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)

Two patients who developed the neuroleptic malignant syndrome (NMS) are described, and pertinent literature is reviewed. A 30-year-old man developed NMS, apparently as a result of haloperidol treatment of chronic undifferentiated schizophrenia. Treatment with cooling blankets, acetaminophen, dantrolene sodium, and bromocriptine mesylate decreased abnormal vital signs, but catatonia continued. After 30 treatments with electroconvulsive therapy over a one-month period, the patient's catatonia was resolved, and he was discharged on no medication with the schizophrenia in remission. The second patient was a 22-year-old woman who developed NMS after five weeks of therapy with haloperidol and thiothixene for an acute episode of abnormal behavior. She did not respond to therapy with cooling blankets, acetaminophen, antibiotics, and amobarbital sodium. Dantrolene sodium therapy produced no improvement except for some relief of muscular rigidity. Electroconvulsive therapy (22 treatments over one month) successfully decreased the patient's elevated liver enzymes and leukocyte count, but periodic temperature elevations and catatonia continued. Prompt diagnosis and treatment of NMS are essential, as the mortality rate is 20%. Acute lethal catatonia and malignant hyperthermia are considered in differential diagnosis. Both central and peripheral pathophysiologic mechanisms are probably involved in NMS, and most cases are seen in patients with psychiatric illness. Onset of NMS does not seem related to duration of neuroleptic therapy and, in susceptible persons, additional factors may be required to trigger onset of NMS. Symptoms, including diffuse muscular rigidity, akinesia, and fever, develop within 24-72 hours. Neurologic symptoms may develop or worsen, and leukocytosis and elevated levels of liver enzymes occur. Death can result from respiratory or cardiovascular failure, and rhabdomyolysis can lead to acute renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection and management of the neuroleptic malignant syndrome. 614 37

Dantrolene sodium, a hydantoin analogue, is efficacious in the therapy of malignant hyperthermia (MH). In order to improve our knowledge of the mode of action of dantrolene, we have examined the influence of dantrolene sodium on: (1) twitch and resting tensions, in the absence and the presence of caffeine, of intact skeletal muscle fascicles; and (2) caffeine induced tension rises of single chemically skinned skeletal muscle fascicles. We have found that dantrolene appears to exert its beneficial action on malignant hyperthermia susceptible (MHS) skeletal muscle by an indirect action on the sarcoplasmic reticulum (SR). Thus dantrolene inhibits twitch tensions of skeletal muscle fascicles, probably by indirectly preventing the release of calcium from the SR. To a lesser extent dantrolene inhibits caffeine induced contractures of skeletal muscle fascicles, probably by indirectly accelerating the uptake of calcium into the SR. Because the former effect is greater than the latter in vivo dantrolene sodium is effective only when given prior to total loss of calcium from the SR. Vigilant temperature and EKG monitoring of all patients during anaesthesia is, therefore, essential.
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PMID:Dantrolene--in vitro studies in malignant hyperthermia susceptible (MHS) and normal skeletal muscle. 670 79

A 13 year old girl who had suffered from an abortive form of malignant hyperthermia during tonsillectomy eight years before was scheduled for orthopaedic surgery. Dantrolene sodium, 3 mg/kg orally, was given prophylactically the day before surgery; preanaesthetic medication consisted of Thalamonal, a fixed combination of droperidol and fentanyl; anaesthesia was induced with methohexitone and maintained as neurolept anaesthesia with fentanyl and droperidol; tubocurarine was administered for tracheal intubation and intraoperative neuromuscular blockade. Using this anaesthetic regimen no adverse reaction was triggered.
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PMID:[Anaesthesia in a patient susceptible to malignant hyperthermia (author's transl)]. 710 32

Malignant hyperpyrexia (MH) is a syndrome with a mortality of 60%, triggered by a broad variety of anesthetic agents. The most significant recent advance influencing the clinician's ability to safely manage MH individuals is the emergence of dantrolene sodium as both a prophylactic and a therapeutic agent. The purpose of this presentation is to review recent clinical and laboratory studies and advances which are the basis for establishing the pathophysiology of this syndrome and pharmacology of treatment. The FDA has recently approve intravenous Dantrium for treatment of malignant hyperpyrexia. Intravenous and oral Dantrium has much theoretical support and experimental evidence which suggests it will significantly reduce the mortality previously associated with this syndrome.
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PMID:Malignant hyperpyrexia: an update for the otolaryngologist. 724 87

The pharmacogenetic syndrome of malignant hyperthermia (MH) in response to general anaesthesia, though rare, is usually fatal when it does occur. A case of anaesthetic-induced MH arising in a 10-year-old girl during intranasal antrostomy and successfully treated with dantrolene sodium (Dantrium; SKF) is described. A treatment protocol for MH is appended. The importance of an awareness on the part of the clinician together with prompt reaction to early tell-tale signs is stressed.
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PMID:Dantrolene sodium in the treatment of malignant hyperthermia. A case report. 730 73

Administration of succinylcholine (SCh) to chicks produces rigid paralysis and death due to respiratory impairment. The mechanism of the SCh effect is probably related to the multiple innervation of muscle fibres, leading to excessive intracellular accumulation of calcium. This situation may be similar to that in malignant hyperpyrexia (MH) occurring in mammals. Dantrolene sodium, phenytoin and procain, drugs used against MH, were found to afford protection against SCh rigidity and death in chicks. It is suggested that the chick can be used as a convenient model for rapid screening of drugs potentially active against NH.
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PMID:The chick as a model for malignant hyperpyrexia. 735 89

