www.hbr.org
DIFFERENT VOICE
Sleep is a stranger to many
managers. Research by leading
scientists shows just how
dangerous that problem is.
Sleep Deficit
The Performance Killer
A Conversation with Harvard Medical School
Professor Charles A. Czeisler
•
Reprint R0610B
Sleep is a stranger to many managers. Research by leading scientists
shows just how dangerous that problem is.
DIFFERENT VOICE
Sleep Deficit
The Performance Killer
COPYRIGHT © 2006 HARVARD BUSINESS SCHOOL PUBLISHING CORPORATION. ALL RIGHTS RESERVED.
A Conversation with Harvard Medical School
Professor Charles A. Czeisler
At 12:30 AM on June 10, 2002, Israel Lane Joubert
and his family of seven set out for a long drive
home following a family reunion in Beaumont,
Texas. Joubert, who had hoped to reach home
in faraway Fort Worth in time to get to work by
8 AM, fell asleep at the wheel, plowing the family’s
Chevy Suburban into the rear of a parked 18wheeler. He survived, but his wife and five of his
six children were killed.
The Joubert tragedy underscores a problem of
epidemic proportions among workers who get
too little sleep. In the past five years, driver fatigue has accounted for more than 1.35 million
automobile accidents in the United States alone,
according to the National Highway Traffic Safety
Administration. The general effect of sleep deprivation on cognitive performance is well-known:
Stay awake longer than 18 consecutive hours, and
your reaction speed, short-term and long-term
memory, ability to focus, decision-making capacity, math processing, cognitive speed, and spatial
orientation all start to suffer. Cut sleep back to
five or six hours a night for several days in a row,
and the accumulated sleep deficit magnifies
harvard business review • hbr.org • october 2006
these negative effects. (Sleep deprivation is implicated in all kinds of physical maladies, too,
from high blood pressure to obesity.)
Nevertheless, frenzied corporate cultures still
confuse sleeplessness with vitality and high performance. An ambitious manager logs 80-hour
work weeks, surviving on five or six hours of sleep
a night and eight cups of coffee (the world’s
second-most widely sold commodity, after oil) a
day. A Wall Street trader goes to bed at 11 or midnight and wakes to his BlackBerry buzz at 2:30 AM
to track opening activity on the DAX. A road warrior lives out of a suitcase while traveling to Tokyo, St. Louis, Miami, and Zurich, conducting
business in a cloud of caffeinated jet lag. A negotiator takes a red-eye flight, hops into a rental car,
and zooms through an unfamiliar city to make a
delicate M&A meeting at 8 in the morning.
People like this put themselves, their teams,
their companies, and the general public in serious jeopardy, says Dr. Charles A. Czeisler, the
Baldino Professor of Sleep Medicine at Harvard
Medical School.1 To him, encouraging a culture
of sleepless machismo is worse than nonsensi-
page 1
Sleep Deficit •• •D IFFERENT V OICE
cal; it is downright dangerous, and the antithesis of intelligent management. He notes that
while corporations have all kinds of policies designed to prevent employee endangerment—
rules against workplace smoking, drinking,
drugs, sexual harassment, and so on—they
sometimes push employees to the brink of selfdestruction. Being “on” pretty much around the
clock induces a level of impairment every bit as
risky as intoxication.
As one of the world’s leading authorities on
human sleep cycles and the biology of sleep and
wakefulness, Dr. Czeisler understands the physiological bases of the sleep imperative better than
almost anyone. His message to corporate leaders
is simple: If you want to raise performance—
both your own and your organization’s—you
need to pay attention to this fundamental biological issue. In this edited interview with senior editor Bronwyn Fryer, Czeisler observes that top executives now have a critical responsibility to take
sleeplessness seriously.
What does the most recent research tell us
about the physiology of sleep and cognitive
performance?
Four major sleep-related factors affect our
cognitive performance. The kinds of work and
travel schedules required of business executives
today pose a severe challenge to their ability to
function well, given each of these factors.
The first has to do with the homeostatic drive
for sleep at night, determined largely by the
number of consecutive hours that we’ve been
awake. Throughout the waking day, human beings build up a stronger and stronger drive
for sleep. Most of us think we’re in control of
sleep—that we choose when to go to sleep and
when to wake up. The fact is that when we are
drowsy, the brain can seize control involuntarily. When the homeostatic pressure to sleep
becomes high enough, a couple thousand neurons in the brain’s “sleep switch” ignite, as discovered by Dr. Clif Saper at Harvard Medical
School. Once that happens, sleep seizes the
brain like a pilot grabbing the controls. If you’re
behind the wheel of a car at the time, it takes
just three or four seconds to be off the road.
The second major factor that determines
our ability to sustain attention and maintain
peak cognitive performance has to do with the
total amount of sleep you manage to get over
several days. If you get at least eight hours of
sleep a night, your level of alertness should re-
harvard business review • hbr.org • october 2006
main stable throughout the day, but if you
have a sleep disorder or get less than that for
several days, you start building a sleep deficit
that makes it more difficult for the brain to
function. Executives I’ve observed tend to
burn the candle at both ends, with 7 AM breakfast meetings and dinners that run late, for
days and days. Most people can’t get to sleep
without some wind-down time, even if they
are very tired, so these executives may not
doze off until 2 in the morning. If they average four hours of sleep a night for four or
five days, they develop the same level of cognitive impairment as if they’d been awake for
24 hours—equivalent to legal drunkenness.
Within ten days, the level of impairment is the
same as you’d have going 48 hours without
sleep. This greatly lengthens reaction time,
impedes judgment, and interferes with problem solving. In such a state of sleep deprivation, a single beer can have the same impact
on our ability to sustain performance as a
whole six-pack can have on someone who’s
well rested.
The third factor has to do with circadian
phase—the time of day in the human body that
says “it’s midnight” or “it’s dawn.” A neurological timing device called the “circadian pacemaker” works alongside but, paradoxically, in
opposition to the homeostatic drive for sleep.
This circadian pacemaker sends out its strongest drive for sleep just before we habitually
wake up, and its strongest drive for waking one
to three hours before we usually go to bed, just
when the homeostatic drive for sleep is peaking. We don’t know why it’s set up this way,
but we can speculate that it has to do with the
fact that, unlike other animals, we don’t take
frequent catnaps throughout the day. The circadian pacemaker may help us to focus on that
big project by enabling us to stay awake
throughout the day in one long interval and by
allowing us to consolidate sleep into one long
interval at night.
In the midafternoon, when we’ve already
built up substantial homeostatic sleep drive,
the circadian system has not yet come to the
rescue. That’s typically the time when people
are tempted to take a nap or head for the closest Starbucks or soda machine. The caffeine in
the coffee temporarily blocks receptors in the
brain that regulate sleep drive. Thereafter, the
circadian pacemaker sends out a stronger and
stronger drive for waking as the day progresses.
page 2
Sleep Deficit •• •D IFFERENT V OICE
Putting yourself or others
at risk while driving or
working at an impaired
level is bad enough;
expecting your employees
to do the same is just
irresponsible.
Provided you’re keeping a regular schedule, the
rise in the sleep-facilitating hormone melatonin will then quiet the circadian pacemaker
one to two hours before your habitual bedtime,
enabling the homeostatic sleep drive to take
over and allow you to get to sleep. As the homeostatic drive dissipates midway through the
sleep episode, the circadian drive for sleep increases toward morning, maintaining our ability to obtain a full night of sleep. After our
usual wake time, the levels of melatonin begin
to decline. Normally, the two mutually opposing processes work well together, sustaining
alertness throughout the day and promoting a
solid night of sleep.
The fourth factor affecting performance has
to do with what’s called “sleep inertia,” the grogginess most people experience when they first
wake up. Just like a car engine, the brain needs
time to “warm up” when you awaken. The part
of your brain responsible for memory consolidation doesn’t function well for five to 20 minutes after you wake up and doesn’t reach its
peak efficiency for a couple of hours. But if you
sleep on the airplane and the flight attendant
wakes you up suddenly upon landing, you may
find yourself at the customs station before you
realize you’ve left your laptop and your passport behind. There is a transitional period between the time you wake up and the time your
brain becomes fully functional. This is why you
never want to make an important decision as
soon as you are suddenly awakened—ask any
nurse who’s had to awaken a physician at night
about a patient.
Most top executives are over 40. Isn’t it true
that sleeping also becomes more difficult
with age?
Yes, that’s true. When we’re past the age of 40,
sleep is much more fragmented than when
we’re younger. We are more easily awakened
by disturbances such as noise from the external environment and from our own increasing aches and pains. Another thing that increases with age is the risk of sleep disorders
such as restless legs syndrome, insomnia, and
sleep apnea—the cessation of breathing during
sleep, which can occur when the airway collapses many times per hour and shuts off the
flow of oxygen to the heart and brain, leading
to many brief awakenings.
Many people gain weight as they age, too. Interestingly, chronic sleep restriction increases
harvard business review • hbr.org • october 2006
levels of appetite and stress hormones; it also
reduces one’s ability to metabolize glucose and
increases the production of the hormone ghrelin, which makes people crave carbohydrates
and sugars, so they get heavier, which in turn
raises the risk of sleep apnea, creating a vicious
cycle. Some researchers speculate that the
epidemic of obesity in the U.S. and elsewhere
may be related to chronic sleep loss. Moreover,
sleep-disordered breathing increases the risk of
high blood pressure and heart disease due to
the strain of starving the heart of oxygen many
times per hour throughout the night.
As we age, the circadian window during which
we maintain consolidated sleep also narrows.
That’s why airline travel across time zones can
be so brutal as we get older. Attempting to sleep
at an adverse circadian phase—that is, during
our biological daytime—becomes much more
difficult. Thus, if you take a 7 PM flight from
New York to London, you typically land about
midnight in your home time zone, when the
homeostatic drive for sleep is very strong, but
the local time is 5 AM. Exposure to daylight—
the principal circadian synchronizer—at this
time shifts you toward Hawaiian time rather
than toward London time. In this circumstance,
the worst possible thing you can do is rent a car
and drive to a meeting where you have to impress people with your mental acuity at the
equivalent of 3 or 4 in the morning. You might
not even make the meeting, because you very
easily could wrap your car around a tree. Fourteen or 15 hours later, if you’re trying to go to
bed at 11 PM in the local time zone, you’ll have a
more difficult time maintaining a consolidated
night’s sleep.
So sleep deprivation, in your opinion, is a
far more serious issue than most executives
think it is.
Yes, indeed. Putting yourself or others at risk
while driving or working at an impaired level is
bad enough; expecting your employees to do
the same is just irresponsible. It amazes me that
contemporary work and social culture glorifies
sleeplessness in the way we once glorified people who could hold their liquor. We now know
that 24 hours without sleep or a week of sleeping four or five hours a night induces an impairment equivalent to a blood alcohol level of .1%.
We would never say, “This person is a great
worker! He’s drunk all the time!” yet we continue to celebrate people who sacrifice sleep.
page 3
Sleep Deficit •• •D IFFERENT V OICE
A company’s sleep policy
should not permit
anyone, under any
circumstances, to take an
overnight flight and then
drive to a business
meeting somewhere—
period.
The analogy to drunkenness is real because,
like a drunk, a person who is sleep deprived has
no idea how functionally impaired he or she
truly is. Moreover, their efficiency at work will
suffer substantially, contributing to the phenomenon of “presenteeism,” which, as HBR has
noted, exacts a large economic toll on business.
[See Paul Hemp’s article “Presenteeism: At
Work—But Out of It,” HBR October 2004.]
Sleep deprivation is not just an individual
health hazard; it’s a public one. Consider the
risk of occupational injury and driver fatigue.
In a study our research team conducted of hospital interns who had been scheduled to work
for at least 24 consecutive hours, we found that
their odds of stabbing themselves with a needle
or scalpel increased 61%, their risk of crashing a
motor vehicle increased 168%, and their risk of
a near miss increased 460%. In the U.S., drowsy
drivers are responsible for a fifth of all motor
vehicle accidents and some 8,000 deaths annually. It is estimated that 80,000 drivers fall
asleep at the wheel every day, 10% of them run
off the road, and every two minutes, one of
them crashes. Countless innocent people are
hurt. There’s now a vehicular homicide law in
New Jersey (and some pending in other states)
that includes driving without sleep for more
than 24 hours in its definition of recklessness.
There’s a man in Florida who’s serving a 15-year
prison term for vehicular homicide—he’d been
awake for 30-some hours when he crashed his
company’s truck into a group of cars waiting for
a light to change, killing three people. I would
not want to be the CEO of the company bearing responsibility for those preventable deaths.
Sleep deprivation among employees poses
other kinds of risks to companies as well.
With too little sleep, people do things that no
CEO in his or her right mind would allow.
All over the world, people are running heavy
and dangerous machinery or guarding secure
sites and buildings while they’re exhausted.
Otherwise intelligent, well-mannered managers do all kinds of things they’d never do if they
were rested—they may get angry at employees,
make unsound decisions that affect the future
of their companies, and give muddled presentations before their colleagues, customers, the
press, or shareholders.
What should companies be doing to address
the sleep problem?
People in executive positions should set behav-
harvard business review • hbr.org • october 2006
ioral expectations and develop corporate sleep
policies, just as they already have concerning
behaviors like smoking or sexual harassment.
It’s important to have a policy limiting scheduled work—ideally to no more than 12 hours a
day, and exceptionally to no more than 16 consecutive hours. At least 11 consecutive hours of
rest should be provided every 24 hours. Furthermore, employees should not be scheduled
to work more than 60 hours a week and not be
permitted to work more than 80 hours a week.
When working at night or on extended shifts,
employees should not be scheduled to work
more than four or five consecutive days, and
certainly no more than six consecutive days.
People need at least one day off a week, and
ideally two in a row, in order to avoid building
up a sleep deficit.
Now, managers will often rationalize overscheduling employees. I hear them say that if
their employees aren’t working, they will be
out partying and not sleeping anyway. That
may be true for some irresponsible individuals,
but it doesn’t justify scheduling employees to
work a hundred hours a week so that they can’t
possibly get an adequate amount of sleep. Of
course, some circumstances may arise in which
you need someone to remain at work for more
than 16 consecutive hours. The night security
guard, for example, can’t just walk off the job if
his replacement isn’t there, so you will need to
have a provision for exceptional circumstances,
such as offering transportation home for a
sleep-deprived worker.
Companies also need executive policies. For
example, I would advise executives to avoid
taking red-eye flights, which severely disrupt
sleep. If someone must travel overnight internationally, the policy should allow the executive to take at least a day to adapt to the sleep
deprivation associated with the flight and the
new time zone before driving or conducting
business. Such a policy requires some good
schedule planning, but the time spent making
the adjustments will be worth it, for the traveler will be more functional before going
into that important meeting. And the sleep
policy should not permit anyone, under any circumstances, to take an overnight flight and
then drive to a business meeting somewhere—
period. He or she should at least be provided a
taxi, car service, or shuttle.
Companies can do other things to promote
healthy sleep practices among employees.
page 4
Sleep Deficit •• •D IFFERENT V OICE
What’s New in Sleep?
Sleep science is advancing on a number of frontiers that, over time, may
cause us to rethink everything from
our personal habits to public policy.
Here’s a short sampling of these
new developments.
Sleep is power. Your mother was
right—to perform at your best, you
need sleep. Discoveries about sleep
cycles have given researchers new
insight into the specific roles sleep
plays in overall health and performance. For example, there is growing evidence that sleep aids in immune function, memory consolidation, learning, and organ function.
“Some researchers now think sleep
may be the missing link when it
comes to overall health, safety, and
productivity,” says Darrel Drobnich,
the senior director of government
and transportation affairs for the National Sleep Foundation. One new
field of study is looking at a specific
correlation between sleep and productivity, and the benefits of what
sleep researchers call a “power
nap”—a 20-minute period of sleep in
the afternoon that heads off problems associated with cumulative
sleep deficit.
Move over, Ambien. Ambien, the
sleep aid from drugmaker SanofiAventis, is now de rigueur for the
sleepless, ringing up $1.4 billion annually in U.S. sales alone. While Ambien
has fewer side effects than most overthe-counter sleep aids, it’s still a blunt
instrument, neurophysiologically
speaking. “All of the current products
on the market, including Ambien,
take a sledgehammer to specific receptors in the brain,” says Dr. Robert
harvard business review • hbr.org • october 2006
McCarley, the head of psychiatry at
Boston VA Medical Center and a professor of psychiatry at Harvard Medical School. “They have several negative side effects, ranging from
disassociated states of consciousness
to potential addiction. They also tend
to lose their effectiveness over time.”
Researchers hope a new family of
sleep-inducing drugs will function
closer to the body’s natural sleep
mechanisms and so avoid problems
associated with sedatives like Ambien. One such new drug—Rozerem,
from Japanese drug giant Takeda—
targets melatonin receptors in the
brain. As researchers learn more
about the body’s internal sleep mechanisms, McCarley believes, sleep aids
will inevitably improve.
On the other side of the equation, the
pharmaceutical company Cephalon is
now marketing modafinil, a drug that
helps people function well on very little
sleep without suffering the ill effects of
common stimulants. Sold under the
commercial trade name Provigil in the
U.S., modafinil was originally prescribed to treat narcolepsy; it’s now
used to promote wakefulness among
those who can’t afford to go to sleep
(such as field soldiers in war zones).
Studies have shown that subjects taking
modafinil are able to stay alert with
only eight hours of sleep during an 88hour period. While modafinil sounds
like a dream drug, no one yet knows
what effects may result from more than
occasional use.
Car drowse alarms. By the end of
the decade, automakers will offer cars
outfitted with devices designed to
keep drowsy drivers from falling
asleep at the wheel. Some may use
cameras to scan drivers’ eyes for
droopiness, or to sense when people
are loosening their grip on the steering wheel, and then sound an alarm.
In 2005, Ford and Volvo announced
that they were working on a system
called Driver Alert, consisting of a
camera that measures the distance
between the vehicle and the markings
on the surface of the road. If the
driver starts to swerve, an alarm goes
off and a text warning appears on the
dashboard. Another approach under
consideration by the U.S. National
Highway Traffic Safety Administration is the development of “intelligent” highways equipped with specialized sensors that continuously
track vehicle trajectory and speed.
Tomorrow’s workforce needs
sleep now. Businesses need an educated workforce; ironically, school is interfering. The current high school
schedule in the U.S., which typically
begins around 7:20 AM, threatens the
neurological development and health
of adolescents, whose homeostatic
drive operates differently from adults’.
Most teens experience a delayed sleep
phase, in which melatonin is released
around 11 PM—an hour later than in
most adults. Students who finally go to
sleep by midnight and wake at 6 experience a chronic sleep deficit, which
disrupts their ability to learn and puts
them and you at risk on the roads. In
the U.S., researchers and sleep advocates are now working closely with
school districts, communities, and educators to change school start times so
that students can get more sleep.
—Bronwyn Fryer
page 5
Sleep Deficit •• •D IFFERENT V OICE
Educational programs about sleep, health, and
safety should be mandatory. Employees should
learn to set aside an adequate amount of time
for sleep each night and to keep their bedrooms dark and quiet and free of all electronic
devices—televisions, BlackBerries, and so on.
They should learn about the ways alcohol and
caffeine interfere with sleep. When someone is
sleep deprived, drinking alcohol only makes
things worse, further eroding performance
and increasing the propensity to fall asleep
while also interfering with the ability to stay
asleep. Additionally, companies should provide annual screening for sleep disorders in
order to identify those who might be at risk.
For example, this past year our team launched
a Web-based screening survey that any law enforcement officer in the U.S. can take to help
identify whether he or she is suffering from
sleep apnea, restless legs syndrome, narcolepsy, or other sleep disorders. Those whose answers place them at high risk are referred for
evaluation and treatment by a specialist accredited by the American Academy of Sleep
Medicine. [Accredited sleep centers may be
found at www.sleepcenters.org.]
Finally, I would recommend that supervisors
undergo training in sleep and fatigue management and that they promote good sleep behavior.
People should learn to treat sleep as a serious
matter. Both the company and the employees
bear a shared responsibility to ensure that everyone comes to work well rested.
This corporate sleep policy of yours sounds
a little draconian, if not impossible, given
people’s crazy schedules.
I don’t think it’s draconian at all. Business travelers expect that their pilots won’t drink before
flying an airplane, and all of us expect that no
driver on the highway will have a blood alcohol
level above the legal limit. Many executives already realize that the immediate effect of sleep
loss on individuals and on overall corporate
performance is just as important. A good sleep
policy is smart business strategy. People think
they’re saving time and being more productive
by not sleeping, but in fact they are cutting
their productivity drastically. Someone who has
adequate sleep doesn’t nod off in an important
meeting with a customer. She can pay attention
to her task for longer periods of time and bring
her whole intelligence and creativity to bear on
the project at hand.
harvard business review • hbr.org • october 2006
What do you think about the use of drugs
that help people fall asleep or that shut off
the urge to sleep?
These agents should be used only after a thorough evaluation of the causes of insomnia or
excessive daytime sleepiness. Patients too often
think there’s a silver bullet for a problem like
insomnia, and doctors too easily prescribe pills
as part of a knee-jerk reaction to patient requests during the final minutes of an office
visit. The causes of insomnia are subtle and
need to be carefully investigated. These can be
from too much caffeine, an irregular schedule,
anxiety or depression, physical problems such
as arthritis, use of other medications, and so
on—and only a careful evaluation by a doctor
experienced in sleep medicine can uncover
the causes. I once saw a professor who complained of difficulty sleeping at night, and only
after taking a careful history did we find that he
was drinking 20 cups of coffee a day. He didn’t
even realize he was drinking that much and
didn’t think about the fact that so much caffeine, which has a six- to nine-hour half-life,
would interfere with his ability to sleep. Prescribing a sleeping pill for his insomnia without
identifying the underlying cause would have
been a mistake.
There are non-pharmacological treatments
for insomnia that seem very promising, by the
way. Cognitive behavioral therapy, or CBT,
helps people recognize and change thoughts
and behaviors that might be keeping them
awake at night. A researcher named Dr. Gregg
Jacobs at Harvard Medical School has reported
that CBT works better over both the short and
the long term than sleeping pills do.
Sometimes executives simply have to function without much sleep. What are some
strategies they can use to get by until they
can go to bed?
Though there is no known substitute for
sleep, there are a few strategies you can use to
help sustain performance temporarily until
you can get a good night’s sleep. Obviously,
executives can drink caffeine, which is the
most widely used wake-promoting therapeutic in the world. Naps can be very effective at
restoring performance, and if they are brief—
less than a half hour—they will induce less
grogginess upon awakening. Being in a novel
or engaging circumstance will also help you
stay alert. Exercise, standing in an upright po-
page 6
Sleep Deficit •• •D IFFERENT V OICE
sition, and exposure to bright light are all
very helpful. Human beings are amazingly
sensitive to light. In fact, the color of light
may also be important. Exposure to shorter
wavelength blue light is particularly effective in suppressing melatonin production,
thereby allowing us to stay awake during
our biological night. Photon for photon,
looking up at the blue sky, for example, is
more effective in both resetting our biological clock and enhancing our alertness than
looking down at the green grass.
