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.
general anaesthesia
melatonin
midazolam
paediatric anxiety
perioperative care
premedication
Journal
British journal of anaesthesia
ISSN: 1471-6771
Titre abrégé: Br J Anaesth
Pays: England
ID NLM: 0372541
Informations de publication
Date de publication:
10 Nov 2023
10 Nov 2023
Historique:
received:
21
06
2023
revised:
06
10
2023
accepted:
11
10
2023
medline:
13
11
2023
pubmed:
13
11
2023
entrez:
12
11
2023
Statut:
aheadofprint
Résumé
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. 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 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. Melatonin was less effective than midazolam at reducing preoperative anxiety in children, although the early termination of the trial increases the likelihood of bias. ISRCTN registry: ISRCTN18296119.
Sections du résumé
BACKGROUND
BACKGROUND
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.
METHODS
METHODS
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
RESULTS
RESULTS
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.
CONCLUSION
CONCLUSIONS
Melatonin was less effective than midazolam at reducing preoperative anxiety in children, although the early termination of the trial increases the likelihood of bias.
CLINICAL TRIAL REGISTRATION
BACKGROUND
ISRCTN registry: ISRCTN18296119.
Identifiants
pubmed: 37953202
pii: S0007-0912(23)00565-2
doi: 10.1016/j.bja.2023.10.011
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Investigateurs
Sondos Albadri
(S)
Laura Armstrong
(L)
Simon Atkins
(S)
Margaret Babb
(M)
Claire Biercamp
(C)
Katie Biggs
(K)
Mike Bradburn
(M)
Jaimie Buckley
(J)
Julie Child-Cavill
(J)
Sean Cope
(S)
Simon Crawley
(S)
Munya Dimairo
(M)
Enass Duro
(E)
Ayman Eissa
(A)
Laura Flight
(L)
Jacqui Gath
(J)
Gil Gavel
(G)
Tim Geary
(T)
Fiona Gilchrist
(F)
Padma Gopal
(P)
Jamie Hall
(J)
Kate Hutchence
(K)
Puran Khandelwal
(P)
Pranav Kukreja
(P)
Ian Leeuwenberg
(I)
James Limb
(J)
Amanda Loban
(A)
Katie Mellor
(K)
Nuria Masip
(N)
Anthony Moores
(A)
Vimmi Oshan
(V)
Edward Pickles
(E)
Jaydip Ray
(J)
Helen Rodd
(H)
Sian Rolfe
(S)
Elena Sheldon
(E)
Richard Simmonds
(R)
Rachel Smith
(R)
Ashok Sundar
(A)
Anna Thomason
(A)
Simon Waterhouse
(S)
Graham Wilson
(G)
Julian Yates
(J)
Tracey Young
(T)
Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.