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

BACKGROUND: Beneficial 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. METHODS: The 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. RESULTS: Sixty-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. CONCLUSIONS: Our 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.