but it is subject to remodeling and can undergo change as a result of local and systemic pathologic processes. The dynamic forces of the formation of new bone by osteoblasts and the resorption of bone by osteoclasts are subtle but ever-present. This is the basis for orthodontic treatment. The movement of teeth during orthodontic therapy occurs as osteoclasts are activated and cause the resorption of the alveolar process in the front of the moving teeth while osteoblast-stimulated bone deposition occurs behind the moving teeth. The ideal situation is a balance between these processes, but problems can occasionally occur when osteoclastic activity exceeds osteoblastic activity, resulting in a net loss of the alveolar process and tooth loss.

The progression of gingivitis to periodontal disease is associated with a progressive loss of tissue attachment, deterioration of the periodontal ligament, and loss of the alveolar process. The complex interactions between pathogenic bacteria and the host response that can combine to cause the detachment of the periodontal ligament, the loss of the bone of the alveolar process, and the loss of teeth are many, and it is beyond the scope of this course to address each. However, it is a common problem among adults and a leading cause of tooth loss. Preventive maintenance, good oral hygiene, and early intervention when periodontal disease develops remain the foundation for a healthy periodontium and for the retention of teeth.

Diseases and Conditions Affecting the Alveolar Bone

The basal bone of the maxilla and mandible can be adversely affected by pathologic processes, which subsequently undermines support for the alveolar process. Radiation therapy for oral and pharyngeal malignancies that irradiates bone will cause hyalinization of the associated osseous blood vessels. The decreased perfusion of blood can cause ischemia and ultimately necrosis of the bone. Known as osteoradionecrosis, this condition can occur any time after the completion of radiotherapy and can involve small or large segments of bone that no longer function to support the alveolar process.

Osteoporosis can cause a significant decrease in bone density and a structural deterioration of the osseous architecture. Many studies suggest that patients with osteoporosis have decreased oral bone density and an increased rate of loss of the bone of the alveolar process [28]. Beyond the loss of support for the teeth, bone affected by osteoporosis has an increased risk of pathologic fracture.

4. THE ORAL MUCOSA

Within the restricted confines of the oral cavity, the variation of the composition of the oral mucosa reflects its multiple functions. An intact oral mucosa protects the underlying tissues from desiccation, physical trauma, chemical and mechanical irritation, and the penetration of pathogenic micro-organisms from the oral cavity. The integrity of the oral mucosa can be compromised due to mechanical trauma, various oral lesions, and ulcerative mucosal lesions that arise from chemotherapy for systemic malignancies or radiotherapy used to treat oral and pharyngeal malignancies. In such cases, bacterial and fungal organisms have access to deeper tissue layers and can cause local, regional, or systemic infections of varying severity. Speaking, chewing, and swallowing all depend upon harmony among the varied components of the oral mucosa. This section will review how the functions of the oral mucosa reflect the underlying histology.

KERATINIZED (MASTICATORY) MUCOSA

All of the oral mucosal tissues have an outer layer of stratified squamous epithelial cells, referred to as the mucosa proper, and an underlying connective tissue layer, known as the lamina propria. The latter layer contains numerous small loops of blood vessels, nerve fibers, and a dense network of collagen fibers that provide support for the mucosa proper. Keratinized tissue incorporates the protein keratin into the surface layers of the mucosa proper. Keratinization increases the tissue's strength and resistance to mechanical forces, but it decreases the flexibility. Tissues of the oral mucosa that are keratinized include the mucosa that overlies the hard palate, the attached gingiva, and the external surface of the free gingiva. The internal epithelial surface of the free gingiva that constitutes the crevicular (sulcular) epithelium and the junctional epithelium are not keratinized. The dorsal surface of the tongue has keratinized and non-keratinized areas and is considered specialized mucosa. These tissues will be discussed later in this section.

Masticatory mucosa is designed to withstand compressive and shearing forces during mastication and the abrasive nature of food against soft tissue. In order for the masticatory mucosa to perform these functions and retain its original shape, the tissue must be firmly secured. The junction between the epithelial cells of the mucosa proper and the underlying lamina propria is a convoluted border that extends the available surface area for attachment and allows for a stronger union between the layers. In the free and attached gingiva, fingerlike extensions called rete pegs extend from the epithelial layer into the lamina propria and provide a more secure mechanical attachment [29]. The epithelial attachment of the junctional epithelium secures the attached gingiva to the tooth. Because there are few elastic fibers in the connective tissue, movement and flexibility in the gingiva is ideal in order to withstand masticatory forces and protect the underlying tissue [17].

Collagen fibers in the lamina propria (which collectively form the gingival ligament) aid in securing the free and attached gingiva to the cementum and the bone of the alveolar process, but they are not strictly considered to be a part of the periodontal ligament. The dentogingival fibers are the most numerous and extend from the cementum at the cervical aspect of the root to the lamina propria of both the free and attached gingiva. The alveologingival fibers connect the bone of the alveolar crest with the lamina propria. A group of fibers encircle the tooth in the cervical area and band other proximate fiber groups together to attach the free gingiva to the tooth. The two remaining fiber groups, the dentoperiosteal fibers and the transeptal fibers, do not have attachments with the free or attached gingival [4].

The free and attached gingiva do not have a distinct submucosal layer. The attached gingiva is tightly bound via dense collagen fibers to the periosteum, a double layer of connective tissue that overlies and nourishes the bone of the alveolar process. The juncture of the mucosa proper and lamina propria with the periosteum is called the mucoperiosteum. The concerted effort of these varied collagenous fiber connections provides the gingival tissue with the support and resilience needed to consistently function as masticatory mucosa.

The mucosa that overlies the hard palate is also considered masticatory mucosa, as the tongue thrusting a bolus of food against the hard palate aids in the breakdown of food. In addition, complete or partial dentures use the unyielding hard palate as a sturdy foundation to which masticatory stresses can be transferred. The palatal mucosa is bound tightly to the bone of the hard palate by dense connective tissue. Pronounced ridges of epithelial tissue called rugae extend horizontally across the anterior region of the hard palate and also assist with food breakdown.

The demarcation of the midline of the hard palate is known as the median raphe, under which no submucosa exists. The lateral regions of the anterior hard palate have a submucosa that contains adipose tissue. Beneath the surface of the posterior and lateral region of the hard palate are minor salivary glands that produce only mucous secretions. Local anesthetic injections are more painful on the hard palate and surgical flaps are more difficult to create because the mucosa is bound so tightly to the underlying palatal bone.

LINING MUCOSA

Most of the mucosa present in the oral cavity is categorized as lining mucosa, which is flexible and distensible. This includes the mucosa of the inside of the lips (labial) and cheeks (buccal), the ventral surface of the tongue and the floor of the mouth beneath it, and the alveolar mucosa beginning at the attached gingiva and blending with the labial or buccal mucosa. Lining mucosa consists of stratified squamous epithelium that, unlike the masticatory mucosa, is not keratinized. This tissue is designed for movement during function, and the histology reflects this function.

The collagen fibers are thinner and less organized than those present in the masticatory mucosa. Elastic fibers, which are scarce in the tightly bound masticatory mucosa, are more plentiful in the lining mucosa. This is because this tissue is designed to be stretched and moved but must have the elasticity and resilience to return to its original shape. The submucosal layer of the lining mucosa is also loosely organized, which further facilitates its freedom of movement. Lining mucosa has a well-developed capillary network, resulting in its red hue. Lining mucosa has a glossy and smooth appearance. The rete pegs that extend from the epithelium into the lamina propria are shorter than those seen in the masticatory mucosa, which also confers a higher degree of tissue mobility. The thinness of the tissue makes it more prone to injury compared to the thicker and more secured masticatory mucosa; however, its cells have a fast turnover rate, so healing occurs quickly.

All lining mucosa has a submucosal layer, but its attachment to the underlying tissues varies by region. The submucosa of the labial and buccal mucosa has a firm attachment to the underlying muscle, while the tissue in the floor of the mouth is loosely attached to the underlying muscles. The submucosa of the alveolar mucosa maintains a loose attachment with the underlying periosteum of the maxilla or mandible. The lining mucosa of the ventral surface of the tongue is thin, with a submucosal layer that is not distinct but is attached to the underlying muscles [3]. Most malignant oral lesions initially present on lining mucosa, as the thinness facilitates the infiltration of malignant cells. In particular, intraoral squamous cell carcinomas have a predilection for the floor of the mouth and the ventral surface of the tongue.

SPECIALIZED MUCOSA OF THE TONGUE

The mucosa on the superior surface or dorsum of the tongue is an entirely different entity in structure and function compared to the ventral (inferior) surface of the tongue. This tissue contains specialized elements to facilitate the sensation of taste and the function of mastication.

The tongue is divided into the anterior two-thirds (or body) and the posterior one-third (or base) and each has different embryologic origins. The dorsum of the tongue is masticatory mucosa, the epithelium of which contains numerous projections called papillae, most of which are filiform papillae. These flame-like projections have a surface layer of keratinized stratified squamous epithelium suited for the masticatory function of compressing a bolus of food against the hard palate. The mucosa between the filiform papilla is not keratinized. There are no taste buds present in the filiform papillae.

Some patients may develop benign migratory glossitis (or geographic tongue), a condition that involves the filiform papillae. With this condition, the temporary loss or desquamation of the filiform papillae leaves irregular and erythematous areas, although the location of these areas can change daily. The papillae will regenerate, but the condition often recurs. The etiology of these lesions is unknown, although genetic, autoimmune, and environmental factors have been implicated. There is no common or universally effective treatment, and no cure is available. The exposed mucosal surfaces can be sensitive to thermal, acidic, or mechanical stimuli, so treatment is usually palliative. Although the lesions resolve spontaneously, they should be monitored and any lesions that do not heal should be biopsied.

Scattered among the filiform papillae on the dorsum of the tongue are the mushroom-shaped fungiform papillae that contain taste buds on their superior surface. The fungiform papillae have a thin epithelial surface that may or may not be keratinized and a vascular connective tissue core, which gives the structures a red appearance. The fungiform papillae are fewer in number but larger than the filiform papillae.

Foliate papillae are found in grooves along the posterior and lateral surface of the tongue. These papillae are larger than the fungiform papillae but are fewer in number. The epithelial surface is not keratinized. There are several taste buds present in the lateral borders of the foliate papillae bilaterally.

The circumvallate papillae are located at the junction of the body and base of the tongue. They are large, round structures, each surrounded by a trough. The superior surface of the circumvallate papillae features a keratinized connective tissue core. However, the epithelium of the lateral walls is not keratinized, and numerous taste buds are present on this surface. Minor salivary glands, the glands of von Ebner, secrete serous fluid into the base of the trough that surrounds these papillae, which is a self-cleansing mechanism and allows for taste renewal.

Effects of Radiation on Taste Buds

Taste buds are very sensitive to the ionizing radiation used postsurgically for the treatment of oral, head, and neck malignancies. Cumulative doses of as little as 6,000 centigray (cGy) of radiation can cause irreversible damage to the taste buds, and this level is reached and even exceeded for most patients receiving radiation [33]. The location of the lesion being irradiated and the total cumulative dose of radiation will determine which taste buds are damaged and to what extent. Radiation-induced damage of the salivary glands can compound this problem, as food particles not dissolved by saliva will not come into contact with the taste buds.

