Sleep Dysfunction and Sleep-Disordered Breathing P3 Research Summit

1
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

2
Journal of the Canadian Medical Association 2006
3
(No Transcript)
4
(No Transcript)
5
Outline

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

6
Outline

• Basic clinical aspects of sleep/sleep-disordered
  breathing

7
Differential Diagnosis of Hypersomnia

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

8
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
9
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)

10
Normal Sleep Architecture
11
Physiology of Normal Sleep

• NREM Sleep (80)
• ? Sympathetic nerve activity,
• HR, and BP (nocturnal dipping)
• ? Cerebral blood flow
• Regular breathing pattern
• ? Minute Ventilation
• ? Muscle tone

• REM Sleep (20)
• 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
12
(No Transcript)
13
Definitions and Severity Criteria

• Apnea Cessation of airflow gt 10 sec (valid
  measure of breathing)
• Hypopnea Decrease in airflow by 30, associated
  with a gt4 oxygen desaturation (best
  inter/intrascorer reliability)
• Severity Criteria
• Mild 5-15 events per hour
• Moderate gt15-30 events per hour
• Severe gt30 events per hour

AASM Task Force Sleep 1999
14
Prevalence in Middle Aged Adults
AHI Apnea Hypopnea Index
Young NEJM 1993
15
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)

16
Pathogenesis of Obstructive Sleep Apnea
White AJRCCM 2005
17
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)

18
(No Transcript)
19
Sleep Apnea Cycle
Apnea
Sleep
Hypoxia
Reoxygenation
Pleural pressure ?
Sympathetic activation
Ventilation
Arousal
20
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 trend0.002

• Peppard NEJM 2000

21
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
22
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 20053532034-2041
Yaggi NEJM 2005
23
Modalities of Treatment

• Behavioral
• Weight reduction
• Position training
• Surgery
• Tracheostomy
• Bariatric Surgery
• Upper airway modification Uvulopalatopharyngoplas
  ty (UPPP),
• Maxillo-mandibular advancement
• Application of Devices
• Mandibular advancement devices
• Continuous positive airway pressure (CPAP)

24
Positive Airway Pressure(CPAP)
25
Outline

• Basic clinical aspects of sleep/sleep-disordered
  breathing
• Interactions between pain, sleep, opiods, central
  sleep apnea

26
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
  8-13Hz
• 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
27
Alpha-Delta Sleep
25 seconds
28
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

• Lentz J Rheumatol 1999
• Onen J Sleep Res 2001
• Kundermann Pain Res Manage 2004

29
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

• Hicks Percept Mot Skills 1978
• Ukponmwan Gen Pharmacol 1984
• Kundermann Pain Res Manage 2004

30
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
31
PAIN
IMPAIRED SLEEP
OPIODS
32
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

WalkerJ Clin Sleep Med 2007
33
Central Sleep Apnea and Ataxic Breathing
WalkerJ Clin Sleep Med 2007
34
Determining Risk of Vascular Events by Apnea
MonitoringVA CSRD Merit Review Program

• DREAM

35
Adaptive Pressure Support Servo-ventilation
(APPSV)
Treated Cheyne-Stokes Respiration
Untreated Cheyne-Stokes Respiration
Teschler AJRCCM 2001
36
APPSV A Novel Treatment for Sleep Apnea
Associated with Use of Opiods
Javaheri J Clin Sleep Med 2008
37
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?
38
VA HSRD Merit Review Program
39
Outline

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

40
Sleep and TBI

• 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.
  2007349-56.
• 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

41
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