Insomnia

 

Objectives

After completing this activity, professionals will

  • recognize that many different sleep disorders exist,
  • understand that nearly everyone, at some time, experiences difficulty sleeping,
  • understand that external and internal factors affect sleep and sleep patterns, and
  • understand that treatments are available for sleep disorders.
Introduction

Sleep is a behavioral state that is a natural part of every individual’s life. We spend about one-third of our lives asleep. Nonetheless, people generally know little about the importance of this essential activity. Sleep is not just something to fill time when a person is inactive. Sleep is a required activity, not an option. Even though the precise functions of sleep remain a mystery, sleep is important for normal motor and cognitive function. We all recognize and feel the need to sleep. After sleeping, we recognize changes that have occurred, as we feel rested and more alert. Sleep actually appears to be required for survival. Rats deprived of sleep will die within two to three weeks, a time frame similar to death due to starvation.

It is not normal for a person to be sleepy at times when he or she expects to be awake. Problem sleepiness may be associated with difficulty concentrating, memory lapses, loss of energy, fatigue, lethargy, and emotional instability. The prevalence of problem sleepiness is high and has serious consequences, such as drowsy driving or workplace accidents and errors. Lifestyle factors and undiagnosed or untreated sleep disorders can cause problem sleepiness. Lifestyle factors include not getting enough sleep, having an irregular sleep schedule, and using alcohol or certain medications. Of the more than 70 known sleep disorders, the most common are obstructive sleep apnea, insomnia, narcolepsy, and restless legs syndrome. Large numbers of individuals suffering from these sleep disorders are unaware of—and have not been diagnosed or treated for—their disorder.

Problem sleepiness may be associated with difficulty concentrating, memory lapses, loss of energy, fatigue, lethargy, and emotional instability.

Problem sleepiness can be deadly. Approximately 100,000 automobile crashes each year result from drivers who were “asleep at the wheel.” In a survey of drivers in New York State, approximately 25 percent reported they had fallen asleep at the wheel at some time.Crashes in which the driver falls asleep are especially common among young male drivers. One large study found that in over 50 percent of fall-asleep crashes, the driver was 25 years old or younger.In addition to the high risk of automobile crashes, problem sleepiness can cause difficulties with learning, memory, thinking, and feelings, which may lead to poor school and work performance and difficulty with relationships. Furthermore, problem sleepiness leads to errors and accidents in the workplace.

Very few textbooks provide any scientific information about changes that occur in the body during sleep and how those changes affect our ability to move and think. Of course, we’ve heard that a good night’s sleep will help us perform better on a test the next day, but is this based on scientific fact, or is it just a continuing myth? The lack of information in textbooks may be due to the fact that sleep research is only recently gaining recognition. A great deal remains to be learned through scientific studies, including an answer to the key question, What is the function of sleep? Although its function remains unclear, research is providing a great deal of information about what happens in the brain and body during sleep and how the body regulates sleep.

Misconceptions about Sleep

People may have misconceptions about what causes us to sleep, what occurs during sleep, how our body responds to a lack of sleep, and what function(s) sleep fulfills.

Misconception 1: Sleep is time for the body in general and the brain specifically to shut down for rest.
Sleep is an active process involving specific cues for its regulation. Although there are some modest decreases in metabolic rate, there is no evidence that any major organ or regulatory system in the body shuts down during sleep.Some brain activity, including delta waves, increases dramatically. Also, the endocrine system increases secretion of certain hormones during sleep, such as growth hormone and prolactin. In REM sleep, many parts of the brain are as active as at any time when awake.

Misconception 2: Getting just one hour less sleep per night than needed will not have any effect on daytime functioning.
When daily sleep time is less than an individual needs, a “sleep debt” develops. Even relatively modest daily reductions in sleep time (for example, one hour) can accumulate across days to cause a sleep debt. If the debt becomes too great, it can lead to problem sleepiness. Although the individual may not realize his or her sleepiness, the sleep debt can have powerful effects on daytime performance, thinking, and mood.

The biological clock that times and controls a person’s sleep/wake cycle will attempt to function according to a normal day/night schedule even when that person tries to change it.

Misconception 3: The body adjusts quickly to different sleep schedules.
The biological clock that times and controls a person’s sleep/wake cycle will attempt to function according to a normal day/night schedule even when that person tries to change it. Those who work night shifts naturally feel sleepy when nighttime comes. A similar feeling that occurs during travel is known as jet lag.This conflict, set up by trying to be active during the brain’s biological nighttime, leads to a decrease in cognitive and motor skills. The biological clock can be reset, but only by appropriately timed cues and even then, by one to two hours per day at best.Problems resulting from a mismatch of this type may be reduced by behaviors such as sleeping in a dark, quiet room, getting exposure to bright light at the right time, and altering eating and exercise patterns. Because humans function best when they sleep at night and act in the daytime, the task for a person who must be active at night is to retrain the biological clock (by light cues).

Misconception 4: People need less sleep as they grow older.
Older people don’t need less sleep, but they often get less sleep. That’s because the ability to sleep for long periods of time and to get into the deep, restful stages of sleep decreases with age. Many older people have more fragile sleep and are more easily disturbed by light, noise, and pain than when younger. They are also more likely to have medical conditions that contribute to sleep problems.

Misconception 5: A “good night’s sleep” can cure problems with excessive daytime sleepiness.
Excessive daytime sleepiness can be associated with a sleep disorder or other medical condition. Sleep disorders, including sleep apnea (that is, absence of breathing during sleep), insomnia, and narcolepsy, may require behavioral, pharmacological, or even surgical intervention to relieve the symptoms.Extra sleep may not eliminate daytime sleepiness that may be due to such disorders.

Major Concepts Related to the Biology of Sleep

Research is providing a scientific foundation for understanding sleep’s physiology, rhythms, and implications for our health. Although much remains to be learned, this research is clarifying a number of important issues relating to sleep.

3.1 Sleep is a dynamic process. Sleep is not a passive event, but rather an active process involving characteristic physiological changes in the organs of the body. Scientists study sleep by measuring the electrical changes in the brain using electroencephalograms (EEGs). Typically, electrodes are placed on the scalp in a symmetrical pattern. The electrodes measure very small voltages that scientists think are caused by synchronized activity in very large numbers of synapses (nerve connections) in the brain’s outer layers (cerebral cortex). EEG data are represented by curves that are classified according to their frequencies. The wavy lines of the EEG are called brain waves. An electrooculogram (EOG) uses electrodes on the skin near the eye to measure changes in voltage as the eye rotates in its socket. Scientists also measure the electrical activity associated with active muscles by using electromyograms (EMGs). In this technique, electrodes are placed on the skin overlaying a muscle. In humans, the electrodes are placed under the chin because muscles in this area demonstrate very dramatic changes during the various stages of sleep.

In practice, EEGs, EOGs, and EMGs are recorded simultaneously on continuously moving chart paper or digitized by a computer and displayed on a high-resolution monitor. This allows the relationships among the three measurements to be seen immediately. The patterns of activity in these three systems provide the basis for classifying the different types of sleep.

Studying these events has led to the identification of two basic stages, or states, of sleep: non–rapid eye movement (NREM) and rapid eye movement (REM).

Sleep is a highly organized sequence of events that follows a regular, cyclic program each night. Thus, the EEG, EMG, and EOG patterns change in predictable ways several times during a single sleep period. NREM sleep is divided into four stages according to the amplitude and frequency of brain wave activity. In general, the EEG pattern of NREM sleep is slower, often more regular, and usually of higher voltage than that of wakefulness. As sleep gets deeper, the brain waves get slower and have greater amplitude. NREM Stage 1 is very light sleep; NREM Stage 2 has special brain waves called sleep spindles and K complexes; NREM Stages 3 and 4 show increasingly more high-voltage slow waves. In NREM Stage 4, it is extremely hard to be awakened by external stimuli. The muscle activity of NREM sleep is low, but the muscles retain their ability to function. Eye movements normally do not occur during NREM sleep, except for very slow eye movements, usually at the beginning. The body’s general physiology during these stages is fairly similar to the wake state.

