Circadian Rhythms and Shift Work



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Circadian Rhythms and Shift Work

  • Vicken Y. Totten MD:

  • Emergency Physician

  • and Career-long Shift Worker




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



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=11856



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





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



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





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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