Melatonin and Melatonin Agonists as Adjuncts for Sleep and Sedation in Critical Illness: A Systematic Review
CCCF ePoster library. Farina S. Nov 7, 2018; 233441; 14
Sasha Farina
Sasha Farina
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Introduction: Critically ill patients experience poor quality of sleep and may develop abnormal sleep-related phenomena1,2. Timely management of sleep disturbances for critically ill patients is vital due to poor health outcomes such as the development of delirium, prolonged stays in the intensive care unit (ICU), and increased mortality3-6. Critically ill patients may exhibit disturbed diurnal rhythms with altered patterns of melatonin secretion. Melatonin is a molecule that exerts chronobiologic effects on sleep and biorhythms and aministration of melatonin and melatonin receptor agonists (collectively referred to as MMA) have the potential to safely improve natural sleep, provide sedation, and may prevent or treat delirium7,8. We conducted a systematic review to assess the efficacy of MMAs for the promotion of sleep and reduction in sedative use in the ICU.

Methods: We performed a systematic search of the following databases: MEDLINE, EMBASE, the Cochrane database, Web of Science, CINAHL, PsycINFO, Scopus, and clinical practice guidelines. No language restrictions were applied and all study designs were eligible except for case studies. Studies could include critically ill adults and or children but not neonates. Two reviewers independently screened the retrieved articles for studies that evaluated the use of melatonin for sleep or reduction of sedatives in critically ill patients. Data from eligible studies is being extracted and after the quality assessment, data was pooled for statistical analysis if at least 2 trials reported the outcome of interest.

Results: Our search strategy yielded 1431 citations, of which 1391 were excluded based on title and abstract. After full-text reviews of 40 citations, we identified 6 eligible RCTs with a total of 343 patients; 5 ongoing RCTs were identified.  All included trials examined melatonin compared to either a placebo, a benzodiazepine, or non-drug sleep strategy. We found no difference in quantity of sleep between those who received melatonin and those who did not (mean difference -0.01, moderate quality evidence (n=3 studies, 119 subjects).  We also found no difference in duration of mechanical ventilation or ICU length of stay. There was insufficient data to pool on sleep quality, agitation, or sedative drug consumption. Adverse events were rarely identified.

Conclusions: We found limited moderate-quality evidence that melatonin does not alter sleep quantity compared to non-melatonin strategies. Furthermore, we found the methods for assessing sleep and defining sedative consumption varied between trials limiting our ability to pool results.


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