The EEG recorded during REM sleep shows very fast and desynchronized activity that is more random than that recorded during NREM sleep. It actually looks similar to the EEG (low voltage with a faster mix of frequencies) from when we are awake. REM sleep is characterized by bursts of rapid eye movements. The eyes are not constantly moving, but they dart back and forth or up and down. They also stop for a while and then jerk back and forth again. Always, and just like waking eye movements, both eyes move together in the same direction. Some scientists believe that the eye movements of REM sleep relate to the visual images of dreams, but why they exist and what function they serve, if any, remain unknown. Additionally, while muscle tone is normal in NREM sleep, we are almost completely paralyzed in REM sleep. Although the muscles that move our bodies go limp, other important muscles continue to function in REM sleep. These include the heart, diaphragm, eye muscles, and smooth muscles such as those of the intestines and blood vessels. The paralysis of muscles in the arms and legs and under the chin show electrical silence in REM sleep. On an EMG, the recording produces a flat line. Small twitches can break through this paralysis and look like tiny blips on the flat line.

Sleep is a cyclical process. During sleep, people experience repeated cycles of NREM and REM sleep, beginning with an NREM phase. This cycle lasts approximately 90 to 110 minutes and is repeated four to six times per night. As the night progresses, however, the amount of deep NREM sleep decreases and the amount of REM sleep increases. Figure 4 graphically depicts the pattern of cycling we experience. The term ultradian rhythm (that is, rhythm occurring within a period of less than 24 hours) is used to describe this cycling through sleep stages.

The chart in Figure 4 is called a hypnogram. Hypnograms were developed to summarize the voluminous chart recordings of electrical activities (EEG, EOG, and EMG) collected during a night’s sleep. Hypnograms provide a simple way to display information originally collected on many feet of chart paper or stored as a large file on a computer.

We can make several observations about the hypnogram in Figure 4. First, the periods of NREM and REM sleep alternate during the night. Second, the deepest stages of NREM sleep occur in the first part of the night. Third, the episodes of REM sleep are longer as the night progresses. This hypnogram also indicates two periods during the night when the individual awakened (at about six and seven hours into the night).

It is useful to distinguish between sleep and the state induced during general anesthesia or seen in people who are in a coma. While these latter individuals are often said to be “asleep,” their conditions are not readily reversible (that is, they cannot be awakened by a strong stimulus), and they do not exhibit the same brain wave patterns characteristic of true sleep.

3.2 Physiological changes during sleep. Table 1 summarizes some basic physiological changes that occur in NREM and REM sleep.

Table 1. Comparison of Physiological Changes During NREM and REM Sleep
Physiological Process During NREM During REM
brain activity decreases from wakefulness increases in motor and sensory areas, while other areas are similar to NREM
heart rate slows from wakefulness increases and varies compared with NREM
blood pressure decreases from wakefulness increases (up to 30 percent) and varies from NREM
blood flow to brain does not change from wakefulness in most regions increases by 50 to 200 percent from NREM, depending on brain region
respiration decreases from wakefulness increases and varies from NREM, but may show brief stoppages (apnea); coughing suppressed
airway resistance increases from wakefulness increases and varies from wakefulness
body temperature is regulated at lower set point than wakefulness; shivering initiated at lower temperature than during wakefulness is not regulated; no shivering or sweating; temperature drifts toward that of the local environment
sexual arousal occurs infrequently increases from NREM (in both males and females)

The functions of many organ systems are also linked to the sleep cycle, as follows:

  • Endocrine system. Most hormone secretion is controlled by the circadian clock or in response to physical events. Sleep is one of the events that modify the timing of secretion for certain hormones. Many hormones are secreted into the blood during sleep. For example, scientists believe that the release of growth hormone is related in part to repair processes that occur during sleep. Follicle stimulating hormone and luteinizing hormone, which are involved in maturational and reproductive processes, are among the hormones released during sleep. In fact, the sleep-dependent release of luteinizing hormone is thought to be the event that initiates puberty. Other hormones, such as thyroid-stimulating hormone, are released prior to sleep.
  • Renal system. Kidney filtration, plasma flow, and the excretion of sodium, chloride, potassium, and calcium all are reduced during both NREM and REM sleep. These changes cause urine to be more concentrated during sleep.
  • Alimentary activity. In a person with normal digestive function, gastric acid secretion is reduced during sleep. In those with an active ulcer, gastric acid secretion is actually increased and swallowing occurs less frequently.

3.3 Sleep and the brain. Sleep is actively generated in specific brain regions. These sites have been identified through studies involving electrical stimulation, damage to specific brain regions, or other techniques that identify sleep-inducing sites. The basal forebrain, including the hypothalamus, is an important region for controlling NREM sleep and may be the region keeping track of how long we have been awake and how large our sleep debt is. The brainstem region known as the pons is critical for initiating REM sleep. As depicted in Figure 5, during REM sleep, the pons sends signals to the visual nuclei of the thalamus and to the cerebral cortex (this region is responsible for most of our thought processes). The pons also sends signals to the spinal cord, causing the temporary paralysis that is characteristic of REM sleep. Other brain sites are also important in the sleep process. For example, the thalamus generates many of the brain rhythms in NREM sleep that we see as EEG patterns.

3.4 Sleep patterns. Sleep patterns change during an individual’s life. In fact, age affects sleep more than any other natural factor. Newborns sleep an average of 16 to 18 hours per day. By the time a child is three to five years old, total sleep time averages 10 to 12 hours, and then it further decreases to 7 to 8 hours per night by adulthood. One of the most prominent age-related changes in sleep is a reduction in the time spent in the deepest stages of NREM (Stages 3 and 4) from childhood through adulthood. In fact, this change is prominent during adolescence, when about 40 percent of this activity is lost and replaced by Stage 2 NREM sleep. In addition to these changes, the percentage of time spent in REM sleep also changes during development. Newborns may spend about 50 percent of their total sleep time in REM sleep. In fact, unlike older children and adults, infants fall asleep directly into REM sleep. Infant sleep cycles generally last only 50 to 60 minutes. By two years of age, REM sleep accounts for 20 to 25 percent of total sleep time, which remains relatively constant throughout the remainder of life.Young children have a high arousal threshold, which means they can sleep through loud noises, especially in the early part of the night. For example, one study showed that 10-year-olds were undisturbed by a noise as loud as the sound of a jet airplane taking off nearby.

Although most humans maintain REM sleep throughout life, brain disorders like Alzheimer’s and Parkinson’s are characterized by decreasing amounts of REM sleep as the diseases progress. Also, elderly individuals exhibit more variation in the duration and quality of sleep than do younger adults. Elderly people may also exhibit increased sleep fragmentation (arousals from sleep that occur as either short or more extended awakenings). Figure 6 depicts these developmental changes in sleep patterns.

Teenagers, on average, require about nine or more hours of sleep per night to be as alert as possible when awake.

Several issues are important to consider. First, individual sleep needs vary. For instance, eight hours of sleep per night appears to be optimal for most adults, although some may need more or less. Teenagers, on average, require about nine or more hours of sleep per night to be as alert as possible when awake. If sleep needs are not met, a progressive sleep debt occurs and eventually the body requires that the debt be paid. It does not appear that we are able to adapt to getting less sleep than our bodies require. Not getting enough sleep, while still allowing us to function in a seemingly normal manner, does impair motor and cognitive functions. Caffeine and other stimulants cannot substitute for sleep, but they do help to counteract some of the effects of sleep deprivation.

3.5 Biological clock. An internal biological clock regulates the timing for sleep in humans. The activity of this clock makes us sleepy at night and awake during the day. Our clock cycles with an approximately 24-hour period and is called a circadian clock (from the Latin roots circa = about and diem = day). In humans, this clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus in the brain (see Figure 7).The SCN is actually a very small structure consisting of a pair of pinhead-size regions, each containing only about 10,000 neurons out of the brain’s estimated 100 billion neurons.

