Adverse Eects of Sleep Deprivationin the ICU

Rachel E. Salas, MDa,*, Charlene E. Gamaldo, MDb,c

aDepartment of Neurology, Johns Hopkins School of Medicine, 5501 Hopkins Bayview Circle,

Allergy and Asthma Center1B.75A, Baltimore, MD 21224, USAbDepartment of Neurology, Johns Hopkins School of Medicine, 5501 Hopkins Bayview Circle,

Allergy and Asthma Center1B.76A, Baltimore, MD 21224, USAcDepartment of Medicine, Division of Pulmonary/Critical Care, Johns Hopkins

School of Medicine, 5501 Hopkins Bayview Circle, Allergy

and Asthma Center1B.76A, Baltimore, MD 21224, USA

The hospital is not conducive to sleep. Patients commonly recount ma-jor issues with sleep initiation and poor sleep quality during their hospitalstay [1]. Moreover, patients in the ICU are particularly susceptible to sleepdisruption secondary to environmental and medical issues. Despite the fre-quency of sleep disruption in the ICU, the quality of critically ill patientssleep is often overlooked. When questioned following discharge from theICU, patients frequently report the occurrence of sleep disruption duringtheir stay, suggesting that sleep disruption in the ICU is widespread. Dis-turbed sleep patterns result in the undesirable consequences of daytimesleepiness, lethargy, irritability, confusion, and poor short-term memory[2]. The potential negative neurologic sequelae from sleep loss may oftenlead to additional tests to evaluate for change in mentation (eg, frequentneurologic checks, head CTs, or MRIs), potentially resulting not only inan increased nancial burden to an already strained health care systembut also in extended hospital stays. Patients requiring additional work-upbecause of their sleep-related change in alertness are less able to receivethe care and services, such as physical and occupational therapy, that ben-et timely discharges. In fact, increasing evidence supports the concept thatsleep disturbance in the ICU can aect patient mortality during hospitali-zation and after discharge from the unit. The level of impact of the ICUexperience on a patient seems to be multifactorial; hence, this article

Crit Care Clin 24 (2008) 461476* Corresponding author.

E-mail address: rsalas3@jhmi.edu (R.E. Salas).

0749-0704/08/$ - see front matter 2008 Elsevier Inc. All rights reserved.doi:10.1016/j.ccc.2008.02.006 criticalcare.theclinics.com

y tosuer from the consequences of insucient sleep even before their ICU ad-

be an important cause of sleep disturbance. A signicant increase in sleep

disruption has been found in patients who have higher disease severityscores [5]. One study reported that ICU patients who had higher AcutePhysiology and Chronic Health Evaluation (APACHE) scores had a higherawakening index, shorter sleep time, and decreased slow-wave sleep thandid healthy volunteers in the same environment [6]. Insomnia attributablemission. Inadequate sleep and unhealthy sleep practices are a universalproblem aecting individuals at all ages. In the 2002 National Sleep Foun-dation annual survey, nearly 40% of adults 30 to 64 years old and 44% ofyoung adults 18 to 29 years old reported that daytime sleepiness is so se-vere that it interferes with work and social functioning at least a fewdays each month [4]. Older adults average 7.0 hours of sleep on weeknightsand 7.1 hours on weekends [4], whereas younger adults average 6.7 hoursof sleep on weeknights, which increases to 7.6 hours on weekends [4].Optimal daytime performance with minimal sleepiness seems to requireat least 7.5 to 8.5 hours of sleep at night with few interruptions [4]. An in-sucient amount of sleep can result in poor daytime functioning, whichmay interfere with patient mortality while in the ICU. It is therefore impor-tant that ICU physicians are aware of the severe chronic sleep loss oftenendured by their patients to minimize aspects of the ICU that could com-pound the eects of their chronic sleep loss with superimposed hospital-induced acute sleep loss.

Medical illness

Several studies have shown that underlying medical illness may contrib-ute to the sleep disruption experienced by patients while in the hospital.There have been limited studies showing the correlation between the degreeof medical illness and sleep in the ICU; however, the severity of illness maysleepiness [3] in the general population, and many patients are likeldiscusses the following issues essential to understanding the factors associ-ated with sleep loss in the ICU: (1) core elements to consider from thebaseline sleep history, (2) impact of the ICU environment on the ICU pa-tients sleep pattern, and (3) overall systematic impact of sleep deprivationon the ICU patient.

Baseline sleep history of the ICU patient

Chronic insucient sleep: an epidemic at all ages

Insucient sleep is the most common cause of daytime fatigue and

462 SALAS & GAMALDOto medical conditions is another potential sleep disorder that may be en-countered in the ICU that is caused by a pre-existing medical condition.The insomnia may involve a problem with sleep initiation or maintenance,which impacts overall sleep quality and daytime functioning.

nes

theearly afternoon awakenings. The elderly are particularly susceptible toa circadian rhythm sleep disorder (CRD), as a persistent sleep patternthat is disruptive due to changes in the circadian timekeeping system or mis-alignment between the endogenous circadian rhythm and societal factors.The recurrent misalignment results in signicant diculties with sleep initi-ation or duration that leads to problems with insomnia, excessive daytimesleepiness, and a decreased level of social and occupational functioning[19]. Individuals across all ages are prone to developing a CRD. Adolescentsare more prone to the CRD delayed phase type that takes on the classicnight-owl characteristics of late night sleep initiation and late morning/attempt to treat with CPAP or bilevel pressure may be of benet.The International Classication of Sleep Disordersd2nd edition deSleep and pain

Pain was identied as one of the leading stressors in the hospital by thepatients, relatives, and health care professionals in one survey [7]. Chronicpain syndromes are known to be associated with alterations in sleep conti-nuity and sleep architecture. Although studies show that approximately50% of patients who have various chronic pain syndromes complain ofsignicant sleep disturbance [811], less is known about acute pain in theICU. Nonetheless, it has been established that sleep disruption negativelyaects the opioid system and pain perception.

