Circadian Rhythms and Shift Work n n Vicken

Circadian Rhythms and Shift Work n n Vicken Y. Totten MD: Emergency Physician and Career-long Shift Worker Circadian Rhythms and Shift Work 1

Circadian Rhythms and Shift Work 2

SLEEP in literature n n 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 Circadian Rhythms and Shift Work 3

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Goals and Objectives: n n n Describe normal sleep structure Discuss Circadian Rhythm Disorders Describe types of shift work patterns Offer concrete shiftwork suggestions Provide a resource list Circadian Rhythms and Shift Work 5

Biologic Rhythm Control n n 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. Circadian Rhythms and Shift Work 6

Biologic rhythms n n All body systems change rhythmically 90 minute alertness cycle Monthly fertility cycle Sleep/wake generally 23 -26 hour cycle Circadian Rhythms and Shift Work 7

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Rhythm disorders n n 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 Rhythms and Shift Work 9

Circadian disruption n 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 Circadian Rhythms and Shift Work 10

Causes of circadian rhythm disorders n n n Genetics Medications Pregnancy Shift work time zone changes Circadian Rhythms and Shift Work 11

Normal Sleep Architecture: Stages of sleep n n Non-REM (NREM) sleep - Stages I-IV brain idle, body mobile REM - Body paralyzed, Brain active (more metabolically active than during waking) Circadian Rhythms and Shift Work 12

Stage 1 - transition period. n n Normally 10 minutes. Eyes rove. Most people awakened during Stage 1 claim they are not asleep. “Micro-Sleeps” Driving while fatigued Circadian Rhythms and Shift Work 13

Stage 2 - Deeper, fewer eye movements. n n n Shallowest restorative sleep. About half of adult sleep in Stage 2. 20 min. before progressing to next stage. Circadian Rhythms and Shift Work 14

Stages 3/4 - Slow wave sleep (SWS), (delta sleep) n n n 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. Circadian Rhythms and Shift Work 15

REM sleep n n n brain on, body off. Vital for psychological well-being; Isolated REM deprivation -> 1 st irritability > psychosis -> death EEG similar to wakefulness. Dreams, irregular pulse, respiration, increased BP, loss of muscle tone, and absent spinal reflexes. Circadian Rhythms and Shift Work 16

REM sleep n n 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 Circadian Rhythms and Shift Work 17

“Core Sleep” n n 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. Circadian Rhythms and Shift Work 18

“Sleepiness” n n n 2 components: core versus optional missing core sleep (physiologic) -- disrupts physiologic systems missing optional sleep (psychological) -mostly psychological / mood effects Circadian Rhythms and Shift Work 19

Excess Sleepiness in Shift Workers Up to 45% of night-shift workers experience ES. Up to 36% of rotatingshift workers experience ES. Circadian Rhythms and Shift Work 20

Circadian disruption n n 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. Circadian Rhythms and Shift Work 21

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Adverse Health effects of shiftwork n n 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 shiftworkers, 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 Circadian Rhythms and Shift Work 23

Inter-relationships are complex n n n Obesity, pregnancy, high fat diets and circadian rhythm Npas 2 is a key organizer of the circadian system; if maternal diet is high fat, the fetal liver fetal histone code is maltranscribed, and leads to appetite and circadian disorders in the offspring. www. bcm. edu/obgyn/index. cfm? pmid=11 856 Circadian Rhythms and Shift Work 24

Common Circadian Rhythm Disorders n n Jet Lag or Rapid Time Zone Change Syndrome: Delayed Sleep Phase Syndrome (DSPS) Advanced Sleep Phase Syndrome (ASPD) Shift Work Sleep Disorder (SWSD) Circadian Rhythms and Shift Work 25

Jet Lag / Shift work n n 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. Circadian Rhythms and Shift Work 26

Zeitgibers (from Gr. “Time Tellers”) n n n 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 Circadian Rhythms and Shift Work 27

Night Owls vs. Morning Larks n n n 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 Circadian Rhythms and Shift Work 28

Delayed Sleep Phase Syndrome (DSPS) n n n 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” Circadian Rhythms and Shift Work 29

Advanced sleep-phase syndrome (ASPS) n n n 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” Circadian Rhythms and Shift Work 30

Non 24 -Hour Sleep Wake Disorder (N 24 HS/W disorder): n n 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. Circadian Rhythms and Shift Work 31

Definitions for Emergency Medicine n n On - call On duty Sleep deprivation Chronodisruption Circadian Rhythms and Shift Work 32

On Call versus On Duty n n n “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’ Circadian Rhythms and Shift Work 33

Sleep deprivation n 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 Circadian Rhythms and Shift Work 34

Shift work prevalence n n n 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 Circadian Rhythms and Shift Work 35

Shift work definition n n 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 Circadian Rhythms and Shift Work 36

Shift length n n 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 Circadian Rhythms and Shift Work 37

Serious adverse health consequences of shift work n n n 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 Circadian Rhythms and Shift Work 38

Shift work is also linked to: n n drug and alcohol abuse altered immune response infertility in women high divorce rate. Circadian Rhythms and Shift Work 39

Cardiovascular effects of shift work is. . . n n n 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) Circadian Rhythms and Shift Work 40

Tolerance to shift work n n n 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. Circadian Rhythms and Shift Work 41

Shift work patterns n n n most work has been done on 8 hour shifts 12 hour shifts no longer permitted in most industries rotating shifts isolated shifts random shifts Circadian Rhythms and Shift Work 42

