SLEEP DEPRIVATION

Jeffrey Lin, M.D. Fellow, Sleep Medicine Stanford University Medical Center 5/6/2009

http://davidavery.files.wordpress.com/2008/04/sleep-deprived.jpg

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 sleep deprivation

HISTORY OF SLEEP DEPRIVATION

1894: Marie De Manaceine conducted the first documented animal studies

Kept puppies awake for 5 days

1896: Patrick and Gilbert conducted the first human studies

90 hour sleep deprivation REM sleep deprivation

1960: Dement conducted first partial 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

https:/.../attachments/34242959/flowerpot.jpg

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...

RANDY GARDNER
Stayed awake for a high school science project 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 signs of astereognosis Day 3 Moodiness, some sign of ataxia, inability to repeat tongue twisters Day 4 Irritability and uncooperative attitude, memory lapses and difficulty concentrating. First illusion/delusion

Moorcroft, W.H. Sleep, Dreaming & Sleep Disorders (1993)

TIMELINE OF EVENTS
Day 5 More hallucinations Day 6 Speech slowing and difficulty naming 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)

TIMELINE OF EVENTS
Day 11 Expressionless appearance, speech slurred and without intonation. Unable to perform serial 7s past 65 because he forgot what he was doing. Final day Appeared in a press conference. I wanted to prove that bad things didnt happen if you went without sleep.

Moorcroft, W.H. Sleep, Dreaming & Sleep Disorders (1993)

TIMELINE OF EVENTS
Day 12 - Fell asleep for 14 hrs and 40 minutes Stayed awake for 24 hrs, then slept a normal eight hours

Moorcroft, W.H. Sleep, Dreaming & Sleep Disorders (1993)

HOW MUCH SLEEP?

Quantity of sleep
How long a patient would sleep if left to awaken spontaneously How alert the patient feels after different quantities of sleep

Quality of sleep

Appropriate distribution of sleep stages Synchronization of process C and S

Pressman, Mark. Definition and consequences of sleep deprivation. UpToDate

Timing of sleep

QUALITY OF SLEEP

Arousals can occur

Spontaneously Secondary to sleep disorders

More frequent the arousal, more sleepiness during the day

Artificially disrupting sleep 60 times/hr X 2 days equals 40 60 hrs of total sleep deprivation Sleep disturbance 5 times/hr can affect performance Even acoustic tones that only caused EEG arousals increased daytime sleepiness
Bonnet, MH. Effect of sleep disruption on sleep performance and mood. Sleep 1985; 8:11 Martin, 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 the propensity 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

HOW MUCH SLEEP?

There is wide variation American average 6 hrs and 40 min

Most desire 40 more min

Societal pressures are decreasing the average 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

MORTALITY AND SLEEP

CONSEQUENCES OF SLEEP DEPRIVATION

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 IN CONCENTRATION

Redwine L, et al. J Clin Endocrinol Metab 2000 Oct; 85(10):3597-603

IMPARED IMMUNE FUNCTION

IL-6 level rise was delayed in the PSD group

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 show such shift

Redwine L, et al. J Clin Endocrinol Metab 2000 Oct; 85(10):3597-603

IMPARED IMMUNE FUNCTION

25 subjects, restricted to 6 hrs of sleep X 1 wk 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

IMPARED IMMUNE FUNCTION

42 healthy men Two 2-hr naps daily Vs. total sleep deprivation X 4 days Blood draws every 6 hrs Compared to PSD subjects, TSD subjects had elevated TNF-alpha and IL-6 levels on day 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

Ansch, Browman, Mitler, and Walsh. Sleep: A Scientific Perspective (1988)

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)

SOCIETAL EFFECTS

www.personalfinanceanalyst.com/.../

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

MAGGIES LAW

July 20, 1997: Maggie McDonnell was killed in a head-on collision 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 falling asleep was not a crime August 2003: Maggies 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 Safety regulations

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 a week

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

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

9 + 4.4 minutes

4.8 + 4.1 minutes

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

HOUSESTAFF VS. FACULTY

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

HOUSESTAFF VS. FACULTY

On Call HS 2.7 hrs 44% 25 Not On Call HS 7.2 hrs FAC p Value < 0.001 12.5% 15 < 0.001

Sleep Asleep at light Citations

Accidents

20

11

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

TREATMENT FOR SLEEP DEPRIVATION

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TREATMENT FOR SLEEP DEPRIVATION

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

TREATMENT FOR SLEEP DEPRIVATION

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

hrs Obligatory sleep vs. Facultative sleep

Kushida, CA. Sleep Deprivation: Basic Science, Physiology, and Behavior. 2005. Marcel Dekker

SLECTIVE SLEEP DEPRIVATION

Recovery sleep from selective SWS deprivation same as total sleep deprivation
SWS increased on night 1 REM increased on nights 2 and 3

Recovery sleep from selective REM sleep deprivation 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

http://www.usdoj.gov/dea/pubs/abuse/5-stim.htm

PHARMACOLOGIC TREATMENT
Name Usual Dose Half Life Pros Cons

Caffeine (NoDoz) (Starbucks)

Methylphenidate (Ritalin)

200-400 mg q4h

4-5 hrs

Legal

Mildly effective. Tremors, diarrhea, diuretic. Tolerance.

Not as effective compared to other meds. Not approved for aviators. Delayed onset of action.