Primary sleep disorders

Many hospitalized patients reported having excessive daytime somno-lence, insomnia, snoring, and restless legs syndrome before hospitalization[12]. Primary sleep disorders may result in chronically decreased continuityof sleep, increased sleep deprivation, and associated impairments in daytimefunctioning, including fatigue, cognitive decits, and excessive daytimesleepiness. Acutely ill patients who have sleep-disordered breathing, suchas sleep apnea, may develop respiratory failure or have diculty beingweaned from mechanical ventilation [13,14]. Cardiovascular problems,such as dysrhythmias, myocardial ischemia, and heart failure, also are asso-ciated with sleep-disordered breathing [15]. Sleep-disordered breathing isalso common, especially in cardiac patients [16]. Sleep-disordered breathingmay be serendipitously discovered in the ICU because of continuous pulseoximetry, which has been used in the past as a screener for sleep apnea,especially in countries with limited resources [17]. Patients who havesleep-disordered breathing have increased health care costs secondary tocardiovascular risk and other comorbid conditions, such as obesity, diabe-tes, and hypertension [18]. For patients who have known sleep apnea, an

463ADVERSE EFFECTS OF SLEEP DEPRIVATION IN THE ICUCRD advanced phase type, which involves early morning awakenings andmore daytime napping [20,21]. Moreover, elderly who have even a milddegree of dementia can be susceptible to sundowning, which is another man-ifestation of circadian rhythm misalignment. Elderly individuals who have

mayaints

and sedation, likely to further exacerbate their symptoms. For this reason,

lence [19]. The environmental factors disrupting sleep were identied and

include medical interventions, diagnostic procedures, patientsta interac-tions, light, and noise, with noise being the most common disruptive envi-ronmental factor reported in the ICU [23].

Noise

Noise has been found to cause damaging physiologic eects, includingdelayed healing [24], impaired immune function [25], and increased bloodpressure [26], heart rate [27], and overall stress [28]. Noise may also increasemedical mistakes [29,30] and impair the concentration and mental eciencyof the sta [31], which could ultimately increase length of hospital stay andmorbidity of patients. Alarms, phones, televisions, beepers, ventilation ma-chines, housekeeping, and conversations have all been reported to be majorcontributors to ICU noise. Several studies have shown that noise in the ICUcan peak above the recommended values of the Environmental Protectionit is imperative that the ICU treatment team is aware of any pre-existingsleep disorders that may be exacerbated further in the ICU.

Impact of the ICU environment on sleep: iatrogenic environmentalsleep disorder

Several diverse factors often contribute to poor sleep quality, includingenvironmental factors, such as noise and ambient light, nursing interven-tions, medications, patientventilator interactions, anxiety, and preexistingchronic conditions, along with the acute illness itself. The InternationalClassication of Sleep Disordersd2nd edition denes environmental sleepdisorder, as a sleep disturbance due to a disturbing environmental factorthat causes a complaint of either insomnia or daytime fatigue or somno-associated symptoms manifest during hospitalization, these patientsbe perceived as being agitated or confused leading to the use of restrvisual impairment are more likely to have impaired nighttime sleep than vi-sually unimpaired elderly subjects [22]. The awareness of patients inherentcircadian sleep patterns is crucial to understanding the impact of the ICUsetting on patients sleepwake behaviors.

Rapid eye movement (REM) sleep behavior disorder and other parasom-nias may also occur during hospitalization in the ICU, which may confoundmedical management. Along these same lines, patients who have restless legssyndrome may report limb dysesthesias associated with an overwhelmingurge to get up out of bed as part of their clinical phenomenology. If these

464 SALAS & GAMALDOAgency for day (45 dB) and night (35 dB). Despite the excess noise in theICU setting, studies [32,33] have shown that noise only contributes to a smallpercentage of arousals and awakenings during sleep, suggesting that thereare indeed multiple factors contributing to disrupted sleep in the ICU.

ls to

oursucedbetter sleep; however, one study revealed that lowering the light levels induceda greater variation of light, which may impair sleep quality [36]. Moreover,another study indicates that dyssynchronization of the melatonin secretion,which is aected by light, is common in critically ill and mechanicallyventilated patients [37]. It is yet to be determined whether an impairment ofthe melatonin rhythm may play a role in the development of sleep distur-bances and delirium in intensive care patients; therefore, melatonin replace-ment as a potential treatment option is currently not suggested [38].

Stapatient interactions

Despite the increased sophistication of monitoring systems in hospitals to-day, there are still frequent stapatient interactions leading to sleep disrup-tion. Studies have found that the mean number of stapatient interactionsranged from 42 to 51 per night in the ICU [39,40]. One study found that therethe day (6 AMmidnight) and 128 to 1445 lux during nighttime h(midnight6 AM) [23]. One might assume that this decrease in light prodaddress issues such as noise by implementing a quiet time, providing earplugs, eliminating intercom use, reducing phone and alarm volumes, closingdoors, and in some cases altering the routine of housekeeping [34]. Somecenters have even incorporated wireless individualized paging to addressthe beepers and intercoms. Other interventions, such as soundproonghospital rooms, have been considered to decrease noise. Overall, most ofthe hospitals that have implemented a sleep protocol report improvementin their patients and families level of hospital satisfaction.

