Department of Anesthesiology and Critical Care, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Department of Anesthesiology and Critical Care, Graduate School of Biomedical Sciences, Hirohima University, Hiroshima, Japan.
J Anesth. 2018 Aug;32(4):616-623. doi: 10.1007/s00540-018-2526-4. Epub 2018 Jun 25.
Malignant hyperthermia (MH) is an inherited muscle disorder caused by abnormal elevations of intracellular calcium (Ca) in skeletal muscle. There are several reports of myotoxicity caused by local anesthetics, and the increased intracellular Ca is considered to be an important cause. However, there is insufficient evidence regarding myotoxicity in MH-susceptible individuals when large doses of local anesthetics are administered. This study investigated the effect of MH predisposition on myotoxicity.
Human skeletal muscle samples were obtained from 22 individuals to determine susceptibility to MH, and were evaluated according to whether their Ca-induced Ca release (CICR) rates were accelerated or not. This study was performed using surplus muscle that remained after the CICR rate test. We calculated the 50% effective concentration (EC) values of three local anesthetics, namely lidocaine, levobupivacaine, and ropivacaine using the ratiometric dye Fura-2 AM. Significance was tested using the unpaired t test.
In the accelerated and unaccelerated groups, respectively, the mean ± SD of the EC values were 1.52 ± 0.72 and 1.75 ± 0.37 mM for lidocaine (p = 0.42), 0.72 ± 0.36 and 0.79 ± 0.46 mM for levobupivacaine (p = 0.68), and 1.21 ± 0.35 and 1.62 ± 0.57 mM for ropivacaine (p = 0.06). These values were similar in individuals with and without MH predisposition.
The myotoxicity of local anesthetics was equivalent in individuals with and without predisposition to MH.
恶性高热（MH）是一种由骨骼肌细胞内钙离子（Ca）异常升高引起的遗传性肌肉疾病。有几例报道称局麻药可引起肌毒性，而细胞内 Ca 的增加被认为是一个重要原因。然而，当给予大剂量局麻药时，MH 易感个体的肌毒性证据不足。本研究旨在探讨 MH 易感性对肌毒性的影响。
从 22 名个体中获得骨骼肌样本，以确定对 MH 的易感性，并根据其 Ca 诱导的 Ca 释放（CICR）率是否加速来评估。这项研究是在 CICR 率测试后剩余的肌肉上进行的。我们使用比率染料 Fura-2 AM 计算了三种局麻药（利多卡因、左布比卡因和罗哌卡因）的 50%有效浓度（EC）值。使用未配对 t 检验进行显著性检验。
在加速和未加速组中，EC 值的平均值±标准差分别为利多卡因 1.52±0.72 和 1.75±0.37mM（p=0.42），左布比卡因 0.72±0.36 和 0.79±0.46mM（p=0.68），罗哌卡因 1.21±0.35 和 1.62±0.57mM（p=0.06）。MH 易感个体和非易感个体的这些值相似。
局麻药的肌毒性在 MH 易感个体和非易感个体中相似。