Dantrolene effectively treats malignant hyperthermia (MH) hut the current form, Dantrium, must be dissolved to a 0.33 mg/mL, pH 9.5 solution. This study describes lecithin-coated microcrystal formulations of sodium dantrolene (MC-NaD) and neutral dantrolene (MC-D) which reconstitute to 200 mg/mL within 1 min. In rats, the pharmacokinetics and pharmacodynamics of MC-NaD and Dantrium were similar: half-lives of 3.1 h, volume distributions of 0.54 and 0.59 L/kg, and 95% effective dose (ED95) values for depression of skeletal muscle twitch height (ED95T) of 2.6 +/- 0.7 and 2.8 +/- 0.5 mg/kg. In swine, the ED95T values for MC-NaD and Dantrium were also similar (2.8 +/- 0.4 vs 2.7 +/- 0.6 mg/kg), but MC-D and Dantrium were only similar at doses more than 2.5 mg/kg (ED95T: 3.5 +/- 0.4 vs 2.7 +/- 0.5 mg/kg). In susceptible swine, MC-NaD successfully treated five of six MH episodes and prevented MH in three of four swine. However, MC-NaD caused marked pulmonary hypertension in swine, while MC-D caused only a mild response that was eliminated by filtration. Likewise, MC-D caused no pulmonary response in dogs. These observations suggest that MC-D has potential to improve the treatment of MH.
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PMID:Intravenous lecithin-coated microcrystals of dantrolene are effective in the treatment of malignant hyperthermia: an investigation in rats, dogs, and swine. 861

Binge drinking of alcohol, cocaine overdose, or overexertion can lead to rhabdomyolysis characterized by elevated creatine kinase (CK) and myoglobin in the serum, myoglobinuria, and muscle tenderness. Our previous studies showed that ethanol, cocaine, and electrical stimulation enhanced the leakage of CK from isolated soleus and extensor digitorum longus (EDL) muscles of rat. Dantrolene sodium was reported to reduce the muscle damage and elevated serum CK levels in exercised rats. The present study was aimed at testing whether dantrolene can reduce the enhanced leakage of CK from isolated rat soleus and EDL muscles caused by ethanol, cocaine, and electrical stimulation. After 4-hr incubation in oxygenated physiological solution at 37 degrees C, the mean leakage of CK was 1.56 units/mg of muscle in soleus and 0.89 units/mg in EDL. Ethanol at 0.2% increased the leakage of CK by 47% (p < 0.05) in soleus and by 26% in EDL. Cocaine at 1 mM increased the leakage of CK by 55% (p < 0.05) in soleus and by 27% in EDL. Electrical stimulation at 1 Hz for 4 hr increased the mean leakage of CK by 100% (p < 0.05) in soleus and 127% (p < 0.05) in EDL. Dantrolene sodium reduced the enhanced leakage of CK caused by ethanol, cocaine, and electrical stimulation significantly in soleus and slightly in EDL. Dantrolene may involve myoplasmic free Ca2+ in these beneficial effects as in malignant hyperthermia, and may be useful in the treatment of rhabdomyolysis associated with acute alcoholic myopathy, cocaine overdose, and overexertion.
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PMID:Dantrolene sodium reduces the enhanced leakage of creatine kinase caused by ethanol, cocaine, and electrical stimulation in isolated fast and slow muscles of rat. 904 74

This report describes a 13-month-old-girl with Duchenne's muscular dystrophy (DMD) who had radical repair for tetralogy of Fallot safely. Patients with DMD are considered to be at risk of malignant hyperthermia (MH). Drugs for induction and maintenance were chosen from a list of agents rarely associated with MH. To wash out the inhalation anesthetics from the equipment, oxygen was circulated continuously for 24 hours. Dantrolene sodium was kept readily available in case of MH occurrence. Differential diagnosis during surgery is difficult in term of the episodes of MH and complications of cardiac surgery, as cardiac surgery is also associated with tachycardia, tachyarrhythmias, metabolic asidosis and red colored urine, which are frequently accompanied by MH. Although increased levels of CK, GOT, LDH and myoglobin strongly support the diagnosis of MH, such evidence can only be confirmed after operation. Fortunately, these factors recovered to the normal range without treatment by dantrolene sodium. During the cardiac surgery, treatment of MH may be delayed due to its late confirmation.
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PMID:[Anesthetic management of a patient with Duchenne's muscular dystrophy undergoing radical repair for tetralogy of Fallot]. 945 83

The administration of intravenous dantrolene in a parturient susceptible to malignant hyperthermia has been associated with post partum uterine atony. We examined the effect of dantrolene sodium for injection (Dantrium Intravenous) on spontaneous contractility of uterine smooth muscle from women in term pregnancy in an isolated preparation. Dantrolene sodium for injection at 5 microg/ml and 10 microg/ml had no effect on the spontaneous contractility of the uterine muscle preparations. At a cumulative concentration of 20 microg/ml, a mild depression (16 +/- 14%) in the frequency of spontaneous contractions was noted. However, a similar depression in the muscle preparations treated with mannitol suggests that the depression observed with the dantrolene was likely due to the mannitol that was included in the dantrolene formulation rather than to dantrolene sodium itself. We conclude that dantrolene sodium has no effect on the spontaneous contractility of uterine smooth muscle. The depression of uterine muscle activity observed with dantrolene for injection appears attributable to the mannitol.
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PMID:Effect of dantrolene sodium on contractility of isolated human uterine muscle. 1563 10


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