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ANNALSATS Articles in Press. Published on 20-October-2017 as 10.1513/AnnalsATS.201709-757LE
Page 1 of 5
Reply: A New Direction: Sleep and Neuropsychological Impairment after Critical Illness
Brian J. Anderson MD MS1, Mark E. Mikkelsen MD MS1,2
1
Division of Pulmonary, Allergy, and Critical Care Medicine, Perelman School of Medicine at the
University of Pennsylvania; 2Center for Clinical Epidemiology and Biostatistics, Perelman School
of Medicine at the University of Pennsylvania
Corresponding Author:
Brian J. Anderson, MD, MS
Pulmonary, Allergy, and Critical Care Division
Perelman School of Medicine
University of Pennsylvania
3400 Spruce Street, 5048 Gates Building
Philadelphia, PA 19104
Phone: 215-662-7915
Email: brian.anderson@uphs.upenn.edu
Financial Support: None
Disclosures: For each of the above authors, no financial or other potential conflicts of interest
exist.
Word Count: 616
Copyright © 2017 by the American Thoracic Society
ANNALSATS Articles in Press. Published on 20-October-2017 as 10.1513/AnnalsATS.201709-757LE
We read with interest the letter written by Harrison et el. (1), in response to the study of
psychiatric symptoms in survivors of acute respiratory distress syndrome (ARDS) completed by
Spencer-Segal and colleagues (2) and our accompanying editorial (3). In raising the question of
whether obstructive sleep apnea (OSA) might play a role in the development of psychiatric
morbidity in survivors of critical illness, Harrison and colleagues provide a stark reminder that
powerful insights can be gained by drawing on the expertise of clinicians and researchers from
separate but often tightly related fields. We agree that the effect of sleep disordered breathing
on outcomes of critical illness survivors deserves consideration, and more importantly that the
contribution of sleep disruption in general deserves further investigation.
Sleep disturbance in the intensive care unit (ICU) is incredibly common and is a major
source of anxiety and stress during the ICU stay (4, 5). Although the mean total sleep time is
generally preserved, ICU patients experience prolonged sleep latency, fragmented sleep,
numerous arousals, and decreased sleep efficiency, with a larger proportion of time spent in
stage 2 sleep and less time spent in deeper restorative stage 3 and REM sleep (4, 5). Nearly 50%
of all sleep that critically ill patients get occurs in the daytime (4, 5). The ICU environment is a
perfect setup for poor sleep, often having high levels of noise, frequent interruptions for
patient care, and abnormal light exposure (4, 5). Pain and anxiety are common in patients with
critical illnesses and can also disrupt sleep (4, 5). Paradoxically, and unfortunately, many of the
medications that are commonly used in the ICU can further disrupt sleep. Opiates,
benzodiazepines, Propofol and even some commonly used antibiotics have negative impacts on
sleep architecture (4, 5). And beware that what may appear beneficial, may actually be harmful
(e.g., decreased sleep latency of benzodiazepines comes at the cost of reduced depth and
Copyright © 2017 by the American Thoracic Society
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ANNALSATS Articles in Press. Published on 20-October-2017 as 10.1513/AnnalsATS.201709-757LE
duration of restorative sleep). Further, at the pathophysiologic level, many critical illnesses are
associated with elevations in cytokines that also influence sleep (4, 5).
Given how disrupted sleep is in critically ill patients, it’s no surprise that many
hypothesize that this sleep disruption negatively impacts short and long-term outcomes. Sleep
deprivation can cause respiratory muscle fatigue and decrease the ventilatory response to
hypercapnea, potentially contributing to difficulty weaning from mechanical ventilation(4).
Although not well studied, sleep deprivation has also been thought to result in impaired
immune function, potentially leaving critically ill patients at higher risk for secondary infections
(4). Poor sleep also results in a lack of energy which could potentially interfere with attempts at
physical therapy and functional recovery in ICU survivors (4). Sleep deprivation has also been
linked with depressive symptoms, delirium, and cognitive impairment, raising the question of
whether sleep disruption in the ICU might play a role in the development of long-term
psychiatric morbidity and cognitive impairment in ICU survivors. In fact, a recent systematic
review revealed that 22-57% of ICU survivors still experience disrupted sleep 3-6 months after
their hospitalization and patients with poor sleep had more symptoms of anxiety, depression
and post-traumatic stress disorder (6). Based on all of these data, we are left wondering what
impact sleep disruption due to either OSA or critical illness has on ICU outcomes, and further
research is desperately needed.
In our search to improve the care and lives of ICU survivors, we need to remain mindful
that interdisciplinary research can be the catalyst to important breakthroughs. By drawing on
the insights and expertise from disparate fields, spanning neurology, psychology, sleep, critical
care, rehabilitation, endocrinology and immunology, we can more efficiently and effectively
Copyright © 2017 by the American Thoracic Society
ANNALSATS Articles in Press. Published on 20-October-2017 as 10.1513/AnnalsATS.201709-757LE
reduce the burden of psychiatric, cognitive and functional impairments experienced by ICU
survivors.
Copyright © 2017 by the American Thoracic Society
Page 4 of 5
ANNALSATS Articles in Press. Published on 20-October-2017 as 10.1513/AnnalsATS.201709-757LE
Page 5 of 5
References
1. Harrison MC, Dunn RB, Kear J. Comments on 'stressing the brain ... Acute respiratory
distress syndrome'. Ann Am Thorac Soc 2017. 10.1513/AnnalsATS.201708-653LE
2. Spencer-Segal JL, Hyzy RC, Iwashyna TJ, Standiford TJ. Psychiatric symptoms in survivors of
acute respiratory distress syndrome. Effects of age, sex, and immune modulation. Ann Am
Thorac Soc 2017;14(6):960-967.
3. Anderson BJ, Mikkelsen ME. Stressing the brain: The immune system, hypothalamicpituitary-adrenal axis, and psychiatric symptoms in acute respiratory distress syndrome
survivors. Ann Am Thorac Soc 2017;14(6):839-841.
4. Kamdar BB, Needham DM, Collop NA. Sleep deprivation in critical illness: Its role in physical
and psychological recovery. J Intensive Care Med 2012;27(2):97-111.
5. Pisani MA, Friese RS, Gehlbach BK, Schwab RJ, Weinhouse GL, Jones SF. Sleep in the
intensive care unit. Am J Respir Crit Care Med 2015;191(7):731-738.
6. Altman MT, Knauert MP, Pisani MA. Sleep disturbance after hospitalization and critical
illness: A systematic review. Ann Am Thorac Soc 2017;14(9):1457-1468.
Copyright © 2017 by the American Thoracic Society
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