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19 Sleep inCritical Illness
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deprivation, the levels of sleep deprivation and stress imposed by these models may
not generalize to critically ill patients. Last, it is unclear whether acute-on-chronic
sleep disruption predisposes critically ill patients to a hyper-inammatory state.
Overall, the collective body of research provides a biological plausibility for the
sleep-immunity association, particularly in critically ill patients who experience
sepsis as a common cause of mortality [119–121]. Sepsis survivors have poor longterm prognosis, with infection as the most common reason for rehospitalization
[122]. For critically ill patients, an intact immune system may play a vital role in
noninfectious processes such as wound healing and tissue repair (e.g., after trauma,
surgery, or acute myocardial infarction). Understanding the sleep-immune axis in
the critically ill is of paramount importance. The awareness to improve sleep may
have an immediate implication in immune-related ICU outcomes (e.g., enhanced
pathogen clearance and improved recovery from sepsis) as well as long-term consequences (e.g., mounting an adequate adaptive immune response for a robust acquired
immunity).
441
Sleep Disruption andCognition
A comprehensive pathophysiological review of the relationship between sleep,
delirium, and cognition is outside the scope of this chapter, but briey is believed to
include common pathophysiologic pathways, mechanisms, and neurotransmitters
[34, 123]. Sleep disruption likely plays a role in the development of delirium, and
vice versa, though a causal relationship has not been established [124, 125].
Approximately one-third of critically ill patients experience delirium, including up
to 80% of those receiving mechanical ventilation [123]. Patients experiencing delirium are at high risk of devastating outcomes, including longer duration of mechanical ventilation and prolonged ICU and hospital length of stay [126]. Over the past
decade, increased attention has been paid to the long-term sequelae of ICU delirium, in particular its association with severe and disabling long-term neurocognitive
impairments [127–129]. Another study observed an eightfold increase in developing dementia for elderly (>85-year-old) patients who developed delirium during
their hospital stay [130].
Risk factors for delirium in the ICU include critical illness, older age, preexisting
cognitive impairments, and genetic predisposition [123]. Disrupted sleep has
received particular attention as a modiable risk factor for delirium in the ICU and
is supported by observational studies demonstrating increased mental status change
frequency among critically ill patients experiencing more sleep interruptions [131]
and higher delirium incidence after thoracic surgery in patients reporting sleep
deprivation [132]. More objectively, a study involving PSG in mechanically ventilated patients demonstrated a higher rate of incident delirium in patients with REM
suppression [133].
The interaction between pharmacological agents and delirium has been studied
extensively, with benzodiazepine infusions being identied consistently as a risk
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factor for delirium development [125, 134–138]. Several studies have examined
strategies to prevent or treat delirium, with inconclusive results [83]. Antipsychotics
are traditionally administered off-label for delirium, but have not been shown to be
effective in large studies [139, 140]. Dexmedetomidine has been a subject of interest as it has a favorable deliriogenicity prole [141, 142] and may act via the ventrolateral preoptic nucleus of the hypothalamus [143], thus promoting biological
sleep rather than sedation seen with benzodiazepines and propofol. However, a
large, randomized control trial did not show any major benets of dexmedetomidine
when compared with usual care [144]. Thus, strategies to address delirium have
largely focused on non-pharmacological strategies such as sleep promotion and
early mobility and, from a pharmacological perspective, avoidance of deliriogenic
medications such as benzodiazepines (Table 19.2) [72, 83]. As sleep-focused
improvement efforts have been shown to reduce delirium in ICU settings [28, 29],
design and implementation of larger interventions is a high priority [145], in large
part due to heightened awareness of delirium and its associated short- and long-term
consequences [83].
M. T. Y. Lam et al.
Future Directions
This chapter highlights the important intersection between sleep and critical illness
and reviews some of the short- and long-term consequences when sleep is disrupted
during critical illness. However, a dearth of data highlights the vast array of research
opportunities in the area. Further research is needed to evaluate the role of ICUrelated sleep disruption on clinically important patient outcomes, in particular on
immunity and cognition. Circadian rhythms are also gaining attention in the ICU, in
particular in the context of balancing the provision of potentially lifesaving treatments while minimizing the short- and long-term impairments imposed by critical
illness itself. While multicomponent bundled interventions are recommended for all
critically ill patients, the ideal strategy to optimize sleep and associated outcomes
remains unknown and represents a complex and fascinating topic of future
investigation.
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Rahmani et al [n=140] (187)
Bagheri-Nesami et al [n=90] (186)
Chen et al [85] (185)
Cho et al [n=60] (184)
Karadag et a [n=60] (183)
Hajibagheri et al [60] (182)
Cho et al [56] (181)
Moeini et al [n=64] (180)
Hsu et al [n=60] (179)
Shinde and Anjum [n=60] (178)
Oshvandi et al [n=60] (177)
Nerbass et al [n=57] (176)
Richards [n=69] (27)
Afshar et al [n=60] (175)
Williamson [n=60] (174)
Gragert [n=40] (173)
Su et al [n=28] (172)
Chlan et al [n=373] (171)
Richardson [n=36] (170)
Daneshmandi et al [n=60] (169)
Mashayekhi et al [n=60] (168)
Babaii [n=60] (167)
Hu et al [n=45] (166)
Bajwa et al [n=100] (165)
Mashayekhi et al [n=90] (164)
Dave et al [n=50] (163)
Yazdannik et al [n=50] (32)
Le Guen et al [n=41] (162)
Jones and Dawson [n=100] (161)
Ryu et al [58] (160)
Richardson at al [n=64] (159)
Van Rompaey et al [n=136] (158)
Neyse et al [n=60] (157)
Scotto et al [n=88] (31)
Haddock [n=18] (156)
Boyko et al [n=17] (155)
Patel et al [n=338] (29)
Kamdar et al [n=300] (28)
Walder et al [n=17] (154)
Hansen et al [n=37] (153)
Foster and Kelly [n=32] (152)
Maidl et al [n=129] (151)
Faraklas et al [n=130] (150)
Li et al [n=55] (30)
Dennis et al [n=50] (55)
Monsen and Edell-Gustafsson [n=23] (149)
Olson et al [n=239] (148)
Kahn et al [n= all ICU staff] (147)
443
Table 19.2 Interventions to promote sleep in the ICU setting
sound
↓ Average peak
Behavioral
Intervention Impact
↓ Delirium
and/or noise
↑ Sleep quality
↓ Ambient light
Modification
(e.g. quiet time,
clustering of care)
↓ Anxiety
Ear Plugs ↑ Sleep quality
Eye Mask ↑ Sleep quality
↓ Sedative use
↑ Subjective sleep
Music
White Noise ↑ Subjective sleep
(men)
↑ Sleep quality
↑ Sleep efficiency
Massage
Aromatherapy ↑ Sleep quality
↓ Waking
↑ Sleep quality
Acupressure
Foot reflexology ↑ Subjective sleep
Guided Imagery No improvement
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Acknowledgments Dr. Malhotra is funded by the NIH.He reports income related to medical
education from LivaNova and Equillium and serves on a DSMB for Corvus. ResMed provided a
philanthropic donation to UC San Diego. Dr. Kamdar is supported by a Paul B.Beeson Career
Development Award through the National Institutes of Health/National Institute on Aging (K76
AG059936).
Dr. Lam is supported by the Academic Sleep Pulmonary Integrated Research/Clinical
Fellowship through the American Thoracic Society and by the NIH (5T32HL134632-04).
M. T. Y. Lam et al.
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