1. Fatigue Management in Shift Work NESS 2010 Newton, MA Christopher P. Landrigan, MD, MPH Director, Sleep and Patient Safety Program, Brigham and Women’s Hospital Research Director, Children’s Hospital Boston Inpatient Pediatrics Service Assistant Professor of Pediatrics and Medicine, Harvard Medical School

2. Disclosures and Acknowledgement Dr. Landrigan has served as a paid consultant to: 1)Vital Issues in Medicine, developing an educational course for physicians on Shift Work Disorder; this work was supported by a grant from Cephalon, Inc. to Vital Issues in Medicine. 2)In addition, Dr. Landrigan has received monetary awards, honoraria, and travel reimbursement from multiple academic and professional organizations for delivering lectures on the quality of inpatient care, sleep deprivation, resident performance, and safety. Some of the slides developed for this presentation were developed with the support of Vital Issues in Medicine Thanks to the Harvard Work Hours, Health, and Safety Group for providing additional slides

3. (Lisbon Falls, ME, 13 Jun 01) – Trucker Jorge Rosario of Orlando, FL, after being awake for 32 hours, fell asleep at the wheel of his tractor trailer, crashed, and killed Mark Leek, Pablo Jaramillo and Geraldo Perez-Guerrero while they were stopped at a red light on US 27 (1998). On 8 Jun 01, a Florida court sentenced Rosario to 15 years in a Florida State prison. The trial judge, in issuing the sentence, stated, “… you decided to get behind the wheel. It ’ s like taking a shotgun and shooting into the crowd. There was a chance you took, and you lost big. ” (Ledger, Lakeland, Fl.) … The three families settled lawsuits totaling $10 million against Rosario, Whirlpool Corp., GPC Driving Inc. and KENCO Logistic Services. Case #1 (Source: Parents Against Tired Truckers Photo courtesy of Florida Department of Corrections)

4. Case #2 Heather Brewster’s car was rear-ended by a medical resident who had just completed a 36-hour hospital shift Brewster… –suffered massive brain injuries –was in a coma for weeks –became permanently disabled –was declared incompetent by the courts Heather Brewster, pictured in 2002 Photo courtesy of the Brewster family; Story available at http://www.npr.org/templates/story/story.php?storyId=4512366 http://www.npr.org/templates/story/story.php?storyId=4512366

5. Who Works Shift Hours? Top Occupations Shift Workers (1000s) % of Total Force Production202124.4 Transportation & material moving190028.5 Food preparation & serving156840.4 Sales & related occupations146415.2 Office & administrative support14589.9 Health care practice & technical113824.6 Protection services112550.6 Management6129.8 Cleaning & maintenance60917.5 Personal care & service54228.1 Health care support53428.0 Installation, maintenance & repair48811.4 Construction & extraction2569.8 Community & social services23712.7 Arts, entertainment, media & sports22114.7 TOTAL14,17317.5 33% 22% 17% 20% 3% 5% Data source: Bureau of Labor Statistics (2004).Approximately 99.8 million workers >16 years. Available at: www.bls.gov/news.release/flex.t05/htmwww.bls.gov/news.release/flex.t05/htm

6. Starting Times for Full-Time Workers 26% of the U.S. Labor Force at Risk for SWD Source: Bureau of Labor Statistics, May 2004 data; available at http://www.bls.gov/news.release/flex.t07.htm Start time unknown: 1.5% 4:30 AM 8:30 AM 12:30 PM 4:30 PM 8:30 PM 12:30 AM 0.7% 8.6% 51.5% 6:30 AM 2:30 AM 10:30 AM 2:30 PM 6:30 PM 10:30 PM 15.6% 1.1% 1.2% 3.1% 1.0% 1.1% 0.8% 1.3% 0.2% Start Time Varies 12.2% Elevated risk for SWD Day and evening shift workers 25.9% 72.6% Unknown risk 1.5%

7. Biological Time of Day (circadian rhythms) Consecutive Waking Hours Night Sleep Duration Sleep Inertia DETERMINANTS OF ALERTNESS AND PERFORMANCE

8. Courtesy of D. Weaver, Univ Massachusetts Medical School, Worcester, MA Human Circadian Pacemaker in Suprachiasmatic Nucleus (SCN) of Hypothalamus SCN

9. Cajochen et al. Am J Physiol 1999 NTSB Study (SS1995/01) Temporal distribution of fatigue-related single vehicle truck accidents

10. Performance Efficiency Over 24 Hours 24:00 03:00 06:00 09:00 12:00 15:00 18:00 21:00 Efficiency assessed in 3 studies by: 1) delays in answering phone calls; 2) errors in reading meters; and 3) time taken by spinners to tie broken threads. Folkard S, Tucker P. Occup Med. 2003;53:95-101.