THE VERMILION ZONE OF THE LIPS

The vermilion zone is the margin of the lips between the skin on the exterior surface and the labial mucosa on the interior surface. This thin epithelial layer is keratinized, with capillary loops in its connective tissue core that allow a copious surface perfusion of blood and account for the vermilion (red) color of the lips. The tissue of the vermilion zone is considered a specialized mucosa. It has a dense submucosal layer with a firm attachment to the underlying musculature [34].

There are no mucous glands in the vermilion zone, so saliva is necessary to keep the area moist. Excessive desiccation of the vermilion zone due to extremes of temperature or excessive exposure to the wind leads to the condition known as "chapped lips." Commercial lip balms can palliate the symptoms associated with this problem.

This area may also show evidence of sun damage. The vermilion zone of the lower lip has more exposure to solar radiation compared to the slightly invaginated upper lip and is thus more prone to the development of squamous cell carcinoma.

5. THE SALIVARY GLANDS

Before the major and minor salivary glands and their unique histology can be discussed, it is essential to review the main components of saliva and their contribution to oral health. Saliva is a unique substance that functions as a tissue lubricant, as a medium for the remineralization of enamel, as an antimicrobial agent, and as a critical component in the self-cleansing mechanism for the teeth. Adequate salivary flow is essential for good oral health, as the decreased flow of saliva increases retention of plaque on the teeth and the mucosa and thus increases the risk of caries and periodontal disease. It is 99.5% water, with an assortment of 0.5% solutes accounting for the remainder [35].

Mucous secretions in saliva provide tissue lubrication, which is especially significant for patients who wear partial or complete dentures. Inadequate lubrication of the tissues supporting these prostheses can cause ulcerations and preclude their use. Immunoglobulin A (IgA), which can inhibit the adherence of some strains of streptococci bacteria to the oral mucosa, is secreted in saliva from the parotid salivary glands and the minor salivary glands [36]. Lysozyme, a hydrolytic enzyme secreted by the major and minor salivary glands, disrupts the structural integrity of the cell walls of certain bacteria [37]. Amylase is an enzyme in saliva that begins the breakdown of carbohydrates contained in food while it is in the oral cavity. Remineralization of small areas of enamel is mediated through an exchange of calcium and phosphate ions present in the saliva. There are trace amounts of several other organic and inorganic solutes in saliva that contribute to the overall health of the oral and maxillofacial complex.

Saliva originates in one of the three paired major salivary glands (parotid, sublingual, and submandibular) and numerous minor salivary glands. The basic secreting units of each gland are the acini. Serous acini produce a watery secretion, and mucous acini produce a thick, viscous secretion. The parotid gland produces serous secretions only, while the sublingual and submandibular glands produce both mucous and serous secretions. The minor salivary glands are widely distributed in the mucosa and submucosa of the oral cavity and produce predominantly mucous secretions. The major salivary glands are considered tubuloacinar, as their secretions are produced by acini and the initial portion of the duct system that transports these secretions into the oral cavity [34]. They are also considered exocrine glands, because their secretions must be brought to the surface by a series of ducts and tubes. This is in contrast to endocrine glands, such as the pituitary and adrenal glands, whose hormones enter the bloodstream directly. The production of saliva is an involuntary activity regulated by the sympathetic and parasympathetic divisions of the autonomic nervous system.

THE PAROTID GLAND

The parotid salivary glands are probably the best known among the major salivary glands. They are the largest among the major salivary glands, but they produce only about 20% of the total saliva [27]. Each parotid gland is wrapped in a subcutaneous connective tissue capsule located anterior and inferior to the ear and lies to the exterior of both the masseter and buccinators muscles. The parotid (Stensen) duct pierces the buccinator muscle and enters the oral cavity in a papilla on the buccal mucosa opposite the maxillary first or second molar area. As noted, the secretions of the parotid gland are purely serous in nature. The acinar cells that produce the secretions appear pyramidal and have an abundance of secretory vesicles called zymogen granules within the cytoplasm. Alpha amylase, a substance that begins the digestion of starches, is produced by the serous acini [1]. The ducts in the parotid gland are more than a conduit for saliva to the oral cavity; they are also involved in the secretion and absorption of varied substances.

The ducts originating in the secreting acini are narrow and intercalated and absorb chloride from and secrete bicarbonate ion into the acinar secretion. These ducts are lined with cuboidal or columnar cells. Striated (secretory) ducts continue from the intercalated ducts and resorb sodium and secrete potassium. A series of smaller excretory ducts merge to form a larger excretory duct that will discharge the saliva into the oral cavity. Myoepithelial cells with actin-containing contractile filaments lie adjacent to the acinar secretory cells and the intercalated ducts. The contraction of these myoepithelial cells helps to propel the contents of the secreting acinar cells into the lumen of the ducts and beyond. Bicarbonate secretion from the parotid gland is an important component of the buffering capacity of the oral cavity. A decrease in the bicarbonate production causes an increase in the acidity (lower pH) of the oral environment, which favors the proliferation of cariogenic bacteria and the resident fungal organism Candida albicans.

THE SUBMANDIBULAR GLAND

The submandibular gland is considered a mixed gland because its secretions are both serous and mucous, though serous secretions predominate. These bilateral glands are located inferior and medial to the posterior aspect of the mandible and superior to the digastric muscles. They enter the oral cavity via Wharton ducts. Small mucosal papilla (called sublingual caruncles) near the anterior midline on either side of the lingual frenum in the floor of the mouth mark the entrance of Wharton ducts into the oral cavity. Submandibular glands are smaller in size than the parotid glands, but they account for approximately 70% of salivary production [1]. The duct system and myoepithelial cells associated with the serous acini of the parotid gland remain unchanged in the submandibular gland [3]. However, mucous acini are also present and are responsible for the production of mucus, a glycoprotein-laden, viscous secretion whose primary functions are lubrication and protection of the tissue [31]. Each mucous cell contains numerous membrane-bound secretory granules, and the collective amount of mucus within these granules compresses the nucleus within each cell toward the cell membrane. After these granules have discharged their contents into the lumen of each acinar unit, the compression of the nucleus against the cell membrane is relaxed. Microscopically, the mucous acini have a pale appearance compared to the darker-staining granules of the serous acini.

THE SUBLINGUAL GLAND

The sublingual gland is also a mixed gland, with the mucous secretions predominating over the serous secretions. It is the smallest of the major salivary glands and produces about 5% of the salivary volume [27]. The sublingual gland is anterior to the submandibular gland and lies just beneath the mucosa of the floor of the mouth, between the mandible and the genioglossus muscle. Its inferior border is the mylohyoid muscle [30]. Unlike the parotid and submandibular glands, the sublingual gland does not have a connective tissue capsule surrounding it nor is it a single unit. It is comprised of a posterior portion (the greater sublingual gland) and an anterior portion (the lesser sublingual gland) with a duct system for each portion. The greater sublingual gland drains into a main duct (Bartholin duct), while the lesser sublingual gland drains into smaller multiple ducts (the ducts of Rivinus) [23]. Bartholin duct may unite with Wharton duct or may open in the floor of the mouth with individual sublingual papilla. The basic histology of the mucous and serous units is consistent with that of the parotid and submandibular glands.

MINOR SALIVARY GLANDS

As noted, the minor salivary glands are scattered throughout the oral cavity. Their highest concentration exists in the buccal, labial, palatal, and lingual mucosa. There is one duct per secreting unit rather than a main duct, like that present in the major salivary glands. The minor salivary glands may be serous, mucous, or mixed, and together they secrete about 5% of all the saliva produced. Mucus is the primary secretion of the minor salivary glands. Approximately 70% of all the mucus secreted originates from the minor salivary glands [12]. Like the sublingual glands, the minor glands have a low but continuous level of salivary production.

SALIVARY GLAND PATHOLOGY

The multiple functions of saliva are often unappreciated until their reduction is of sufficient magnitude to adversely affect oral health and overall quality of life. This section will highlight a few among the numerous pathologic entities that directly target the salivary glands and can cause an interference with their appropriate functions.

Radiation-Induced Xerostomia

Radiation therapy administered for oral or head and neck malignancies may damage the salivary glands, even if efforts are made to shield them from collateral damage. Common cumulative doses of radiation for oral malignancies (most often squamous cell carcinomas) fall into the range of 5,000–7,000 cGy. The serous acini of the major and minor salivary glands can experience a 50% decrease in their secretory activity when a cumulative dose of 1,000 cGy of radiation has been reached [26]. When a dose of 4,000 cGy of radiation has been achieved, a permanent reduction in salivary production from irradiated glands will occur [21].

The resulting xerostomia (dry mouth) is irreversible. For these patients, even the basic functions of life, such as eating, chewing, speaking, and swallowing, can become challenging. A decrease in the self-cleansing action of saliva and the antibacterial actions of lysozyme and IgA can result in a greater incidence of caries and periodontal disease. A decrease in the lubricating function in saliva can make the use of partial or complete dentures difficult or impossible.

Sjögren Syndrome

Sjögren syndrome is an autoimmune disease affecting the moisture-producing glands of the body. It features keratoconjunctivitis sicca (dry eyes) and xerostomia (dry mouth) as two of the classic presentations. The third presentation is a systemic connective tissue disease similar to lupus or rheumatoid arthritis. Approximately 4 million Americans have this disease, about 90% of whom are women [20]. The pathophysiology of Sjögren syndrome is characterized by a progressive infiltration of CD4+ and T-cell lymphocytes and plasma cells into the supporting tissue and acinar units of the salivary glands.

Fibrosis of the affected salivary gland tissue ensues, followed by a permanent decrease in the production of saliva [19]. These patients often experience the same oral health and quality of life issues seen in patients with oral cancer after radiation therapy. Patients with Sjögren syndrome may also have compromised dexterity, which can decrease their ability to brush and floss properly. Impaired ability to perform oral hygiene coupled with increased plaque retention due to hyposalivation can seriously undermine the oral health of these patients.

Medication-Induced Xerostomia

Many medications can decrease the flow of saliva as a known side effect. In some cases, alternative medications may provide the equivalent pharmacologic efficacy, but this is not always an option. Long-term or lifetime use of medications that cause xerostomia requires patients to maintain excellent oral hygiene. Periodic recall appointments should be scheduled on the basis of the patient's ability to maintain oral hygiene.

Sialolithiasis

Sialolithiasis is a benign condition in which calcium-laden crystalized minerals known as sialoliths, salivary calculi, or salivary stones become deposited in a salivary gland or a salivary duct. It is the most common disease affecting the salivary glands. More than 80% of cases occur in the submandibular gland or its duct, 6% involve the parotid gland, and only about 2% involve the sublingual and minor salivary glands [11]. The exact etiology of sialoliths is not known.

