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)