Circadian Rhythms and Shift Work 2010 VT

Circadian Rhythms
and
Shift Work
 Vicken Y. Totten MD:

 Emergency Physician
and Career-long Shift Worker
Circadian Rhythms and Shift Work 1

SLEEP in literature
 Sleep, that knits the ravell'd sleave of care,
 The death of each day's life, sore labour's bath,
 Balm of hurt minds, great nature's second course,
 Chief nourisher in life's feast.
• - Shakespeare, Macbeth, Act II, Scene I

Goals and Objectives:
 Describe normal sleep structure
 Discuss Circadian Rhythm Disorders
 Describe types of shift work patterns
 Offer concrete shiftwork suggestions
 Provide a resource list

Biologic Rhythm Control
 Innate rhythms poly-genetically determined
 Master clock in suprachiasmatic nucleus of
the rostro-ventral hypothalamus.
 Mediated by light/dark cycles via cryptopsin
receptors in retina, skin and possibly
pituitary
 Humans: Day = alert / Night = sleep.

Biologic rhythms
 All body systems change rhythmically
 90 minute alertness cycle
 Monthly fertility cycle
 Sleep/wake generally 23-26 hour cycle

Rhythm disorders
 Normally, biologic cycles kept in synch by
signal substances such as melatonin,
cortisol and others
 Disruption in these systems have profound
health implications.
 Disrupted by both internal and external
signals
 Cycles re-synchronize at different rates
Circadian disruption
 De-synchronization of innate biologic /
circadian cycles.
 Chronically in shiftwork and briefly from
jetlag.
 Medicine is far behind industry in
recognizing the implications of shift work

Causes of circadian rhythm
disorders
 Genetics
 Medications
 Pregnancy
 Shift work
 time zone changes

Normal Sleep Architecture:
Stages of sleep
 Non-REM (NREM) sleep - Stages I-IV
brain idle, body mobile
 REM - Body paralyzed, Brain active (more
metabolically active than during waking)

Stage 1 - transition period.
 Normally 10 minutes. Eyes rove.
 Most people awakened during Stage 1
claim they are not asleep.
 “Micro-Sleeps”
 Driving while fatigued

Stage 2 - Deeper, fewer eye
movements.
 Shallowest restorative sleep.
 About half of adult sleep in Stage 2.
 20 min. before progressing to next stage.

Stages 3/4 - Slow wave sleep
(SWS), (delta sleep)
 Most restorative & restful; vital for physical
recuperation.
 Majority occurs early in the sleep period.
 Difficult to arouse from SWS.
 First stage to be “made up” after sleep
deprivation.
 SWS deprivation causes fatigue, muscle
aches.
REM sleep
 brain on, body off.
 Vital for psychological well-being;
 Isolated REM deprivation -> 1st irritability -
> psychosis -> death
 EEG similar to wakefulness.
 Dreams, irregular pulse, respiration,
increased BP, loss of muscle tone, and
absent spinal reflexes.
REM sleep
 First episode occurs after 90-120 minutes of
NREM sleep.
 Recurs in about 90 minute cycles, getting
more frequent towards awakening
 REM periods become longer as night
progresses.
 REM disorders include sleepwalking / talking /
night terrors

“Core Sleep”
 Horne: first three SWS cycles with their
REM periods
 "optional" sleep the rest of the night:
more REM, less SWS
 Core sleep: about 5 hours for most
persons
 Only core sleep made up.

“Sleepiness”
 2 components: core versus optional
 missing core sleep (physiologic) -- disrupts
physiologic systems
 missing optional sleep (psychological) --
mostly psychological / mood effects

