Why do we Sleep? No Idea • Sleep to avoid attracting predators in the night • Highly conserved. All vertebrates sleep • “Unlearning” mechanism whereby sleep erases unwantedthoughts or erroneous information Benefits of Sleep • Replenishes glucose and neurotransmitters in the brain • Sleep determines our waking success in terms of: • Mood, Alertness, Energy, Thinking, Productivity, and Safety • Promotes General Health and Longevity
Evolution of Sleep • Rest but no sleep – amphibians, fish
• Non-REM sleep only – lower reptiles
• A little REM – chameleons, – chameleons, crocodiles, birds (when babies) – echidna
• REM and NonREM
– All placental mammals
Development of Sleep • Babies spend 16 hours sleeping, initially half in REM. REM sleep in infants represents a larger percentage of the total sleep at the expense of stages III and IV. Until age 3-4 months, newborns transition from wake into REM sleep. Thereafter, wake begins to transition directly into NREM. • Over lifespan, total sleep decreases • Over lifespan, proportion of REM decreases
In elderly persons, the time spent in stages III and IV sleep decreases by 10–15% and the time in stage II increases by 5% compared to young adults, representing an overall decrease in total sleep duration. Latency to fall asleep and the number and duration of overnight arousal periods increase. Thus to have a fully restorative sleep, the total time in bed must increase. If the elderly person does not increase the total time in bed, complaints of insomnia and chronic sleepiness may occur.
Sleep Facts • Adults need an average 8.2 hours of sleep per 24 hours1 • Impairment of performance occurs occurs with as little as 2 hours less sleep than normal per night2 • Sleep debt from restricting sleep to 5 hours a night accumulatess with time, and awareness of sleepiness accumulate declines2 • The significance of circadian timing is rarely addressed when considering the effects of shift work
• National Heart, Lung, and Blood Institute Working Group on Problem Sleepiness. 1997. • Carskadon MA, et al. Sleep restriction. In: Monk T, ed. Sleep, Sleep, Sleepiness Sleepiness and
Performance. 1991.
Purpose of Sleep • Excessive sleep deprivation kills rats • Sleep deprivation makes people more tired
How Much Sleep Is Enough? • The amount that allows you to feel alert when rested and relaxed (eg, grand rounds) • There is little variation of sleep need (8.2 hours) among individuals • 1 night with 2 hours less than your usual sleep is sufficient to produce significant decrements in waking performance • After several nights of 5-hour sleep, most adults do not realize they are pathologically sleepy
Carskadon MA, et al. In: Monk T, ed. Sleep, Sleep, Sleepiness and Performance. 1991. Sleepiness
• Sleep-reversible state of consciousness • Brain relatively more responsive to internal than to external stimuli (visual, auditory, and other environmental stimuli) during dur ing the transition from wake to sleep • Historically, sleep a passive state initiated through withdrawal of sensory input. • Currently, of sensory awareness believed to be a factor in sleep,withdrawal but an active initiation mechanism that facilitates brain withdrawal recognized.
Why Do We Feel Sleepy? The 2-Process Model • 2 processes combined determine sleep propensity and the duration of sleep – Homeostatic sleep drive: • Process driven by amount of time awake • Linear and cumulative—one gets progressively more tired with each passing hour (“sleep load” increases)
– Circadian rhythm: • Process driven by biological clock (time of day) • Cyclical—periods of sleepiness occur at roughly the same times each day
Increases
Combined Sleep Processes The physiological pressure to sleep progresses linearly
Sleep
Sleep
The biological
s s e n i p e e l S
pressure to sleep occurs cyclically
Wake
Decreases
Wake
Noon
Midnight
Time (48 hours)
Noon
Midnight
• Sleep is an active process that cycles at an ultradian rhythm of about 90 minutes.
• Normal sleep is divided into NREM & REM • NREM has 4 stages
i) Stage I (Light sleep or slow wave sleep) ii) Stage II iii) Stage III (SWS) iv) Stage IV (Deep or delta wave sleep) (SWS)
• In adults, sleep of 8-8.4 hours is considered fully restorative. In some cultures, total sleep often is divided into an overnight sleep period of 6-7 hours and a midafternoon nap of 1-2 hours. •sleep. StageItIoccurs is considered a transition between upon falling asleep and duringwake briefand arousal periods within sleep and usually accounts for 510% of total sleep time. Stage II occurs throughout the sleep period andIV represents 40-50% of totalinsleep time. Stages III and delta sleep occur mostly the first third of the night. They are distinguished from each other only by the percentage of delta activity and represent up to 20% of total sleep time. REM represents 20-25% of total sleep time.