While all these things can help an executive function in an emergency, I must reiterate that he or she should still not drive
when sleep deprived, even if a cup of coffee
harvard business review • hbr.org • october 2006
or a walk on a sunny day seems to help for a
little while.
Do you get enough sleep?
Like everyone else, I try to, but I don’t always
achieve it.
1. Dr. Czeisler is the incumbent of an endowed professorship donated to Harvard by Cephalon and consults for a
number of companies, including Actelion, Cephalon, CocaCola, Hypnion, Pfizer, Respironics, Sanofi-Aventis, Takeda,
and Vanda.
Reprint R0610B
To order, see the next page
or call 800-988-0886 or 617-783-7500
or go to www.hbr.org
page 7
Further Reading
The Harvard Business Review
Paperback Series
Harvard Business Review OnPoint
articles enhance the full-text article
with a summary of its key points and
a selection of its company examples
to help you quickly absorb and apply
the concepts. Harvard Business
Review OnPoint collections include
three OnPoint articles and an
overview comparing the various
perspectives on a specific topic.
Here are the landmark ideas—both
contemporary and classic—that have
established Harvard Business Review as required
reading for businesspeople around the globe.
Each paperback includes eight of the leading
articles on a particular business topic. The
series includes over thirty titles, including the
following best-sellers:
Harvard Business Review on Brand
Management
Product no. 1445
Harvard Business Review on Change
Product no. 8842
Harvard Business Review on Leadership
Product no. 8834
Harvard Business Review on Managing
People
Product no. 9075
Harvard Business Review on Measuring
Corporate Performance
Product no. 8826
For a complete list of the Harvard Business
Review paperback series, go to www.hbr.org.
To Order
For reprints, Harvard Business Review
OnPoint orders, and subscriptions
to Harvard Business Review:
Call 800-988-0886 or 617-783-7500.
Go to www.hbr.org
For customized and quantity orders
of reprints and Harvard Business
Review OnPoint products:
Call Rich Gravelin at
617-783-7626,
or e-mail him at
[email protected]
page 8
TRANSACTIONS OF THE AMERICAN CLINICAL AND CLIMATOLOGICAL ASSOCIATION, VOL. 117, 2006
THE GORDON WILSON LECTURE
WORK HOURS, SLEEP AND PATIENT SAFETY IN
RESIDENCY TRAINING
CHARLES A. CZEISLER, PH.D., M.D.
BOSTON, MASSACHUSETTS
Case Presentation
In February, 2005, I was asked by the Department of Anesthesia
at the Brigham and Women’s Hospital in Boston to attend their
Morbidity and Mortality Weekly Report rounds to discuss a fallasleep motor vehicle crash that had occurred on February 20, 2005 in
one of their trainees. The trainee was a 39-year-old white male who
was in his fifth postgraduate year of training as an anesthesia fellow
(Case A.F.). At about 3 pm on February 20, 2005, A.F. fell asleep at
the wheel and collided with a stopped vehicle while he was en route
home from a 7-hour work shift at the Brigham and Women’s Hospital. There was no injury to the fellow, to the other driver or to her
5-year-old child—and hence there is no litigation involved—which is
why I am able to present Case A.F. to you today. A.F. reported a
similar incident four years earlier in which he had fallen asleep at
the wheel while driving his car at high speed on an expressway
during a commute home from a ⬎30-hour extended duration work
shift in his first postgraduate year of training. In that incident, A.F.
was awoken by a rumble strip on the expressway and thereby
avoided a potentially catastrophic motor vehicle crash. He said that
he understood that the ⬎30-hour shift had made him vulnerable to
the fall-asleep incident while driving on the highway during his
PGY1 year. However, he wondered why he experienced a fall-asleep
crash during his PGY5 year, after working a much shorter, sevenFrom the Division of Sleep Medicine, Department of Medicine, Brigham and Women’s
Hospital and Division of Sleep Medicine, Harvard Medical School, Boston
Dr. Czeisler serves or has served as a paid consultant for Actilion, Avera Pharmaceuticals,
Inc., Axon Sleep Research Laboratories, Cephalon, Hypnion, Lifetrac, Neurocrine, SanofiAventis, Pfizer, Respironics, Takeda, Unilever and Vanda Pharmaceuticals; owns equity
interest in Hypnion, Lifetrac and Vanda and has received clinical trial research contracts and
investigator-initiated research grants from Cephalon and Pfizer. Dr. Czeisler’s laboratory has
received unrestricted research and education funds from Cephalon and he serves as the
incumbent of an endowed professorship provided to Harvard University by Cephalon.
159
160
CHARLES A. CZEISLER
hour shift. To address this question, I initiated a series of steps
comparable to those which might be undertaken by investigators
(such as local or state police departments or the National Transportation Safety Board) evaluating if sleepiness or sleep deprivation
were a probable contributing factor to a transportation accident.
Work-hour and Sleep-wake History
As a PGY-5 anesthesia fellow, A.F.’s work schedule required that
he be “on call” from home for the intensive care unit for two out of
every three weeks. He reported that his sleep habits were as follows:
(1) during non-call/non-work nights (which occurred 6 times per
month) his nightly sleep episode was from 10 pm to 6:30 am; (2)
during non-call/work nights (which occurred 7–14 times per month)
his nightly sleep episode was from 10 pm to 4:30 am; (3) during
on-call/work nights (which occurred 7–21 times per month) his
nightly sleep episode was from 10 pm to 4:30 am and he was awoken
by 3– 4 pages from the intensive care unit per night. Finally, A.F.
noted that he and his wife were typically awoken once per night by
one of their three young children for about 20 minutes per night.
Pharmacologic History
A.F. denied alcohol or hypnotic drug use prior to the crash. He
admitted using caffeine, which he reportedly administered in the form
of “three shots of espresso” each morning and which he said he “titrated to effects” during the remainder of the day (typically two more
small cups of coffee). He reported that he avoided caffeine most afternoons, including the day of the crash, in order to avoid disturbing his
subsequent night of sleep.
Hospital Paging Records
The times at which A.F. was paged were downloaded from the
Brigham and Women’s Hospital paging system records and are illustrated together with his reported sleep-wake times, as recollected
by history, during the prior four nights, in Figure 1. On the night
before the crash, A.F. was paged twice at the beginning of his sleep
episode, then awoken by a page from the ICU again at about 1:30 am,
then awoken by a page just before 2 am and then awoken by a page
again at approximately 3 am before his final page during that sleep
episode, which was at about 3:30 am. He arose at 4:30 am, showered,
dressed and ate breakfast (including three shots of espresso) prior to
commencing a 50-mile commute into the hospital at 5:45 am.
RESIDENT WORK HOURS, SLEEP AND PATIENT SAFETY
161
FIG. 1. The sleep-wake times, commute times and pages (from the Brigham and
Women’s Hospital paging records) of a PGY-5 Anesthesia Fellow leading up to motor
vehicle crash.
Sleep Disorders Evaluation
A.F. was referred to Dr. David White, who then directed the Brigham
and Women’s Hospital Sleep Disorders Service, for an evaluation. He
reported a history of loud snoring, particularly when sleep deprived and
when sleeping on his back. He denied weight change, restless legs,
history of sleep attacks or limb weakness with extreme emotion (cataplexy) or a history of difficulty falling asleep or staying asleep. His
physical examination was unremarkable (Height: 6⬘3⬙; Weight: 180 lbs;
BMI: 22.5). Dr. White ordered a polysomnographic recording, which
revealed an hourly apnea/hypopnea index (AHI) of 20.5, with an AHI of
47 per hour when supine and 2 per hour when sleeping on his side.
Oxygen desaturations to 86 percent were recorded during the apneic
events. Dr. White diagnosed A.F. with positional sleep-related breathing
disorder and behaviorally induced insufficient sleep syndrome.
In order to put the results of this evaluation into context, it is
important to understand the physiology of sleep and wakefulness.
Background on Determinants of Alertness and Performance
Multiple factors influence the ability to sustain effective waking
neurocognitive performance in young healthy individuals not taking
162
CHARLES A. CZEISLER
medications. These include consecutive waking hours; nightly sleep
duration; biological time of day (i.e., circadian phase); and the recency
of the last sleep episode (i.e., sleep inertia). While the effects of these
circadian and homeostatic sleep regulatory processes can be modified
by environmental conditions, physical activity and pharmacological
agents (i.e., stimulant and hypnotic agents), there is no countermeasure known that can consistently overcome the impact of adverse
circadian phase and/or sleep deprivation on performance. The interaction of these regulatory processes can create an imposing biological
force which can overpower an individual’s ability to sustain alert
wakefulness and remain attentive. This leads to impaired neurocognitive performance, including reduced memory consolidation, and deterioration of waking performance marked by increased rates of attentional failures (1). These consequences of misalignment of circadian
phase and the wake-sleep schedule, cumulative sleep deprivation and
lengthy prior wakefulness are particularly evident while attempting to
sustain attention for a continuous duration of time (e.g., for 10 –20
minutes or more) while performing a routine, highly over-learned task
such as driving a motor vehicle.
The Sleep Homeostat
Without sleep, alertness and neurocognitive performance exhibit a
steady deterioration attributable to sleep loss, onto which a rhythmic
circadian variation is superimposed (2–18). Among individuals who
win the struggle to remain awake, 24 hours of sleep deprivation has
been shown to impair neurobehavioral performance to an extent that is
comparable to a level of 0.10 percent blood alcohol content (19). In fact,
the duration of time it takes to react to a visual stimulus (simple
reaction time) averages three times longer after 24 hours of wakefulness than before an individual has stayed up all night (20) (Figure 2).
Moreover, this is when the risk of attentional failures—in which the
eyes begin rolling around in their sockets at the transition from wakefulness to sleep—is greatest. Within several days, chronic sleep restriction has been demonstrated to yield impairment in neurobehavioral
performance and a risk of attentional failures that increased to a level
comparable to that seen with acute total sleep deprivation (21,22). In
fact, six hours of time in bed per night for a week or two brings the
average young adult to the same level of impairment as 24 hours of
wakefulness, whereas 4 hours of time in bed per night gets there in
four to six days and induces a level of impairment comparable with 48
hours of wakefulness (i.e., two consecutive days and nights without
sleep) after 10 days of restriction. As with alcohol intoxication, chron-
RESIDENT WORK HOURS, SLEEP AND PATIENT SAFETY
163
FIG. 2. Laft-hand column: Time courses of core body temperature, endogenous
plasma melatonin, mean eye blink rate per 30-s epoch during Karolinska drowsiness test
(KDT), incidence of slow eye movements (SEMs, percentage of 30-s epochs containing at
least 1 SEM/5-min interval), and incidence of stage 1 sleep (% of 30-s epochs containing
at least 15 s of stage 1 sleep per 5-min interval) are shown, averaged across 10 subjects ⫾
SE. Right-hand column: Time course of subjective sleepiness as assessed on Karolinska
sleepiness scale (KSS; highest possible score ⫽ 9, lowest possible score ⫽ 1), psychomotor
vigilance performance [mean, median, 10% slowest and fastest reaction times in ms
(logarithmic scale)], cognitive performance (numbers of attempt in 4-min 2-digit addition
task), and memory performance (number of correct word pairs in probed recall memory
task) are shown averaged across 10 subjects ⫾ SE. All data were binned in 2-h intervals
and expressed with respect to elapsed time since scheduled waketime. Vertical reference
line indicates subject’s habitual bedtime. Reprinted with permission from Cajochen et al
(20). Copyright 1999 American Physiological Society.
ically sleep-deprived individuals tend to underestimate the extent to
which their performance is impaired, despite increasing impairment
evident in objective recordings of the rate of lapses of attention (23).
Objective measures of performance, including reaction time and memory, worsen. The effects of recurrent nights of sleep restriction are not
overcome with a single night of sleep. Increasing sleep deprivation
leads to an increased probability of experiencing lapses of attention,
164
CHARLES A. CZEISLER
episodes of automatic behavior and/or falling asleep while attempting
to remain awake. In a condition of chronic sleep deprivation, even
when wakefulness is scheduled during an appropriate circadian phase,
the probability of a sleep-related attentional failure or neurocognitive
performance failure while waking is markedly increased (23,24). Moreover, repeated interruptions of sleep, such as is experienced by physicians when they are on call, degrade the restorative quality of sleep
compared to an equal amount of consolidated sleep. This is thought to
be a primary basis for the excessive daytime sleepiness associated with
sleep disorder breathing, which induces many brief arousals during
the night. Interestingly, just being on call disturbs sleep, even when
the individual is not called (25,26). Dr. Marshall Wolf and I learned
this firsthand when recording the sleep of interns in a study that we
did with Dr. Gary Richardson and that Dr. Wolf presented to this
group fifteen years ago (27). As shown in Figure 3, the sleep of this
young intern was acutely disturbed while he was on call, with little
deep slow wave sleep and many awakenings that were not accounted
for by the two pages that were received. This intern remained awake
for almost an hour after being awakened by a page the second time.
FIG. 3. Polysomnographic recording of sleep in an intern on call. The figure depicts
the hypnogram and the effects of two pages during the night in an intern from the group
not covered by a night float. “Pager” indicates an electronically recorded page was issued
to the intern’s beeper at the time indicated on the X-axis. “Begin/End sleep period”
indicate the times recorded by the intern for these events in the diary. This record
demonstrates the variable impact of pages during sleep. The first page, from one of the
nursing stations, occurred at approximately 4.08 am. The page occurred while the intern
was in stage 4 and produced only a brief movement without unambiguous awakening.
Approximately 28 minutes later, the same nursing station paged again, this time
awakening the intern from REM sleep. The intern subsequently remained awake for
almost an hour despite no additional pager activity. Reprinted with permission from
Richardson et al (26). Copyright 1996 Associated Professional Sleep Societies, LLC.
RESIDENT WORK HOURS, SLEEP AND PATIENT SAFETY
165
The impact on the brain of resulting insufficient sleep is only beginning
to be appreciated. Positron Emission Tomography (PET) imaging has
revealed that sleep deprivation is associated with decreased metabolism in the thalamus, the pre-frontal cortex and the parietal cortex
(28). Metabolic studies have demonstrated that such sleep curtailment
also has adverse effects on the metabolic and immune systems.
Sleep Attacks and Sleep Drunkenness
Individuals struggling to stay awake in the face of elevated sleep
pressure—whether due to acute total sleep deprivation, chronic sleep
restriction or repeated interruption of sleep (due to external interruptions or the presence of a sleep disorder)—are not always able to do so
by the sheer force of will. Sleep deprivation greatly increases the risk
that an individual will succumb to the increased sleep pressure when
their brain initiates an involuntary transition from wakefulness to
sleep. This transition is initiated by the ventrolateral preoptic (VLPO)
area of the hypothalamus, which Saper et al. have identified as the
brain’s “sleep switch” (29). Another region of the hypothalamus, the
suprachiasmatic nucleus (SCN), which serves as the central neural
pacemaker of the circadian timing system, interacts with the VLPO
such that there are two times of day at which such an involuntary
transition from wakefulness to sleep is most probable: in the latter half
of the night near the habitual wake time and in the mid-afternoon. Of
course, once an individual has lost the struggle to stay awake and
makes the transition from wakefulness to sleep, driving performance is
much worse than that of a drunk driver, as the individual is unresponsive to the environment. Moreover, sometimes drowsy drivers linger in
an intermediate state between sleep and wakefulness. The operator of
a motor vehicle in this sleep-like condition—which probably represents
a transitional state in which part of the brain is asleep while part of the
brain remains awake—may maintain full pressure on the accelerator
pedal and proceed for a considerable distance, even negotiating gradual turns, but fail to heed stop signals or respond appropriately to
traffic conditions in a timely manner. This intermediate state, which
has been termed “automatic behavior syndrome” or “sleep drunkenness” is characterized by retention of the ability to turn the steering
wheel and to carry out rudimentary tasks and to provide semi-automatic responses to stimuli without appropriate cortical integration,
often resulting in a complete loss of situational awareness and judgment (30). Some of you may have experienced this state when you
suddenly realize that you have no idea how you went from point A to
point B on the expressway—as if there were a missing segment in the
166
CHARLES A. CZEISLER
video of life. One drowsy driver who steered his car toward an oncoming car and then tracked it as the other driver swerved to avoid him
reported “waking up” from this state just in time to observe vividly
through his windshield a terrified look on the face of the other driver
only a moment before he killed her in a head-on collision (31). A
similarly impaired NASA ground controller working in the Mission
Control Room of the Johnson Space Center during the middle of the
night shift sent a Space Shuttle careening into a spin while crew
members were asleep when he repeatedly overrode automatically generated coordinates designed to keep the shuttle on track.
Circadian Rhythmicity
Circadian rhythms, i.e., biological rhythms oscillating with an approximate period of twenty-four hours (from the Latin words: circa—
about and dies—a day), are present at all levels of biological complexity
from unicellular organisms to humans. Circadian rhythms are endogenous (i.e., internally generated), self-sustaining oscillations; therefore, rhythmicity persists in the absence of periodic external time cues.
In humans, many physiological processes, including the body temperature cycle, endocrine patterns, renal and cardiac function, subjective
alertness, sleep-wake behavior and performance vary according to the
time of day (4,20,32–37). The circadian contribution to variations in
alertness and performance is generated by a light-sensitive circadian
pacemaker that also drives the circadian rhythms of core body temperature, plasma cortisol and plasma melatonin (5,38 –50). The endogenous circadian clock is a major determinant of the timing and internal
architecture of sleep in humans (5,6). Spontaneous sleep duration,
sleepiness, REM sleep propensity, and both the ability and the tendency to sleep vary markedly with circadian phase or biological time of
day and interact with a homeostatic process to regulate sleep propensity and daytime alertness and neurocognitive performance (7–10,51–
53). As noted above, deep within the brain, two bilaterally paired
clusters of hypothalamic neurons comprising the SCN of the hypothalamus act as the central neural pacemaker for the generation and/or
synchronization of circadian rhythms (54 – 60). This endogenous circadian pacemaker is a major determinant of daily variations in subjective alertness and cognitive performance (4,9,11,12,20,24,38). These
and other studies have shown that there is a prominent circadian
variation in objective and subjective measures of alertness, performance (psychomotor, vigilance, memory) and attention or ability to
concentrate, with a nadir in the latter half of the usual sleep time, just
before our usual wake time (Figure 2). Similarly, the peak drive for
RESIDENT WORK HOURS, SLEEP AND PATIENT SAFETY
167
waking emanating from the hypothalamic circadian pacemaker occurs
a couple of hours before our habitual bedtime. This paradoxical relationship between the output of the circadian pacemaker and the timing
of the sleep-wake cycle is thought to help consolidate sleep and wakefulness in humans (8). Thus, under ordinary circumstances as the
homeostatic drive for sleep increases throughout the 16-hour waking
day, the circadian pacemaker sends out a stronger and stronger drive
for waking during the latter half of the habitual waking day. Then,
near the peak of the circadian drive for waking, about 1–2 hours before
the habitual bedtime, the hormone melatonin is released. Activation of
melatonin receptors on the surface of human SCN neurons suppresses
the firing of those neurons. Since the SCN continues to oscillate with
a near-24-hour period in the absence of SCN neuronal firing, this
action of melatonin is thought to quiet the wake-promoting signal
emanating from the SCN, thereby allowing us to fall asleep at our
habitual hour. Similarly, the SCN sends out a strong drive promoting
sleep in the latter half of the night, which helps to consolidate sleep
once the pressure for deep slow-wave sleep is satiated in the first half
of the night. The latter half of the night is richest in REM sleep, which
has a very prominent circadian rhythm in its propensity. When one
stays awake all night, in the latter half of the night near the habitual
wake time, elevated homeostatic drive for sleep interacts with the circadian peak of sleep propensity to create a critical zone of vulnerability.
In the absence of periodic time cues, the period of the human circadian pacemaker is slightly longer than 24 hours (61,62). In order for
the biological clock to coordinate its function with the timing of events
in the external world that operates on a 24 hour schedule, daily
information from the environment must therefore reach the circadian
pacemaker. The circadian pacemaker is essentially reset by a small
amount each day by this external stimulus in order to maintain synchrony with the 24-hour day (5,40,61).
Light is the principal environmental synchronizer of the mammalian
SCN. The SCN is connected to specialized intrinsically photosensitive
retinal ganglion cells containing the newly discovered photopigment
melanopsin via a monosynaptic pathway called the retinohypothalamic tract (RHT), the presumed conduit by which information from
the external light-dark cycle reaches the circadian clock. Properly
timed exposure to light and darkness can rapidly shift the phase of the
endogenous circadian pacemaker in humans (34,38 –50,63,64). Both
the magnitude and direction of the phase shifts induced by light are
dependent on the timing, duration, intensity and wavelength of the
light exposure (39,40,46 – 49,64 –70). On average, light exposure occur-
168
CHARLES A. CZEISLER
ring during the first half of the biological night resets the circadian clock
to a later hour; light received in the latter half of the biological night
resets the circadian clock to an earlier hour. Thus, the circadian pacemaker of an individual living on a conventional schedule of day work and
night sleep is synchronized by the naturally occurring light- dark cycle to
oscillate at the same period as the Earth’s solar day, i.e., 24 hours.
Sleep Inertia
Fifty years ago, following a crash inquiry, scientists in the U. S. Air
Force Laboratory discovered that performance is markedly degraded
during the transition from wakefulness to sleep (71– 83). The extent to
which this phenomenon, now called sleep inertia, interferes with neurobehavioral performance is related to the depth of the prior sleep
episode (78). Thus, agents that interfere with sleep, such as caffeine,
can mute the effect of sleep inertia (84). Remarkably, as we recently
reported, the adverse impact of sleep inertia on performance can far
exceed the impact of total sleep deprivation (83) (Figure 4). Once
residents are able to get to sleep, these house officers—who are often
subjected to acute total sleep deprivation after days, weeks or months
of chronic sleep restriction— often experience very deep sleep. When
this occurs while residents are on call in the hospital, they may be
required to make critical care decisions or perform life-saving medical
FIG. 4. Impact of sleep inertia on cognitive performance upon awakening compared with
24 hours without sleep. Reprinted with permission from Wertz et al. (83). Copyright
2006 American Medical Association.
RESIDENT WORK HOURS, SLEEP AND PATIENT SAFETY
169
procedures in an impaired state due to profound sleep inertia (15,83).
Moreover, at times of night when they have the greatest patient care
responsibilities due to the lack of on-site faculty supervision, resident
physicians—who sleep on average just 2.6 hours while working 30hour extended duration “on-call” shifts (85)—are likely to descend
rapidly into deep stages 3 and 4 sleep during those two-hour naps, and
then attempt to care for patients in an impaired confusional state—
characterized by grogginess, disorientation in time or space, slowed
mentation and slowed speech—immediately upon awakening.
