Myotoxicity of local anesthetics is equivalent in individuals with and without predisposition to malignant hyperthermia

Abstract

Purpose

Malignant hyperthermia (MH) is an inherited muscle disorder caused by abnormal elevations of intracellular calcium (Ca²⁺) in skeletal muscle. There are several reports of myotoxicity caused by local anesthetics, and the increased intracellular Ca²⁺ 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.

Methods

Human skeletal muscle samples were obtained from 22 individuals to determine susceptibility to MH, and were evaluated according to whether their Ca²⁺-induced Ca²⁺ 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 (EC₅₀) 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.

Results

In the accelerated and unaccelerated groups, respectively, the mean ± SD of the EC₅₀ 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.

Conclusion

The myotoxicity of local anesthetics was equivalent in individuals with and without predisposition to MH.

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