Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tonsillectomy in adults and older children is typically accompanied by 7 to 14 days of pain. On the basis of clinical observations of patients treated perioperatively with dantrolene sodium for malignant hyperthermia, we hypothesized that pharyngeal muscle spasms are a major factor in tonsillectomy pain. We entered 113 patients, 11 years of age and older, into a double-blind, placebo-controlled study to evaluate the effectiveness of dantrolene sodium in reduction of tonsillectomy pain. Patients were randomly assigned either dantrolene (1.5 mg/kg per day) or placebo orally four times a day for 5 days postoperatively. On a standardized questionnaire, the patient recorded pain, diet, activity level, analgesics, and side effects, daily for 2 weeks. Also, alkaline phosphatase (alk phos) and serum aspartate aminotransferase (SGOT) levels were determined before the operation and 2 weeks after. Patients who received dantrolene had no significant differences in subjective pain, diet, or activity level scores from those of patients who received placebo. Dantrolene patients did, however, require significantly less analgesic use than placebo patients (p = 0.034, 0.015, and 0.005 for postoperative days 2, 3, and 4, respectively). There was no significant difference in side effects or changes in liver enzyme between the dantrolene and placebo groups. We conclude that dantrolene sodium, given in the dosage noted, is effective in reduction of analgesic requirements after tonsillectomy.
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PMID:Oral dantrolene sodium for tonsillectomy pain: a double-blind study. 312 47

Pigs, crossbreeds of Swedish Landrace and Yorkshire, females and castrated males about 6 months old, were exposed to experimental stress. The pigs were either considered normal or shown to be susceptible to develop malignant hyperthermia when tested with halothane at about 6 weeks of age (stress-susceptible pigs). The stress was of the restraint type, produced by two different myorelaxant agents, the depolarizing succinylcholine or the non-depolarizing pancuronium. The blood levels of the catecholamines (CA) noradrenaline (NA) and adrenaline (A) were measured during the stress. The severity of myocardial cell necrosis observed 1 to 2 days after the stress was morphologically graded. In normal pigs the levels of NA during the stress and the degree of myocardial cell necrosis were about the same after both succinylcholine and pancuronium. In stress-susceptible pigs, however, succinylcholine produced very high NA and A levels and severe heart lesions, whereas after pancuronium the NA and A levels were rather low and the heart lesions significantly reduced when compared to those after succinylcholine-induced stress. After pretreatment with dantrolene intravenously the succinylcholine-induced stress only induced slightly increased blood CA levels and no signs of myocardial cell necrosis in pigs susceptible to develop malignant hyperthermia. Dantrolene, an efficient drug in treatment of malignant hyperthermia, probably acts by interfering with release of calcium from the sarcoplasmic reticulum in skeletal muscles. The results indicate that peripheral sympathetic neurones in MHS pigs also react abnormally, probably due to defective calcium turn-over.
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PMID:Disordered catecholamine release in pigs susceptible to malignant hyperthermia. 319 47

Sixty-two suspected crises of anaesthetic malignant hyperthermia (MH) were collected between 1969 and 1988 by a retrospective inquiry which lasted four years. 33 patients (53%) died whilst 29 survived. 20 cases were confirmed to be MH, either directly or indirectly by way of muscle biopsy and halothane and caffeine contracture tests carried out according to the European MH group protocol by two laboratories. This group included 11 of the deaths, one family member of whom, at least, is sensitive (MHS), 7 MHS survivors and 2 survivors too young to undergo muscle biopsy but belonging to MHS families. 21 cases were highly suspect of MH: 15 of the deaths which occurred in a typical way, and 6 patients of three different families who have suffered from anaesthetic deaths which, clinically, suggested MH. Another 15 were possible MH cases, all survivors, including one case of Steinert's disease and a brother of a case of central core disease. 2 cases were still being debated, because they had equivocal results for the caffeine test (MHEc); the last 4 had negative muscle biopsies and were excluded. 33 close relatives of the MH patients were diagnosed as MHS. 44 others were found to be free from the genetic predisposition. It was strongly recommended to yet 11 others that they carry the MHS card because they were MHEc. The clinical, surgical and anesthetic pictures were always as described in the literature. The anaesthetic protocols included inhalational agents in 90% of cases; these were combined with suxamethonium in 55% of cases. Dantrolene was only used in 32% of cases, and then at inadequate doses and very often too late; this probably explains the large number of treatment failures. The number of severe forms of MH was also very high in this series (70%). The need to increase the means of prevention and screening for MH in France is stressed.
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PMID:[Registration of peranesthetic cases of malignant hyperthermia in France. An update]. 322 47

