Efficacy of chloral hydrate oral solution for sedation in pediatrics: a systematic review and meta-analysis

Objective: Chloral hydrate (CH), as a sedation agent, is widely used in children for diagnostic or therapeutic procedures. However, it has not come into the market and is currently only used as hospital preparation in China. This review aims to systematically evaluate the efficacy of CH in children of all age groups for sedation before medical procedures.

Materials and methods: Seven electronic databases and three clinical trial registry platforms were searched and the deadline was September 2018. Randomized controlled trials (RCTs) evaluating the efficacy of CH for sedation in children were included by two reviewers. The extracted information included success rate of sedation, sedation latency and sedation duration. The Cochrane risk of bias tool was applied to assess the risk of bias. The outcomes were analyzed by Review Manager 5.3 software and expressed as relative risks (RR) or Mean Difference (MD) with 95% confidence interval (CI). Heterogeneity was assessed with I-squared (I²) statistics.

Results: A total of 24 RCTs involving 3564 children of CH for sedation were included in the meta-analysis. Compared to placebo group, CH group had a significant increase in success rate of sedation when used for painless and painful procedure (RR=4.15, 95% CI [1.21, 14.24], P=0.02; RR=1.28, 95% CI [1.17, 1.40], P<0.01), which included 22 and 455 children for this analysis, respectively. Compared to midazolam group, CH group had a significant increase in success rate of sedation (RR=1.63, 95% CI [1.48, 1.79], I²=0%, P<0.00001), sedation latency (MD=13.29, 95% CI [11.42, 15.16], I²=0%, P<0.00001) and sedation duration (MD=17.52, 95% CI [10.3, 24.71], I²=0%, P<0.05), which included 1052, 710 and 727 children for this analysis, respectively. Compared to diazepam, there was no significant difference in success rate of sedation (RR=0.93, 95% CI [0.80, 1.08], I²=52%, P=0.32), which included 230 children for this analysis. Compared to dexmedetomidine, there was no significant difference in the success rate of sedation (RR=0.92, 95% CI [0.80, 1.06], I²=48%, P=0.27) and sedation latency (RR=-1.09, 95% CI [-2.45, 0.26], I²=26%, P=0.11), which included 512 and 371 children for this analysis, respectively. Compared to barbiturates, there was no significant difference in the success rate of sedation (RR=1.03, 95% CI [0.94, 1.13], I²=50%, P=0.58) and sedation duration (MD=-0.72, 95% CI [-1.78, 0.34], I²=38%, P=0.18), which included 749 and 210 children for this analysis, respectively.

Conclusions: From the extrapolation of the existing literature, CH oral solution is an appropriate effective alternative for sedation in pediatrics.