Symptoms of sialolithiasis can include pain, swelling, and even suppuration in the affected area. Palpation, occlusal radiographs, and imaging studies aid in the diagnosis. Smaller sialoliths may be flushed out if the patient increases fluid intake and sialogogues are taken to stimulate salivary production. Warm, moist heat coupled with massage of the affected duct or gland may also be helpful [6]. Surgical removal is usually required for larger sialoliths that do not respond to more conservative means of treatment.

6. CONCLUSION

The oral environment is a unique conglomeration of diverse hard and soft tissues with varied cellular compositions. These tissues are coordinated together in a manner that allows us to speak, masticate, swallow, and enjoy a positive quality of life. The functions of the teeth, mucosa, and salivary glands are a reflection of the underlying cellular composition.

This course has provided a brief overview of the histology and physiology of the structures treated by members of the dental team each day. The complexity of the cellular composition and physiology of structures discussed should instill a sense of respect and a renewed commitment to treat the teeth and the oral mucosa in a manner that promotes optimal oral and overall health and the best possible quality of life.

Works Cited

1. Scheid RC, Weiss G. Woelfel's Dental Anatomy. 9th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2016.

2. Boskey AL. Mineralization of bones and teeth. Elements. 2007;3:387-393.

3. Berkowitz BKB, Holland GR, Moxham BJ. Oral Anatomy, Embryology and Histology. 5th ed. revised. Edinburgh: Mosby; 2017.

4. Antonio N. Ten Cate's Oral Histology: Development, Structure and Function. 8th ed. St. Louis, MO: Mosby; 2014.

5. U.S. Department of Health and Human Services. Healthy People 2020: Oral Health. Available at https://www.healthypeople.gov/2020/topics-objectives/topic/oral-health. Last accessed December 9, 2019.

6. Pietz DM, Bach DE. Submandibular sialolithiasis. Gen Dent. 1987;35:494-496.

7. Rogers AH (ed). Molecular Oral Microbiology. Norfolk: Caister Academic Press; 2008.

8. Cochrane NJ, Cai F, Huq NL, Burrow MF, Reynolds EC. New approaches to enhanced remineralization of tooth enamel. J Dent Res. 2010;89(11):1187-1197.

9. U.S. Department of Health and Human Services Federal Panel on Community Water Fluoridation. U.S. Public Health Service recommendation for fluoride concentration in drinking water for the prevention of dental caries. Public Health Rep. 2015;130(4):318-331.

10. Buzalaf MA, Pessan JP, Honório HM, ten Cate JM. Mechanisms of action of fluoride for caries control. Monogr Oral Sci. 2011;22: 97-114.

11. Siddiqui SJ. Sialolithiasis: an unusually large submandibular salivary stone. Br Dent J. 2002;193:89-91.

12. Avery JK, Steele PF, Avery N (eds). Oral Development and Histology. 3rd ed. New York, NY: Thieme Medical Publishers; 2002.

13. Love RM, Jenkinson HF. Invasion of dentinal tubules by oral bacteria. Crit Rev Oral Biol Med. 2002;13(2):171-183.

14. Marieb EN, Hoehn K. Human Anatomy and Physiology. 10th ed. San Francisco, CA: Pearson; 2015.

15. Beltrami D. Gingival Crevicular Fluid. Available at http://flipper.diff.org/app/items/info/379. Last accessed December 9, 2019.

16. Kinane DF, Mombelli A. Periodontal Disease. Basel: Karger; 2012.

17. Oh SL. Attached gingiva: histology and surgical augmentation. Gen Dent. 2009;57(4):381-385.

18. Reddy S. Essentials of Clinical Periodontology and Periodontics. 4th ed. New Delhi: Jaycee Bros. Medical Publishers; 2014.

19. Little JW, Falace DA, Miller CS, Rhodus NL. Little and Falace's Dental Management of the Medically Compromised Patient. 8th ed. St. Louis, MO: Mosby; 2012.

20. Sjögren's Syndrome Foundation. About Sjögren's. Available at https://www.sjogrens.org/home/about-sjogrens. Last accessed December 9, 2019.

21. Barker BF, Barker GJ. Oral management of the patient with cancer in the head and neck region. J Calif Dent Assoc. 2001;29(8): 619-623.

22. Nanci A. Ten Cate's Oral Histology: Development, Structure and Function. 8th ed. St. Louis, MO: Mosby; 2012.

23. Smith SK, Karst NS. Head and Neck Histology and Anatomy: A Self-Instructional Program. Stamford, CT: Prentice Hall; 1999.

24. Sadatullah S. Periodontal Ligament. Available at https://www.slideshare.net/syedsadatullah/periodontal-ligament-6056478. Last accessed December 9, 2019.

25. University of Pennsylvania and Temple University. Histology of the Periodontium. Available at http://dental.pitt.edu/periohistology-0. Last accessed December 9, 2019.

26. Baharudin A, Khairuddin A, Nizam A, Samsuddin AR. Evaluation of irradiated salivary gland function in patients with head and neck tumors treated with radiotherapy. J Laryngol Otol. 2009;123(1):108-113.

27. Quizlet. Flashcards: DHYG Glands/Ducts. Available at https://quizlet.com/3417308/dhyg-glandsducts-flash-cards. Last accessed December 9, 2019.

28. Sidiropoulou-Chatzigiannis S, Kourtidou M, Tsalikis L. The effect of osteoporosis on periodontal status, alveolar bone and orthodontic tooth movement: a literature review. J Int Acad Periodontal. 2007;9(3):77-84.

29. Itoiz ME, Carranza FA. Gingiva. In: Newman MG, Takei HH, Klokkevold PR, Carranza FA (eds). Carranza's Clinical Periodontology. 12th ed. Philadelphia, PA: Saunders; 2014: 46-67.

30. Rosen FS. Anatomy and Physiology of the Salivary Glands. Available at https://www.utmb.edu/otoref/grnds/salivary-gland-2001-01/salivary-gland-2001-01.pdf. Last accessed December 9, 2019.

31. Histology at Southern Illinois University School of Medicine. Glands of the Gastrointestinal System. Available at http://www.siumed.edu/~dking2/erg/glands.htm. Last accessed December 9, 2019.

32. Wiegand A, Schwerzmann M, Sener B, et al. Impact of toothpaste slurry abrasivity and toothbrush filament stiffness on abrasion of eroded enamel: an in vitro study. Acta Odontol Scand. 2008;66(4):231-235.

33. Rankin KV, Jones DL (eds). Oral Health in Cancer Therapy: A Guide for Health Care Professionals. Austin TX: DOEP, Texas Cancer Council; 1999.

34. University of Western Australia. Blue Histology: Oral Cavity and Oesophagus. Available at http://www.lab.anhb.uwa.edu.au/mb140. Last accessed December 9, 2019.

35. de Almeida Pdel V, Grégio AM, Machado MA, de Lima AA, Azevedo LR. Saliva composition and functions: a comprehensive review. J Contemp Dent Pract. 2008;9(3):72-80.

36. Nieves A, Fitzgerel-Blue W. Saliva: Of Emerging Importance in the Medical and Dental Worlds. Available at https://www.rdhmag.com/pathology/temporomandibular-joint-dysfunction/article/16407983/saliva-of-emerging-importance-in-the-medical-and-dental-worlds. Last accessed December 9, 2019.

37. Salama R. Biochemistry of Saliva. Available at https://www.slideshare.net/drwalidsalem/composition-of-saliva-2010. Last accessed December 9, 2019.

55181 • Local Anesthetics in Dentistry

Mark J. Szarejko, DDS, FAGD

www.netce.com

Copyright © 2020 NetCE, All rights reserved.

The use of local anesthetics in dentistry has a long history of efficacy and safety. Very few dental procedures are accomplished without them, and often, this group of medications is taken for granted by both patients and clinicians. This course will review the history of local anesthetic use in dentistry and the current group of local anesthetics in use clinically. Properties that distinguish these medications from each other, indications/contraindications for use, the use of vasoconstrictors to prolong anesthesia, utilization of buffering solutions to prevent pain, and potential medical emergencies will be discussed.

Table of Contents

55181 • Local Anesthetics in Dentistry

Course Overview

Audience

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Division Planner

Division Planner Disclosure

Director of Development and Academic Affairs

Director Disclosure Statement

About the Sponsor

Disclosure Statement

Implicit Bias in Health Care

1. INTRODUCTION

2. AN HISTORICAL PERSPECTIVE

3. CHEMICAL CLASSIFICATION OF LOCAL ANESTHETICS

4. THE PHYSIOLOGY OF LOCAL ANESTHETICS

5. LOCAL ANESTHETIC AGENTS

VASOCONSTRICTORS

LIDOCAINE

ARTICAINE

BUPIVACAINE

PRILOCAINE

MEPIVACAINE

6. ADJUNCTIVE MEDICATIONS

TOPICAL ANESTHETICS

REVERSAL AGENTS

7. BUFFERING LOCAL ANESTHETIC SOLUTIONS

8. TREATMENT OF LOCAL ANESTHETIC-INDUCED MEDICAL EMERGENCIES

9. CONCLUSION

Works Cited

55181 • Local Anesthetics in Dentistry

Education Category. Pharmacology

Release Date. 02/01/2020

Expiration Date. 01/31/2023

Course Overview

The use of local anesthetics in dentistry has a long history of efficacy and safety. Very few dental procedures are accomplished without them, and often, this group of medications is taken for granted by both patients and clinicians. This course will review the history of local anesthetic use in dentistry and the current group of local anesthetics in use clinically. Properties that distinguish these medications from each other, indications/contraindications for use, the use of vasoconstrictors to prolong anesthesia, utilization of buffering solutions to prevent pain, and potential medical emergencies will be discussed.

Audience

This course is designed for all dental professionals whose patients may be administered local anesthetics.

Course Objective

The purpose of this course is to provide dental professionals with a comparative perspective on the use of local anesthetics.

Learning Objectives

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

1. Outline the history of local anesthetics.

2. Compare and contrast ester-type and amide-type local anesthetics.

3. Describe the basic neurophysiologic mechanisms of action of local anesthetics.

4. List the most common local anesthetics used in dentistry today, including pharmacologic properties and contraindications.

5. Discuss the available topical anesthetics used in conjunction with local anesthetics in dentistry.

6. Analyze the action of buffering solutions and anesthetic reversal agents.

Faculty

Mark J. Szarejko, DDS, FAGD, received his dental degree from the State University of New York at Buffalo in 1985. He received fellowship from the Academy of General Dentistry in 1994.

Faculty Disclosure

Contributing faculty, Mark J. Szarejko, DDS, FAGD, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Division Planner

William E. Frey, DDS, MS, FICD

Division Planner Disclosure

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

Director of Development and Academic Affairs

Sarah Campbell

Director Disclosure Statement

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

About the Sponsor

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

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

Disclosure Statement

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

Implicit Bias in Health Care

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

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

1. INTRODUCTION

Every day, dental patients undergo a variety of painless procedures, largely due to the efficacy of modern local anesthetics. "Painless dentistry" with the use of local anesthetics has become such a normal expectation that these medications are often taken for granted.

