Recognizing and Treating Excessive Sleepiness in Primary Care: Reports From 2007


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Release Date: December 28, 2007



Excessive Sleepiness Research: 2007 in Review

Judge "Nodd" and the High Cost of Excessive Sleepiness

 

Perhaps a good place to begin a review of sleepiness research this year would be with a recent article about the misadventures of a 56-year-old judge, Ian Dodd, who fell from grace after falling asleep on the job.[1] Apparently, in 1992 and 1993, he was seen sleeping during trials that involved corporate fraud and shootings, and even when listening to a rape victim's testimony. During proceedings against a group of cocaine smugglers, the defense attorney passed notes to court officers sitting near the judge, asking them to wake him up. The jury noticed this as well, and nicknamed him "Judge Nodd." Some months before formal complaints were made, the unfortunate judge sought medical help, was found to have sleep apnea, and was treated successfully. Despite his improvement, formal proceedings were lodged on the basis of past cases. He was stripped of his driver's license and put on permanent medical leave to avoid a judicial inquiry.

This dramatic case is apparently not as unusual as it might sound; the authors of this paper describe 14 other examples of judicial napping on the job. These cases serve as good reminders that although attention to sleepiness in the workplace has often been focused on blue-collar workers such as truck drivers, this is an issue of concern in the professions as well. Most of us are familiar with efforts to reduce the long hours put in by house staff. It is important to note that there are now cases of legal proceedings started against physicians whose errors are attributed to sleepiness.[2]

Prevalence of Sleepiness

The report of subjective sleepiness is very high in the general population. Depending on the wording used in questionnaires, reports of sleepiness often run in the range of 5% to 15% or more of the population. This year, a detailed study of more than 2000 adults in Norway indicated that 17% of the population scored as significantly sleepy on a standard questionnaire, the Epworth Sleepiness Scale (ESS).[3] The factors that were associated with sleepiness form a good introduction to our discussion of recent research; they included a history of working nights, symptoms of cataplexy (an aspect of narcolepsy), having breathing pauses during sleep, or periodic limb movements during sleep. Thus, sleepiness in this population seems associated with symptoms of a number of sleep disorders as well as shift work. In this article we will look at new developments in these areas.

Idiopathic Hypersomnolence

Recent years have witnessed a growing recognition of narcolepsy, a disorder first described in the 1880s that involves irresistible episodes of sleepiness, as well as cataplexy (sudden loss of tone of the weight-bearing muscles), and sometimes sleep paralysis and hypnogogic hallucinations. Diagnosis is made by a Multiple Sleep Latency Test (MSLT), in which patients are studied during 4 daytime naps. Patients with narcolepsy fall asleep unusually quickly, and on at least 2 occasions enter rapid eye movement (REM) sleep very rapidly.

An article appearing this year describes a case series of 77 patients with a related but different disorder, idiopathic hypersomnia.[4] In this condition, patients complain of chronic sleepiness, with or without very prolonged nighttime sleep. In some cases they have great difficulty waking up in the morning and exhibit confusion and automatic behavior, known as 'sleep drunkenness.' Typically, patients describe taking long daytime naps, from which (in contrast to narcolepsy) they awaken unrefreshed. Sleep studies show increased slow-wave sleep, and the MSLT demonstrates sleepiness but not the REM-onset sleep episodes of narcolepsy. A diagnosis of idiopathic hypersomnia also requires that other causes of sleepiness such as drugs, metabolic disorders, and sleep-disturbed breathing are ruled out. This study is a good reminder to be aware of a group of chronically sleepy individuals who have no evidence of traditional causes of sleepiness but who nonetheless need and can benefit from treatment with stimulants.

Obstructive Sleep Apnea

Sleep apnea is by far the most common reason for sleepiness in patients seen at most sleep disorder centers. A worrisome aspect of this disorder is its association with myocardial infarction and stroke. This past year has seen several interesting developments concerning these complications. A study by Faulx and colleagues[5] has helped clarify the association between sleep-disordered breathing and cardiovascular disease. They examined urinary albumin secretion, which has been used as a surrogate for endothelial dysfunction, in patients with obstructive sleep apnea (OSA), and found that it was greatly elevated, especially in patients with severe OSA. This has been taken to suggest that endothelial dysfunction may be the mediating step between OSA and cardiovascular pathology. Of interest, a recent study by Drager and colleagues[6] found that continuous positive airway pressure (CPAP) treatment reverses various measures of atherosclerosis. Twelve patients with OSA who were free of comorbidities were given 4 months of CPAP and compared with 12 patients with OSA who received no treatment. Treated patients experienced reductions of carotid intima-media thickness, pulse-wave velocity, C-reactive protein, and catecholamines. This finding is striking in that these effects occurred after such a short period of CPAP; it also suggests that OSA may be an independent risk factor for atherosclerosis.

Although CPAP is a very effective treatment for OSA, a limiting factor is patient adherence, both to initiating the treatment at home and in sticking with it. A recent Australian study[7] examined the utility of short-term cognitive-behavioral therapy on CPAP adherence in 96 men. The therapy, accomplished in two 1-hour sessions, included watching a video of real CPAP patients, and discussing issues of self-efficacy (belief in one's ability to accomplish a goal), creating a more positive attitude, and learning a relaxation strategy. Compared with a treatment-as-usual group who received only a mask fitting and information, the therapy patients were using CPAP 2.9 hours per night more than the controls at 28 days. Only 4 of the therapy patients did not initiate home CPAP after the titration study, compared with 15 of the controls. It seems, then, that even brief cognitive-behavioral therapy, which has also been shown to be useful for patients with insomnia and those with asthma, may be helpful in improving adherence to CPAP, at least in the short term.

