Sleep Deprivation 05-09

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SLEEP DEPRIVATION

Jeffrey Lin, M.D.

Fellow, Sleep MedicineStanford University Medical Center

5/6/2009

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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



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



DISK-OVER-WATER METHOD

http://web.bvu.edu/faculty/ferguson/Course_Material/polysomnographs/Sleep%20Deprivation%20Data/Apparatus.jpg



FLOWER POT METHOD

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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



RANDY GARDNER

www.kk.org/quantifiedself/2007/10/eleven-days...

http://www.kk.org/quantifiedself/2007/10/eleven-days-awake-selfexperime.php






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



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)



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




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.”




TIMELINE OF EVENTS

Day 12 - Fell asleep for 14 hrs and 40minutes

Stayed awake for 24 hrs, then slept anormal eight hours




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



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



SLECTIVE SLEEP DEPRIVATION

Selective REM deprivation increases thepropensity of a subject to enter REM sleep

Night 1 – 17 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



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



MORTALITY AND SLEEP



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)



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



VARIATIONS INCONCENTRATION





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





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




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



PSYCHOLOGICAL EFFECTS

Irritability

Poor concentration

Aggression

Apathy

Time and place disorientation

Loss of emotional control

Paranoia

Sleepiness




PSYCHOMOTOR CHANGES

Perceived exhaustion on endurance test

Decrements in speed and accuracy

Most obvious on long and monotonous tasks




SOCIETAL EFFECTS

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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



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



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



GROUNDING TIME



Reddy, R. et al. Chest 2009; 135:81-85




4.8 + 4.1 minutes9 + 4.4 minutes



HOUSESTAFF VS. FACULTY

Marcus CL, Loughlin GM. Sleep 1996; 19:763-766



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



TREATMENT FOR SLEEPDEPRIVATION

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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




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




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



PHARMACOLOGIC TREATMENT

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PHARMACOLOGIC TREATMENT


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



CAFFEINE ANYONE?

LIABILITIES OF SLEEP



LIABILITIES OF SLEEPDEPRIVATION

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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)



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



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)



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



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)



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.



DNA DAMAGE IN BRAIN CELLSAndersen ML, Ribeiro DA, et. Al. Prog Neurophychopharmacol Biol Psychiatry. 2009 Feb 28.

SLEEP DEPRIVATION AND



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 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





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




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



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

Sleep Deprivation 05-09

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