Pharmacotherapy for sleep during critical illness and beyond

Sleep is a complex process thought to be regulated by both a circadian system closely tied to ambient light and a homeostatic process characterized by increasing pressure to sleep commensurate with increasing duration of wakefulness. Critical illness is often a complex, multi-system physiological insult characterized by high levels of stress hormones and inflammatory biomarkers as well as pain and anxiety which negatively impacts sleep. Sleep loss may potentiate physiological disturbances and is increasingly being linked to poor ICU outcomes. The current gold standard for improving the sleep of ICU patients is to bundle multiple non-pharmacologic interventions; medication should only be prescribed for sleep when those measures failed to produce the desired results. Medication administered to facilitate sleep has had disappointing results in the ICU and may have unintended consequences such as increasing the risk of delirium and falls. In general, pharmacotherapies used to induce sleep (hypnotics) have focused on targeting specific points along the arousal/sleep pathway. Another approach has been to enhance chronotropy both by non-pharmacologic measures as well as by melatonin supplementation or administration of melatonin receptor agonists. There have been some efforts to promote wakefulness as an effort to leverage the homeostatic pressure to sleep at night rather than allowing sleep to occur intermittently throughout the 24 h day as occurs during critical illness. This review will summarize the current data regarding the pharmacologic management of sleep in the ICU and propose one potential approach.