Another question that arises is: How many hours of CPAP are enough? A study by Weaver and colleagues[8] examined sleepiness and functioning in 149 patients with severe OSA before treatment and after 3 months of CPAP. Not surprisingly, the nightly duration of use varied widely across the group. The thresholds beyond which additional hours produced little benefit were 4 hours for improvements on the ESS, 6 hours on the MSLT, and 7.5 hours for a measure of functional outcomes related to sleepiness. It appears, then, that the optimal amount of CPAP depends on the measure of sleepiness being used, with approximately 7 hours being best for functional outcomes.

It is also important to remember that some patients have a good response to CPAP in terms of ventilation, but remain very sleepy.[9] In these cases, it is useful to go back and look for other co-existing disorders such as narcolepsy and idiopathic hypersomnia, as well as poor sleep habits. Animal research suggests that frequent episodes of hypoxia can damage brain areas involved in regulating wakefulness, and it is possible that this process could occur in patients with OSA.

Modafinil has been used to treat this residual sleepiness in patients with OSA. A multicenter, multinational, study examined the effect of 12 months of adjunctive modafinil on 175 patients who were receiving nasal CPAP for OSA. Treatment with modafinil maintained a significant effect on measures of wakefulness, functional status, and general health, compared with the patients' baselines (all P < .05), and was generally well tolerated.[10]

Another important consideration is the possibility of depression, which frequently appears in OSA patients. In this latter case, patients may complain of sleepiness, but the symptom is not confirmed by objective measures such as the MSLT. Treatment, of course, would be with antidepressants, preferably using an agent with minimal sedating properties.

Other Causes of Sleepiness

Sleepiness is also associated with obesity independent of sleep-disordered breathing. In a study of more than 1000 patients presenting for obesity surgery, sleepiness, as measured by the ESS, was independent of sleep study measures including apnea/hypopnea index, and inflammatory measures such as C-reactive protein.[11] Anthropometric measures and markers of the metabolic syndrome accounted for only 3% of the variance in ESS scores. Symptoms of depression and low energy contributed to 10% of the sleepiness scores, while sleep disturbance was the single biggest influence on ESS scores, accounting for 30% of the variance. The clinical message seems to be that, although it is important to consider sleep-disordered breathing in obese patients, one should not be too quick to assume that sleepiness is due to OSA, and to consider other causes as well.

Parkinson's Disease

Parkinson's Disease (PD) is traditionally associated with sleep disturbances, but a number of patients also complain of daytime sleepiness. Interestingly, there does not seem to be a clear association with age or duration of illness. A recent study of dopamine transporter binding has found that sleepiness was correlated with the degree of nigrostriatal dopaminergic degeneration.[12] Investigators reported no association of sleepiness with degree of motor impairment or depression scores. The clinical implication seems to be that daytime sleepiness should be included in the symptomatology of PD, and it remains to be seen whether administration of sleeping pills to consolidate sleep will improve daytime wakefulness. At the time of this writing, at least 2 pharmaceutical houses are sponsoring studies of the use of hypnotics in patients with PD.

On the topic of PD, this year has also seen the appearance of a case series pointing out that sleepwalking and related behaviors may also be associated with this disorder.[13] Some have speculated that this results from neurodegenerative changes at the brainstem level.

Premenstrual Syndrome and Pain

Sleepiness can also be characteristic of premenstrual syndrome. A study of 10 women with significant premenstrual symptoms compared with 9 who had mild symptoms found little or no difference in nocturnal sleep or daytime naps during the late luteal phase.[14] By contrast, those with significant premenstrual symptoms were sleepier and less alert during the daytime, and had higher nocturnal temperatures.

A study of healthy women has also emphasized the role of sleep in managing pain.[15] Subjects were divided into 3 groups: controls were allowed to sleep undisturbed, a forced awakening group was awakened once an hour for 3 nights, and a restricted sleep group received partial sleep deprivation by delaying bedtime. Sleep in the latter 2 groups was reduced by about 50%. The study found that the forced awakening group, but not the restricted sleep group, had an increase in sensitivity to pain and spontaneous pain during the daytime. This observation suggests that disruption of sleep continuity may be relatively more important than simple sleep restriction in exacerbating the response to pain. The implication is that an important aspect of helping pain patients is to address the quality of their sleep in general, and their sleep continuity in particular.

Physicians in Training

A source of daytime sleepiness familiar to all of us is the sleepiness that results from limited sleep during medical training. A recent study of Family Practice residents at Texas A&M University found that even after the implementation of mandated reductions in work hours, residents remained very sleepy.[16] Three-fourths of residents who were not on night-float schedules and who were not post-call nonetheless were found to have pathologic levels of sleepiness on the MSLT. Paradoxically, those who were on night-float schedules and were post-call did somewhat better. Both groups reported similar degrees of subjective sleepiness. More than 80% said that they had driven while they were sleepy.

