Sleep Deprivation 05-09
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SLEEP DEPRIVATION
Jeffrey Lin, M.D.
Fellow, Sleep MedicineStanford University Medical Center
5/6/2009
https://reader009.{domain}/reader009/html5/0512/5af701ed32277/
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OBJECTIVE
History of sleep deprivation studies
Animal Studies
Defining sleep deprivation
Consequences of sleep deprivation
Treatment of sleep deprivation
Liabilities of sleep deprivation
Current studies regarding sleepdeprivation
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HISTORY OF SLEEPDEPRIVATION
1894: Marie De Manaceine conducted the firstdocumented animal studies Kept puppies awake for 5 days
1896: Patrick and Gilbert conducted the first human
studies 90 hour sleep deprivation
1960: Dement conducted first partial sleep deprivation REM sleep deprivation
1964: Randy Gardner stayed awake for 264 hrs 1989: Rechtschaffen performed sleep deprivation
studies with mice using the disk-over-water method
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DISK-OVER-WATER METHOD
http://web.bvu.edu/faculty/ferguson/Course_Material/polysomnographs/Sleep%20Deprivation%20Data/Apparatus.jpg
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FLOWER POT METHOD
https:/.../attachments/34242959/flowerpot.jpg
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ANIMAL STUDIES
Scrawny appearance w/ disheveled fur. Severe lesions on the tail and paws...no apparent cause
was found Increased food intake; consumption doubled during the
latter phases of deprivation Increased energy expenditure; doubled during the latter
phases of deprivation Decrease in body temperature, beginning about half way
through the survival period
Weight loss; 18% - 20% drop in body weight. Death; all experimental animals (but no control animals)
died after 11-32 days of deprivation No significant post-mortem differences in the brains or
other major organs
Bergmann, Fang, Kushida, Everson, & Rechtschaffen, 1986
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RANDY GARDNER
www.kk.org/quantifiedself/2007/10/eleven-days...
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RANDY GARDNER
Stayed awake for a high school scienceproject
Had 2 of his friends keep him awake
Clinical condition monitored
Dr. William Dement
Lt. Cmdr. John Ross
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TIMELINE OF EVENTS
Day 1 – Woke at 6 am and ready to go
Day 2 – Difficulty focusing eyes and signsof astereognosis
Day 3 – Moodiness, some sign of ataxia,inability to repeat tongue twisters
Day 4 – Irritability and uncooperativeattitude, memory lapses and difficultyconcentrating. First illusion/delusion
Moorcroft, W.H. Sleep, Dreaming & Sleep Disorders (1993)
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TIMELINE OF EVENTS
Day 5 – More hallucinations
Day 6 – Speech slowing and difficultynaming common objects
Day 7 – Irritability and speech slurring
Day 8 – Increased memory lapses
Day 9 – Episodes of fragmented thinking Day 10 – Paranoia focused on a radio
show. Able to beat Dr. Dement on pinball
Moorcroft, W.H. Sleep, Dreaming & Sleep Disorders (1993)
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TIMELINE OF EVENTS
Day 11 – Expressionless appearance,speech slurred and without intonation.Unable to perform serial 7’s past 65
because he forgot what he was doing.
Final day – Appeared in a pressconference. “I wanted to prove that bad
things didn’t happen if you went withoutsleep.”
Moorcroft, W.H. Sleep, Dreaming & Sleep Disorders (1993)
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TIMELINE OF EVENTS
Day 12 - Fell asleep for 14 hrs and 40minutes
Stayed awake for 24 hrs, then slept anormal eight hours
Moorcroft, W.H. Sleep, Dreaming & Sleep Disorders (1993)
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HOW MUCH SLEEP?
Quantity of sleep How long a patient would sleep if left to
awaken spontaneously
How alert the patient feels after differentquantities of sleep
Quality of sleep Appropriate distribution of sleep stages
Timing of sleep Synchronization of process C and S
Pressman, Mark. Definition and consequences of sleep deprivation. UpToDate
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QUALITY OF SLEEP
Arousals can occur
Spontaneously
Secondary to sleep disorders
More frequent the arousal, more sleepinessduring the day
Artificially disrupting sleep 60 times/hr X 2 daysequals 40 – 60 hrs of total sleep deprivation
Sleep disturbance 5 times/hr can affect performance
Even acoustic tones that only caused EEG arousalsincreased daytime sleepiness
Bonnet, MH. Effect of sleep disruption on sleep performance and mood. Sleep 1985; 8:11Martin, S, Wraith, PK, Deary, IJ, Douglas, NJ. The effect of nonvisible sleep fragmentation on daytime function. AJRCCM 1997; 155:1596
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SLECTIVE SLEEP DEPRIVATION
Selective REM deprivation increases thepropensity of a subject to enter REM sleep
Night 1 – 17 awakenings
Night 2 – 42 awakenings
Night 3 – 68 awakenings
Subjects required 5-7 times as many
arousals to deprive them of SWS vs. REM
Agnew HW Jr et. Al. Percept Mot Skills 1967;24:851-8
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HOW MUCH SLEEP?
