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

Xu Zhang; Yan Bai; Min Shi; Shaopeng Ming; Xiaogao Jin; Yubo Xie

doi:10.21037/tp-21-105

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

Transl Pediatr. 2021 Apr;10(4):929-957. doi: 10.21037/tp-21-105.

Authors

Xu Zhang¹, Yan Bai², Min Shi¹, Shaopeng Ming³, Xiaogao Jin⁴, Yubo Xie¹

Affiliations

¹ Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
² Department of Anesthesiology, The Second Affiliated Hospital of Guilin Medical University, Guilin, China.
³ Department of Anesthesiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China.
⁴ Department of Anesthesiology, The Affiliated Hospital of Guilin Medical University, Guilin, China.

Abstract

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.

Keywords: Dexmedetomidine (DEX); children; emergence agitation (EA); general anesthesia; meta-analysis; sequential trial analysis (TSA).