When reading this article, this writer was reminded of a recent case at the University of Texas Medical Branch in Galveston, in which a resident going home post-call accidentally drove off a boulevard, over a high embankment, nearly ending up in the Gulf of Mexico. It is a good reminder that even with the mandated reduced work hours, residency remains a time of significant sleep deprivation.

Supported by an independent educational grant from Cephalon.


References

  1. Grunstein RR, Banerjee D. The case of "Judge Nodd" and other sleeping judges -- media, society, and judicial sleepiness. Sleep. 2007;30:625-632.  
  2. Grunstein RR, Rogers NL. Medical work hours: time for a Maggie's Law for doctoring? Intern Med J. 2005;35:269-271.
  3. Pallesen S, Nordhus IH, Omvik S, Sivertsen B, Tell GS, Bjorvatn B. Prevalence and risk factors of subjective sleepiness in the general adult population. Sleep. 2007;30:619-624.  
  4. Anderson KN, Pilsworth S, Sharples LD, Smith IE, Schneerson JM. Idiopathic hypersomnia: a study of 77 cases. Sleep. 2007;30:1274-1281.  
  5. Faulx MD, Storfer-Isser A, Kirchner HL, Jenny NS, Tracy RP, Redline S. Obstructive sleep apnea is associated with increased urinary albumin excretion. Sleep. 2007;30:923-929.  
  6. Drager LF, Bortolotto LA, Figueiredo AC, Krieger EM, Lorenzi GF. Effects of continuous positive airway pressure on early signs of atherosclerosis in obstructive sleep apnea. Am J Respir Crit Care Med. 2007;176:706-712.  
  7. Richards D, Bartlett DJ, Wong K, Malouff J, Grunstein RR. Increased adherence to CPAP with a group cognitive behavioral treatment intervention: a randomized trial. Sleep. 2007;30:635-640.  
  8. Weaver TE, Maislin G, Dinges D, et al. Relationship between hours of CPAP use and achieving normal levels of sleepiness and daily functioning. Sleep. 2007;30:711-719.  
  9. Santamaria J, Iranzo A, Ma Montserrat J, de Pablo J. Persistent sleepiness in CPAP treated obstructive sleep apnea patients: evaluation and treatment. Sleep Med Rev. 2007;11:195-207.  
  10. Hirshkowitz M, Black J. Effect of adjunctive modafinil on wakefulness and quality of life in patients with excessive sleepiness-associated obstructive sleep apnoea/hypopnoea syndrome: a 12-month, open-label extension study. CNS Drugs. 2007;21:407-416.  
  11. Dixon JB, Dixon ME, Anderson ML, Schachter L, O'Brien PE. Daytime sleepiness in the obese: not as simple as obstructive sleep apnea. Obesity (Silver Spring). 2007;15:2504-2511.  
  12. Happe S, Baier PC, Helmschied K, et al. Association of daytime sleepiness with nigrostriatal dopaminergic degeneration in early Parkinson's disease. J Neurol. 2007;254:1037-1043.  
  13. Poryazova R, Waldvogel D, Bassetti CL. Sleepwalking in patients with Parkinson disease. Arch Neurol. 2007;64:1524-1527.  
  14. Lamarche LJ, Driver HS, Wiebe S, Crawford L, DE Koninck JM. Nocturnal sleep, daytime sleepiness, and napping among women with significant emotional/behavioral premenstrual symptoms. J Sleep Res. 2007;16:262-268.  
  15. Smith MT, Edwards RR, McCann UD, Haythornthwaite JA. The effects of sleep deprivation on pain inhibition and spontaneous pain in women. Sleep. 2007;30:494-505.  
  16. Surani S, Subramanian S, Aguillar R, Ahmed M, Varon J. Sleepiness in medical residents: impact of mandated reduction in work hours. Sleep Med. 2007;8:90-93.  

Case Vignette: Central Sleep Apnea in a Patient Presenting With Daytime Fatigue and Sleepiness

History of Present Illness

 

The patient is a 52-year-old black man who comes to our sleep clinic with the chief complaint of waking up because of difficulty breathing. He also reports that he snores on a regular basis.

The girlfriend who accompanied him to the clinic reports frequently witnessing pauses in his breathing when he sleeps, and that these are bothersome enough that she has actually awakened him, fearful that he has died. In general, he sleeps flat on his back but occasionally wakes up gasping for air. He only rarely feels refreshed and ready to go upon waking up in the morning, and frequently feels tired during the day. He sleep-talks rarely but denies sleepwalking. He also denies any symptoms of sleep paralysis, hallucinations, or cataplexy, or ever acting out during dreams. He has no symptoms suggestive of restless legs syndrome or bruxism, and no history of epilepsy or head trauma.

He smokes 1 pack of cigarettes per day. He denies drinking alcohol or using illicit drugs. He generally goes to bed at 10 PM, and has no difficulty falling asleep but often watches TV before sleeping. He reports a usual waking time around 7 AM. He occasionally worked nights in the past, but has no job currently.

Past Medical History

This patient is known to have type 2 diabetes mellitus and hypertension. He also is known to have stage 3 NYHA class II congestive heart failure related to nonischemic dilated cardiomyopathy. He receives carvedilol, digoxin, and lisinopril. He has no history of lung, thyroid, or neurologic diseases. His family history is not significant for any sleep disorders.

