SLEEP DISORDERED BREATHING: A DANGER TO HEALTH AND SAFETY
From the 14th Annual Symposium on Advances in Diagnosis and Treatment of Sleep Apnea
Educational Objectives
| The goal of this program is to improve the management of obesity hypoventilation syndrome (OHS) and obstructive sleep
apnea (OAS) and its consequences, including its impact on commercial drivers. After hearing and assimilating this program,
the participant will be better able to:
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 | 1. Define OHS and OSA and the spectrum of conditions associated with them.
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| 2. Choose among treatment options such as weight loss, continuous airway pressure (CPAP), and bi-level positive airway
pressure for patients with sleep-related breathing disorders.
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| 3. Recognize the associations between OSA and cardiovascular disease, and evaluate the effects of treatment on cardiac
function.
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| 4. Review data on the connection between motor vehicle accidents and OSA, especially in commercial drivers.
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| 5. Report on guidelines for and medicolegal implications of OSA in commercial drivers.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning
committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts
of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health
care and not a proprietary business or commercial interest. For this program, Dr. Kuna reported grant support and loaned
equipment from Respironics, Inc. Dr. Claman, Dr. Pack, and the planning committee reported nothing to disclose.
Acknowledgements
Lectures given by Drs. Claman, Kuna, and Pack were recorded at the 14th Annual Symposium on Advances in Diagnosis
and Treatment of Sleep Apnea and Snoring, held February 15 to 17, 2008, in San Francisco, CA, and sponsored
by the University of Pennsylvania Health System, Penn Sleep Centers, and the University of California, San Francisco,
School of Medicine. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation
in the production of this program.
| OBESITY HYPOVENTILATION SYNDROME —David Claman, MD, Clinical Professor of Medicine, and Director,
Sleep Disorders Center, University of California, San Francisco, School of Medicine
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| Complications of obstructive sleep apnea (OSA): cardiovascular—hypertension, heart failure, stroke, arrhythmias, pulmonary
hypertension; additional complications—excessive daytime sleepiness (EDS); motor vehicle accidents; hypoxemia
leads (infrequently) to polycythemia; obesity hypoventilation syndrome (OHS); overlap syndrome—chronic
obstructive pulmonary disease (COPD), and rapid eye movement (REM) sleep-related hypoxemia, combined with sleep
apnea
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| Obesity hypoventilation syndrome: definition—combination of obesity (BMI >30) plus hypercapnia (determined by
awake daytime arterial blood gas measurement); symptoms—EDS, fatigue, and morning headaches, similar to those of
OSA; oximetry useful in identifying; if hypoxemia present, consider lung disease or hypoventilation; 90% of patients
with OHS have sleep-disordered breathing (apnea-hypopnea index [AHI] >5); use pulmonary function tests (PFTs) to
rule out other causes of hypercapnia; arterial blood gases (ABGs) most accurate test for hypoxemia, but may need sleep
study to recognize as complication of OSA; apneic desaturations last 10 to 20 sec, so when prolonged desaturations (3-20
min) seen during polysomnography (PSG), consider evaluation for hypoxemia
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| Hypercapnia in OSA: multicenter study of 1100 patients to evaluate hypercapnia in sleep apnea—excluded patients
with obstructive lung disease; overall prevalence of daytime hypercapnia 11%; prevalence increased with increasing BMI
(7% with BMI <30, 10% with BMI 30-40, almost 25% with BMI >40 [morbidly obese]); ventilation control
mechanisms—waking drive to breathe (poorly understood); sleeping breathing depends on metabolic control from carbon
dioxide (linear response within physiologic range); if hypercapnia present due to hypoxemia, oxygen level produces
some drive to breathe; effects of carbon dioxide and oxygen synergistic; differential diagnosis of hypercapnia—patients
with breathing limitations (chest wall, neuromuscular, or obstructive lung diseases) distinguished by PFTs; patients with
central control problems, eg, congenital central hypoventilation syndrome (PHOX2B mutation), brainstem lesions, carotid
body diseases, metabolic alkalosis; patients with combined defects (COPD and sleep apnea); vicious cycle consisting
of episodes of hypercapnia and hypoxemia that cause arousals, sleep fragmentation that blunts ventilation control,
and hypoxemia that further degrades ventilation control
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| Treatment of OHS: weight loss most effective; CPAP for patients with mild hypercapnia, bi-level treatment or noninvasive
ventilation for patients with significant hypercapnia; study showed ventilation control improved rapidly (4-6 days) after
