Sleep Apnea Syndromes: Hirshkowitz M

Kushida CA, Littner MR, Hirshkowitz M, Morgenthaler TI, Alessi CA, Bailey D, Boehlecke B, Brown TM, Coleman J, Friedman L, Kapen S, Kapur VK, Kramer M, Lee-Chiong T, Owens J, Pancer JP, Swick TJ, Wise MS, Anonymous00039. · Stanford University Center of Excellence for Sleep Disorders, Stanford, CA, USA. · Sleep. · Pubmed #16553024 No free full text.

Abstract: Positive airway pressure (PAP) devices are used to treat patients with sleep related breathing disorders (SRBD) including obstructive sleep apnea (OSA). Currently, PAP devices come in three forms: (1) continuous positive airway pressure (CPAP), (2) bilevel positive airway pressure (BPAP), and (3) automatic self-adjusting positive airway pressure (APAP). After a patient is diagnosed with OSA, the current standard of practice involves performing full, attended polysomnography during which positive pressure is adjusted to determine optimal pressure for maintaining airway patency. This titration is used to find a fixed single pressure for subsequent nightly usage. A task force of the Standards of Practice Committee of the American Academy of Sleep Medicine reviewed the available literature. Based on this review, the Standards of Practice Committee developed these practice parameters as a guideline for using CPAP and BPAP appropriately (an earlier review and practice parameters for APAP was published in 2002). Major conclusions and current recommendations are as follows: 1) A diagnosis of OSA must be established by an acceptable method. 2) CPAP is effective for treating OSA. 3) Full-night, attended studies performed in the laboratory are the preferred approach for titration to determine optimal pressure; however, split-night, diagnostic-titration studies are usually adequate. 4) CPAP usage should be monitored objectively to help assure utilization. 5) Initial CPAP follow-up is recommended during the first few weeks to establish utilization pattern and provide remediation if needed. 6) Longer-term follow-up is recommended yearly or as needed to address mask, machine, or usage problems. 7) Heated humidification and a systematic educational program are recommended to improve CPAP utilization. 8) Some functional outcomes such as subjective sleepiness improve with positive pressure treatment in patients with OSA. 9) CPAP and BPAP therapy are safe; side effects and adverse events are mainly minor and reversible. 10) BPAP may be useful in treating some forms of restrictive lung disease or hypoventilation syndromes associated with hypercapnia.

Kushida CA, Morgenthaler TI, Littner MR, Alessi CA, Bailey D, Coleman J, Friedman L, Hirshkowitz M, Kapen S, Kramer M, Lee-Chiong T, Owens J, Pancer JP, Anonymous00038. · Stanford University Center of Excellence for Sleep Disorders, CA, USA. · Sleep. · Pubmed #16494092 No free full text.

Abstract: These practice parameters are an update of the previously published recommendations regarding use of oral appliances in the treatment of snoring and Obstructive Sleep Apnea (OSA). Oral appliances (OAs) are indicated for use in patients with mild to moderate OSA who prefer them to continuous positive airway pressure (CPAP) therapy, or who do not respond to, are not appropriate candidates for, or who fail treatment attempts with CPAP. Until there is higher quality evidence to suggest efficacy, CPAP is indicated whenever possible for patients with severe OSA before considering OAs. Oral appliances should be fitted by qualified dental personnel who are trained and experienced in the overall care of oral health, the temporomandibular joint, dental occlusion and associated oral structures. Follow-up polysomnography or an attended cardiorespiratory (Type 3) sleep study is needed to verify efficacy, and may be needed when symptoms of OSA worsen or recur. Patients with OSA who are treated with oral appliances should return for follow-up office visits with the dental specialist at regular intervals to monitor patient adherence, evaluate device deterioration or maladjustment, and to evaluate the health of the oral structures and integrity of the occlusion. Regular follow up is also needed to assess the patient for signs and symptoms of worsening OSA. Research to define patient characteristics more clearly for OA acceptance, success, and adherence is needed.

Kushida CA, Littner MR, Morgenthaler T, Alessi CA, Bailey D, Coleman J, Friedman L, Hirshkowitz M, Kapen S, Kramer M, Lee-Chiong T, Loube DL, Owens J, Pancer JP, Wise M. · Stanford University Center of Excellence for Sleep Disorders, Stanford, CA, USA. · Sleep. · Pubmed #16171294 No free full text.