Biological clocks are genetically programmed physiological systems that allow organisms to live in harmony with natural rhythms, such as day/night cycles and the changing of seasons. The most important function of a biological clock is to regulate overt biological rhythms like the sleep/wake cycle. The biological clock is also involved in controlling seasonal reproductive cycles in some animals through its ability to track information about the changing lengths of daylight and darkness during a year.

Biological rhythms are of two general types. Exogenous rhythms are directly produced by an external influence, such as an environmental cue. They are not generated internally by the organism itself, and if the environmental cues are removed, the rhythm ceases. Endogenous rhythms, by contrast, are driven by an internal, self-sustaining biological clock rather than by anything external to the organism. Biological rhythms, such as oscillations in core body temperature, are endogenous. They are maintained even if environmental cues are removed.

Because the circadian clock in most humans has a natural day length of just over 24 hours, the clock must be entrained, or reset, to match the day length of the environmental photoperiod (that is, the light/dark, or day/night, cycle).

Because the circadian clock in most humans has a natural day length of just over 24 hours, the clock must be entrained, or reset, to match the day length of the environmental photoperiod (that is, the light/dark, or day/night, cycle). The cue that synchronizes the internal biological clock to the environmental cycle is light. Photoreceptors in the retina transmit light-dependent signals to the SCN. Interestingly, our usual visual system receptors, the rods and cones, are apparently not required for this photoreception.Special types of retinal ganglion cells are photoreceptive, project directly to the SCN, and appear to have all the properties required to provide the light signals for synchronizing the biological clock.At the SCN, the signal interacts with several genes that serve as “pacemakers.”

Endogenous sleep rhythms can be depicted graphically. Figure 8 shows a day-by-day representation of one individual’s sleep/wake cycle. The black lines indicate periods of sleep, and the gray lines indicate periods of wakefulness. The upper portion of the figure (days 1 through 9) represents this individual’s normal sleep/wake cycle. Under these conditions, the individual is exposed to regularly timed exposure to alternating daylight and darkness, which has entrained this person’s sleep/wake cycling to a period of 24 hours.

Contrast this upper portion of the figure with the middle portion (days 10 through 34). In the middle portion, this individual has been isolated from normal environmental cues like daylight, darkness, temperature variation, and noise variation. There are two important points to be derived from this portion of the figure. First, this individual’s sleep/wake cycle continues to oscillate in the absence of external cues, stressing that this rhythm is endogenous, or built in. Second, in the absence of external cues to entrain circadian rhythms, this individual’s clock cycles with its own natural, built-in rhythm that is just over 24 hours long. Consequently, without environmental cues, the individual goes to bed about one hour later each night. After 24 days, the individual is once again going to bed at midnight. The lower portion of Figure 8 depicts the change in the sleep/wake cycle after the individual is once again entrained to a 24-hour day containing the proper environmental cues.

Another interesting rhythm that is controlled by the biological clock is the cycle of body temperature, which is lowest in the biological night and rises in the biological daytime. This fluctuation persists even in the absence of sleep. Activity during the day and sleep during the night reinforce this cycle of changes in body temperature, as seen in Figure 9.

The release of melatonin, a hormone produced by the pineal gland, is controlled by the circadian clock in the SCN. Its levels rise during the night and decline at dawn in both nocturnal and diurnal species. Melatonin has been called the hormone of darkness because of this pattern. The SCN controls the timing of melatonin release; melatonin then feeds back on the SCN to regulate its activity. In mammals, for example, most of the brain receptors for melatonin are located in the SCN. Research has demonstrated that administering melatonin can produce shifts in circadian rhythms in a number of species including rats, sheep, lizards, birds, and humans. These effects are most clearly evident when melatonin is given in the absence of light input. Thus, for example, giving melatonin to blind people can help set their biological clocks. Melatonin is available as an over-the-counter nutritional supplement. Although claims are made that the supplement promotes sleep, the evidence for this is inconclusive. Potential side effects of long-term administration of melatonin remain unknown, and its unsupervised use by the general public is discouraged.

In addition to synchronizing these daily rhythms, biological clocks can affect rhythms that are longer than 24 hours, especially seasonal rhythms. Some vertebrates have reproductive systems that are sensitive to day length. These animals can sense changes in day length by the amount of melatonin secreted. The short days and long nights of winter turn off the reproductive systems of hamsters, while in sheep the opposite occurs. The high levels of melatonin that inhibit reproduction in hamsters stimulate the reproductive systems of sheep, so they breed in winter and give birth in the spring.

Biological clocks exist in a wide range of organisms, from cyanobacteria (blue-green algae) to humans. Clocks enable organisms to adapt to their surroundings. Although scientists currently believe that clocks arose through independent evolution and may use different clock proteins, they all share several regulatory characteristics. In particular, they are maintained by a biochemical process known as a negative feedback loop.

Much of what is known about clock regulation has come from studying the fruit fly Drosophila melanogaster, from which biological clock genes were first cloned. Two genes called period (per) and timeless (tim) were found to cycle with a 24-hour, or circadian, rhythm.The genes are active early in the night and produce mRNA that is then translated into the proteins PER and TIM. These proteins begin to accumulate in the cytoplasm. After the proteins have reached high enough levels, PER protein binds to TIM protein, forming a complex that enters the cell’s nucleus. In the nucleus, the PER-TIM complexes bind to the per and tim genes to suppress further transcription. This creates what is called a negative feedback loop. After a while, the PER and TIM proteins degrade, and transcription from the per and tim genes begins again.

This description of Drosophila’s clock is a simplified one. Other genes have been identified that produce proteins involved with regulating the circadian clock. For example, the proteins CLOCK, CYCLE, and VRILLE are transcription factors that regulate expression of the per and tim genes. Other proteins, like the enzymes DOUBLE-TIME and SHAGGY, can alter the periodicity of the clock through chemical modification (phosphorylation) of PER and TIM. Mutations have been identified in clock genes that speed up, slow down, or eliminate the periodicity of the circadian clock in flies. Interestingly, similar genes and proteins have been identified in mammals, and studies indicate that the mammalian clock is regulated in much the same way as that of the fly. Developmental changes in the circadian clock occur from infancy to childhood to adolescence, and further changes occur as adults age. Very little is known about specific genes and mediators responsible for the normal development of the circadian clock.

Jet lag results from the inability of our circadian clock to make an immediate adjustment to the changes in light cues that come from a rapid change in time zone.

One negative consequence of our circadian cycle afflicts travelers who rapidly cross multiple time zones. Jet lag produces a number of unwanted effects including excessive sleepiness, poor sleep, loss of concentration, poor motor control, slowed reflexes, nausea, and irritability. Jet lag results from the inability of our circadian clock to make an immediate adjustment to the changes in light cues that an individual experiences when rapidly crossing time zones. After such travel, the body is in conflict. The biological clock carries the rhythm entrained by the original time zone, even though the clock is out of step with the cues in the new time zone. This conflict between external and internal clocks and signals is called desynchronization, and it affects more than just the sleep/wake cycle. All the rhythms are out of sync, and they take a number of days to re-entrain to the new time zone. Eastward travel generally causes more severe jet lag than westward travel, because traveling east requires that we shorten our day and adjust to time cues occurring earlier than our clock is used to.