There are a number of other factors that can have an impact on
alertness and performance. These include the length of time on task,
the level of environmental stimulation, the level of physical activity,
posture, the level of task stimulation/novelty, and the use of pharmacologic agents with stimulant or hypnotic properties. Caffeine is the
most widely used drug in the world. In fact, coffee beans are the second
most widely traded commodity in the world, second only to oil. Caffeine
administration can reduce the adverse impact of misalignment of
circadian phase as well as increased homeostatic pressure on neurobehavioral performance (86). However, the dose and timing of administration is not always optimal. Specialty brand coffee, such as that
available from retail outlets such as Starbucks and Dunkin’ Donuts,
contain 3– 4 times as much caffeine per ounce as does home brewed
coffee. Super-size (e.g., 24 ounce) servings can thus contain more than
a gram of caffeine, as much caffeine as an entire 10-cup pot of homebrewed coffee. When taken in the morning, these large doses of caffeine
are being administered when sleep pressure is lowest, with levels
declining throughout the day. When taken in the evening, caffeine—
which has a 6- to 9-hour half life—may interfere with recovery sleep.
When used as a wake-promoting therapeutic, the minimum effective
dose of caffeine should be taken at the optimal time to help sustain
performance when adequate sleep cannot be obtained. However, neither caffeine nor other wake-promoting therapeutics are a substitute
for sleep. In fact, in a study of fatal-to-the-driver truck crashes, the
National Transportation Safety Board (NTSB) found that plasma caffeine levels were highest in drivers involved in fatigue-related crashes
(87). The NTSB interpreted high plasma caffeine data from those
drivers as indicating that the drivers were taking caffeine to try to
combat their fatigue. Unfortunately, even high levels of caffeine were
insufficient to save those drivers from the effects of fatigue, which the
NTSB found to be the leading cause of fatal crashes in those trucker
drivers, equal to the fraction of crashes caused by both drugs and
alcohol combined (87).
170
CHARLES A. CZEISLER
Underlying Medical Condition and Age
A number of medical conditions and/or the medications used to treat
those conditions are associated with increased sleep tendency, increased risk of lapses of attention and increased risk of sleep-related
accidents (88). These include primary sleep disorders, such as narcolepsy and sleep apnea, as well as sleep disturbance secondary to a
medical condition or its treatment. Obstructive sleep apnea patients,
for example, with an apnea/hypopnea index greater than 10, have a
6-fold increase in risk of traffic accidents (89). Age decreases the risk of
sleep-related lapses of attention at night; in fact, young people are at
the greatest risk of the hazards of sleep loss (90). Thus, at first blush,
one might hypothesize that senior staff rather than new trainees
should be assigned to work marathon overnight shifts. However, before
you hastily assign all extended duration night work to your chiefs of
service, I would caution you to recognize that as we get older, it
becomes more and more difficult to obtain the recovery sleep that is
needed following sleep deprivation. In fact, even when sleep deprived,
older people have a great deal of difficulty sleeping at an adverse
circadian phase (10,16,91).
Graduate Medical Education and Sleep
Extended duration work shifts, like many other features of graduate
medical education in the United States, were the product of the postgraduate medical education curriculum developed by William Steward
Halsted, M.D. Professor Halsted, who was Surgeon-in-Chief at the
Johns Hopkins Hospital, was internationally renowned for his innovations in medical education. He founded the surgical training program
at the Johns Hopkins Hospital in the 1890s, which served as a model
for postgraduate medical education. He required physicians-in-training to live in the hospital (they were quite literally residents) and
discouraged them from marrying so that they could devote themselves
to medicine (92). He required residents to be on a “q1” call schedule, i.e.
they were on call 362 of 365 days per year. He taught devotion to the
profession by example, working heroic hours with his trainees. Only
recently was it revealed how he maintained this grueling sleep-deprived schedule. Professor Halsted was in fact addicted to cocaine, an
addiction that was an unfortunate by-product of his pioneering work
developing cocaine as a surgical anesthetic (93). He spent more than a
year in a rehabilitation program at a Rhode Island hospital trying to
shed his cocaine addiction prior to his appointment as the first Professor of Surgery at Johns Hopkins Medical School. However he only
RESIDENT WORK HOURS, SLEEP AND PATIENT SAFETY
171
gained an addiction to morphine there, which had been used to treat
his cocaine addiction (93).
Today, the use of powerful stimulants to allow personnel to remain
awake during extended duration work shifts is restricted to certain
branches of the military, such as the United States Air Force, which
still distributes methamphetamine routinely to pilots required to fly
lengthy missions and to other critical military personnel. Of course,
neither medical school faculty nor their hospital trainees are allowed
to use cocaine or methamphetamine to stay awake for long hours, nor
should they be allowed to do so. Yet, based on a 19th century tradition
dated to the time of Halsted, academic medical centers continue to
single out physicians-in-training as the only group of hospital employees who are required to work for 30 consecutive hours and to work
more than double the standard work week. Using a validated survey
instrument, we found that in 2002–2003, half of the interns we studied
worked more than 80 hours per week, with 11% working more than
100 hours per week (Figure 5). Some were required to work more than
120 hours per week (85), which is remarkable given that there are only
168 hours in a week. During that year, we estimate that physiciansin-training worked 20,000 shifts in the United States that exceeded 40
consecutive hours, with about 2,000 shifts exceeding 64 consecutive
FIG. 5. A total of 17,003 person-months of data were collected from a nationwide
sample during 2002–2003. The distribution of the percentages of reported weeks with a
given range of work hours is shown in this chart. Reprinted with permission from Barger
et al (85). Copyright 2005 Massachusetts Medical Society.
172
CHARLES A. CZEISLER
hours (85) (Figure 6). Theoretically, the work-hour reforms instituted
by the Accreditation Council of Graduate Medical Education (ACGME)
in 2003 should have reduced the duration of the longest of these shifts
to 30 consecutive hours, although there has been no independent
FIG. 6. The longest shifts reported by participants are shown in the chart at the top.
The chart at the bottom shows the number of surveys in which participants reported
shifts that exceeded 40 hours. Reprinted with permission from Barger et al (85). Copyright 2005 Massachusetts Medical Society.
RESIDENT WORK HOURS, SLEEP AND PATIENT SAFETY
173
verification that these voluntary guidelines are being consistently
enforced. Moreover, the new ACGME guidelines largely sanctioned
what was already the status quo in most hospitals, since interns
averaged 70.7 ⫾ 26.0 work hours per week (85) before the ACGME
instituted an 80- to 88-hour limit (averaged over four weeks) and the
average duration of the extended duration “on-call” shifts was 32.0 ⫾
3.7 hours before the ACGME instituted their limit of 30 consecutive
work hours per shift. On many of these marathon ⬃30-hour shifts, we
found that trainees obtained little or no sleep (85) (Figure 7). Even
among interns who spent the greatest amount of time in the hospital
per week, less than 5% of that time was spent sleeping (85) (Figure 8).
In fact, we found that interns averaged only 2.6 ⫾ 1.7h of sleep on
extended duration (⬎24-hour) work shifts, and that those who were
covered by night floats only obtained an additional half hour of sleep (85).
The recent discovery that memory consolidation and learning depends on the sleep obtained after training on a task has called into
question the wisdom of keeping residents awake all night as part of
their education (94 –98). In order to address the impact of such schedules on patient care, the Harvard Work Hours, Health and Safety
Group (HWHHSG) conducted a clinical trial for the Medical Intensive
Care (MICU) and the Coronary Care (CCU) Units at the Brigham and
Women’s Hospital in Boston (1, 99). Interns were randomly assigned to
work a three week rotation in the CCU or the MICU either on the
traditional “q3” schedule, in which they worked an extended duration
(⬃30 hour) work shift every other shift, or an intervention schedule in
which the 30-hour extended duration work shift was split in half such
that no scheduled work shift exceeded 16 consecutive hours. Dr. Steven
Lockley, Dr. Daniel Aeschbach and our colleagues in the HWHHSG
examined the relationship between work hours, sleep and the ability to
sustain attention in these trainees. We found that on the traditional
schedule, 85% of all work hours occurred on extended duration (⬎24h)
work shifts, whereas none of their work time was spent on extended
duration shifts on the intervention schedule (1) (Figure 9). Moreover,
on the traditional schedule, interns were twice as likely to have slept
less than 2 hours in the 24 hours prior to each hour worked, whereas
on the intervention schedule, they were twice as likely to have obtained at least 8 hours of sleep in the prior 24 hours (1). We found that
the interns worked fewer hours and slept more hours per week on the
interventional schedule, and that there was a negative correlation
between hours worked and hours slept (1) (Figure 10). We found that
interns working extended duration shifts were twice as likely to expe-
174
CHARLES A. CZEISLER
FIG. 7. The greatest number of hours without sleep as a percentage of monthly
reports is shown in the chart at the top. The chart at the bottom shows the number of
surveys in which participants reported more than 40 continuous hours without sleep.
Reprinted with permission from Barger et al (85). Copyright 2005 Massachusetts Medical
Society.
RESIDENT WORK HOURS, SLEEP AND PATIENT SAFETY
175
FIG. 8. This chart shows the average number of hours that interns spent asleep in the
hospital, awake in the hospital, studying or working in relation to their program but
outside the hospital, and working outside of the program. T bars indicate standard
deviations. Interns reported spending an average of 193.4 ⫾ 88.8 of their waking hours
in the hospital each month participating in direct patient care (e.g., examining patients;
writing progress notes; interpreting diagnostic tests, radiographic studies, and pathological specimens; and consulting with other physicians), 43.3 ⫾ 47.0 hours in duties not
directly related to patient care (e.g., completing other paperwork and scheduling tests),
23.5 ⫾ 20.1 hours in structured learning sessions (including classes, laboratories, and
grand rounds), and 7.3 ⫾ 16.4 hours teaching students or house staff. Reprinted with
permission from Barger et al (85). Copyright 2005 Massachusetts Medical Society.
rience attentional failures while working at night than were interns
scheduled to work no more than 16 consecutive hours (1) (Figure 11).
But what about patient care? Prior research at the Brigham and
Women’s Hospital had found that discontinuity in patient care (patient
handoffs) increased the risk of preventable adverse events (100), although this increase could be eliminated by use of a computerized sign
out system (101). Reduction in the duration of extended work shifts by
half would necessarily double the number of required handoffs of care.
Thus, we wondered which was safer for the patient, a tired intern who
remained with the patient throughout the night after admission, or a
better-rested intern to whom care of the patient was transferred. In
order to answer that question, we teamed up with the Patient Safety
Center for Excellence led by Dr. David Bates at the Brigham and
Women’s Hospital and obtained research support for a study from the
Agency for Healthcare Research and Quality and the National Insti-
176
CHARLES A. CZEISLER
FIG. 9. Proportion of total work hours plotted against the duration of the shift during
the Traditional Schedule (top chart) and the Intervention Schedule (bottom chart).
Reprinted with permission from Lockley et al (1). Copyright 2004 Massachusetts Medical Society.
tute for Occupational Safety and Health. Dr. Christopher Landrigan,
Dr. Jeffrey Rothschild and our colleagues in the HWHHSG then hired
a team of physicians to monitor these interns around the clock while
they worked in the MICU and CCU (99). In addition, we hired research
nurses to review the medical records of their patients and search for
medical errors. Finally, we presented all events noted by these observers to a panel of reviewers who were blind to condition and rated each
event. Only serious medical errors were analyzed.
Interns working extended duration “on call” shifts made 35.9% more
serious medical errors, including more than 5 times as many serious
diagnostic mistakes, as interns scheduled to work no more than 16
RESIDENT WORK HOURS, SLEEP AND PATIENT SAFETY
177
FIG. 10. Subjective mean hours of work per week (top left), duration of sleep (top
right), and the relationship between the duration of work and the duration of sleep
(bottom chart) for 20 interns during the Traditional schedule and the Intervention
schedule (open symbols). Reprinted with permission from Lockley et al (1). Copyright
2004 Massachusetts Medical Society.
consecutive hours (99). We found that interns working extended duration shifts made more serious mistakes that reached the patients than
those who worked shorter shifts, notwithstanding the fact that there
were twice as many handoffs of patient care with the intervention
schedule (99). We found that most of the serious medical errors were
due to slips and lapses, i.e., failures to carry out intended plans of
action, rather than knowledge-based mistakes (105).
In a companion nationwide survey study supported by the National
Institute of Occupational Safety and Health, Dr. Laura Barger, Dr.
Najib Ayas and our colleagues in the Harvard Work Hours, Sleep and
Safety Group evaluated the impact of extended duration work shifts on
178
CHARLES A. CZEISLER
FIG. 11. Mean (⫹SE) number of attentional failures among the 20 interns as a group
and individually while working overnight (11 pm to 7 am) during the Traditional
schedule (filled bar) and the Intervention schedule (open bar). Reprinted with permission from Lockley et al (1). Copyright 2004 Massachusetts Medical Society.
the risk of motor vehicle crashes among interns. We gathered 1,417
person-years of monthly survey data from 2,737 interns nationwide in
2002–2003. During that time, interns reported 320 motor vehicle
crashes. Eighty-two percent of those crashes were documented by a
police report, insurance claim, automobile repair record, medical
record, photograph of the damaged vehicle or a written description of
the motor vehicle crash. More than forty percent of the motor vehicle
crashes were judged to be consequential, i.e., leading to treatment in
an emergency department, more than one thousand dollars property
damage or filing of a police report. No additional motor vehicle crashes
were identified by a search of the Social Security Death Index or
through participant’s emergency contacts.
In a prospective analysis of scheduled shifts (across individuals), we
found that for each extended duration work shift scheduled per month,
interns had an 8.8 percent (CI: 3.2%–14.4%) increased monthly risk of
any reported motor vehicle crash, and a 16% (95% CI: 7.6% to 24.4%)
increased monthly risk of a reported motor vehicle crash on the commute from work. Trainees who work 10 extended duration shifts per
month on a “q3” schedule would thus have a 160% increased monthly
risk of a reported motor vehicle crash on the commute from work. In a
separate case-controlled analysis of the same data set, we found that
the odds ratio for reporting a motor vehicle crash during the commute
RESIDENT WORK HOURS, SLEEP AND PATIENT SAFETY
179
from the hospital was 2.3 times (95% CI: 1.6 to 3.3) greater after an
extended duration (⬎24h) work shift than after a non-extended work
shift (85). The odds ratio for reporting a near miss crash was 5.9 (95%
CI: 5.4 to 6.3) during the commute from work after an extended
duration work shift as compared to the commute from a non-extended
duration work shift (85).
Overall, based on this work, we found that the traditional practice of
scheduling interns very long work weeks and extended duration work
shifts was hazardous both to the intern themselves as well as to their
patients (106). For this reason, the Sleep Research Society (SRS) which
represents more than a thousand sleep scientists in the United States,
together with the National Sleep Foundation (NSF) in Washington
have endorsed legislation in Massachusetts that would limit resident
work hours. This legislation is sponsored by Massachusetts State
Senator Richard Moore, who requested guidance from the SRS regarding establishment of safer work hours for medical and surgical trainees. Table 1 illustrates the features of the pending legislation. Of note,
the SRS and NSF recommend that all physicians be required to notify
their patients and receive permission from the patients before caring
for them if the physician has slept less than 2 hours in the prior 24
hours. In fact, a nationwide NSF poll found that 86 percent of people
would feel anxious about their safety if they learned that their surTABLE 1
Pending Massachusetts Legislation endorsed by Sleep Research Society and National Sleep
Foundation
Schedule Feature
Proposed Directive
Weekly Work Hours
Optimal maximum: 60 hours per week
Fixed limit: 80 hours in any week
Consecutive Work Hours
Optimal maximum of 10 consecutive hours
Fixed maximum of 18 consecutive hours
Maximal frequency of 18-hour
night shifts
No more than one 18-hour overnight shift
every 3 days
Minimum Hours Off per Day
- after 10-hour shift
Minimum Hours Off
- Optimum ⱖ12 consecutive hours off/day;
minimum of 10 hours off per day
- Minimum of 16 consecutive hours off/day
- after ⱖ18-hour shift
High-intensity settings
Optimal limits required
Patient notification
Caring physician awake 22 of prior 24 hours
Consecutive Hours Off Duty
per Week
Optimum ⱖ48 consecutive hours off/week
Minimum 36 consecutive hours off/week,
including two consecutive nights weekly.
Minimum of 60 consecutive hours off duty
each month.
180
CHARLES A. CZEISLER
geons had been on duty more than 24 hours, and 70% would likely ask
for a different doctor (102). Given the findings that I have reported to
you today, the SRS and NSF have concluded that a patient has the
right to know if his/her physician were sleep deprived, so that the
patient can decide whether or not be treated by that physician.
Probable Cause of Sleep-related Crash in Case A.F.
As shown in the initial case I presented today, there are many
pathways that can lead physicians to become sleep deprived. The
practice of scheduling physicians to be on call for weeks at a time
covering busy services from home may seem innocuous compared to
the practice of requiring physicians-in-training to work 30 consecutive
hours. However, both sleep curtailment and frequent interruptions of
sleep, alone or in combination as in this case, can lead to chronic
cumulative sleep deprivation that can severely degrade performance
and increase the risk of harm or injury. Case A.F. fell asleep at the
wheel and crashed into a car with a 5-year old passenger after having
been awake for only 10 hours, but he had been averaging only 5.8
hours per night of interrupted on-call sleep, and had worked seven
consecutive days without a day off. The crash occurred in the midafternoon nap zone, which made him more vulnerable to the impact of
sleep deprivation. In addition to behaviorally induced insufficient sleep
syndrome, the trainee suffered from positional sleep-related breathing
disorder. Taken together, this crash was certainly not an accident. A
comprehensive fatigue management program that includes education
regarding the principles of sleep and circadian physiology, implementation of safer policies regarding work hours (such as the limits endorsed by the SRS and NSF), and a comprehensive program to screen
for sleep disorders would greatly reduce the risk of sleep-related errors
and accidents like this one. Like alcohol-related crashes, sleep-related
motor vehicle crashes are a preventable cause of injury. The National
Highway Transportation Safety Administration estimates that there
are more than 250,000 drowsy driver crashes annually; the Institute of
Medicine estimates that drowsy driver crashes account for 20 percent
of all injuries in motor vehicle crashes (107). With approximately
100,000 residents in training nationwide, steps should be taken to
eliminate this preventable cause of injury.
Legal, Moral and Ethical Considerations
Given that drivers in the United States (Colorado, Massachusetts,
Michigan and Florida) and Britain have been convicted of driving when
impaired by sleepiness, and that the State of New Jersey has recently
RESIDENT WORK HOURS, SLEEP AND PATIENT SAFETY
181
amended its vehicular homicide statute to add driving after 24 hours
without sleep to the definition of “reckless,” the legal and ethical question
is raised as to who should be held responsible for the next motor vehicle
crash in which a sleep-deprived resident kills or maims another motorist
or pedestrian. No one falls asleep at the wheel without having struggled
to stay awake beforehand, so the driver certainly bears legal and moral
responsibility just as a drunk driver would. However, institutions that
have put their trainees in harm’s way by requiring them to work for so
many consecutive hours that they are virtually incapacitated by sleep
deprivation cannot reasonably walk away from their responsibility to
care for those who have been injured by sleep-deprived trainees. Take for
example the case of Dr. Sook Im Hong. Dr. Hong was in the second week
of her internship at Rush-Presbyterian-St. Luke’s Medical Center in
Chicago when she fell asleep at the wheel after a 36-hour hospital shift
and rear-ended another car, causing massive brain injuries to Heather
Brewster (103). It is shocking to me that Rush Medical Center Attorney
George F. Galland, Jr. succeeded in arguing that under Illinois law, the
institution that required Dr. Hong to work for 36 consecutive hours does
not bear any responsibility for the lifelong care of Ms. Brewster, a former
college volleyball star who was a graduate student in physical therapy at
the time of the crash. By arguing, on one hand, that the intern alone
bears responsibility for sleep-related errors and accidents, and by requiring, on the other hand, that interns work 30-hour shifts as a condition of
their employment, interns are being put in a “Catch 22” bind while they
are at work. Moreover, given that appeals courts in two states (Oregon
and West Virginia) have ruled that an employer’s responsibility for
fatigue-related crashes can continue even after they have left work—
similar in concept to the dramshop tort liability incurred by establishments serving alcohol to drivers subsequently involved in alcohol-related
motor vehicle crashes—it is likely that courts will eventually hold hospitals that require trainees to work extended duration work shifts, notwithstanding evidence of the hazards of this practice, similarly liable.
What about the trainees’ physicians? In California, physicians have an
obligation to report to the Department of Motor Vehicles patients with
conditions characterized by lapses of consciousness. Given that the interns working traditional 30-hour shifts in our study averaged more than
five lapses of attention per night (99), do California physicians therefore
have an obligation to report all house staff with behaviorally induced
insufficient sleep syndrome under their care to the California Department
of Motor Vehicles? All these questions will be left for the courts to decide.
But let us move beyond the legal questions. What moral or ethical
responsibility should be borne by the program director who required a
182
CHARLES A. CZEISLER
trainee to work an extended duration shift that resulted in such an
accident? What about the department chair or hospital president who
requires or allows the program director to do so, knowing that such
schedules increase the risk of motor vehicle crashes by more than
160%? Does the ACGME bear responsibility for continuing to sanction
extended duration work shifts in the face of evidence that has revealed
the hazards of such shifts? In my view, too many trainees on the
thresholds of a medical career have already been killed or seriously
injured in sleep-related crashes— or have killed or seriously injured
others in sleep-related crashes—while attempting to commute home
after working extended duration shifts. Even Professor Halsted never
envisioned one of his charges getting behind the wheel of a car and
attempting to drive at a speed of 60 miles per hour after working for 30
consecutive hours. These marathon work shifts are a vestige of a
bygone era in which the pace of the hospital was much slower at night.
There were no intensive care units in 19th century hospitals. There
were no all night hospital laboratories. Resident physicians were not
routinely expected to stay up all night admitting patients who had
been kept in a holding area of the Emergency Department until the
late evening. Hospitals today are round-the-clock operations focused
on reducing patient length of stay by admitting patients only during
the most acute phase of their illnesses. The work schedules to which
our trainees are scheduled must now be changed to recognize that
trainees can no longer sleep in the hospital. Moreover, resident physicians are now allowed to leave the hospital, live in the community
and raise families. Our institutional training practices must therefore
allow our trainees to take on these additional responsibilities during
their training without endangering themselves, their families or others. Given the dictum “Physician, do no harm,” I would urge you as the
leaders of American medicine to implement policies that eliminate the
practice of scheduling trainees to work extended duration shifts. In
the meantime, until this practice has been eliminated, our data indicate that institutions have an obligation—at the very least—to provide
round trip transportation to trainees who are required to work extended duration shifts, as it is unsafe to expect or even allow them to
drive with inadequate sleep. For this reason, the SRS, NSF and American Academy of Sleep Medicine have recently endorsed model drowsy
driver legislation in Massachusetts. Of course, provision of transportation for trainees after extended duration work shifts begs the question as to whether it is appropriate for physicians who are too tired to
drive home from work to be caring for patients (104).