Abstract: These practice parameters are an update of the previously-published recommendations regarding the indications for polysomnography and related procedures in the diagnosis of sleep disorders. Diagnostic categories include the following: sleep related breathing disorders, other respiratory disorders, narcolepsy, parasomnias, sleep related seizure disorders, restless legs syndrome, periodic limb movement sleep disorder, depression with insomnia, and circadian rhythm sleep disorders. Polysomnography is routinely indicated for the diagnosis of sleep related breathing disorders; for continuous positive airway pressure (CPAP) titration in patients with sleep related breathing disorders; for the assessment of treatment results in some cases; with a multiple sleep latency test in the evaluation of suspected narcolepsy; in evaluating sleep related behaviors that are violent or otherwise potentially injurious to the patient or others; and in certain atypical or unusual parasomnias. Polysomnography may be indicated in patients with neuromuscular disorders and sleep related symptoms; to assist in the diagnosis of paroxysmal arousals or other sleep disruptions thought to be seizure related; in a presumed parasomnia or sleep related seizure disorder that does not respond to conventional therapy; or when there is a strong clinical suspicion of periodic limb movement sleep disorder. Polysomnography is not routinely indicated to diagnose chronic lung disease; in cases of typical, uncomplicated, and noninjurious parasomnias when the diagnosis is clearly delineated; for patients with seizures who have no specific complaints consistent with a sleep disorder; to diagnose or treat restless legs syndrome; for the diagnosis of circadian rhythm sleep disorders; or to establish a diagnosis of depression.

Littner MR, Kushida C, Wise M, Davila DG, Morgenthaler T, Lee-Chiong T, Hirshkowitz M, Daniel LL, Bailey D, Berry RB, Kapen S, Kramer M, Anonymous00029. · VA Greater Los Angeles Healthcare System, CA, USA. · Sleep. · Pubmed #15700727 No free full text.

Abstract: Characterization of excessive sleepiness is an important task for the sleep clinician, and assessment requires a thorough history and in many cases, objective assessment in the sleep laboratory. These practice parameters were developed to guide the sleep clinician on appropriate clinical use of the Multiple Sleep Latency Test (MSLT), and the Maintenance of Wakefulness Test (MWT). These recommendations replace those published in 1992 in a position paper produced by the American Sleep Disorders Association. A Task Force of content experts was appointed by the American Academy of Sleep Medicine to perform a comprehensive review of the scientific literature and grade the evidence regarding the clinical use of the MSLT and the MWT. Practice parameters were developed based on this review and in most cases evidence based methods were used to support recommendations. When data were insufficient or inconclusive, the collective opinion of experts was used to support recommendations. These recommendations were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine. The MSLT is indicated as part of the evaluation of patients with suspected narcolepsy and may be useful in the evaluation of patients with suspected idiopathic hypersomnia. The MSLT is not routinely indicated in the initial evaluation and diagnosis of obstructive sleep apnea syndrome, or in assessment of change following treatment with nasal continuous positive airway pressure (CPAP). The MSLT is not routinely indicated for evaluation of sleepiness in medical and neurological disorders (other than narcolepsy), insomnia, or circadian rhythm disorders. The MWT may be indicated in assessment of individuals in whom the inability to remain awake constitutes a safety issue, or in patients with narcolepsy or idiopathic hypersomnia to assess response to treatment with medications. There is little evidence linking mean sleep latency on the MWT with risk of accidents in real world circumstances. For this reason, the sleep clinician should not rely solely on mean sleep latency as a single indicator of impairment or risk for accidents, but should also rely on clinical judgment. Assessment should involve integration of findings from the clinical history, compliance with treatment, and, in some cases, objective testing using the MWT. These practice parameters also include recommendations for the MSLT and MWT protocols, a discussion of the normative data available for both tests, and a description of issues that need further study.

Littner M, Hirshkowitz M, Kramer M, Kapen S, Anderson WM, Bailey D, Berry RB, Davila D, Johnson S, Kushida C, Loube DI, Wise M, Woodson BT, Anonymous00013, Anonymous00014. · VA Greater Los Angeles Healthcare System, Sepulveda, CA, USA. · Sleep. · Pubmed #14572131 No free full text.

Abstract: Insomnia is a common and clinically important problem. It may arise directly from a sleep-wake regulatory dysfunction and/or indirectly result from comorbid psychiatric, behavioral, medical, or neurological conditions. As an important public-health problem, insomnia requires accurate diagnosis and effective treatment. Insomnia is primarily diagnosed clinically with a detailed medical, psychiatric, and sleep history. Polysomnography is indicated when a sleep-related breathing disorder or periodic limb movement disorder is suspected, initial diagnosis is uncertain, treatment fails, or precipitous arousals occur with violent or injurious behavior. However, polysomnography is not indicated for the routine evaluation of transient insomnia, chronic insomnia, or insomnia associated with psychiatric disorders.

