OBJECTIVES: Melatonin has wide-ranging effects on the body, including the regulation of circadian rhythm, and potentiation of cellular immune and antioxidant activities. In critically ill patients, endogenous melatonin has been shown to be markedly deranged and reduced. Therefore, the purpose of this systematic review and meta-analysis was to determine if exogenous supplementation of melatonin improves patient-centered outcomes.
DATA SOURCES: We searched five electronic databases.
STUDY SELECTION: Randomized clinical trials (RCTs) that compared melatonin to no melatonin in adults admitted to the ICU were identified.
DATA EXTRACTION: We aggregated data as relative risks, mean differences (MDs), and standard mean differences (SMDs) using a random-effects model. Supporting evidence for each effect was evaluated for certainty using the Grading Recommendations, Assessment, Development, and Evaluations approach.
DATA SYNTHESIS: In total, 32 RCTs (n = 3895 patients) were included. We found that melatonin may reduce delirium (relative risk [RR] 0.72; 95% CI, 0.58-0.89; low certainty), may slightly reduce ICU length of stay (MD -0.57 d; 95% CI, -0.95 to -0.18 d; low certainty), and may improve reported sleep quality (SMD 0.54; 95% CI, 0.01-1.07; low certainty). Melatonin may result in a slight reduction in the frequency of adverse events (low certainty). Evidence was uncertain with regards to the frequency of sleep awakenings, anxiety level, agitation, and post-traumatic stress disorder incidence (all very low certainty), as well as to ICU mortality and post-ICU functional status (both low certainty).
CONCLUSIONS: Our findings suggest that melatonin administration in the critically ill may improve perceived sleep and reduce delirium, without increasing adverse effects. Certainty of evidence was negatively affected by the risk of bias and inconsistency. Future RCTs should focus on identifying optimal dosing, administration timing, improving measurements of sleep outcomes, and target populations.
| Specialty | Score |
|---|---|
| Internal Medicine | |
| Intensivist/Critical Care |
This well conducted meta-analysis included 32 RCTs (3895 patients) and compared patients admitted to ICU receiving melatonin vs not. All ICU patients were included, with notable heterogeneity amongst studt dosing (25 studies <10mg, 7 >10mg) and timing of melatonin (21 nocte, 6 throughout the day, 5 unknown). The authors showed a significant reduction in delirium (RR: 0.72 0.5 to 0.89), ICU LoS (MD -0.57 to -0.95 to -0.18) and perceived sleep quality. No difference in sleep quantity, number of awakenings, adverse events, anxiety, agitation, functional outcomes, or mortality were observed. The authors should be commended for their efforts, sleep and delirium are notoriously challenging to study in ICU due to the large number of confounders, notably admission diagnosis, drugs in use and pre morbid cognitive function. Overall there was a trend towards some potential benefit with little associated risk, future studies of timing, dose and specific patient groups should be conducted.
Interesting systematic review. ICU delirium and poor sleep are important problems. Melatonin has few side effects and might be worth trying. I am not in ICU attending currently, but would try this given its safety profile. This is a bit less relevant to my hospitalist colleagues.
This article is most pertinent to MDs who work in the ICU but may also spill over into the care of other admitted patients.
Useful topic but note that most of the outcomes have moderate-to-high heterogeneity with no exploration of the source of the heterogeneity.
, McMaster University