RESIDENT WORK HOURS, SLEEP AND PATIENT SAFETY
183
Summary
The work schedules of physicians in training require them to work
extraordinarily long work shifts and long work weeks. These schedules, which are based on a tradition that dates back to the 19th century,
result in acute and chronic sleep deprivation. Sleep deprivation, misalignment of circadian phase and sleep inertia adversely impact cognitive performance and increase the risk of error and accident. Interns
working extended duration shifts make significantly more serious
medical errors while caring for patients in intensive care units, and
make five times as many serious diagnostic mistakes. In addition to
the deleterious effects of extended duration work shifts on patient
safety, we also found that the risk of motor vehicle crashes is more
than doubled driving home from work after such shifts. We conclude
that the practice of working extended duration work shifts, which
continues to be allowed by new ACGME regulations, are hazardous to
both interns and their patients. Academic medical centers are urged to
eliminate this now-dangerous tradition.
ACKNOWLEDGMENTS
Supported by grants from the National Institute for Occupational Safety and Health
(1 R01 OH07567), which provided a certificate of confidentiality for data protection, and
by the Agency for Healthcare Research and Quality (R01 HS12032 and F32 HS14130);
Brigham and Women’s Hospital General Clinical Research Center supported by the
National Center for Research Resources (M01 RR02635); National Heart, Lung, and
Blood Institute fellowships in the Program and Training in Sleep, Circadian, and
Respiratory Neurobiology at Brigham and Women’s Hospital (T32 HL-79010); Wellcome
Trust, United Kingdom (060018/B/99/Z); Canadian Institutes of Health research/British
Columbia Lung Association. Dr. Czeisler is supported in part by the National Space
Biomedical Research Institute through the National Aeronautics and Space Administration (NCC9-58).
Special thanks to collaborators Steven W. Lockley, PhD, Christopher P. Landrigan,
MD, MPH, Laura K. Barger, PhD, Najib T. Ayas, MD, MPH, Jeffrey M. Rothschild, MD,
David W. Bates, MD, Bernard Rosner, PhD, Frank E. Speizer, MD, Joel T. Katz, MD,
Craig M. Lilly, MD, Peter H. Stone, MD, Daniel Aeschbach, PhD, John W. Cronin,
MD, Erin E. Evans, RPSGT, Brian E. Cade, MS, Clark J. Lee, JD, Elisabeth Burdick, MS
and Rainu Kaushal, MD, MPH. I am indebted to the interns who took time from their
busy work schedules to participate in this study; the National Resident Matching
Program and the Association of American Medical Colleges (especially Jordan J. Cohen,
MD, Paul Jolly, PhD) for providing access to the interns; DeWitt C. Baldwin, Jr., MD,
Steven R. Daugherty, PhD and Steven K. Howard, MD for their advice in the design of
these studies;Victor J. Dzau, MD, Anthony D. Whittemore, MD, Jeffrey Otten, Matthew
Van Vranken, Gary L. Gottlieb, MD, MBA, and Joseph B. Martin, MD, PhD, for their
support and encouragement of this work.
184
CHARLES A. CZEISLER
REFERENCES
1. Lockley SW, Cronin JW, Evans EE et al. Effect of reducing interns’ weekly work hours
on sleep and attentional failures. N Engl J Med 2004; 351:1829 –1837.
2. Jewett ME. Models of circadian and homeostatic regulation of human performance and
alertness. Harvard University, 1997.
3. Jewett ME, Borbély AA, Czeisler CA. Proceedings of the workshop on biomathematical
models of circadian rhythmicity, sleep regulations, and neurobehavioral function in
humans. J Biol Rhythms 1999; 14:429 – 630.
4. Johnson MP, Duffy JF, Dijk DJ, Ronda JM, Dyal CM, Czeisler CA. Short-term memory,
alertness and performance: A reappraisal of their relationship to body temperature. J
Sleep Res 1992; 1:24 –29.
5. Czeisler CA, Khalsa SBS. The human circadian timing system and sleep-wake regulation. In: Kryger MH, Roth T, Dement WC, editors. Principles and Practice of Sleep
Medicine. Philadelphia: W.B. Saunders Company, 2000: 353–374.
6. Czeisler CA, Dijk DJ. Human circadian physiology and sleep-wake regulation. In: Takahashi JS, Turek FW, Moore RY, editors. Handbook of Behavioral Neurobiology: Circadian Clocks. New York: Plenum Publishing Co., 2001: 531–569.
7. Dijk DJ, Czeisler CA. Contribution of the circadian pacemaker and the sleep homeostat
to sleep propensity, sleep structure, electroencephalographic slow waves, and sleep
spindle activity in humans. J Neurosci 1995; 15:3526 –3538.
8. Dijk DJ, Czeisler CA. Paradoxical timing of the circadian rhythm of sleep propensity
serves to consolidate sleep and wakefulness in humans. Neurosci Lett 1994; 166:63– 68.
9. Wyatt JK, Ritz-De Cecco A, Czeisler CA, Dijk DJ. Circadian temperature and melatonin
rhythms, sleep, and neurobehavioral function in humans living on a 20-h day. Am J
Physiol 1999; 277:R1152–R1163.
10. Dijk DJ, Duffy JF, Riel E, Shanahan TL, Czeisler CA. Ageing and the circadian and
homeostatic regulation of human sleep during forced desynchrony of rest, melatonin and
temperature rhythms. J Physiol 1999; 516.2:611– 627.
11. Dijk DJ, Duffy JF, Czeisler CA. Circadian and sleep/wake dependent aspects of subjective alertness and cognitive performance. J Sleep Res 1992; 1:112–117.
12. Czeisler CA, Dijk DJ, Duffy JF. Entrained phase of the circadian pacemaker serves to
stabilize alertness and performance throughout the habitual waking day. In: Ogilvie
RD, Harsh JR, editors. Sleep Onset: Normal and Abnormal Processes. Washington,
D.C.: American Psychological Association, 1994: 89 –110.
13. Klein T, Martens H, Dijk DJ, Kronauer RE, Seely EW, Czeisler CA. Chronic non-24hour circadian rhythm sleep disorder in a blind man with a regular 24-hour sleep-wake
schedule. Sleep 1993; 16:333–343.
14. Boivin DB, Czeisler CA, Dijk DJ et al. Complex interaction of the sleep-wake cycle and
circadian phase modulates mood in healthy subjects. Arch Gen Psychiatry 1997; 54:145–
152.
15. Jewett ME, Wyatt JK, Ritz-De Cecco A, Khalsa SB, Dijk DJ, Czeisler CA. Time course
of sleep inertia dissipation in human performance and alertness. J Sleep Res 1999;
8:1– 8.
16. Dijk DJ, Duffy JF, Czeisler CA. Contribution of circadian physiology and sleep homeostasis to age-related changes in human sleep. Chronobiol Int 2000; 17:285–311.
17. Wright Jr. KP, Hull JT, Czeisler CA. Relationship between alertness, performance, and
body temperature in humans. Am J Physiol Regul Integr Comp Physiol 2002;
289:R1370 –R1377.
18. Cajochen C, Wyatt JK, Czeisler CA, Dijk DJ. Separation of circadian and wake durationdependent modulation of EEG activation during wakefulness. Neuroscience 2002;
114:1047–1060.
19. Dawson D, Reid K. Fatigue, alcohol and performance impairment. Nature 1997;
RESIDENT WORK HOURS, SLEEP AND PATIENT SAFETY
185
388:235.
20. Cajochen C, Khalsa SBS, Wyatt JK, Czeisler CA, Dijk DJ. EEG and ocular correlates of
circadian melatonin phase and human performance decrements during sleep loss. Am J
Physiol 1999; 277:R640 –R649.
21. Van Dongen HP, Dinges D. Sleep debt and cumulative excess wakefulness. Sleep 2003;
26:249 –250.
22. Czeisler CA. Quantifying consequences of chronic sleep restriction. Sleep 2003; 26:247–
248.
23. van Dongen HPA, Maislin G, Mullington JM, Dinges DF. The cumulative cost of additional wakefulness: Dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation. Sleep 2003; 26:117–126.
24. Durmer JS, Dinges DF. Neurocognitive consequences of sleep deprivation. Semin Neurol 2005; 25:117–129.
25. Torsvall L, Åkerstedt T. Disturbed sleep while being on call: an EEG study of ships’
engineers. Sleep 1988; 11:35–38.
26. Richardson GS, Wyatt JK, Sullivan JP et al. Objective assessment of sleep and alertness
in medical house-staff and the impact of protected time for sleep. Sleep 1996; 19:718 –
726.
27. Wolf MA, Richardson GS, Czeisler CA. Improved Sleep: a means of reducing the stress
of internship. The transactions of the American Clinical and Climatological Association.
New York: Waverly Press, 1990: 255–231.
28. Thomas M, Sing H, Belenky G et al. Neural basis of alertness and cognitive performance
impairments during sleepiness. I. Effects of 24 h of sleep deprivation on waking human
regional brain activity. J Sleep Res 2000; 9:335–352.
29. Saper CB, Scammell TE, Lu J. Hypothalamic regulation of sleep and circadian rhythms.
Nature 2005; 437:1257–1263.
30. Guilleminault C, Phillips R, Dement WC. A syndrome of hypersomnia with automatic
behavior. Electroenceph Clin Neurophysiol 1975; 38:403– 413.
31. State of Florida v. Jorge Rosario. 2D04 – 4561. 2004. District Court of Appeal of Florida,
Second District.
32. Czeisler CA, Winkelman JW, Richardson GS. Disorders of sleep and circadian rhythms. In:
Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, editors. Harrison’s
Principles of Internal Medicine. New York: McGraw-Hill, Inc., 2000: 1–78.
33. Czeisler CA. Human circadian physiology: internal organization of temperature, sleepwake, and neuroendocrine rhythms monitored in an environment free of time cues.
Stanford University, 1978.
34. Allan JS, Czeisler CA. Persistence of the circadian thyrotropin rhythm under constant
conditions and after light-induced shifts of circadian phase. J Clin Endocrinol Metab
1994; 79:508 –512.
35. El Hajj Fuleihan G, Klerman EB, Brown EN, Choe Y, Brown EM, Czeisler CA. The
parathyroid hormone circadian rhythm is truly endogenous—a general clinical research
center study. J Clin Endocrinol Metab 1997; 82:281–286.
36. Waldstreicher J, Duffy JF, Brown EN, Rogacz S, Allan JS, Czeisler CA. Gender differences in the temporal organization of prolactin (PRL) secretion: evidence for a sleepindependent circadian rhythm of circulating PRL levels—a clinical research center
study. J Clin Endocrinol Metab 1996; 81:1483–1487.
37. Czeisler CA, Jewett ME. Human circadian physiology: Interaction of the behavioral rest—
activity cycle with the output of the endogenous circadian pacemaker. In: Thorpy MJ, editor.
Handbook of Sleep Disorders. New York: Marcel Dekker, Inc., 1990: 117–137.
38. Czeisler CA, Johnson MP, Duffy JF, Brown EN, Ronda JM, Kronauer RE. Exposure to
bright light and darkness to treat physiologic maladaptation to night work. N Engl
J Med 1990; 322:1253–1259.
39. Czeisler CA. The effect of light on the human circadian pacemaker. In: Waterhouse JM,
186
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
58.
59.
60.
61.
CHARLES A. CZEISLER
editor. Circadian Clocks and Their Adjustment. Chichester (Ciba Found. Symp. 183):
John Wiley and Sons, Inc., 1995: 254 –302.
Czeisler CA, Wright Jr. KP. Influence of light on circadian rhythmicity in humans. In:
Turek FW, Zee PC, editors. New York: Marcel Dekker, Inc., 1999: 149 –180.
Czeisler CA, Kronauer RE, Allan JS et al. Bright light induction of strong (type 0)
resetting of the human circadian pacemaker. Science 1989; 244:1328 –1333.
Jewett ME, Kronauer RE, Czeisler CA. Light-induced suppression of endogenous circadian amplitude in humans. Nature 1991; 350:59 – 62.
Czeisler CA, Chiasera AJ, Duffy JF. Research on sleep, circadian rhythms and aging:
Applications to manned spaceflight. Exp Gerontol 1991; 26:217–232.
Shanahan TL, Czeisler CA. Light exposure induces equivalent phase shifts of the
endogenous circadian rhythms of circulating plasma melatonin and core body temperature in men. J Clin Endocrinol Metab 1991; 73:227–235.
Duffy JF, Kronauer RE, Czeisler CA. Phase-shifting human circadian rhythms: Influence
of sleep timing, social contact and light exposure. J Physiol (Lond) 1996; 495:289 –297.
Jewett ME, Kronauer RE, Czeisler CA. Phase-amplitude resetting of the human circadian pacemaker via bright light: A further analysis. J Biol Rhythms 1994; 9:295–314.
Jewett ME, Rimmer DW, Duffy JF, Klerman EB, Kronauer RE, Czeisler CA. Human
circadian pacemaker is sensitive to light throughout subjective day without evidence of
transients. Am J Physiol 1997; 273:R1800 –R1809.
Shanahan TL, Zeitzer JM, Czeisler CA. Resetting the melatonin rhythm with light in
humans. J Biol Rhythms 1997; 12:556 –567.
Boivin DB, Czeisler CA. Resetting of circadian melatonin and cortisol rhythms in humans by ordinary room light. Neuroreport 1998; 9:779 –782.
Shanahan TL, Kronauer RE, Duffy JF, Williams GH, Czeisler CA. Melatonin rhythm
observed throughout a three-cycle bright-light stimulus designed to reset the human
circadian pacemaker. J Biol Rhythms 1999; 14:237–253.
Czeisler CA, Weitzman ED, Moore-Ede MC, Zimmerman JC, Knauer RS. Human sleep: Its
duration and organization depend on its circadian phase. Science 1980; 210:1264 –1267.
Czeisler CA, Zimmerman JC, Ronda JM, Moore-Ede MC, Weitzman ED. Timing of REM
sleep is coupled to the circadian rhythm of body temperature in man. Sleep 1980;
2:329 –346.
Dijk DJ, Shanahan TL, Duffy JF, Ronda JM, Czeisler CA. Variation of electroencephalographic activity during non-rapid eye movement and rapid eye movement sleep with
phase of circadian melatonin rhythm in humans. J Physiol (Lond) 1997; 505.3:851– 858.
Ralph MR, Foster RG, Davis FC, Menaker M. Transplanted suprachiasmatic nucleus
determines circadian period. Science 247; 975–978. 1990.
Edgar DM, Dement WC, Fuller CA. Effect of SCN lesions on sleep in squirrel monkeys:
Evidence for opponent processes in sleep-wake regulation. J Neurosci 1993; 13:1065–1079.
Klein DC, Moore RY, Reppert SM. Suprachiasmatic nucleus: The mind’s clock. New
York: Oxford University Press, 1991.
Mumford GK, Benowitz NL, Evans SM et al. Absorption rate of methylxanthines following capsules, cola and chocolate. Eur J Clin Pharmacol 1996; 51:319 –325.
Weaver DR. The suprachiasmatic nucleus: A 25-year retrospective. J Biol Rhythms
1998; 13:100 –112.
Welsh DK, Logothetis DE, Meister M, Reppert SM. Individual neurons dissociated from
rat suprachiasmatic nucleus express independently phased circadian firing rhythms.
Neuron 1995; 14:697–706.
Moore RY. Organization of the mammalian circadian system. In: Waterhouse JM, editor. Circadian clocks and their adjustment. Chichester (Ciba Foundation Symp 183):
John Wiley and Sons, Inc., 1994: 88 –99.
Czeisler CA, Duffy JF, Shanahan TL et al. Stability, precision, and near-24-hour period
of the human circadian pacemaker. Science 1999; 284:2177–2181.
RESIDENT WORK HOURS, SLEEP AND PATIENT SAFETY
187
62. Wright Jr. KP, Hughes RJ, Kronauer RE, Dijk DJ, Czeisler CA. Intrinsic near-24-h
pacemaker period determines limits of circadian entrainment to a weak synchronizer in
humans. Proc Natl Acad Sci USA 2001; 98:14027–14032.
63. Czeisler CA, Allan JS, Strogatz SH et al. Bright light resets the human circadian pacemaker independent of the timing of the sleep-wake cycle. Science 1986; 233:667– 671.
64. Khalsa SBS, Jewett ME, Cajochen C, Czeisler CA. A phase response curve to single
bright light pulses in human subjects. J Physiol 2003; 549(Pt 3):945–952.
65. Boivin DB, Duffy JF, Kronauer RE, Czeisler CA. Sensitivity of the human circadian
pacemaker to moderately bright light. J Biol Rhythms 1994; 9:315–331.
66. Boivin DB, Duffy JF, Kronauer RE, Czeisler CA. Dose-response relationships for resetting of human circadian clock by light. Nature 1996; 379:540 –542.
67. Zeitzer JM, Dijk DJ, Kronauer RE, Brown EN, Czeisler CA. Sensitivity of the human
circadian pacemaker to nocturnal light: Melatonin phase resetting and suppression.
J Physiol (Lond) 2000; 526:695–702.
68. Shanahan TL, Czeisler CA. Physiological effects of light on the human circadian pacemaker. Seminars in Perinatology 2000; 24:299 –320.
69. Klerman EB, Shanahan TL, Brotman DJ et al. Photic resetting of the human circadian
pacemaker in the absence of conscious vision. J Biol Rhythms 2002; 17:548 –555.
70. Lockley SW, Brainard GC, Czeisler CA. High sensitivity of the human circadian melatonin rhythm to resetting by short wavelength light. J Clin Endocrinol Metab 2003;
88:4502– 4505.
71. Langdon DE, Hartman B. Performance upon sudden awakening. School of Aerospace
Medicine 1961; 62–17:1– 8.
72. Hartman BO, Langdon DE. A second study on performance upon sudden awakening.
TR-65– 61, 1–10. 1965. Brooks AFB, TX, U.S. Air Force.
73. Hartman BO, Langdon DE, McKenzie RE. A third study on performance upon sudden
awakening. TR-65– 63, 1– 4, 1965. Brooks, TX, U.S. Air Force.
74. Koulack D, Schultz KJ. Task performance after awakenings from different stages of
sleep. Percept Mot Skills 1974; 39:792–794.
75. Dinges DF, Orne MT, Orne EC. Assessing performance upon abrupt awakening from
naps during quasi-continuous operations. Behavior Research Methods, Instruments &
Computers 1985; 17:37– 45.
76. Balkin TJ, Badia P. Relationship between sleep inertia and sleepiness: Cumulative
effects of four nights of sleep disruption/restriction on performance following abrupt
nocturnal awakenings. Biol Psychol 1988; 27:245–258.
77. Balkin TJ, Braun AR, Wesensten NJ et al. The process of awakening: A PET study of
regional brain activity patterns mediating the re-establishment of alertness and consciousness. Brain 2002; 125:2308 –2319.
78. Dinges DF. Sleep Inertia. In: Carskadon MA, editor. Encyclopedia of Sleep and Dreaming. New York: Macmillillan Publishing Company, 1993: 553–554.
79. Ferrara M, De Gennaro L. The sleep inertia phenomenon during the sleep-wake transition: theoretical and operational issues. Aviat Space Environ Med 2000; 71:843– 848.
80. Bruck D, Pisani D. The effects of sleep inertia on decision-making performance. J Sleep
Res 1997; 8:95–103.
81. Achermann P, Werth E, Dijk DJ, Borbély AA. Time course of sleep inertia after nighttime and daytime sleep episodes. Archives Italiennes de Biologie 1995; 134:109 –119.
82. Naitoh P, Kelly T, Babkoff H. Sleep inertia: Best time not to wake up. Chronobiol Int
1993; 10:109 –118.
83. Wertz AT, Ronda JM, Czeisler CA, Wright KP, Jr. Effects of sleep inertia on cognition.
JAMA 2006; 295:163–164.
84. van Dongen HPA, Price NJ, Mullington JM, Szuba MP, Kapoor SC, Dinges DF. Caffeine
eliminates psychomotor vigilance deficits from sleep inertia. Sleep 2001; 24:813– 819.
85. Barger LK, Cade BE, Ayas NT et al. Extended work shifts and the risk of motor vehicle
188
CHARLES A. CZEISLER
crashes among interns. N Engl J Med 2005; 352:125–134.
86. Wyatt JK, Cajochen C, Ritz-De Cecco A, Czeisler CA, Dijk DJ. Low-dose, repeated
caffeine administration for circadian-phase-dependent performance degradation during
extended wakefulness. Sleep 2004; 27:374 –381.
87. National Transportation Safety Board. Safety Study: Fatigue, Alcohol, Other Drugs, and
Medical Factors in Fatal-to-the-Driver Heavy Truck Crashes (Volume 1). NTSB/SS-90/01,
1–181, 1990. Washington, DC, National Transportation Safety Board.
88. Carter N, Ulfberg J, Nystrom B, Edling C. Sleep debt, sleepiness and accidents among
males in the general population and male professional drivers. Accid Anal Prev 2003;
35:613– 617.
89. Teran-Santos J, Jimenez-Gomez A, Cordero-Guevara J. The association between sleep
apnea and the risk of traffic accidents. Cooperative Group Burgos-Santander. N Engl
J Med 1999; 340:847– 851.
90. Åkerstedt T, Czeisler CA, Dinges DF, Horne JA. Accidents and Sleepiness: A consensus
statement from the International Conference on Work Hours, Sleep and Accidents,
Stockholm, 8 –10 September 1994. J Sleep Res 1994; 3:195.
91. Dijk DJ, Duffy JF. Circadian regulation of human sleep and age-related changes in its
timing, consolidation and EEG characteristics. Ann Med 1999; 31:130 –140.
92. Farley P. Recreating the residency. Yale Medicine, 30 –36. 2004.
93. Markel H. The accidental addict. N Engl J Med 2005; 352:966 –968.
94. Stickgold R. Sleep-dependent memory consolidation. Nature 2005; 437:1272–1278.
95. Stickgold R, Scott L, Rittenhouse C, Hobson JA. Sleep-induced changes in associative
memory. J Cognitive Neurosci 1999; 11:182–193.
96. Stickgold R, Whidbee D, Schirmer B, Patel V, Hobson JA. Visual Discrimination task
improvement: A multi-step process occurring during sleep. J Cognitive Neurosci 2000;
12:246 –254
97. Stickgold R, James L, Hobson JA. Visual discrimination learning requires sleep after
training. Nat Neurosci 2000; 3:1237–1238.
98. Huber R, Ghilardi MF, Massimini M, Tononi G. Local sleep and learning. Nature 2004;
430:78 – 81.
99. Landrigan CP, Rothschild JM, Cronin JW et al. Effect of reducing interns’ work hours
on serious medical errors in Intensive Care Units. N Engl J Med 2004; 351:1838 –1848.