Light

Light is also amajor cause of sleep disruption in the ICU setting [23]. Lightis the primary environmental cue (zeitgeber) responsible for setting the circa-dian clock and can shift the phase response curve depending on the timing andintensity of light exposure. Light levels in the 100 to 500 lux range have beenshown to aect nocturnal melatonin secretion and levels in the 300 to 500 luxrange may have an eect on the human circadian pacemaker [35]. One studyshowed that patients in the ICU maintained daynight rhythms over a 7-dayperiod, withmeanmaximum light levels ranging from 1602 to 5089 lux duringare also involved [6].In recent years, some ICUs have implemented various sleep protocoSynchronous audio, video, and polysomnographic recording in seven venti-lated patients showed that 20% of the recorded arousals and awakeningswere related to noise and 10% to patient care activities, whereas the causesof the remaining 70% were not identied, indicating that unknown factors

465ADVERSE EFFECTS OF SLEEP DEPRIVATION IN THE ICUwere 8 stapatient interactions per hour of patient sleep, with most of theseinteractions attributable to nursing activities, such as wound dressing, adjust-ment of intravenous drips, and administration of medications [6]. Nurseswere also found routinely to provide daily baths for patients between 02:00

to vary signicantly in dierent ICUs [33].

entlyunable to entrain their respiratory activity to a mechanical ventilator and

tics,anorectics, antiepileptics, and dopaminergic agents.Systematic look at the impact of sleep loss on the ICU patienthypertensive agents, hypolipidemic agents, corticosteroids, antipsychomay require heavy sedation and occasionally even paralysis to achievesatisfactory patientventilator synchrony.

Medications

Several medication used in the ICU can cause sleep disruption. For exam-ple, benzodiazepines may increase sleep time eciency, decrease sleeplatency, and decrease awakenings, which overall seems to improve sleepquality and quantity. Nevertheless, benzodiazepines may also decreaseslow wave sleep and REM sleep, increase cortical activity and sleep spindles,but also decrease EEG amplitude at high doses [4345]. Narcotics have beenshown to suppress slow-wave sleep and REM sleep and increase arousalsand sleep stage 1 [46]. Inotropic medications, such as dopamine, may causecortical activation and therefore increase arousals during sleep also. Furtherstudies are needed to see the eects of these commonly used medications onsleep patterns in the ICU setting. Insomnia can be a side eect of severalmedications commonly used in the ICU that include antidepressants, anti-sleep fragmentation in ventilated patients [42]. ICU patients are frequRespiration and ventilated ICU patients

Aside from the environmental factors and medical illness severity aect-ing the sleep patterns of the ICU patient, mechanical ventilation is yetanother factor that confounds overall sleep. The discomfort of the endotra-cheal tube, inability to communicate adequately, and the stress and anxietyof being intubated are also experienced by the ventilated ICU patient. Butwhat about the mechanical ventilation itself and the eect it has on sleep?There seems to be a circadian pattern to respiration and respiratory control,even in the absence of sleep. Functional residual capacity, forced expiratoryvolumes, and airway resistance change periodically with the time of day.Resting pulmonary ventilation, tidal volume, and breathing rate also followcircadian patterns, responding dierently to hypercapnia or hypoxia atvarious times of the day [41]. Studies in ICU patients have revealed severeand 05:00 on 55 of the 147 study nights in the ICU [39]. As expected, sleepdisruptions caused by patient interventions or diagnostic tests were found

466 SALAS & GAMALDOImpact on sleep quality and quantity

In one study, 29% of patients received a prescription for a hypnotic drugwhile in hospital, with no evidence of preadmission hypnotic use [47]. These

ders.rmal

sleep patterns did not return to patients who had acute myocardial infarc-

tion until 9 days after discharge from the ICU [49].

Polysomnography (PSG) studies have demonstrated decreased total sleeptime, fragmentation, and altered sleep architecture in ICUs [4952]. Despitehaving a relatively normal amount of sleep in the ICU, approximately 50% ofthe total sleep occurs during the day, which suggests that most patients do notobtain sleep during the optimal nocturnal time frame. A distinct increase instage 1 of non-REM sleep and a concomitant decrease in slow-wave sleepand REM sleep are also apparent in ICU patients [50,5255]. Recent researchhas concluded that sleep cannot be identied by PSG in all critically illpatients, because of illness- and drug-induced EEG changes. In these patients,particular EEG features are characteristic of coma and sometimes also a stateof pathologic wakefulness, in which behavioral correlates of wakefulness,such as sustained chin EMG activity, coincide with EEG features of slow-wave sleep. This nding suggests that the sleep patterns of ICU patientsmay be even more aected than believed originally.

Disrupted sleep can also result in added anxiety and pain to patients.Roehrs and colleagues [56] found that the loss of 4 hours of sleep andREM-specic sleep loss is associated with hyperalgesia symptoms thefollowing day. ICU patients are also at risk for developing adjustmentinsomnia, which is insomnia in association with an identiable stressorthat lasts for less than 3 months.

Impact on the cardiovascular system

In a study of cardiovascular autonomic modulation during 36 hours oftotal sleep deprivation, the 18 normal subjects studied demonstrated in-creased sympathetic and decreased parasympathetic cardiovascular modula-tion and decreased baroreex sensitivity [57]. In addition, frequent arousalsduring sleep are associated with elevated catecholamine release andincreased blood pressure [58].