The use of dantrolene to reverse severe unexplained postanaesthetic muscle rigidity in a previously "healthy" 13-year-old male is described. Anaesthesia was induced with thiopentone. After intubation with pancuronium, the patient had an entirely uneventful nitrous oxide, oxygen and halothane anaesthetic. Immediately following reversal of the relaxant, the patient developed generalized muscle tightness and rigidity involving the trunk and extremities. This was prolonged and severe enough to interfere with adequate ventilation. The patient also had a prolonged recovery from the anaesthetic. After ruling out malignant hyperthermia and some other causes of rigidity, a tentative diagnosis of myotonia was made. The symptoms responded to IV dantrolene in a total dose of 2.0 mg.kg-1. Further testing failed to establish a definite diagnosis. Dantrolene could be a useful drug in treating such unexplained muscle rigidity.
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PMID:Reversal of prolonged postoperative muscle rigidity by dantrolene: a case report. 340 20

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle triggered when susceptible subjects are exposed to volatile anesthetic agents and/or depolarizing muscle relaxants. We have used Ca2+ selective microelectrodes to measure in vivo the intracellular free [Ca2+] in skeletal muscle of MH susceptible swine before and after the administration of dantrolene. We have investigated the effectiveness of this muscle relaxant in preventing clinical MH and the relationship between the resting intracellular free [Ca2+] and the probability of inducing the MH syndrome. The resting intracellular free [Ca2+] was 0.41 +/- 0.01 microM (M +/- SEM), which agrees with our previous measurements in susceptible swine. The administration of 0.5, 1, 2, 2.5 and 3 mg/Kg Dantrolene, reduced the intracellular free [Ca2+] to 0.31, 0.21, 0.09, 0.08, 0.08 microM respectively. The 0.5 mg/Kg dose induced a moderate decrease of [Ca2+]i and failed to prevent the MH syndrome after exposure to halothane (2%). The 1 mg/Kg dose produced a further reduction in [Ca2+]i and was sufficient to prevent the clinical syndrome in 2 out of 3 animals. The 2.5 mg/Kg dose was uniformly protective in all animals. These results suggest that the mechanism by which dantrolene protects susceptible animals exposed to triggering agents is by reducing the intracellular free [Ca2+] in skeletal muscle.
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PMID:Dantrolene prevents the malignant hyperthermic syndrome by reducing free intracellular calcium concentration in skeletal muscle of susceptible swine. 342 16

The electrophysiological effects of an intravenous dantrolene infusion (10 mg kg-1) were evaluated in healthy, anaesthetized dogs by intracardiac electrophysiological study. Dantrolene administration resulted in a significant prolongation of the refractory periods of the right atrium and ventricle, while the functional refractory period of the AV node was not altered. A slight increase of AV nodal conduction, measured as atrial-His bundle interval, without any change in infranodal conduction, measured as His bundle-ventricular interval, was observed during sinus rhythm. Dantrolene had no significant effects on surface ECG parameters. We conclude that intravenously administered dantrolene, at the maximal recommended doses, has primary effects on electrophysiological parameters. These findings support the hypothesis that the beneficial effects of dantrolene on cardiac arrhythmias associated with malignant hyperthermia may be related to its intrinsic activity on the electrophysiological properties of the heart, but confirmation requires further investigations on induced arrhythmias in experimental models.
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PMID:Electrophysiological effects of intravenous dantrolene on canine heart. 342 81

Dantrolene sodium acts primarily by affecting calcium flux across the sarcoplasmic reticulum of skeletal muscle. Recently, dantrolene has been used very successfully in the treatment of several rare hypercatabolic syndromes which have previously been associated with high mortality rates. In malignant hyperthermia, where early diagnosis and treatment usually with intravenous dantrolene in association with other supportive measures (and often subsequent dantrolene therapy) is performed, recovery is seen in virtually 100% of patients. There is a rapid resolution of hyperthermia, dysrhythmias, muscle rigidity, tachycardia, hypercapnia, mottled or cyanotic skin, and metabolic acidosis, and a slower normalisation of myoglobinuria and elevated serum creatine phosphokinase levels. In patients with family history or previous episodes of malignant hyperthermia, prophylactic treatment with dantrolene prior to anaesthesia prevents the syndrome occurring in most cases. Where malignant hyperthermia has developed patients have been successfully treated with further dantrolene therapy. Dantrolene has also been used successfully in the treatment of a few cases of heat stroke and the neuroleptic malignant syndrome--both of which have many similarities to malignant hyperthermia. Dantrolene is well established in the treatment of patients with muscle spasticity where it generally improves at least some of the components of spasticity (i.e. hyper/hypotonia, clonus, muscle cramps and spasms, resistance to stretch and flexor reflexes, articular movement, neurological and motor functions and urinary control). However, in some patients, particularly those with multiple sclerosis, dantrolene may not be effective, and in many cases muscular strength may diminish. Long term dantrolene therapy has been associated with hepatic toxicity and may cause problems in patients treated for disorders of muscle spasticity. Thus, dantrolene offers a unique advance in the therapy available for the treatment of hypercatabolic disorders and is also useful in the treatment of muscle spasticity of various aetiology.
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PMID:Dantrolene. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in malignant hyperthermia, the neuroleptic malignant syndrome and an update of its use in muscle spasticity. 352 59

