Efficacy of melatonin vs. midazolam for oral premedication in children: a systematic review and meta-analysis.

Introduction: Achieving appropriate levels of premedication and parental separation is needed for smooth induction of anesthesia and prevention of perioperative complications. Both melatonin and midazolam are used for the premedication in children, but we do not have consensus on which premedication is superior among them.

Evidence acquisition: A systematic review of randomized controlled trials comparing the efficacy and safety of use of midazolam and melatonin as premedication in children aged 1-15 years was conducted. Patients who received drugs other than melatonin or midazolam as premedication were excluded. PubMed, Embase, Scopus, Google Scholar were searched and the last search was done in December 2022.

Evidence synthesis: Full text of ten articles with a total of 774 participants (442 melatonin, 332 midazolam) were eligible. The data extracted were synthesized after quality assessment. The outcomes appraised included: sedation, anxiety in preoperative room and during induction. Among four studies examining sedation, there were no significant differences between melatonin and midazolam (SMD=0.03, 95% CI - 0.35 to 0.40, P=0.88, I²⁼81%). There were no significant differences between melatonin and midazolam among two studies examining anxiety in pre-operative room (SMD=-0.04, 95% CI -4.58,4.50, P=0.99, I²⁼0%) and anxiety during anesthesia induction as an outcome (SMD=-1.38, 95% CI -4.81 to 2.05, P=0.43, I²⁼0%).

Conclusions: The review showed that melatonin is comparable to midazolam in achieving sedation for facilitating inhalational induction in pediatric patients. The review showed no significant difference in reduction of anxiety in the preoperative room and during induction of anesthesia when either melatonin or midazolam is used as premedicants. Heterogeneity in premedication doses, parameters assessed, outcomes measured, and scales that quantify efficacy resulted in the inconsistencies in how the medications were compared and hence resulted in difficulties in data synthesis. Future studies comparing efficacy of premedication need to consider the proposed standardizations in methodology for achieving optimal results that are a fair comparison of the two medications.