Insucient sleep increases the risk for acute myocardial infarction in re-discriminate between these two potential causes of persistent sleep disorRepetitive whole-night EEG studies, however, demonstrated that nodata suggest that poor sleep develops during hospitalization and is ubiqui-tous among patients. In a study by Halfens and colleagues [48], inpatientswho took sleep medication for at least 5 days were more likely to remainon those sleep medications after discharge home than were patients whodid not receive hypnotics. This nding suggests that inpatient sleep distur-bance may have some long-term sequelae, although the impact of underly-ing medical illness cannot be ruled out. Current studies do not allow us to

467ADVERSE EFFECTS OF SLEEP DEPRIVATION IN THE ICUlation to an elevated activity in the sympathetic nervous system [59,60].More recently, a case report showing a spontaneous coronary dissection as-sociated with sleep deprivation presenting with acute myocardial infarctionwas described, further supporting the role sleep plays in morbidity [61].

stent

oses

tionthat the performed task results in a globally diminished response [74].

ium.Circadian rhythm abnormalities may also contribute to ICU delirImpact on mentation

Delirium in the ICU, otherwise known as ICU syndrome, is a well-recog-nized phenomenon. Currently there has been no documented relationshipbetween sleep deprivation and delirium. A potential relationship betweenthese two may lead to heightened attention toward sleep deprivation inthe ICU because sleep deprivation and delirium commonly co-occur. Inthis section, evidence suggesting a relationship between sleep deprivationand ICU syndrome are discussed.

Relationship of sleep deprivation and nightmares to deliriumIntense dreaming andnightmares are often reported by patients in the ICU.

Schelling and colleagues [75] reported that 64% of patients who had acuterespiratory distress syndrome recalled traumatic nightmares during theirstay in the ICU. Between 40% and 57% of the delirious ICU patients reportvivid dreams as one of the main contributors to their spectrum of uctuatinglevels of consciousness, paranoid delusions, and hallucinations [7678].

Relationship of circadian rhythm disturbance to deliriumto the point that the brain becomes so exhausted from sleep deprivaa dual threat to competent decision making by modulating activation innucleus accumbens and insula, brain regions associated with risky decisionmaking and emotional processing [69]. Increased functional MRI brainresponses can be observed after sleep deprivation [70,71], especially whencomplex items are studied [72,73]. These studies demonstrate that corticalfunction compensates for sleep deprivation initially by recruiting newregions of the cortex normally dormant when the brain is imaged undernormal sleep-restored conditions [72]. Compensations are maintained upwithin the prefrontal cortex [68], a region of the brain important for perality, emotion regulation, and behavioral inhibition. Sleep deprivation pbehavioral manifestations of sleep loss [6265]. During prolonged sleep dep-rivation, there is an increase in self-reported feelings of depressed mood, an-ger, frustration, tension, and anxiety [64,66]. Without adequate sleep,negative reactions to adverse experiences seem to be signicantly magnied,whereas positive reactions to pleasant events are often subdued [67]. Sleepdeprivation is associated with signicant reductions in glucose metabolism

son-Changes in mood constitute one of the most prominent and consiImpact on mood

468 SALAS & GAMALDODelirious patients in general may display a reversal of the circadian cycle,with daytime somnolence and nocturnal restlessness and agitation [79].One type of CRD likely common in the ICU is irregular sleepwake type,which is characterized by lack of a clearly dened circadian rhythm of sleep

ross

One other CRD likely to be encountered in the ICU is the free-running

type. The typical internal circadian clock has a cycle length that is slightlylonger than 24 hours. The internal circadian rhythm can only remain alignedto the 24-hour lightdark cycle through exposure to zeitgebers, such assunlight and physical activity. The internal clock relies heavily on a stronglight input during early waking hours and minimal light input during even-ing hours to remain entrained with a 24-hour cycle. Without this powerfulzeitgeber, the internal clock defaults to its natural 24-hour cycle length.In the ICU setting, zeitgebers, such as light exposure and physical activity,conducive to entraining the circadian clock are minimal. As a result, a pa-tients natural sleep and wake time shifts to a later time with each successiveday as demonstrated in the actigraphy illustration of a free-running clock(see Fig. 1) [3].

Some patients who have Alzheimer disease also show a cyclic worseningof agitation and confusion during the late afternoon to early evening, withimprovement or disappearance of these symptoms during the day. There isgrowing evidence that such sundowning behaviors are caused by circadiandisturbances, particularly a phase delay of body temperature [80]. Patientswho have dementia can vary widely in the timing and robustness of their ag-itation rhythms; for example, Martin and colleagues [81] found that thepeak for agitated behavior in a sample of nursing home residents occurredin the early afternoon rather than during the evening. A trend for agitationhas been found to worsen in the winter months and in patients awakeningfrom sleep in darkness [82].

Impact on metabolic/endocrine function

Although little is known regarding the eect of acute sleep deprivation onmetabolic function, studies in rats reveal that chronic sleep deprivation re-sults in a state of negative energy balance with increased energy expenditure[8386], whereas other studies nd no change in the hypothalamic-pituitaryaxis during sleep deprivation [87,88].