This course will begin with the history of local anesthetics, including the development of the predecessors of today's agents and their chemical classification. The physiology of neural conduction and the process by which local anesthetics interrupt this process to induce a temporary loss of sensation will be discussed, as it is critical to the understanding of how local anesthetics act. The most frequently used agents will be explored, including indications and contraindications of use and pharmacologic properties. Other components in anesthetic solutions, such as vasoconstrictors and preservatives, will also be discussed. The development and use of buffering solutions and anesthetic reversal agents will be reviewed, with a focus on their role facilitating the diminution of local anesthesia.

Although local anesthetics are largely safe, clinicians should not become complacent about their use, as medical emergencies are possible following their use. Clinicians should use their best judgement in selecting a local anesthetic based on the patient's medical history and the planned dental procedure(s).

2. AN HISTORICAL PERSPECTIVE

The use of modern local anesthetics was preceded by centuries of attempts to control acute and chronic odontogenic pain and to prevent pain during dental procedures. While these early methods are primitive by today's standards, their continual refinement and progression has led to a modern armamentarium of options to control and prevent pain related to dental procedures effectively and safely.

Today, cocaine is recognized as a harmful illicit drug, but it was also the predecessor of the current group of local anesthetics used in dentistry. Cocaine is derived from the coca plant (Erythroxylum coca or Erythroxylum novogranatense) native to western South America [1]. Indigenous groups would chew the leaves of the coca plant to elevate mood, aid digestion, and suppress the appetite [2]. In 1859, the chief alkaloid of coca was isolated and named "cocaine."

Cocaine is one of the only naturally occurring local anesthetics, along with neurotoxins (e.g., tetrodotoxin), menthol (derived from mint), and eugenol (derived from certain essential oils, such as clove). All modern local anesthetics are synthetic in origin. In 1884, Dr. Karl Koller introduced the use of cocaine for analgesic purposes in the field of ophthalmology [3]. The same year, Dr. William Halstead (a physician) used an injection of cocaine to successfully anesthetize the inferior alveolar nerve for the painless extraction of a patient's mandibular tooth [4]. Advertisements for over-the-counter cocaine drops that promised an instantaneous cure from toothache pain were promoted as early as 1885 [5].

The initial use of cocaine for medical purposes was done without knowledge of its adverse effects. Cocaine is an intensely vasoactive substance that can cause an extreme increase in blood pressure and heart rate, which can lead to death. Tolerance (i.e., increasing doses of cocaine needed to achieve euphoria) can develop very quickly. Cocaine use disorder and dependence are difficult to treat, and extended and escalating use is life-threatening. Many pioneers in the early medical use of cocaine, including Dr. Halstead, became addicted to cocaine via self-experimentation [3].

Given the acute and chronic adverse effects associated with cocaine, the search continued for a local anesthetic that would safely provide the desired anesthetic effects. In 1904, the German chemist Alfred Einhorn introduced the local anesthetic procaine, later more commonly known by its brand name, Novocain [6]. Although procaine, an ester-type local anesthetic, is no longer available in dental cartridges in the United States, "Novocain" is still used colloquially as an umbrella term for all local anesthetics. In 1948, lidocaine, an amide-type local anesthetic, was introduced by Nils Lofgren of Astra Pharmaceuticals [7]. Lidocaine is still widely used today, and for many it remains the "gold standard" of local anesthetics. Several additional local anesthetics have been developed since lidocaine was introduced, improving the ability of dental clinicians to safely provide profound local anesthesia.

3. CHEMICAL CLASSIFICATION OF LOCAL ANESTHETICS

The pharmacologic properties of local anesthetics are directly related to their molecular structure. The basic chemical structure of a local anesthetic consists of an aromatic ring (which enhances lipid solubility) and an intermediate ester or an amide chain and a terminal amine [8]. As such, all of these agents are classified as either an ester type or an amide type.

Procaine is an ester-type local anesthetic, as is the topical anesthetic benzocaine. However, the injectable local anesthetics commonly used in dentistry today are all classified as amides, including articaine, bupivacaine, lidocaine, mepivacaine, and prilocaine. Although articaine is technically classified as an amide-type local anesthetic, it is the only one that contains a thiophene (sulfur-containing) ring and an additional ester ring [9,46].

Amide-type local anesthetics have the same basic chemical structure of the ester types, but with an intermediate amide group (rather than an ester) and a terminal amine that enhances water solubility. The ability to obtain profound intraoral anesthesia is facilitated with the use of amide formulations compared with ester formulations, and as noted, they are greatly favored in the United States [11]. The risk of an allergic reaction is also significantly lower with amide-type local anesthetics compared with ester-types, but the amide-type has a slightly greater risk of systemic toxicity, usually dose related. The positive attributes of amide-type local anesthetics outweigh the potential for adverse systemic effects.

4. THE PHYSIOLOGY OF LOCAL ANESTHETICS

Local anesthetics used in dentistry induce a temporary loss of sensation in the various divisions of the maxillary and mandibular branches of the trigeminal nerve (i.e., cranial nerve V). Local anesthetics prevent the generation and propagation of nerve impulses in response to painful stimuli from procedures such as oral or periodontal surgery, restorative dentistry, or endodontic treatment.

Neurons are the basic structural cell of the nervous system and can be broadly categorized as either primary sensory (afferent) or motor (efferent). Sensory neurons are responsible for the transmission of sensory impulses, including painful stimuli, to the central nervous system (CNS). These neurons have three major components: the dendrites, the axon, and the cell body. The dendrites, also referred to as the peripheral process, are composed of branched terminal endings of the nerve that propagate stimulation received from other cells and conduct an impulse to the CNS. The impulse continues along the axon, a cable-like, myelinated structure that conducts the message to the brain or spinal cord. While an axon may appear to be a continuous, uninterrupted structure, there are small gaps in the myelin sheath at intervals of about 1 mm, known as nodes of Ranvier. The cell body is not involved in the transmission of neural impulses but functions to provide the metabolic needs of the neuron. The terminal endings of the axon form synapses with various nuclei of the CNS for the interpretation of the initial stimulus.

The propagation of an impulse along a neuron is an electrochemical event. Various concentrations of sodium, potassium, and chloride ions in the extracellular fluid that surrounds the axons and the axoplasm leave the interior of the axon with a negative electric potential of -70 mV when the neuron is in its resting state [12]. When the receptors in the peripheral zone perceive a stimulus, the initiation of a nerve impulse begins with a rapid increase of axon membrane permeability, a process known as depolarization. This features opening of sodium channels in the axon membrane that allow for an influx of sodium ions and a temporary reversal of the electric potential of the axon; the interior of the axon acquires an electric potential of +40 mV [13]. Repolarization returns the neuron to its normal resting electric potential. The process begins anew when a subsequent stimulus is encountered.

Local anesthetics exert their effect by binding to the intracellular surfaces of the sodium channels [14]. This action blocks the influx of sodium ions into the interior of the axon, which prevents depolarization of the axon and inhibits a sensory nerve impulse. When the local anesthetic diffuses away from the axon, normal sensory function returns. The type of anesthetic used and the inclusion of a vasoconstrictor (e.g., epinephrine) will influence the duration of this action. Certain factors, such as the presence of active infection in the area to be anesthetized, heightened patient anxiety, or inaccurate deposition of the agent, may affect the ability of a local anesthetic to achieve the appropriate level of anesthesia.

5. LOCAL ANESTHETIC AGENTS

Before any use of a local anesthetic, it is imperative to complete a review of the patient's medical history. Patients who report a history of adverse systemic effects after receiving an injection of a local anesthetic should be questioned as to the nature of the problem and the manner by which it was resolved. If necessary, previous clinicians should be contacted to determine the dose of the anesthetic used, whether the reaction was immediate or delayed, and the medical intervention required.

Though local anesthetic injections are very commonly used for dental procedures, it is important not to be complacent. Errors in injection technique can lead to an intravascular injection, which can cause adverse effects such as seizures and cardiovascular events. While serious adverse systemic effects are rare, careful injection technique can minimize their occurrence. Clinicians should always have the training and the equipment available to provide an immediate response in the event that a medical emergency develops after the injection of a local anesthetic or any other acute medical problem.

VASOCONSTRICTORS

The local anesthetics discussed in this section are all amide-type local anesthetics. As a group, these medications are classified as vasodilators. However, vasodilation in an area in which a local anesthetic is deposited is undesirable, as increased blood flow will expedite the elimination of the drug and decrease its duration of action. There is also an increased risk of rapid systemic absorption, with a commensurate increased risk of systemic toxicity. To combat this, vasoconstrictors have been added to most local anesthetics used in dentistry. Because most local anesthetics contain a vasoconstrictor, it is essential to understand their mechanism of action, pharmacologic effects, and potential problems associated with their use.

Most commonly, the vasoconstrictor epinephrine is added in a 1:100,000 concentration. Concentrations of 1:200,000 and 1:50,000 also exist, though the latter is rarely used due to its strong sympathomimetic (stimulant) cardiovascular effects. Epinephrine in its varied concentrations is used in conjunction with all local anesthetics except mepivacaine, with which a 1:20,000 concentration of levonordefrin is used. Levonordefrin in its 1:20,000 concentration has the approximate pharmacologic potency of 1:100,000 epinephrine [15,46]. Though the 1:100,000 concentration of epinephrine appears to offer no advantage in prolonging anesthesia compared to a 1:200,000 concentration, an improved ability to achieve hemostasis is facilitated with concentrations of 1:100,000 or greater [16].

Vasoconstrictors stimulate the contraction of the smooth muscle layer in blood vessels, which results in constriction of the blood vessels in the area and decreases the perfusion of blood. This decreased flow of blood to the anesthetized area favors the retention of the local anesthetic for an increased duration, increases the depth and profundity of anesthesia, and delays the systemic absorption of the local anesthetic (thereby decreasing the potential for systemic toxicity). The ability to achieve hemostasis is also facilitated when vasoconstrictors are included in local anesthetic solutions.

There has been concern about the use of epinephrine in patients with hypertension or ischemic heart disease due to the stimulant cardiovascular effects. The ability to obtain deep and prolonged anesthesia with the inclusion of epinephrine can minimize the potential for breakthrough pain during a dental procedure, thus minimizing the potential for a pain-related increase in blood pressure. In one study, the use of one to two cartridges of lidocaine with 1:100,000 epinephrine in the dental treatment of patients with cardiovascular disease was associated with a low frequency of adverse cardiovascular events [17]. Other studies have shown that the benefits of the extended duration of anesthesia associated with the co-administration of epinephrine are greater than the risk of a hypertensive crisis or cardiovascular problems during dental treatment [18]. However, caution is advised in applying the results of these studies to all patients with hypertension or cardiovascular disease, as the degree of morbidity can vary considerably. Vital signs should be taken before the administration of local anesthesia and ideally monitored during treatment. Dental treatment should be deferred in cases of elevated blood pressure. If there is any concern about the ability of a patient with hypertension or cardiovascular disease to tolerate the use of a local anesthetic with a vasoconstrictor, the patient's physician should be consulted first.

