口服水合氯醛用于先天性心脏病患儿心脏彩超检查镇静的药效学

Pharmacodynamics of oral chloral hydrate sedation for echocardiography in pediatric patients with congenital heart disease

目的 评价口服水合氯醛用于先天性心脏病患儿心脏彩超检查镇静的药效学.方法 拟行日间心脏彩超检查的先天性心脏病患儿200例,5 ～ 620日龄,性别不限,ASA分级Ⅱ-Ⅳ级.第1例患儿口服水合氯醛的剂量为50 mg/kg,采用序贯法确定下一例患儿水合氯醛剂量,相邻剂量升高或降低的幅度为10％.基于剂量-效应关系模型进行药效学分析,确定患儿口服水合氯醛镇静的50％和95％有效剂量（E D50和ED95）及其95％可信区间（CI）.将协变量（年龄、性别、用药时段、禁食时间、用药前2h内有睡眠、早产和紫绀型先天性心脏病）纳入剂量-效应关系模型,评价各协变量对水合氯醛镇静药效学的影响.结果 口服水合氯醛用于先天性心脏病患儿心脏彩超检查镇静的ED50为42.2 mg/kg（95％ CI 40.2～44.2 mg/kg）;ED95为67.4 mg/kg（95％CI 53.7 ～ 81.1 mg/kg）.各协变量均不影响口服水合氯醛镇静的药效学（P＞0.05）.将禁食时间和早产纳入剂量-效应关系模型时,剂量-效应关系曲线斜率的95％CI包括0;将年龄分层后纳入剂量-效应关系模型时,难以拟合或数据严重偏离临床.结论 口服水合氯醛用于先天性心脏病患儿心脏彩超检查镇静的ED50和ED95分别为42.2mg/kg（95％CI 40.2～ 44.2 mg/kg）和67.4 mg/kg（95％ CI 53.7 ～ 81.1 mg/kg）;性别、用药时段、用药前有睡眠和紫绀型先天性心脏病不影响其药效学;年龄、禁食时间和早产对其影响仍需进一步确定.

Objective To evaluate the pharmacodynamics of oral chloral hydrate sedation for echocardiography in pediatric patients with congenital heart disease （CHD）.Methods Two hundred ASA physical status Ⅱ-Ⅳ pediatric patients with CHD, aged 5-620 days,scheduled for elective echocardiography,were enrolled in the study.The dose of oral chloral hydrate was set at 50 mg/kg in the first pediatric patient.The oral dosage was determined by up-and-down sequential experiment.Each time the oral dose increased/decreased by 10% in the next pediatric patient.The pharmacodynamics was analyzed based on the dose-response model to determine the 50% effective dose （ED50）,95% effective dose （ED95） and 95% confidence interval （95% CI） of chloral hydrate for sedation.The covariates （age,gender,time period of administration,fasting time,sleeping at 2 h before sedation,premature and cyanotic CHD） were introduced into the dose-response model,and the effect of each covariate on the pharmacodynamics of chloral hydrate sedation was evaluated.Results The ED50 of chloral hydrate for sedation during echocardiography was 42.2 mg/kg （95 % CI 40.2-44.2 mg/kg）, ED95 was 67.4 mg/kg （95% CI 53.7-81.1 mg/kg） in the pediatric patients with CHD.Each covariate provided no effect on the pharmacodynamics of chloral hydrate sedation （P 〉 0.05）.When fasting time and premature were introduced into the dose-response model,95% CI of the slope of dose-response curve included 0.When age which was stratified was introduced into the dose-response model,it was difficult to fit or the data seriously deviated from the clinical data.Conclusion The ED50 and ED95 of chloral hydrate for sedation during echocardiography were 42.2 mg/kg （95% CI 40.2-44.2 mg/kg） and 67.4 mg/kg （95%CI 53.7-81.1 mg/kg）,respectively,in the pediatric patients with CHD.Gender,time period of administration,sleeping before sedation and cyanotic CHD do not affect the pharmacodynamics of oral chloral hydrate sedation,while the effect of age,fasting time and premature needs further determination.