• Sleep is a normal active physiological state which serves a poorly understood but apparently vital function.
  • Sedation does not seem to have the same restorative function.
  • The sleep of ICU patients is fragmented, light, non-circadian, and decreased in quantity.
  • In ICU, sleep quality is poor because of noise, light pollution, constant care-related awakenings, pain, and the lack of REm sleep resulting from the use of sedatives.
  • Monitoring sleep in ICU is complicated by the presence of non-standard EEG activity
  • Non-pharmacological measures to reduce sleep disruption include limiting noise, dimming light at night, and using relaxation techniques (eg, white noise or calming music, biofeedback,  massage)
  • Pharmacological measures may involve the use of melatonin, short acting sedatives (eg. zolpidem) and reducing reliance on classical sedative agents (benzodiazepines and propofol)

The topic of sleep disturbance in the ICU has been of some considerable interest, considering how many articles pop up when you look up "sleep disturbance in the ICU". Much of the information I used to generate the discussion section for  Question 25 from the first paper of 2008 has been derived from this excellent article from the The Open Critical Care Medicine Journal. The LITFL page on sleep in the ICU also offers an excellent brief overview, perfect for pre-exam cramming.

Physiology of normal sleep

For a while, Physiology in Sleep by Orem (a 2012 book from Elsevier) is available in Google books. This was my main resource for this section. Specifically, Appendix A by Orem and Keeling is a gold mine of concise information. Orem have published "the first comprehensive work on physiology in sleep since Kleitman's monograph, "Sleep and Wakefulness," published in 1963". Their work covers the unadulterated human organism, sleeping in a natural state. In the ICU patient, such an environment usually does not exist due to the influence of critical illness and mild-altering drugs, but it is worth know about normal sleep anyway. Who knows, perhaps one day one of your patients might sleep normally. I wouldn't rule it out.

normal adult hypnogram demonstrating the architecture of sleep cycles

Airway effect of normal sleep

  • Respiratory muscles (particularly upper airway muscles)  are atonic during sleep
  • Mucociliary clearance is reduced during sleep
  • Airway reflexes are altered during sleep
  • Airway smooth muscle tone decreases
  • Cough is essentially impossible during sleep of most kinds
  • Laryngeal stimulation produces apnoea

Cardiovascular effects of sleep

  • Blood pressure decreases during sleep.The lowest blood pressure occurs during Stage 3 and 4 of NREM sleep
  • Heart rate slows during sleep.It is lowest and most regular in deep NREM
  • Cardiac output decreases during sleep
  • Transient vasoconstriction events occur during sleep Death from cardiac disorders occurs most frequently during sleep, between 5am and 6am (during REM sleep).
  • There is central inhibition of the baroreflex during REM sleep: cats in REM sleep responded poorly (i.e. did not increase their blood pressure) in response to the occlusion of their carotid artery.

Respiratory effects of sleep

  • Total body oxygen consumption is higher in REM sleep, but sill lower than in wakefulness
  • Minute ventilation decreases during NREM sleep
  • Respiration is rapid and irregular in NREM sleep
  • Medullary sensitivity to hypoxia and hypercapnea decreases
  • The PaCO2 rises by 3-7mmHg during stage N3 sleep

Neurological effects of sleep

  • Cerebral blood flow increases during REM sleep and changes heterogeneously during NREM sleep
  • Intracranial pressure increases during REM sleep, but not NREM sleep
  • Brain temperature increases in REM sleep and decreases in NREM sleep

Endocrine effects of sleep

  • All pituitary hormones except ACTH are secreted more vigorously during sleep - growth hormone, prolactin, TSH, etc.
  • There are also increased levels of vasopressin and aldosterone.
  • Body temperature decreases during sleep and increases transiently during REM sleep
  • Thermoregulation is lost. Sweating and shivering is impossible during REM sleep.