Epinephrine is an endogenous hormone produced by the adrenal gland and is an important component of the "fight-or-flight" response. An allergy to epinephrine is not possible given its production in the body. However, an inadvertent intravascular injection of a local anesthetic containing epinephrine can produce untoward symptoms such as tachycardia, heart palpitations, chest tightness, anxiety, and diaphoresis. If these symptoms emerge, the patient should be seated in an upright position and monitored closely until they resolve, usually within a few minutes. Symptoms that worsen require emergency medical treatment by the staff and contact of emergency medical services.

There are relatively few absolute contraindications to the use of epinephrine in local anesthetics. Patients with unstable angina, refractory arrhythmias, untreated or uncontrolled hypertension, or uncontrolled hyperthyroidism should not receive any elective dental treatment until they are medically stabilized. Epinephrine is also contraindicated in patients with pheochromocytoma, a tumor of the medulla of the adrenal gland that results in hypersecretion of endogenous epinephrine, with subsequent elevated blood pressure [19]. Emergency dental procedures for these patients should be performed in a hospital or an outpatient hospital center.

The life span of epinephrine and levonordefrin is extended by the inclusion of antioxidants such as sodium metabisulfite in the local anesthetic solution, and patients with an allergy to sulfites may experience an allergic reaction to the sodium metabisulfite preservative. These patients should be treated with an anesthetic that does not contain a vasoconstrictor in order to avoid a systemic allergic response [49].

LIDOCAINE

Since its introduction in 1948, lidocaine has become the most commonly used local anesthetic in the United States and remains the "gold standard" to which all other local anesthetics are compared [13]. It is available without epinephrine and with 1:50,000, 1:100,000, and 1:200,000 concentrations of epinephrine. As noted, the formulation with 1:100,000 epinephrine is used most frequently. Lidocaine is available in a 2% formulation in a 1.7-mL cartridge (containing 34 mg lidocaine) or a 1.8-mL cartridge (containing 36 mg lidocaine). The maximum recommended dose (MRD) of 2% lidocaine for adults and children older than 12 years of age is 7 mg per kg of body weight, to a maximum of 300 mg. Children younger than 12 years of age should receive a maximum of 4.5 mg per kg of body weight up to 100–150 mg [14]. The lowest possible dose of 2% lidocaine to provide the anesthesia required should be used, and the MRD should rarely be attained. During full-mouth extractions or full-mouth restorative rehabilitation, it is important to keep an accurate record of the number of cartridges used.

The onset of anesthesia for 2% lidocaine with 1:100,000 epinephrine is about five minutes, with a duration of approximately one hour for pulpal anesthesia and three to five hours for soft tissue anesthesia [46]. Amide-type anesthetics like lidocaine are metabolized by the liver and excreted by the kidneys, so the presence of hepatic and/or renal disease can compromise metabolism. For patients with these conditions, consultation with the patient's physician may be necessary in order to determine the dose of lidocaine that can be metabolized and excreted safely under these conditions. The 2% lidocaine formulation with 1:50,000 epinephrine should not be used for patients with hypertension or cardiovascular disease given the enhanced stimulant effect; a lower epinephrine concentration should be used [21].

ARTICAINE

Articaine is the most recent addition to the dental local anesthetic market in the United States. Although it has been used in Germany since 1976, approval for use in the United States was granted in 2000 [22,23]. Initial approval of articaine was delayed because it contained the banned preservative methylparaben [24]. Sodium metabisulfite is now used as the preservative in articaine plus epinephrine, so use of this local anesthetic should be avoided in patients with sulfite allergies.

Articaine is available in a 4% formulation in 1.7-mL cartridges with 1:100,000 or 1:200,000 epinephrine concentration; one cartridge contains 68 mg of articaine. Although articaine is classified as an amide-type local anesthetic, as discussed, it has a unique chemical structure, with a thiophene ring and an additional ester ring [25,46,59]. The thiophene ring increases the lipid solubility of articaine and promotes faster absorption though the lipid component of the neuron membrane. This should translate to a faster onset of anesthesia compared with other amide-type local anesthetics, but studies have been conflicting [26,27,28]. Some studies have suggested that there is no significant difference in the onset of anesthesia of articaine and other local anesthetics, such as lidocaine and prilocaine [26]. One study suggested that articaine did have a faster onset of anesthesia when compared with lidocaine, and other studies have suggested that a faster onset of anesthesia with articaine was found with anterior but not posterior teeth [27,28,58]. Given the variable results of these studies, it cannot be stated with scientific certainty that the onset of anesthesia of articaine is faster than that of lidocaine or prilocaine.

The ester side chain also influences the way articaine is metabolized. The other amide local anesthetics are primarily metabolized in the liver. Due to the presence of the ester side chain, approximately 90% to 95% of articaine is metabolized in the plasma by plasma carboxylesterase, with only about 5% to 10% undergoing metabolism by the liver [29]. Because the metabolism of articaine has minimal reliance on hepatic metabolism, it is the anesthetic of choice for patients with compromised liver function, including those with hepatitis C or cirrhosis. Articaine plasma metabolism is much quicker than the hepatic metabolism of other amide-type local anesthetics, resulting in a shorter half-life (20 minutes) compared with lidocaine (90 minutes) [8]. In lengthy dental procedures, when additional doses of a local anesthetic are required, the expedited clearance of articaine minimizes the occurrence of an accumulation of toxic levels of this anesthetic.

The onset of infiltration anesthesia for articaine with 1:100,000 or 1:200,000 concentration of epinephrine is approximately one to two minutes, and the onset for anesthesia with a mandibular block is two to three minutes for articaine with a 1:200,000 concentration of epinephrine [13]. There does not appear to be a significant difference in the duration of pulpal anesthesia between articaine with 1:100,000 or 1:200,000 concentration of epinephrine [57]. The 1:200,000 concentration is preferred for patients with hypertension or cardiovascular disease.

The MRD of articaine for adults is 7 mg per kg of body weight up to 500 mg per appointment. Children older than 4 years of age have an MRD of 5 mg per kg, significantly lower than the allowed maximum for adults [30]. Clinicians who rarely treat children should be cognizant of this difference to avoid using a toxic dose. This anesthetic is not recommended for children younger than 4 years of age.

Articaine has an exceptional ability to penetrate dense cortical bone to the extent that some studies have noted that maxillary buccal infiltration has produced anesthesia on the corresponding palatal area without the need for a separate injection for the palate, although this needs to be replicated in future studies [31,32]. There are also some concerns that articaine's 4% solution may confer a higher risk of prolonged paresthesia or anesthesia following blocks of the inferior alveolar (mandibular) nerve, and reports on this issue have been conflicting. Mitigating factors, such as nerve damage during the surgical removal of mandibular molars (especially third molars) or direct trauma from the needle striking the inferior alveolar nerve during an injection, can also result in prolonged anesthesia or paresthesia.

International studies have observed an increase in nerve injuries the year after articaine was introduced [33]. However, a retrospective study in the United States that analyzed data of patients with nerve dysfunction following an injection of a local anesthetic did not duplicate these data. In this analysis, lidocaine was used in 35% of cases of nerve dysfunction, compared with articaine, which was used in 30% of cases [34]. Clinicians should keep abreast of new studies and developments to determine if the use of articaine is appropriate for their patients.

BUPIVACAINE

Bupivacaine has been available in cartridge form in the United States since 1983 [13]. Bupivacaine is an analogue of mepivacaine, another amide-type of local anesthetic, but with a fourfold increase in potency and toxicity [21]. Bupivacaine is only available in a 0.5% formulation with a 1:200,000 concentration of epinephrine. Bupivacaine binds strongly to sodium channel proteins, which causes a protracted closing of these channels and prevents initiation and propagation of nerve impulse for an extended time, resulting in a prolonged anesthetic effect [35]. It takes 6 to 10 minutes for the onset of anesthesia, which is the slowest of all amide anesthetics. As such, this is not the anesthetic of choice for short-to-intermediate dental procedures. It also has the longest duration of both pulpal and soft tissue anesthesia, making it an ideal anesthetic for lengthy restorative procedures and to prevent post-surgical emergence of pain. After an inferior alveolar nerve block, the duration of pulpal anesthesia is approximately 1.5 hours; the duration of soft tissue anesthesia can extend up to 12 hours [20,35].

While the extended duration of anesthesia is desirable for certain cases, it can also increase the potential for iatrogenic tissue trauma (i.e., patients accidentally biting anesthetized soft tissue of the lip, cheek, or tongue). Bupivacaine should not be used in patients who have poor neuromuscular control, including those with Parkinson disease, residual neuromuscular coordination problems due to cerebral palsy or stroke, or the advanced stages of degenerative neuromuscular diseases such as multiple sclerosis. Similarly, patients with cognitive impairment that precludes their ability to comprehend and remember post-operative instructions may also have an increased potential for soft tissue damage when anesthesia is extended.

A 1.8-mL cartridge of 0.5% bupivacaine contains 9 mg of the drug. The MRD of bupivacaine for adults and children 12 years of age and older is 90 mg per appointment, or 10 cartridges. Although 10 cartridges is allowable, this is a large dose and clinicians should strive to use the minimum dose necessary to provide the appropriate depth and duration of anesthesia required for the procedure. Bupivacaine is not recommended for patients younger than 12 years of age [14,59]. Because bupivacaine preparations include a 1:200,000 concentration of epinephrine, the considerations outlined for this vasoconstrictor should also be taken into account.

PRILOCAINE

Prilocaine first entered the U.S. dental market in 1971 [36]. It is currently available in a 4% formulation with a 1:200,000 concentration of epinephrine. Because prilocaine is associated with fewer vasodilation properties than lidocaine, it is also available plain, with no vasoconstrictor. Prilocaine plain is ideal for patients who have allergies to sulfites, as it is free of sodium metabisulfite.

The time for onset of anesthesia and duration of pulpal and soft tissue anesthesia vary depending on the affected arch (maxillary or mandibular), whether infiltration or an inferior alveolar nerve block was used, and whether the plain formulation or the formulation including epinephrine is used. When prilocaine plain is used for maxillary teeth, the onset of anesthesia is two to three minutes, with a duration of pulpal anesthesia of about 15 minutes and soft tissue anesthesia of about 1 to 1.5 hours. When prilocaine with 1:200,000 epinephrine is used for the maxillary teeth, the onset of anesthesia is about 2 minutes, with a duration of pulpal anesthesia of about 45 minutes and a duration of soft tissue anesthesia of approximately 2 hours. When anesthesia for mandibular molars requires blocking the inferior alveolar nerve, the onset of anesthesia for prilocaine plain is 5 minutes or more, with the duration of pulpal anesthesia being 1 to 1.5 hours while soft tissue anesthesia may extend to 2.5 hours. When prilocaine with 1:200,000 epinephrine is used for anesthetizing mandibular molars by the nerve block, the onset of anesthesia ranges between two to four minutes. In this case, the duration of pulpal anesthesia is approximately 1.5 hours, while soft tissue anesthesia can extend to 3 hours. Prilocaine plain is suitable for shorter procedures, and prilocaine with 1:200,000 epinephrine can be used for short and intermediate dental procedures [37,46].