Normal Sleep Patterns in Young Adults AWAKE
REM
a t S e l S
p e
es g
The frequency of Stages alters during the been night - in The first REM period of Waking usually transitions For the purpose ofsleep analysis, overnight sleep has One cycle of REM-nonREM The proportion of REM sleep the early hours of be sleep SWS dominates, divided into 3may equal time periods: sleepfalls in whereas therapidly firstREM third the night less than into NREM sleep followed by lasts aboutmore 90-100 minutes sleep occurs often in the second part of sleep. The of the night night, , which comprises the percentage portion of REM sleep duringthird night alters with age in of and plateaus at 25% until it falls further inin REM 10 minutes and then duration, followed while byofhighest and, 4-5 cycles occur during NREM; sleep ininthe middle the night; and -sleep old age. Children have more sleep time and newborn babies REM sleep lasts for 50%, pre-mature the last may exceed 60 NREM the last third of 9-hour the night,sleep the majority of which is REM. normal 8to stage 4 sleep than adults. infants 80% & in adults for 20%. minutes. Awakening after a night full night's sleep is usually from REM period during sleep.. sleep
REM Stage NREM
1 2 3 4
1
2
3
4
5
6
7
8
Hours of Sleep
Adapted from Berger RJ. The sleep and dream cycle. In: Kales A, ed. Sleep
Physiology & Pathology: A Symposium. Symposium. Philadelphia: J.B. Lippincott; 1969.
Sleep spindles begin
Human Sleep Stages
Awake— Awake—low low voltage-random, fast
50µ V 1 sec
Drowsy—8 Drowsy— 8 to 12 cps-alpha c ps-alpha waves waves
Stage 1—3 1—3 to 7 cps-theta waves Theta Waves
appearing the secondin month of life with a density greater than that seen in adults . After the first year the spindles begin decreasing in density progressand toward adult patterns. K complexes begin by the sixth month o life.
Human Sleep Stages 2—12 to 14 cps-sleep spindles and K complexes Stage 2—12 sleep spindle
K complex
Stage 3/4—1/2 3/4—1/2 to 2 cps-delta waves>75µV
REM Sleep—low waves* Sleep—low voltage-random, fast with sawtooth waves* *
*
Brain Waves in Sleep • Waking – low amplitude, high frequency
• Stage 1 – mostly theta waves
• Stage 2 – sleep spindles • brief period of high amp,high f
– K-complex
• Stage 3 – appearance of delta waves
• Stage 4 (slow wave sleep) – mostly delta
• REM – like Stage 1, but with REM
Physiology of Sleep I
Circadian Cycle • The Biological Clock…the that operates on a 24-hour cycle regular bodily rhythms • Independent of environmental stimulus • Maintain appropriate sleep and wakefulness cycle SCN•(Suprachiasmatic Nucleus) Photoreceptors that containing Melanopsin • Synchronization of the circadian cycle with the day/night cycle • Regulates body temperature, hormone secretion, urine production, and blood pressure to match the Circadian Cycle • Stimulation of Pineal gland that releases Melatonin – Neuro-hormone that promotes sleep
Diencephalic sleep zone (Post hyp+ ant hyp N) Medullary synchronizing zone (RF at level of NTS) Basal forebrain sleep zone Serotonin agonist- suppression of sleep Serotonin antagonist (ritanserin)- SWS inc Adenosine- Sleep increase, Role of Coffee?
PGD2- medial POA of hyp- SWS + Rem inc PGE2- Wake Resrpine depletes serotonin and catecholmine, blocks SWS and REM but increases PGO spike Barbiturates Dec SWS
Functional dissociation b/w brainstem and cerebral cortex
Cerebral cortex
Intralamin ar nuclei of thalamus
Rostral
Histamine Posteroinfundibualr region
Inhibitory signal Ant Hyp POA Brainstem RF & Post Hyp 1) Dec in ascending cholinergic pathway 2) Dec cortical
Pontine reticular
responsiveness
Centre inhibited
GABA + Ach
NREM is an active state that is maintained partly through oscillations between the thalamus and the cortex. The 3 major oscillation systems are sleep spindles, delta oscillations, and slow cortical oscillations. Sleep spindles, a hallmark of stage II sleep, are generated by bursts of hyperpolarizing GABAnergic thalamic reticular neurons. These bursts inhibit thalamocortical projection neurons.