In humans, sleep loss is multifactorial, presenting with other syndromesillustrating the fragmented episodes of wake and sleep that occur aceach 24-hour period [3].and wake. The sleepwake pattern is temporally disorganized so that sleepand wake periods vary throughout the 24-hour period, which results in spo-radic bouts of insomnia alternating with somnolence. Predisposing factorsto this sleep disorder include poor sleep hygiene and lack of exposure toexternal synchronizing agents such as light, activity, and social schedules.The restactivity of an irregular sleepwake type is depicted in Fig. 1,

469ADVERSE EFFECTS OF SLEEP DEPRIVATION IN THE ICUthat lead to morbidity. Studies also show that sleep-deprived humans,similar to rats, have elevated metabolic rate [89], increased sympathetictone and cortisol [90], and increased food intake concomitant with elevatedserum ghrelin but decreased leptin [90]. Sleep deprivation has been shown to

Fig. 1. Activity records of mice. Each record is double-plotted according to convention, so that

each days data are presented both to the right of and beneath the day preceding. Times of

wheel-running activity are indicated by dark blue. On days 1 to 6, mice were maintained under

a 12-hour light/12-hour dark cycle. Mice were then transferred to continuous darkness by

allowing lights to go out at the usual time and then to remain o through the remaining

days of data collection. (Top) Activity record of a mouse with an inherent circadian cycle

with a free-running period length of approximately 23.7 hours illustrating an advanced-phase

circadian rhythm disorder. (Middle) Activity record of a mouse with a free-running period

and inherent circadian cycle that lengthened over time to approximately 24.8 hours representing

a delayed-phase circadian rhythm disorder. (Bottom) Activity record of a mouse with a free-

running inherent circadian rhythm process demonstrating an unentrained circadian rhythm

process. (From Kryger MH, Roth T, Dement WC, editors. Principles and practice of sleep

medicine. 4th edition. Philadelphia: Elsevier/Saunders; 2005. p. 365; with permission.)

470 SALAS & GAMALDO

Table 1

Multisystemic eects of acute sleep deprivation on body systemsImpact on immune function

Sleep deprivation has been found to alter immune responses [91] and canciated with type 2 diabetes [90].

have negative eects on glucose metabolism and to enhance variables asso-

Disruption of circadian rhythms Basal vasomotor tone Natural killer cells Antibody titers following inuenza virus immunization Lymphokine-activated killer activity Interleukin-2 production Alteration of endocrine and metabolic functions Cortisol release pattern alteration Glucose tolerance Insulin resistance Sympathetic cardiovascular modulation Parasympathetic cardiovascular modulation Baroreex sensitivity Catecholamine release Blood pressure Anxiety Hyperalgesic following day 471ADVERSE EFFECTS OF SLEEP DEPRIVATION IN THE ICUincrease circulating levels of inammatory markers, such as interleukin(IL)6, tumor necrosis factor, and C-reactive protein [9294], with signi-cant elevations after only one night of sleep loss [94]. Sleep deprivationcan also result in decreased natural killer cells [95], lower antibody titersafter inuenza virus immunization [96], reduced lymphokine-activated killeractivity, and reduced IL-2 production [97].

Nonspecic modulation of the immune response and decreases in aspectsof cellular immune function have been shown in patients undergoing total orpartial sleep deprivation [98]. There is a sleep-dependent increase in IL-7 con-centration that is associated with increased REM sleep supporting the posi-tive inuence of sleep on T cell function [99]. Healthy adults may show anincrease in IL-6 after only 12 nights of partial sleep deprivation (4 hoursper night) [100]. IL-6 is one of the proinammatory cytokines associatedwith reduced pain tolerance, perhaps identifying one mechanism for com-plaints of hyperalgesia reported after sleep deprivation. Despite these results,the eects of sleep loss on the immune system clinically remain speculative.

Summary

Sleep deprivation has been linked to numerous health ramications(Table 1). Optimizing sleep quantity and quality in the ICU is vital to

References[1] Southwell M, Wistow G. In-patient sleep disturbance: the views of sta and patients. Nurs

Times 1995;91:2931.

[2] Hodgson LA.Why dowe need sleep? Relating theory to nursing practice. J AdvNurs 1991;

16:150310.

[3] Kryger MH, Roth T, Dement WC. Principles and practice of sleep medicine. Philadelphia:

Elsevier/Saunders; 2005.

[4] Sleep in America pollsNational Sleep Foundation [online]. Available at: http://

www.sleepfoundation.org/site/c.huIXKjM0IxF/b.2417353/k.6764/Sleep_in_America_Polls.

htm. Accessed September 21, 2007.

[5] Parthasarathy S. Sleep during mechanical ventilation. Curr Opin Pulm Med 2004;10:

48994.

[6] Gabor JY, Cooper AB, Crombach SA, et al. Contribution of the intensive care unit

environment to sleep disruption in mechanically ventilated patients and healthy subjects.

Am J Respir Crit Care Med 2003;167:70815.

[7] NovaesMA, Aronovich A, Ferraz MB, et al. Stressors in ICU: patients evaluation. Inten-

sive Care Med 1997;23:12825.

[8] Smith MT, Perlis ML, Smith MS, et al. Sleep quality and presleep arousal in chronic pain.

J Behav Med 2000;23:113.

[9] Pilowsky I, Crettenden I, Townley M. Sleep disturbance in pain clinic patients. Pain 1985;

23:2733.

[10] Morin CM, Gibson D, Wade J. Self-reported sleep and mood disturbance in chronic pain

patients. Clin J Pain 1998;14:3114.

[11] Ohayon MM. Relationship between chronic painful physical condition and insomnia.a patients overall health. Poor sleep can be deleterious to patient outcomeand may lead to further testing resulting in higher medical costs and ex-tended hospital stays. The medical community needs to be aware of andavoid potential factors that can promote poor sleep. Strategies for achievingoptimal sleep must involve consideration of the four main topics discussedin this article. Emphasis on good sleep quality in the ICU remains an impor-tant concern that has previously been overlooked.

The following elements should be considered to help minimize sleepdisruption in the ICU:

Awareness of patients baseline sleep history and patterns is essential foroptimizing their sleep quality in the ICU.

The ICU team should be constantly aware that the commonly prescribedmedications for the ICU may aect sleep.