100. Petersen LA, Brennan TA, O’Neil AC, Cook EF, Lee TH. Does housestaff discontinuity
of care increase the risk for preventable adverse events? [see comments]. Ann Intern
Med 1994; 121:866 – 872.
101. Petersen LA, Orav EJ, Teich JM, O’Neil AC. Using a computerized sign-out program to
improve continuity of inpatient care and prevent adverse events. Joint Commission
Journal on Quality Improvement 1998; 24:77– 87.
102. National Sleep Foundation. Executive summary of the 2002 “Sleep in America” poll.
WB&A Market Research, editor. 1– 43. 2002. Washington, D.C., National Sleep Foundation. 4-2-2002.
103. Safety of Medical Residents’ Long Hours Questioned. Washington, D.C.: National Public
Radio, February 28, 2005. (Accessed March 25, 2006 at http://www.npr.org/templates/
story/story.php?storyId⫽4512366)
104. Hunt KE. Post-Call Accidents. N Engl J Med 2005; 352:1491.
105. Rothschild JM, Landrigan CP, Cronin JW et al. The critical care safety study: The
incidence and nature of adverse events and serious medical errors in intensive care. Crit
Care Med 2005; 33:1694 –1700.
106. Lee CJ. Federal regulation of hospital resident work hours: Enforcement with real
teeth. J Health Care Law and Policy, Univ Maryland, in press.
107. Institute of Medicine, Committee on Sleep Medicine and Research, Colten HR, Altevogt
BM (eds.). Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem.
The National Academies Press, Washington, D.C., 2006.
Medical and Genetic Differences in the Adverse Impact of Sleep Loss on Performance:
Ethical Considerations for the Medical Profession
Charles A. Czeisler, Ph.D., M.D., F.R.C.P.
Division of Sleep Medicine, Department of Medicine, Brigham and Women’s Hospital and
Division of Sleep Medicine, Harvard Medical School, Boston, MA.
Please address all correspondence and requests for reprints to:
Charles A. Czeisler, Ph.D., M.D., F.R.C.P.
Division of Sleep Medicine, Department of Medicine
Brigham and Women’s Hospital, Harvard Medical School
221 Longwood Avenue, Suite 438, Boston, MA 02115
Tel (617) 732-4013; Fax (617) 732-4015
[email protected]
Citation Format: Czeisler CA. Medical and Genetic Differences in the Adverse Impact of Sleep
Loss on Performance: Ethical Considerations for the Medical Profession. Trans Am Clin
Climatol Assoc 2009; in press.
© 2009 American Clinical and Climatological Association
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
Abstract
The Institute of Medicine recently concluded that–on average–medical residents make more
serious medical errors and have more motor vehicle crashes when they are deprived of sleep. In the
interest of public safety, society has required limitations on work hours in many other safety
sensitive occupations, including transportation and nuclear power generation. Those who argue in
favor of traditional extended duration resident work hours often suggest that there are interindividual differences in response to acute sleep loss or chronic sleep deprivation, implying that
physicians may be more resistant than the average person to the detrimental effects of sleep
deprivation on performance, although there is no evidence that physicians are particularly resistant
to such effects. Indeed, recent investigations have identified genetic polymorphisms that may
convey a relative resistance to the effects of prolonged wakefulness on a subset of the healthy
population, although there is no evidence that physicians are over-represented in this cohort.
Conversely, there are also genetic polymorphisms, sleep disorders and other inter-individual
differences that appear to convey an increased vulnerability to the performance-impairing effects of
24 hours of wakefulness. Given the magnitude of inter-individual differences in the effect of sleep
loss on cognitive performance, and the sizeable proportion of the population affected by sleep
disorders, hospitals face a number of ethical dilemmas. How should the work hours of physicians be
limited to protect patient safety optimally? For example, some have argued that, in contrast to other
professions, work schedules that repeatedly induce acute and chronic sleep loss are uniquely
essential to the training of physicians. If evidence were to prove this premise to be correct, how
should such training be ethically accomplished in the quartile of physicians and surgeons who are
most vulnerable to the effects of sleep loss on performance without unacceptably compromising
patient safety? Moreover, once it is possible to identify reliably those most vulnerable to the
adverse effects of sleep loss on performance, will academic medical centers have an obligation to
Page 2 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
evaluate the proficiency of both residents and staff physicians under conditions of acute and chronic
sleep deprivation? Should work-hour policy limits be modified to ensure that they are not
hazardous for the patients of the most vulnerable quartile of physicians, or should the limits be
personalized to enable the most resistant quartile to work longer hours? Given that the prevalence
of sleep disorders has increased in our society overall, and increases markedly with age, how should
fitness for extended duration work hours be monitored over a physician’s career? In the spirit of the
dictum to do no harm, advances in understanding the medical and genetic basis of inter-individual
differences in the performance vulnerability to sleep loss should be incorporated into the
development of work-hour policy limits for both physicians and surgeons.
Page 3 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
Introduction
After a comprehensive review of the medical and scientific literature as part of a year-long study
initiated at the behest of the United States Congress and supported by the Agency for Healthcare
Research and Quality, the Institute of Medicine (IOM) Committee on Optimizing Graduate Medical
Trainee (Resident) Hours and Work Schedules to Improve Patient Safety concluded this past year
that working for more than 16 consecutive hours without sleep is unsafe for both physicians in
training (residents) and their patients (1). This latest IOM report builds on earlier work by the IOM
Committee on Sleep Medicine and Research, which conducted an independent review of the
adverse effects of sleep loss on neurobehavioral performance, learning, cognition, health and safety
(2). The IOM recommendations are consistent with the recommendations promulgated by the
Association for American Medical Colleges (AAMC) in 2001 that resident physician work shifts be
limited to no more than 12 consecutive hours in all high intensity clinical settings, such as intensive
care units (ICUs) and emergency departments (3). Nearly forty years ago, it was recognized that—
on average—interns made twice as many mistakes detecting cardiac arrhythmias when they were
sleep deprived as compared to when they were more well rested (4). More recently, laparoscopic
surgical simulator studies have revealed that, on average, error rates doubled in residents when they
performed simulated surgery after a night on call as compared to when they were more well rested
(5) (Fig. 1). In a meta-analysis cited by the IOM, which was conducted by Accreditation Council on
Graduate Medical Education (ACGME) Senior Vice President of Field Activities, Dr. Ingrid
Philibert, she concluded that after 24-30 hours of sleep deprivation, individual cognitive
performance of the average person drops from the 50th to the 15th percentile of their performance
when rested (6), and that clinical performance of physicians drops from the 50th to the 7th percentile
of their performance when rested (6). There is also growing evidence that sleep plays an essential
role in learning and memory consolidation, and that chronic sleep deprivation has many deleterious
Page 4 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
health consequences, including an increased risk of obesity, diabetes, depression and cardiovascular
disease (2;7-15).
The conclusion that acute sleep loss impairs both cognitive and psychomotor performance and
increases the risk of error among healthy young adults in both laboratory evaluations (16;17) and in
clinical settings (18) is consistent with previously published laboratory research on participant
volunteers (2;19;20) and with the field data (21-26). As shown in Fig. 2, sleep deprivation
combined with misalignment of circadian phase creates a critical zone of vulnerability in the latter
half of the night (17). Paradoxically, instead of slowing down to preserve accuracy as reaction time
increases, sleep deprivation often leads people to make hasty decisions based on inadequate
information (27). This results in increased rates of errors on selective attention tasks that require a
search for targets in the visual field (27). 40% of interns working extended duration ‘on call’ shifts
slept less than 2 hours in a 30-hour interval, and more than 15% obtained less than 1 hour of sleep
during that interval (24) (Fig. 3). Residents randomized to work extended duration (>24 hour) shifts
experienced twice as many attentional failures (22) and—on average—made 36% more serious
errors caring for patients in intensive care units, including 460% more serious diagnostic mistakes,
as compared to the same physicians when they were scheduled to work no more than 16
consecutive hours in intensive care units (23). Nationwide, interns have a 168% increased risk of a
motor vehicle crash driving home from extended duration (>24-hour) shifts (24) and were 73%
more likely to suffer from a percutaneous injury when performing a procedure after their 20th hour
of work than during shifts that averaged less than 12 hours in duration (26).
On average, after being awake for 24 hours, impairment on a simple reaction time test in
individuals who remain awake during testing is comparable with the impairment observed at a
blood alcohol concentration of 0.10 g/dL (17;28). In a survey of 2,737 resident physicians, our
group found that one out of five first-year residents reported making a fatigue-related mistake that
Page 5 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
injured a patient, and one out of twenty first-year residents reported making a fatigue-related
mistake that resulted in the death of a patient (25). In months when interns worked more than 5
extended duration (>24-hour) work shifts, the risks of such fatigue-related injuries and deaths
increased by 700 and 300%, respectively.
Many within and outside the profession of medicine have hailed the IOM report as a longoverdue acknowledgement by the medical profession of the dangers of an obviously hazardous
tradition (29). Yet, many conscientious physicians and surgeons argue vehemently that working for
24 consecutive hours is safe and that working such long hours is essential for the training of
physicians and inherent in the practice of medicine (30;31). What might be fueling such a
passionate difference of opinion?
Wherever I have presented data on the average impact of sleep loss on performance, the most
common question that I have been asked is about inter-individual differences. “Aren’t some people
more resistant to the effects of sleep loss than others?” The follow-up comments by such
questioners usually reveals an underlying premise that individuals in certain professions (e.g., police
officers, fire fighters, physicians, surgeons, aviators, special forces, astronauts) may be more
resistant than the average person to the effects of acute sleep loss or chronic sleep restriction on
performance. In fact, even among healthy young adults, there are profound inter-individual
differences in the impact of sleep loss on performance (2;32-38). In addition, healthy sleepers are
likely to be much more resistant to the effects of sleep loss than the 50 to 70 million Americans who
suffer from chronic disorders of sleep and wakefulness (2). In this paper, I will review the evidence
for such differences and address the ethical implications of such diversity both for residents and for
practicing physicians.
Page 6 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
Inter-individual differences in tolerance to sleep loss in healthy young adults
Differences in vulnerability to sleep loss due to prior sleep-wake history. The ability to sustain
attention, maintain cognitive performance and prevent attentional failures deteriorates when sleep is
chronically restricted to 7 or fewer hours per night for a week or longer (2;39-41) (Fig. 4). Many
habitually short sleepers may be harboring substantial sleep debt, as reflected by higher sleep
tendency, suggesting that their habitually short sleep durations may not reflect a reduced underlying
sleep need (42;43). Long work weeks together with commuting time often require others, who are
not habitually short sleepers, to restrict the time available for sleep. This occurs to physicians during
residency training, when weekly sleep durations are curtailed as weekly work hours increase
(22;24;44). Yet, our data also reveal up to a two-hour difference in average nightly sleep durations
among interns working the same number of hours per week in an ICU (22).
There are many factors that may lead to the inter-individual differences in the average amount
of sleep obtained by residents working the same number of hours in the hospital, including
differences in their responsibilities outside the hospital. The very concept of residency has changed
since it was first introduced in the U.S. at the Johns Hopkins University School of Medicine by
Professor William Stewart Halsted in the 1890s. At the time, residents were required to live at the
hospital and were discouraged from marrying (45). In contrast, today residents live outside the
hospital and many of these young physicians have families and become new parents during
residency. The sleep of new mothers and fathers is often interrupted and curtailed by newborns,
resulting in increased daytime fatigue (46;47). Multiple births exacerbate post-partum sleep
deprivation and daytime fatigue, particularly for fathers (48). Children with sleep or health
problems may also lead to sleep fragmentation, sleep deprivation and increased daytime fatigue in
parents (49;50). Behaviorally induced insufficient sleep syndrome affects 7% of patients with
excessive daytime sleepiness (EDS) in Japan and is associated with a high motor vehicle crash risk
Page 7 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
(51). Both acute and chronic sleep loss, whether cause by work schedules, family responsibilities,
social activities or health problems, will degrade tolerance and increase performance vulnerability
to the sleep deprivation imposed by extended duration (>24-hour) work shifts.
Moreover, preliminary evidence suggests that even after 8 to 12 hours of recovery sleep,
individuals with a history of recent exposure to chronic sleep loss may be more vulnerable to the
effects of re-exposure to sleep restriction, exhibiting nearly double the deterioration in performance
on a vigilance task upon acute sleep restriction to 4 hours of time in bed as compared with their
response to the same challenge when their recovery sleep was not preceded by exposure to chronic
sleep debt (52). Thus, resident work schedules that cause chronic sleep restriction and provide for
only one night of recovery sleep per week may generate a deterioration of performance that
becomes progressively greater with additional weeks of sleep curtailment. Despite intermittent
opportunities for recovery sleep, individuals exposed to such schedules may become increasingly
vulnerable to the adverse effects of sleep loss on performance. Four weeks of scheduled sleep
extension (14 hours per night) can reduced fatigue and increased energy levels, but only after an
average of more than 30 hours of accumulated sleep debt has been repaid (53). Irregularity in the
timing of sleep and wakefulness can impede circadian adaptation to altered work-rest schedules
(54); loss of circadian entrainment, in turn, impairs cognitive performance (55). Thus, available
evidence indicates that prior sleep-wake history, including exposure to both acute and chronic sleep
restriction, to sleep extension, and to irregular sleep-wake schedules, may greatly affect an
individual’s resiliency in the face of sleep loss (2).
Age-related differences in the vulnerability to sleep loss. Thirty consecutive hours of sleep loss
induces marked deterioration in neurobehavioral functions in health young participants (17). So
long as participants remain awake, average reaction time after 24 hours without sleep is three times
longer than when the same individuals are rested (17) (Fig. 2). The risk of lapses of attention is
Page 8 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
much higher during the latter half of the night, with the slowest 10% of reaction times lengthening
to nearly six seconds after 24 hours without sleep (17). Remarkably, the impact of a single night of
acute sleep deprivation on such measures is much less pronounced in older participants over the age
of 55 years (56-58) (Fig. 5). This may be due to age-related loss of neurons in the ventro-lateral preoptic (VLPO) area of the hypothalamus, which enables mammals to make the transition from
wakefulness to sleep; age-related loss of VLPO neurons may also explain why the prevalence of
insomnia rises with age. Because older people have greater difficulty obtaining recovery sleep at an
adverse circadian phase (59), they are more vulnerable to the effects of a sequence of night shifts
(60). Nonetheless, the data reveal that young adults are most severely affected by acute sleep
deprivation; in fact, 55% of sleep-related motor vehicle crashes occur in drivers age 25 years or
younger (61) (Fig. 6). Thus, it is both ironic and alarming that young resident physicians in this
most vulnerable age group are subjected to acute sleep deprivation during 30-hour shifts twice per
week while caring for patients and these young physicians then attempt to commute home from
work.
Trait differences in vulnerability to sleep loss. There are also inter-individual differences in the
vulnerability of well-rested, healthy young adults to sleep loss. In my laboratory, among healthy
participants who have maintained a schedule of 8 hours of sleep at the same time each night for
three weeks, we have found that approximately one-quarter of the participants account for roughly
two-thirds of the attentional failures recorded during ~30 hours of wakefulness. Interestingly, interindividual differences in the vulnerability to sleep loss in healthy young adults appear to be task
dependent, such that reaction time in a sustained attention task is most affected by sleep loss in
some individuals as compared to others, whereas sleep loss most adversely affects working memory
in other individuals (32;34). Van Dongen and his colleagues have found that when subjects are
brought back to the laboratory for repeat visits, the same ones remain particularly vulnerable while
Page 9 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
others remain resistant to the adverse effects of sleep loss on cognitive performance. While all the
subjects studied had more lapses of attention when performing the psychomotor vigilance task
(PVT, a measure of simple reaction time) after a night without sleep, some individuals averaged
only 10 lapses per 20-minute PVT test (about one lapse of attention every 2 minutes), whereas other
individuals experienced nearly 100 lapses of attention per 20-minute PVT test (nearly five lapses of
attention every minute) (32) (Fig. 7). In a relatively homogeneous sample of healthy young adults,
they reported that stable individual trait differences accounted for 67% to 92% of the variance in the
cognitive performance decrement induced by sleep loss (Fig. 7). These inter-individual differences
appear to be trait differences, since they persist even when participants are either comparably sleep
satiated (12 hours in bed per night for a week) or comparably sleep restricted (6 hours in bed per
night for a week) before they stay awake all night (32).
While the performance of most people deteriorates significantly when wakefulness extends
beyond 16-18 hours, there are considerable inter-individual differences in the magnitude of this
effect. There are likely also inter-individual differences in the effects of exposure to chronic partial
sleep deprivation for several weeks.
Potential genetic vulnerability to sleep loss. Genetic polymorphisms may account for
differences in the tolerability to acute sleep loss. A variable length tandem repeat polymorphism in
the PER3 gene (PER35/5) has been reported to confer a particular vulnerability to the performanceimpairing effects of 24 hours of wakefulness in those with 5 rather than 4 copies of the sequence on
both chromosomes (62;63). This polymorphism is present in about 10-15% of the population. When
individuals with the PER35/5 polymorphism are deprived of sleep at an adverse circadian phase,
their cognitive performance at night is significantly worse than individuals with the PER34/4
genotype (63) (Fig. 8). Individuals with the PER35/5 polymorphism reportedly experience
significantly more attentional failures, as measured by slow rolling eye movements, than individuals
Page 10 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
with the PER34/4 polymorphism. Executive functioning of the brain’s pre-frontal cortex is said to be
particularly compromised by the PER35/5 polymorphism (Fig. 8). On the other hand, a haplotype of
the adenosine A2A receptor gene (ADORA2A), may be associated with resistance to the effects of
sleep loss on performance (64). These preliminary data suggest that it may soon be possible to
identify from a simple cheek swab a subset of individuals who will exhibit minimal perform
degradation when deprived of sleep and another subset whose performance will deteriorate
markedly when they are sleep deprived.
Food, drugs and pharmaceutical agents
Soporific agents. Sleepiness is one of the most frequent side effects of prescription medications,
including some anti-depressants, statins, anti-hypertensive agents, hypnotics, anti-anxiety
medications, pain management medications, anti-epileptic agents, muscle relaxants and medications
to block stomach-acid secretion. Many common over-the-counter drugs have effects on sleep
propensity. For example, diphenhydramine is sold under various trade names, including Benadryl®
for relief of allergies. Few who take diphenhydramine for allergies realize that, because of its action
as an anti-histamine, the very same drug—diphenhydramine—is also the active ingredient in many
of the most popular over-the-counter sleeping pills in the U.S. It is marketed as an over-the-counter
sleep aid under the trade names Unisom,® Nytol,® Sominex,® Tylenol Simply Sleep® and, with
acetaminophen, in Tylenol PM.® Thus, many people attempting to control their allergies during the
daytime may be unwittingly taking a sleeping pill on their way to work, and thereby greatly
reducing their tolerance to sleep loss. Diphenhydramine affects the areas of the brain that control
the transition from wakefulness to sleep and thereby impairs performance. Even some newer ‘nonsedating’ anti-histamines cause drowsiness in a substantial fraction of patients. Some decongestants,
in turn, disrupt nocturnal sleep, which can increase sleep pressure the following day.
Page 11 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
Stimulants and drugs of abuse. Stimulants and drugs of abuse can have a profound effect on the
ability to sustain alertness and performance in the face of sleep loss. Caffeine is the most widely
used psycho-active agent in the world. In fact, it is the most widely used drug in the world, fueling
our 24/7 society. Because caffeine antagonizes the actions of adenosine (65), a neuromodulator that
mediates the sleep-inducing effects of prolonged wakefulness (66), at the adenosine A2A receptor,
it can mask some of the effects of sleep deprivation on sleep propensity. Caffeine is marketed in
coffee, colas and so-called energy drinks, and mixed with alcoholic beverages to increase the
amount of alcohol that consumers can drink before becoming overcome with alcohol-induced
fatigue. Caffeine is also available in tablet form, gum and in energy bars. Caffeine enhances
performance during the daytime, although we have found that chronic caffeine administration in
subjects on a demanding schedule may increase sleepiness, perhaps due to interference with
recovery sleep (67).
The National Transportation Safety Board (NTSB) found that plasma caffeine levels were
highest in drivers involved in fatigue-related fatal crashes (68). The NTSB concluded that the high
levels of caffeine were insufficient to save those drivers from the effects of fatigue, which the
NTSB found to be the leading cause of heavy truck crashes, equal to the fraction of crashes caused
by both drugs and alcohol combined (68). Moreover, while 80 to 90% of adults report regular
consumption of caffeine-containing beverages and foods, some people who avoid or limit caffeine
consumption report experiencing adverse effects of caffeine—such as anxiety, tachycardia,
nervousness or tremors—even at low to moderate doses (69). Twin studies have yielded heritability
estimates of up to 77% for caffeine use and for tolerance to the side effects of caffeine, leading to
the recent discovery that a genetic polymorphism in the adenosine A2 receptor gene is associated
with both reduced caffeine consumption (69) and with greater subjectively and objectively
measured sensitivity to the adverse effects of caffeine on sleep (70). Thus, while most physicians
Page 12 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
use caffeine extensively to cope with sleep deprivation induced by extended duration work shifts
and long work weeks, hundreds of thousands of physicians may be less able to avail themselves of
the wake-promoting effects of caffeine due to a genetic variation in the adenosine 2A receptor that
increases their sensitivity to the side effects of caffeine.
With 7.74% of children ages 4-17 diagnosed with ADHD and 4.33% (6.2% of boys and 2.4% of
girls) receiving ADHD medications, amphetamines and other stimulants used to treat ADHD are
now readily available (71). An unintended consequence of this popularity is that one-third of
college students illegally use the mixed amphetamine salts in Adderall to “stay awake to study”
when academic workload is high (72). It is unknown whether the illegal use of such stimulant
medications, which can induce insomnia, will persist when this cohort of students enters medical
school and then residency training. If so, this trend would hark back to the man who established and
directed the first surgical residency program at Johns Hopkins in the 1890s, as it was cocaine use
(73) that enabled Professor William Stewart Halsted, who laid the foundation for present-day
graduate medical education work-hour policies, to maintain his reputation as an indefatigable
surgeon (74). Sedation, sleep deprivation and insomnia are common side effects of opiates, to which
Dr. Halsted was also addicted (75-77). In healthy subjects, morphine and methadone decrease deep
slow wave sleep (78). It is also likely that opiates increase the risk of attentional failures and
degrade performance under conditions of sleep deprivation.
Alcohol, another major drug of abuse, is a central nervous system depressant that increases
sleep propensity during wakefulness but disrupts sleep consolidation after sleep onset. One third of
U.S. medical students regularly drink alcohol excessively (79). An estimated 4.9% of emergency
medicine residents meet diagnostic criteria for alcoholism (80). An estimated 10-12% of practicing
physicians in the United States develop a substance use disorder (81), with 50% of physicians in
rehab centers treated for abuse of alcohol, 36% for opiates and 8% for stimulants (81).
