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

Eur J Anaesthesiol 2015 Jul 29

Authors: Mihara T et al

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; I#$##x0200A;#$#equals;#$##x0200A;0%]. However, TSA corrected the 95% CI to 0.07 to 1.47 and showed that 22.5% of the required information size (RIS) was achieved. The effect of melatonin compared with that of midazolam was not statistically significant (risk ratio 0.48, 95% CI 0.15 to 1.52) with significant heterogeneity (I#$##x0200A;#$#equals;#$##x0200A;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#$##x0200A;#$#equals;#$##x0200A;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).