Noise is the most common environmental sleep disrupter in the ICU.Light, diagnostic tests, and patientsta interactions also interfere withpatient sleep quality in the ICU.

Implementing behavioral protocols in the ICU may reduce a patientssleep disturbance, morbidity, and mortality while increasing their over-all satisfaction.

472 SALAS & GAMALDOJ Psychiatr Res 2005;39:1519.

[12] Meissner HH, Riemer A, Santiago SM, et al. Failure of physician documentation of sleep

complaints in hospitalized patients. West J Med 1998;169:1469.

[13] Noureddine SN. Sleep apnea: a challenge in critical care. Heart Lung 1996;25:3742, quiz

434.

[14] Olson EJ, Simon PM. Sleep-wake cycles and the management of respiratory failure. Curr

Opin Pulm Med 1996;2:5006.

[15] Bradley TD. Sleep disturbances in respiratory and cardiovascular disease. J PsychosomRes

1993;37(Suppl 1):137.

[16] Saito T, Yoshikawa T, Sakamoto Y, et al. Sleep apnea in patients with acute myocardial

infarction. Crit Care Med 1991;19:93841.

[17] Chiner E, Signes-Costa J, Arriero JM, et al. Nocturnal oximetry for the diagnosis of the

sleep apnoea hypopnoea syndrome: amethod to reduce the number of polysomnographies?

Thorax 1999;54:96871.

[18] BahammamA, Delaive K, Ronald J, et al. Health care utilization in males with obstructive

sleep apnea syndrome two years after diagnosis and treatment. Sleep 1999;22:7407.

[19] American Academy of SleepMedicine. International classication of sleep disorders: diag-

nostic and codingmanual. 2nd edition.Westchester, IL: Academy of SleepMedicine; 2005.

[20] Hayter J. Sleep behaviors of older persons. Nurs Res 1983;32:2426.

[21] WebbWB, Campbell SS. Awakenings and the return to sleep in an older population. Sleep

1980;3:416.

[22] AsplundR. Sleep, health and visual impairment in the elderly. ArchGerontolGeriatr 2000;

30:715.

[23] Meyer TJ, Evelo SE, BauerMS, et al. Adverse environmental conditions in the respiratory

and medical ICU settings. Chest 1994;105:12116.

[24] Wysocki AB. The eect of intermittent noise exposure onwound healing.AdvWoundCare

1996;9:359.

[25] Redwine L, Hauger RL, Gillin JC, et al. Eects of sleep and sleep deprivation on interleu-

kin-6, growth hormone, cortisol, and melatonin levels in humans. J Clin EndocrinolMetab

2000;85:3597603.

[26] Tochikubo O, Ikeda A, Miyajima E, et al. Eects of insucient sleep on blood pressure

monitored by a new multibiomedical recorder. Hypertension 1996;27:131824.

[27] KatoM, Phillips BG, SigurdssonG, et al. Eects of sleep deprivation on neural circulatory

control. Hypertension 2000;35:11735.

[28] Topf M, BookmanM, Arand D. Eects of critical care unit noise on the subjective quality

of sleep. J Adv Nurs 1996;24:54551.

[29] Murthy VS, Malhotra SK, Bala I, et al. Detrimental eects of noise on anaesthetists.

Can J Anaesth 1995;42:60811.

[30] Balogh D, Kittinger E, Benzer A, et al. Noise in the ICU. Intensive Care Med 1993;19:

3436.

[31] Smith A. A review of the eects of noise on human performance. Scand J Psychol 1989;30:

185206.

[32] Gabor JY, CooperAB,Hanly PJ. Sleep disruption in the intensive care unit. Curr OpinCrit

Care 2001;7:217.

[33] Freedman NS, Kotzer N, Schwab RJ. Patient perception of sleep quality and etiology of

sleep disruption in the intensive care unit. Am J Respir Crit Care Med 1999;159:115562.

[34] Lower JS, Bonsack C, Guion J. Peace and quiet. Nurs Manage 2003;34:40A40D.

[35] Boivin DB, Duy JF, Kronauer RE, et al. Dose-response relationships for resetting of

human circadian clock by light. Nature 1996;379:5402.

[36] Walder B, Francioli D,Meyer JJ, et al. Eects of guidelines implementation in a surgical in-

tensive care unit to control nighttime light and noise levels. Crit CareMed 2000;28:22427.

[37] Perras B, Meier M, Dodt C. Light and darkness fail to regulate melatonin release in

critically ill humans. Intensive Care Med 2007;33:19548.

473ADVERSE EFFECTS OF SLEEP DEPRIVATION IN THE ICU[38] Olofsson K, Alling C, Lundberg D, et al. Abolished circadian rhythm of melatonin secre-

tion in sedated and articially ventilated intensive care patients. Acta Anaesthesiol Scand

2004;48:67984.

[39] Tamburri LM, DiBrienza R, Zozula R, et al. Nocturnal care interactions with patients in

critical care units. Am J Crit Care 2004;13:10212, quiz 1145.

[40] Celik S, OztekinD,AkyolcuN, et al. Sleep disturbance: the patient care activities applied at

the night shift in the intensive care unit. J Clin Nurs 2005;14:1026.

[41] Mortola JP. Breathing around the clock: an overview of the circadian pattern of respira-

tion. Eur J Appl Physiol 2004;91:11929.

[42] Cooper AB, Gabor JY, Hanly PJ. Sleep in the critically ill patient. Semin Respir Crit Care

Med 2001;22:15364.

[43] Qureshi A, Lee-Chiong T Jr. Medications and their eects on sleep. Med Clin North Am

2004;88:75166, x.