11. Biological Time of Day (circadian rhythms) Consecutive Waking Hours Night Sleep Duration Sleep Inertia DETERMINANTS OF ALERTNESS AND PERFORMANCE

12. Jewett et al., 2000 Hours of Driving National Transportation Safety Board Acute Sleep Deprivation and Performance

13. “...after [19] hours of sustained wakefulness (at 3 am) cognitive psychomotor performance decreased to a level equivalent to the performance impairment observed at a blood alcohol concentration of 0.05 %.... After 24 hours of sustained wakefulness (at 8 am) cognitive psychomotor performance decreased to a level equivalent to the performance deficit observed at a blood alcohol concentration of roughly 0.10 %.” - D. Dawson and K. Reid, Nature 388: 235, 1997.

14. Biological Time of Day (circadian rhythms) Consecutive Waking Hours Night Sleep Duration Sleep Inertia DETERMINANTS OF ALERTNESS AND PERFORMANCE

15. Van Dongen et al. Sleep 2003 Chronic Sleep Deprivation and Performance “Heavy Call” and Resident Performance p=0.06 p=0.01 Arnedt et al. JAMA 2005

16. Biological Time of Day (circadian rhythms) Consecutive Waking Hours Night Sleep Duration Sleep Inertia DETERMINANTS OF ALERTNESS AND PERFORMANCE

17. Wertz et al., JAMA 2006 Time Course of Deficits from Sleep Inertia Fighters All aircraft Hours since 6 am wake time 1 2 3 4 5 6 7 Aircraft Accident Data (Israeli Airforce) Ribak et al., Aviat. Space Environ. Med., 1983 Sleep Inertia

18. Chronic sleep restriction progressively degrades reaction time, particularly during circadian night. Cohen DA, et al. Science Translational Medicine 2010

19. Shift Work Coping Problems Personal Factors Age ≥50 years “Morning-type” person (“lark”) Heavy domestic workload Second job (“moonlighting”) History of… –Sleep disorders –Medical illness Adapted from: Monk TH. Shift Work. In: Principles and Practice of Sleep Medicine. 3rd ed. 2000:600.

20. Degrees of Excessive Sleepiness During times of rest or when little attention is required During daily activities requiring moderate attention Marked impairment and severe sleepiness during activities requiring mild-to-moderate attention Severity Falling asleep or nodding off… Adapted from: International Classification of Sleep Disorders Diagnostic and Coding Manual. 1st ed. Westchester, IL: American Academy of Sleep Medicine; 2000:23. Riding in a car Watching TV Reading During conversation Eating a meal Driving Walking Watching a movie Attending a concert In a meeting

21. Relative Risk for Injuries and Accidents Morning Afternoon Night 1 23 4 By Shift By Successive Nights Folkard S, Tucker P. Occup Med. 2003;53:95-101.

22. Effects of 24-hour Shifts on Safety OR: 2.3 (95% CI, 1.6-3.3) Barger LK et al. NEJM 2005; 352:125-134 Motor Vehicle CrashesPercutaneous Injuries OR: 1.6 (95%CI, 1.5-1.8) Ayas, et al. JAMA 2006; 296:1055-1062 Extended shifts Non- extended shifts

23. 100 Car Study Virginia Tech and NHTSA Naturalistic study of 100 cars for one year 82 crashes, 761 near-crashes Fatigue contributing cause in: 20% of all MVCs & 16% of all near- crashes Suggests could be as many as 8,000 fatigue-related fatal crashes in U.S. each year http://www.vtti.vt.edu/PDF/100-Car_Fact-Sheet.pdf