Clinical Evaluation

The patient is overweight with a body mass index of 28.3 kg/m2. He has a Mallampati class 4 oropharyngeal airway, indicating a relatively narrowed oropharyngeal passage (the higher the class, the greater the risk). Lung auscultation reveals few inspiratory crackles at the bases bilaterally but otherwise is clear to auscultation without wheeze. A 2/6 holosystolic murmur is audible and heard best at the apex. The patient's extremities demonstrate chronic stasis changes with 1+ edema bilaterally but no clubbing or cyanosis. His Epworth sleepiness score is 15 out of 24 (a score of < 10 is considered normal; above that suggests hypersomnolence). His most recent echocardiogram shows left ventricle ejection fraction of 25% to 30% with severe global hypokinesis.

An overnight polysomnography (PSG) shows an apnea-hypopnea index of 47.5 per hour (< 5 per hour are normal) and minimal snoring (Figures 1, 2, and 3). The apnea-hypopnea events caused desaturations but no hypoxia or arousals, and the apneic events were predominantly central in type. The breathing pattern showed continuous cycles of crescendo and decrescendo changes in breathing amplitude, ending in hypopneas and apneas with arousals occurring at the hyperpnea stage. The sleep latency was shortened at 3 minutes, suggesting sleep pressure, but the REM sleep latency was normal. The periodic limb movement index was 0.0 per hour. The mean sleep oxygen saturation was 98%.

120-second epoch of PSG showing 2 central apneas (flat line in airflow, thoracic and abdominal channels
Figure 1. 120-second epoch of PSG showing 2 central apneas (flat line in airflow, thoracic and abdominal channels; in central apnea, the absence of airflow is without respiratory effort, unlike obstructive apnea where there is presence of effort but no airflow). Note the fall in oxygen saturation which lags after the occurrence of event.
Overlapped epoch of 30 seconds showing arousal secondary to central apnea.
Figure 2. Overlapped epoch of 30 seconds showing arousal secondary to central apnea. Note low amplitude mixed frequency EEG of Stage 1 sleep changing to high amplitude alpha frequency EEG of arousal (alpha frequency 8-12 Hz are more prominent in occipital channels O2-A1 and O1-A2 than in central channels C4-A1 and C3-A2, although still nicely seen in C3-A2).
A limited polygraph recording of 300-second epoch showing only the airflow, thoracic, abdominal, and oxygen saturation channels.
Figure 3. A limited polygraph recording of 300-second epoch showing only the airflow, thoracic, abdominal, and oxygen saturation channels. Note the abrupt cessation and appearance of airflow waveform. In pure Cheyne-Stokes breathing pattern, there is a crescendo-decrescendo hyperpnea interspersed among central apneas, and cycle lasts more than 45 seconds. Here, this typical pattern is missing and cycle lasts less than 30 seconds.

Management and Clinical Course

The patient's symptoms and PSG result support the diagnosis of central sleep apnea (CSA) syndrome most likely related to his heart failure. Initially, he is prescribed CPAP, but he is unable to tolerate it and is switched to bilevel positive airway pressure (BiPAP) therapy in addition to his existing medical therapy. He is also instructed to maintain a regular sleep/wake schedule as much as possible, avoid watching TV in bed, and aim for a minimum of 8 hours of nighttime sleep. In addition, he meets with a nutritionist who counsels him about a healthy diet to encourage weight loss.

One month later, at a follow-up visit, the patient reports that he is sleeping better. He generally feels good and no longer suffers daytime fatigue to the extent that he had in the recent past.

Heart Failure and Associated Sleep Disorders

Cardiovascular diseases remain the most common cause of both morbidity and mortality in the industrialized world.[1,2] Sleep disorders are also highly prevalent, estimated to affect more than 40 million Americans.[3] Hence disorders of sleep and cardiovascular disease frequently coexist.

Sleep-related breathing disorders (SRBD) are by far the most common sleep disorders encountered at the sleep centers. There are 2 major types of SRBD in the general population, namely obstructive (OSA) and CSA, with the former being more common.[4]

The Sleep Heart Health Study has shown the importance of SRBD as a contributing factor in the pathogenesis of myriad metabolic and cardiovascular disorders.[5] The widespread implications of SRBD on the cardiovascular system are summarized in Table 1.

Table 1. Cardiovascular Manifestations of Sleep Related Breathing Disorders (SRBD)[5-10]

Systemic hypertension
Pulmonary hypertension
Left ventricular hypertrophy
Left ventricular systolic and diastolic dysfunction
Congestive heart failure
Arrhythmias (atrial fibrillation)
Nocturnal angina
Increased platelet aggregability
Ischemic cardiovascular/cerebrovascular events
Sudden cardiac death (questionable)

In the context of heart failure, SRBD occurs with markedly greater frequency[8,9] compared with the general population, especially in patients with left ventricular ejection fraction (LVEF) < 40%.[11-13] Epidemiologic studies demonstrate a prevalence of 40% to 70% in ambulatory male patients with NYHA Class II & III.[12] There is compelling evidence that SRBD contributes to the pathophysiology and progression of this devastating disorder.[14-16] Thus, prompt recognition, appropriate diagnosis, and early institution of treatment is vital to improve the overall prognosis and quality of life in patients with heart failure. The 3 primary SRBDs are listed in Table 2. In the context of the case patient, our discussion will focus on CSA.

