Clonidine for preventing emergence agitation in infants (PREVENT AGITATION II): Protocol and statistical analysis plan.
Child
Humans
Infant
Clonidine
/ therapeutic use
Emergence Delirium
/ prevention & control
Anesthetics, Inhalation
Sevoflurane
Anesthesia, General
/ adverse effects
Psychomotor Agitation
/ prevention & control
Double-Blind Method
Anesthesia Recovery Period
Methyl Ethers
Randomized Controlled Trials as Topic
clonidine
emergence agitation
infants
sevoflurane
Journal
Acta anaesthesiologica Scandinavica
ISSN: 1399-6576
Titre abrégé: Acta Anaesthesiol Scand
Pays: England
ID NLM: 0370270
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
13
01
2023
accepted:
20
01
2023
medline:
21
4
2023
pubmed:
11
2
2023
entrez:
10
2
2023
Statut:
ppublish
Résumé
Emergence agitation is a common clinical condition in children. Symptoms pertaining to the spectrum of early postoperative negative behavior typically occur upon emergence from anesthesia. Clonidine is an effective adjunctive agent for the prevention of emergence agitation in children, but evidence in the smallest age groups is sparse We aim to investigate the efficacy and safety of an intraoperative bolus of intravenous clonidine for preventing emergence agitation in children 3-12 months of age. This is a randomized, placebo-controlled, double-blind trial. We will enroll 320 patients aged 3-12 months who have been scheduled for general anesthesia maintained with sevoflurane and opioid. The randomization is parallel and stratified by age group, sex, and site. The investigational medicinal product will be administered intravenously ~20 min before the anticipated end of the surgical procedure. The intervention is clonidine 3 μg/kg and placebo is isotonic saline in a corresponding volume. The primary outcome is the incidence of emergence agitation as assessed on the Watcha scale, that is, any Watcha score >2 during participants' stay in the postanesthetic care unit. Secondary outcomes are the proportion of participants with postoperative pain, with postoperative nausea and vomiting, and a composite safety outcome. Statistical analysis will be conducted according to the Statistical Analysis Plan with the intention-to-treat population for our primary analyses. The PREVENT AGITATION II trial will contribute valuable knowledge on efficacy for the prevention of emergence agitation and safety in infants.
Sections du résumé
BACKGROUND
Emergence agitation is a common clinical condition in children. Symptoms pertaining to the spectrum of early postoperative negative behavior typically occur upon emergence from anesthesia. Clonidine is an effective adjunctive agent for the prevention of emergence agitation in children, but evidence in the smallest age groups is sparse We aim to investigate the efficacy and safety of an intraoperative bolus of intravenous clonidine for preventing emergence agitation in children 3-12 months of age.
METHODS
This is a randomized, placebo-controlled, double-blind trial. We will enroll 320 patients aged 3-12 months who have been scheduled for general anesthesia maintained with sevoflurane and opioid. The randomization is parallel and stratified by age group, sex, and site. The investigational medicinal product will be administered intravenously ~20 min before the anticipated end of the surgical procedure. The intervention is clonidine 3 μg/kg and placebo is isotonic saline in a corresponding volume.
RESULTS
The primary outcome is the incidence of emergence agitation as assessed on the Watcha scale, that is, any Watcha score >2 during participants' stay in the postanesthetic care unit. Secondary outcomes are the proportion of participants with postoperative pain, with postoperative nausea and vomiting, and a composite safety outcome. Statistical analysis will be conducted according to the Statistical Analysis Plan with the intention-to-treat population for our primary analyses.
CONCLUSION
The PREVENT AGITATION II trial will contribute valuable knowledge on efficacy for the prevention of emergence agitation and safety in infants.
Substances chimiques
Clonidine
MN3L5RMN02
Anesthetics, Inhalation
0
Sevoflurane
38LVP0K73A
Methyl Ethers
0
Types de publication
Clinical Trial Protocol
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
663-669Subventions
Organisme : Lippmann Fonden
Organisme : Oberstinde Kirsten Jensa la Cours Legat
Organisme : Rigshospitalet
Informations de copyright
© 2023 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.
Références
Kain ZN, Caldwell-Andrews AA, Maranets I, et al. Preoperative anxiety and emergence delirium and postoperative maladaptive behaviors. Anesth Analg. 2004;99(6):1648-1654.
Somaini M, Engelhardt T, Fumagalli R, Ingelmo PM. Emergence delirium or pain after anaesthesia: how to distinguish between the two in young children: a retrospective analysis of observational studies. Br J Anaesth. 2016;116(3):377-383.