Excess Sleepiness in Shift Workers
Up to 45% of night-shift Up to 36% of rotating-

workers experience ES. shift workers experience
ES.
Circadian disruption
 Day /awake and night / sleep are the
normal human condition.
 When switching to a day / sleep and night
/ awake, various physiologic cycles
become desynchronized
 Hospitalization with loss of ‘Zeitgibers”
 Re-synchronization at different rates
 Generally, all systems can shift 1 hr per
day.
Adverse Health effects of shiftwork
 Breast Cancer, Endometrial Cancer : increased in
women who are not exposed to enough
darkness; mechanism unclear; proposed
mechanism is melatonin deficiency.
 Prostate Cancer: increased most in rotating shift
workers when compared to fixed-night shift-
workers, who have an extremely minimal risk.
 Peptic Ulcer Disease /Obesity / Cardiovascular
Disease
 Pregnancy Issues: night work and high work
load increase the risk of spontaneous abortion
Inter-relationships are complex
 Obesity, pregnancy, high fat diets and
circadian rhythm
 Npas2 is a key organizer of the circadian
system; if maternal diet is high fat, the
fetal liver fetal histone code is mal-
transcribed, and leads to appetite and
circadian disorders in the offspring.
 www.bcm.edu/obgyn/index.cfm?pmid=11
856
Common Circadian Rhythm
Disorders
 Jet Lag or Rapid Time Zone Change
Syndrome:
 Delayed Sleep Phase Syndrome (DSPS)
 Advanced Sleep Phase Syndrome (ASPD)
 Shift Work Sleep Disorder (SWSD)

Jet Lag / Shift work
 Personal cycles out of synchrony with local
conditions.
 Sleepy when alertness is required; alert
when sleep required
 Caused by travel across time zones, shift
work and sometimes by adolesnce
 Can cause chronodysruption, since
different systems re-synchronize at
different rates.
Zeitgibers (from Gr. “Time Tellers”)
 the physical and social clues which tell us
what time it is.
 Most powerful is light.
 Others include taste and
 smell of usual breakfast
 food, going to work,
 sound of daytime activities

Night Owls vs. Morning Larks
 Night people = easier adjustment to shift
work
 Tend to be phase delayed
 Day people = harder with shift change;
more stable once adjusted
 Tend to be more synchronized and more
resistant to re-setting
 Residency survey: EP s have more night
types than normal populations
Delayed Sleep Phase Syndrome
(DSPS)
 A disorder of sleep timing.
 People with DSPS tend to fall asleep very
late
 Difficulty waking up in time for work,
school, or social engagements
 Common, perhaps normal in adolescence
 “Owls”

Advanced sleep-phase syndrome
(ASPS)
 ASPS persistent early evening sleep onset
time (between 6:00 pm and 9:00 pm) and
spontaneous early morning wake-up time
(between 3:00 am and 5:00 am).
 Variably associated with inadquate sleep.
 Less common than DSPS
 Associated with extreme age and
depression.
 “Larks”
Non 24-Hour Sleep Wake Disorder
(N24HS/W disorder):
 Innate 23-25 hr cycles constantly reset by
zeitgibers
 Normal sleep pattern but inate cylce is
neither firm nor maintained.
 Struggles with “Free cycling”
 Inconsistent insomnia that occurs at
different times each night.

Definitions for
Emergency
Medicine
 On - call
 On duty
 Sleep deprivation
 Chronodisruption
On Call versus On Duty
 “On call”: night work between working days =
pure sleep deprivation
 Possibility of sleep while on call
 Usually does not cause circadian rhythm
disruptions -- body cycles remain in phase
 “On duty” implies expected time of usual type of
work
 Isolated night shifts “on duty” (less than once
per week) physiologically function as ‘on call’
Sleep deprivation
 loss of "optional sleep" (sleeping less than
one's habit) causes drowsiness, no other
serious effects
 "core sleep" deprivation (less than 5 hours
of slow wave sleep)
 Sleep deprivation causes both physiologic
and psychological ill effects

Shift work prevalence
 Not a new phenomenon, but now vastly
more frequent.
 25% of American workers are shift
workers at some point in their lives.
 Invention of the light bulb: 1883

Shift work definition
 Work a defined period of time, then off for
a period
 Working time can be at any time of the
24-hr day
 Fixed shifts -- working the same time
every day
 Rotating shifts -- working time of day
changes from time to time
Shift length
 length of shift: most common is 8 hours
 others are 10, 12 and 6 hours
 more mistakes made in the last 4 hours of
a 12 hour shift than in the first 8 hours
 Shift changes become more difficult after
age 40

Serious adverse health
consequences of shift work
 20% decrease in life span
 62% sleep disturbance
 higher rate of accidents on the job
 high risks of fatal commuting accidents
 800% risk of ulcers
 1500% incidence of depression and mood
swings

Shift work is also linked to:
 drug and alcohol abuse
 altered immune response
 infertility in women
 high divorce rate.