Page 13 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
These various agents, used commonly by a substantial fraction of practicing physicians and
residents, have a profound effect on sleep-wake homeostasis and vulnerability to the effects of acute
and chronic sleep loss on alertness and performance. Even low doses of alcohol synergistically
interact with sleep loss to greatly increase sleep propensity, degrade driving performance and
increase crash risk in a driving simulator (82-84). Healthy professional drivers who were awake for
18 to 21 hours and were exposed to legal low-dose alcohol (blood alcohol concentration of 0.03
g/dL) had significantly more attentional failures and greater variation in both lane position and
speed in a driving simulator than they did when their blood alcohol concentration exceeded 0.05
g/dL—a level associated with significantly increased risk of a motor vehicle crash (85). Few
programs have adopted the random drug testing procedures recently introduced for anesthesia
residents, but not for practicing physicians, at the Massachusetts General Hospital in Boston (86).
Therefore, physicians whose performance has been compromised by the use of such agents—even
on non-work days—are not being identified and are being scheduled to work lengthy shifts of the
same duration (e.g., 30 consecutive hours) and at the same frequency (e.g., twice per week) as those
who have not used such agents. The practice of scheduling physicians to work for 30 consecutive
hours without sleep does not take into account the widespread use among physicians of
psychoactive agents that affect tolerance to sleep loss.
Impact of medical condition on vulnerability to sleep loss
A number of medical conditions and/or the medications used to treat those conditions are
associated with increased sleep tendency, increased risk of attentional failures and increased risk of
sleep-related errors and accidents (87). These common conditions make it more difficult to sustain
wakefulness during the day and increase performance vulnerability to sleep loss. For example,
pregnancy is a non-pathologic condition that often interferes with sleep, particularly in the last
Page 14 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
trimester, induces fatigue and can greatly affects stamina and the ability to cope with sleep loss. Yet
many residents are scheduled to work 30-hour shifts throughout pregnancy. Many infectious
diseases also increase sleep tendency, including the common cold, mononucleosis and hepatitis.
Other conditions, such as chronic pain and nocturnal asthma, cause chronic sleep loss that reduces
tolerance to further sleep deprivation. Primary sleep disorders, such as narcolepsy and sleep apnea,
as well as disturbances of sleep or wakefulness secondary to a medical condition or its treatment
can affect tolerance to sleep loss. While there are 90 recognized sleep disorders (2), I have selected
five to illustrate the issues raised by these common conditions, which collectively affect at least one
out of five residents and practicing physicians in the U.S.
Sleep-related breathing disorders. Obstructive sleep apnea/hypopnea (OSAHS) syndrome
results in sleep fragmentation and consequent daytime sleepiness. EDS is reported in about 80% of
patients with OSAHS, 80 to 90% of whom remain undiagnosed and untreated; it often takes several
years from the time a patient presents to a physician with symptoms until the correct diagnosis is
made (2). Performance related to executive functions such as verbal fluency, planning and
sequential thinking—the purview of the frontal cortex, an area of the brain that imaging studies has
revealed to be exquisitely sensitive to sleep loss—is very adversely affected by OSAHS (88).
Vigilance and the ability to sustain attention are also degraded in patients with OSAHS. Reaction
times on a sustained attention task in patients with mild to moderate OSAHS have been reported to
be comparable to or worse than those of a young adult with a blood alcohol concentration of 0.080
g/dL (89). Untreated patients with OSAHS perform much more poorly in a driving simulator (in
terms of lane deviations, tracking errors, off-road events and collisions with obstacles) and are 6 to
10 times (i.e., about 500% to 1,000%) more likely to have an actual motor vehicle crash than people
without OSAHS (90-103).
Page 15 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
It is not known how many physicians in training or practicing physicians suffer from OSAHS.
Snoring and the occurrence of attentional failures when driving a motor vehicle are cardinal
symptoms of OSAHS (2). Obesity is the most prominent risk factor for OSAHS (2), though OSAHS
can occur without obesity. Obesity confers such a high risk of OSAHS that Medical Advisory
Board of the Federal Motor Carriers Safety Administration (FMCSA) has recommended mandatory
objective OSAHS screening of all commercial motor vehicle drivers with a body mass index (BMI)
greater than 30 kg/m2, as measured at the bi-annual commercial driver license (CDL) physical
exam. Data from available cohorts suggest that at least 50,000 practicing physicians and up to
10,000 residents would be affected if similar criteria were applied to those seeking to obtain or
renew a license to practice medicine, as an estimated 6% to 18% of practicing physicians (104-107)
and 10% of residents (108) are obese (BMI > 30 kg/m2). Since long work hours leave little time for
exercise, and sleep restriction increases ghrelin levels, decreases leptin levels and increases
carbohydrate craving, appetite and weight (2), physicians in training gain weight during residency
(109;110), exacerbating the condition.
Thus, it is likely that a significant fraction of both residents and practicing physicians are at risk
for OSAHS. Nearly two decades ago, the prevalence of OSAHS in the U.S. was estimated to be 4%
of adult men and 2% of adult women (111). With the increased prevalence of obesity in the U.S.
(112), the prevalence of OSAHS among both residents and practicing physicians is now at least 3 to
4 times higher. We have recently found that over one-third of a younger cohort of 4,471 North
American employed law enforcement officers (mean age: 38.5 + 8.3 years; mean BMI: 28.7 ± 4.6
kg/m2) screened with a sensitive and specific survey instrument were at high risk for OSAHS (113).
Fortunately, for the 10 to 20% of OSAHS patients who are correctly diagnosed and treated,
there are a number of therapies available that can improve the subjective sleepiness associated with
this condition. Splinting the airway open with continuous positive airway pressure (CPAP)
Page 16 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
treatment has been the standard treatment for this condition for more than two decades. While the
symptoms of OSAHS, including the increased risk of motor vehicle crashes, are usually
significantly improved with CPAP treatment (101;114-116), less than half of patients diagnosed
with OSAHS actually use CPAP for at least 4 hours on 70% of observed nights (117). Moreover,
while the impact of CPAP treatment on the most widely used objective measure of daytime
sleepiness, the Multiple Sleep Latency Test (MSLT), is statistically significant, it is rather modest in
size, with the improvement in sleep latency averaging less than one minute (118).
Thus, a substantial fraction of patients who are compliant with CPAP therapy remain
pathologically sleepy. Daily use of modafinil (200 mg.) has been demonstrated to be effective as an
adjunct therapy in the treatment of residual subjective sleepiness in this population of OSAHS
patients treated with CPAP (119). However, subjective sleepiness was only normalized (Epworth
Sleepiness Scale < 10) in half of the modafinil-treated patients and objective sleep tendency, as
measured by the MSLT, was not significantly improved by modafinil treatment (119). In summary,
OSAHS is likely to have a substantial prevalence among physicians and most physicians with this
condition will remain impaired by EDS for the following reasons: lack of diagnosis and treatment in
80-90% of those affected, failure to comply with nasal CPAP treatment in half of those diagnosed,
and residual impairment notwithstanding compliance with CPAP treatment and adjunctive
pharmacotherapy in others (2). Increased sleepiness and neurobehavioral deficits due to chronic
sleep loss and sleep fragmentation will likely render physicians afflicted with OSAHS much more
susceptible to the adverse effects of acute and chronic sleep deprivation induced by extended
duration work schedules typically required of both residents and practicing physicians.
Shift Work Disorder. Excessive sleepiness and/or insomnia that occur in association with work
that is scheduled during hours usually reserved for sleep are symptomatic of a condition known as
Circadian Rhythm Sleep Disorder (CRSD), Shift Work Type (Shift Work Disorder, SWD) (120).
Page 17 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
About 5 to 10% of such workers suffer chronically from moderate to severe SWD (121). Most
employees nod off or fall asleep regularly while working at night or while commuting to or from
night work (122). One-third of nurses who work at night report that they fall asleep in the hospital
every week of night work (123), with half admitting that they fall asleep at the wheel while driving
to or from the hospital; twice as many night-working nurses reported making medication errors or
having motor vehicle crashes as compared to those who worked the day and evening shifts, but did
not work at night (123).
Extended duration work shifts that routinely exceed 24 consecutive hours combined with very
long work weeks that do not allow sufficient time for sleep can elicit attentional failures during
work in most if not all employees (22), effectively inducing SWD in all workers in the same way
that depriving people of food will eventually induce malnutrition in all people who are starved.
Exposure to less extreme work schedules reveals considerable variability in the ability of
individuals to cope with the demands of work schedules that require employees to work during
times that they would otherwise be asleep. Continuous polysomnographic monitoring of 80 licensed
commercial drivers without OSAHS during 7,500 hours of long-haul trucking operations revealed
that more than half of the long-haul truck drivers experienced episodes of drowsy driving, mostly
during night driving (124). Predictably, these episodes of drowsy driving were not distributed
evenly across the 80 drivers. In fact, more than half of the drowsy driving episodes occurred in just
8 (10%) of the 80 drivers (124), revealing the differential vulnerability of this subset of drivers to
the sleep deprivation and circadian misalignment associated with night driving. This is consistent
with the differential vulnerability to nocturnal sleep loss observed in laboratory studies (32;3537;125;126). A number of countermeasures and treatments can be effective in treating the
symptoms of SWD, including improvements in work scheduling, use of properly timed exposure to
light, administration of nutritional supplements such as caffeine and melatonin, and use of
Page 18 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
pharmacologic agents such as the wake-promoting therapeutic modafinil (22-24;67;122;127-130),
although none eliminate them.
Insomnia. Insomnia is the most common sleep disorder, with symptoms of disturbed sleep
affecting most adults at some time in their lives (2). The clinical definition of insomnia is a chronic
(> 6 months) complaint of latency to sleep onset or awakenings from sleep of at least a half hour
occurring at least three times per week. The prevalence of insomnia associated with a daytime
complaint of increased sleepiness or fatigue is 8% to 18% (131). Broadly, insomnia may be
psychophysiologic or secondary to the sleep environment, an irregular sleep schedule, a sleeprelated movement disorder, a psychiatric condition, a medical condition, a medication or substance,
or a CRSD such as SWD (2). Insomnia in non-depressed adults is a risk factor for depression (132).
Insomnia syndrome, which includes increased daytime sleepiness, it is associated with an increased
rate of work absenteeism, reduced productivity and increased risk of accidents (2;133).
Narcolepsy. Narcolepsy is a neurological sleep disorder characterized by “EDS that typically is
associated with cataplexy and other REM sleep phenomena such as sleep paralysis and hypnogogic
hallucinations (120).” Cataplexy, a sudden muscular weakness often brought on by strong emotion,
together with disturbed nocturnal sleep, are hallmarks of this condition, which affects about 5 out of
every 10,000 adults in the U.S. Thus, an estimated 50 resident physicians and 400 practicing
physicians in the United States have narcolepsy, assuming that the affected individuals have not
self-selected out of the profession. Since narcolepsy often presents late in the second decade or in
the third decade of life, affected individuals may already be in medical school or in a residency
program before clinical symptoms are manifested. Despite the severity of sleep-wake impairment
associated with this primary sleep disorder, it often takes more than five years from the time of
symptom presentation to a physician until the correct diagnosis is made. Patients with narcolepsy
often have difficulty sustaining attention during the day, and must rely on wake-promoting
Page 19 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
therapeutics to reduce EDS and minimize the occurrence of sleep attacks. This may be due to a
deficiency of the hypothalamic neurotransmitter orexin (hypocretin), which is often associated with
narcolepsy. Patients with narcolepsy perform more poorly on a driving simulator and have a
significantly higher rate of motor vehicle crashes than do control subjects (99).
Psychiatric Disorders. Sleep disturbance is often secondary to a number of psychiatric disorders
and other conditions that may render affected individuals more susceptible to the effects of sleep
deprivation. These include several medical and psychiatric disorders such as depression, which is
common among practicing physicians and residents. A recent large-scale multi-site study revealed
that 12% of medical students and residents had probable major depression and 9.2% had probable
mild/moderate depression (134). Burnout has been reported by half of medical students in two
studies (135;136); 11.2% of the medical students reported suicidal ideation. 20% of pediatric
residents meet screening criteria for depression, and 74% meet the criteria for burnout (137).
Sleep disturbance is one of the most common symptoms of burnout, anxiety disorders and mood
disorders, including depressive disorders and bipolar disorder. Burnout is also associated with
persistent insomnia (138), with increased arousals and sleep fragmentation (139). Abrupt
awakenings often occur in anxiety disorders, such as post-traumatic stress disorder, in which sleep
is frequently disturbed by nightmares. Burnout, which is precipitated by occupational stress, induces
EDS and mental fatigue throughout the day, which may be a consequence of the sleep disturbance
(139). While insomnia is one of the most common features of mood disorders, hypersomnia can
occur as well, especially during depressive episodes. Changes in sleep architecture, including
reductions in deep slow wave sleep and earlier onset of REM sleep, occur in depression. Acute
sleep deprivation can have an immediate anti-depressant effect, although its therapeutic effect is
reversed as soon as recovery sleep is obtained. Sleep disturbance is one of the most common
residual symptoms after effective treatment of depression, estimated to continue in up to 44% of
Page 20 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
patients in remission (131). For these reasons, the cognitive performance of physicians with mood
disorders is likely to be more vulnerable to the effects of sleep loss and misalignment of circadian
phase. Many of the medications used to treat these patients have side effects that affect sleep
tendency. The adverse effects of depression and its treatment on sleep and consequent daytime
functioning probably contribute the increased risk of medical errors in depressed pediatric residents,
who make 6.2 times as many medication errors per resident month as residents who are not
depressed (137).
Ethical Considerations
The evidence upon which the ACGME and the IOM have relied in developing resident workhour policy limits has been largely derived from laboratory studies of healthy subjects who have
passed physical examinations and volunteered to participate in relatively brief sleep restriction or
sleep deprivation studies. In continuing to sanction every other work shift to be 30-consecutive
hours in duration (Fig. 9) throughout years of residency training, the ACGME has implicitly
assumed that the population of residents is entirely healthy, highly resistant to the effects of sleep
deprivation, and free of concurrent family responsibilities, premises that are not accurate. Working
such long hours that the risk of unnecessary patient injury rises sharply violates the ethical principle
of nonmaleficence (140). The principle of beneficence requires implementation of safer work
schedules that reduce risk by not scheduling physicians to care for patients after 16 hours without
sleep. Exhausted physicians who have worked >16 consecutive hours without sleep should not
endanger themselves and others by driving automobiles (141;142). Since 24-hours of wakefulness
degrades performance comparably to alcohol intoxication (28;143-147), the principle of autonomy
requires that physicians respect the right of the patient to be informed of the impairment and to
withhold consent to the risk of receiving care from sleep-deprived providers (140). The principle of
Page 21 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
justice requires that those most vulnerable to sleep loss not shoulder a disproportionately large
burden [i.e., a higher rate of fatigue-related errors, accidents and adverse health effects (2)] than
those who are resistant to sleep loss (140), particularly for the convenience or financial benefit of
teaching faculty or academic medical centers.
Systematic falsification of resident work-hour records (Fig.10)(1;148-150), which the IOM
found to be widespread (1) and the ACGME recently admitted after years of official denial (151),
violates the principle of truthfulness and honesty (140). It sets a regrettable precedent for trainees,
especially when it occurs out of fear of reprisal from (152) or with the tacit approval, awareness or
expectation of residency program directors or institutional leaders (151). Falsification of work-hour
records by those who have caused harm have led to felony convictions, hefty fines and
imprisonment, not only for those who falsified reports but for chief executives and supervisors
complicit in the falsifications of work-hour records (153-163). At its core, resident work hour
reform is an issue of human dignity for patient and physician (140). Burdening a physician with a
workload that s/he cannot carry creates an ethical dilemma in which—on the one hand—the more
hours that the physician works, the greater is the risk to both the patient and to the physician,
whereas—on the other hand—the physician cannot ethically stop working and abandon a patient in
need of medical care. Sleep deprivation should not be presented as a proxy for dedication.
Education about the impact of sleep deprivation and sleep disorders on performance, health and
safety should be provided so that physicians and trainees understand that working when sleep
deprived constitutes working in an impaired state, comparable to being under the influence of
alcohol (1;2;17;28;82-84;143-147). 30-hour work shifts are not necessary for training physicians,
since GME programs in many other countries (1)(Table) and in the U.S. have eliminated them years
ago, including the surgical residency training program at the Brigham and Women’s Hospital in
Boston. As in other safety-sensitive industries in the U.S. and in residency training in other
Page 22 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
countries (1;164), work-hour limits for residents should be based on work hours that are safer for
most people, not a select few (Table). Prior to the threat of federal legislation (151), many medical
and surgical training programs in the U.S. required residents to work 120 to 140 hours per week
(21;24), as they currently do in El Salvador (165)(Table). 25 years ago, the tragic death of Libby
Zion thrust the issue of resident work hours onto the national stage (166). As the IOM has recently
concluded, now is the time for meaningful resident physician work-hour limits (1), which the
federal government has the authority to implement (167) and for which the boards of directors of
the Sleep Research Society and the National Sleep Foundation have endorsed enforcement by law
or regulation (21;168;169).
Conflict Of Interest Disclosure
Dr. Czeisler is/was a consultant for: Actelion, Ltd.; Cephalon, Inc.; Delta Air Lines, Inc.; Eli
Lilly and Co.; Garda Síochana Inspectorate; Global Ground Support; Johnson & Johnson;
Koninklijke Philips Electronics, N.V.; Portland Trail Blazers; Respironics, Inc; Sanofi-Aventis
Groupe; Sepracor, Inc.; Sleep Multimedia, Inc.; Somnus Therapeutics, Inc.; University of
Wisconsin; Vanda Pharmaceuticals, Inc.; and Zeo, Inc.; and received royalties from McGraw Hill
and Penguin Press. Dr. Czeisler owns an equity interest in Lifetrac, Inc.; Somnus Therapeutics, Inc.;
Vanda Pharmaceuticals, Inc.; and Zeo, Inc. Dr. Czeisler has also received research support from
Cephalon, Inc.; Tempur Pedic International, Inc; and Resmed, Inc. The Sleep and Health Education
Program of the Harvard Medical School Division of Sleep Medicine has received support from
Cephalon, Inc.; Takeda Pharmaceuticals North America, Inc.; Sanofi-Aventis Groupe; and
Sepracor, Inc. Dr. Czeisler has received awards with monetary stipends from the American Clinical
and Climatological Association; American Academy of Sleep Medicine; Association for PatientOriented Research; National Institute for Occupational Safety and Health and National Sleep
Page 23 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
Foundation; and the Sleep Research Society. Dr. Czeisler is the incumbent of an endowed
professorship provided to Harvard University by Cephalon, Inc. and holds a number of process
patents in the field of sleep/circadian rhythms (e.g., photic resetting of the human circadian
pacemaker). Since 1985, Dr. Czeisler has also served as an expert witness on various legal cases
related to sleep and/or circadian rhythms.
Acknowledgments
The author acknowledges the cooperation of the National Residency Matching Program and
Association of American Medical Colleges, which until 2006 provided access to medical student
contact information for survey distribution, and wishes to thank Theresa L. Shanahan, M.D. for her
advice, Laura K. Barger, Ph.D., Steven W. Lockley, Ph.D., Christopher P. Landrigan, M.D.,
M.P.H., Clark J. Lee, J.D., and Shantha W. Rajaratnam, Ph.D. for their thoughtful comments on the
manuscript, Ms. Lorna Preston for editorial assistance on this manuscript, and collaborators Daniel
Aeschbach, Ph.D., Erik K. Alexander, M.D., Najib T. Ayas, M.D., David W. Bates, M.D., Brian
Cade, B.S., John W. Cronin, M.D., Erin Evans, B.A., James A. Gordon, M.D., M.P.A., Joel T. Katz,
M.D., Craig M. Lilly, M.D., Conor O’Brien, B.A., Jeffrey M. Rothschild, M.D., Joseph M. Ronda,
M.S., Frank E. Speizer, M.D., Peter H. Stone, M.D., Bernard A. Rosner, Ph.D. and Marshall Wolf,
M.D. for their contributions to the work reviewed herein.
Supported in part by grants from the Agency for Healthcare Research and Quality (AHRQ)
(RO1 HS12032; K08 HS13333; U18 HS015906; F32 HS14130); the National Institute of
Occupational Safety and Health (RO1 OH07567); the National Institute on Aging (P01 AG09975;
R01 AG06072); the National Heart, Lung, and Blood Institute (R01 HL52992;T32 HL07901; F33HL-09588); National Institute of Mental Health (RO1 MH-45130); National Center for Research
Resources (M01 RR02635); the Swiss National Foundation (823A-046640); the Wellcome Trust,
Page 24 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
United Kingdom (060018/B/99/Z); the US Air Force Office of Scientific Research (F49620–95–10388); The Medical Foundation; The Harold Whitworth Pierce Charitable Trust; the Canadian
Institutes of Health Research; the British Columbia Lung Association; the University of British
Columbia; the University of Colorado; and by the Brigham and Women’s Hospital and the Division
of Sleep Medicine, Harvard Medical School. Dr. Czeisler is supported in part by the National Space
Biomedical Research Institute, through the National Aeronautics and Space Administration (NCC
9-58).
Figure Legends
Figure 1: Effect of Partial Sleep Loss during Hospital Call on Errors Committed by Surgeons
during Simulated Surgery. Simulated laparoscopic surgery performance of surgical residents
(median age 34) measured by a laparoscopic surgery simulator (task 6 of the MIST-VR, Mentice
Medical Simulation, Gothenburg, Sweden) before and after a night on call (17.5 hours from 3:30
pm to 9 am; median reported sleep time 1.5 h; range 0-3 h). Horizontal bands indicate median
number of errors on this task, boxes show 25th and 75th centiles, and whisker lines show the
highest and lowest error values. Figure and legend reprinted with permission from: Grantcharov TP,
Bardram L, Funch-Jensen P, Rosenberg J. BMJ 2001;323:1222-1223 (5).
Figure 2: Impact of Acute Total Sleep Deprivation on Reaction Time Performance. Time course
of psychomotor vigilance task (PVT) performance [mean, median, 10% slowest and fastest reaction
times in milliseconds (logarithmic scale)] during more than 28 hours of continuously monitored
wakefulness under constant environmental and behavioral conditions are shown averaged across 10
subjects ± standard error of the mean. All data are binned from 10-minute PVT tests administered at
2-hour intervals and expressed with respect to elapsed time since wake time (designated as a
Relative Clock Hour of 8), which was scheduled at its habitual hour. Figure and legend reprinted
Page 25 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
with permission from: Cajochen C, Khalsa SBS, Wyatt JK, Czeisler CA, Dijk D-J. Am J Physiol
277: R640-R649, 1999 (17).
Figure 3: Sleep Duration in the Hospital. Average hours that interns reportedly slept in the
hospital during extended duration (greater than 24 hour) on-call shifts as a percentage of 17,003
monthly survey reports collected from 2,737 resident physicians. Average hours of sleep obtained
during extended duration shifts reported by interns for each week were averaged over the four
weeks of each month to derive the value for each monthly survey report. Figure and legend
reprinted with permission from: Barger LK, Cade BE, Ayas N, Cronin JW, Rosner B, Speizer FE,
Czeisler CA, N Engl J Med 2005;352:125-134 (24).