Littner M, Hirshkowitz M, Davila D, Anderson WM, Kushida CA, Woodson BT, Johnson SF, Merrill SW, Anonymous00004. · VA Greater Los Angeles Healthcare System, and UCLA School of Medicine, Sepulveda, CA, USA. · Sleep. · Pubmed #11902424 No free full text.

Abstract: Continuous positive airway pressure (CPAP) is used to treat patients with the obstructive sleep apnea syndrome (OSAS). The current standard is for an attendant technician to titrate CPAP during full polysomnography to obtain a fixed single pressure. The patient uses CPAP nightly at this fixed single pressure. Recently, devices using new technology that automatically titrate positive airway pressure (APAP) have become available. Such devices continually adjust pressure, as needed, to maintain airway patency (APAP titration). These adjustments can be made with or without attendant technician intervention. Data obtained during APAP titration can be used to provide a fixed single pressure for subsequent treatment. Alternatively, APAP devices can be used in self-adjusting mode for treatment (APAP treatment). A task force of the Standards of Practice Committee of the American Academy of Sleep Medicine reviewed the available literature. Based on this review, the Standards of Practice Committee developed these practice parameters as a guide to the appropriate use of APAP. Recommendations are as follows: 1) A diagnosis of OSAS must be established by an acceptable method. 2) APAP titration and APAP treatment are not currently recommended for patients with congestive heart failure, significant lung disease (e.g., chronic obstructive pulmonary disease), daytime hypoxemia and respiratory failure from any cause, or prominent nocturnal desaturation other than from OSA (e.g., obesity hypoventilation syndrome). In addition, patients who do not snore (either due to palate surgery or naturally) should not be titrated with an APAP device that relies on vibration or sound in the device's algorithm. 3) APAP devices are not currently recommended for split-night studies since none of the reviewed research studies examined this issue. 4) Certain APAP devices may be used during attended titration to identify by polysomnography a single pressure for use with standard CPAP for treatment of OSA. 5) Once an initial successful attended CPAP or APAP titration has been determined by polysomnography, certain APAP devices may be used in the self-adjusting mode for unattended treatment of patients with OSA. 6) Use of unattended APAP to either initially determine pressures for fixed CPAP or for self-adjusting APAP treatment in CPAP naïve patients is not currently established. 7) Patients being treated with fixed CPAP on the basis of APAP titration or being treated with APAP must be followed to determine treatment effectiveness and safety, and 8) a re-evaluation and, if necessary, a standard attended CPAP titration should be performed if symptoms do not resolve or the CPAP or APAP treatment otherwise appears to lack efficacy.

Littner M, Kushida CA, Hartse K, Anderson WM, Davila D, Johnson SF, Wise MS, Hirshkowitz M, Woodson BT. · VA Greater Los Angeles Healthcare System, Sepulveda, CA, USA. · Sleep. · Pubmed #11480657 No free full text.

Abstract: Laser-assisted uvulopalatoplasty (LAUP) is an outpatient surgical procedure which is in use as a treatment for snoring. LAUP also has been used as a treatment for sleep-related breathing disorders, including obstructive sleep apnea. The Standards of Practice Committee of the American Academy of Sleep Medicine reviewed the available literature, and developed these practice parameters as a guide to the appropriate use of this surgery. Adequate controlled studies on the LAUP procedure for sleep-related breathing disorders were not found in peer-reviewed journals. This is consistent with findings in the original practice parameters on LAUP published in 1994. The following recommendations are based on the review of the literature: LAUP is not recommended for treatment of sleep-related breathing disorders. However, it does appear to be comparable to uvulopalatopharyngoplasty (UPPP) for treatment of snoring. Individuals who are candidates for LAUP as a treatment for snoring should undergo a polysomnographic or cardiorespiratory evaluation for sleep-related breathing disorders prior to LAUP and periodic postoperative evaluations for the development of same. Patients should be informed of the best available information of the risks, benefits, and complications of the procedure.

Jayaraman G, Sharafkhaneh H, Hirshkowitz M, Sharafkhaneh A. · Department of Medicine, Baylor College of Medicine and Michael E. DeBakey VA Medical Center, Houston, TX, USA. · Ther Adv Respir Dis. · Pubmed #19124383 No free full text.