Cardiovascular effects of shift
work is ...
 linked to chronic hypertension
 increased cardiovascular mortality
 (risk worse than smoking a pack of
cigarettes per day)
 risk for dysrhythmias (PVC, MAT, SVT)
 risk of sinus arrest (up to 12 sec in one
study)

Tolerance to shift work
 Better in younger persons (under 40, or
pre-menopausal)
 Better in childless persons
 Better in natural owls than natural larks
 20% of people have no trouble changing
shifts,
 60% have moderate hardship, and
 20% have extreme difficulty.
Shift work patterns
 most work has been done on 8 hour shifts
 12 hour shifts no longer permitted in most
industries
 rotating shifts
 isolated shifts
 random shifts

Shift schedules
 Optimum: days only; in synchronous with
your own best working time
 Next best: same shift every day, even if
not most suited to your optimal time; or
isolated nights
 Worst: randomly rotating shifts

Rotation patterns: Swing shifts
 Phase advance: one week days, one week
evenings, one week nights
 Phase retreat: (Southern Swing): one
week days, one week nights, one week
evenings
 Of the two, phase advance is more
physiologic and more easily tolerated

Randomly changing
 almost universally condemned
 forbidden by most unions
 highest physiologic risk and stress
 practiced mostly by physicians

Isolated nights
 defined as less than one night per week
 equivalent to a bad night on call

Important!
 One can adjust by 1-2 hrs. / 24, or one
week to move forward by one (8 hr) shift
 Therefore, maintain the same schedule
when not working
 most permanent night workers switch to
day-life when not at work and reap the
same ill effects as random-shift changers
 Optimal: one month or more between
changes
What about physicians?
 MD = Maximum Denial
 Socialized to ignore their own needs
 Trained to be ‘tough’
 poor role models

Cardiovascular effects in
physicians:
 palpitations and dysrhythmias
 Brodsky M, Wu D, Denes P, Kanakis C,
Rosen KM: Arrhythmias documented by 24
hour continuous electrocardiographic
monitoring in 50 male medical students
without apparent heart disease. Am J
Cardiology 1977;39:390-395

Cardiovascular effects
 sinus arrest with syncope in residents
 Guilleminault C, Pool P, Motta J, Gillis AM:
Sinus arrest during REM sleep in young
adults. NEJM: 1984;311:1006-10

More studies
 Physicians aren’t immune to poor health
effects of shift work
 Åkerstedt T, Knutsson A, Alfredsson L, Theorell T: Shift work
and cardiovascular disease. J Work Environ Health: 1984;
10:409-414
 Åkerstedt T. Psychological and psychophysiological effects of
shift work. Scand J Work Environ Health. 1990;16(suppl
1):67-73

Performance of physicians
 Poor performance with micro-sleeps (non-
restorative) during rote tasks
 Documented micro and mini-sleeps during
drive home even in those who did not think
they had slept
 Åkerstedt et al: Physicians during and following
night call duty--41 hour ambulatory recording of
sleep. Electroencephalography & Clinical
Neurophysiology: 1990; (76) 193-196
Physician learning
 Decreased performance, learning of
deleterious habits and physiologic harm.
 Asken MJ, Raham DC: Resident
Performance and Sleep Deprivation: A
Review. J. Med Educ 1983;58:382-388

Overall performance
 Found that shift work affected rote tasks
and the highest intellectual tasks equally
as much; moderately challenging but well
known tasks suffered least. Implication for
physicians: we make more mistakes on
the more serious cases
 Tilley et al The sleep and performance of shift
workers. Human Factors, 1982; 24: 624-41

Exercise tolerance
 Sleep deprivation had little effect on acute
exercise tolerance in normal persons
 Chen H: Effects of 30-h sleep loss on
cardiorespiratory functions at rest and in
exercise. Med Sci Sports and Exerc: 1991;
23(2):193-198

Shift length
 Used temperature as a marker for slowing of
physiologic activities
 Concluded that 12 hour shifts lead to
increased mistakes poorer per-hour
productivity
 Daniel J, Potasova A; Oral temperature and
performance in 8 h and 12 h shifts .
Ergonomics 32(7):689-96 , 1989 Jul.