[44] Borbely AA,Mattmann P, LoepfeM, et al. Eect of benzodiazepine hypnotics on all-night

sleep EEG spectra. Hum Neurobiol 1985;4:18994.

[45] Achermann P, Borbely AA. Dynamics of EEG slow wave activity during physiological

sleep and after administration of benzodiazepine hypnotics. Hum Neurobiol 1987;6:

20310.

[46] Cronin AJ, Keifer JC, Davies MF, et al. Postoperative sleep disturbance: inuences of

opioids and pain in humans. Sleep 2001;24:3944.

[47] Frighetto L, Marra C, Bandali S, et al. An assessment of quality of sleep and the use of

drugs with sedating properties in hospitalized adult patients. Health Qual Life Outcomes

2004;2:17.

[48] Halfens R, Cox K, Kuppen-VanMerwijk A. Eect of the use of sleep medication in Dutch

hospitals on the use of sleep medication at home. J Adv Nurs 1994;19:6670.

[49] BroughtonR, BaronR. Sleep patterns in the intensive care unit and on the ward after acute

myocardial infarction. Electroencephalogr Clin Neurophysiol 1978;45:34860.

[50] Aurell J, Elmqvist D. Sleep in the surgical intensive care unit: continuous polygraphic

recording of sleep in nine patients receiving postoperative care. Br Med J (Clin Res Ed)

1985;290:102932.

[51] Buckle P, Pouliot Z, Millar T, et al. Polysomnography in acutely ill intensive care unit

patients. Chest 1992;102:28891.

[52] Hilton BA. Quantity and quality of patients sleep and sleep-disturbing factors in a respira-

tory intensive care unit. J Adv Nurs 1976;1:45368.

[53] Orr WC, Stahl ML. Sleep disturbances after open heart surgery. Am J Cardiol 1977;39:

196201.

[54] Kavey NB, Ahshuler KZ. Sleep in herniorrhaphy patients. Am J Surg 1979;138:6837.

[55] Cooper AB, ThornleyKS, YoungGB, et al. Sleep in critically ill patients requiringmechan-

ical ventilation. Chest 2000;117:80918.

[56] Roehrs T, HydeM, Blaisdell B, et al. Sleep loss and REM sleep loss are hyperalgesic. Sleep

2006;29:14551.

[57] ZhongX,HiltonHJ,GatesGJ, et al. Increased sympathetic and decreased parasympathetic

cardiovascular modulation in normal humans with acute sleep deprivation. J Appl Physiol

2005;98:202432.

[58] Loredo JS, Ziegler MG, Ancoli-Israel S, et al. Relationship of arousals from sleep to sym-

pathetic nervous system activity and BP in obstructive sleep apnea. Chest 1999;116:6559.

[59] Liu Y, Tanaka H, , Fukuoka Heart Study Group. Overtime work, insucient sleep, and

risk of non-fatal acute myocardial infarction in Japanese men. Occup Environ Med

2002;59:44751.

[60] Ayas NT,White DP,Manson JE, et al. A prospective study of sleep duration and coronary

heart disease in women. Arch Intern Med 2003;163:2059.

[61] Suh SY, Kim JW, Choi CU, et al. Spontaneous coronary dissection associated with sleep

deprivation presenting with acute myocardial infarction. Int J Cardiol 2007;115:e789.

474 SALAS & GAMALDO[62] Dinges DF, Pack F, Williams K, et al. Cumulative sleepiness, mood disturbance, and

psychomotor vigilance performance decrements during a week of sleep restricted to

4-5 hours per night. Sleep 1997;20:26777.

[63] Lieberman HR, Bathalon GP, Falco CM, et al. Severe decrements in cognition function

and mood induced by sleep loss, heat, dehydration, and undernutrition during simulated

combat. Biol Psychiatry 2005;57:4229.

[64] Orton DI, Gruzelier JH. Adverse changes in mood and cognitive performance of house

ocers after night duty. BMJ 1989;298:213.

[65] Scott JP, McNaughton LR, Polman RC. Eects of sleep deprivation and exercise on

cognitive, motor performance and mood. Physiol Behav 2006;87:396408.

[66] Caldwell JA, Caldwell JL, Smith JK, et al. Modanils eects on simulator performance

and mood in pilots during 37 h without sleep. Aviat Space Environ Med 2004;75:77784.

[67] Zohar D, Tzischinsky O, Epstein R, et al. The eects of sleep loss on medical residents

emotional reactions to work events: a cognitive-energy model. Sleep 2005;28:4754.

[68] Thomas M, Sing H, Belenky G, et al. Neural basis of alertness and cognitive performance

impairments during sleepiness. I. Eects of 24 h of sleep deprivation on waking human

regional brain activity. J Sleep Res 2000;9:33552.

[69] Venkatraman V, Chuah YM, Huettel SA, et al. Sleep deprivation elevates expectation of

gains and attenuates response to losses following risky decisions. Sleep 2007;30:6039.

[70] Drummond SP, Brown GG, Gillin JC, et al. Altered brain response to verbal learning

following sleep deprivation. Nature 2000;403:6557.

[71] Drummond SP, Brown GG. The eects of total sleep deprivation on cerebral responses to

cognitive performance. Neuropsychopharmacology 2001;25:S6873.

[72] Drummond SP, Brown GG, Salamat JS, et al. Increasing task diculty facilitates the

cerebral compensatory response to total sleep deprivation. Sleep 2004;27:44551.

[73] Durmer JS, Dinges DF. Neurocognitive consequences of sleep deprivation. Semin Neurol

2005;25:11729.