Abstract: Obstructive sleep apnea (OSA) is associated with serious comorbid illnesses and diminished quality of life. At this time, continuous positive airway pressure (CPAP) therapy is the treatment of choice. However, only half of those individuals who accept CPAP are still using it at the end of one year. Furthermore, efficacy for improving self-reported sleepiness appears to be greater for patients with severe sleep apnea and severe sleepiness than other patient groups. Some patients, notwithstanding optimized therapy and therapeutic adherence continue experiencing excessive daytime somnolence. Consequently, other treatment modalities have developed, including oral appliances, surgery and pharmacotherapy. It is widely believed, albeit not empirically demonstrated, that an effective medication to treat OSA would elicit better acceptance and adherence than having to use a machine for many hours on a nightly basis. Nonetheless, paucity of data (i.e. lack of large-scale randomized controlled trials), variability of perceived and actual benefits, and adverse side-effects of the drugs thus far tested have prevented the use of pharmacotherapy until now. In this paper we review the outcome data from published trials designed to evaluate efficacy and safety of various medications proposed for treating obstructive sleep apnea.

Hirshkowitz M. · Department of Medicine and Menninger Department of Psychiatry, Baylor College of Medicine, Houston, USA. · J Fam Pract. · Pubmed #18687238 No free full text.

Abstract: Several conditions commonly seen in the primary care setting are known to be associated with obstructive sleep apnea (OSA), including hypertension, obesity, coronary artery disease, and type 2 diabetes, and should alert the physician to the possibility of this sleep disorder. The pathophysiology of OSA increases the risk of ischemic heart disease, decreases cardiac function, and elevates the risk of stroke. Treatment of OSA along with appropriate therapy for associated comorbidities presents an opportunity to simultaneously improve both conditions. Up to 56% of patients with OSA have hypertension. Addressing OSA can help improve this condition. More than 50% of patients with OSA experience depression. Treatment of OSA can lessen depressive symptoms associated with this sleeping disorder.

Hirshkowitz M, Sharafkhaneh A. · Department of Psychiatry, Baylor College of Medicine, Houston, Texas, USA. · Neurol Clin. · Pubmed #16243612 No free full text.

Abstract: This article discusses normal human sleep. Discoveries leading to an understanding of human sleep, electroencephalographic definitions, and general characteristics of normal human sleep are presented. Actuarial data for a first laboratory night are provided. Finally, the mechanisms governing sleep and wakefulness are reviewed and a model of normal sleep mechanisms going awry is outlined as an aid for understanding abnormal sleep associated with sleep disorders.

Hirshkowitz M, Sharafkhaneh A. · Department of Psychiatry, Baylor College of Medicine, Houston, Texas, USA. · Semin Respir Crit Care Med. · Pubmed #16052419 No free full text.

Abstract: Positive airway pressure is standard therapy for patients with obstructive sleep apnea. It comes in three basic varieties: (1) continuous positive airway pressure (CPAP), (2) bilevel positive airway pressure (BPAP), and (3) autotitrating positive airway pressure (APAP). When properly titrated, positive airway pressure devices minimize the number of sleep-related breathing disorder events, often producing dramatic results. Sleep-related breathing may completely normalize, specific stages of sleep may selectively rebound due to having been chronically suppressed, sleep microstructure may improve, and the patient may awaken feeling refreshed for the first time in years. The specific indications and criteria for recommending APAP, BPAP, and CPAP therapy are reviewed. The titration process is presented in a step-by-step manner and titration grading is explained. Issues surrounding the interface, acceptance, utilization, and side-effects are discussed. Finally, we present an assortment of approaches for troubleshooting clinical problems commonly encountered among patients being treated with positive airway pressure therapy.

Hirshkowitz M, Schmidt MH. · Department of Psychiatry, Baylor College of Medicine, Houston Veterans Affairs Medical Center Sleep Center, TX, USA. · Sleep Med Rev. · Pubmed #15994100 No free full text.

Abstract: Involuntary sleep-related erections (SREs) occur naturally during REM sleep in sexually potent men and other mammals. The regularity of their pattern and non-volitional nature made SREs useful clinically for differentiating psychogenic and organic erectile dysfunction (ED) in candidates for surgical intervention. Normative data available for different age groups added to the attractiveness of SRE measurement for clinical decision-making. Clinical SRE testing is less commonly applied today with the advent of minimally invasive medical therapies for ED. Nonetheless, as an objective measure of erectile function, SRE recording for research provides a precise technique for examining the mechanisms of erection and is still conducted to resolve legal disputes. SRE alterations provoked hormonally and pharmacologically are discussed. Different SRE patterns are associated with comorbid factors and some of these are illustrated, described, or both. Recording techniques developed for rats have proved extremely valuable for furthering our understanding of brain centers mediating erectile response. Data from lesion and stimulation studies are examined in the present review, moving us a step closer to understanding the underpinnings of erectile function.