In general, the human circadian clock appears better able to adjust to a longer day than a shorter day. For example, it is easier for most people to adjust to the end of daylight savings time in the fall when we have one 25-hour day than to the start of daylight savings time in the spring, when we have a 23-hour day. Similarly, traveling from the West Coast of the United States to the East Coast produces a loss of three hours—a 21-hour day. Thus, travelers may find it difficult to sleep because of the three-hour difference between external cues and their internal clock. Likewise, travelers may find it difficult to awaken in the morning. We may try to go to sleep and wake up at our usual local times of, say, 11 p.m. and 7 a.m., but to our brain’s biological clock, the times are 8 p.m. and 4 a.m. Other circadian rhythm problems include

  • Monday morning blues. By staying up and sleeping in an hour or more later than usual on the weekends, we provide our biological clock different cues that push it toward a later nighttime phase. By keeping a late sleep schedule both weekend nights, our internal clock becomes two hours or more behind our usual weekday schedule. When the alarm rings at 6:30 a.m. on Monday, our body’s internal clock is now set for 4:30 a.m. or earlier.
  • Seasonal affective disorder (SAD). A change of seasons in autumn brings on both a loss of daylight savings time (fall back one hour) and a shortening of the daytime. As winter progresses, the day length becomes even shorter. During this season of short days and long nights, some individuals develop symptoms similar to jet lag but more severe. These symptoms include decreased appetite, loss of concentration and focus, lack of energy, feelings of depression and despair, and excessive sleepiness. Too little bright light reaching the biological clock in the SCN appears to bring on this recognized form of depression in susceptible individuals. Consequently, treatment often involves using light therapy.
  • Shift work. Unlike some animals, humans are active during daylight hours. This pattern is called diurnal activity. Animals that are awake and active at night (for example, hamsters) have what is known as nocturnal activity. For humans and other diurnally active animals, light signals the time to awake, and sleep occurs during the dark. Modern society, however, requires that services and businesses be available 24 hours a day, so some individuals must work the night shift. These individuals no longer have synchrony between their internal clocks and external daylight and darkness signals, and they may experience mental and physical difficulties similar to jet lag and SAD.

3.6 Homeostasis and sleep. The relationship of circadian rhythms to sleep is relatively well understood. Continuing studies in genetics and molecular biology promise further advances in our knowledge of how the circadian clock works and how a succession of behavioral states adapt to changes in light/dark cycles. In addition to the circadian component, there is a fundamental regulatory process involved in programming sleep. Consider that the longer an individual remains awake, the stronger the desire and need to sleep become. This pressure to sleep defines the homeostatic component of sleep. The precise mechanism underlying the pressure that causes us to feel a need to sleep remains a mystery. What science does know is that the action of nerve-signaling molecules called neurotransmitters and of nerve cells (neurons) located in the brainstem and at the base of the brain determines whether we are asleep or awake. Additionally, there is recent evidence that the molecule adenosine (composed of the base adenine linked to the five-carbon sugar ribose) is an important sleepiness factor: it appears to “keep track” of lost sleep and may induce sleep. Interestingly, caffeine binds to and blocks the same cell receptors that recognize adenosine.This suggests that caffeine disrupts sleep by binding to adenosine receptors and preventing adenosine from delivering its fatigue signal. The homeostatic regulation of sleep helps reinforce the circadian cycle. We usually sleep once daily because the homeostatic pressure to sleep is hard to resist after about 16 hours, and then while we sleep, our closed eyes block the light signals to the biological clock. See Figure 11.

3.7. Dreams. An intriguing occurrence during sleep is dreaming. Although reports of dreaming are most frequent and vivid when an individual is aroused from REM sleep, dreams do occur at sleep onset and during NREM sleep as well. During an average night’s sleep, about two hours are spent dreaming, mostly during REM sleep. Although some dreams are memorable because of their extraordinary or bizarre nature, other dreams reflect realistic experiences. Despite this realism, REM dreams are usually novel experiences, like a work of fiction, instead of a replay of actual events. Pre-sleep stimuli do not seem to affect dream content. In fact, the source of the content of any given dream is unknown. REM sleep and dreams are associated with each other, but they are not synonymous. While REM sleep is turned on and off by the pons, two areas in the cerebral hemispheres (areas far from the pons that control higher mental functions) regulate dreaming.

REM sleep and dreaming can be dissociated from one another, as seen after the administration of certain drugs or in cases of brain damage either to the pons (loss of REM sleep but not of dreaming) or to the frontal areas (no dreaming but REM sleep cycle unaffected). Consequently, REM sleep appears to be just one of the triggers for dreaming. Using scanning techniques that assess brain activity, scientists have determined which areas of the brain are active during REM sleep dreaming.These areas are illustrated in Figure 12. Brain regions that are inactive during dreaming include those that regulate intelligence, conscious thought, and higher-order reasoning. Higher-order reasoning is that part of brain function responsible for processing experiences into memory and regulating vision while we are awake. The significance of dreaming to one’s health and the meaning of dreams remain mysteries.

Scientists still do not fully understand the functions of sleep.

3.8 Functions of sleep. Animal studies have demonstrated that sleep is essential for survival. Consider studies that have been performed with laboratory rats. While these animals will normally live for two to three years, rats deprived of REM sleep survive an average of only five months. Rats deprived of all sleep survive only about three weeks.In humans, extreme sleep deprivation can cause an apparent state of paranoia and hallucinations in otherwise healthy individuals. However, despite identifying several physiological changes that occur in the brain and body during sleep, scientists still do not fully understand the functions of sleep. Many hypotheses have been advanced to explain the role of this necessary and natural behavior.The following examples highlight several of these theories:

Hypothesis: Restoration and recovery of body systems. This theory recognizes the need of an organism to replenish its energy stores and generally repair itself after a period of energy consumption and breakdown (wakefulness). The brain remains active during sleep, and the low metabolic rate characteristic of sleep is thought to be conducive to biosynthetic reactions. There is little, if any, evidence that more repair occurs during sleep than during rest or relaxed wakefulness. In fact, whole-body protein synthesis decreases during sleep, which is consistent with sleep being a period of overnight fasting.

Hypothesis: Energy conservation. This theory states that we sleep to conserve energy and is based on the fact that the metabolic rate is lower during sleep. The theory predicts that total sleep time and NREM sleep time will be proportional to the amount of energy expended during wakefulness. Support for this theory is derived from several lines of evidence. For example, NREM and REM sleep states are found only in endothermic animals (that is, those that expend energy to maintain body temperature). Species with greater total sleep times generally have higher core body temperatures and higher metabolic rates. Consider also that NREM sleep time and total sleep time decrease in humans, with age, as do body and brain metabolism. In addition, infectious diseases tend to make us feel sleepy. This may be because molecules called cytokines, which regulate the function of the immune system, are powerful sleep inducers. It may be that sleep allows the body to conserve energy and other resources, which the immune system may then use to fight the infection.

Hypothesis: Memory consolidation. The idea here is that sleeping reinforces learning and memory, while at the same time, helping us to forget or to clear stores of unneeded memories. During the course of a day we are inundated with experiences, some of which should be remembered while others need not be. Perhaps sleep aids in rearranging all of the experiences and thoughts from the day so that those that are important are stored and those that are not are discarded. A recent study of songbirds suggests that sleep may play an important role in learning.Young birds listened to the songs of adult birds and began to practice and refine their own songs. The scientists were able to monitor the firing of individual brain cells involved with singing. They found that if sleeping birds listened to a recording of their own song, their neurons would later fire in a pattern nearly identical to that of song production though no sound was produced. The researchers speculate that the birds dream of singing; they relay and rehearse their songs and strengthen the nerve patterns required for song production. Sleep appears to be important for human learning as well. People who get plenty of deep NREM sleep in the first half of the night and REM sleep in the second half improve their ability to perform spatial tasks. This suggests that the full night’s sleep plays a role in learning—not just one kind of sleep or the other.

Hypothesis: Protection from predation. Inactivity during sleep may minimize exposure to predators. At the same time, however, sleep decreases sensitivity to external stimuli and may, as a consequence, increase vulnerability to predation.

Hypothesis: Brain development. This proposed function of sleep is related to REM sleep, which occurs for prolonged periods during fetal and infant development. This sleep state may be involved in the formation of brain synapses.

Hypothesis: Discharge of emotions. Perhaps dreaming during REM sleep provides a safe discharge of emotions. As protection to ourselves and to a bed partner, the muscular paralysis that occurs during REM sleep does not allow us to act out what we are dreaming. Additionally, activity in brain regions that control emotions, decision making, and social interactions is reduced during sleep. Perhaps this provides relief from the stresses that occur during wakefulness and helps maintain optimal performance when awake.

Unfortunately, each of these hypotheses suffers from flaws. Most fail because they cannot offer a mechanism for why sleep is more valuable than simply resting while remaining awake. In others, the shortcomings are more subtle.