There is wide variation
American average 6 hrs and 40 min
Most desire 40 more min
Societal pressures are decreasing theaverage sleep time
Wehr: 8.5 hrs Sleep < 4 hrs or > 10 hrs have increased
mortality
Wehr, TA et. Al. Am J Physiol 1993; 265:R846-57
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MORTALITY AND SLEEP
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MORTALITY AND SLEEP
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CONSEQUENCES OF SLEEPDEPRIVATION
Physical effects
Increased appetite
Temperature disregulation
Shakiness
Headaches
Increased pain sensitivity
Decreased in immune function
Ansch, Browman, Mitler, and Walsh. Sleep: A Scientific Perspective (1988)
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IMPARED IMMUNE FUNCTION
31 healthy males
Night 1 : uninterrupted sleep
Night 2 : awake until 3 am Blood drawn every 30 min
Sleep monitored by EEG
Redwine L, et al. J Clin Endocrinol Metab 2000 Oct; 85(10):3597-603
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VARIATIONS INCONCENTRATION
Redwine L, et al. J Clin Endocrinol Metab 2000 Oct; 85(10):3597-603
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IMPARED IMMUNE FUNCTION
IL-6 level rise was delayed in the PSDgroup
Elevated levels of IL-6 associated with Stages
1,2, and R
IL-6 levels during SWS similar to awake
Similar findings with GH release
Cortisol and melatonin levels did not showsuch shift
Redwine L, et al. J Clin Endocrinol Metab 2000 Oct; 85(10):3597-603
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IMPARED IMMUNE FUNCTION
25 subjects, restricted to 6 hrs of sleep X 1wk
IL-6 was increased in both sexes
TNF – alpha was increased in men
Peak cortisol secretion was lower
More pronounced in men
Vgontzas AN et. Al. J Clin Endocrinol Metab 2004 May;89(5):2119-26
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IMPARED IMMUNE FUNCTION
42 healthy men
Two 2-hr naps daily Vs. total sleepdeprivation X 4 days
Blood draws every 6 hrs
Compared to PSD subjects, TSD subjects
had elevated TNF-alpha and IL-6 levels onday 4
Shearer WT, et al. J Allergy Clin Immunol 2001 Jan;107(1):165-70
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PSYCHOLOGICAL EFFECTS
Irritability
Poor concentration
Aggression
Apathy
Time and place disorientation
Loss of emotional control
Paranoia
Sleepiness
Ansch, Browman, Mitler, and Walsh. Sleep: A Scientific Perspective (1988)
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PSYCHOMOTOR CHANGES
Perceived exhaustion on endurance test
Decrements in speed and accuracy
Most obvious on long and monotonous tasks
Ansch, Browman, Mitler, and Walsh. Sleep: A Scientific Perspective (1988)
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SOCIETAL EFFECTS
www.personalfinanceanalyst.com/.../
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SOCIETAL EFFECTS
24 – hour society
Car accidents : 90,000 per year
American Airlines 1420 crash Chernobyl disaster
Exxon Valdez grounding
Shift work On-Call duties
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MAGGIE’S LAW
July 20, 1997: Maggie McDonnell was killed in a head-oncollision in Clementon, NJ The driver of the van had been awake for 30 hrs and smoked
crack cocaine before the crash
He was acquitted because the lawyer argued that fallingasleep was not a crime
August 2003: Maggie’s law passed in NJ If a fatal accident was caused by a driver who stayed awake >
24 hrs, they can be charged with vehicular homicide, up to 10
years in prison, and $100,000 fine August 2005: Man was sentenced to 5 yrs in state prison
for killing another driver after being sleep deprived for >24 hrs
Death by auto o vessell. N.J.S.2C.11-5, pub. L. 2003 c. 143. August 5, 2003
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COMMERCIAL DRIVERS
August 2005: US Federal Motor Carrier Safetyregulations
Drivers may only drive for 11 hrs in any one day
Must have 10 hrs free from duty the day before work Workday can not be longer than 14 hrs
Restriction on the total number of hrs worked in aweek
Prevalence of drivers sleeping < 5 hrs: 13.5%
Federal Motor Carrier Safety Administration. HOS regulations. 2005
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GROUNDING TIME
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Reddy, R. et al. Chest 2009; 135:81-85
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Reddy, R. et al. Chest 2009; 135:81-85
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Reddy, R. et al. Chest 2009; 135:81-85
4.8 + 4.1 minutes9 + 4.4 minutes
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HOUSESTAFF VS. FACULTY
Marcus CL, Loughlin GM. Sleep 1996; 19:763-766
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HOUSESTAFF VS. FACULTY
On CallHS
Not OnCall HS
FAC p Value
Sleep 2.7 hrs 7.2 hrs < 0.001
Asleep atlight
44% 12.5% < 0.001
Citations 25 15
Accidents 20 11