Renal effects of sleep

  • Urine output decreases
  • Urinary excretion of electrolytes also decreases

Gastrointestinal function during sleep

  • Experts cannot seem to agree. It seems different experiments have yielded different answers as to what the gut is doing during sleep (is it more motile? less?) In short, nobody knows.
  • Oesophageal motility is certainly decreased
  • The secretion of saliva slows, and swallowing is impossible.
  • Rectal tone is preserved

Effects of sedation on sleep

Sedation is nothing like sleep. The two resemble each other because sedative drugs tend to affect GABA neurotransmission, and natural sleep is the effect of hypothalamic GABA-ergic inhibition of arousal pathways. The similarity ends there.  Weinhouse et al (2011) present a polysomnograph of a critically ill sedated patient, demonstrating that the majority of the time is maintained in N1 sleep, with microarousals every ten seconds. That doesn't sound restful. N1 stage sleep is the earliest and most shallow stage; if a person is woken from N1 stage sleep they frequently will not be able to identify the fact that they went to sleep at all.

In fact, critical illness makes it difficult to identify whether a patient is asleep at all. Sedation and encephalopathy make for anomalous-looking EEG patterns, which makes it difficult to identify sleep on the bases of multi channel polysomnography (more on that later). During a 24 hour period of ICU stay, there may be some periods of EEG activity which resemble N2 and N3 sleep, but they are scattered throughout the day and night in short periods.

Physiological Differences Between Sleep and Sedation
Domain Sleep Sedation
Physiological basis
  • An essential biologic function necessary for life
  • Not that.
  • Cyclical, initiated by circadian rhythms
  • Dose-dependent
  • Shortened sleep latency (i.e. N1  is shorter: you fall asleep faster with sedatives)
  • Easily reversed by external stimuli
  • Not necessarily
Pattern of EEG activity
  • Cyclic progression of stages defined by well-established EEG criteria
  • Distorted EEG to such an extent that standard EEG criteria are difficult to apply
  • Generally, sedatives and opioids decrease REM sleep and increase Stage N2 sleep.
Cerebral metabolism
  • 22% reduction in cerebral glucose metabolism during NREM sleep
  • 55% reduction in cerebral glucose metabolism, when propofol is titrated just to the point of loss of consciousness

Propofol sedation and normal sleep

Specific sedative effects have been studied. For instance, Tung et al (2004) experimented on some sleeping rats, and found that the rats who got propofol infusions during their normal sleep did not exhibit any signs of sleep deprivation. Ergo, normal restorative functions of sleep were preserved in spite of propofol sedation. Of course, it is difficult to generalise this to human ICU patients. Those are usually not in a normal sleep state to begin with, and they are constantly being woken up.  Not to mention that they usually operate at a slightly different cortical intensity to the rats. (in rats, subtle signs of sleep deprivation may be difficult to assess). Lastly, the differences in cerebral glucose metabolism (55% decreased with propofol, compared to a 22% decrease with normal NREM sleep) demonstrate crudely how different propofol sedation is to real sleep.

Dexmedetomidine sedation and normal sleep

Dex sedation may demonstrate some features which resemble normal sleep. There is apparently some FMRI similarity between them (Coull et al, 2004). Also, clinically, patients on dexmedetomidine seem to be enjoying an experience more closely resembling sleep on clinical criteria; they arouse easily from their sedation, and are more cognitively intact when they do so. Unfortunately, the patients don't seem to care: most report a poorer quality sleep with dexmedetomidine than with propofol (Corbett et al, 2005).