3.9 Evolution of sleep. Sleep is ubiquitous among mammals, birds, and reptiles, although sleep patterns, habits, postures, and places of sleep vary greatly. Consider the following:

  • Sleep patterns. Mammals generally alternate between NREM and REM sleep states in a cyclic fashion as described earlier, although the length of the sleep cycle and the percentage of time spent in NREM and REM states vary with the animal. Birds also have NREM/REM cycles, although each phase is very short (NREM sleep is about two and one-half minutes; REM sleep is about nine seconds). Additionally, birds do not lose muscle tone during REM sleep, a good thing for animals that sleep while standing or perching. Most scientific studies have failed to demonstrate REM sleep in reptiles. These findings have led some scientists to suggest that REM sleep may be a later evolutionary development related to warm-blooded animals.
  • Sleep habits. Some mammals, such as humans, sleep primarily at night, while other mammals, such as rats, sleep primarily during the day. Furthermore, most (but not all) small mammals tend to sleep more than large ones (see Table 2 for examples). In some cases, animals have developed ways to sleep and concurrently satisfy critical life functions. These animals engage in unihemispheric sleep, in which one side of the brain sleeps while the other side is awake. This phenomenon is observed most notably in birds (like those that make long, transoceanic flights) and aquatic mammals (like dolphins and porpoises). Unihemispheric sleep allows aquatic mammals to sleep and continue to swim and surface to breathe. It allows animals to keep track of other group members and watch for predators. In fact, there is recent scientific evidence that mallard ducks can increase their use of unihemispheric sleep as the risk of predation increases.
  • Sleep postures. A wide variety of postures are seen: from sleeping curled up (dogs, cats, and many other animals), to standing (horses, birds), swimming (aquatic mammals, ducks), hanging upside down (bats), straddling a tree branch (leopard), and lying down (humans).
  • Sleep places. Again, there is great variety, especially for mammals: burrows (rabbits), open spaces (lions), underwater (hippopotami), nests (gorillas), and the comfort of one’s own bed (humans).
Table 2. Representative Total Sleep Requirements for Various Species
Species Average Total Sleep Time (hours/day)
brown bat 19.9
python 18.0
owl monkey 17.0
human infant 16.0
tiger 15.8
squirrel 14.9
golden hamster 14.3
lion 13.5
gerbil 13.1
rat 12.6
cat 12.1
mouse 12.1
rabbit 11.4
jaguar 10.8
duck 10.8
dog 10.6
bottle-nosed dolphin 10.4
baboon 10.3
chimpanzee 9.7
guinea pig 9.4
human adolescent 9.0
human adult 8.0
pig 7.8
gray seal 6.2
goat 5.3
cow 3.9
sheep 3.8
elephant 3.5
donkey 3.1
horse 2.9
giraffe 1.9
 

Sleep may also occur among lower life forms, such as fish and invertebrates, but it is hard to know because EEG patterns are not comparable to those of vertebrates. Consequently, investigating sleep in species other than mammals and birds has relied on the identification of specific behavioral characteristics of sleep: a quiet state, a typical species-specific sleep posture, an elevated arousal threshold (or reduced responsiveness to external stimuli), rapid waking due to moderately intense stimulation (that is, sleep is rapidly reversible), and a regulated response to sleep deprivation. Recent research demonstrates that even the fruit fly Drosophila melanogaster responds similarly to mammals when exposed to chemical agents that alter sleep patterns.

Comparative studies have explored the evolution of sleep. Although REM sleep is thought to have evolved from NREM sleep, recent studies suggest that NREM and REM sleep may have diverged from a common precursor sleep state.

3.10 Sleep loss and wakefulness. About 30 to 40 percent of adults indicate some degree of sleep loss within any given year, and about 10 to 15 percent indicate that their sleep loss is chronic or severe.In addition, millions of Americans experience problems sleeping because of undiagnosed sleep disorders or sleep deprivation. Adolescents and shift workers are at very high risk of problem sleepiness due to sleep deprivation and the desynchronized timing of sleep and wakefulness, respectively.

Sleep and wakefulness are linked in part to the activity of the circadian clock. Recent studies show that individual preferences for morning and evening activity may have a biological basis.In addition, studies show that adolescents experience a delay in the circadian timing system that results in a tendency for them to stay up later and sleep in later.Loss of sleep creates an overwhelming and uncontrollable need to sleep and affects virtually all physiological functions. Sleep loss causes problems with memory and attention, complex thought, motor responses to stimuli, performance in school or on the job, and controlling emotions. Sleep loss may also alter thermoregulation and increase the risk for various physical and mental disorders.

Many adolescents are chronically sleep-deprived and hence at high risk of drowsy-driving crashes.

Sleep loss affects personal safety on the road. The National Highway Traffic Safety Administration has estimated that approximately 100,000 motor vehicle crashes each year result from a driver’s drowsiness or fatigue while at the wheel.Driving at night or in the early to mid afternoon increases the risk of a crash because those are times that our biological clocks make us sleepy. Drowsy driving impairs a driver’s reaction time, vigilance, and ability to make sound judgments. Many adolescents are chronically sleep-deprived and hence at high risk of drowsy-driving crashes. In one large study of fall-asleep crashes, over 50 percent occurred with a driver 25 years old or younger.

Problem sleepiness is feeling sleepy at inappropriate times.

Problems with sleep can be due to lifestyle choices and can result in problem sleepiness—that is, feeling sleepy at inappropriate times. Environmental noise, temperature changes, changes in sleeping surroundings, and other factors may affect our ability to get sufficient restful sleep. Short-term problem sleepiness may be corrected by getting additional sleep to overcome the sleep deficit. In other cases, problem sleepiness may indicate a sleep disorder requiring medical intervention. Alcohol abuse can cause or exacerbate sleep disorders by disrupting the sequence and duration of sleep states. Alcohol does not promote good sleep, and consuming alcohol in the evening can also exacerbate sleep apnea problems.