Costi D, Cyna AM, Ahmed S, et al. Effects of sevoflurane versus other general anaesthesia on emergence agitation in children. Cochrane Database Syst Rev. 2014;(9):CD007084.
Yasui Y, Masaki E, Kato F. Sevoflurane directly excites locus coeruleus neurons of rats. Anesthesiology. 2007;107(6):992-1002.
Voepel-Lewis T, Malviya S, Tait AR. A prospective cohort study of emergence agitation in the pediatric postanesthesia care unit. Anesth Analg. 2003;96(6):1625-1630.
Dahmani S, Delivet H, Hilly J. Emergence delirium in children: an update. Curr Opin Anaesthesiol. 2014;27(3):309-315.
Jamadarkhana S, Gopal S. Clonidine in adults as a sedative agent in the intensive care unit. J Anaesthesiol Clin Pharmacol. 2010;26(4):439-445.
Wang JG, Belley-Coté E, Burry L, et al. Clonidine for sedation in the critically ill: a systematic review and meta-analysis. Crit Care. 2017;21(1):75.
Pichot C, Ghignone M, Quintin L. Dexmedetomidine and clonidine: from second- to first-line sedative agents in the critical care setting? J Intensive Care Med. 2012;27(4):219-237.
Pickard A, Davies P, Birnie K, Beringer R. Systematic review and meta-analysis of the effect of intraoperative α2-adrenergic agonists on postoperative behaviour in children. Br J Anaesth. 2014;112(6):982-990.
Blaudszun G, Lysakowski C, Elia N, Tramèr MR. Effect of perioperative systemic α2 agonists on postoperative morphine consumption and pain intensity: systematic review and meta-analysis of randomized controlled trials. Anesthesiology. 2012;116(6):1312-1322.
Afshari A. Clonidine in pediatric anesthesia: the new panacea or a drug still looking for an indication? Curr Opin Anaesthesiol. 2019;32(3):327-333.
Ydemann M, Nielsen BN, Henneberg S, et al. Intraoperative clonidine for prevention of postoperative agitation in children anaesthetised with sevoflurane (PREVENT AGITATION): a randomised, placebo-controlled, double-blind trial. Lancet Child Adolesc Health. 2018;2(1):15-24.
Hong H, Hahn S, Choi Y, et al. Evaluation of propofol in comparison with other general anesthetics for surgery in children younger than 3 years: a systematic review and meta-analysis. J Korean Med Sci. 2019;34(15):e192.
Chan A, Tetzlaff JM, Altman DG, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;158(3):200-207.
European Medicines Agency (EMA). Guideline for good clinical practice E6(R2). Commun Hum Med Prod. 2016;6:1-68.
World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. Jama. 2013;310(20):2191-2194.
European Commision Enterprise and Industry Directorate-General. EU GMP Annex 13: Investigational Medicinal Products. EudraLex The Rules Governing Medicinal Products in the European Union; 2010.
Watcha MF, Ramirez-Ruiz M, White PF, Jones MB, Lagueruela RG, Terkonda RP. Perioperative effects of oral ketorolac and acetaminophen in children undergoing bilateral myringotomy. Can J Anaesth. 1992;39(7):649-654.
Sikich N, Lerman J. Development and psychometric evaluation of the pediatric anesthesia emergence delirium scale. Anesthesiology. 2004;100(5):1138-1145.
Bajwa SA, Costi D, Cyna AM. A comparison of emergence delirium scales following general anesthesia in children. Paediatr Anaesth. 2010;20(8):704-711.
Merkel SI, Voepel-Lewis T, Shayevitz JR, Malviya S. The FLACC: a behavioral scale for scoring postoperative pain in young children. Pediatr Nurs. 1997;23(3):293-297.
Malviya S, Voepel-Lewis T, Tait AR, Merkel S, Tremper K, Naughton N. Depth of sedation in children undergoing computed tomography: validity and reliability of the University of Michigan Sedation Scale (UMSS). Br J Anaesth. 2002;88(2):241-245.
Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)-a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377-381.
Jenkins BN, Kain ZN, Kaplan SH, et al. Revisiting a measure of child postoperative recovery: development of the post hospitalization behavior questionnaire for ambulatory surgery. Pediatr Anesth. 2015;25(7):738-745.
International Committee of Medical Journal Editors. Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals [Internet]; 2019. http://www.icmje.org/icmje-recommendations.pdf. Accessed 1 December 2021.