The MAGIC trial: a pragmatic, multicentre, parallel, noninferiority, randomised trial of melatonin versus midazolam in the premedication of anxious children attending for elective surgery under general anaesthesia.


Bolt, Robert, Hyslop, Marie C, Herbert, Esther, Papaioannou, Diana E ORCID: 0000-0002-6259-0822, Totton, Nikki ORCID: 0000-0002-1900-2773, Wilson, Matthew J, Clarkson, Janet, Evans, Christopher, Ireland, Nicholas ORCID: 0000-0002-3665-0641, Kettle, Jennifer ORCID: 0000-0002-2776-1243 et al (show 6 more authors) (2024) The MAGIC trial: a pragmatic, multicentre, parallel, noninferiority, randomised trial of melatonin versus midazolam in the premedication of anxious children attending for elective surgery under general anaesthesia. British journal of anaesthesia, 132 (1). pp. 76-85.

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Abstract

<h4>Background</h4>Child anxiety before general anaesthesia and surgery is common. Midazolam is a commonly used premedication to address this. Melatonin is an alternative anxiolytic, however trials evaluating its efficacy in children have delivered conflicting results.<h4>Methods</h4>This multicentre, double-blind randomised trial was performed in 20 UK NHS Trusts. A sample size of 624 was required to declare noninferiority of melatonin. Anxious children, awaiting day case elective surgery under general anaesthesia, were randomly assigned 1:1 to midazolam or melatonin premedication (0.5 mg kg<sup>-1</sup>, maximum 20 mg) 30 min before transfer to the operating room. The primary outcome was the modified Yale Preoperative Anxiety Scale-Short Form (mYPAS-SF). Secondary outcomes included safety. Results are presented as n (%) and adjusted mean differences with 95% confidence intervals.<h4>Results</h4>The trial was stopped prematurely (n=110; 55 per group) because of recruitment futility. Participants had a median age of 7 (6-10) yr, and 57 (52%) were female. Intention-to-treat and per-protocol modified Yale Preoperative Anxiety Scale-Short Form analyses showed adjusted mean differences of 13.1 (3.7-22.4) and 12.9 (3.1-22.6), respectively, in favour of midazolam. The upper 95% confidence interval limits exceeded the predefined margin of 4.3 in both cases, whereas the lower 95% confidence interval excluded zero, indicating that melatonin was inferior to midazolam, with a difference considered to be clinically relevant. No serious adverse events were seen in either arm.<h4>Conclusion</h4>Melatonin was less effective than midazolam at reducing preoperative anxiety in children, although the early termination of the trial increases the likelihood of bias.<h4>Clinical trial registration</h4>ISRCTN registry: ISRCTN18296119.

Item Type: Article
Uncontrolled Keywords: MAGIC collaborative, Humans, Midazolam, Melatonin, Premedication, Anesthesia, General, Double-Blind Method, Anxiety, Child, Female, Male
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences > School of Dentistry
Depositing User: Symplectic Admin
Date Deposited: 06 Feb 2024 11:12
Last Modified: 06 Feb 2024 11:12
DOI: 10.1016/j.bja.2023.10.011
Open Access URL: https://doi.org/10.1016/j.bja.2023.10.011
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3178478
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