More than 70 sleep disorders have been described, the most common of which are

  • Insomnia, the most prevalent sleep disorder, is characterized by an inability to fall asleep and/or by waking up during the night and having difficulty going back to sleep. Primary insomnia is more common in women than men and tends to increase with age. Short-term or transient insomnia may be caused by emotional or physical discomfort, stress, environmental noise, extreme temperatures, or jet lag, or may be the side effect of medication. Secondary insomnia may result from a combination of physical or mental disorders, undiagnosed or uncontrolled sleep disorders (that is, sleep apnea, restless legs syndrome, narcolepsy, and circadian rhythm disorders), and effects of prescription or nonprescription medications. Treatment will differ for primary and secondary causes of insomnia. Treatment may include behavioral aspects, such as following a specific nighttime routine, improving sleep environment, reducing caffeine and alcohol intake, or reducing afternoon napping. Pharmacological treatments may alleviate symptoms in specific cases. Some individuals try to overcome the problem of insomnia by drinking alcoholic beverages. Alcohol inhibits REM sleep and the deeper, restorative stages of sleep, and therefore does not promote good, restful sleep.
  • Obstructive sleep apnea is a potentially life-threatening disorder in which breathing is interrupted during sleep.
  • Obstructive sleep apn ea (OSA) is a potentially life-threatening disorder in which breathing is interrupted during sleep. An estimated 12 million Americans have OSA. This condition may be associated with bony or soft tissue that limits airway dimensions and is made worse in the presence of excess fatty tissue. Repetitive episodes of no effective breath, very shallow breaths, or adequate breaths but with high airway resistance can occur 20 to 30 times per hour or more. These episodes cause temporary drops in blood oxygen and increases in carbon dioxide levels, which lead to frequent partial arousals from sleep. Limitations in upper-airway dimensions are typically associated with chronic loud snoring. The frequent arousals result in ineffective sleep and account for the chronic sleep deprivation and the resultant excessive daytime sleepiness that is a major hallmark of this condition. Additional effects include morning headaches, high blood pressure, heart attacks, heart-rhythm disorders, stroke, and decreased life expectancy. OSA also occurs in children and is generally related to enlarged tonsils or adenoids. It occurs equally often in boys and girls and is most common in preschool-age children. Because many of the factors contributing to OSA appear to have significant genetic influences (such as bony dimensions of upper airways), genetic risk factors are likely important in the occurrence of OSA. Treatment for adult OSA can include behavioral therapy (losing weight, changing sleeping positions, and avoiding alcohol, tobacco, and sleeping pills), use of mechanical devices (continuous positive airway pressure to force air through the nasal passages, or dental appliances that reposition the lower jaw and tongue), and surgery to increase the size of the airway
  • Restless legs syndrome (RLS) is a neurologic movement disorder that is often associated with a sleep complaint. People with RLS have unpleasant leg sensations and an almost irresistible urge to move the legs. Symptoms are worse during inactivity and often interfere with sleep. RLS sufferers report experiencing creeping, crawling, pulling, or tingling sensations in the legs (or sometimes the arms) that are relieved by moving or rubbing them. Sitting still for long periods becomes difficult; symptoms are usually worse in the evening and night and less severe in the morning. Periodic leg movements, which often coexist with restless legs syndrome, are characterized by repetitive, stereotyped limb movements during sleep. Periodic limb movement disorder can be detected by monitoring patients during sleep. Some people with mild cases of RLS can be treated by exercise, leg massages, and eliminating alcohol and caffeine from the diet. Others require pharmacological treatment, and it may take some time to determine the right medication or combination of medications for the individual. Estimates suggest that RLS may affect between 10 and 15 percent of the population.
  • Narcolepsy is a chronic sleep disorder that usually becomes evident during adolescence or young adulthood and can affect both men and women.In the United States, it affects as many as 250,000 people, although fewer than half are diagnosed. The main characteristic of narcolepsy is excessive and overwhelming daytime sleepiness (even after adequate nighttime sleep). A person with narcolepsy is likely to become drowsy or to fall asleep at inappropriate times and places. Daytime sleep attacks may occur with or without warning and may be irresistible. In addition, nighttime sleep may also be fragmented. Three other classic symptoms, which may not occur in all people with narcolepsy, are cataplexy (sudden muscle weakness often triggered by emotions such as anger, surprise, laughter, and exhilaration), sleep paralysis (temporary inability to talk or move when falling asleep or waking up), and hypnagogic hallucinations (dreamlike experiences that occur while dozing or falling asleep). People with narcolepsy have difficulty staying awake, and in extreme conditions, narcoleptic episodes can occur during periods of activity. Narcolepsy is not the same as simply becoming tired or dozing in front of the TV after a day’s work.

REM sleep in people with narcolepsy frequently occurs at sleep onset instead of after a period of NREM sleep. Consequently, researchers believe that the symptoms of narcolepsy result from a malfunction in some aspect of REM sleep initiation. Some scientists believe that the immune system causes narcolepsy by attacking the nervous system (that is, an autoimmune response). In this view, exposure to an unknown environmental factor results in an immune response against nerve cells in the brain circuits that control arousal and muscle tone. The discovery of a narcolepsy gene in dogs indicates that genetic risk factors for narcolepsy may also be pertinent in humans.Studies of narcoleptic dogs suggest that altered receptors for a specific neurotransmitter in the hypothalamus can cause cataplexy and the other symptoms of narcolepsy. Many individuals with narcolepsy appear to have a deficiency of this hypothalamic transmitter. There is no definitive cure for narcolepsy, but several treatment options alleviate various symptoms. Treatment is individualized depending on the severity of the symptoms, and it may take weeks or months for the optimal regimen to be worked out. Treatment is primarily by medications, but lifestyle changes are also important.

  • Sleep walking, sleep talking, and sleep terrors are more common in children than adults. Children generally have no memory of such events, usually do not require treatment, and usually outgrow the disorder.
    Parasomnias are sleep disorders that involve a range of behaviors that occur during sleep.These include sleepwalking, sleep talking, enuresis (bed-wetting), and sleep terrors, which are NREM disorders that occur early in the night. Many of the parasomnias (including sleepwalking, sleep talking, and sleep terrors) are more common in children. Children generally have no memory of such events, usually do not require treatment, and usually outgrow the disorder. Enuresis may respond to drug treatment, and like other parasomnias in children, it generally resolves as the child becomes older.

REM sleep behavior disorder is a parasomnia that occurs later in the night than NREM disorders. It differs from the parasomnias discussed previously because it usually affects middle-aged or elderly individuals. Frequently, sufferers will also have a neurological disorder. The temporary muscle paralysis that normally occurs during REM sleep does not occur in this disorder. Because the muscles are not paralyzed, individuals may act out potentially violent behaviors during sleep and cause injuries to themselves or their bed partners.

Restless Leg Syndrome

Restless legs syndrome (RLS) causes a powerful urge to move your legs. Your legs become uncomfortable when you are lying down or sitting. Some people describe it as a creeping, crawling, tingling, or burning sensation. Moving makes your legs feel better, but not for long. RLS can make it hard to fall asleep and stay asleep.

In most cases, there is no known cause for RLS. In other cases, RLS is caused by a disease or condition, such as anemia or pregnancy. Some medicines can also cause temporary RLS. Caffeine, tobacco, and alcohol may make symptoms worse.

Lifestyle changes, such as regular sleep habits, relaxation techniques, and moderate exercise during the day can help. If those don't work, medicines may reduce the symptoms of RLS.

Most people with RLS also have a condition called periodic limb movement disorder (PLMD). PLMD is a condition in which a person's legs twitch or jerk uncontrollably, usually during sleep. PLMD and RLS can also affect the arms.


Management of obstructive sleep apnea in adults: a clinical practice guideline from the American College of Physicians.


Bibliographic Source(s)


Qaseem A, Holty JE, Owens DK, Dallas P, Starkey M, Shekelle P, for the Clinical Guidelines Committee of the American College of Physicians. Management of obstructive sleep apnea in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2013 Sep 24;159:471-83. [198 references]

Guideline Status
This is the current release of the guideline.

This guideline meets NGC's 2013 (revised) inclusion criteria.

• Guideline Classification
• Related Content

Scope
Disease/Condition(s)
Obstructive sleep apnea (OSA)
Guideline Category
Management
Treatment
Clinical Specialty
Family Practice
Internal Medicine
Nursing
Otolaryngology
Pulmonary Medicine
Sleep Medicine
Surgery
Intended Users
Advanced Practice Nurses
Physician Assistants
Physicians
Respiratory Care Practitioners
Guideline Objective(s)
To present the evidence and provide clinical recommendations on the management of obstructive sleep apnea (OSA) in adults
Target Population
Adults with obstructive sleep apnea (OSA)

Interventions and Practices Considered
1. Weight loss through intensive weight loss interventions
2. Continuous positive airway pressure (CPAP)
• Fixed CPAP
• Auto-CPAP
• C-Flex
3. Mandibular advancement devices (MADs)

Note: Other obstructive sleep apnea (OSA) treatments, including positional therapy, oropharyngeal exercise, palatal implants, surgical interventions, pharmacologic therapy, and atrial overdrive pacing, were considered but no recommendations were made because of insufficient evidence.

Major Outcomes Considered
• Cardiovascular disease (such as heart failure, hypertension, stroke, and myocardial infarction)
• Type 2 diabetes
• Death
• Sleep study measures (such as the Apnea–Hypopnea Index [AHI])
• Measures of cardiovascular status (such as blood pressure)
• Measures of diabetes status (such as hemoglobin A1c levels)
• Quality of life

Methodology


Methods Used to Collect/Select the Evidence
Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases

Description of Methods Used to Collect/Select the Evidence
The Tufts Evidence-based Practice Center conducted the systematic evidence review. The literature search included studies identified using MEDLINE (1966 to September 2010), the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews and included peer-reviewed studies on adult human patients published in English. Further details about the methods and inclusion and exclusion criteria applied in the evidence review are available in the full Agency for Healthcare Research and Quality (AHRQ) report (see the "Availability of Companion Documents" field). No randomized, controlled trial (RCT) on obstructive sleep apnea (OSA) treatment with regard to mortality outcomes was identified.

