Oral melatonin as part of multimodal anxiolysis decreases emergence delirium in children whereas midazolam does not: A randomised, double-blind, placebo-controlled study.

BACKGROUND: Pre-operative anxiety is a risk factor for emergence delirium in children and a multimodal approach including sedatives and nonpharmacological measures is the current strategy to tackle this anxiety. The efficacy of oral melatonin as a component of multimodal anxiolytic strategy to decrease emergence delirium is not well studied. OBJECTIVE: The aim of this study was to evaluate the efficacy of a multimodal anxiolytic strategy including oral melatonin or midazolam to decrease emergence delirium after sevoflurane anaesthesia. DESIGN: A randomised, double-blind, parallel arm, placebo-controlled trial. SETTING: Tertiary care teaching hospital from July 2019 till January 2020. PARTICIPANTS: Children in the age group of 3 to 8 years who received sevoflurane anaesthesia for elective ambulatory procedures. INTERVENTIONS: Children were randomised to receive oral premedication with either melatonin 0.3 mg kg-1, midazolam 0.3 mg kg-1 or honey as placebo. All the children received standardised nonpharmacological measures involving multiple techniques to allay anxiety. The anaesthetic plan was also standardised. MAIN OUTCOME MEASURES: The primary outcome was the incidence of emergence delirium as assessed by the Watcha scale in the postanaesthesia care unit. The secondary outcomes were pre-operative anxiety assessed using a modified Yale Preoperative Anxiety scale, patient compliance with mask induction using the Induction Compliance Checklist and postoperative sedation. RESULTS: Data from 132 children were analysed. Melatonin significantly reduced the incidence of emergence delirium compared to placebo: 27 vs. 50%, respectively, an absolute risk reduction of 23.3 [95% confidence interval 3.7 to 42.9), P = 0.03]. Melatonin also significantly reduced the risk of emergence delirium compared with midazolam: 27 vs. 56%, respectively, an absolute risk reduction of 29.2 (95% CI 9.5 to 48.8). The midazolam group had a similar incidence of emergence delirium as placebo. Sedation scores were similar in the three groups postoperatively. The incidence and score of pre-operative anxiety as well as the compliance with mask induction were similar in the three groups. CONCLUSIONS: A multimodal anxiolytic approach including oral melatonin, as opposed to oral midazolam, significantly reduced emergence delirium after sevoflurane anaesthesia. TRIAL REGISTRATION: CTRI/2019/06/019850 in Clinical Trial Registry of India (www.ctri.nic.in).