Effects of melatonin premedication to prevent emergence agitation after general anaesthesia in children: A systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Emergence agitation is a common phenomenon in children recovering from general anaesthesia. An emergence agitation reaction increases the risk of injuring the surgical repair, the patient and the caregivers.

OBJECTIVE: The objective of this study is to examine the efficacy of melatonin premedication in emergence agitation prevention.

DESIGN: A systematic review and meta-analysis of randomised controlled trials (RCTs) with trial sequential analysis (TSA) and meta-regression analysis.

DATA SOURCES: We searched MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, Web of Science, clinicaltrials.gov and UMIN Clinical Trials Registry up to 4 April 2014.

ELIGIBILITY CRITERIA: RCTs reporting effects of melatonin on the incidence of emergence agitation in children who underwent general anaesthesia were included.

RESULTS: Four studies (358 participants) were analysed. A conventional random-effects meta-analysis showed that compared with placebo, melatonin premedication may be effective in emergence agitation prevention [risk ratio 0.31, 95% confidence interval (CI) 0.16 to 0.60; I2 = 0%]. However, TSA corrected the 95% CI to 0.07 to 1.47 and showed that 22.5% of the required information size (RIS) was achieved. The effect of melatonin compared with that of midazolam was not statistically significant (risk ratio 0.48, 95% CI 0.15 to 1.52) with significant heterogeneity (I2 = 36.8%). TSA-adjusted 95% CI could not be calculated because of the small information size (4% of RIS). Meta-regression showed that, compared with midazolam, melatonin dose was significantly correlated with the effect (P = 0.024). The risk ratios (95% CI) of low and high-dose melatonin were 1.02 (0.39 to 2.65) and 0.22 (0.08 to 0.58), respectively. There was no effect of melatonin compared with dexmedetomidine (risk ratio 1.0, 95% CI 0.15 to 6.55). TSA-adjusted 95% CI could not be calculated (0.9% of RIS).

CONCLUSION: Compared with placebo, melatonin premedication may be effective in preventing emergence agitation in children (GRADE: low). This TSA suggests that further studies are required to confirm the results. Compared with midazolam, high-dose melatonin might have a significant effect in preventing emergence agitation (GRADE: very low). The study protocol was registered in the UMIN Clinical Trials Registry (registration number: UMIN000011841).