Schwartz JR, Hirshkowitz M, Erman MK, Schmidt-Nowara W. · Integris Sleep Disorders Center of Oklahoma, 4200 S. Douglas, Suite 313, Oklahoma City, OK 73109, USA. · Chest. · Pubmed #14665500 links to  free full text

Abstract: STUDY OBJECTIVES: The purpose of this 12-week study was to evaluate the efficacy and safety of adjunct modafinil to treat excessive sleepiness in patients with obstructive sleep apnea (OSA) who experience residual sleepiness despite regular nasal continuous positive airway pressure (nCPAP) use. DESIGN: Twelve-week, open-label trial. SETTING: Twenty-two centers in the United States. PATIENTS: We studied 125 patients with moderate-to-severe OSA (ie, respiratory disturbance index > or =15) before nCPAP therapy and residual daytime sleepiness (Epworth sleepiness scale [ESS] score > or =10) despite effective and regular nCPAP therapy. Patients were studied after completing a 4-week, double-blind, placebo-controlled trial of nCPAP plus modafinil for the treatment of residual daytime sleepiness. Interventions and measurements: Patients received individually titrated doses of modafinil (200 to 400 mg qd). Sleepiness was assessed using the ESS, quality of life was evaluated using the Functional Outcomes of Sleep Questionnaire (FOSQ), and the overall clinical effect was indexed using the clinical global impression of change scale. Adverse events, nCPAP use, and vital sign measurements were also recorded. RESULTS: The significant improvements in daytime wakefulness and sleep-related functional status observed with modafinil treatment during the 4-week, double-blind study were maintained throughout 12 weeks of open-label treatment: week 12 ESS, 7.8 (4.7) vs 14.4 (3.1) at double-blind baseline; week 12 FOSQ, 3.3 (0.6) vs 14.4 (2.7) at double-blind baseline (mean [SD]). The percentage of patients rated as clinically improved increased from 83% after 1 week to > or =93% after 2 to 12 weeks of open-label treatment. Mean (SD) nCPAP use decreased from 6.3 (1.3) h/night at baseline to 5.9 (1.4) h/night (p = 0.004) during open-label treatment. The most common adverse events were headache (28%), anxiety (16%), and nervousness (14%). CONCLUSIONS: Modafinil remained effective and well tolerated as an adjunct therapy for residual daytime sleepiness even after 12 weeks of daily dosing in patients with OSA receiving nCPAP therapy.

Roth T, Schwartz JR, Hirshkowitz M, Erman MK, Dayno JM, Arora S. · Henry Ford Sleep Disorders Center, Detroit, MI 48202, USA. · J Clin Sleep Med. · Pubmed #17993041 links to  free full text

Abstract: STUDY OBJECTIVES: Modafinil is a wake-promoting agent shown to improve wakefulness in patients with excessive sleepiness (hypersomnolence) associated with shift work sleep disorder, obstructive sleep apnea, or narcolepsy. Safety and tolerability data from 6 randomized, double-blind, placebo-controlled studies were combined to evaluate modafinil across these different patient populations. METHODS: One thousand five hundred twenty-nine outpatients received modafinil 200, 300, or 400 mg or placebo once daily for up to 12 weeks. Assessments included recording of adverse events and effects of modafinil on blood pressure/heart rate, electrocardiogram intervals, polysomnography, and clinical laboratory parameters. RESULTS: Two hundred seventy-three patients with shift work sleep disorder, 292 with obstructive sleep apnea, and 369 with narcolepsy received modafinil; 567 received placebo. Modafinil was well tolerated versus placebo, with headache (34% vs 23%, respectively), nausea (11% vs 3%), and infection (10% vs 12%) the most common adverse events. Adverse events were similar across all patient groups. Twenty-seven serious adverse events were reported (modafinil, n = 18; placebo, n = 9). In modafinil-treated patients, clinically significant increases in diastolic or systolic blood pressure were infrequent (n = 9 and n = 1, respectively, < 1% of patients). In the studies, 1 patient in the modafinil group and 1 in the placebo group had a clinically significant increase in heart rate. New clinically meaningful electrocardiogram abnormalities were rare with modafinil (n = 2) and placebo (n = 4). Clinically significant abnormalities in mean laboratory parameters were observed in fewer than 1% of modafinil-treated patients at final visit. Modafinil did not affect sleep architecture in any patient population according to polysomnography. CONCLUSIONS: Modafinil is well tolerated in the treatment of excessive sleepiness associated with disorders of sleep and wakefulness and does not affect cardiovascular or sleep parameters.