Each 1.7-mL cartridge of prilocaine contains 68 mg of the active anesthetic. The MRD of both forms of prilocaine is 6 mg per kg of body weight for adults, with a maximum cumulative dose of 400 mg, or less than six cartridges per appointment [13,59].

As with the 4% articaine solution, concerns regarding the potential for neurotoxicity have also been raised about 4% prilocaine. Studies exploring the relationship between the use of 4% prilocaine for inferior alveolar (mandibular) nerve blocks and the subsequent development of an oral paresthesia of the lip and/or tongue reveal that there is a very slightly increased risk. A 2010 report reviewed 10 years of U.S. cases of oral paresthesia involving articaine, bupivacaine, lidocaine, mepivacaine, and prilocaine [38]. The overall incidence of oral paresthesias for all local anesthetics was one case per 13.8 million cartridges used. Prilocaine alone was associated with an incidence of one case of oral paresthesia for every 2 million cartridges used [38]. A 2015 analysis of the U.S. Food and Drug Administration Adverse Event Reporting System showed similar results, with prilocaine having the greatest association with paresthesia [60]. While the risk of an oral paresthesia after the use of prilocaine for mandibular blocks is small, it is greater than the composite risk of all of the other amide-type anesthetics combined.

Prilocaine is also associated with a rare but potentially serious problem called methemoglobinemia. (This complication is also theoretically possible with articaine and benzocaine, but no cases have been reported with appropriate dental use.) This can occur due to congenital errors of metabolism or by the use of medications that increase plasma concentrations of methemoglobin. Methemoglobin is a variant of hemoglobin that is incapable of binding oxygen, and methemoglobinemia is diagnosed when red blood cells contain more than 1% methemoglobin [8]. A metabolite of prilocaine, o-toluidine, can stimulate the formation of methemoglobin, potentially to the point of toxicity. This problem is unlikely to occur when the MRD of prilocaine is not exceeded.

Patients will become symptomatic when the proportion of methemoglobin exceeds 10% to 15% [39]. Cyanosis is usually evident in the nail beds and the lips; other symptoms include fatigue, shortness of breath, and mental status changes. Patients who develop methemoglobinemia require intravenous administration of methylene blue to reverse the problem [36]. Supplemental oxygen is not useful, as methemoglobin does not carry oxygen. Hereditary methemoglobinemia is an absolute contraindication for the use of prilocaine.

Prilocaine is metabolized by the liver and excreted by the kidneys. If hepatic or renal disease is present, the patient's physician should be consulted about the ability to use this agent or the need to adjust the dose.

Lidocaine/Prilocaine Combination

In 2003, a needle-free combination of lidocaine 25 mg/g and prilocaine 25 mg/g in a gel formulation was approved for dental use [40]. These local anesthetics are combined in preloaded cartridges and are introduced circumferentially around the gingival sulcus of a tooth that is to undergo a root planing and scaling procedure. The onset of anesthesia is 30 seconds and the duration is approximately 20 minutes. The intent is to provide local anesthesia for the contiguous periodontal tissues without residual numbness of the lip, tongue, or cheek. This formulation is considered a local anesthetic that is applied subgingivally (rather than a topical anesthetic). Lidocaine/prilocaine (brand name Oraqix) is available in 1.7-g cartridges. The MRD per appointment is 8.5 grams, or five cartridges [14,59]. These are both amide anesthetics, so they undergo hepatic metabolism and renal excretion. Because prilocaine is a component of this formulation, it should not be used in patients with a history of hereditary methemoglobinemia.

MEPIVACAINE

Mepivacaine is available in two distinct formulations in the United States. Because it produces less vasodilation, it is available with no vasoconstrictor as 3% plain or in a 2% formulation with 1:20,000 levonordefrin.

Mepivacaine 3% Plain

Mepivacaine 3% plain is available under several brand names in 1.7-mL cartridges. It was originally approved in 1960 for use as a local anesthetic in dentistry [41]. The onset of anesthesia is similar to that of lidocaine. When mepivacaine 3% is used for a block of the inferior alveolar (mandibular) nerve, the duration of pulpal anesthesia is 40 minutes; this reduces to only about 20 minutes when used for infiltration anesthesia. Soft tissue anesthesia lasts approximately three hours when the mandibular block is utilized and about two hours when administered via infiltration [42]. As such, this anesthetic is ideal for procedures of short duration.

The MRD of mepivacaine 3% plain for children younger than 10 years of age is 5–6 mg per kg of body weight, with an absolute maximum of 270 mg per appointment. Adults and children older than 10 years of age may be dosed a maximum of 6.6 mg per kg of body weight, up to 300 mg [14]. Given that each cartridge contains 51 mg of active anesthetic, no more than five to six cartridges should be used [13,59].

As with all local anesthetics, the lowest cumulative dose possible should be used to achieve anesthesia and complete the dental procedure. This is particularly essential when mepivacaine 3% plain is used in children. The short duration of 3% mepivacaine minimizes the potential for traumatization of anesthetized soft tissue; however, it is 1.5 times more toxic than the 2% formulation [43]. Therefore, the use of mepivacaine 3% plain in children, especially those younger than 5 years of age, should be administered via infiltration and restricted to the smallest dose whenever possible.

Mepivacaine 3% plain undergoes metabolism in the liver and is excreted by the kidneys, so an adjustment of the dosage may be required in the presence of hepatic or renal disease.

Mepivacaine 2% with 1:20,000 Levonordefrin

The 2% formulation of mepivacaine is the only amide-type anesthetic in the United States that uses levonordefrin as the vasoconstrictor rather than epinephrine. In a formulation of 1:20,000, levonordefrin is 5 times more concentrated than 1:100,000 epinephrine and 10 times more concentrated than epinephrine in a 1:200,000 concentration. Like epinephrine, levonordefrin has stimulant effects on the cardiovascular system (i.e., elevates systolic and diastolic blood pressure and mean arterial pressure), so it should be used with caution in patients with cardiovascular disease and/or hypertension [44,59]. The physiologic effects of levonordefrin are similar to those of norepinephrine, another catecholamine that is secreted by the medulla of the adrenal gland.

Mepivacaine 2% with 1:20,000 levonordefrin has a depth and duration of pulpal and soft tissue anesthesia that is similar to lidocaine with 1:100,000 epinephrine; however, it does not provide the same degree of hemostasis [45]. As such, this is not the anesthetic/vasoconstrictor of choice for oral or periodontal surgical procedures, especially those involving multiple teeth or quadrants.

The addition of 1:20,000 levonordefrin extends the duration of anesthesia compared with 3% mepivacaine plain. Pulpal anesthesia lasts approximately 1.5 hours after inferior alveolar (mandibular) nerve block and approximately 1 hour after infiltration administration for maxillary teeth. Soft tissue anesthesia extends to approximately five hours after a mandibular block and approximately three hours after infiltrative administration [42,46].

Mepivacaine 2% with 1:20,000 levonordefrin is available in 1.7-mL cartridges, with 34 mg of mepivacaine per cartridge. The MRD for adults is 400 mg mepivacaine per appointment, and the maximum pediatric dose per appointment is 6.6 mg per kg of body weight or 180 mg, whichever is less [14,59].

Elevated blood pressure can occur at doses that are well below the MRD, and clinicians should keep in mind that excessive blood plasma levels of levonordefrin can produce an adverse cardiovascular event. The inclusion of levonordefrin requires the addition of a preservative (e.g., sodium metabisulfite); patients with a sulfite allergy can be administered 3% mepivacaine plain, but the 2% formulation should be avoided.

6. ADJUNCTIVE MEDICATIONS

Many patients fear that injections of a local anesthetic will be painful, and this is one of the reasons that people may defer necessary dental treatment. In addition, patients may complain about the awkward feeling of residual "numbness" following the administration of local anesthetic that can temporarily interfere with eating, speaking, and swallowing. Medications are available to minimize the discomfort associated with injections of local anesthetics and hasten the return to "normal" feeling of tissues that were anesthetized.

TOPICAL ANESTHETICS

Topical anesthetics may be used to minimize the pain associated with the initial penetration of the anesthetic needle. These agents are available as gels, sprays, or muco-adherent patches and are an excellent means to increase patient comfort during an injection procedure. Because these medications undergo systemic absorption, they should not be applied to areas in which the tissue is ulcerated and/or highly inflamed. The most frequently used options include benzocaine and lidocaine.

Benzocaine

Benzocaine gel in a concentration of 20% is the most common topical anesthetic used in dentistry. It is marketed under several brand names and is available in many flavors to enhance patient acceptance. Benzocaine is not water-soluble, so it must be combined with other substances (e.g., alcohol, propylene glycol, polyethylene glycol) in order to make it suitable for application to the oral mucosa [13]. The tissue of the intended injected site should be isolated and dried prior to the application of benzocaine, as salivary contamination can dilute the drug and negate its effectiveness.

Benzocaine 20% formulations penetrate the oral mucosa to a depth to 2–3 mm and minimize the sensation of the initial insertion of the needle. Benzocaine 20% is also available in a liquid spray formulation, but this application can make it difficult to control the amount used and lacks the tissue adherence of the gel formulations. This will minimize the anesthetic effect and can also result in patients swallowing the topical preparation, causing transient anesthesia of the pharyngeal region and difficulty in speaking and swallowing. Inhalation of a spray of benzocaine 20% that is misdirected toward the oropharynx can lead to potentially serious problems such as laryngospasm.

Ester-type local anesthetics and articaine (because of its additional ester ring) are associated with a higher incidence of allergic reactions because their metabolism yields a p-aminobenzoic acid (PABA) metabolite [10]. Inflammation or ulceration at the site of benzocaine application suggests a hypersensitivity reaction and requires the use of an alternative topical anesthetic. If a patient displays a hypersensitivity reaction to topical benzocaine, articaine should not be used due to the potential for cross-sensitivity. If a flavored topical anesthetic is used, care should be taken to ensure that patients (particularly children) do not ingest the formulation. As noted for prilocaine, methemoglobinemia is a rare but potential adverse effect of benzocaine use, especially when used in the spray formulation in children [11].

Topical benzocaine 20% has the same mechanism of action as injectable local anesthetics. It decreases the neuron membrane permeability to sodium ions, thus blocking the initiation and conduction of a nerve impulse. However, the area involved and the duration of action are much less than that of an injectable anesthetic. As with all anesthetics, the smallest possible dose of benzocaine 20% should be used. Patients with a history of allergic reaction to ester formulations or hereditary methemoglobinemia should use an alternative topical anesthetic.

Lidocaine

Lidocaine is used as both an injectable and a topical anesthetic. Topically, it is available as a 2% or 5% gel, 2% solution, 4% or 5% solution, 5% ointment, or 10% spray [61]. Lidocaine 5% topicals have a similar potency to 20% benzocaine; however, its onset of action is more delayed, requiring at least three minutes to achieve adequate anesthesia. It is effective on alveolar mucus but not on the palatal mucous membrane [61].