The functions of NREM sleep speculative, several theories have been put forth. - One theory : that decreased metabolic demand facilitates replenishment of glycogen stores. -Another theory, which utilizes neuronal plasticity, suggests that the oscillating depolarizations and hyperpolarizations consolidate memory and remove redundant or excess synapses.
During NREM sleep, the metabolic demand of the brain decreases. This is supported by oxygen positron emission tomography (PET) studies, which show that, during NREM sleep, the blood flow throughout the entire brain progressively decreases.
REM sleep is generated by mesencephalic and pontine cholinergic neurons, hence these are referred to as REM-on neurons. As REM sleep initiates, monoadrenergic locus ceruleus (NA) and serotonergic raphe neurons become inactive and are called REM-off neurons.
Control of REM by Pontine Nuclei
Physiologic correlates of Sleep states NREM- HR & BP inc & reverse during REM Cardiac dysrhythmia- REM sleep fR regular- NREM Opp during REM High PCO2 PCO2 d during uring N NREM REM due to dec in VE SWS- inc GH, dec TSH, ACTH cortisol axis NREM Sleep- Attenuated thermoregulatory fn to cold and heat, REM complete unresponsiveness
REM Sleep
•• EEG remarkably to awakestate Eachissleep cycle is similar 90 minutes • Increasing REM intervals • Characterization: ••Increase Rapid EyeinMovement (REM)Heart Rate, and Blood Pressure, Metabolism • Paralysis of large muscles (Tone of sk ms in neck dec) • Genital Arousal • Dreaming and Visual Hallucinations • Lack of self-reflection • Lack of Volitional Control • periodic skeletal muscle twitches, pupil dilation, and increased respiratory rate
Active Brain in an Inactive Body
PET studies also show that, during REM sleep, blood flow increases in the thalamus and the primary visual, motor, and sensory cortices, while remaining comparatively decreased in the prefrontal and parietal associational regions. The increase in blood flow to the primary cortical regions may explain the vivid nature of REM while the continued decrease in dreaming, blood flow to the prefrontal cortex may explain the unquestioningg acceptance of even the most unquestionin bizarre dream content.
An essential method in human clinical and basic sleep research is polysomnography. It is composed of measuring electroencephalogram (EEG), electrooculogram (EOG) and electromyogram (EMG)
Figure :Placement of electrodes of polysomnographic measurement
The Description of Brain Waves • Two parameters – frequency • the number of waves per second, measured as Hertz, Hz
– amplitude • the height of waves, measured in EEG recordings as microvolts, or V
• Synchronization
• synchronized: waves are aligned with each other in time • desynchronized: waves occur randomly with each other in time
• Eyemovements – E lectro lectroocula g raph raph (EOG)
• Muscle tension – E lectro lectromyo g raph raph (EMG)
Additional Bodily Changes • Decreased threshold of awareness of external events • Vestibular activation during REM • Autonomic arousal in REM • Genital arousal in REM
Impact and Recognition of Sleep Deprivation
What Is Good Performance? • • • • •
Motivation Ability to see the “big picture” Memory for details Prompt decision making Accurate and consistent motor performance
• Good communication • Contingency planning • Professionalism
Clinical Signs of Excessive Sleepiness
• Irritability, moodiness, and disinhibition • Frontal lobe signs – Apathy, impoverished speech, flattened affect – Impaired memory – Inflexible thinking and impaired planning skills—an inability to be novel or to multitask
• Intrusive sleepiness – Microsleeps (5 to 10 seconds) cause lapses in attention – Nodding off when sedentary – REM phenomena (hypnagogic hallucinations) Dinges D, et al. In: Monk T, ed. Sleep,
Sleepiness and Performance. Performance. 1991. Rosekind MR, et al. Behav Med . 1996.
Less than 3 hrs/night: Results of Deprivation • Increase in Blood Pressure • Increase in blood Glucose level • Decrease in Leptin level • Hypertension, Obesity, Heart Attack, and Stroke Less than 6 hrs/night: • Increase in Cytokine level • Inflammation of arteries, Hypertension, and Stroke • Increase in production of C-Reactive Proteins by the Liver • Breaks down heart chambers • Increase in risk of Type-II Diabetes • Reduction of resistance to Viral Infections
laboratory studies indicate that nocturnal sleep periods reduced by as little as 1.3 to 1.5 hours for 1 night result in reduction of daytime alertness by as much as 32% as measured by the Multiple Sleep Latency Test (MSLT).