Hirshkowitz M, Black J. · Michael E. DeBakey Veterans Affairs Medical Center - Sleep Diagnostic Clinic, Houston, Texas, USA. · CNS Drugs. · Pubmed #17447828 No free full text.

Abstract: OBJECTIVE: To evaluate the long-term effect on wakefulness, functional status and quality of life and tolerability of adjunctive modafinil in continuous positive airway pressure (CPAP)-treated patients with residual excessive sleepiness (ES) associated with obstructive sleep apnoea/hypopnoea syndrome (OSA/HS). STUDY DESIGN: 12-month, open-label extension of a 12-week, randomised, double-blind, placebo-controlled study. SETTING: Thirty-seven centres in the US and four in the UK. PATIENTS: Two hundred and sixty-six patients experiencing ES associated with OSA/HS who completed at least 8 weeks of the 12-week double-blind study, and who received adequate education and intervention efforts to encourage use of nasal CPAP (nCPAP). INTERVENTION: Patients receiving nCPAP therapy were administered modafinil 200 mg/day during week 1, 300 mg/day during week 2, and then 200, 300 or 400 mg/day, based on the investigator's assessment of efficacy and tolerability, for the remainder of the study. MAIN OUTCOME MEASURES: Assessments included the Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ) and Short Form-36 Health Survey (SF-36). RESULTS: One hundred and seventy five patients (66%) completed the study. Modafinil maintained a significant effect on wakefulness, as shown by improvement in the ESS total score at months 3, 6, 9 and 12 compared with baseline (all p < 0.0001). Modafinil also improved functional status (FOSQ total score) and general health (SF-36 mental and physical component scores) at months 6 and 12 compared with baseline (all p < 0.05).Modafinil was well tolerated. The most common adverse events reported were infection (11.3%), headache (9.4%) and nervousness (9.0%). Serious adverse events were reported in 13 patients, with two of these events (mild bradycardia and severe syncope, both in the same patient) considered to be possibly related to modafinil. There were few clinically meaningful changes in clinical laboratory data, vital signs, physical examination findings or ECG results. Important changes included significant increase in blood pressure in six patients, five of whom had a history of hypertension. CONCLUSIONS: Adjunctive modafinil maintained effects on wakefulness and functional outcomes, and improved quality of life in patients with OSA/HS experiencing residual ES over a 12-month period. Modafinil was well tolerated during long-term therapy.

Sharafkhaneh A, Sharafkhaneh H, Bredikus A, Guilleminault C, Bozkurt B, Hirshkowitz M. · Department of Medicine at Baylor College of Medicine, Houston, TX, USA. · Sleep Med. · Pubmed #17157066 No free full text.

Abstract: BACKGROUND AND PURPOSE: Obstructive sleep apnea (OSA) is associated with cardiovascular disease. Preliminary studies suggested breathing improvement in patients with apnea and heart disease when atrial overdrive pacing was applied during sleep. However, more recent studies do not show significant beneficial effect for atrial overdrive pacing in OSA. To further investigate this relationship, we conducted a randomized clinical trial evaluating the effect of atrial overdrive pacing on sleep-related breathing events in subjects with OSA and systolic heart failure. PATIENTS AND METHODS: We screened 33 subjects with symptoms consistent with OSA. On a screening overnight polysomnography (PSG), 15 subjects with mean age of 74 years (standard deviation (SD) 6.6) and ejection fraction of 38% (SD 14.4%) had OSA defined as having an apnea/hypopnea index (AHI) of > or =15 per hour of sleep. These subjects underwent additional PSGs including a night with atrial overdrive pacing (O), a night with pacemaker rate set at 40-50 beats per minutes (N), and a positive airway pressure titration night. The O and N nights were consecutive and the order was randomized. For O, the pacemaker rate was set at 15 beats higher than the average nightly heart rate (determined from the screening night). RESULTS: At baseline, mean AHI was 34.8 (15.5) and mean SaO(2) nadir was 85% (3.2%). Average heart rate was significantly higher on O nights compared to N nights (p<0.005). The apnea index (AI) was statistically lower on O nights compared to N nights (18+/-16.6 vs. 24+/-18.9, p<0.05). However, AHI and minimum and average O(2) saturations did not differ significantly between O and N nights. Interestingly, AHI improved statistically significantly on O nights in younger subjects. CONCLUSIONS: While statistically reliable, the small pacing-related reduction in sleep-disordered breathing (SDB) events is of unknown clinical significance. By contrast, continuous positive airway pressure (CPAP) dramatically improved AHI, AI, respiratory arousal index, and O(2) saturation. Thus our data suggest that overdrive pacing exerts a mild effect on respiratory events in some heart failure patients with OSA; however, atrial overdrive pacing was not therapeutically effective for improving airway patency and sleep-related respiratory function.