REVERSAL AGENTS

The ability to maintain prolonged anesthesia after the completion of oral or periodontal surgery and endodontic therapy is essential. However, many procedures, including basic restorative procedures, do not require extended anesthesia. When protracted anesthesia is not required, an extended period of "numbness" in the lip, tongue, and cheek can make basic functions such as masticating, speaking, and swallowing difficult and can increase the risk of iatrogenic soft tissue damage (i.e., biting oral soft tissues that remain anesthetized). This can be a special concern among children and patients with acquired or congenital neuromuscular diseases or muscle control problems.

In 2008, phentolamine mesylate, an anesthetic reversal agent, was approved for dental use in the United States [47]. Originally developed in the 1950s to decrease elevated blood pressure associated with pheochromocytoma, phentolamine mesylate is classified as a vasodilator [48]. It is supplied in 1.7-mL cartridges under the brand name OraVerse and is the only reversal agent available for local anesthetic agents used in dentistry. Each cartridge contains 0.4 mg of the drug. In adults, dosing is dependent on the number of cartridges of anesthetics used; 0.2 mg of phentolamine mesylate should be administered for each one-half cartridge (i.e., 0.4 mg per one cartridge). Phentolamine mesylate acts as an alpha-adrenergic receptor antagonist that competes with vasoconstrictors (e.g., epinephrine) for the same receptor sites [59]. This results in decreased vasoconstriction and more vasodilation, which promotes an expedited uptake of the local anesthetic and a return to normal sensation for the patient.

A study published in the Journal of the American Dental Association evaluated the effectiveness of phentolamine mesylate in reducing the duration of anesthesia [50]. A group of 115 children between 6 and 11 years of age were divided into either a treatment group (receiving an injection of phentolamine mesylate) or a placebo group. The median time for return of normal lip sensation in the treatment group was 60 minutes; time to return to normal sensation was more than twice as long (135 minutes) in the placebo group. Of the 38 patients who had dental procedures performed on the mandibular arch, there was a 120-minute reduction in the median time that it took to regain normal sensation in the lip. The 34 patients with dental procedures completed on the maxillary arch experienced a 52.5-minute reduction in the median time that it took to regain normal sensation in the lip with the administration of phentolamine mesylate [50]. Subsequent studies have shown similar effectiveness [62].

The expedited return to normal sensation decreases the risk of iatrogenic tissue damage and facilitates the return to normal oral function. However, as with any medication, there are potential adverse effects. Injection site pain and reports of transient paresthesia have been associated with phentolamine mesylate use [14]. Because phentolamine mesylate is a vasodilator, its concurrent use with other medications that cause vasodilation can lead to an unsafe decrease in blood pressure. This includes phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil, vardenafil) used in the treatment of erectile dysfunction and nitrates used to treat ischemic heart disease; use of these medications precludes the simultaneous use of phentolamine mesylate. Phentolamine mesylate is also contraindicated in patients who are younger than 6 years of age, who weigh less than 15 kg (33 lbs), who have a history of angina or myocardial infarction, or who have a known hypersensitivity to phentolamine mesylate [42]. The initial use of phentolamine mesylate as an anesthetic reversal agent in dentistry has provided encouraging results. Long-term studies and continued research are essential to determine if any problems or contraindications emerge with its continued use.

7. BUFFERING LOCAL ANESTHETIC SOLUTIONS

Pain that patients perceive after the initial penetration of the needle can be caused by advancement of the needle through the tissue layers (especially while blocking the inferior alveolar nerve of the mandibular arch) or pressure of the anesthetic solution against mucosal tissue that is bound tightly to the underlying bone, such as on the hard palate. However, the acidic chemical composition of the local anesthetic solution may also cause pain.

Local anesthetic solutions that are "plain" (no vasoconstrictor) have a pH of approximately 5.9, while those containing epinephrine or levonordefrin have a pH of approximately 3.5, which classifies these as solutions with weak-to-moderate acidity [51]. The "sting" or "burning" patients feel during the injection of a local anesthetic is a result of this acidity. This may also account for post-injection soft tissue trauma. Manufacturers have addressed this issue by developing a system to increase the pH of a local anesthetic solution to increase patient comfort and minimize the potential for acidity-related soft tissue trauma after the injection.

Local anesthetic solutions are combined with an acid (hydrogen chloride) to form a salt (hydrochloride) to facilitate water-solubility. The additional use of sodium metabisulfite in solutions with vasoconstrictors further decreases the pH. A chairside system has been developed by which an 8.4% sodium bicarbonate solution can be mixed with a standard cartridge of a local anesthetic solution to increase the pH. A mixing pen is used to transfer some of the 8.4% sodium bicarbonate solution from a separate cartridge into the 1.8- or 1.7-mL local anesthetic cartridge, with a connector used to secure the two cartridges together during the transfer process [52]. The chemical interaction between the sodium bicarbonate and the hydrochloride of the local anesthetic solution produces both carbon dioxide and water. The use of this buffering system increases the pH of lidocaine with epinephrine from 3.3 (moderate acid) to 7.4 (weak base) and also increases the amount of ionized anesthetic available to penetrate the neuron [53,49]. This allows for a more comfortable injection and promotes a faster onset of anesthesia.

Initial results from the use of this system are encouraging. However, research and long-term studies are needed to further explore the advantages and disadvantages of this system. The initial and recurring cost associated with use of this system may be offset by the ability to obtain profound anesthesia more quickly and with less pain, potentially allowing the clinician to treat more patients.

8. TREATMENT OF LOCAL ANESTHETIC-INDUCED MEDICAL EMERGENCIES

Although local anesthetics are generally safe, medical emergencies can occur with their use. Therefore, all staff should have a clear understanding of possible adverse events and how they can be safely managed.

Although vasoconstrictors should be avoided in patients with sulfite compound allergy, they usually play an important role in minimizing the rapid systemic dissemination of the local anesthetic. Both epinephrine and levonordefrin constrict blood vessels in the injection area, resulting in a slower systemic absorption and decreasing the chance of systemic toxicity. Aspirating before injecting slowly also minimizes the chance that the local anesthetic will be injected directly into a blood vessel, decreasing the rate of systemic circulation. Direct intravascular injection of an entire cartridge of a local anesthetic can have adverse effects on both cerebral and cardiac tissues.

The prevention of toxicity from local anesthetics involves more than a careful injection technique. A patient's age, weight, medical conditions, and current medications can all influence the metabolism and clearance of local anesthetics. The most common cause of local anesthetic toxicity is an overdose of the medication relative to the age and weight of the patient. This occurs most often in pediatric patients, but excessive doses can occur in adults, particularly elderly individuals [54]. Some local anesthetics, such as bupivacaine, are not recommended for use in patients younger than 12 years of age. Children do not have the capability to metabolize and excrete local anesthetics as well as healthy adults. In addition, the elderly, adults with low body weight, and those with chronic illness(es) may have a diminished capacity to metabolize and excrete local anesthetics. Clinicians should avoid using the same dose on each patient without regard to these factors.

Systemic disease can also affect an individual's ability to metabolize and excrete local anesthetics. Amide-type local anesthetics undergo metabolism primarily in the liver and excretion is via the kidneys. Diseases such as hepatitis and cirrhosis can adversely affect hepatic function and decrease the liver's ability to metabolize these anesthetics; a dose that is usually appropriate for the age and weight of a healthy patient can gradually accumulate to toxic levels. Patients with impaired renal function, especially those with end-stage renal disease and those on dialysis, will have difficulty excreting metabolized local anesthetics. These patients' physicians and specialists should be consulted about an appropriate dosing schedule. When multiple quadrants of restorative treatment are performed, full-mouth extractions completed, or multiple doses are administered in the same area in patients who are having difficulty achieving a state of anesthesia, the maximum allowable local anesthetic dose for the patient can be achieved quickly.

The concurrent use of certain medications can also alter the metabolism of local anesthetics. Medications such as phenytoin, meperidine, and desipramine compete with local anesthetics for the same protein binding sites, which can decrease efficacy of both drugs [13]. Cimetidine, which is in common use for the treatment of gastroesophageal reflux disease and ulcers, can decrease the rate at which lidocaine is metabolized in the liver, as both medications compete for the same hepatic enzymes [55]. These instances of competitive drug metabolism can cause a local anesthetic to be retained longer, and a toxic accumulation may be reached faster if the dose is not adjusted.

The manifestations of toxicity to local anesthetics and their vasoconstrictors can have different clinical appearances. When a local anesthetic with epinephrine is injected into a blood vessel and distributed systemically, patients may experience tachycardia, heart palpitations, and anxiety. This is usually a transient reaction that subsides in a few minutes. However, patients should be monitored to assure that it is not the beginning of a more progressive toxic reaction. Furthermore, patients should never be left alone after a local anesthetic has been injected.

Local anesthetics can cross the blood-brain barrier and can exert a depressant or excitatory action on both the CNS and the cardiovascular system. Some toxic reactions to local anesthetics can occur rapidly after the injection, while others may be delayed for several minutes. A clinically evident excitatory phase, featuring excessive talking, apprehension, and excitability, may be present during these reactions. Among the local anesthetics used, the lack of this phase occurs more frequently with lidocaine [56,60]. Patients can progress to demonstrate signs of slurred speech, diaphoresis, nausea, vomiting, tachycardia, and an increased rate of breathing when the degree of toxicity is minimal to moderate. When higher doses of a local anesthetic cause more severe acute toxicity, the patient may develop seizures, CNS depression, hypotension, bradycardia, and a decreased respiratory rate.

When any sign of local anesthetic toxicity emerges, members of the dental care team should begin monitoring the vital signs. Fortunately, most reactions to a local anesthetic toxicity are mild and self-limiting, with only the use of supplemental oxygen needed to assist the patient. More severe reactions occur within one minute of administration of the local anesthetic and can lead to seizures and unconsciousness. When this occurs, one staff member should contact emergency medical services while the dentist and others are monitoring the airway, breathing, and circulation of the patient. If the patient has seizures that do not appear to be decreasing in intensity, a benzodiazepine may be used. The dental staff should stabilize the patient until emergency help has arrived. In rare cases, this may involve the administration of cardiopulmonary resuscitation and/or the use of an automated external defibrillator. An analysis should be completed to determine the cause of the toxic reaction so recurrence can be prevented.

9. CONCLUSION

This course has provided an overview of the local anesthetics used in dentistry today. These injectable medications have an outstanding safety record and consistent efficacy in achieving anesthesia. Although local anesthetics are widely used, clinicians should avoid becoming complacent about their use; adverse reactions can occur. Clinicians should not hesitate to consult with the patient's physician or specialist if there is any underlying medical condition that could challenge the patient's ability to receive, metabolize, or excrete a local anesthetic. Consideration of all aspects of the use of local anesthetics allows them to be used in a way that minimizes the potential for an untoward event while maximizing the comfort and safety of the patient.

Works Cited

1. National Institute on Drug Abuse. Drug Facts: Cocaine. Available at https://www.drugabuse.gov/publications/drugfacts/cocaine. Last accessed December 11, 2019.

