Oral melatonin as part of multimodal anxiolysis decreases emergence delirium in children whereas midazolam does not

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)