Hirshkowitz M, Black JE, Wesnes K, Niebler G, Arora S, Roth T. · Michael E. DeBakey VAMC Sleep Center, Baylor College of Medicine, Houston, TX 77030, USA. · Respir Med. · Pubmed #16908126 No free full text.

Abstract: OBJECTIVE: Armodafinil is the R-enantiomer of racemic modafinil and has a significantly longer half-life than the S-enantiomer. This study evaluated armodafinil 150 mg/day as an adjunct treatment for residual excessive sleepiness in patients with obstructive sleep apnea/hypopnea syndrome (OSA/HS) who were otherwise well controlled with nasal continuous positive airway pressure (nCPAP). We assessed the ability of armodafinil to improve wakefulness and cognition and reduce fatigue in this population. METHODS: In this 12-week, randomized, double-blind study, patients (n=259) received armodafinil (150 mg) or placebo once daily. Efficacy assessments at baseline and weeks 4, 8, and 12 included the Maintenance of Wakefulness Test (MWT), Clinical Global Impression of Change (CGI-C), Cognitive Drug Research battery, Epworth Sleepiness Scale, and Brief Fatigue Inventory. RESULTS: At final visit, mean (SD) MWT sleep latency increased from baseline by 2.3 (7.8) min with armodafinil and decreased by 1.3 (7.1) min in the placebo group (P=0.0003). Armodafinil improved clinical condition (CGI-C, 71% vs. 53% for armodafinil and placebo, respectively; P=0.0069). Armodafinil significantly improved episodic secondary memory (P=0.0102) and patient-estimated wakefulness (P<0.01) and reduced fatigue (P<0.05) compared with placebo. Armodafinil did not adversely affect nCPAP use. The most common adverse event associated with armodafinil was headache. Sleep macroarchitecture was not altered by armodafinil. CONCLUSION: Adjunct treatment with armodafinil significantly improved alertness, overall clinical condition, and long-term memory. Armodafinil also reduced fatigue and the impact of sleepiness on daily activities in patients with OSA/HS who have residual excessive sleepiness notwithstanding regular use of nCPAP. Armodafinil was well tolerated.

Sharafkhaneh A, Giray N, Richardson P, Young T, Hirshkowitz M. · Department of Medicine at Baylor College of Medicine, VAMC Sleep Center, Houston, TX 77030, USA. · Sleep. · Pubmed #16335330 No free full text.

Abstract: STUDY OBJECTIVES: We conducted the present study to determine whether psychiatric disorders are commonly associated with sleep apnea in Veterans Health Administration beneficiaries. METHOD: The Veterans Health Administration maintains several centralized databases containing healthcare data for more than 4 million veterans. We reviewed data from 1998 to 2001 and identified patient records having International Classification of Diseases-Ninth Edition-Clinical Modification codes indicating sleep apnea and various psychiatric conditions. Subsequently, we compared age, sex, ethnicity, and prevalence of comorbid psychiatric conditions for Veterans Health Administration beneficiaries with and without sleep apnea. RESULTS: Out of 4,060,504 unique cases, 118,105 were identified as having sleep apnea (estimated prevalence of 2.91%). Mean age at the time of diagnosis was 57.6 years. Psychiatric comorbid diagnoses in the sleep apnea group included depression (21.8%), anxiety (16.7%), posttraumatic stress disorder (11.9%), psychosis (5.1), and bipolar disorders (3.3%). Compared with patients not diagnosed with sleep apnea, a significantly greater prevalence (P < .0001) was found for mood disorders, anxiety, posttraumatic stress disorder, psychosis, and dementia in patients with sleep apnea. CONCLUSIONS: Sleep apnea is associated with a higher prevalence of psychiatric comorbid conditions in Veterans Health Administration beneficiaries. This association suggests that patients with psychiatric disorders and coincident symptoms suggesting sleep-disordered breathing should be evaluated for sleep apnea.

Black JE, Hirshkowitz M. · Stanford Sleep Disorder Clinic, Stanford University, Stanford, CA 94305, USA. · Sleep. · Pubmed #16171291 No free full text.