Marcus CL, Loughlin GM. Sleep 1996; 19:763-766
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TREATMENT FOR SLEEPDEPRIVATION
www.flickr.com/photos/doncolleen/1528345670/
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TREATMENT FOR SLEEPDEPRIVATION
Limiting time on task
Physical fitness
Exercise Rest breaks (5-20 min)
Napping
SLEEP
Kushida, CA. Sleep Deprivation: Basic Science, Physiology, and Behavior. 2005. Marcel Dekker
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TREATMENT FOR SLEEPDEPRIVATION
Recovery sleep
Sleep onset latency shorter
Arousal threshold increased
Increased in SWS first, followed by REM
Increased sleep time
For 1 night of TSD, sleep time may increase 2-4
hrsObligatory sleep vs. Facultative sleep
Kushida, CA. Sleep Deprivation: Basic Science, Physiology, and Behavior. 2005. Marcel Dekker
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SLECTIVE SLEEP DEPRIVATION
Recovery sleep from selective SWSdeprivation same as total sleep deprivation
SWS increased on night 1
REM increased on nights 2 and 3
Recovery sleep from selective REM sleepdeprivation different
SWS does not increase
REM increased on all 3 nights
Agnew HW Jr et. Al. Percept Mot Skills 1967;24:851-8
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PHARMACOLOGIC TREATMENT
http://www.usdoj.gov/dea/pubs/abuse/5-stim.htm
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PHARMACOLOGIC TREATMENT
Kushida, CA. Sleep Deprivation: Basic Science, Physiology, and Behavior. 2005. Marcel Dekker
Name Usual Dose Half Life Pros Cons
Caffeine
(NoDoz)
(Starbucks)
200-400 mg q4h 4-5 hrs Legal Mildly effective.
Tremors, diarrhea, diuretic.
Tolerance.
Methylphenidate
(Ritalin)
10 mg q4-6h 1-2 hrs Short half life
Low abuse potential
Few CV effects
Not as effective compared to othermeds.
Not approved for aviators.
Pemoline
(Cylert)
37.5 mg daily 12 hrs Low abuse potential
Few CV effects
Delayed onset of action.
Dextroamphetamine
(Dexedrine)
5-10 mg q 4-6h 10 hrs Very effective
Approved for military
aviators
Moderate abuse potential
Elevated pulse and BP
Modafinil
(Provigil)
100-200 mg q8h 14 hrs Effective
Low abuse potential
Few CV effects
Nausea
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CAFFEINE ANYONE?
LIABILITIES OF SLEEP
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LIABILITIES OF SLEEPDEPRIVATION
www.westsofeastdean.co.uk/large_gavel.html
LIABILITIES OF SLEEP
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LIABILITIES OF SLEEPDEPRIVATION
Error of omission – Individual fails torespond quickly to a situation
Error of commission – Individual creates
unnecessary risk of harm Drivers are liable for consequences of
falling asleep if they were aware of the
risks associated with their sleepdisturbance and did not take measures toreduce those risks
People V. Schaffer. 364 N.E. 2d 109 (III App. 1977)
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DRIVER LIABILITY
Evidence of a person sleeping whiledriving = Negligence Drivers bear the burden of rebutting the
presumption of negligence Recklessness
Sufficient rest preceding the crash
Time driving prior to crash
Prior warning that sleep was impending
Recklessness = Monetary judgment
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EMPLOYER LIABILITY
May be liable to an employee or third party if theaccident occurred within the scope of employment
Employee fell asleep while driving a company truckhome, causing a serious crash and injuring others
Employer was liable because the employee had a load of tires todeliver on the way home
On-call employee was driving back to work in a companyvehicle and fell asleep, causing injuries to others Employer was not liable because the employee was on a
personal errand
Mayes vs. Goodyear Tire & Rubber Co., 144 S.W. 3d 50 (Tex. App. 2004)J&C Drilling Co. Vs. Salaiz, 866 S.W. 2d 632 (Tex. App. 1993)
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CLINICIAN LIABILITY
Diagnostic evaluation is warranted when a sleepdisorder is suspected
All patients who have sleep disorders should be warnedabout risk of operating a motor vehicle or dangerousmachinery while sleepy For the high-risk population, they should be advised not to drive
until therapy has been instituted and proven effective
Clinicians are liable if they fail to inform the patientregarding risks of medical condition/treatment
Clinicians are not responsible for the actions of patients
who fail to take measures to reduce their risk, althoughthe risk of liability may be higher if they are required bystate statute to report a driver to the DMV
Joy vs. Eastern Maine Medical Center, 529 A.2d 1364 (Me. 1987)
CURRENT STUDIES IN SLEEP
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CURRENT STUDIES IN SLEEPDEPRIVATION
“Distinct effects of acute and chronic sleep
loss on DNA damage in rats.”