10 mg q4-6h

1-2 hrs

Short half life Low abuse potential Few CV effects Low abuse potential Few CV effects

Pemoline (Cylert)

37.5 mg daily

12 hrs

Dextroamphetamine (Dexedrine)

5-10 mg q 4-6h

10 hrs

Very effective Approved for military aviators Effective Low abuse potential Few CV effects

Moderate abuse potential Elevated pulse and BP

Modafinil (Provigil)

100-200 mg q8h

14 hrs

Nausea

Kushida, CA. Sleep Deprivation: Basic Science, Physiology, and Behavior. 2005. Marcel Dekker

CAFFEINE ANYONE?

LIABILITIES OF SLEEP DEPRIVATION

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LIABILITIES OF SLEEP DEPRIVATION

Error of omission Individual fails to respond 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 sleep disturbance and did not take measures to reduce those risks

People V. Schaffer. 364 N.E. 2d 109 (III App. 1977)

DRIVER LIABILITY

Evidence of a person sleeping while driving = 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 the accident occurred within the scope of employment Employee fell asleep while driving a company truck home, causing a serious crash and injuring others

Employer was liable because the employee had a load of tires to deliver on the way home

On-call employee was driving back to work in a company vehicle 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 sleep disorder is suspected All patients who have sleep disorders should be warned about risk of operating a motor vehicle or dangerous machinery 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 patient regarding risks of medical condition/treatment Clinicians are not responsible for the actions of patients who fail to take measures to reduce their risk, although the risk of liability may be higher if they are required by state statute to report a driver to the DMV

Joy vs. Eastern Maine Medical Center, 529 A.2d 1364 (Me. 1987)

CURRENT STUDIES IN SLEEP DEPRIVATION

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) ASSAY

Damaged DNA have more broken strands Travels further toward the anode The longer the comet tail, the more DNA damage is present
Andersen ML, Ribeiro DA, et. Al. Prog Neurophychopharmacol Biol Psychiatry. 2009 Feb 28.

DNA DAMAGE IN BRAIN CELLS

Andersen ML, Ribeiro DA, et. Al. Prog Neurophychopharmacol Biol Psychiatry. 2009 Feb 28.

SLEEP DEPRIVATION AND ATHLETES

Effects of sleep deprivation on cardiorespiratory functions of the runners and 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 ATHLETES - REST

Variable Spirometric fxn Oxygen uptake (VO2) CO2 production (VCO2) Heart Rate Respiratory quotient (R) Minute ventilation (VE) Volleyball players Unchanged Unchanged Increased Unchanged Unchanged Unchanged Runners Unchanged Increased Increased Unchanged Unchanged Unchanged

Arterial oxygen saturation (SaO2)

Unchanged

Unchanged

Azboy O, Kaygisiz Z. Acta Physiol Hung. 2009 Mar;96(1):29-36

SLEEP DEPRIVATION AND ATHLETES - EXERCISE

Variable Time to exhaustion Oxygen uptake (VO2) CO2 production (VCO2) Heart Rate (HR) Respiratory quotient (R) Minute ventilation (VE) Volleyball players Decreased Unchanged Unchanged Unchanged Unchanged Decreased Runners Decreased Unchanged Unchanged Unchanged Unchanged Decreased

Arterial oxygen saturation (SaO2)

Unchanged

Unchanged

Azboy O, Kaygisiz Z. Acta Physiol Hung. 2009 Mar;96(1):29-36

SHORT NAPS AND ATHLETIC PERFORMANCE

The role of a short post-lunch nap in improving cognitive, motor, and sprint performance in participants with partial sleep deprivation. 10 healthy males with partial sleep deprivation (23:00 to 3:00) Between 13:00 to 13:30

Napped Sat quietly

Assess alertness, short-term memory, intra-aural temperature, heart rate, choice reaction time, grip strength, 2m and 20m sprint
Waterhouse J, Atkinson G, Edwards B, ReillyT. J Sports. Sci. 2007 Dec;25(14):1557-66

PERFORMANCE FACTORS
Waterhouse J, Atkinson G, Edwards B, ReillyT. J Sports. Sci. 2007 Dec;25(14):1557-66

Nap Alertness Sleepiness Short-term memory Choice reaction time accuracy Choice reaction time speed Grip strength 2 M sprint time 20 M sprint time Improved Decreased Improved Improved Same Same 1.019 s 3.878 s

No Nap Same Same Same Same Same Same 1.060 s 3.971 s

P Value < 0.05 < 0.05 < 0.05 < 0.05 NS NS 0.031 0.013

TAKE HOME POINTS

Sleep is important

Total sleep time Sleep quality Timing of sleep Physical consequences Psychiatric consequences Economic consequences Societal consequences Proper amount time allotted for sleep Well-timed naps Medications to help regulate sleep vs. stay awake

Sleep deprivation can result in adverse outcomes

Treatment is effective

THANKS!

www.azfotos.com/people/children/boy-pictures.htm www.firstpeople.us/pictures/bear/Sleeping-Bea... www.all-creatures.org/ak/photo-sleepkitty.html colintellsyouwheretogo.blog.co.uk/page/2/

ANIMAL STUDIES
Heat seeking behavior Increased food intake Weight loss Increased metabolic rate Increased plasma norepinephrine Decreased plasma thyroxine Increased T3/T4 ratio

Rechtschaffen, A, and Bergmann, B. Behavioural Brain Research 69 (1995) 55-63