24. Gastrointestinal Disorders in Night-Shift Workers Day Shift Rotating Shift Prevalence of Ulcers in Workers Experiencing Insomnia or Excessive Sleepiness Prevalence of Ulcers in Workers Experiencing Insomnia or Excessive Sleepiness % of Workers % of Nurses Day Shift Rotating Shift Functional Bowel Disorders *P <0.05 vs no insomnia or ES Drake CL, et al. Sleep. 2004;27:1453-62 †P = 0.04 vs day shift. Zhen Lu W, et al. Eur J Gastroenterol Hepatol. 2006;18:623-627. 6.0 12.5 Night Shift 15.4 * * † 38 20

25. Shift Work and the Risk for Coronary Heart Disease in 79,109 Nurses *P <0.05 vs no shift work. Kawachi I, et al. Circulation.1995;92:3178-3182. Relative Risk (95% CI) No Shift Work Any Shift Work 1.00 1.23 Fatal CHD Nonfatal MI 1.00 1.41 1.38 Total CHD * *

26. Studies Demonstrating a Significant Risk for Cancer Among Shift Workers Type of CancerOdds Ratio95% CIReference Breast cancer Night shift ≥0.5 year Night shift >6 years 1.5* 1.7* 1.3 – 1.7 1 “Graveyard shift” (any) Shift work ≥5.7 hours/week 1.6* 2.3* 1.0 – 2.5 1.0 – 5.3 2 Rotating nights; ≥30 years1.36*1.04 – 1.783 Rotating shift work: >20 years1.79*1.06 – 3.014 Prostate cancer Rotating shift work3.0*1.2 – 7.75 *P <0.05 vs comparator group. 1) Hansen J. Epidemiology. 2001;12:74-77; 2) Davis S, et al. J Natl Cancer Inst. 2001;93:1557- 1562; 3) Schernhammer ES, et al. J Natl Cancer Inst. 2001;93:1563-1568. 4) Schernhammer ES, Epidemiology 2006;17:108-111; 5) Kubo T, et al. Am J Epidemiol. 2006;164:549-555.

27. Fatigue Management

28. Systemic Changes: Schedule Design and Other Workplace Interventions Eliminate shifts >12-16 hours Limit the number of consecutive night shifts –The fewer, the better –>4 12-hour night shifts associated with greatly increased risk of performance lapses 1 Schedule rotating workers to rotate “clockwise” Screen workers for sleep disorders Educate workers about the risks of driving and working while sleep deprived

29. Rotating shift work schedules that disrupt sleep are improved by applying circadian principles Czeisler CA, Moore-Ede MC, Coleman RM. Science 1982; 217:460-463 Intervention changed workers’ rotation from “phase advance” to “phase delay”, and increased time on rotation to 21 days Significant improvements in worker satisfaction and productivity (22%, p<0.001) after change

30. Philadelphia Police Department Center for Design of Industrial Schedules. 1988. Boston, MA. Circadian-based scheduling intervention (change from phase advance to phase delay) At Baseline: −Over 50% of officers reported moderate to severe problem with sleep quality −Over 70% admitted falling asleep on the job during the night shift Post-intervention: −Four-fold reduction in poor quality sleep −29% decline in sleep episodes at work −40% decline in patrol car crashes −38% increase in family satisfaction

31. Effect of Implementing a Sleep and Circadian Science–Based Intervention Schedule on Interns’ Serious Medical Errors Lockley SW, et al., Landrigan CP, et al. N Engl J Med. 2004;351:1829-1837; 1838-1848.

32. Bright Light and Sleep/ Darkness for Alleviating Maladaptation to Shift Work 54 subjects Simulated 4-day, 3-night shift work 38-hour constant routine (CR) Light during 8-hr “shift work” –Bright (~2500 lux) –Room (~150 lux) Sleep –Fixed 8 hr; darkened room –Free schedule Nighttime alertness –P <0.01: bright light vs room light –P <0.01: fixed sleep vs free sleep Bright Free Bright Fixed Room Free Room Fixed Horowitz TS, et al. Am J Physiol Endocrinol Metab. 2001;281:384-391.