Sleep deprivation of rats
24 hrs
96 hrs
21 days
Evaluate DNA damage in blood, brain,liver, and heart cells
Andersen ML, Ribeiro DA, et. Al. Prog Neurophychopharmacol Biol Psychiatry. 2009 Feb 28.
SINGLE CELL GEL (COMET)
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SINGLE CELL GEL (COMET)ASSAY
Damaged DNA have more broken strands
Travels further toward the anode
The longer the comet tail, the more DNA
damage is presentAndersen ML, Ribeiro DA, et. Al. Prog Neurophychopharmacol Biol Psychiatry. 2009 Feb 28.
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DNA DAMAGE IN BRAIN CELLSAndersen ML, Ribeiro DA, et. Al. Prog Neurophychopharmacol Biol Psychiatry. 2009 Feb 28.
SLEEP DEPRIVATION AND
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SLEEP DEPRIVATION ANDATHLETES
“Effects of sleep deprivation on
cardiorespiratory functions of the runnersand volleyball players during rest and
exercise.” Spirometric at rest and incremental
exercise on ergometer
Following one night of sleep One night of sleep deprivation (25-30 hrs)
Azboy O, Kaygisiz Z. Acta Physiol Hung. 2009 Mar;96(1):29-36
SLEEP DEPRIVATION AND
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SLEEP DEPRIVATION ANDATHLETES - REST
Variable Volleyball players Runners
Spirometric fxn Unchanged Unchanged
Oxygen uptake (VO2) Unchanged Increased
CO2 production (VCO2) Increased Increased
Heart Rate Unchanged Unchanged
Respiratory quotient (R) Unchanged Unchanged
Minute ventilation (VE) Unchanged Unchanged
Arterial oxygen saturation(SaO2)
Unchanged Unchanged
Azboy O, Kaygisiz Z. Acta Physiol Hung. 2009 Mar;96(1):29-36
SLEEP DEPRIVATION AND
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SLEEP DEPRIVATION ANDATHLETES - EXERCISE
Variable Volleyball players Runners
Time to exhaustion Decreased Decreased
Oxygen uptake (VO2) Unchanged Unchanged
CO2 production (VCO2) Unchanged Unchanged
Heart Rate (HR) Unchanged Unchanged
Respiratory quotient (R) Unchanged Unchanged
Minute ventilation (VE) Decreased Decreased
Arterial oxygen saturation(SaO2)
Unchanged Unchanged
Azboy O, Kaygisiz Z. Acta Physiol Hung. 2009 Mar;96(1):29-36
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PERFORMANCE FACTORS
Nap No Nap P Value
Alertness Improved Same < 0.05
Sleepiness Decreased Same < 0.05
Short-term memory Improved Same < 0.05
Choice reaction timeaccuracy
Improved Same < 0.05
Choice reaction time
speed
Same Same NS
Grip strength Same Same NS
2 M sprint time 1.019 s 1.060 s 0.031
20 M sprint time 3.878 s 3.971 s 0.013
Waterhouse J, Atkinson G, Edwards B, ReillyT. J Sports. Sci. 2007 Dec;25(14):1557-66
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TAKE HOME POINTS
Sleep is important Total sleep time Sleep quality Timing of sleep
Sleep deprivation can result in adverse outcomes Physical consequences Psychiatric consequences Economic consequences Societal consequences
Treatment is effective Proper amount time allotted for sleep Well-timed naps Medications to help regulate sleep vs. stay awake
THANKS!
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ANIMAL STUDIES
Heat seeking behavior
Increased food intake
Weight loss
Increased metabolic rate
Increased plasma norepinephrine
Decreased plasma thyroxine Increased T3/T4 ratio