Strategies to improve health for
shift workers
 sleep hygiene
 napping at work
 shift rotation patterns
 food & exercise
 social life

If you must be a shift worker:
 Learn how to sleep well
 Learn how to change your circadian
rhythms smoothly
 Use circadian principles to make your work
and home life better
 Educate your schedule-maker
 Educate and enlist your family

Living the Strategic Life
 Avoid vigorous exercise at least 4 hours
prior to bedtime (Regular exercise is
recommended.)
 Avoid cigarettes, alcohol, and caffeine 4-6
hours prior to bedtime
 Avoiding large meals and excessive fluids
just before bedtime

Light therapy:
 Timing of light
 Minimum of 30-60 minutes not long after
wakening to promote adaptation and
wakefullness
 Re-synchronising ASPS light in the early evening
and nighttime hours delays the cycle
 DSPS light therapy in the early morning hours
stimulates morning alertness and an earlier
bedtime.

Environmental control
 Light – adequate at work (6,000-7,000
Lux)
 Dark – during sleep time (less than full
moon) (consider eye shades)
 Noise – shut out during sleep. Isolate
sleep room, use earplugs
 Room temperature – warm sleepers vs
cool sleepers
 Exercise, Diet
Sleep Hygiene
 Temperature: between 22 - 24 C
 Bedroom: Condition yourself that Bed =
Sleep time
 Ritual: helps to create a ‘stimulus-
response’ conditioning
 Keep sleep time sacred, and minimize
care-giving responsibilities during that
time.
Diet
 troubled by early awakening? => try
bedtime snack.
 Milk products seem to improve sleep.
 Alcohol: a single drink can help tense
people relax, but alcohol actually alters
sleep structure by postponing REM
 Great care to eat appropriately during the
working / waking time
Exercise
 Athletes: get more delta

(SWS, restorative) sleep.
 Time of day important:
pm exercise has more
effect.
 Exercise should be
completed more than
one hour before sleep
time Circadian Rhythms and Shift Work 69
Light – most important for
humans
 intensity is important: 7,000 Lux
 about the same as a heavily overcast day
 most indoor lighting is inadequate
 new ‘energy saving’ fixtures are even more
inadequate
 implication to hospital administration: high intensity
lights over physicians / nurses working areas
improves productivity and minimizes mistakes.

Timing of light pulses is
important
 2-3 hours of high intensity light within one
hour of awakening
 implication for shift workers: either go
outside while the sun is still up before
going to work the night shift, or buy and
use a high intensity light at home
 Fluorescents in windows.

Drugs and Pharmacology
 Drugs to sleep or to wake or re-
synchronize
 MDs: temptation and access to non-legal
drug use
 health care shift workers are at high risk
for drug addiction

Melatonin
 Melatonin is a re-synchronizer
 used in the treatment of circadian rhythm
sleep disorder especially in blind persons
 OTC “diet supplement” dosing guidelines
not established. My use: 6-6-3-3

Melatonin
 3-6 mg, taken one hour prior to desired
(new) sleep time
 Diminished (genetically?) in aging.
 Full effects of chronic exposure not yet
known.
 Not FDA regulated, but seems to be
extremely safe for brief use as in phase
adjustment.
Melatonin stimulant Ramelteon
(Rozerem)
 Rx only.
 stimulates melatonin release
 Ramelteon promotes the onset of sleep
and helps normalize circadian rhythm
disorders.
 Ramelteon is approved by the Food and
Drug Administration (FDA) for insomnia
characterized by difficulty falling asleep.
Hypnotics: Benzodiazipines
 Benzodiazepines: short acting for sleep
onset or napping. Triazolam (Halcion)
 Medium or long-acting: for sleep
maintenance. estazolam [ProSom]
quazepam [Doral]
 Possibility of rebound insomnia