initiation of treatment; progesterone recommended only when patient noncompliant with bi-level treatment and declines
tracheotomy; retrospective comparison study of CPAP vs. bi-level treatment—54 morbidly obese OHS patients (33%
women), 87% with AHI >5; 3 patients started with CPAP alone, most started with bi-level treatment plus O2 ; at follow-
up, 16 on CPAP and only 30 still needed bi-level, 31 still needed O2 ; conclusion—OHS patients may need bi-level treatment
plus O2 ; careful monitoring and adjustment of therapy required as treatment progresses
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| OHS spectrum of abnormalities: apnea, hypopnea, sleep fragmentation, and blunting of ventilatory response; sleep hypoventilation
during REM or non-REM sleep; prolonged hypoventilation because of partial upper airway obstruction;
may also overlap with COPD; patient 1—fragmentation with periodic desaturations and hypoxemia; hypoxemia persisted
with low level of CPAP, and flow limitation present (suggesting partial airway obstruction that increased work of
breathing enough to diminish response); with higher CPAP level, flow limitation absent and oxygenation improved, ie,
sufficient positive pressure needed to open airway; patient 2—sleep-related hypoventilation; low level of saturation,
with flow limitations at baseline; lacked pattern of desaturation-resaturation; CPAP alone made saturation worse; bi-level
treatment required, ie, ventilation supported by difference between higher inspiratory pressure and lower expiratory pressure;
no flow limitation, and saturation improved
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| Molecular mechanisms (leptin): adipocyte-derived signaling factor that increases with BMI (overall fat mass predicts serum
leptin); receptors in hypothalamus; may modulate respiratory control in pulmonary disease; conflicting data on
whether leptin levels decrease or increase during treatment
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| SLEEP APNEA AND CARDIOVASCULAR DISEASE —Samuel T. Kuna, MD, Associate Professor, Department of Medicine,
University of Pennsylvania, and Chief, Pulmonary, Critical Care, and Sleep Section, Philadelphia Veterans Affairs
Medical Center, Philadelphia, PA
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| Increased mortality associated with OSA: data show CPAP treatment improves cardiovascular function and reduces risk
for cardiovascular events; sleep apnea and CVD have common risk factors (obesity, male sex, age); unknown whether
sleep apnea independently predicts CVD
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| Effects on cardiovascular function: acute—bradycardia during apnea episode, tachycardia during arousal; transient increase
in systemic arterial pressure associated with desaturation and arousal; do not see increase in pressure in pulmonary
artery (PA); however, repeated deoxygenation and reoxygenation leads to diurnal increase in PA pressure and to pulmonary
hypertension in some patients; vasoconstriction caused by hypoxia and hypercapnia leads to increase in PA pressure
and dilation of heart chambers on right side, right-sided congestive heart failure (CHF), and increased carbon dioxide retention
(pickwickian syndrome); elevated PA pressure believed to lead to atrial fibrillation (most common arrhythmia in
OSA)
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| Sleep Heart Health Study:association study; found 4-fold increase in frequency of atrial fibrillation in patients with more
severe OSA, as well as increased frequency of nonsustained ventricular tachycardia and complex ventricular ectopy; patients
matched for age, sex, ethnicity, and BMI, but significant differences in cardiovascular risk factors between groups
of different OSA severity; study also found increased prevalence of CVD in OSA patients (even at AHIs below diagnostic
threshold), but found no progressive increase in risk with increasing severity of OSA (except for stroke); limitations of
study—low number of patients in severe disease category; patients older, and population not random; randomized controlled
trial not ethically possible because of efficacy of CPAP
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| Observational study (Marin et al): measured cardiovascular events and death rates in 5 patient groups over 10 yr; compared
OSA patients on CPAP, untreated patients with severe OSA (patients who refused CPAP or were nonadherent), patients
with untreated mild to moderate OSA, snorers, and age- and weight-matched controls; findings—2-fold higher
risk for cardiovascular events in untreated severe OSA; risk in patients on CPAP (≥4 hr per night) similar to that in controls;
similar results in another study of mild to moderate OSA; however, patients not adhering to CPAP may not adhere
to other treatments (eg, antihypertensives, statins, diet, exercise); ongoing study finds similar adherence to CPAP and refill
rate for statin prescriptions; cannot yet conclude that OSA independent predictor of CVD
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| Evaluation of surrogate measures:randomized controlled trial showed decreased blood pressure in CPAP (1 mo) group vs
control; meta-analysis showed treatment of OSA reduced mean systemic arterial blood pressure; subset of patients (eg,
already hypertensive, more severe OSA) might respond more than others, so results not conclusive; mediators linking
OSA to CVD—increased sympathetic activity, inflammatory response, increased insulin resistance, changes in endothelial
function, C-reactive protein (CRP); CRP (inflammatory biomarker synthesized in liver), can increase with obesity but
increased more in OSA patients; CRP levels decreased after CPAP use
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| Patients with congestive heart failure: CPAP increased left ventricular ejection fraction; Cheyne-Stokes respiration in
CHF—breathing waxes and wanes, not necessarily separated by period of central apnea (absence of thoracic and abdominal
effort); periodic breathing during non-REM sleep driven by carbon dioxide apneic threshold; patient on bi-level
positive airway pressure (bi-PAP)—carbon dioxide level drops during sleep; if bi-PAP turned off when patient hypocapnic,
apneic episode occurs until carbon dioxide level rises above threshold again; patient with high ventilatory response
to hypoxia—may over-breathe during apneic episodes, causing carbon dioxide level drop below apneic threshold; patient
over-breathes again, causing another hypocapnic apnea
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| Canadian Positive Airway Pressure for Patients with Central Sleep Apnea and Heart Failure Trial (CANPAP): multicenter
study; no significant difference in survival between CPAP group and control group (conventional care); study
stopped because interim analysis showed decreased survival in CPAP-treated group and because of low recruitment rate;
difficulty recruiting patients as more patients treated with β-blockers; medical treatment of underlying heart failure best
treatment for central sleep apnea; problems with study—both CPAP and control groups had AHI >40 at outset, but AHI
for CPAP group reduced only to 20 during treatment (AHI >15 inclusion criteria for study); subgroup analysis of CPAP-
treated patients who achieved AHI <15 found improved survival; significant differences in cardiovascular risk and disease
in subgroups make study inconclusive
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| Adaptive servoventilation: new treatment; instrument senses flow and continuously adjusts pressure to keep tidal volume constant;
comparative study—patients with Cheyne-Stokes respiration; supplemental O2 or CPAP improved AHI, bi-PAP improved
AHI more, and adaptive servoventilation best; currently investigating adaptive servoventilation for complex sleep
apnea
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| SHOULD PATIENTS WITH SLEEP APNEA DRIVE? —Allan I. Pack, MB, ChB, PhD, Professor of Medicine; Chief, Division
of Sleep Medicine; and Director, Center for Sleep and Respiratory Neurobiology, University of Pennsylvania School
of Medicine, Philadelphia
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| Review of data: severe untreated OSA increases risk for automobile accidents, but association less clear for mild to moderate
OSA (AHI ranges 5-15 or 15-30); one analysis of accident records for 460 patients showed no increase in accident
frequency over previous 3 yr for patients with mild to moderate OSA but significant increase for patients with severe disease;
study of self-reported accidents had similar conclusion; recent study showed 2-fold increase in odds ratio for patients
with mild, moderate, and severe OSA
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| Predictors of accident risk: conflicting data highlight poor correlation between AHI and sleepiness; meta-analysis of studies
that looked at patients with OSA and sleepiness (obstructive sleep apnea syndrome [OSAS]) showed 2-fold increase
in accident risk; controversy over necessity of restricting driving in patients with AHI <30 who are not sleepy; search for
better predictors—off-road events, driving simulator, Epworth sleepiness score, respiratory disturbance index (RDI),
and psychomotor vigilance test (PVT) for reaction time not conclusive; currently no predictive tools
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| Effect of treatment: comparison of accident rates in CPAP users 3 yr before and after initiation of CPAP (study not intent-
to-treat); CPAP users had same accident rate as controls
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| Sleep apnea in commercial drivers: large relatively obese population; many have sleep apnea; 2 studies—one random,
one selected sample; apnea and cumulative partial sleep deprivation decreased performance; 32% had Epworth sleepiness
scores >10, and many had abnormal multiple sleep latency tests and PVT scores; sleep <5 hr similar to severe sleep apnea
and very common; identification—BMI 33 (minimizes false positives and false negatives; 77% sensitivity, 71%
specificity) and area under receiver operating curve of 0.80; current collaborative recommendations from National Sleep
Foundation, American College of Chest Physicians, and Occupational Medicine Society; evidence-based guidelines—