Table 2. Sleep-Related Breathing Disorders in Heart Failure[17]

Central sleep apnea (Cheyne-Stokes respiration)
Obstructive sleep apnea
Mixed type (combination of both central sleep apnea and obstructive sleep apnea)

Central Sleep Apnea

CSA with Cheyne-Stokes respiration (CSR) is a form of periodic breathing in which central apnea or hypopneas alternate with periods of hyperventilation. Although used interchangeably sometimes, the American Academy of Sleep Medicine recommends differentiating pure CSA from CSA that is associated with CSR because no crescendo-decrescendo breathing is seen in primary CSA. The distinctive feature of CSR is its long recovery period which reflects the long circulation time indicative of systolic heart failure. This differentiates CSR from other periodic breathing with CSA conditions (idiopathic form), in which the recovery arm is abrupt and short rather than smooth and prolonged.[11]

Clinical Features

Patients with CSA are usually thin and do not snore heavily, and despite having fragmented sleep due to arousals, most of the time they do not complain of excessive daytime somnolence.[11] For this reason, the Epworth Sleepiness Scale is probably not useful in evaluating heart failure patients. Patients who awaken during the peak of ventilation after apnea may complain of paroxysmal nocturnal dyspnea which, again, can be easily attributed to heart failure rather than SRBD. Moreover, the symptoms resulting from CSA usually overlap with the classic heart failure symptoms, such as orthopnea, cough, neurocognitive problems, nocturia, waking up unrested, nocturnal dyspnea, sleep fragmentation, and fatigue.[11] Thus, in heart failure patients, CSA remains occult.[12]

Pathophysiology of Central Sleep Apnea Related to Heart Failure

The left ventricular filling pressures are increased in heart failure along with enhanced central and peripheral chemosensitivity. This results in pulmonary congestion that activates the J receptors (vagal irritant receptors), ultimately stimulating hyperventilation and hypocapnia. Central apnea comes about because the increase in ventilation causes the PaCO2 to be driven below the threshold for ventilation. Apnea persists until PaCO2 rises above the threshold, require stimulating ventilation.[17] CSA will elicit chemical, neural, and homodynamic oscillations similar to those observed in OSA.

Diagnosis

A high index of suspicion is required to adequately recognize CSA and CSR in patients with heart failure patients because the clinical picture may not be entirely clear. Standard overnight PSG is the diagnostic modality of choice. It can differentiate different forms of SRBD and is also helpful in gauging severity by measuring the apnea- hypopnea index. PSG should be considered if risk factors CSR are present in patients with heart failure (Table 3).

Table 3. Risk Factors for Cheyne-Stokes Respirations in Patients With Heart Failure[11,17]

Male sex
Age greater than 60
Presence of atrial fibrillation
Hypocapnia (awake PaCo2 of 38 mm Hg or less)
Ventricular tachycardia
Low left ventricular ejection fraction (< 40%)
Higher NYHA Class (III & IV)
Excess premature ventricular beats and couplets
Refractory congestive heart failure with standard medical management
Note: Obesity is not a risk factor; women with heart failure rarely develop CSR, which may explain better prognosis compared with men.

Implications for Heart Failure

The 3 largest studies of CSA in patients with heart failure reported a CSA prevalence of 28% to 40%.[8,9,13] CSA remained an independent risk factor for death or cardiac transplantation.[11] This pathologic relationship may be attributed to marked neurohumoral activation, surges in blood pressure and heart rate, and a greater propensity for lethal arrhythmias induced by CSA.[15,16]

Treatment

CSA is likely arising as a consequence of heart failure, so its presence should alert the astute physician to optimize the pharmacologic treatment for heart failure, which includes the combination of angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, digoxin, and diuretics. Patients with heart failure who are on beta-blockers have a lower prevalence and severity of CSR than those who are not receiving beta-blockers.[18]

If CSA persists, however, a variety of therapeutic options are available:

Pharmaceuticals. Acetazolamide is a carbonic anhydrase inhibitor and causes a mild metabolic acidosis. This in turn stimulates the chemoreceptors in the carotid bodies and central chemoreceptors, thus acting as a respiratory stimulant.[19] It has been successfully used in the treatment of idiopathic CSA and periodic breathing at higher altitude. However, it cannot be recommended for therapy for CSA in heart failure patients because its long-term safety and effectiveness in such patients remains to be demonstrated.

Theophylline is a phosphodiesterase inhibitor, but its competitive nature with adenosine is what drives increased ventilation. Studies have shown efficacy in CSA[20] but potential arrhythmogenic effects and phosphodiesterase inhibition are major concerns for their long-term use.

Oxygen. Multiple studies have shown that nocturnal oxygen supplementation with a flow of 2-3 L/min improves the quality of sleep, sleep-related breathing events, and oxygen desaturation.[21] It also reduces the sympathetic activity and urinary norepinephrine excretion.[21] We need prospective, placebo-controlled, long-term studies to determine whether this form of treatment has the potential to improve the morbidity and mortality of patients with heart failure.