[74] Stricker JL, Brown GG, Wetherell LA, et al. The impact of sleep deprivation and task

diculty on networks of fMRI brain response. J Int Neuropsychol Soc 2006;12:5917.

[75] Schelling G, Stoll C, Haller M, et al. Health-related quality of life and posttraumatic stress

disorder in survivors of the acute respiratory distress syndrome. Crit Care Med 1998;26:

6519.

[76] McGuire BE, Basten CJ, Ryan CJ, et al. Intensive care unit syndrome: a dangerous misno-

mer. Arch Intern Med 2000;160:9069.

[77] Wilson VS. Identication of stressors related to patients psychologic responses to the

surgical intensive care unit. Heart Lung 1987;16:26773.

[78] Dyer I. Preventing the ITU syndrome or how not to torture an ITU patient! Part 2. Inten-

sive Crit Care Nurs 1995;11:22332.

[79] Henry WD, Mann AM. Diagnosis and treatment of delirium. Can Med Assoc J 1965;93:

115666.

[80] Volicer L, Harper DG, Manning BC, et al. Sundowning and circadian rhythms in

Alzheimers disease. Am J Psychiatry 2001;158:70411.

[81] Martin JL, Marler MR, Harker JO, et al. A multicomponent nonpharmacological inter-

vention improves activity rhythms among nursing home residents with disrupted sleep/

wake patterns. J Gerontol A Biol Sci Med Sci 2007;62:6772.

[82] Bliwise DL, Carroll JS, Lee KA, et al. Sleep and sundowning in nursing home patients

with dementia. Psychiatry Res 1993;48:27792.

[83] Everson CA, Bergmann BM, Rechtschaen A. Sleep deprivation in the rat: III. Total sleep

deprivation. Sleep 1989;12:1321.

[84] Bergmann BM, Everson CA, Kushida CA, et al. Sleep deprivation in the rat: V. Energy use

and mediation. Sleep 1989;12:3141.

[85] KushidaCA,BergmannBM,RechtschaenA. Sleep deprivation in the rat: IV. Paradoxical

sleep deprivation. Sleep 1989;12:2230.

475ADVERSE EFFECTS OF SLEEP DEPRIVATION IN THE ICU[86] Koban M, Swinson KL. Chronic REM-sleep deprivation of rats elevates metabolic rate

and increases UCP1 gene expression in brown adipose tissue. Am J Physiol Endocrinol

Metab 2005;289:E6874.

[87] Rechtschaen A, Bergmann BM. Sleep deprivation in the rat: an update of the 1989 paper.

Sleep 2002;25:1824.

[88] Rechtschaen A, Bergmann BM. Sleep deprivation in the rat by the disk-over-water

method. Behav Brain Res 1995;69:5563.

[89] Bonnet MH, Arand DL. 24-hour metabolic rate in insomniacs and matched normal

sleepers. Sleep 1995;18:5818.

[90] Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt on metabolic and endocrine

function. Lancet 1999;354:14359.

[91] Born J, Lange T, Hansen K, et al. Eects of sleep and circadian rhythm on human circulat-

ing immune cells. J Immunol 1997;158:445464.

[92] Vgontzas AN, Zoumakis E, Bixler EO, et al. Adverse eects of modest sleep restriction on

sleepiness, performance, and inammatory cytokines. J Clin Endocrinol Metab 2004;89:

211926.

[93] Shearer WT, Reuben JM, Mullington JM, et al. Soluble TNF-alpha receptor 1 and IL-6

plasma levels in humans subjected to the sleep deprivation model of spaceight. J Allergy

Clin Immunol 2001;107:16570.

[94] Meier-Ewert HK, Ridker PM, Rifai N, et al. Eect of sleep loss on C-reactive protein, an

inammatory marker of cardiovascular risk. J Am Coll Cardiol 2004;43:67883.

476 SALAS & GAMALDO[95] Ozturk L, Pelin Z, Karadeniz D, et al. Eects of 48 hours sleep deprivation on human

immune prole. Sleep Res Online 1999;2:10711.

[96] Spiegel K, Sheridan JF, Van Cauter E. Eect of sleep deprivation on response to immuni-

zation. JAMA 2002;288:14712.

[97] Irwin M, McClintick J, Costlow C, et al. Partial night sleep deprivation reduces natural

killer and cellular immune responses in humans. FASEB J 1996;10:64353.

[98] Dinges DF, Douglas SD, Hamarman S, et al. Sleep deprivation and human immune

function. Adv Neuroimmunol 1995;5:97110.

[99] Benedict C, Dimitrov S, Marshall L, et al. Sleep enhances serum interleukin-7 concentra-

tions in humans. Brain Behav Immun 2007;21:105862.

[100] Haack M, Kraus T, Schuld A, et al. Diurnal variations of interleukin-6 plasma levels

are confounded by blood drawing procedures. Psychoneuroendocrinology 2002;27:

92131.

Adverse Effects of Sleep Deprivation in the ICUBaseline sleep history of the ICU patientChronic insufficient sleep: an epidemic at all agesMedical illnessSleep and painPrimary sleep disorders

Impact of the ICU environment on sleep: iatrogenic environmental sleep disorderNoiseLightStaff-patient interactionsRespiration and ventilated ICU patientsMedications

Systematic look at the impact of sleep loss on the ICU patientImpact on sleep quality and quantityImpact on the cardiovascular systemImpact on moodImpact on mentationRelationship of sleep deprivation and nightmares to deliriumRelationship of circadian rhythm disturbance to delirium

Impact on metabolic/endocrine functionImpact on immune function

SummaryReferences