Effect of different administration and dosage of dexmedetomidine in the reduction of emergence agitation in children: a meta-analysis of randomized controlled trials with sequential trial analysis.

Abstract

BackgroundBeneficial effects of dexmedetomidine (DEX) against emergence agitation (EA) in children remain controversial. We performed a more comprehensive meta-analysis to evaluate the protective effect of different administration routes, timing, patterns, and doses of DEX on EA in children.MethodsThe randomized controlled trials about DEX preventing EA in children were searched in PubMed, Cochrane Library, Embase, and Web of Sciences up to October 7, 2020. The traditional meta-analysis and subgroup analysis were performed to study the influence of DEX on EA in children. The sequential trial analysis (TSA) further analyzed the pooled results to evaluate meta-analyses’ robustness. Grading of recommendation, assessment, development, and evaluation (GRADE) was used to assess evidence quality.ResultsSixty-seven studies with 5,688 pediatric patients were included. DEX significantly decreased EA in children compared to placebo [RR 0.29, 95% confidence intervals (CI): 0.25–0.34] and midazolam (RR 0.34, 95% CI: 0.25–0.45), with firm evidence from TSA. Notably, using DEX significantly reduced severe EA incidence (RR 0.23, 95% CI: 0.16–0.32), with firm evidence by TSA and high quality of GRADE. Pre-specified subgroup analyses revealed firm and high-quality evidence for a reduction of EA, only if the perineural route administers DEX (RR 0.24, 95% CI: 0.14–0.41), as premedication (RR 0.27, 95% CI: 0.20–0.36), as continuous dosage (RR 0.25, 95% CI: 0.18–0.33), at high dose (RR 0.24, 95% CI: 0.18–0.31). The pooled results also showed that DEX reduced the incidence of PONV compared to placebo (RR 0.43, 95% CI: 0.33–0.55). Evidence for DEX’s influence on other secondary outcomes (emergence time, time in PACU, rescue analgesia, hypotension, and bradycardia) is insufficient to draw any conclusion.ConclusionsOur findings confirm the beneficial effects of DEX on EA, severe EA, and PONV in children. There was firm and high-quality evidence for the efficacy of DEX in preventing EA in children when perineural routes administered DEX, as premedication, as continuous dosage, and at a high dose. The best dose, route, patterns, and timing of DEX and influence on other outcomes call for further studies.