Physiological effects of sleep deprivation include: hypoxemia, insulin resistance, elevated sympathetic activity, and blunted arousal response.
Increases
Circadian Rhythm
s s e n i p e e l S
Most vulnerable times to feel sleepy are 5-8 AM and 2-4 PM (independent of lunch) Most likely times to feel alert are 10 AM to 12 noon, and again in the evening
Decreases 12
Time (h)
24
University of Virginia Center for Biological Timing. Available at:
Performance Errors Meter Reading Error Errors s Sweden
11,000
N = 74,927
10,000 9000
s r o 8000 r r E f 7000 o . o N 6000
5000 4000
Time of Day Midnight
6 AM
Noon
6 PM
Midnight
Mitler MM, et al. Sleep Sleep.. 1988.
Vehicle Accident Data Fatigue-Related Accidents International Data
1200
N = 6052
1100 1000 900 s t n e d i c c A f o .
800
o N
300
700 600 500 400 200 100 Time of Day
Midnight
6 AM
Noon
6 PM
Midnight
Mitler MM, et al. Sleep Sleep.. 1988.
Overlay of Vehicle Accident Data, Performance Errors, and Circadian Rhythm
Midnight
6 AM
Noon
6 PM
Midnight
Survey of Pediatric On-Call House Staff and Faculty
House Staff (on call every 4th night) N = 70
Faculty Members (sleep undisturbed) N = 85
87%
87%
2.7 ± 0.9
6.5 ± 0.8
Fell asleep at stop light
44%
12.5%
P <.001 <.001
Fell asleep while driving* Fell asleep at the wheel†
23% 49%
8% 13%
NS P <.001 <.001
Response rate Average hours sleep
Statistical significance
*While car in motion †
While car in motion or at stop light
Marcus CL, et al. Sleep Sleep.. 1996.
National Survey of 963 Emergency Medicine Residents Motor Vehicle Accidents 8% had >1 MVAs
N = 963 (1554 polled, 62% response rate)
(mean = 1.3 accidents)
76 (8%)
26% 74%
74% of MVAs were related MVA = motor vehicle accident
to night shift
Steele MT, et al. Acad al. Acad Emerg Med . 1999.
National Survey of 963 Emergency Medicine Residents (continued)
Near-Crashes
N = 963 (62% response rate)
80% 553 (58%) 20%
58% had >1 near-crashes (mean = 2.6 near-crashes)
80% of near-crashes were related to night shift
Steele MT, et al. Acad al. Acad Emerg Med . 1999.
Sleep Deprivation and Medical Performance
Patient Care Is Jeopardized • During laparoscopic surgery after a night on call with an average sleep time of 1.5 hours1: – Fine motor control degrades – More time taken to complete surgery – More complications postop
• Prescribing errors2made connected with physical and mental well being : – Tired – Hungry – Unwell
•
Grantcharov TP, et al. BMJ . 2001.
Unwell
•
Dean B, et al. Lancet . 2002.
Studies on Impact of Sleep Deprivation • Why do studies in the clinical setting produce mixed results when laboratory studies clearly show the impact of sleep deprivation on performance? – Lack of well-rested residents for control groups • Studies essentially compare effects of chronic partial sleep restriction (residents not on call) versus chronic partial sleep restriction plus short-term sleep loss (residents on call or immediately post call)
– Differences in general health status and sleep/wake habits – Failure to control for caffeine and food intake, recent physical activity, and ambient temperatures – Effects on specific tasks may be overcome by motivation and focused attention; more difficult to measure continuous
performance
Impact of Sleep Deprivation on Resident Health • Increased risk of obstetrical complications for pregnant residents versus other working women1 – Premature labor is twice as common – Preeclampsia is twice as likely
• High rates of depression occur among residents2 – 30% of first-year residents report depressive symptoms for an average of 5 months – Some reported to have suicidal ideation with plan – Among married residents, 46% in depressed group versus 7% in the nondepressed group had marital problems prob lems (none of the depressed individuals had ever had martial problems prior to depression onset)
1. Osborn LM, et al. J Fam Pract . 1990. 2. Valko RJ, et al. Dis Nerv Syst . 1975.
The Cultural Environment “We believe that long hours are an inherent part of our profession, and if we don’t train in the way we will work in the future, we will not be able to function adequately. This is analogous to pilots; if they don’t practice flying flying at night, how can we expect them to fly at night?” “Who are we? The answer is that we are physicians, a highly selected group, and we are not representative of the population as a whole.”