Abstract: STUDY OBJECTIVES: Nasal continuous positive airway pressure (nCPAP) usually reduces sleepiness in patients with obstructive sleep apnea/hypopnea syndrome. However, even with regular use of nCPAP, some patients experience residual excessive sleepiness. We evaluated the efficacy and safety of the wake-promoting agent modafinil for treating residual excessive sleepiness in nCPAP-treated patients. DESIGN: 12-week, multicenter, randomized, double-blind, parallel-group, placebo-controlled trial. PATIENTS: Patients aged 18 to 70 years diagnosed with obstructive sleep apnea/hypopnea syndrome and having residual excessive sleepiness during nCPAP therapy were eligible. INTERVENTIONS: Once-daily modafinil, 200 mg or 400 mg, or placebo. MEASUREMENTS AND RESULTS: Assessments included the Maintenance of Wakefulness Test, Epworth Sleepiness Scale, Clinical Global Impression of Change, and Functional Outcomes of Sleep Questionnaire. Both doses of modafinil significantly improved mean (SD) sleep latency on the Maintenance of Wakefulness Test at weeks 4, 8, and 12 compared with placebo (week 12: modafinil 400 mg, 15.0 [5.3] minutes; 200 mg, 14.8 [5.3] minutes; placebo, 12.6 [5.8] minutes; P < .0001). The Epworth Sleepiness Scale score decreased more in patients taking modafinil compared with those in the placebo group (week 12: modafinil 400 mg, -4.5 [4.3]; 200 mg, -4.5 [4.7]; placebo, -1.8 [3.5]; P < .0001). At week 12, overall clinical condition improved for 61% and 68% of patients treated with modafinil 200 mg and 400 mg, respectively, versus 37% of placebo-treated patients (P < .001). Modafinil was generally well tolerated and did not adversely affect nighttime sleep or nCPAP use. CONCLUSIONS: These results confirm previous shorter-term controlled trials, indicating modafinil is a useful adjunct therapy for improving wakefulness in patients with residual excessive sleepiness associated with obstructive sleep apnea/hypopnea syndrome who were treated with nCPAP.

Sharafkhaneh A, Richardson P, Hirshkowitz M. · VAMC Sleep Center 111i, Baylor College of Medicine, 2002 Holcombe Blvd., Houston, TX 77030, USA. · Sleep Med. · Pubmed #15222990 No free full text.

Abstract: BACKGROUND AND PURPOSE: In the present study we attempt to determine the prevalence of International Classification of Disease-ninth revision, Clinical Modification (ICD-9 CM) coded sleep apnea with cardiovascular and metabolic co-morbidities in Veterans Health Administration (VHA) beneficiaries. PATIENTS AND METHODS: Using VHA administrative databases, we gathered available medical information on more than 4 million veterans using the VHA during the period between 1998 and 2001. We identified database entries for codes indicating sleep apnea using the ninth revision of the Clinical Modification of the International Classification of Diseases (ICD-9 CM); and tabulated demographic data including age, gender, ethnicity, and cardiovascular and metabolic co-morbidities. RESULTS: We found 118,105 unique cases (out of 4,060,504) with sleep apnea ICD-9 CM codes (prevalence of 2.91%). Mean age at diagnosis was 57.6 with more than 38% older than 65 years. Comorbid diagnoses in this group included hypertension (60.1%), obesity (30.5%), diabetes mellitus (32.9%), cardiovascular disease (including MI and angina) (27.6%), heart failure (13.5%), and cerebrovascular accident (including Transient Ischemic Attack (TIA)) (5.7%). CONCLUSIONS: We found a high prevalence of diagnosed sleep apnea among VHA beneficiaries. Additionally, cardiovascular and metabolic conditions were common in these patients.

Raj R, Hirshkowitz M. · Department of Medicine, VAMC Sleep Disorders and Research Center (III i) and Baylor College of Medicine, 2002 Holcombe Blvd., Room 6C-344, Houston, TX 77030, USA. · Sleep Med. · Pubmed #14592357 No free full text.

Abstract: BACKGROUND: New Medicare criteria for prescribing continuous positive airway pressure (CPAP) recognize hypopnea as a sleep disordered breathing event. In so doing, hypopnea was redefined as requiring a 4% oxygen desaturation. The criteria omit electroencephalogram (EEG) arousals from the definition. This study was designed to assess how the new Medicare guideline changes CPAP eligibility. METHODS: Polysomnograms from 113 consecutive patients with obstructive sleep apnea were scored using both a definition for hypopnea that considered EEG arousals and the new Medicare definition that does not consider EEG arousal. CPAP eligibility was evaluated and compared. RESULTS: Sixteen percent of all patients and 41% of patients apnea+hypopnea index </=20 did not qualify for CPAP under the new Medicare guidelines. CONCLUSIONS: The new Medicare guidelines may underestimate OSA event occurrence and thereby deny CPAP therapy to many patients.