Figure 4: Repeated Nights of Sleep Loss Result in Cumulative Cognitive Impairment. Higher
number of attentional performance failures on the PVT indicates poorer performance and more
unstable alertness. Upper panel shows the average number of lapses of attention recorded during 10minute PVT tests administered eight times daily (every two hours) during 14 consecutive days
when the amount of time in bed was limited to 4 hours, 6 hours or 8 hours per night. Lower panel
shows the average number of lapses of attention recorded during 10-minute PVT tests administered
four times daily during 7 consecutive days when the amount of time in bed was limited to 3 hours, 5
hours, 7 hours or 9 hours per night. B signifies data from the baseline day. Figure and legend
reprinted with permission from the 2006 IOM Report entitled: Sleep Deprivation and Sleep
Disorders: An Unmet Public Health Problem (2).
Figure 5: Subjective Sleepiness, Reaction Time, Lapses of Attention, and Attentional Failures
Across 26 Hours of Wakefulness in Young and Older Participants. Group average data (± standard
error of the mean) are plotted with respect to time since scheduled awakening for 11 healthy older
(mean age 68.1 + 3.6 years; range 65 to 76 years; filled symbols) and 26 healthy young (mean age
21.9 + 3.3 years; range 18 to 29 years; open symbols) adults. Dashed box indicates time of usual
Page 26 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
sleep episode. Subjective sleepiness ratings from the Karolinska Sleepiness Scale (KSS; scale range
from 1 = very alert to 9 = very sleepy) are presented in Panel A. Mean reaction time (RT, in
milliseconds) from each 10-minute PVT is presented in Panel B. As indicated in the first 16 hours
of data, the RT on the PVT in well-rested individuals averages ~250 milliseconds during the
daytime, with minimal variability. The total number of lapses of attention (RT >500 milliseconds)
from each 10-minute PVT are presented in Panel C. Well-rested individuals typically have very few
(<5 per test administration) lapses of attention under these conditions. Attentional failures, defined
as intrusions of slow eye movements (SEM) from continuous electro-oculographic recordings
during EEG-verified wakefulness, were summed hourly and are presented in Panel D. Well-rested
individuals typically have very few SEM under these conditions. Figure and legend reprinted with
permission from: Duffy JD, Willson HJ, Wang W, Czeisler CA. J Am Geriatr Soc 2009; In Press.
(56).
Figure 6: Age Distribution of Crashes in Which Driver Was Not Intoxicated But Judged to Have
Been Asleep. Data from 4,333 fall asleep crashes in North Carolina, where standard crash report
forms, as mandated by state law, include ‘fatigued’ and ‘asleep’ in driver condition. Data for years
1990-1992, inclusive. In 55% of fall-asleep crashes, driver was age 25 or younger. Peak age of
crashes was at age 20 years. Figure and legend reprinted with permission from: Pack AI, Pack AM,
Rodgman E, Cucchiara A, Dinges DF, Schwab CW. Accid Anal Prev 27: 769, 1995 (61).
Figure 7: Neurobehavioral responses to total sleep deprivation after two different prior sleep
extension conditions. Each episode of sleep deprivation followed a week during which time the
participants spent 12 hours in bed each night. The average number of lapses on 20-minute PVT tests
administered every two hours over the last 24 hours of total sleep deprivation is shown. The
abscissa shows the 19 individual participants, who were arbitrarily assigned the labels A through U.
The participants are ordered by the magnitude of their impairment (averaged over the 2 sleep
Page 27 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
deprivations), with the most resistant participants on the left and the most vulnerable participants on
the right. Responses in the first exposure to sleep deprivation following 7 days of prior sleep
extension (mean ± standard deviation of the average nightly sleep duration of 8.5 ± 1.0 hours) are
marked by boxes; responses in the second exposure to sleep deprivation following 7 days of prior
sleep extension (mean ± standard deviation of the average nightly sleep duration of 8.8 ± 1.3 hours)
are marked by diamonds. The panel reveals that subjects differed substantially in their responses to
acute sleep deprivation, while the responses were relatively stable within subjects between the two
exposures to acute sleep deprivation. Figure and legend reprinted with permission from: Van
Dongen HPA, Baynard MD, Maislin G, Dinges DF. Sleep 2004; 27: 423-433 (32).
Figure 8: Polymorphism in Period Gene and Vulnerability to Sleep Loss. Left Hand Side:
Deterioration of waking performance and increase of theta EEG activity and slow eye movements
during sleep deprivation is greater in PER35/5 than in PER34/4 participants. Time course of central
EEG theta (5–8 Hz) activity during wakefulness (Panel A), incidence of slow eye movement
(SEMs) (percentage of 30 s epochs containing at least one SEM) (Panel B), and waking
performance (composite performance score) (Panel C) are plotted relative to the timing of the
plasma melatonin rhythm (Panel D) in ten PER35/5 (open symbols) and 14 PER34/4 (filled symbols)
homozygotes. EEG theta activity, SEMs, and waking performance data were averaged per 2-hour
intervals, relative to the midpoint of the melatonin rhythm. (* indicates a significant difference
between genotypes, p < 0.05; upper abscissa indicates approximate wake duration.) Right Hand
Side: Overnight performance on the paced visual serial addition task in PER35/5 and PER34/4
participants. Mean numbers of correct responses are plotted relative to the midpoint of the
melatonin rhythm (Panel E). Overnight performance on the serial reaction time task in PER35/5 and
PER34/4 participants. Mean switch costs, i.e., increase in time to respond to random rather than
learned sequences of stimuli, are plotted relative to the melatonin midpoint. Higher values indicate
Page 28 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
poorer performance (Panel F). Overnight performance on spatial N-Back performance in relation to
memory load in PER35/5 and PER34/4 participants. Mean numbers of correct responses, are plotted
separately for the 1-, 2-, and 3-back, relative to the melatonin midpoint (Panel G). Overnight
performance on verbal N-Back performance in relation to memory load in PER35/5 and PER34/4
participants. Mean numbers of correct responses are plotted separately for the 1-, 2-, and 3-back,
relative to the melatonin midpoint (Panel H). * P < 0.05, Bonferroni corrected. Error bars represent
the standard error of the mean. Figures and legends reprinted with permission from: Viola et al.,
Curr Biol, 2007 (62) (left hand side); and Groeger JA, Viola AU, Lo JC, von Schantz M, Archer
SN, Dijk DJ. Sleep 2008;31:1159 (63) (right hand side).
Figure 9: Illustration of Eight Consecutive Days of a Typical Resident Physician Work Schedule
Sanctioned by Current 2009 ACGME Guidelines. Every other shift is 30 hours in duration on this
schedule. Because each 30-hour shift includes two calendar days, this schedule results in the
resident physician spending every third night in the hospital. Black bar indicates scheduled 30-hour
shifts. Hatched bar indicates an 8- to 10-hour swing shift, when resident physicians are not
scheduled to work overnight. Box on right indicates how many hours residents are not scheduled to
work for each 24-hour interval, beginning at 6 am each day.
Figure 10: Reported Non-Compliance with ACGME Work-Hour Limits as Reported by
Residents Non-Confidentially to the ACGME vs. Confidentially to the Harvard Work-Hours Health
and Safety (HWHS) Group. After the ACGME implemented the 2003 limits on resident physicians
work hours, 83.6% of interns reported to the HWHS Group work hours that were in violation of the
ACGME standards during 1 or more months. Working shifts greater than 30 consecutive hours was
reported by 67.4% of interns (open bar, middle pair). Averaged over 4 weeks, 43.0% of interns
reported working more than 80 hours weekly (open bar, right pair), and 43.7% reported not having
1 day in 7 off work duties (data not shown). Violations were reported during 61.5% of months
Page 29 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
during which interns worked exclusively in inpatient settings. Violations were reported to the
HWHS Group from 85.4% of the 707 represented residency programs (open bar, left pair). During
the same reporting period, the ACGME reported near-universal compliance with the ACGME
standards (filled bars), claiming that only 5.0% of residency training programs were not compliant
with the standards and that only 3.3% of surveyed residents reported violations of the 80-hour rule.
Differences between the ACGME and HWHS Group data were statistically significant on each of
these measures (p < 0.001). Data and legend from: Landrigan CP, Barger LK, Cade BE, Ayas NT,
Czeisler CA. JAMA 2006;296:1063 (148) Figure courtesy of Christopher P. Landrigan, M.D.,
M.P.H.
Page 30 of 48
Table. Summary of work-hour regulations for various occupations in selected countries.
Current Work-Hour Regulations
Occupation
U.S. Airplane Pilots (1-2 pilot airplanes): 1950s
U.S. Nuclear Power Plant Operators: 1982; 2009
U.S. Railroad Operators: 1907, modified 1969 & 1976
U.S. Interstate Truck and Bus Drivers
E.U. All Occupations (including resident physicians and
practicing physicians): 2004; 2009
New Zealand Resident Physicians: 1985
U.S. Resident Physicians
El Salvador Resident Physicians
Limits
<8 daily flight hours
<16 daily work hours
>8-12 hours rest required (since 1985)
<34 hours flight time per week
<16 consecutive work hours
<72 work hours per week
>34 consecutive hours off every 9 days
<12 work hours per day
>8-10 hours rest required per day
<11 driving hours within a 14-hour interval
<14 consecutive hours from start to end of work
>10 consecutive rest hours
<60 work hours per 7 days; <70 work hours per 8 days
>34 consecutive hours off between work weeks
<13 consecutive work hours
<56 work hours per week until 2009; 48 hours thereafter
>11 hours rest time per day
<16 consecutive work hours (labor agreement)
<72 work hours per week
UNLIMITED: no federal laws of regulations
Self regulation by profession (ACGME): 2003
<30 consecutive work hours (two allowed per week)
<80 work hours per week (averaged over 4 weeks)
Monitoring by self-report (84% non-compliance)
UNLIMITED
Extended duration work shifts (36 hours) and long (>120
hours) work weeks common during internship
References
(1) Institute of Medicine of the National Academies. Resident Duty Hours: Enhancing Sleep,
Supervision, and Safety. Ulmer C, Wolman DM, Johns MME, editors. 1-322. 2008.
Washington, D.C., The National Academies Press.
(2) Institute of Medicine. Sleep disorders and sleep deprivation: An unmet public health
problem. Colten HR, Alteveogt BM, editors. ISBN:0-309-66012-2, 1-500. 2006.
Washington, D.C., National Academies Press.
(3) AAMC. Assuring Quality Patient care and Quality Education. Association of American
Medical Colleges 2001;1-10.
(4) Friedman RC, Bigger JT, Kornfield DS. The intern and sleep loss. N Engl J Med 1971;
285:201-203.
(5) Grantcharov TP, Bardram L, Funch-Jensen P, Rosenberg J. Laparoscopic performance after
one night on call in a surgical department: prospective study. B M J 2001; 323:1222-1223.
(6) Philibert I. Sleep loss and performance in residents and nonphysicians: a meta-analytic
examination. Sleep 2005; 28(11):1392-1402.
(7) Stickgold R. Sleep-dependent memory consolidation. Nature 2005; 437(7063):1272-1278.
(8) Walker MP, Stickgold R, Alsop D, Gaab N, Schlaug G. Sleep-dependent motor memory
plasticity in the human brain. Neuroscience 2005; 133(4):911-917.
(9) Walker MP, Stickgold R. Sleep-dependent learning and memory consolidation. Neuron
2004; 44(1):121-133.
(10) Walker MP, Brakefield T, Morgan A, Hobson JA, Stickgold R. Practice with sleep makes
perfect: Sleep-dependent motor skill learning. Neuron 2002; 35:205-211.
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
(11) Stickgold R, Whidbee D, Schirmer B, Patel V, Hobson JA. Visual discrimination task
improvement: A multi-step process occurring during sleep. J Cognitive Neurosci 2000;
12(2):246-254.
(12) Stickgold R, James L, Hobson JA. Visual discrimination learning requires sleep after
training. Nat Neurosci 2000; 3(12):1237-1238.
(13) Hill S, Tononi G, Ghilardi MF. Sleep improves the variability of motor performance. Brain
Res Bull 2008; 76(6):605-611.
(14) Huber R, Ghilardi MF, Massimini M, Tononi G. Local sleep and learning. Nature 2004;
430(6995):78-81.
(15) King CR, Knutson KL, Rathouz PJ, Sidney S, Liu K, Lauderdale DS. Short sleep duration
and incident coronary artery calcification. JAMA 2008; 300(24):2859-2866.
(16) Dinges DF, Orne MT, Whitehouse WG, Orne EC. Temporal placement of a nap for
alertness: Contributions of circadian phase and prior wakefulness. Sleep 1987; 10(4):313329.
(17) Cajochen C, Khalsa SBS, Wyatt JK, Czeisler CA, Dijk DJ. EEG and ocular correlates of
circadian melatonin phase and human performance decrements during sleep loss. Am J
Physiol 1999; 277:R640-R649.
(18) Veasey S, Rosen R, Barzansky B, Rosen I, Owens J. Sleep loss and fatigue in residency
training. A Reappraisal. JAMA 2002; 288(9):1116-1124.
(19) Dinges DF, Kribbs NB. Performing while sleepy: Effects of experimentally-induced
sleepiness. In: Monk TH, editor. Sleep, Sleepiness and Performance. Chichester, UK: John
Wiley and Sons, Ltd., 1991: 97-128.
(20) Durmer JS, Dinges DF. Neurocognitive consequences of sleep deprivation. Semin Neurol
2005; 25(1):117-129.
Page 33 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
(21) Czeisler CA. The Gordon Wilson Lecture: Work hours, sleep and patient safety in residency
training. Trans Am Clin Climatol Assoc 2006; 117:159-189.
(22) Lockley SW, Cronin JW, Evans EE, Cade BE, Lee CJ, Landrigan CP et al. Effect of
reducing interns' weekly work hours on sleep and attentional failures. N Engl J Med 2004;
351(18):1829-1837.
(23) Landrigan CP, Rothschild JM, Cronin JW, Kaushal R, Burdick E, Katz JT et al. Effect of
reducing interns' work hours on serious medical errors in intensive care units. N Engl J Med
2004; 351(18):1838-1848.
(24) Barger LK, Cade BE, Ayas NT, Cronin JW, Rosner B, Speizer FE et al. Extended work
shifts and the risk of motor vehicle crashes among interns. N Engl J Med 2005; 352:125134.
(25) Barger LK, Ayas NT, Cade BE, Cronin JW, Rosner B, Speizer FE et al. Impact of extendedduration shifts on medical errors, adverse events, and attentional failures. PLoS Med 2006;
3(12):e487.
(26) Ayas NT, Barger LK, Cade BE, Hashimoto DM, Rosner B, Cronin JW et al. Extended work
duration and the risk of self-reported percutaneous injuries in interns. JAMA 2006;
296(9):1055-1062.
(27) Horowitz TS, Cade BE, Wolfe JM, Czeisler CA. Searching night and day: a dissociation of
effects of circadian phase and time awake on visual selective attention and vigilance.
Psychol Sci 2003; 14(6):549-557.
(28) Dawson D, Reid K. Fatigue, alcohol and performance impairment. Nature 1997; 388:235.
(29) USA Today Editorial Board. Our view on doctors in training: Sleep deprivation studies fail
to wake up teaching hospitals. Why are residents still working marathon shifts, endangering
patients? USA Today 2006 Dec 19.
Page 34 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
(30) Fischer JE. Surgeons: employees or professionals? Am J Surg 2005; 190(1):1-3.
(31) Leach DC. Opposing view: More hours, better doctors. Good patient care is complex;
residents are students, not workers. USA Today 2006 Dec 19.
(32) Van Dongen HPA, Baynard MD, Maislin G, Dinges DF. Systematic interindividual
differences in neurobehavioral impairment from sleep loss: evidence of trait-like differential
vulnerability. Sleep 2004; 27:423-433.
(33) Leproult R, Colecchia EF, Berardi AM, Stickgold R, Kosslyn SM, Van Cauter E. Individual
differences in subjective and objective alertness during sleep deprivation are stable and
unrelated. Am J Physiol Regul Integr Comp Physiol 2003; 284:R280-R290.
(34) Frey DJ, Badia P, Wright Jr. KP. Inter- and intra-individual variability in performance near
the circadian nadir during sleep deprivation. J Sleep Res 2004; 13(4):305-315.
(35) Van Dongen HPA, Vitellaro KM, Dinges DF. Individual differences in adult human sleep
and wakefulness: leitmotif for a research agenda. Sleep 2005; 28(4):479-496.
(36) Van Dongen HPA. Brain activation patterns and individual differences in working memory
impairment during sleep deprivation. Sleep 2005; 28(4):386-388.
(37) Van Dongen HPA. Shift work and inter-individual differences in sleep and sleepiness.
Chronobiol Int 2006; 23(6):1139-1147.
(38) Chuah YM, Venkatraman V, Dinges DF, Chee MW. The neural basis of interindividual
variability in inhibitory efficiency after sleep deprivation. J Neurosci 2006; 26(27):71567162.
(39) Van Dongen HPA, Maislin G, Mullington JM, Dinges DF. The cumulative cost of additional
wakefulness: Dose-response effects on neurobehavioral functions and sleep physiology
from chronic sleep restriction and total sleep deprivation. Sleep 2003; 26(2):117-126.
Page 35 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
(40) Belenky G, Wesensten NJ, Thorne DR, Thomas ML, Sing HC, Redmond DP et al. Patterns
of performance degradation and restoration during sleep restriction and subsequent
recovery: A sleep dose-response study. J Sleep Res 2003; 12:1-12.
(41) Dinges DF. Sleep debt and scientific evidence. Sleep 2004; 27:1050-1052.
(42) Klerman EB, Dijk DJ. Interindividual variation in sleep duration and its association with
sleep debt in young adults. Sleep 2005; 28:1253-1259.
(43) Dinges DF. Can habitual sleep duration harbor sleep debt? Sleep 2005; 28:1209-1210.
(44) Czeisler CA. Work hours and sleep in residency training. Sleep 2004; 27(3):371-372.
(45) Farley P. Recreating the residency. Yale Medicine , 30-36. 2004. Yale Medicine Magazine.
(46) Gay CL, Lee KA, Lee SY. Sleep patterns and fatigue in new mothers and fathers. Biol Res
Nurs 2004; 5(4):311-318.
(47) Lee SY, Lee KA. Early postpartum sleep and fatigue for mothers after cesarean delivery
compared with vaginal delivery: an exploratory study. J Perinat Neonatal Nurs 2007;
21(2):109-113.
(48) Damato EG, Burant C. Sleep patterns and fatigue in parents of twins. J Obstet Gynecol
Neonatal Nurs 2008; 37(6):738-749.
(49) Martin J, Hiscock H, Hardy P, Davey B, Wake M. Adverse associations of infant and child
sleep problems and parent health: an Australian population study. Pediatrics 2007;
119(5):947-955.
(50) McCann D. Sleep deprivation is an additional stress for parents staying in hospital. J Spec
Pediatr Nurs 2008; 13(2):111-122.
(51) Komada Y, Inoue Y, Hayashida K, Nakajima T, Honda M, Takahashi K. Clinical
significance and correlates of behaviorally induced insufficient sleep syndrome. Sleep Med
2008; 9(8):851-856.
Page 36 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
(52) Banks S, Van Dongen H, Dinges D. Response to sleep restriction depends upon pre-existing
sleep debt. Sleep Abstract Supplement[30], A119. 2007.
(53) Wehr TA, Moul DE, Barbato G, Giesen HA, Seidel JA, Barker C et al. Conservation of
photoperiod-responsive mechanisms in humans. Am J Physiol 1993; 265:R846-R857.
(54) Horowitz TS, Cade BE, Wolfe JM, Czeisler CA. Efficacy of bright light and sleep/darkness
scheduling in alleviating circadian maladaptation to night work. Am J Physiol Endocrinol
Metab 2001; 281:E384-E391.
(55) Wright Jr. KP, Hull JT, Hughes RJ, Ronda JM, Czeisler CA. Sleep and wakefulness out of
phase with internal biological time impairs learning in humans. J Cognitive Neurosci 2006;
18:508-521.
(56) Duffy JF, Willson HJ, Wang W, Czeisler CA. Healthy older adults better tolerate sleep
deprivation than young adults. J Am Geriatr Soc 2009; In Press.
(57) Adam M, Rétey JV, Khatami R, Landolt H-P. Age-related changes in the time course of
vigilant attention during 40 hours without sleep in men. Sleep 2006; 29(1):55-57.
(58) Blatter K, Graw P, Munch M, Knoblauch V, Wirz-Justice A, Cajochen C. Gender and age
differences in psychomotor vigilance performance under differential sleep pressure
conditions. Behav Brain Res 2006; 168(2):312-317.
(59) Dijk DJ, Duffy JF, Riel E, Shanahan TL, Czeisler CA. Ageing and the circadian and
homeostatic regulation of human sleep during forced desynchrony of rest, melatonin and
temperature rhythms. J Physiol (Lond) 1999; 516.2:611-627.
(60) Folkard S. Shift work, safety, and aging. Chronobiol Int 2008; 25(2):183-198.
(61) Pack AI, Pack AM, Rodgman E, Cucchiara A, Dinges DF, Schwab CW. Characteristics of
crashes attributed to the driver having fallen asleep. Accid Anal Prev 1995; 27(6):769-775.
Page 37 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
(62) Viola AU, Archer SN, James LM, Groeger JA, Lo JCY, Skene DJ et al. PER3
Polymorphism Predicts Sleep Structure and Waking Performance. Curr Biol 2007; 17:1-6.
(63) Groeger JA, Viola AU, Lo JCY, von Shantz M, Archer SN, Dijk DJ. Early morning
executive functioning during sleep deprivation is compromised by a PERIOD3
polymorphism. Sleep 2008; 31(8):1159-1167.
(64) Bodenmann S, Hohoff C, Grietag C, Deckert J, Retey J, Landolt H-P. Genetic variation in
the adenosine A2A receptor gene modulates performance on the psychomotor vigilance
task. Sleep and Biological Rhythms 5, A47. 2007.
(65) Dunwiddie TV, Masino SA. The role and regulation of adenosine in the central nervous
system. Annu Rev Neurosci 2001; 24:31-55.
(66) Porkka-Heiskanen T, Strecker RE, Thakkar M, Bjørkum AA, Greene RW, McCarley RW.
Adenosine: A mediator of the sleep-inducing effects of prolonged wakefulness. Science
1997; 276:1265-1268.
(67) Wyatt JK, Cajochen C, Ritz-De Cecco A, Czeisler CA, Dijk DJ. Low-dose repeated caffeine
administration for circadian-phase-dependent performance degradation during extended
wakefulness. Sleep 2004; 27(3):374-381.
