Pharmacokinetics of Dantrolene in the CVVH/PE Treatment of Malignant Hyperthermia in a 14-year-old Chinese Boy: A Case Report and Literature Review
Xiaoxiao Li 1a, 2#, Chao Li 1b#, Yang Zhou 1c#, Xin Xiong 1a, Chuhui Wang 1a,2, Congya Zhou 1a,2, Bin Han1c, Li Yang 1a*, Xiangyang Guo1c*
1a Department of Pharmacy, b Department of Critical Care, c Department of Anesthesiology, Peking University Third Hospital, Beijing, China
2 Department of Pharmacy Administration and Clinical Pharmacy School of Pharmaceutical Sciences, Peking University, Beijing, China
# Xiaoxiao Li, Chao Li, and Yang Zhou contributed equally to this work
* Corresponding authors:
Li Yang M.Sc.,
Department of Pharmacy, Peking University Third Hospital
Add: 49 North Garden Rd., Haidian District Beijing 100191, P.R.China
Telephone: 86-10-82265743
Email: lilianyangli@163.com
Xiangyang Guo M.D.,
Department of Anesthesiology, Peking University Third Hospital
Add:49 North Garden Rd., Haidian District Beijing 100191, P.R.China
Telephone: 86-10-82267276
Email: puthmzk@hsc.pku.edu.cn
Abstract: Malignant hyperthermia (MH) is a rare life-threatening response that triggered by exposure to specific anesthetics commonly used during surgery interventions. Dantrolene is a well-known drug which used as first-line therapy for MH. A 14-year-old Chinese boy with a mutation in RYR1 whose muscle biopsy diagnosis was central core disease (CCD) occurred MH after cervical spine surgery underwent general anesthesia without volatile anesthetics or succinylcholine. The MH crisis treatment workflow was started and intravenous dantrolene was used soon which combined with sequent continuous veno-venous hemofiltration (CVVH) and plasma exchange (PE) therapy. We explored the pharmacokinetics of dantrolene during the treatment and the results showed that a one-compartment model with first-order absorption and elimination was sufficient to characterize dantrolene pharmacokinetics. The clearance estimate for dantrolene was 0.43 mL/(min*kg) and volume of distribution was 0.61 L/kg. The clearance of dantrolene was significantly affected by CVVH and PE.
Keywords: malignant hyperthermia (MH); dantrolene; pharmacokinetics; continuous veno-venous hemofiltration (CVVH); plasma exchange (PE)