Bian Yong, Zhou Siyi, Hou Huiyan, Xu Tao, Huang Yue
Department of Anesthesiology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Anesthesiology, the International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Transl Pediatr. 2021 Nov;10(11):2941-2951. doi: 10.21037/tp-21-247.
Oral administration of midazolam syrup is one of the most favorable methods of premedication, the optimal dose of midazolam and midazolam with S-ketamine for preschool children has not been determined. This prospective, double-blind, randomized, sequential dose-finding study was designed to estimate the 90% effective doses of oral midazolam with and without intranasal S-ketamine in a grade III child medical center.
Eighty successive children were recruited and randomly allocated to midazolam group and midazolam with S-ketamine group. The initial oral doses of midazolam were 0.25 mg/kg in both groups, and the dose of midazolam for the next child was based on the response of the preceding child as the biased coin up-and-down designed. The primary outcome was parental separation anxiety score = 1 throughout the period of transferring from premedication center to the operation room 30 min after premedication. Secondary outcomes were the preoperative and post-operative observations. Finally, the 90% effective dose and 95% confidence intervals were estimated by isotonic regression.
The 90% effective dose of oral midazolam or oral midazolam with intranasal S-ketamine was 0.461 mg/kg (95% confidence interval: 0.425-0.488) and 0.253 mg/kg (95% confidence interval: 0.242-0.278), respectively. Oral midazolam with intranasal S-ketamine was quicker onset (8.9±3.8 19.7±7.4 min, P<0.001), had less incidence of behavioral changes (7.5% 32.5%, P=0.010) and faster recovery (21.6±14.1 31.6±13.5 min, P=0.002) than solely oral midazolam.
A suggestion of oral midazolam 0.3 mg/kg with intranasal small dose of S-ketamine could be used as premedication for preschool children.
Chinese Clinical Trial Registry.
口服咪达唑仑糖浆是最常用的术前用药方法之一，但尚未确定学龄前儿童使用咪达唑仑及咪达唑仑与S-氯胺酮联合使用的最佳剂量。本前瞻性、双盲、随机、序贯剂量探索研究旨在评估在一家三级儿童医疗中心口服咪达唑仑单独使用及联合鼻内给予S-氯胺酮时的90%有效剂量。
连续招募80名儿童，随机分为咪达唑仑组和咪达唑仑联合S-氯胺酮组。两组咪达唑仑初始口服剂量均为0.25mg/kg，下一名儿童的咪达唑仑剂量根据前一名儿童的反应按照偏倚硬币上下法确定。主要结局为用药30分钟后从术前用药中心转运至手术室期间家长分离焦虑评分为1。次要结局为术前和术后观察结果。最后，通过等渗回归估计90%有效剂量和95%置信区间。
口服咪达唑仑或口服咪达唑仑联合鼻内给予S-氯胺酮的90%有效剂量分别为0.461mg/kg（95%置信区间：0.425-0.488）和0.253mg/kg（95%置信区间：0.242-0.278）。口服咪达唑仑联合鼻内给予S-氯胺酮起效更快（8.9±3.8对19.7±7.4分钟，P<0.001），行为改变发生率更低（7.5%对32.5%，P=0.010），恢复更快（21.6±14.1对31.6±13.5分钟，P=0.002）。
建议口服0.3mg/kg咪达唑仑联合鼻内给予小剂量S-氯胺酮可作为学龄前儿童的术前用药。
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