JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE) ›› 2021, Vol. 41 ›› Issue (10): 1313-1317.doi: 10.3969/j.issn.1674-8115.2021.10.007

• Clinical research • Previous Articles     Next Articles

Half effective bolus dose of dexmedetomidine of children derived from the up-and-down experimental data based on the analysis of nonlinear mixed effects model with allometric equation

Wen-yin XU1(), Zhen-ling HUANG2, Yong-lei HUANG2(), Rui-dong ZHANG1, Lu WANG1, Ying ZHANG1, Jie BAI1, Ji-jian ZHENG1   

  1. 1.Department of Anesthesiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
    2.Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China
  • Online:2021-10-28 Published:2021-09-22
  • Contact: Yong-lei HUANG;
  • Supported by:
    Shanghai Science and Technology Commission Medical Guidance;Science and Technology Support Project(17411965500)

Abstract: Objective

·To explore the application of nonlinear mixed effects model based on the allometric equation on up-and-down data to determine the half effective dose (ED50) in pediatric patients.


·Twenty-two pediatric patients aged 2 to 12 years with obstructive sleep apnea (OSA) who were undergoing drug-induced sleep endoscopy (DISE) were enrolled. All patients received intravenous bolus S+-ketamine 0.5 mg/kg. At the same time, a predetermined bolus dose of dexmedetomidine was infused continuously over 10 min for anesthesia induction. The bolus dose of dexmedetomidine was calculated according to the Dixon up-and-down method with initial dose 1.0 μg/kg and step size 1.2 times. DISE was conducted 10 min after dexmedetomidine infusion, and the response of the patients to the procedure was recorded. Dixon-Massey formula and nonlinear mixed effects model fitting are used to calculate ED50.


·There were 9 and 13 children with successful and failed sedation. The value of dexmedetomidine ED50, 1.9 μg/kg, calculated by Dixon-Massey formula was similar to the fitting value, 2.0 μg/kg, of nonlinear mixed effects model. The introduction of allometric equation significantly improved the model (P<0.05). After normalizing adults' body weight to 70 kg, the ED50 and ED95 were 5.76×(body weight/70) μg/kg and 11.5×(body weight/70) μg/kg, and the slope (γ) of the dose-response relationship of dexmedetomidine is 4.25.


·The experimental data from the up-and-down method can be fitted with a nonlinear mixed effects model based on the allometric equation. Compared with the Massey formula, the advantage is that the ED50, ED95 and γ can be determined at the same time, and this method helps to determine the possible effect of covariates.

Key words: children, dexmedetomidine, nonlinear mixed effects, allometric, up-and-down method

CLC Number: