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
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 __________ __________
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
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
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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