2. Drug Enforcement Administration Museum. Cannabis, Coca and Poppy: Nature's Addictive Plants. Available at https://www.deamuseum.org/ccp. Last accessed December 11, 2019.

3. McLeod IK. Local Anesthetics. Available at https://emedicine.medscape.com/article/873879-overview. Last accessed December 11, 2019.

4. Goldie MP. The Evolution of Analgesia and Anesthesia in Oral Health Care. Available at https://www.rdhmag.com/career-profession/personal-wellness/article/16404914/the-evolution-of-analgesia-and-anesthesia-in-oral-health-care. Last accessed December 11, 2019.

5. Calcaterra N. Cocaine and Dentistry. Available at http://directionsindentistry.net/cocaine-dentistry-local-anesthetic/. Last accessed December 11, 2019.

6. National Inventors Hall of Fame. Alfred Einhorn. Available at https://www.invent.org/inductees/alfred-einhorn. Last accessed December 11, 2019.

7. Reed KL. A brief history of anesthesiology in dentistry. Tex Dent J. 2002;119(3):219-224.

8. Becker DE, Reed KL. Essentials of local anesthetic pharmacology. Anesth Prog. 2006;53(3):98-108.

9. Bajwa SJS, Jindal R. Use of Articaine in loco-regional anesthesia for day care surgical procedures. J Anaesthesiol Clin Pharmacol. 2012;28(4):444-450.

10. Eggleston ST, Lush LW. Understanding allergic reactions to local anesthetics. Ann Pharmacother. 1996;307(7-8):851-857.

11. American Dental Association. ADA/PDR Guide to Dental Therapeutics. 5th ed. Montvale, NJ: Physicians' Desk Reference; 2009.

12. Marieb EN, Hoehn K. Human Anatomy and Physiology. 10th ed. San Francisco, CA: Pearson Education, Inc.; 2015.

13. Malamed SF. Handbook of Local Anesthesia. 7th ed. St. Louis, MO: Mosby; 2019.

14. Wynn RL, Meiller TF, Crossley HL. Drug Information Handbook for Dentistry. 25th ed. Hudson, OH: Lexicomp; 2019.

15. Paarmann C. Decision Making and Local Anesthesia: Selecting the Most Appropriate Local Anesthetic. Available at https://dimensionsofdentalhygiene.com/article/decision-making-and-local-anesthesia/. Last accessed December 11, 2019.

16. Tofoli GR, Ramacciato JC, de Oliveira PC, Volpato MC, Groppo FC, Ranali J. Comparison of effectiveness of 4% articaine associated with 1:100,000 or 1:200,000 epinephrine in inferior alveolar nerve block. Anesth Prog. 2003;50(4):164-168.

17. Little JW, Falace DA, Miller CS, Rhodus NL. Little and Falace's Dental Management of the Medically Compromised Patient. 9th ed. St. Louis, MO: Mosby; 2018.

18. Patton LL, Glick M (eds). The ADA Practical Guide to Patients with Medical Conditions. 2nd ed. Hoboken, NJ: Wiley and Sons, Inc.: 2016.

19. Balakrishnan R, Ebenezer V. Contraindications of vasoconstrictors in dentistry. Biomed Pharmacol J. 2013;6(2):409-414.

20. Dimensions of Dental Hygiene. Up Close with Amide Anesthetic Agents. Available at https://dimensionsofdentalhygiene.com/article/up-close/. Last accessed December 11, 2019.

21. Budenz AW. Local anesthetics in dentistry: then and now. J Calif Dent Assoc. 2003;31(5):388-396.

22. Malamed SF, Gagnon S, Leblanc D. Efficacy of articaine: a new amide local anesthetic. J Am Dent Assoc. 2000;131(5):635-642.

23. U.S. Food and Drug Administration. Drug Approval Package: Septocaine (Articaine). Available at https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/022010_septocaine_toc.cfm. Last accessed December 11, 2019.

24. Dembo JB. Articaine: anecdote and science. Today's FDA. 2009;21(4):15-17.

25. Malamed SF, Gagnon S, Leblanc D. Articaine hydrochloride: a study of the safety of a new amide local anesthetic. J Am Dent Assoc. 2001;132(2):177-185.

26. Mikesell P, Nusstein J, Reader A, Beck M, Weaver J. A comparison of articaine and lidocaine for inferior alveolar nerve blocks. J Endod. 2005;31(4):265-270.

27. Costa CG, Tortamano IP, Rocha RG, Francischone CE, Tortamano N. Onset and duration periods or articaine and lidocaine on maxillary infiltration. Quintessence Int. 2005;36(3):197-201.

28. Evans G, Nusstein J, Drum M, Reader A, Beck M. A prospective, randomized double-blind comparison of articaine and lidocaine for maxillary infiltrations. J Endod. 2008;34(4):389-393.

29. National Library of Medicine. Septocaine: Articaine Hydrochloride and Epinephrine Bitartrate Injection, Solution. Available at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fbb95791-d582-4fb4-81df-3084eb069b10. Last accessed December 11, 2019.

30. Haas DA. An update on local anesthetics in dentistry. J Can Dent Assoc. 2002;68(9):546-551.

31. Uckan S, Dayangac E, Araz K. Is permanent maxillary tooth removal without palatal anesthesia possible? Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;102(6):733-735.

32. Haas DA, Harper DG, Saso MA, Young ER. Lack of differential effect by Ultracaine (articaine) and Citanest (prilocaine) in infiltration anesthesia. J Can Dent Assoc. 1991;57(3):217-223.

33. Hillerup S, Jensen R. Nerve injury caused by mandibular block analgesia. Int J Oral Maxillofac Surg. 2006;35(5):437-443.

34. Pogrel MA. Permanent nerve damage from inferior alveolar nerve blocks: an update to include articaine. J Calif Dent Assoc. 2007;35(4):271-273.

35. Paganelli MA, Popescu GK. Actions of bupivacaine, a widely used local anesthetic, on NMDA receptor responses. J Neurosci. 2015;35(2):831-842.

36. Becker DE, Reed KL. Local anesthetics: review of pharmacological considerations. Anesth Prog. 2012;59(2):90-103.

37. Drugs.com. Citanest Plain Dental Injection. Available at https://www.drugs.com/pro/citanest-plain-dental-injection.html. Last accessed December 11, 2019.

38. Garisto GA, Gaffen AS, Lawrence HP, Tenenbaum HC, Haas DA. Occurrence of paresthesia after dental local anesthetic administration in the United States. J Am Dent Assoc. 2010;141(7):836-844.

39. Prchal JT, Gregg X. Hemoglobinopathies: methemoglobinemia, polycythemia and unstable hemoglobins. In: Goldman L, Schafer AI (eds). Goldman-Cecil Medicine. 25th ed. New York, NY: Elsevier; 2015.

40. U.S. Food and Drug Administration. Drug Approval Package: Oraqix (Lidocaine and Prilocaine) Periodontal Gel. Available at https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/021451s000_OraqixTOC.cfm. Last accessed December 11, 2019.

41. Brockmann WG. Mepivacaine: a closer look at its properties and current utility. Gen Dent. 2014;62(6):70-75.

42. Logothetis D. Local anesthetic agents: a review of the current options for dental hygienists. CDHA Journal. 2011:27(2):6-11.

43. Chin KL, Yagiela JA, Quinn CL, Henderson KR, Duperon DF. Serum mepivacaine concentrations after intraoral injection in young children. J Calif Dent Assoc. 2003;31(10):757-764.

44. Robertson VJ, Taylor SE, Gage TW. Quantitative and qualitative analysis of the pressor effects of levonordefrin. J Cardiovasc Pharmacol. 1984;6(5):929-935.

45. Logothetis DD. Local Anesthesia for the Dental Hygienist. 2nd ed. St. Louis, MO: Mosby; 2016.

46. Webb LJ. Dental Anesthesia: Overview of Injectable Agents Useful for Nonsurgical Periodontal Therapy. Available at https://www.rdhmag.com/patient-care/article/16409431/dental-anesthesia-overview-of-injectable-agents-useful-for-nonsurgical-periodontal-therapy. Last accessed December 11, 2019.

47. Drugs.com. OraVerse Approval History. Available at https://www.drugs.com/history/oraverse.html. Last accessed December 11, 2019.

48. Wynn RL. Oraverse: A Newly Approved Drug that is Effective in Children in Reversing Soft-Tissue Local Anesthesia. Available at https://www.lexi.com/individuals/dentistry/newsletters.jsp?id=january_09. Last accessed December 11, 2019.

49. Kattan S, Lee SM, Hersh EV, et al. Do buffered local anesthetics provide more successful anesthesia than nonbuffered solutions in patients with pulpally involved teeth requiring dental therapy? A systematic review. JADA. 2019;150(3):165-177.

50. Tavares M, Goodson JM, Studen-Pavlovich D, et al. Reversal of soft-tissue local anesthesia with phentolamine mesylate in pediatric patients. J Am Dent Assoc. 2008;139(8):1095-1104.

51. Malamed SF. Buffering local anesthetic solutions. The Pulse. 2011;44(1):7-9.

52. Logothetis DD. Anesthetic buffering: new advances for use in dentistry. RDH Magazine. 2013;1:61-66.

53. Stewart JH, Cole GW, Klein JA. Neutralized lidocaine with epinephrine for local anesthesia. J Dermatol Surg Oncol. 1989;15(10):1081-1083.

54. Malamed SF. Allergy and toxic reactions to local anesthetics. Dentistry Today. 2003.

55. Wood M. Pharmacokinetic drug interactions in anesthetic practice. Clin Pharmacokinet. 1991;21(4):285-307.

56. Munson ES, Tucker WK, Ausinsch B, Malagodi MH. Etidocaine, bupivacaine, and lidocaine seizure thresholds in monkeys. Anesthesiology. 1975;42(4):471-478.

57. McEntire M, Nusstein J, Drum M, Reader A, Beck M. Anesthetic efficacy of 4% articaine with 1:100,000 epinephrine versus 4% articaine with 1:200,000 epinephrine as a primary buccal infiltration in the mandibular first molar. J Endod. 2011;37(4):450-454.

58. Saraf SP, Saraf PA, Kamatagi L, et al. A comparative evaluation of anesthetic efficacy of articaine 4% and lidocaine 2% with anterior middle superior alveolar nerve block and infraorbital nerve block: an in vivo study. J Conserv Dent. 2016;19(6):527-531.

59. LexiComp Online. Available at https://online.lexi.com. Last accessed December 11, 2019.

60. Piccinni C, Gissi DB, Gabusi G, et al. Paraesthesia after local anaesthetics: an analysis of reports to the FDA adverse event reporting system. Basic Clin Pharmacol Toxicol. 2015;117(1):52-56.

61. Lee HS. Recent advances in topical anesthesia. J Dent Anesth Pain Med. 2016;16(4):237-244.

62. Daubländer M, Liebaug F, Niedeggen G, Theobald K, Kürzinger ML. Effectiveness and safety of phentolamine mesylate in routine dental care. J Am Dent Assoc. 2017;148(3):149-156.