PubMed · 10490170
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J Heggie. 1999. Malignant hyperthermia.. https://doi.org/10.1007/bf03012993
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STUDY DESIGN: Single-subject case (a quadriplegic female, 56 years). OBJECTIVES: To describe a new case of eosinophilic pleural effusion induced by dantrolene chronic administration. SETTING: Physical medicine and rehabilitation unit in a teaching hospital, France. METHODS: Diagnosis of an eosinophilic pleural effusion induced by dantrolene without any respiratory symptoms, except a decrease of breath sounds on the right lung base. RESULTS: Chest radiograph revealed a right-sided pleural effusion, and blood cell count a significant peripheral eosinophilia. Thoracenthesis contained 85% of eosinophils. The other explorations eliminated other causes of pleural effusion. The diagnosis of drug-induced effusion was almost sure and led us to discontinue the dantrolene. After 3 months, she had completely recovered. These characteristics, similar to the eight other cases described in the literature, are essential for the diagnosis of pleural effusion induced by dantrolene. CONCLUSION: Dantrolene, a long-acting skeletal muscle relaxant, is well known to induce liver side effects but it can also induce pleural pericarditis. The pathogenesis is still not clearly identified, but similarities of chemical structures of dantrolene and nitrofurantoine make us think that it could be the same mechanism. The association between dantrolene and nitrofurantoine may have contributed to the expression of the pleural effusion.
Human malignant hyperthermia is a life-threatening genetic sensitivity of skeletal muscles to volatile anaesthetics and depolarizing neuromuscular blocking drugs occurring during or after anaesthesia. The skeletal muscle relaxant dantrolene is the only currently available drug for specific and effective therapy of this syndrome in man. After its introduction, the mortality of malignant hyperthermia decreased from 80% in the 1960s to < 10% today. It was soon discovered that dantrolene depresses the intrinsic mechanisms of excitation-contraction coupling in skeletal muscle. However, its precise mechanism of action and its molecular targets are still incompletely known. Recent studies have identified the ryanodine receptor as a dantrolene-binding site. A direct or indirect inhibition of the ryanodine receptor, the major calcium release channel of the skeletal muscle sarcoplasmic reticulum, is thought to be fundamental in the molecular action of dantrolene in decreasing intracellular calcium concentration. Dantrolene is not only used for the treatment of malignant hyperthermia, but also in the management of neuroleptic malignant syndrome, spasticity and Ecstasy intoxication. The main disadvantage of dantrolene is its poor water solubility, and hence difficulties are experienced in rapidly preparing intravenous solutions in emergency situations. Due to economic considerations, no other similar drugs have been introduced into routine clinical practice.
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