Oral melatonin as part of multimodal anxiolysis decreases emergence delirium in children whereas midazolam does not: A randomised, double-blind, placebo-controlled study.
Study Goal
The researchers aimed to evaluate whether oral melatonin, as part of a multimodal anxiolytic strategy, reduces emergence delirium in children after sevoflurane anesthesia compared to midazolam or placebo.
Results Summary
Melatonin significantly reduced the incidence of emergence delirium compared to both placebo (27% vs. 50%) and midazolam (27% vs. 56%), with no significant differences in sedation scores or pre-operative anxiety among the groups.
Population
Children aged 3 to 8 years undergoing elective ambulatory procedures with sevoflurane anesthesia.
Effective Dosage
0.3 mg/kg of melatonin, administered orally as a single premedication dose.
Duration
Single-dose intervention administered pre-operatively.
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
oral melatonin 0.3 mg kg-1 | decrease | emergence delirium | Children in the age group of 3 to 8 years who received sevoflurane anaesthesia for elective ambulatory procedures | 27 vs. 50%, respectively, an absolute risk reduction of 23.3 | significantly reduced the incidence of | #1 |
oral melatonin 0.3 mg kg-1 | decrease | emergence delirium | Children in the age group of 3 to 8 years who received sevoflurane anaesthesia for elective ambulatory procedures | 27 vs. 56%, respectively, an absolute risk reduction of 29.2 | significantly reduced the risk of | #2 |
midazolam 0.3 mg kg-1 | no change | emergence delirium | Children in the age group of 3 to 8 years who received sevoflurane anaesthesia for elective ambulatory procedures | - | had a similar incidence of | #3 |
oral melatonin 0.3 mg kg-1 | no change | sedation scores | Children in the age group of 3 to 8 years who received sevoflurane anaesthesia for elective ambulatory procedures | - | were similar | #4 |
midazolam 0.3 mg kg-1 | no change | sedation scores | Children in the age group of 3 to 8 years who received sevoflurane anaesthesia for elective ambulatory procedures | - | were similar | #5 |
honey as placebo | no change | sedation scores | Children in the age group of 3 to 8 years who received sevoflurane anaesthesia for elective ambulatory procedures | - | were similar | #6 |
oral melatonin 0.3 mg kg-1 | no change | pre-operative anxiety | Children in the age group of 3 to 8 years who received sevoflurane anaesthesia for elective ambulatory procedures | - | were similar | #7 |
midazolam 0.3 mg kg-1 | no change | pre-operative anxiety | Children in the age group of 3 to 8 years who received sevoflurane anaesthesia for elective ambulatory procedures | - | were similar | #8 |
honey as placebo | no change | pre-operative anxiety | Children in the age group of 3 to 8 years who received sevoflurane anaesthesia for elective ambulatory procedures | - | were similar | #9 |
oral melatonin 0.3 mg kg-1 | no change | compliance with mask induction | Children in the age group of 3 to 8 years who received sevoflurane anaesthesia for elective ambulatory procedures | - | were similar | #10 |
midazolam 0.3 mg kg-1 | no change | compliance with mask induction | Children in the age group of 3 to 8 years who received sevoflurane anaesthesia for elective ambulatory procedures | - | were similar | #11 |
honey as placebo | no change | compliance with mask induction | Children in the age group of 3 to 8 years who received sevoflurane anaesthesia for elective ambulatory procedures | - | were similar | #12 |
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).