Positive airway devices. Nasal continuous positive airway pressure (nCPAP) has shown promising results in treating CSA from systolic heart failure. Several studies have demonstrated the benefit of nCPAP on LVEF, reducing urinary epinephrine secretion, increasing the distance walked in 6 minutes, and reducing cardiac sympathetic activity.[22] The largest randomized controlled trial to date (CANPAP) failed to show a benefit on the transplantation-free survival,[23] but the main limitation of the trial was the inability to reduce the apnea-hypopnea index (AHI) to below 15, which was the inclusion criterion. Later, the same group performed a post-hoc analysis and showed that early suppression of CSA to an AHI below 15 per hour may improve both LVEF and transplant-free survival.[24]

Pressure support ventilation such as bilevel positive airway pressure (BiPAP) or adaptive servo-ventilation (ASV) treatment should be offered to patients who are refractory, noncompliant, or unable to tolerate CPAP. Whereas CPAP operates at the same pressure level during expiration and inspiration, pressure support ventilation acts at a lower pressure during expiration and a higher pressure during inspiration, which actively supports it. ASV is a newer form of noninvasive pressure support treatment that has shown excellent results in open-label studies.[25,26]

Heart transplantation. Heart transplantation can eliminate CSR by virtue of reversing the homodynamic features of heart failures responsible for generation of CSA.[27] Unfortunately, follow-up studies have shown that patients develop OSA related to steroid treatment and obesity.[28]

Addressing Excessive Fatigue and Sleepiness in Patients With CSA

Maximizing pharmacotherapy for underlying cardiac disease, along with CPAP and BiPAP, are the only therapeutic modalities that have been studied for CSA. In most cases, improving the patient's cardiac and respiratory status and sleep will also ameliorate the patient's fatigue and daytime sleepiness. Arousals occur at the height of the hyperpnea phase, leading to sleep fragmentation and subsequent daytime symptoms of sleepiness. Treatment with CPAP or BiPAP is aimed at breaking this cycle and thus eliminating arousals, with consequent consolidation of sleep and improvement in daytime symptoms. Wake-promoting agents may be potentially risky in patients with CSA. If symptoms of fatigue and excessive sleepiness persist despite optimal treatment as described, exploring other causes for fatigue, such as secondary depression, hypothyroidism, and noncompliance, should be pursued.

Supported by an independent educational grant from Cephalon.


References

  1. American Heart Association. Heart disease and stroke statistics - 2003 update. Available at: http://www.americanheart.org/downloadable/heart/10590179711482003HDSStatsBookREV7-03.pdf Accessed December 7, 2007.
  2. American Heart Association. International cardiovascular disease statistics - 2003 update. Available at: http://www.americanheart.org/downloadable/heart/1077185395308FS06INT4(ebook).pdf Accessed December 7, 2007.
  3. Report of the National commission on Sleep Disorders Research. Wake up America: A national sleep alert. Washington, DC: US Government Printing Office; 1995.
  4. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep disordered breathing among middle aged adults. N Engl J Med. 1993;328:1230-1235.  
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  6. Peppard PE, Young T, Palta M et al. Prospective study of the association between sleep-disordered breathing and hypertension. N Eng J Med. 2000;342:1378-1384.
  7. Kanagala R, Murali NS, Friedman PA, et al. obstructive sleep apnea and the recurrence of atrial fibrillation. Circulation. 2003;107:2589-2594.  
  8. Sin D, Fitzgerald F, Parker J, Newton G, Florias J, Bradley T. Risk factors for central and obstructive sleep apnea in 450 patients with and without congestive heart failure. Am J Respir Crit Care Med. 1999;160:1101-1106.  
  9. Javeheri S, Parker TJ, Liming JD, et al. Sleep apnea in 81 ambulatory male patients with stable heart failure. Types and their prevalences, consequences and presentations. Circulation. 1998;97:2154-2159.  
  10. Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med. 2005;353:2034-2041.  
  11. Javaheri S. Central sleep apnea in congestive heart failure: prevalence, mechanisms, impact, and therapeutic options. Semin Respir Crit Care Med. 2005;26:44-55.  
  12. Javaheri S, Parker TJ, Wexler L, et al. Occult sleep disordered breathing in stable congestive heart failure patients. Ann Intern Med. 1995;122:487-492.  
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  16. Lanfranchi PA, Braghiroli A, Mazzuero G, et al. Prognostic value of nocturnal Cheyne - Stokes respiration in chronic heart failure. Circulation. 1999;99:1435-1440.  
  17. Bradley TD, Floras JS. Sleep apnea and heart failure: Part II: central sleep apnea. Circulation. 2003;107:1822-1826.  
  18. Tamura A, Kawano Y, Naono S, Kotoku M, Kadota J. Relationship between beta- blocker treatment and the severity of central sleep apnea in chronic heart failure. Chest. 2007;131:130-135.  
  19. Javaheri S. Acetazolamide improves central sleep apnea in heart failure: a double-blind, prospective study. Am J Respir Crit Care Med. 2006;173:234-237.  
  20. Javaheri S, Parker TJ, Wexler L, Liming JD, Lindower P, Roselle GA. Effect of theophylline on sleep-disordered breathing in heart failure. N Engl J Med. 1996;335:562-567.  
  21. Javaheri S, Ahmed M, Parker TJ, et al. Effect of nasal oxygen on sleep-related breathing in ambulatory patients with heart failure. Sleep. 1999;22:1101-1106.  
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Sleepy in America: Findings of the National Sleep Foundation's 2007 Survey of Women

Background

 

The National Sleep Foundation (NSF) has been conducting yearly surveys on sleeping habits, behaviors, and sleep problems for 10 years. The polls have varied to some degree but survey respondents have typically comprised adults age 18 and over from the general population. The NSF has also surveyed several special populations, including older adults (2003), infants and children (2004), and adolescents (2006). This year's poll focused on women's sleep habits, and is available, along with the 5 previous Sleep in America polls, on the NSF Web site.