Shift schedules n n n 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 Circadian Rhythms and Shift Work 43

Rotation patterns: Swing shifts n n n 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 Circadian Rhythms and Shift Work 44

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Randomly changing n n almost universally condemned forbidden by most unions highest physiologic risk and stress practiced mostly by physicians Circadian Rhythms and Shift Work 46

Isolated nights n n defined as less than one night per week equivalent to a bad night on call Circadian Rhythms and Shift Work 47

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Important! n n 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 Circadian Rhythms and Shift Work 49

What about physicians? n n MD = Maximum Denial Socialized to ignore their own needs Trained to be ‘tough’ poor role models Circadian Rhythms and Shift Work 50

Cardiovascular effects in physicians: n n 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 Circadian Rhythms and Shift Work 51

Cardiovascular effects n n 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 Circadian Rhythms and Shift Work 52

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More studies n n n 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 Circadian Rhythms and Shift Work 54

Performance of physicians n n n Poor performance with micro-sleeps (nonrestorative) 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 Circadian Rhythms and Shift Work 55

Physician learning n n 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 Circadian Rhythms and Shift Work 56

Overall performance n n 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 Circadian Rhythms and Shift Work 57

Exercise tolerance n n 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 Circadian Rhythms and Shift Work 58

Shift length n n n 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. Circadian Rhythms and Shift Work 59

Strategies to improve health for shift workers n n n sleep hygiene napping at work shift rotation patterns food & exercise social life Circadian Rhythms and Shift Work 60

If you must be a shift worker: n n n 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 Circadian Rhythms and Shift Work 61

Living the Strategic Life n n n 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 Circadian Rhythms and Shift Work 62

Light therapy: n n 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. Circadian Rhythms and Shift Work 63

Environmental control n n n 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 Circadian Rhythms and Shift Work 64

Sleep Hygiene n n Temperature: between 22 - 24 C Bedroom: Condition yourself that Bed = Sleep time Ritual: helps to create a ‘stimulusresponse’ conditioning Keep sleep time sacred, and minimize care -giving responsibilities during that time. Circadian Rhythms and Shift Work 65

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Diet n n 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 Circadian Rhythms and Shift Work 67

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Exercise n n n 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

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Light – most important for humans n n n 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. Circadian Rhythms and Shift Work 71

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Timing of light pulses is important n n n 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. Circadian Rhythms and Shift Work 73

Drugs and Pharmacology n n n Drugs to sleep or to wake or resynchronize MDs: temptation and access to non-legal drug use health care shift workers are at high risk for drug addiction Circadian Rhythms and Shift Work 74

Melatonin n 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 Circadian Rhythms and Shift Work 75

Melatonin n n 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. Circadian Rhythms and Shift Work 76

Melatonin stimulant Ramelteon (Rozerem) n n 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. Circadian Rhythms and Shift Work 77

Hypnotics: Benzodiazipines n n n Benzodiazepines: short acting for sleep onset or napping. Triazolam (Halcion) Medium or long-acting: for sleep maintenance. estazolam [Pro. Som] quazepam [Doral] Possibility of rebound insomnia Circadian Rhythms and Shift Work 78

Benzodiazepines side effects n n 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 Circadian Rhythms and Shift Work 79

Non-benzodiazepine hypnotics n n Less effect on sleep architecture than benzos, less rebound insomnia Zolpidem (Ambien) moderate to long acting Eszopicline (Lunesta) moderate duragion Zaleplon (Sonata) short acting Circadian Rhythms and Shift Work 80

OTC hypnotics n n Benadryl – 25 -50 mg. Tachyphylaxis Alcohol – disrupts sleep architecture Herbs: hops, valerian, passion flower Marijuana – legal issues, prolonged effects Circadian Rhythms and Shift Work 81

Diphenhydramine / sedative antihistamines n n 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 Circadian Rhythms and Shift Work 82

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Alcohol n n 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 Circadian Rhythms and Shift Work 84

Cheat Sleep: stimulants n n n OTC: primarily caffeine Illegal: Cocaine, “Speed” and various “uppers” Legal: • amphetamines and amphetamine –like drugs • Ampakines and their sucessors Circadian Rhythms and Shift Work 85

Amphetamines n n methylphenidate (Ritalin, Metadate, Concerta) dextroamphetamine Plus amphetamine (Adderall) Dextroamphetamine (Dexedrine) lisdexamfetamine dimesylate – metabolized to methamphetamine (Vyvanse) Circadian Rhythms and Shift Work 86

Ampakines and their successors n n 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 Circadian Rhythms and Shift Work 87

Caffeine n n n harmless in small doses taking caffeine to get through the night shift may interfere with day sleep careful with timing of caffeine intake Circadian Rhythms and Shift Work 88

Optimal phase adjustment strategies n n n bright light early in waking time significant exercise later in waking period optimize sleeping conditions: aluminumfoil 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. Circadian Rhythms and Shift Work 89

Summary n n n 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 Circadian Rhythms and Shift Work 90

Resources n n 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 Circadian Rhythms and Shift Work 91

Enhancing adaption n 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 Circadian Rhythms and Shift Work 92

Best single reference n n "Why we Sleep" by James Horne. Published by Oxford University Press Walton St Oxford OX 2 6 DP 1988 a classic overall reference Circadian Rhythms and Shift Work 93

Web Links n n n n 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 Circadian Rhythms and Shift Work 94