Benzodiazepines side effects
 can disrupt sleep architecture
 may have residual sedative effects lasting
into the next working period
 many are fat soluble and will leach out
over many days
 illegal in some working environments

Non-benzodiazepine hypnotics
 Less effect on sleep architecture than
benzos, less rebound insomnia
 Zolpidem (Ambien) moderate to long
acting
 Eszopicline (Lunesta) moderate duragion
 Zaleplon (Sonata) short acting

OTC hypnotics
 Benadryl – 25-50mg. Tachyphylaxis
 Alcohol – disrupts sleep architecture
 Herbs: hops, valerian, passion flower
 Marijuana – legal issues, prolonged effects

Diphenhydramine / sedative
antihistamines
 sedative antihistamines help induce sleep,
and in some, help maintain sleep
 effect on sleep architecture is minimal
 tachyphylaxis: effects wane within days
 may produce prolonged sedation,
interfering with performance and
maintenance of new schedule when not at
work
Alcohol
 disrupts sleep architecture
 delays REM sleep
 variable effect on sleep latency
 recommendation for shift workers: finish
your alcohol more than one hour before
scheduled sleep time

Cheat Sleep: stimulants
 OTC: primarily caffeine
 Illegal: Cocaine, “Speed” and various
“uppers”
 Legal:
• amphetamines and amphetamine –like drugs
• Ampakines and their sucessors

Amphetamines
 methylphenidate (Ritalin, Metadate,
Concerta)
 dextroamphetamine Plus amphetamine
(Adderall)
 Dextroamphetamine (Dexedrine)
 lisdexamfetamine dimesylate –
metabolized to methamphetamine
(Vyvanse)
Ampakines and their successors
 Modafinil (Provigil, Alertec, Modavigil, Modalert,
Modiodal, Modafinilo, Carim, Vigia)
 analeptic drug manufactured by Cephalon, and
is approved by the FDA for shift workers
 Armodafinil (Nuvigil) is the active (−)-(R)-
enantiomer of the racemic drug modafinil
 Side effects include potentially cognitive
enhancement, and loss of effect of BCPs

Caffeine
 harmless in small doses

 taking caffeine to get through the night
shift may interfere with day sleep
 careful with timing of caffeine intake

Optimal phase adjustment
strategies
 bright light early in waking time
 significant exercise later in waking period
 optimize sleeping conditions: aluminum-
foil on the windows, ear plugs, eye
shades, fan
 stay on the same schedule without varying
by more than an hour as long as you can
 Consider Melatonin.
Summary
 American society is more 24 / 7

 EM always 24 / 7
 Use circadian principles to improve your
well being and prolong your professional
life and your personal life

Resources
 American Academy of Sleep Medicine
One Westbrook Corporate Center, Suite
920
Westchester, IL 60154
(708) 492-0930
 National Sleep Foundation
1522 K Street, NW, Suite 500
Washington, DC 20005

Enhancing adaption
 Rotating shiftwork schedules: can we
enhance physician adaptation to night
shifts?
Smith-Coggins R , Rosekind MR , Buccino
KR , Dinges DF , Moser RP
Acad Emerg Med 1997 Oct;4(10):951-61

Best single reference
 "Why we Sleep" by James Horne.

Published by Oxford University Press
Walton St Oxford OX2 6DP 1988
 a classic overall reference

Web Links
 Northwestern University, Center for Sleep &
Circadian Biology,
 About Circadian Rhythms
National Sleep Foundation,
 Strategies for Shift Workers
 National Sleep Foundation,
 Sleep and the Traveler
 National Institute of Mental Health, How
Biological Clocks Work
 Sleepnet.com

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Circadian Rhythms

 Vicken Y. Totten MD:

Circadian Rhythms and Shift Work 1

• - Shakespeare, Macbeth, Act II, Scene I

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Up to 45% of night-shift Up to 36% of rotating-

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 Athletes: get more delta

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 harmless in small doses

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 American society is more 24 / 7

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 "Why we Sleep" by James Horne.

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