Abstract: We included four studies with 151 randomized participants. Two studies included participants who were mechanically ventilated, one study included a mix of ventilated and non-ventilated participants and in one study participants were being weaned from mechanical ventilation. Three studies reported admission diagnoses, which varied: these included sepsis, pneumonia and cardiac or cardiorespiratory arrest. All studies compared melatonin against no agent; three were placebo-controlled trials; and one compared melatonin with usual care. All studies administered melatonin in the evening. All studies reported adequate methods for randomization and placebo-controlled trials were blinded at the participant and personnel level. We noted high risk of attrition bias in one study and were unclear about potential bias introduced in two studies with differences between participants at baseline. It was not appropriate to combine data owing to differences in measurement tools, or methods used to report data. The effects of melatonin on subjectively rated quantity and quality of sleep are uncertain (very low certainty evidence). Three studies (139 participants) reported quantity and quality of sleep as measured through reports of participants or family members or by personnel assessments. Study authors in one study reported no difference in sleep efficiency index scores between groups for participant assessment (using Richards-Campbell Sleep Questionnaire) and nurse assessment. Two studies reported no difference in duration of sleep observed by nurses. The effects of melatonin on objectively measured quantity and quality of sleep are uncertain (very low certainty evidence). Two studies (37 participants) reported quantity and quality of sleep as measured by polysomnography (PSG), actigraphy, bispectral index (BIS) or electroencephalogram (EEG). Study authors in one study reported no difference in sleep efficiency index scores between groups using BIS and actigraphy. These authors also reported longer sleep in participants given melatonin which was not statistically significant, and improved sleep (described as "better sleep") in participants given melatonin from analysis of area under the curve (AUC) of BIS data. One study used PSG but authors were unable to report data because of a large loss of participant data. One study (82 participants) reported no evidence of a difference in anxiety scores (very low certainty evidence). Two studies (94 participants) reported data for mortality: one study reported that overall one-third of participants died; and one study reported no evidence of difference between groups in hospital mortality (very low certainty). One study (82 participants) reported no evidence of a difference in length of ICU stay (very low certainty evidence). Effects of melatonin on adverse events were reported in two studies (107 participants), and are uncertain (very low certainty evidence): one study reported headache in one participant given melatonin, and one study reported excessive sleepiness in one participant given melatonin and two events in the control group (skin reaction in one participant, and excessive sleepiness in another participant). The certainty of the evidence for each outcome was limited by sparse data with few participants. We noted study limitations in some studies due to high attrition and differences between groups in baseline data; and doses of melatonin varied between studies. Methods used to measure data were not consistent for outcomes, and use of some measurement tools may not be effective for use on the ICU patient. All studies included participants in the ICU but we noted differences in ICU protocols, and one included study used a non-standard sedation protocol with participants which introduced indirectness to the evidence. We found insufficient evidence to determine whether administration of melatonin would improve the quality and quantity of sleep in ICU patients. We identified sparse data, and noted differences in study methodology, in ICU sedation protocols, and in methods used to measure and report sleep. We identified five ongoing studies from database and clinical trial register searches. Inclusion of data from these studies in future review updates would provide more certainty for the review outcomes.

Plain-language summary: The evidence is current to September 2017. We included four studies with 151 participants in the review. All participants were critically ill and were in the ICU. All studies compared melatonin with no agent (an inactive substance called a placebo), or with usual care. We did not combine data from the four included studies. Three studies used nurses and participants to assess sleep and reported no difference in quality and quantity of sleep. Two studies used equipment to measure quality and quantity of sleep, and one of these studies reported no difference in sleep efficiency (how well the person sleeps during night-time hours) according to melatonin use and, according to some analysis, evidence of "better sleep" for those given melatonin. One study reported problems with equipment which led to a loss of data. One study reported no difference in anxiety, and there was no difference in mortality, or length of stay in the ICU. We noted few potential side effects of melatonin (headache in one participant, and excessive sleepiness in another participant). We noted differences between groups in doses of melatonin and two studies reported differences between groups in participant characteristics which could have affected the results. One study had a large loss of data and another study did not use standard anaesthetic drugs to sedate patients. Few studies used appropriate equipment to measure quantity of sleep. We found few studies with few participants that assessed our review outcomes. We judged all evidence to be very low quality, and we could not be certain whether melatonin given to adults in the ICU improves quantity and quality of sleep. We found five ongoing studies in database and clinical trial register searches. Inclusion of these studies in future review updates would provide more certainty for the review outcomes.