Dantrolene is an effective antagonist of anesthesia-induced malignant hyperthermia due to a poorly understood action on skeletal muscle. The present study examines whether the red blood cell can be used as a model to investigate the mechanism of dantrolene action. Halothane (4.7 mM) caused 9% hemolysis of red blood cells. Phospholipase A2 (1 microM) alone caused less than 2% hemolysis, despite high levels (54%) of phosphatidylcholine hydrolysis. Incubation of red blood cells with halothane and phospholipase A2 caused 72% hemolysis. Halothane addition caused 100% hydrolysis of all diacylphosphoglycerides by phospholipase A2, suggesting a mutual potentiation. The major products of phospholipase A2 activity, arachidonic acid and lysophosphatidylcholine, when exogenously added, also greatly increased hemolysis induced by halothane, with arachidonic acid most closely resembling the synergism observed with phospholipase A2. Dantrolene (10 microM) and mepacrine (10 microM) significantly antagonized hemolysis induced by halothane and phospholipase A2 or halothane and exogenously added arachidonic acid and lysophosphatidylcholine. Dantrolene and mepacrine did not antagonize phospholipid hydrolysis or free fatty acid levels. Dantrolene and mepacrine antagonized the synergism between halothane and phospholipase A2 most likely by reducing the lytic action of halothane in the presence of arachidonic acid. The red blood cell is a useful model for studying the antagonism of halothane and phospholipase A2 toxicity by dantrolene and mepacrine.
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PMID:Dantrolene and mepacrine antagonize the hemolysis of human red blood cells by halothane and bee venom phospholipase A2. 366 Apr 10

Effects of dantrolene sodium on catecholamine (CA) release from the perfused dog adrenal medulla was investigated in relation to it's therapeutic action on malignant hyperthermia (MH), in which CAs would play a significant pathophysiological role. Acetylcholine (ACh)-induced CA release was not affected, whereas caffeine-induced CA release was inhibited by dantrolene in a dose-dependent manner (84% inhibition at 10 microM). Dantrolene had no effect on the CA release induced by lasalocid or Na+ deprivation. On the other hand halothane inhibited ACh-induced CA release markedly, Na+ deprivation-induced CA release slightly, but not caffeine-induced CA release at all. The results indicate that dantrolene selectively inhibit caffeine-induced CA release, and that the therapeutic action of dantrolene on MH would be, at least in part, due to inhibition of abnormal release of Ca2+ in the adrenal medullary cells.
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PMID:Selective inhibition by dantrolene of caffeine-induced catecholamine release from perfused dog adrenals. 367 80

Dantrolene sodium, a skeletal-muscle relaxant known to be effective for treatment of malignant hyperthermia, was evaluated for efficacy in treatment of heatstroke. Non-exertional heatstroke was induced in 11 dogs by external heating following barbiturate anesthesia. When core temperature reached 43 degrees C (109.4 degrees F) heating was discontinued and control animals (n = 6) were allowed to cool passively in room air. Treatment animals (n = 5) received 5 mg/kg dantrolene sodium intravenously at the start of room-air cooling. Serial temperatures (pulmonary arterial, rectal, cerebral, and subcutaneous), blood chemistry tests (including electrolytes, liver enzymes, and complete blood count), and hemodynamic parameters (including cardiac output, arterial pressure, and urinary output) were followed for 12 hours after induction of heatstroke. Autopsies, including gross and microscopic examination, were performed on all animals. Dantrolene administration did not significantly affect cooling rates, hemodynamic parameters, pathological changes, or clinical outcome. Statistically significant changes in urinary output and serum creatinine observed in the first hours after dantrolene administration can be attributed to the mannitol vehicle in which the drug was delivered. There were no statistically significant differences in these values at 12 hours. Dantrolene sodium does not appear to enhance passive cooling in treatment of non-exertional canine heatstroke.
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PMID:Dantrolene sodium for treatment of heatstroke victims: lack of efficacy in a canine model. 374 58


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