Preventive and Operational Countermeasures
Preventive and Operational Countermeasures Scheduling • Limit continuous performance schedules to 12-16 hours • Time off duty to protect sleep and sanity
Working With Circadian Rhythm • Know the times of greatest impairment and maximum alertness
Avoid Alcohol
Preventive and Operational Countermeasures Education • No substitute for sleep • Avoid driving between 2 AM and 9 AM • Behavioral changes may indicate dangerous levels of fatigue • Need for performance backups during times of impairment • Interaction between alcohol and sleep loss can be deadly
• Benefits of prophylactic naps
Does Napping Help? Night shift workers after 2-hour nap prior to shift • Prevented sleepiness • Later naps produced a deeper sleep, but workers awakened with grogginess due to sleep inertia
ER residents after 1-hour nap prior to a night shift • EEGs show clearly enhanced awake activity • Reduced stress • Workload perceived as less onerous Dinges DF, et al. Sleep Sleep.. 1997.
Rosekind MR, et al. Behav Med . 1996. Frey R, et al. Crit Care Med . 2002.
Preventive and Operational Countermeasures Pharmacology • Caffeine—widely available, widely accepted – Boosts alertness – Tolerance to benefits develops quickly – Erodes sleep quality – Undesirable side effects on mood – Less-predict Less-predictable able GI absorption; active longer than half-life suggests
Preventive and Operational Countermeasures Pharmacology • Alcohol – Induces sleep initially – Increases fragmentation – Overall, a bad choice for sleep
Sleep Disorders • Narcolepsy (high levels of REM) • Hypersomnia (high levels of NREM) • Parasomnias – Night Night terrors – Sleepwalking – Sleeptalking – Sleeptalking
Narcolepsy • Clinical symptoms: the narcoleptic tetrad – excessive sleepiness during the day – cataplexy – cataplexy • abrupt loss of muscle tone, without loss of awareness
– sleep paralysis • muscle paralysis of sleep
– hypnagogic hallucination
• Waking usually transitions into NREM sleep followed by REM and then followed by NREM • T h hee first REM period of the night may be less than 10 minutes in duration, while the last may exceed 60 minutes. • One cycle of REM-nonREM lasts about 90-100 minutes and, 45 cycles occur during normal 8- to 9-hour sleep period during night
The Cycles of Sleep Stages
For the purpose of analysis, overnight sleep has been divided into 3 equal time periods: sleep in the first third of the night,, which comprises the highest night percentage of NREM; sleep in the middle third of the night; and sleep in the last third of the night, the majority of which is REM. Awakening after a full. night's sleep is usually from REM sleep sleep.
The frequency of sleep Stages alters during the night - in the early hours of sleep SWS dominates, whereas REM sleep occurs more often in the second part of sleep. The portion of REM sleep during night alters with age in newborn babies REM sleep lasts for 50%, pre-mature infants 80% & in adults for 20%.
The proportion of REM sleep falls rapidly and plateaus at 25% until it falls further in old age. Children have4more sleep time and stage sleep than adults.
Summary • In response to the new ACGME standards, this presentation has: – Reviewed the impact of sleep loss and fatigue on cognitive function and performance – Described the signs of fatigue and sleepiness from sleep deprivation – Outlined preventive and operational countermeasures
• While there are short-term countermeasures available, ultimately, the only cure for sleep deprivation is sleep.
Sleep initiation may begin with the emergence of inhibitory signals from the anterior hypothalamic preoptic nucleus directed caudally toward the brainstem reticular corenucleus and posterior posterior The preoptic inhibitshypothalamus. the histaminergic posterior hypothalamic tuberoinfundibularr region through GABA and tuberoinfundibula probably acetylcholine.
The tuberoinfundibular region projects rostrally to the intralaminar nuclei of the thalamus and to the cerebral cortex. Inhibition of the tuberoinfundibular region is a critical step toward falling asleep because it results in functional disconnection between the brain stem and the more rostral thalamus and an d cortex. A decrease in ascending thalamic cholinergic transmissions occursresponsiveness. in association with decreasing cortical In addition to inhibiting higher cortical consciousness, the tuberoinfundibular tract projects caudally into