33. Individual Level Nonpharmacologic interventions –Work schedule changes –Lifestyle changes –Exercise Nonprescription interventions –Light –Melatonin –Caffeine (coffee, tea, colas, energy bars, caffeine tablets) –OTC sleep aids Prescription interventions –Sleep promoting medications –Wake promoting medications

34. Effect of Exogenous Melatonin on Sleep Efficiency in the Presence or Absence of Endogenous Melatonin Endogenous melatonin levels are… –High at night –Low during the daytime Exogenous melatonin… –Increases the duration of sleep occurring out of phase with endogenous melatonin secretion –Attenuates the wake-promoting drive from the circadian system –Has little effect when taken at times when endogenous melatonin is present Melatonin 0.3 mg Placebo Melatonin 5.0 mg Low to Absent Endogenous Melatonin Elevated Endogenous Melatonin * * Wyatt JK, et al. Sleep. 2006;29:609-618. Mean Sleep Efficiency (% ± SEM)

35. Phase Shift in Circadian Rhythms With Melatonin in a Simulated Night-Shift Study Endogenous Dim-Light Melatonin Onset Placebo Melatonin 0.5 mg Melatonin 3.0 mg Sharkey KM, et al. Am J Physiol Regulatory Integrative Comp Physiol. 2002;282:454-63 P <0.05 P <0.001 Mean Phase Shift (hours) 1.7 3.0 3.9 0 1 2 3 4 5

36. Caffeine Baseline Extended Wake Duration 0 8 16 24 4.8 28.642.9 Hours Wyatt JK, et al. Sleep. 2004;27:374-381. Placebo Caffeine Cognition DSST (# correct) Vigilance & Reaction PVT (slowest 10% [msec]) Sleepiness KSS (units) 15 10 5 0 -5 0 1000 2000 0 1 2 3 SLEEPSLEEP SLEEPSLEEP SLEEPSLEEP SLEEPSLEEP SLEEPSLEEP SLEEPSLEEP P <0.05

37. Treating Daytime Insomnia Sleep hygiene –Dark, cool, quiet bedroom –Avoidance of caffeine, tobacco, and alcohol –Consistent sleep & wake times –Regular exercise –Cognitive therapy Nonprescription interventions –Antihistamines Prescription interventions –Benzodiazepines –Nonbenzodiazepines –Sedating antidepressants

38. Shift Work Disorder (SWD): Diagnostic Criteria Adapted from: International Classification of Sleep Disorders Diagnostic and Coding Manual. 2nd ed. Westchester, IL: American Academy of Sleep Medicine; 2005. (1)Insomnia or excessive sleepiness temporally associated with a recurring work schedule that overlaps the usual time for sleep; (2)symptoms must be associated with the shift work schedule over the course of at least one month; (3)circadian and sleep-time misalignment as demonstrated by sleep log or actigraphic monitoring for ≥ 7 days; and (4)sleep disturbance not explained by another sleep disorder, medical or neurological disorder, mental disorder, medication use, or substance use disorder.

39. Modafinil for Excessive Sleepiness in Patients With SWD % of Patients Improved Placebo Modafinil 200 mg *P <0.001 vs placebo. †P = 0.002 for change from baseline vs change from baseline with placebo. Czeisler CA, et al. N Engl J Med. 2005;353:476-486. Minutes 36 74 2.4 3.8 Clinician’s Global Impression of Change (Improvement) Sleep Latency MSLT Sleep Latency MSLT * † Baseline Final Visit

40. Reducing the Effects of Sleepiness When Commuting Shift workers have a greatly increased risk of suffering a motor vehicle crash on the drive home from work 1,2 Measures for the employer –Facilitate establishment of taxi services and/or company car pools –Provide a place for workers to nap before driving home Measures for the employee –Minimize commuting; move closer to the work place or use public transportation –Avoid traveling at high speeds on highways –If you feel sleepy when driving, pull over and nap; rolling down the window and turning up the radio will not work 1) Barger LK, et al. N Engl J Med. 2005;352:125-134; 2) Gold DR, et al. Am J Public Health. 1992;82:1011-4.

41. Summary A large segment of the U.S. population works shifts Shift workers are prone to circadian misalignment, acute sleep deprivation, chronic sleep deprivation, and sleep inertia These forces increase the risk of accidents, injuries, mistakes on the job, and motor vehicle crashes (either on the job or driving home) Systemic interventions to optimize work schedules have been shown to be effective across occupations At an individual level, optimizing sleep hygiene, melatonin, caffeine, and pharmaceuticals can be helpful