expected from Federal Motor Carrier Safety Administration by end of 2008; proposed Web-based national registry of 8
million commercial drivers and accreditation of physicians certifying commercial drivers; propose certification for patients
with untreated OSA if AHI <20 and no daytime sleepiness, or treated OSA; conditional certification (1 mo maximum,
ideally 1 wk) until sleep study completed if BMI >33 (≈2 million [24%] commercial drivers); argument made for
BMI cutoff of 30, but this would require sleep studies in almost half of all commercial drivers; compliance with treatment
must be demonstrated if driver has OSA; overnight PSG preferred for assessment
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| Medicolegal: previous American Thoracic Society (ATS) guideline (being revised) required reporting if patient had previous
sleep-related accident and refused treatment; critical to warn patient about risk and document; high-risk patients must stop
driving and seek sleep study and treatment within days; follow ATS guideline for passenger vehicles; new guidelines expected
for commercial vehicles; definition of high-risk driver—recent fall-asleep accident, repeated near-miss episodes;
maintenance of wakefulness tests not predictive
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Suggested Reading
Arzt M et al: Suppression of central sleep apnea by continuous positive airway pressure and transplant-free survival in heart
failure: a post hoc analysis of the Canadian Continuous Positive Airway Pressure for Patients with Central Sleep Apnea and
Heart Failure Trial (CANPAP). Circulation 115:3173, 2007; Banerjee D et al: Obesity hypoventilation syndrome: hypoxemia
during continuous positive airway pressure. Chest 131:1624, 2007; Barbe F et al: Effect of continuous positive airway
pressure on the risk of road accidents in sleep apnea patients. Respiration 74:44, 2007; Berger KI et al: Obesity hypoventilation
syndrome as a spectrum of respiratory disturbances during sleep. Chest 120:1231, 2001; Bradley TD et al: Continuous
positive airway pressure for central sleep apnea and heart failure. N Engl J Med 353:2025, 2005; Buchner NJ et al: Continuous
positive airway pressure treatment of mild to moderate sleep apnea reduces cardiovascular risk. Am J Respir Crit Care
Med 57:155, 2007; George CF: Reduction in motor vehicle collisions following treatment of sleep apnea with nasal CPAP.
Thorax 56:508, 2001; Gurubhagavatula I et al: Occupational screening for obstructive sleep apnea in commercial drivers.
Am J Respir Crit Care Med 170:371, 2004; Hartenbaum N et al: Sleep apnea and commercial motor vehicle operators:
Statement from the joint task force of the American College of Chest Physicians, the American College of Occupational and
Environmental Medicine, and the National Sleep Foundation. Chest 130:902, 2006; Howard ME et al: Sleepiness, sleep-disordered
breathing, and accident risk factors in commercial vehicle drivers. Am J Respir Crit Care Med 170:927, 2004; Laaban
JP, Chailleux E: Daytime hypercapnia in adult patients with obstructive sleep apnea syndrome in France, before
initiating nocturnal nasal continuous positive airway pressure therapy. Chest 127:710, 2005; Marin JM et al: Long-term cardiovascular
outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive
airway pressure: an observational study. Lancet 365:1046, 2005; Mansfield DR et al: Controlled trial of continuous positive
airway pressure in obstructive sleep apnea and heart failure. Am J Respir Crit Care Med 169:361, 2004; Mehra R et al: Association
of nocturnal arrhythmias with sleep-disordered breathing: The Sleep Heart Health Study. Am J Respir Crit Care
Med 173:910, 2006; Mokhlesi B, Tulaimat A: Recent advances in obesity hypoventilation syndrome. Chest 132:1322, 2007;
Morgenthaler TI et al: Adaptive servoventilation versus noninvasive positive pressure ventilation for central, mixed, and
complex sleep apnea syndromes. Sleep 30:468, 2007; Mulgrew A et al: Risk and Severity of Motor Vehicle Crashes in Patients
with Obstructive Sleep Apnea Hypopnea. Thorax, January 2008; Pack AI et al: Impaired performance in commercial
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Short-term and long-term effects of nasal intermittent positive pressure ventilation in patients with obesity-hypoventilation
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with obesity. Thorax 62:509, 2007; Shahar E et al: Sleep-disordered breathing and cardiovascular disease: cross-sectional
results of the Sleep Heart Health Study. Am J Respir Crit Care Med 163:19, 2001; Shimura R et al: Fat accumulation,
leptin, and hypercapnia in obstructive sleep apnea-hypopnea syndrome. Chest 127:543, 2005; Teschler H et al: Adaptive
pressure support servo-ventilation: a novel treatment for Cheyne-Stokes respiration in heart failure. Am J Respir Crit Care
Med 164:614, 2001; Turkington PM et al: Relationship between obstructive sleep apnoea, driving simulator performance,
and risk of road traffic accidents. Thorax 56:800, 2001; Yokoe T et al: Elevated levels of C-reactive protein and interleukin-6
in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure. Circulation
107:1129, 2003.
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