Sleep in the ICU

Kamdar et al (2012) have many negative things to say about sleep in the ICU population

  • Fragmented and brief: ICU patients end upw ith 20-40 episodes per day of something that resembles sleep, and lasts 10-15 minutes (Freedman et al, 2001).
  • Much of it is in the N1 stage
  • Much of it (50%) is during daytime hours
  • Many microarousals
  • Many actual arousals - Cooper et al (2000) found that the patients were woken 22 times every hour, on average
  • Total sleep time is decreased

Causes of sleep disturbances in the ICU

The following factors have been found to act as negative influences on sleep:

  • Noise: 10-20% of wakings. The EPA recommends no higher than 45 dB in the ICU; however, this is actually quite loud - it is "the sound level recognized internationally as an upper limit for human comfort in residential interior spaces".
  • Constant harsh light; misalignment of circadian cycles - artificial light is of insufficient intensity to act as a zeitgeber
  • Sunlight exposure is limited or nonexistent
  • Erratic stimulus (eg. hourly neuro obs)
  • Appropriately timed meals are replaced by tube feeding
  • Regular nursing care (eg. turns) disturbs nocturnal sleep
  • Sepsis decreased REM sleep by influencing melatonin secretion
  • Sedatives impair normal REM sleep
  • Mechanical ventilation impairs sleep
  • Pain including the discomfort of tubes and drains
  • Anxiety and stress

Consequences of sleep deprivation in ICU patients

The following consequences have been ascribed to sleep deprivation, though in truth there really is no way of testing that.  Several good resources exist for this, for example Kamdar et al, 2012 and  Jolanta Orzeł-Gryglewska's "Consequences of sleep deprivation",  2010.  The experts offer the following list of problems:

  • Respiratory exhaustion: after 1 night without sleep, COPD patients get worse (poorer FEV1 and FVC). Even in normal male subjects, inspiratory muscle endurance is affected (Chen et al, 1989)
  • Decreased ventilatory response to hypercapnea - leading to hypoventilation. "Ventilatory chemosensitivity may be substantially attenuated by even short-term sleep deprivation", claim White et al (1983)
  • Increased total body oxygen consumption (on the basis of a study by Bonnet and Arand (1995) which compared VO2 among insomniacs and good sleepers)
  • Increased risk of ischaemic cardiac events - studied by Liu and Tanaka (2002) in a population of chronically overworked Japanese executives.
  • Delirium - it is either increased in incidence by sleep deprivation, or at least the two conditions share sufficient number of clinical features - for example, inattention, hallucinations and decreased short term memory (Weinhouse et al, 2009)
  • Lasting neurocognitive deficits following critical illness may be exacerbated by sleep deprivation (Jackson et al, 2009), but the link is far from well-established.
  • A hypercatabolic state: some chronically sleep-deprived rats seem to have developed wasting weight loss and malnutrition in spite of increased caloric intake (Everson et al, 1989). In fact, sustained deprivation of sleep ultimately killed the rats. The terminal stage of sleep deprivation in these rats resembled septic shock, wih multiorgan system failure.
  • Increased catecholamine and corticosteroid levels, similar to the stress response of critical illness (Johns et al, 1971)
  • Hyperglycaemia: blunted insulin secretion, decreased sensitivity to insulin, and impaired glucose regulation (Spiegel et al, 2009)
  • Impaired immunity: a release of proinflammatory cytokines and a decline in T-helper cells is observed in short-term sleep deprivation (Everson et al, 1993)

Monitoring of sleep in the ICU

LITFL recommend daily sleep diaries, visual analog scales (VAS), questionnaires, and symptom or quality of life questionnaires with sleep items (subject to recall bias and other problems), direct observation of arousals and motor activity, actigraphy (using movement detectors), BIS and Bispectral index and multichannel polysomnography (gold standard). An excellent recent article by Delaney et al (2015) offers a detailed overview of the issues involved.

Polysomnography,  even though viewed as the gold standard for normal patients, has many barriers to its application in the ICU, particularly in context of the ECG-befuddling effects of exotic sedatives and encephalopathy. To give an extreme example, a patient who has had a hemispherectomy and then went on to develop HSV encephalitis will offer a highly unusual pattern of EEG activity, which will be difficult to interpret within the framework of standard EEG definitions for sleep stages. Drouot et al (2012) found that about 28% of all polysomnography studies collected in the ICU could not be classified using conventional scoring rules.

