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

Abstract

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. Key words: Chloral hydrate; Heart defects, congenital; Conscious sedation; Echocardiography,Doppler, color; Dose-response relationship, drug; Child