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SLEEP DEPRIVATION

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					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
   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




             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 7’s past 65
  because he forgot what he was doing.
 Final day – Appeared in a press
  conference. “I wanted to prove that bad
  things didn’t 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
   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 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
                  MAGGIE’S 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: 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 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   Not On    FAC                p Value
            HS        Call HS
Sleep       2.7 hrs   7.2 hrs                      < 0.001
Asleep at   44%                 12.5%              < 0.001
light
Citations   25                  15
Accidents   20                  11



                                     Marcus CL, Loughlin GM. Sleep 1996; 19:763-766
TREATMENT FOR SLEEP
    DEPRIVATION




              www.flickr.com/photos/doncolleen/1528345670/
     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            200-400 mg q4h   4-5 hrs          Legal                       Mildly effective.
(NoDoz)                                                                           Tremors, diarrhea, diuretic.
(Starbucks)                                                                       Tolerance.

Methylphenidate     10 mg q4-6h      1-2 hrs          Short half life             Not as effective compared to other
(Ritalin)                                             Low abuse potential         meds.
                                                      Few CV effects              Not approved for aviators.

Pemoline            37.5 mg daily    12 hrs           Low abuse potential         Delayed onset of action.
(Cylert)                                              Few CV effects


Dextroamphetamine   5-10 mg q 4-6h   10 hrs           Very effective              Moderate abuse potential
(Dexedrine)                                           Approved for military       Elevated pulse and BP
                                                      aviators

Modafinil           100-200 mg q8h   14 hrs           Effective                   Nausea
(Provigil)                                            Low abuse potential
                                                      Few CV effects




                                      Kushida, CA. Sleep Deprivation: Basic Science, Physiology, and Behavior. 2005. Marcel Dekker
CAFFEINE ANYONE?
LIABILITIES OF SLEEP
    DEPRIVATION




               www.westsofeastdean.co.uk/large_gavel.html
       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                     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   Unchanged                           Unchanged
(SaO2)




                                                  Azboy O, Kaygisiz Z. Acta Physiol Hung. 2009 Mar;96(1):29-36
           SLEEP DEPRIVATION AND
            ATHLETES - 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   Unchanged                           Unchanged
(SaO2)




                                                  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                                No Nap                              P Value


Alertness                    Improved                           Same                                < 0.05

Sleepiness                   Decreased                          Same                                < 0.05


Short-term memory            Improved                           Same                                < 0.05


Choice reaction time         Improved                           Same                                < 0.05
accuracy
Choice reaction time         Same                               Same                                NS
speed
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
            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!




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

				
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