Systematic review and meta-analysis of the effect of intraoperative α2-adrenergic agonists on postoperative behaviour in children

Abstract

Undergoing general anaesthesia is distressing for children, with up to two-thirds demonstrating abnormal behaviours after their procedure, such as emergence delirium (ED) and post-hospitalization behaviour change. The aim of this systematic review was to determine the effect of intraoperative i.v. α₂-adrenergic agonists on postoperative behaviour in children. We included published full-text reports of randomized controlled trials involving children who received i.v. clonidine or dexmedetomidine after induction of general anaesthesia, who were assessed for postoperative behavioural disturbance. After screening of references identified by the search strategy, a data collection form was developed and piloted. Data extraction was performed by one reviewer and checked by a second. Twelve randomized trials met the inclusion criteria. Ten studies (n=669) reported dichotomous data that were included in the pooled analysis of α₂-adrenergic agonists vs placebo. There was strong evidence that i.v. α₂-adrenergic agonists reduced postoperative ED (overall summary odds ratio 0.28, 95% confidence interval 0.19-0.40, P<0.001). No studies examined post-hospitalization negative behaviour changes. There was evidence that α₂-adrenergic agonists prolonged time in the recovery room. No adverse haemodynamic events were reported in any arm of any study. This meta-analysis provides evidence that intraoperative i.v. α₂-adrenergic agonists reduce the incidence of emergency delirium in children. The prolongation of time in recovery is unlikely to be clinically relevant. The absence of data regarding the effect on post-hospitalization behavioural changes provides an opportunity for future research.

Emergence delirium in children

“…There has recently been increased interest in the use of a 2 -adrenergic receptor agonists. A systematic review and meta-analysis by Pickard et al [32], that included 12 randomised trials, concluded that both dexmedetomidine and clonidine reduced the incidence of emergence delirium, although recovery times were prolonged. One study [33] demonstrated that pre-operative infusion of dexmedetomidine reduced the incidence following eye surgery, although as this may be an impractical way to administer the drug whilst the patient is awake, intranasal administration is probably an acceptable alternative [34].…”

Intravenous Clonidine: A Useful and Safety Sedation for Critically Ill Children

“…Several studies describe the beneficial effects of clonidine for premedication in pediatric anesthesia, prevention of emergence agitation, prolongation of postoperative analgesia as a supplement to regional anesthesia, reduction of the incidence of post-operative vomiting, and treatment of emergence delirium [6,[9][10][11][12][13]. Clonidine can also be used in opiate withdrawal treatment, attention deficit/hyperactivity disorder, Tourette's syndrome, schizophrenia and Korsakoff syndrome [1].…”

“…It has a sedative effect mediated by binding to post-synaptic alpha-2 receptors in the pontine locus ceruleus, reducing noradrenergic output and thereby facilitating the firing of inhibitory neurones, mainly, the gamma-aminobutyric acid system. Clonidine has an analgesic action through binding to alpha-2 receptors in the dorsal horn and supra-spinal sites and thereby reduce the release of P substance [1,5,6]. It also causes peripheral vasodilatation and a decrease in systolic blood pressure, heart rate and cardiac output by decreasing sympathetic nervous system activity.…”

Comparative Study and Safe Dose Analysis of Dexmedetomidine in the Prevention of Emergence Agitation and Emergency Delirium in Children Undergoing General Anesthesia

“…Emergence agitation in children was first described in the early 1960s and is characterized by a dissociated state of consciousness in which the child becomes inconsolable, irritable, uncooperative, and sometimes aggressive. Although temporary, it is an extremely distressing event for children, parents, and health professionals [10]. Prevalence of agitation varies from 25% to 80% in the literature, depending on the definition and criteria used by the authors [11].…”