Comparison of the therapeutic effectiveness of a dantrolene sodium solution and a novel nanocrystalline suspension of dantrolene sodium in malignant hyperthermia normal and susceptible pigs - Introduction

A Special Author Introduction
European Journal of Anaesthesiology

ISSN: 0265-0215 • Frequency: 12/year • Subscribe Now

By Jan Karl Schütte

Malignant hyperthermia (MH) is an uncommon autosomal dominant inherited pharmacogenetic syndrome mostly related to mutations of the Ca2+ release channel of sarcoplasmic reticulum of skeletal muscle cells. Several anaesthetic drugs such as halogenated volatile anaesthetics but also succinylcholine may lead to a MH-crisis with potential lethal course including tachycardia, hypercapnia, hypoxaemia, muscle rigidity, metabolic acidosis and severe hyperthermia. Although the incidence of MH reactions is rare (1:50000) the prevalence of genetic mutations is assumed to be 1:3000 in humans. Up to date, more than 90 different mutations of the ryanodine receptor 1 (RyR1) are known and intensive research has been done to develop specific genetic tests to identify mutations with higher frequencies. Besides genetic screening, the diagnostic screening relies on the in-vitro contracture response of muscle biopsies to halothane and caffeine. To date, the only specific and FDA approved drug for treatment of malignant hyperthermia is the hydantoin derivative dantrolene. It was introduced in the year 1967 and led to a marked reduction of MH related mortality. Although anaesthesiologists have used dantrolene sodium solution successfully for years in the treatment of MH, the handling, preparation and administration of dantrolene is highly time consuming and a challenge for the whole anaesthetic team. Reconstitution and administration times can, therefore, cause a significant delay in addressing the MH episode while a faster dantrolene dissolving would lead to a reduction of time stress for the anaesthesia team. Actually, a new product form is a novel nanocrystalline suspension of dantrolene sodium called dantrolene sodium suspension. One mayor characteristic is a greater dissolubility in water, so that the dantrolene sodium suspension can be reconstituted and administered in only 5 ml water. Although, it is not yet approved by the FDA, we compared the therapeutic management and effectiveness of dantrolene sodium to that of dantrolene sodium suspension during fulminant MH crisis in MH susceptible swine and compared the reconstitution and administration times of dantrolene sodium suspension to commonly used dantrolene sodium. In conclusion we could show that preparation and administration of dantrolene sodium suspension was significantly faster than dantrolene sodium, which may offer a clinically significant advantage in the treatment of a fulminant MH crisis. Therefore, dantrolene sodium suspension seems to be a promising new agent in the treatment of MH.

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