Sleep dysfunction and sleep disordered breathing

Sleep dysfunction and sleep disordered breathing

Sleep Dysfunction and Sleep-Disordered Breathing P3 Research Summit Klar Yaggi M.D., M.P.H. Assistant Professor Yale University School of Medicine Section of Pulmonary and Critical Care Journal of the Canadian Medical Association; 2006 Outline

Basic clinical aspects of sleep/sleep-disordered breathing Interactions between pain, sleep, opiods, central sleep apnea Sleep, TBI, and PTSD Outline Basic clinical aspects of sleep/sleep-disordered breathing Differential Diagnosis of Hypersomnia

Sleep-disordered breathing (sleep apnea) Self-imposed sleep restriction Medication effects Narcolepsy Periodic limb movement disorder Circadian rhythm disorders

Epworth Sleepiness Scale Point Scale for chance of dozing in various situations 0= never 1= slight 2= moderate 3= high Situations (8 total) Score

Sitting inactive in a public place Sitting and reading Watching TV Passenger in a car for an hour without a break Lying down to rest in the afternoon Sitting and talking to someone Sitting quietly after lunch without alcohol In a car, while stopped for a few minutes in traffic __________ __________

__________ __________ __________ __________ __________ __________ Johns; Chest 1993 Standard Polysomnography

EEG, EOG, EMG EKG Airflow Chest/abd, bands Pulse oximetry Left/right leg EMG

Presence/stage of sleep Cardiac rate/rhythm Apnea/hypopnea Respiratory effort Arterial oxygen sat Leg movements (PLMs) Normal Sleep Architecture Physiology of Normal Sleep

NREM Sleep (80%) REM Sleep (20%)

Sympathetic nerve activity, HR, and BP (nocturnal dipping) Cerebral blood flow Regular breathing pattern Minute Ventilation Muscle tone

Sympathetic nerve activity, HR, and BP similar to awake Cerebral blood flow Irregular breathing pattern Breathing dependent on diaphragm Absent muscle tone Somers; NEJM 1993 Definitions and Severity Criteria

Apnea: Cessation of airflow > 10 sec (valid measure of breathing) Hypopnea: Decrease in airflow by 30%, associated with a >4% oxygen desaturation (best inter/intrascorer reliability) Severity Criteria: Mild: 5-15 events per hour Moderate: >15-30 events per hour

Severe: >30 events per hour AASM Task Force; Sleep 1999 Prevalence in Middle Aged Adults AHI 5 AHI 5 + daytime somnolence % Men

% Women 24 9 4 2 AHI = Apnea Hypopnea Index

Young; NEJM 1993 Risk Factors for Sleep Apnea

Obesity Increasing age Post-menopausal state Hypothyroidism Alcohol/sedating medications Obstructive lesions of the upper airway Craniofacial abnormalities (e.g. retrognathia) Pathogenesis of Obstructive Sleep Apnea

White; AJRCCM 2005 Common Symptoms Loud snoring Excessive daytime sleepiness Morning headaches (cerebral vasodilation)

Neuropsychiatric and cognitive symptoms Depression/emotional instability Short-term memory loss Impaired concentration Breathing pauses (bed partner history is key) Sleep Apnea Cycle Slee p

Apnea Hypoxia Reoxygenation Pleural pressure Ventilatio n Arousal

Sympathetic activation Sleep Apnea and Incident Hypertension Apnea Hyponea Index Events/hour 0 0.1-4.9 5-14.9 15

Adjusted* Odds Ratio 1.0 1.42 2.03 2.89 *adjusted for baseline hypertension, age, gender, BMI, waist circumference, alcohol, and tobacco use P for trend=0.002

Peppard; NEJM 2000 Other Consequences of Sleep Apnea

Excessive daytime sleepiness Cognitive dysfunction Decreased quality of life Depression Motor vehicle crashes Occupational accidents Pulmonary hypertension Cardiovascular morbidity and mortality Young; AJRCCM 2003

Event-free Survival (TIA, Stroke, Death) Kaplan-Meier Estimates of the Probability of Event-free Survival among Patients with the Obstructive Sleep Apnea Syndrome and Controls Yaggi, H. et al. N Engl J Med 2005;353:2034-2041 Yaggi; NEJM 2005 Modalities of Treatment

Behavioral Weight reduction Position training Surgery Tracheostomy Bariatric Surgery Upper airway modification: Uvulopalatopharyngoplasty (UPPP), Maxillo-mandibular advancement Application of Devices

Mandibular advancement devices Continuous positive airway pressure (CPAP) Positive Airway Pressure (CPAP) Outline Basic clinical aspects of sleep/sleep-disordered breathing Interactions between pain, sleep, opiods, central sleep apnea Chronic Pain Impairing Sleep:

Example of Fibromyalgia and Alpha-Delta Sleep Chronic pain sufferers often have impaired sleep Arousal augmenting aspects of pain may inhibit sleep initiation and continuity Alpha rhythm is an EEG rhythm with a frequency of 813Hz When alpha rhythm intrudes into SWS it is commonly referred to as alpha delta sleep. Alpha intrusion is associated chronic pain syndromes (e.g. fibromyalgia) Increased arousal during slow wave sleep may interfere with restorative function of sleep

Moldofsky; Psychosom Med 1975 Alpha-Delta Sleep 25 seconds Impaired Sleep Contributing to Pain: Selected Human Data Sleep deprivation produces hyperalgesic changes (increased pain sensitivity to noxious stimuli) in healthy subjects1,2

Slow wave sleep deprivation appeared to exert this effect Mainly observed in pressure pain stimulation Recovery of slow wave sleep increases pain tolerance Sleep deprivation produces sleepiness, increased fatigue, negative mood, cognitive impairment which may cause or mimic a modulation of pain processing3 1. Lentz; J Rheumatol 1999 2. Onen; J Sleep Res 2001 3. Kundermann; Pain Res Manage 2004

Impaired Sleep Contributing to Pain: Selected Animal Data Sleep deprivation produces hyperalgesic changes (increased pain sensitivity to noxious stimuli) in rats REM sleep deprivation especially appeared to exert this effect Observed in pressure pain stimulation, electrical stimuli REM sleep deprivation appeared to prevent analgesic action of endogenous/exogenous opiods 1. Hicks; Percept Mot Skills 1978 2. Ukponmwan; Gen Pharmacol 1984

3. Kundermann; Pain Res Manage 2004 Effect of Opiods on Sleep Architecture wakefulness and stage shifts

total sleep time sleep efficiency slow wave sleep REM sleep lighter stage NREM sleep Dimsdale; J Clin Sleep Med 2006 Lautenbacher; Sleep Med Rev, 2006 PAIN OPIODS

IMPAIRED SLEEP Chronic Opiate use as a Risk Factor for Central Sleep Apnea and Ataxic Breathing Observational cohort study of 60 patients taking chronic opiods matched with controls Patients taking chronic opiods Significantly higher AHI (due to central apneas) Lower arterial oxygen saturation Dose-response relationship

Walker;J Clin Sleep Med 2007 Central Sleep Apnea and Ataxic Breathing Walker;J Clin Sleep Med 2007 DREAM Determining Risk of Vascular Events by Apnea Monitoring VA CSR&D Merit Review Program

Adaptive Pressure Support Servo-ventilation (APPSV) Untreated Cheyne-Stokes Respiration Treated Cheyne-Stokes Respiration Teschler; AJRCCM 2001 APPSV: A Novel Treatment for Sleep Apnea Associated with Use of Opiods

Javaheri; J Clin Sleep Med 2008 Does the treatment of coexistent sleep disorders (e.g. sleep apnea) represent a novel therapeutic target help to improve outcomes among patients with pain, PTSD, TBI? VA HSR&D Merit Review Program Outline

Basic clinical aspects of sleep/sleep-disordered breathing Interactions between pain, sleep, opiods, central sleep apnea Sleep, TBI, and PTSD Sleep and TBI 1. Castriotta RJ, Wilde MC, Lai JM, Atanasov S, Masel BE, Kuna ST. Prevalence and consequences of sleep disorders in traumatic brain injury. J Clin Sleep Med. 2007:349-56. 2. Wilde MC, Castritta RJ, Lai JM, Atanasov S, Masel BE, Kuna, ST. Cognitive Impairment in patients with Traumatic Brain Injury and Obstructive Sleep Apnea. Arch Phys Med

Rehabil. 2007: 1284-8 Sleep in PTSD 1. Germain A, Buysee D, Nofzinger E. Sleep Specific Mechanisms Underlying Post-Traumatic Stress Disorder: Integrative review and Neurobiological Hypoetheses. Sleep Med Rev. 2008: 185-195

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