Clinical research

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 XU ,
  • Zhen-ling HUANG ,
  • Yong-lei HUANG ,
  • Rui-dong ZHANG ,
  • Lu WANG ,
  • Ying ZHANG ,
  • Jie BAI ,
  • Ji-jian ZHENG
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  • 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
HUANG Yong-lei, E-mail: 8771@renji.com.

Online published: 2021-09-22

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.

Methods

·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.

Results

·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.

Conclusion

·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.

Cite this article

Wen-yin XU , Zhen-ling HUANG , Yong-lei HUANG , Rui-dong ZHANG , Lu WANG , Ying ZHANG , Jie BAI , Ji-jian ZHENG . 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[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2021 , 41(10) : 1313 -1317 . DOI: 10.3969/j.issn.1674-8115.2021.10.007

References

1 Peltoniemi MA, Hagelberg NM, Olkkola KT, et al. Ketamine: a review of clinical pharmacokinetics and pharmacodynamics in anesthesia and pain therapy[J]. Clin Pharmacokinet, 2016, 55(9): 1059-1077.
2 张剑蔚,宋蕴安,张瑞冬,等.右美托咪定复合氯胺酮用于阻塞型睡眠呼吸暂停综合征患儿行药物诱导睡眠气道镜检查的可行性研究[J].国际麻醉学与复苏杂志,2021,42(02):151-154.
3 Kearns GL, Abdel-Rahman SM, Alander SW, et al. Developmental pharmacology--drug disposition, action, and therapy in infants and children[J]. N Engl J Med, 2003, 349(12): 1157-1167.
4 Allen SM, Madrio ME. Ramsay sedation scale project: small, easy changes for a big effect on patient safety[J]. Crit Care Nurse, 2019, 39(4): 64-66.
5 Bush B, Tobias JD, Lin C, et al. Postoperative bradycardia following adenotonsillectomy in children: does intraoperative administration of dexmedetomidine play a role?[J]. Int J Pediatr Otorhinolaryngol, 2018, 104: 210-215.
6 Dixon WJ. The up-and-down method for small samples[J]. J Am Stat Assoc, 1965, 60(312): 967-978.
7 Beal SL, Sheiner LB. NONMEM user's guide[M]. San Francisco: NONMEM Project Group, University of California, 1992.
8 Ehsan Z, Mahmoud M, Shott SR, et al. The effects of anesthesia and opioids on the upper airway: a systematic review[J]. Laryngoscope, 2016, 126(1): 270-284.
9 Mahmoud M, Mason KP. Dexmedetomidine: review, update, and future considerations of paediatric perioperative and periprocedural applications and limitations[J]. Br J Anaesth, 2015, 115(2): 171-182.
10 Koinig H, Marhofer P. S+-ketamine in paediatric anaesthesia[J]. Paediatr Anaesth, 2003, 13(3): 185-187.
11 Pérez-Guillé MG, Toledo-López A, Rivera-Espinosa L, et al. Population pharmacokinetics and pharmacodynamics of dexmedetomidine in children undergoing ambulatory surgery[J]. Anesth Analg, 2018, 127(3): 716-723.
12 Kazama T, Ikeda K, Morita K, et al. Comparison of the effect-site keOs of propofol for blood pressure and EEG bispectral index in elderly and younger patients[J]. Anesthesiology, 1999, 90(6): 1517-1527.
13 陈怡绮,张马忠,王璐,等.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[J].中华麻醉学杂志,2014,34(2):199-202.
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