These polls are always developed independent of the NSF. This year's Task Force of experts included Kathryn Lee, RN, PhD, Professor of Family Health Care Nursing and the James and Marjorie Livingston Chair School of Nursing, University of California - San Francisco; Meir Kryger, MD, Director of Research & Education, Gaylord Sleep Center, Gaylord Hospital, Wallingford, Connecticut; Fiona Baker, PhD, Sleep Physiologist at the Human Sleep Research Laboratory at SRI International, Menlo Park, California; and Amy Wolfson, PhD, Professor of Psychology at the College of the Holy Cross, Worcester, Pennsylvania.

The poll was conducted via a telephone survey of 1003 women, ages 18-64 years, living in the continental United States, and representative of the telephone households in the United States. Pregnant and postpartum women were oversampled. The survey tool took 25 minutes to complete. Data were collected during the 6 weeks between 9/12/06 and 10/28/06. The margin of error was plus or minus 3% at the 95% confidence level.

Objectives

The primary objectives were not only to determine the general sleep habits of women, but also to investigate more specifically how women's sleep changes during different reproductive stages. The survey also aimed to examine how women's multiple roles and functions affect their sleep, and to identify how often women experience various sleep problems. Specifically, the researchers set out to answer the following questions:

  1. What are the sleep habits of women across their lifespans?

  2. How many women experience various types of sleep problems/disorders?

  3. How often do women experience sleep problems/disorders?

  4. How is women's sleep affected during pregnancy and within 6 months of giving birth?

  5. How is women's sleep affected by life stage (during menstruation, pregnancy, post partum, perimenopause, and postmenopause)?

  6. How do women's multiple roles and lifestyles interact with their sleep?

Sleep and Sacrifice: A Summary of Findings

The survey found that women in the United States are not sleeping well and that this affects all aspects of their lives. As women struggle to "do it all," they sacrifice sufficient, good-quality sleep to accomplish their goals. In addition, women employ many coping strategies to sustain the pace of their daily lives. Finally, a variety of biological and lifestyle factors affect their sleep.

When asked how many nights a week they are getting good sleep, 60% answered that they get a good night's sleep only a few nights per week or less. Furthermore, 67% said that they experience sleep problems at least a few nights each week, and 46% experience sleep problems every night.

Several phenomena have been implicated in women's sleep problems. Hormonal changes throughout the lifespan disturb a woman's ability to get a good night's sleep. Whereas 24% of women of childbearing age reported getting a good night's sleep only a few nights a month or less, that percentage rose to 40% during pregnancy and 55% during the postpartum period. As women left their childbearing and child-rearing years, fewer suffered from poor sleep, with 25% of perimenopausal women and 30% of postmenopausal women reporting getting a good night's sleep only a few nights a month or less.

Lifestyle also appears to significantly affect women's sleep, as women are working and concurrently trying to run their households. Working mothers (72%) and single working women (68%) are more likely to experience sleep problems such as insomnia. Women reported being awakened because of noise (39%), children (20%), and pets (17%); women who allow children (9%) or pets (14%) to share their bed suffer the most disturbed sleep; 47% of women say that they have no choice in the matter, because they have no one helping them care for children at night.

As a consequence of poor sleep, many of the respondents experienced problems with daytime alertness. In fact, of the women who noted daytime sleepiness, 80% experience high stress, 39% spend less time with friends/family, 33% are too tired for sex, 27% drive drowsy at least once per month, and 20% were late for work in the month previous to the survey.

Another consequence of poor sleep was its effect on mood. Roughly 80% of women who reported sleeping poorly also reported being stressed out, anxious, or worried, and 55% admitted to being unhappy, sad, and depressed in the last month. Shift workers (53% vs 36% working a regular schedule), obese women (50% vs 36% nonobese), and/or those who use sleep medication at least a few nights weekly (57% vs 34% who seldom or rarely use sleep medications) were more likely to worry, experience stress or anxiety, and/or feel nervous, tense, sad, depressed, or hopeless about the future. Women with negative mood symptoms were 3 times more likely to experience daytime sleepiness at least a few days per week, 1.5 times more likely to experience a sleep problem at least a few nights per week, 2 times more likely to drive drowsy at least once per month, and 5 times more likely to miss work in the past month because of sleepiness. How are women coping with this daytime sleepiness? In all, 80% accept daytime sleepiness and keep going, and a good many (65%) drink caffeinated beverages to manage; of the latter, 37% drink 3 or more caffeinated beverages a day.

Even though many women were found to be consistently and dangerously sleepy, they are not trying to get more sleep. In many cases, they can't get to sleep earlier, as many are completing household chores (60%) and finishing work related to their jobs (20%). However, some are just trying to get something pleasurable out of the day, with 87% reporting that they watch TV, 51% read, and 37% engage in activities with their children. Noticeably, women don't do much with their spouses during their hours prior to bed.

A total of 29% of poorly sleeping women try sleep aids. More than half of these women use prescription medications (with a ratio of antidepressants to sleep medications of 4:3) but many substitute or also use over-the-counter sleep aids. Of the latter, a sleep medication and pain-reliever combination is most popular, followed by pure sleep medication, and then herbal/alternative remedies; 5% of poorly sleeping women choose alcohol to remedy their insomnia.

Of particular importance, this survey found that when women are tired/sleepy during the day, or simply run out of time, they sacrifice a healthy lifestyle. They forego sleep (52%) and exercise (48%), reduce time spent with family and friends (39%), stop healthy eating (37%), and don't participate in sexual activity (33%). One thing women won't do is sacrifice work: Only 20% of these women put work on the "back burner."

In looking at women's biology, the survey found that women clearly experience more sleep problems than men, and as women progress through different life stages, their changing biology affects the ability to get a good night's sleep. Similar to men, a woman's overall health affects her ability to sleep well such that more comorbidity is associated with more sleep problems. In fact, of the women in fair-to-poor health, 66% experience a sleep disorder symptom at least a few nights per week; 40% are diagnosed with a sleep disorder; 46% experience daytime sleepiness a few days per week; 26% have missed work in the past month because of poor sleep; and 54% use a sleep aid a few nights each week.

A Closer Look at Life Stages and Sleep in Women

The differences in the quality and quantity of sleep that women experience during their 5 reproductive stages is striking. Among women of childbearing age, 67% experience insomnia a few nights per week; 34% report experiencing a sleep disorder such as snoring, sleep apnea, or restless legs syndrome (RLS); 33% say that their sleep is disturbed during the week of their menstrual cycle; and 16% have missed work during the past month because of a sleep problem.

Not surprisingly, pregnant women experience substantial sleep problems: 30% say that they rarely or never get a good night's sleep; 84% have insomnia at least a few nights each week; 40% report sleep disorders such as snoring, sleep apnea, or RLS; and 54% nap at least twice per week. The survey of postpartum women was the first ever in this subgroup. These women report having insomnia at the same rate as pregnant women (84%), but 42% say that they rarely/never get a good night's sleep, which is more than any other group. At least one reason for poor sleep in these new moms is that 47% report having no help with their youngsters. Furthermore, 20% of these hard-working moms who suffer from sleep problems and daytime drowsiness have driven drowsy with children in the car. Finally, 19% of poorly sleeping new moms experience postpartum blues/depression.

Climacterics pose another unique set of sleep problems. The majority of perimenopausal women (59%) experience insomnia a few nights per week, and 43% report symptoms of a sleep disorder such as snoring, sleep apnea, or RLS. Of the nighttime disturbances, noise (36%) and sleeping with pets (20%) are the most common. In all, 20% experience night sweats and hot flashes that awaken them, and they report often having difficulty returning to sleep. After menopause, sleep problems continue and in some cases worsen for these women. This group has the highest incidence of curtailed time in bed: less than 6 hours (14%). Sleep disorders such as snoring or sleep apnea (42%) increase dramatically in this group, as does RLS (22%). Finally, as seen in previous studies, use of sleep aids (41%) is dramatically increased.

Recommendations to Improve Sleep, Health, and Quality of Life

At the end of the survey, the researchers proposed several suggestions for women in their quest towards better sleep, better health, and better quality of life:

Supported by an independent educational grant from Cephalon.




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Author

Wallace Mendelson, MD

Professor of Psychiatry and Clinical Pharmacology (retired), University of Chicago, Chicago, Illinois

Disclosure: Wallace Mendelson, MD, has disclosed that he has served as an advisor or consultant to, and served on the speaker's bureau of, Sepracor, Takeda, Neurocrine, Neurogen, VivoMetrics, and Abiant

Muhammed Faisal Hafeez Khan, MD

Sleep Fellow, Department of Medicine, Duke University Medical Center, Durham, North Carolina

Disclosure: Muhummad Faisal Hafeez Khan, MD, has disclosed no relevant financial relationships.

Ataf Chaudry, MD

Research Fellow, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY

Disclosure: Ataf Chaudry, MD, has disclosed no relevant financial relationships.

Sabin Bista, MBBS

Assistant Professor, Internal Medicine, University of Nebraska, Omaha, Nebraska; Staff Physician, Pulmonary Medicine, Critical Care, Sleep Medicine, and Allergy, University of Nebraska Medical Center, Omaha, Nebraska

Disclosure: Sabin Bista, MD, has disclosed no relevant financial relationships.

Paul Doghramji, MD, FAAFP

Family Physician, Collegeville Family Practice, Collegeville, Pennsylvania

Disclosure: Paul P. Doghramji, MD, has disclosed that he has served as an advisor or consultant to Cephalon, Takeda, sanofi-aventis, Pfizer, and Neurocrine. Dr. Doghramji has also disclosed that he has received grants for educational activities from Cephalon, Takeda, sanofi-aventis, Pfizer, Neurocrine, and Wyeth.

Editor

Priscilla Scherer, RN

Clinical Editor, Medscape, LLC, New York, NY

Disclosure: Priscilla Scherer has disclosed no relevant financial relationships.