Abstract

Background: Ten case reports have described clinical signs and symptoms of malignant hyperthermia (MH) that developed following local anaesthetics. In this study, the In-Vitro effects of dibucaine, an amide local anaesthetic, were compared in skeletal-muscle samples from MH-susceptible (MHS) and normal (MHN) swine. In addition, we investigated the In-Vivo MH trigger potency of dibucaine in MHS swine. Methods: Trigger-free general anaesthesia was induced in six MHS and six MHN swine. Muscle biopsies were obtained. In the In-Vivo experiment, cumulative doses of dibucaine (1, 2, 4, 8, 16, and 32 mg/kg) were administered i.v. In the In-Vitro contracture test (IVCT), dibucaine was added cumulatively to muscle specimens from eight MHS and eight MHN muscles (bath concentrations: 0.1, 0.2, 0.4, 0.6, and 1.0 mmol/l). Results: In the In-Vivo test, no signs or symptoms of MH were observed. In-Vitro contractures developed in all muscle specimens, but they developed significantly faster and were more intense in MHS than in MHN muscles. Conclusion: Dibucaine is not a MH trigger in swine. The IVCT with dibucaine demonstrated overlaps between the diagnostic groups, so that the possibility of 100 % accurate discrimination between MHS and MHN individuals by this means does not seem likely.

Highlights

  • Malignant hyperthermia (MH) is an uncommon inherited pharmacogenetic syndrome of skeletal-muscle cells in humans and various animal species

  • The basis is a genetic disorder of intracellular calcium homeostasis caused by a defect in the ryanodine receptor type 1 (RyR1)

  • Despite the fact that regional anaesthesia is generally considered to be safe in malignant hyperthermia (MH)-susceptible (MHS) patients, nine case reports describing clinical signs and symptoms of putative MH following spinal or epidural anaesthesia have been published [1,2,3,4,5,6,7,8,9]

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Summary

Introduction

Malignant hyperthermia (MH) is an uncommon inherited pharmacogenetic syndrome of skeletal-muscle cells in humans and various animal species. The basis is a genetic disorder of intracellular calcium homeostasis caused by a defect in the ryanodine receptor type 1 (RyR1). It is usually triggered by halogenated volatile anaesthetics and depolarizing muscle relaxants, leading to a hypermetabolic state. Despite the fact that regional anaesthesia is generally considered to be safe in MH-susceptible (MHS) patients, nine case reports describing clinical signs and symptoms of putative MH following spinal or epidural anaesthesia have been published [1,2,3,4,5,6,7,8,9]. Ten case reports have described clinical signs and symptoms of malignant hyperthermia (MH) that developed following local anaesthetics. We investigated the in-vivo MH trigger potency of dibucaine in MHS swine

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