The American College of Physicians (ACP) supplemented the AHRQ review (MEDLINE search, 1946 to October 2012) to identify English-language observational studies in humans reporting death or cardiovascular or cerebrovascular illness associated with OSA treatment strategies (that is, continuous positive airway pressure [CPAP], surgery, or mandibular advancement devices [MADs]), as well as more recent relevant RCTs.

Number of Source Documents
Not stated
Methods Used to Assess the Quality and Strength of the Evidence
Weighting According to a Rating Scheme (Scheme Given)
Rating Scheme for the Strength of the Evidence

This guideline rates the evidence and recommendations by using the American College of Physicians (ACP) guideline grading system, which is based on the system developed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) workgroup (see the "Rating Scheme for the Strength of the Recommendations" field).

Methods Used to Analyze the Evidence
Meta-Analysis of Randomized Controlled Trials
Review of Published Meta-Analyses
Systematic Review with Evidence Tables

Description of the Methods Used to Analyze the Evidence

To guide the recommendations, outcomes were prioritized on the basis of clinical importance, starting with death and including cardiovascular outcomes. In the absence of statistically significant effects on clinical outcomes, symptoms were considered (such as Epworth Sleepiness Scale [ESS] scores) and other physiologic measures (such as the Apnea–Hypopnea Index [AHI]).
The Tufts Evidence-based Practice Center conducted the systematic evidence review. Evidence on the comparative effectiveness of OSA treatments is summarized in the Appendix Table in the original guideline document. Further details on data extraction, quality assessment, and data synthesis are available in the systemic evidence review (see the "Availability of Companion

Documents" field).
Methods Used to Formulate the Recommendations
Expert Consensus

Description of Methods Used to Formulate the Recommendations
This guideline is based on a systematic evidence review sponsored by the Agency for Healthcare Research and Quality (AHRQ) (see the "Availability of Companion Documents" field) that addressed the following key questions related to obstructive sleep apnea (OSA) management:
1. What is the comparative effect of different treatments for OSA in adults?
a. Does the comparative effectiveness of treatments vary based on presenting patient characteristics, OSA severity, or other pretreatment factors? Are any of these characteristics or factors predictive of treatment success?
i. Characteristics: Age, sex, race, weight, bed partner, airway, other physical characteristics, and specific comorbid conditions.
ii. Obstructive sleep apnea severity or characteristics: Baseline questionnaire (and similar tools) results, formal testing results (including hypoxemia levels), baseline quality of life, positional dependency.
iii. Other: Specific symptoms.
2. In patients with OSA who are prescribed nonsurgical treatments, what are the associations of pretreatment, patient-level characteristics with treatment adherence?
3. What is the effect of interventions to improve adherence to device use (positive airway pressure, oral appliances, and positional therapy) on clinical and intermediate outcomes?

Rating Scheme for the Strength of the Recommendations
The American College of Physicians' Guideline Grading System*
Quality of Evidence Strength of Recommendation
Benefits Clearly Outweigh Risks and Burden or Risks and Burden Clearly Outweigh Benefits Benefits Finely Balanced with Risks and Burden
High Strong Weak
Moderate Strong Weak
Low Strong Weak
Insufficient evidence to determine net benefits or risks
*Adopted from the classification developed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) workgroup.
Cost Analysis
Published cost analyses were reviewed.
Method of Guideline Validation
Internal Peer Review
Description of Method of Guideline Validation

This guideline was approved by the American College of Physicians (ACP) Board of Regents on November 17, 2012.

Recommendations

Major Recommendations

The strength of the evidence (high, moderate, low, or insufficient evidence to determine benefits or risks) and strength of recommendations (strong, weak) are defined at the end of the "Major Recommendations" field.

Recommendation 1: The American College of Physicians (ACP) recommends that all overweight and obese patients diagnosed with obstructive sleep apnea (OSA) should be encouraged to lose weight. (Grade: strong recommendation; low-quality evidence)

Obesity is a risk factor for OSA, and evidence showed that intensive weight-loss interventions help reduce Apnea–Hypopnea Index (AHI) scores and improve OSA symptoms. Weight loss is also associated with many other health benefits other than for OSA. Other factors, such as alcohol and opioid use, may be associated with adverse outcomes in patients with sleep apnea, but these factors were not addressed in the evidence review.

Recommendation 2: ACP recommends continuous positive airway pressure (CPAP) treatment as initial therapy for patients diagnosed with OSA. (Grade: strong recommendation; moderate-quality evidence)

In patients with excessive daytime sleepiness who have been diagnosed with OSA, CPAP is the most extensively studied therapy. This treatment has been shown to improve Epworth Sleepiness Scale (ESS) scores, reduce AHI and arousal index scores, and increase oxygen saturation. However, CPAP has not been shown to increase quality of life. Evidence on the effect of CPAP on cardiovascular disease, hypertension, and type 2 diabetes was insufficient. Studies have evaluated various alternative CPAP modifications. Fixed and auto-CPAP, as well as C-Flex, have similar adherence and efficacy. Data were insufficient to determine the comparative efficacy of other CPAP modifications. Greater AHI and ESS scores were generally associated with better adherence to CPAP.

Recommendation 3: ACP recommends mandibular advancement devices (MADs) as an alternative therapy to CPAP treatment for patients diagnosed with OSA who prefer MADs or for those with adverse effects associated with CPAP treatment. (Grade: weak recommendation; low-quality evidence)

Evidence showed that MADs have been used as an alternative to CPAP for treatment of OSA. Patients had AHI scores between 18 and 40 events per hour. Evidence to suggest which patients would benefit most from MADs was insufficient. However, MADs can be considered in patients with adverse effects or for those who do not tolerate or adhere to CPAP.

Definitions:
The American College of Physicians' Guideline Grading System*
Quality of Evidence Strength of Recommendation
Benefits Clearly Outweigh Risks and Burden or Risks and Burden Clearly Outweigh Benefits Benefits Finely Balanced with Risks and Burden
High Strong Weak
Moderate Strong Weak
Low Strong Weak
Insufficient evidence to determine net benefits or risks
*Adopted from the classification developed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) workgroup.
Clinical Algorithm(s)
None provided

Evidence Supporting the Recommendations
Type of Evidence Supporting the Recommendations
The type of supporting evidence is identified and graded for each recommendation (see the "Major Recommendations" field).

Benefits/Harms of Implementing the Guideline Recommendations
Potential Benefits
Appropriate interventions for obstructive sleep apnea (OSA), taking into account the relative benefits and risks associated with each intervention
Potential Harms

Evidence on adverse effects related to various management strategies for obstructive sleep apnea (OSA) was sparse, especially from randomized control trials (RCTs). The Appendix Table in the original guideline document summarizes adverse effects associated with each treatment. Tooth loosening, dental crown damage, and temporomandibular joint pain were the most commonly reported adverse effects with mandibular advancement devices (MADs); however, long-term consequences were not reported. Overall, approximately 5% to 15% of patients treated with continuous positive airway pressure (CPAP) reported adverse effects that they considered to be substantial, but these symptoms were potentially transient. In general, adverse effects in patients treated with CPAP could be alleviated with termination or modification of the treatment. No long-term adverse effects were reported for weight-loss interventions.

Qualifying Statements

Qualifying Statements


• Clinical practice guidelines are "guides" only and may not apply to all patients and clinical situations. Thus, they are not intended to override clinicians' judgment. All American College of Physicians (ACP) clinical practice guidelines are considered automatically withdrawn or invalid 5 years after publication, or once an update has been issued.
• The authors of this article are responsible for its contents, including any clinical or treatment recommendations. No statement in this article should be construed as an official position of the

Department of Veterans Affairs.
Implementation of the Guideline
Description of Implementation Strategy
An implementation strategy was not provided.
Implementation Tools
Mobile Device Resources
Resources
For information about availability, see the Availability of Companion Documents and Patient Resources fields below.