(68) National Transportation Safety Board. Safety Study: Fatigue, Alcohol, Other Drugs, and
Medical Factors in Fatal-to-the-Driver Heavy Truck Crashes (Volume 1). NTSB/SS-90/01,
1-181. 1990. Washington, DC, National Transportation Safety Board.
(69) Cornelis MC, El Sohemy A, Campos H. Genetic polymorphism of the adenosine A2A
receptor is associated with habitual caffeine consumption. Am J Clin Nutr 2007; 86(1):240244.
Page 38 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
(70) Retey JV, Adam M, Khatami R, Luhmann UF, Jung HH, Berger W et al. A genetic variation
in the adenosine A2A receptor gene (ADORA2A) contributes to individual sensitivity to
caffeine effects on sleep. Clin Pharmacol Ther 2007; 81(5):692-698.
(71) Visser SN, Lesesne CA. Mental health in the United States: Prevalence of diagnosis and
medication treatment for attention-deficit/hyperactivity disorder - United States, 2003.
54(34), 842-847. 9-2-2005.
(72) DeSantis AD, Webb EM, Noar SM. Illicit use of prescription ADHD medications on a
college campus: a multimethodological approach. J Am Coll Health 2008; 57(3):315-324.
(73) Markel H. The accidental addict. N Engl J Med 2005; 352(10):966-968.
(74) Cameron JL, Gordon TA, Kehoe MW, McCall N. William Stewart Halsted: letters to a
young female admirer. Ann Surg 2001; 234(5):702-707.
(75) Nicholson B. Responsible prescribing of opioids for the management of chronic pain. Drugs
2003; 63(1):17-32.
(76) Zgierska A, Brown RT, Zuelsdorff M, Brown D, Zhang Z, Fleming MF. Sleep and daytime
sleepiness problems among patients with chronic noncancerous pain receiving long-term
opioid therapy: a cross-sectional study. J Opioid Manag 2007; 3(6):317-327.
(77) Wang D, Teichtahl H, Goodman C, Drummer O, Grunstein RR, Kronborg I. Subjective
daytime sleepiness and daytime function in patients on stable methadone maintenance
treatment: possible mechanisms. J Clin Sleep Med 2008; 4(6):557-562.
(78) Dimsdale JE, Norman D, DeJardin D, Wallace MS. The effect of opioids on sleep
architecture. J Clin Sleep Med 2007; 3(1):33-36.
(79) Frank E, Elon L, Naimi T, Brewer R. Alcohol consumption and alcohol counselling
behaviour among US medical students: cohort study. BMJ 2008; 337:a2155.
Page 39 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
(80) McBeth BD, Ankel FK. Don't ask, don't tell: substance use by resident physicians. Acad
Emerg Med 2006; 13(8):893-895.
(81) McLellan AT, Skipper GS, Campbell M, DuPont RL. Five year outcomes in a cohort study
of physicians treated for substance use disorders in the United States. BMJ 2008; 337:a2038.
(82) Horne JA, Reyner LA, Barrett PR. Driving impairment due to sleepiness is exacerbated by
low alcohol intake. Occup Environ Med 2003; 60(9):689-692.
(83) Banks S, Catcheside P, Lack L, Grunstein RR, McEvoy RD. Low levels of alcohol impair
driving simulator performance and reduce perception of crash risk in partially sleep deprived
subjects. Sleep 2004; 27(6):1063-1067.
(84) Vakulin A, Baulk SD, Catcheside PG, Anderson R, van den Heuvel CJ, Banks S et al.
Effects of moderate sleep deprivation and low-dose alcohol on driving simulator
performance and perception in young men. Sleep 2007; 30(10):1327-1333.
(85) Howard ME, Jackson ML, Kennedy GA, Swann P, Barnes M, Pierce RJ. The interactive
effects of extended wakefulness and low-dose alcohol on simulated driving and vigilance.
Sleep 2007; 30(10):1334-1340.
(86) Fitzsimons MG, Baker KH, Lowenstein E, Zapol WM. Random drug testing to reduce the
incidence of addiction in anesthesia residents: preliminary results from one program. Anesth
Analg 2008; 107(2):630-635.
(87) Carter N, Ulfberg J, Nystrom B, Edling C. Sleep debt, sleepiness and accidents among males
in the general population and male professional drivers. Accid Anal Prev 2003; 35(4):613617.
(88) Beebe DW, Gozal D. Obstructive sleep apnea and the prefrontal cortex: towards a
comprehensive model linking nocturnal upper airway obstruction to daytime cognitive and
behavioral deficits. J Sleep Res 2002; 11(1):1-16.
Page 40 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
(89) Powell NB, Riley RW, Schechtman KB, Blumen MB, Dinges DF, Guilleminault C. A
comparative model: Reaction time performance in sleep-disordered breathing versus
alcohol-impaired controls. Laryngoscope 1999; 109:1648-1654.
(90) George CF, Nickerson PW, Hanly PJ, Millar TW, Kryger MH. Sleep apnoea patients have
more automobile accidents. Lancet 1987; 2:447.
(91) Findley LJ, Bonnie RJ. Sleep apnea and auto crashes: What is the doctor to do? Chest 1988;
94(2):225-226.
(92) Findley LJ, Unverzagt ME, Suratt PM. Automobile accidents involving patients with
obstructive sleep apnea. Am Rev Respir Dis 1988; 138:337-340.
(93) Findley LJ, Fabrizio M, Thommi G, Suratt PM. Severity of sleep apnea and automobile
crashes. N Engl J Med 1989; 320(13):868-869.
(94) Findley LJ, Weiss JW, Jabour ER. Drivers with untreated sleep apnea: A cause of death and
serious injury. Arch Intern Med 1991; 151:1451-1452.
(95) Haraldsson P-O, Carenfelt C, Tingvall C. Sleep apnea syndrome symptoms and automobile
driving in a general population. J Clin Epidemiol 1992; 45(8):821-826.
(96) Findley LJ, Levinson MP, Bonnie RJ. Driving performance and automobile accidents in
patients with sleep apnea. Clin Chest Med 1992; 13(3):427-435.
(97) Gurubhagavatula I, Maislin G, Nkwuo JE, Pack AI. Occupational screening for obstructive
sleep apnea in commercial drivers. Am J Respir Crit Care Med 2004; 170(4):371-376.
(98) George CF, Boudreau AC, Smiley A. Simulated driving performance in patients with
obstructive sleep apnea. Am J Respir Crit Care Med 1996; 154(1):175-181.
(99) Findley L, Unverzagt M, Guchu R, Fabrizio M, Buckner J, Suratt P. Vigilance and
automobile accidents in patients with sleep apnea or narcolepsy. Chest 1995; 108(3):619624.
Page 41 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
(100) Teran-Santos J, Jimenez-Gomez A, Cordero-Guevara J. The association between sleep
apnea and the risk of traffic accidents. Cooperative Group Burgos-Santander. N Engl J Med
1999; 340(11):847-851.
(101) George CF. Sleep. 5: Driving and automobile crashes in patients with obstructive sleep
apnoea/hypopnoea syndrome. Thorax 2004; 59(9):804-807.
(102) Hack MA, Choi SJ, Vijayapalan P, Davies RJ, Stradling JR. Comparison of the effects of
sleep deprivation, alcohol and obstructive sleep apnoea (OSA) on simulated steering
performance. Respir Med 2001; 95(7):594-601.
(103) Pack AI, Maislin G, Staley B, Pack FM, Rogers WC, George CF et al. Impaired
performance in commercial drivers: role of sleep apnea and short sleep duration. Am J
Respir Crit Care Med 2006; 174(4):446-454.
(104) Ajani UA, Lotufo PA, Gaziano JM, Lee IM, Spelsberg A, Buring JE et al. Body mass index
and mortality among US male physicians. Ann Epidemiol 2004; 14(10):731-739.
(105) Neser WB, Thomas J, Semenya K, Thomas DJ, Gillum RF. Obesity and hypertension in a
longitudinal study of black physicians: the Meharry Cohort Study. J Chronic Dis 1986;
39(2):105-113.
(106) Frank E, Wright EH, Serdula MK, Elon LK, Baldwin G. Personal and professional nutritionrelated practices of US female physicians. Am J Clin Nutr 2002; 75(2):326-332.
(107) La Puma J, Szapary P, Maki KC. Physicians recommendations for and personal use of lowfat and low-carbohydrate diets. Int J Obes (Lond) 2005; 29(2):251-253.
(108) Mihalopoulos NL, Berenson GS. Cardiovascular risk factors among internal medicine
residents. Prev Cardiol 2008; 11(2):76-81.
(109) Arora R, Lettieri C, Claybaugh JR. The effects of residency on physical fitness among
military physicians. Mil Med 2004; 169(7):522-525.
Page 42 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
(110) Gutgesell ME, Weltman A, Sowa C, Seip R, Bulatovic A, Woodson S. Fitness, body fat, and
perceived stress in a group of primary care residents. Acad Med 1992; 67(4):286-287.
(111) Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleepdisordered breathing among middle-aged adults. N Engl J Med 1993; 328(17):1230-1235.
(112) CDC. Obesity trends among U.S. adults between 1985 and 2007. 2007.
http://www.cdc.gov/nccdphp/dnpa/obesity/trend/maps/.
(113) Rajaratnam SM, Barger LK, Lockley SW, Cade B, O'Brien C, White D et al. Screening for
sleep disorders in North American police officers. Sleep 30[Abstract Supplement], A209.
2007.
(114) Krieger J, Meslier N, Lebrun T, Levy P, Phillip-Joet F, Sailly JC et al. Accidents in
obstructive sleep apnea patients treated with nasal continuous positive airway pressure: a
prospective study. The Working Group ANTADIR, Paris and CRESGE, Lille, France.
Association Nationale de Traitement a Domicile des Insuffisants Respiratoires. Chest 1997;
112(6):1561-1566.
(115) Sassani A, Findley LJ, Kryger M, Goldlust E, George C, Davidson TM. Reducing motorvehicle collisions, costs, and fatalities by treating obstructive sleep apnea syndrome. Sleep
2004; 27(3):453-458.
(116) Findley L, Smith C, Hooper J, Dineen M, Suratt PM. Treatment with nasal CPAP decreases
automobile accidents in patients with sleep apnea. Am J Respir Crit Care Med 2000; 161(3
Pt 1):857-859.
(117) Weaver TE, Kribbs NB, Pack AI, Kline LR, Chugh DK, Maislin G et al. Night-to-night
variability in CPAP use over the first three months of treatment. Sleep 1997; 20(4):278-283.
Page 43 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
(118) Patel SR, White DP, Malhotra A, Stanchina ML, Ayas NT. Continuous positive airway
pressure therapy for treating sleepiness in a diverse population with obstructive sleep apnea:
results of a meta-analysis. Arch Intern Med 2003; 163(5):565-571.
(119) Pack AI, Black JE, Schwartz JR, Matheson JK. Modafinil as adjunct therapy for daytime
sleepiness in obstructive sleep apnea. Am J Respir Crit Care Med 2001; 164(9):1675-1681.
(120) The International Classification of Sleep Disorders; Diagnostic and Coding Manual. Second
Edition ed. Westchester, IL: American Academy of Sleep Medicine, 2005.
(121) Drake CL, Roehrs T, Richardson G, Walsh JK, Roth T. Shift work sleep disorder:
prevalence and consequences beyond that of symptomatic day workers. Sleep 2004;
27(8):1453-1462.
(122) Czeisler CA, Walsh JK, Roth T, Hughes RJ, Wright Jr. KP, Kingsbury L et al. Modafinil for
excessive sleepiness associated with shift work sleep disorder. N Engl J Med 2005; 353:476486.
(123) Gold DR, Rogacz S, Bock N, Tosteson TD, Baum TM, Speizer FE et al. Rotating shift
work, sleep, and accidents related to sleepiness in hospital nurses. Am J Public Health 1992;
82:1011-1014.
(124) Mitler MM, Miller JC, Lipsitz JJ, Walsh JK, Wylie CD. The sleep of long-haul truck
drivers. N Engl J Med 1997; 337(11):755-761.
(125) Van Dongen HPA, Maislin G, Dinges DF. Dealing with inter-individual differences in the
temporal dynamics of fatigue and performance: importance and techniques. Aviat Space
Environ Med 2004; 75(3 Suppl):A147-A154.
(126) Van Dongen HPA, Caldwell JA, Jr., Caldwell JL. Investigating systematic individual
differences in sleep-deprived performance on a high-fidelity flight simulator. Behav Res
Methods 2006; 38(2):333-343.
Page 44 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
(127) Czeisler CA, Moore-Ede MC, Coleman RM. Rotating shift work schedules that disrupt sleep
are improved by applying circadian principles. Science 1982; 217:460-463.
(128) Czeisler CA, Johnson MP, Duffy JF, Brown EN, Ronda JM, Kronauer RE. Exposure to
bright light and darkness to treat physiologic maladaptation to night work. N Engl J Med
1990; 322:1253-1259.
(129) Czeisler CA, Dijk DJ. Use of bright light to treat maladaption to night shift work and
circadian rhythm sleep disorders. J Sleep Res 1995; 4(Suppl 2):70-73.
(130) Wyatt JK, Dijk DJ, Ritz-De Cecco A, Ronda JM, Czeisler CA. Sleep facilitating effect of
exogenous melatonin in healthy young men and women is circadian-phase dependent. Sleep
2006; 29:609-618.
(131) Principles and Practice of Sleep Medicine. 4th ed. Philadelphia: W.B. Saunders, 2005.
(132) Nutt D, Wilson S, Paterson L. Sleep disorders as core symptoms of depression. Dialogues
Clin Neurosci 2008; 10(3):329-336.
(133) Daley M, Morin CM, LeBlanc M, Gregoire JP, Savard J, Baillargeon L. Insomnia and its
relationship to health-care utilization, work absenteeism, productivity and accidents. Sleep
Med 2008.
(134) Goebert D, Thompson D, Takeshita J, Beach C, Bryson P, Ephgrave K et al. Depressive
symptoms in medical students and residents: a multischool study. Acad Med 2009;
84(2):236-241.
(135) Dyrbye LN, Thomas MR, Massie FS, Power DV, Eacker A, Harper W et al. Burnout and
suicidal ideation among U.S. medical students. Ann Intern Med 2008; 149(5):334-341.
(136) Dyrbye LN, Thomas MR, Huntington JL, Lawson KL, Novotny PJ, Sloan JA et al. Personal
life events and medical student burnout: a multicenter study. Acad Med 2006; 81(4):374384.
Page 45 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
(137) Fahrenkopf AM, Sectish TC, Barger LK, Sharek PJ, Lewin D, Chiang VW et al. Rates of
medication errors among depressed and burnt out residents: prospective cohort study. BMJ
2008; 336(7642):488-491.
(138) Vela-Bueno A, Moreno-Jimenez B, Rodriguez-Munoz A, Olavarrieta-Bernardino S,
Fernandez-Mendoza J, de la Cruz-Troca JJ et al. Insomnia and sleep quality among primary
care physicians with low and high burnout levels. J Psychosom Res 2008; 64(4):435-442.
(139) Ekstedt M, Soderstrom M, Akerstedt T, Nilsson J, Sondergaard HP, Aleksander P.
Disturbed sleep and fatigue in occupational burnout. Scand J Work Environ Health 2006;
32(2):121-131.
(140) University of Washington School of Medicine. Ethics in Medicine.
http://depts.washington.edu/bioethx/tools/princpl.html. 2-27-2009.
(141) Moore RT, Kaprielian R, Auerbach J. Asleep at the wheel. Report of the Massachusetts
commission on drowsy driving. 2-1-2009.
(142) Moore RT. An act relative to health care provider transportation. Senate Docket No. 1901.
1-14-2009.
(143) Falleti MG, Maruff P, Collie A, Darby DG, McStephen M. Qualitative similarities in
cognitive impairment associated with 24 h of sustained wakefulness and a blood alcohol
concentration of 0.05%. J Sleep Res 2003; 12(4):265-274.
(144) Powell NB, Schechtman KB, Riley RW, Li K, Troell R, Guilleminault C. The road to
danger: the comparative risks of driving while sleepy. Laryngoscope 2001; 111(5):887-893.
(145) Williamson AM, Feyer AM. Moderate sleep deprivation produces impairments in cognitive
and motor performance equivalent to legally prescribed levels of alcohol intoxication.
Occup Environ Med 2000; 57:649-655.
Page 46 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
(146) Lamond N, Dawson D. Quantifying the performance impairment associated with fatigue. J
Sleep Res 1999; 8(4):255-262.
(147) Arnedt JT, Owens J, Crouch M, Stahl J, Carskadon MA. Neurobehavioral performance of
residents after heavy night call vs after alcohol ingestion. JAMA 2005; 294(9):1025-1033.
(148) Landrigan CP, Barger LK, Cade BE, Ayas NT, Czeisler CA. Interns' compliance with
accreditation council for graduate medical education work-hour limits. JAMA 2006;
296(9):1063-1070.
(149) Carpenter RO, Austin MT, Tarpley JL, Griffin MR, Lomis KD. Work-hour restrictions as an
ethical dilemma for residents. Am J Surg 2006; 191(4):527-532.
(150) Cull WL, Mulvey HJ, Jewett EA, Zalneraitis EL, Allen CE, Pan RJ. Pediatric residency duty
hours before and after limitations. Pediatrics 2006; 118(6):e1805-e1811.
(151) Nasca TJ. Open letter to the GME community. 2-16-2009.
(152) Madsen T. A whistleblower's story: Reflections on making that report. The New Physician .
2004. The New Physician.
(153) California trucking company safety director and four drivers sentenced for their role in a
false driver's log book scheme. 7-21-2008. U.S. District Court, Fresno, California.
(154) Two sentenced in case involving falsification of truck drivers' logs. 3-11-1998. U.S.
District Court, Abington, VA.
(155) Trucking company, owner sentenced in driver log-fraud case. 1-22-1999. Federal Court,
MN.
(156) Trucking firm and president sentenced in hours-of-service violations. 7-24-2002. U.S.
District Court, Bangor, ME.
(157) Truck driver imprisoned for falsifying his driver's log. 12-16-2003. U.S. District Court,
Philadelphia, PA.
Page 47 of 48
Inter-individual Differences in Sleep-Deprived Performance Vulnerability
Czeisler
(158) South Dakota trucking firm and president ordered to pay over $325,000 in driver logbook
falsification case. 9-22-2005. U.S. District Court, Sioux Falls, SD.
(159) Former executive, dispatcher, and two drivers of Virginia trucking company sentenced for
their roles in falsifying drivers' logbooks. 1-18-2006. U.S. District Court, Lynchburg, VA.
(160) Former owner and dispatcher for Pennsylvania trucking company sentenced in logbook
falsification case. 3-14-2006. U.S. District Court, Williamsport, PA.
(161) Virginia truck driver gets jail time for falsifying logbooks. 8-11-2006. U.S. District Court,
Brunswick, GA.
(162) Four truck drivers sentenced in logbook falsification case. 2009. U.S. District Court,
Fresno, CA.
(163) Pennsylvania truck driver sentenced to 2 years in prison for vehicular homicide relating to
hours-of-service violations. 3-7-2007. State Court, Easton, PA.
(164) Cappuccio FP, Bakewell A, Taggart FM, Ward G, Ji C, Sullivan JP et al. Implementing a 48
h EWTD-compliant rota for junior doctors in the UK does not compromise patients' safety:
assessor-blind pilot comparison. Q J Med 2009.
(165) Fernandez-Taylor KR. Excessive Work Hours of Physicians in Training in El Salvador:
Putting Patients at Risk. PLoS Medicine 2007; 4(7):e205 1-3.
(166) Lerner BH. A life-changing case for doctors in training. The New York Times 2009 Mar 3.
(167) Lee CJ. Federal regulation of hospital resident work hours: Enforcement with real teeth. J
Health Care Law & Policy 2006; 9(1):1-55.
(168) Moore RT. An act relative to safe work hours for physicians in training and protection of
patients. Senate Docket No. 1178. 12-30-2008.
(169) Czeisler CA. President's Message. SRS Bulletin 2005; 11(2):4.
Page 48 of 48
Number or Surgical Errors
14
12
10
8
6
4
2
0
Before
After
Overnight Call
Overnight Call
Figure 1
Elapsed Time Awake (h)
Reaction Time (milliseconds)
0
8
16
24
32
6000
Psychomotor Vigilance
Performance
10% slowest reaction time
mean reaction time
median reaction time
10% fastest reaction time
1000
500
200
8
16
24
8
16
Relative Clock Time (h)
Figure 2
30
↑ Acuity +
↓ LOS Æ
↓ Sleep
>40 %
Percentage of monthly reports
25
20
15
Mean = 2.6 h
sleep/night
10
N = 2,737
5
0
0
>0-1
>1-2
>2-3
>3-4
>4-5
>5-6
>6-7
>7-8
>8
Reported hours of sleep obtained during extended duration w ork shifts
Figure 3
Figure 4
Slow Eye Movements
(number/hour)
Lapses of Attention
(number of RT >500 msec)
Mean RT
(msec)
Subjective Sleepiness
<---alert
sleepy--->
Habitual Sleep Episode
9
A
7
5
3
1
1750
B
1250
750
250
35
C
25
15
5
50
D
40
30
20
10
0
0
2
4
6
8
10
12
14
16
Time Awake (h)
18
20
22
24
26
Figure 5
400
Number of Crashes
350
300
250
200
150
100
50
0
16
22
28
34
40
46
52
58
64
70
76
82
Age of Driver (Years)
Figure 6
(greater impairment →)
PVT performance lapses
120
♦
100
80
60
♦
♦
40
20
0
♦
♦♦
♦ ♦
♦
♦
♦
♦
♦
♦♦
♦
♦
♦
♦
U OQ N F C A G B J HMT K S I R L E
subjects
Figure 7
Paced Serial Addition
Wake Duration (hours)
4
A
Slow Eye Movements
(% of time)
EEG Theta Activity
(μV2/Hz)
C
Waking Performance
composite score
B
8
12
16
20
24
28
25
D
32
36
40
E
* *
*
20
15
*
* *
10
*
*
* *
*
*
*
*
5
16
F
*
*
12
* *
8
4
G
0.50
* * * *
*
0.25
0.00
H
100
Melatonin (pg/ml)
*
80
60
40
20
-16
-12
-8
-4
0
4
8
12
16
20
Time (hours) Relative to Melatonin Midpoint (0)
Figure 8
6
12
Time of Day
18
24
Hours
Off in
24
6
M
Tu
0
Tu
W
W
18
Th
14
F
0
Sa
Su
18
24
M
Tu
0
18
W
14
Th
F
Sa
Su
M
Tu
Figure 9
100
90
80
70
60
50
40
30
20
10
0
p<0.001
p<0.001
p<0.001
ACGME data
HWHS data
% programs % programs % individuals
non-compliant non-compliant non-compliant
80h rule
30h rule
80h rule
•
•
83.6% of residents non-compliant with ACGME limits
Residents non-compliant in 61.5% of inpatient months
Figure 10