Melatonin and Melatonin Agonists to Prevent and Treat Delirium in Critical Illness: A Systematic Review
CCCF ePoster library. Singh T. Nov 7, 2018; 233442; 15
Tishaan Singh
Tishaan Singh
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INTRODUCTION Critically ill patients are at high risk of developing delirium with reported rates of up to 80%.1-3 Some studies have shown abnormal melatonin concentrations to be associated with post-operative and intensive care unit (ICU) delirium.4,5 Exogenous melatonin and melatonin agonists (MMA) have the potential to decrease the incidence and severity of delirium through their regulation of the circadian rhythm as well as hypnotic and sedative-sparing effects.4-9 We conducted a systematic review on the efficacy and safety of MMA for the prevention and treatment of ICU delirium.


OBJECTIVES To assess 1) the effectiveness of MMA compared to placebo or alternative therapy for preventing and treating delirium in critically ill patients and to examine the effect of MMA administration on: 2) duration of delirium; 3) delirium-free and coma-free days; 4) duration of mechanical ventilation; 5) ICU and hospital length of stay; 6) mortality; 7) discharge disposition; 8) long term cognitive outcomes; and 9) adverse events.


METHODS We used methods established by Cochrane to conduct this review. We searched the following databases (inception-June 2018) without language restriction: MEDLINE, Embase, PsychINFO, Cochrane Library, CINAHL, Web of Science, Scopus, and grey literature. We included all randomized (RCT) and non-randomized studies of critically ill patients that assessed MMA for the prevention or treatment of ICU delirium. Two reviewers independently screened the retrieved articles. Data from eligible studies was extracted and pooled for statistical analysis if at least 2 trials reported the outcome of interest.


RESULTS We screened 638 records and included 6 published studies (n=1152 subjects); we identified 5 conference abstracts and 13 ongoing studies for future use. Of the 6 included studies, 4 were RCTs, 1 was a prospective observation study, and 1 was a retrospective chart review. Three studies evaluated ramelteon, 2 melatonin, and 1 L-tryptophan. We found MMA reduced the incidence of delirium (RR 0.53, 95% CI 0.31, 0.90; 6 trials; moderate quality evidence). We found no difference in the duration of delirium (MD -0.91, 95% CI -2.58, 0.76; 3 trials; moderate quality evidence). We also found no difference in the duration of mechanical ventilation, lengths of stay, or mortality. No trial reported on delirium or coma-free days, discharge disposition or cognitive outcomes. Adverse events were rarely identified.



We found moderate-quality evidence that MMAs prevent delirium in critically ill patients. We found moderate quality evidence that MMAs do not shorten the duration of delirium or alter duration of mechanical ventilation.

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