Institute of Medicine (IOM) National Healthcare Quality Report Categories
IOM Care Need
Getting Better
Living with Illness
IOM Domain
Effectiveness
Patient-centeredness
Identifying Information and Availability
Bibliographic Source(s)
Qaseem A, Holty JE, Owens DK, Dallas P, Starkey M, Shekelle P, for the Clinical Guidelines Committee of the American College of Physicians. Management of obstructive sleep apnea in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2013 Sep 24;159:471-83. [198 references]

Adaptation
Not applicable: The guideline was not adapted from another source.
Date Released
2013 Sep 24
Guideline Developer(s)
American College of Physicians - Medical Specialty Society
Source(s) of Funding
Financial support for the development of this guideline comes exclusively from the American College of Physicians (ACP) operating budget.
Guideline Committee
Clinical Guidelines Committee of the American College of Physicians
Composition of Group That Authored the Guideline

Primary Authors: Amir Qaseem, MD, PhD, MHA; Jon-Erik C. Holty, MD, MS; Douglas K. Owens, MD, MS; Paul Dallas, MD; Melissa Starkey, PhD; and Paul Shekelle, MD, PhD
Clinical Guidelines Committee of the American College of Physicians: Paul Shekelle, MD, PhD (Chair); Roger Chou, MD; Molly Cooke, MD; Paul Dallas, MD; Thomas D. Denberg, MD, PhD; Nick Fitterman, MD; Mary Ann Forciea, MD; Robert H. Hopkins Jr., MD; Linda L. Humphrey, MD, MPH; Tanveer P. Mir, MD; Douglas K. Owens, MD, MS; Holger J. Schünemann, MD, PhD; Donna E. Sweet, MD; David S. Weinberg, MD, MSc; and Timothy Wilt, MD, MPH
Financial Disclosures/Conflicts of Interest
Potential Conflicts of Interest
Dr. Shekelle: Personal fees: ECRI Institute, Veterans Affairs; Grants: Agency for Healthcare Research and Quality, Veterans Affairs, Centers for Medicare & Medicaid Services, National Institute of Nursing Research, Office of the National Coordinator for Health Information Technology. All other authors have no disclosures.

Guideline Status
This is the current release of the guideline.
This guideline meets NGC's 2013 (revised) inclusion criteria.
Guideline Availability
Print copies: Available from the American College of Physicians (ACP), 190 N. Independence Mall West, Philadelphia PA 19106-1572.
Availability of Companion Documents
The following are available:
• Qaseem A, Snow V, Owens DK, Shekelle P. The development of clinical practice guidelines and guidance statements of the American College of Physicians: summary of methods. Ann Intern Med. 2010 Aug 3;153(3):194-199. Electronic copies:, Moorthy D, Obadan NO, Patel K, Ip S, Chung M, Bannuru RR, Kitsios GD, Sen S, Iovin RC, Gaylor JM, D'Ambrosio C, Lau J. Diagnosis and treatment of obstructive sleep apnea in adults. Comparative effectiveness review No. 32. (Prepared by Tufts Evidence-based Practice Center under Contract No. 290-2007-10055-1). AHRQ Publication No. 11-EHC052-EF. Rockville, MD: Agency for Healthcare Research and Quality (AHRQ). July 2011.
Print copies: Available from the American College of Physicians (ACP), 190 N. Independence Mall West, Philadelphia PA 19106-1572.
A collection of Recommendation Summaries for all current American College of Physicians Clinical Guidelines is now available for Personal Digital Assistant (PDA) download from the .
Patient Resources
None available
NGC Status
This NGC summary was completed by ECRI Institute on December 12, 2013.

How Is Sleep Apnea Treated?
Sleep apnea is treated with lifestyle changes, mouthpieces, breathing devices, and surgery. Medicines typically aren't used to treat the condition.
The goals of treating sleep apnea are to:
• Restore regular breathing during sleep
• Relieve symptoms such as loud snoring and daytime sleepiness

Treatment may improve other medical problems linked to sleep apnea, such as high blood pressure. Treatment also can reduce your risk for heart disease, stroke, and diabetes.
If you have sleep apnea, talk with your doctor or sleep specialist about the treatment options that will work best for you.

Lifestyle changes and/or mouthpieces may relieve mild sleep apnea. People who have moderate or severe sleep apnea may need breathing devices or surgery.
If you continue to have daytime sleepiness despite treatment, your doctor may ask whether you're getting enough sleep. (Adults should get at least 7 to 8 hours of sleep; children and teens need more.
If treatment and enough sleep don't relieve your daytime sleepiness, your doctor will consider other treatment options.
Lifestyle Changes

If you have mild sleep apnea, some changes in daily activities or habits might be all the treatment you need.
• Avoid alcohol and medicines that make you sleepy. They make it harder for your throat to stay open while you sleep.
• Lose weight if you're overweight or obese. Even a little weight loss can improve your symptoms.
• Sleep on your side instead of your back to help keep your throat open. You can sleep with special pillows or shirts that prevent you from sleeping on your back.
• Keep your nasal passages open at night with nasal sprays or allergy medicines, if needed. Talk with your doctor about whether these treatments might help you.
• If you smoke, quit. Talk with your doctor about programs and products that can help you quit smoking.

Mouthpieces

A mouthpiece, sometimes called an oral appliance, may help some people who have mild sleep apnea. Your doctor also may recommend a mouthpiece if you snore loudly but don't have sleep apnea.
A dentist or orthodontist can make a custom-fit plastic mouthpiece for treating sleep apnea. (An orthodontist specializes in correcting teeth or jaw problems.) The mouthpiece will adjust your lower jaw and your tongue to help keep your airways open while you sleep.
If you use a mouthpiece, tell your doctor if you have discomfort or pain while using the device. You may need periodic office visits so your doctor can adjust your mouthpiece to fit better.

Breathing Devices
CPAP (continuous positive airway pressure) is the most common treatment for moderate to severe sleep apnea in adults. A CPAP machine uses a mask that fits over your mouth and nose, or just over your nose.
The machine gently blows air into your throat. The pressure from the air helps keep your airway open while you sleep.
Treating sleep apnea may help you stop snoring. But not snoring doesn't mean that you no longer have sleep apnea or can stop using CPAP. Your sleep apnea will return if you stop using your CPAP machine or don’t use it correctly.
Usually, a technician will come to your home to bring the CPAP equipment. The technician will set up the CPAP machine and adjust it based on your doctor's prescription. After the initial setup, you may need to have the CPAP adjusted from time to time for the best results.
CPAP treatment may cause side effects in some people. These side effects include a dry or stuffy nose, irritated skin on your face, dry mouth, and headaches. If your CPAP isn't adjusted properly, you may get stomach bloating and discomfort while wearing the mask.
If you're having trouble with CPAP side effects, work with your sleep specialist, his or her nursing staff, and the CPAP technician. Together, you can take steps to reduce the side effects.
For example, the CPAP settings or size/fit of the mask might need to be adjusted. Adding moisture to the air as it flows through the mask or using nasal spray can help relieve a dry, stuffy, or runny nose.
There are many types of CPAP machines and masks. Tell your doctor if you're not happy with the type you're using. He or she may suggest switching to a different type that might work better for you.
People who have severe sleep apnea symptoms generally feel much better once they begin treatment with CPAP.

Surgery

Some people who have sleep apnea might benefit from surgery. The type of surgery and how well it works depend on the cause of the sleep apnea.
Surgery is done to widen breathing passages. It usually involves shrinking, stiffening, or removing excess tissue in the mouth and throat or resetting the lower jaw.
Surgery to shrink or stiffen excess tissue is done in a doctor's office or a hospital. Shrinking tissue may involve small shots or other treatments to the tissue. You may need a series of treatments to shrink the excess tissue. To stiffen excess tissue, the doctor makes a small cut in the tissue and inserts a piece of stiff plastic.
Surgery to remove excess tissue is done in a hospital. You're given medicine to help you sleep during the surgery. After surgery, you may have throat pain that lasts for 1 to 2 weeks.
Surgery to remove the tonsils, if they're blocking the airway, might be helpful for some children. Your child's doctor may suggest waiting some time to see whether these tissues shrink on their own. This is common as small children grow.

 

NIH: National Heart, Lung, and Blood Institute

Author: U.S. Department of Health and Human Services

 

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