Bispectral (BIS) monitoring is barely even validated for use in anaesthetised normal subjects, and its application to sleeping ICU patients is even more dodgy. It suffers from all the deficits of polysomnography in the ICU setting, and is confounded by all the same problems, but it does not offer much opportunity for specialist waveform interpretation, as it reduces the majestic electrochemical complexity of the human consciousness into a single numerical variable. Patel et al (2001) made an attempt to assess sleep in the ICU using BIS, working from the knowledge that BIS at least correlates with EEG during normal sleep. They used a value of over 85 to define "awake", 60-85 as "light sleep" (presumably, N1) and under 60 as "slow wave sleep". REM was detected using a combination of BIS waveform analysis and EMG recordings. The study was frustrated by the fact that the patients did not demonstrate any recognisable sleep stage patterns (eg. there were no rapid eye movements during the stages that were supposed to be REM sleep), and the authors could not arrive at anything solid about the use of BIS for sleep monitoring, concluding only that "traditional classifications of EEG sleep staging are deficient when used to describe sleep in intensive care unit patients". The major advantage of BIS is the fact that it does frequently correlate with the clinically observed state of arousal, and requires little intelligence to interpret.

Actigraphy is performed by the use of a wristwatch-like accelerometer, which tells you when the patient is moving. The obvious limitation of this is the lack of correlation between movement and arousal among ICU patients. The classical extreme example of this is the patient who is paralysed with muscle relaxants.  Beecroft et al (2008) compared it to polysomnography in a group of twelve intubated ICU patients, and concluded that it was "inaccurate and unreliable", as it consistently overestimated sleep time and sleep efficiency.

Subjective behavioural assessment  is basically asking of the bedside nurse whether he or she thinks the patient is asleep or awake. It sure is a cheap method, but also almost useless. For instance, Bourne et al (2007) found that ICU staff consistently mistook sedation for sleep (why wouldn't they, as it looks the same) and overestimated the duration and efficiency of sleep. The limitations are basically the same as those of actigraphy, as the bedside staff really only have movement to go off when determining whether the patient is awake. Not only are they collecting inaccurate data, they also frequently fail to record it (unlike the always-reliable actigraphy robot).

Hybrid systems are being developed. A recent article (Namba et al, 2015) added validity to the use of a wristwatch-like ambulatory sleep monitor (the Watch PAT 200 by Itamar), normally meant for outpatient sleep apnoea studies. That thing measures peripheral arterial tone as a means of estimating autonomic nervous system activity. The utility of these devices in ICU remains to be established; presently it seems like an expensive toy (imagine how many central lines you could buy instead).

Strategies to limit sleep disturbance in the ICU

The best reference for this seems to be the 2015 article by Kamdar et al, which details the implementation of a "multifaceted quality improvement intervention" to improve sleep quality among ICU patients at the Johns Hopkins Hospital Medical ICU. The following list of interventions is largely modelled on their program (see their Table 2); it sounds like a nice program,  even though they did not assess the sleep quality in any objective way.

Non-pharmacological measures to improve sleep in critical illness

  • Noise minimisation
    • Turn television off at night
    • Silence unnecessary alarms
    • Chase the family away after hours
  • Light level fluctuation to model the day-night rhythm (or, actual daylight!)
    • Raise curtains during the day, lower them at night
  • Optimise room temperature
  • Minimisation of mechanical ventilation, and the use of patient-triggered modes
  • Earplugs, eye masks
  • Relaxation techniques (eg, white noise or calming music, biofeedback,  massage)

Pharmacological measures to improve sleep in critical illness

  • Minimise caffeine use (this Kamdar study was at an American ICU, which most likely resembles a regular HDU here in Australia; many of the patients are likely to be extubated and demanding coffee)
  • Atypical antipsychotics for delirium (as opposed to benzodiazepines)
  • Minimise benzodiazepine use
  • Zolpidem, apparently
  • Use of melatonin (the studies are too few, and too heterogeneous, to make recommendations at this stage)


Orem, John, ed. Physiology in sleep. Elsevier, 2012.  - via Googlebooks

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