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)

1. Neuroleptic drugs (antipsychotics) produce numerous side effects which include serious extrapyramidal symptoms consisting of akathisia, dystonia, neuroleptic malignant syndrome, parkinsonian reactions such as postural abnormality, tremor, akinesia or bradykinesia, rigidity, and tardive dyskinesia. 2. Among the complications of neuroleptic chemotherapy, the most serious and potentially fatal complication is malignant syndrome, which is characterized by extreme hyperthermia, "lead pipe" skeletal muscle rigidity causing dyspnea, dysphagia, and rhabdomyolysis, autonomic instability, fluctuating consciousness, leukocytosis, and elevated creatine phosphokinase. 3. Neuroleptic malignant syndrome should be differentiated from malignant hyperthermia, lethal catatonia, and other pathological states producing some of these same symptoms. 4. In addition to neuroleptics, malignant syndrome has been caused by thymoleptics (antidepressants), metoclopramide (antiemetic), metoclopramide combined with cimetidine, tetrabenazine, overdosage of benzodiazepine, phenelzine, dothiepin and alcohol, and amphetamine. 5. Factors leading to and/or facilitating the emergence of neuroleptic malignant syndromes are reportedly organic brain syndrome, dehydration, exhaustion, external heat load, excessive sympathetic discharge, use of long acting neuroleptics, high doses of neuroleptics, rapid dose titration with neuroleptics, abrupt discontinuation of antiparkinsonism agents, and concurrent lithium therapy. 6. Although, the pathogenesis of neuroleptic malignant syndrome is not understood completely, a blockade of dopaminergic receptors in the hypothalamus, spinal cord and striatum, an alteration of dopaminergic-serotonergic transmission in the body, an enhanced synthesis and action of prostaglandin E1 and E2, and a modification of calcium-mediated signal transduction in the body have been suggested. 7. The treatment of malignant syndrome includes immediate withdrawal of neuroleptic drugs, i.v. infusion of dantrolene, and oral administration of bromocriptine; or alternatively i.v. infusion of dantrolene and the combination of levodopa-carbidopa. 8. Other measures to enhance the therapeutic effectiveness of the aforementioned regimens are to include the use of anticholinergic drugs such as benztropine to enhance the effectiveness of bromocriptine, of lorazepam if catatonic symptoms persist, or of electroconvulsive therapy (ECT) if psychotic symptoms persist. 9. These treatments, however, must be "active" rather than "passive", in order to avert fatalities and/or unfortunate sequelae from this iatrogenic and incompletely understood disease.
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PMID:Pathogenesis and treatment of neuroleptic malignant syndrome. 197 19

Although malignant hyperthermia is still a potentially fatal disease that was marked by a high mortality until recently, lasting damage to the patient can now be prevented by early diagnosis and treatment. The following case demonstrates the special value of capnometry in diagnosing this condition. A 34-year-old man admitted for oral surgery showed symptoms of malignant hyperthermia 5 h after induction of anesthesia. Neuroleptanalgesia had been conducted. The patient had received thiopental and fentanyl for induction of anesthesia and alcuronium and succinylcholine for intubation. The first symptom noticed was an elevation of the end-tidal pCO2 as monitored by capnometry. Additional symptoms, such as a pronounced rise in temperature, blood pressure, and heart rate did not develop until 20-25 min later. The end-tidal oxygen concentration decreased from 30 vol.-% to 26 vol.-%. The patient had to be ventilated with a volume of 25 l/min to keep end-tidal pCO2 under 6 kPa. Treatment with dantrolene was started immediately. Not until 3 h after the onset of the first symptoms did the patient's body temperature and the minute volume needed for ventilation return to normal. Postoperative laboratory findings showed only a slight elevation of creatine kinase and serum lactate. Myoglobin was not detected in serum or urine. This case indicates that capnometry permitted immediate adaptation of controlled ventilation to the patient's increased metabolic rate and early initiation of dantrolene treatment, thus preventing more severe disorders and possible consequences for the patient. Other studies have also suggested the special importance of capnometry. Since the patient refused to give his consent, the diagnosis could not be ascertained by muscle biopsy, and had to be based on symptoms.
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PMID:[Early recognition of malignant hyperthermia using capnometry]. 210 75

In pigs, the serotonin-2 (5-HT2) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), 0.8 mg/kg, induced "psychotic" behaviour (e.g., grimacing, backward locomotion, blank stare) and a muscular syndrome, which is known as malignant hyperthermia (MH) in pigs and humans. This syndrome is characterized by generalized skeletal muscle rigidity, leading to an increase in body temperature, marked acidosis, hyperkaliaemia, cyanosis and elevation of lactate, carbon dioxide and the muscle enzyme creatine kinase (CK) in plasma. In pigs which were selectively bred for susceptibility to MH induction by known triggering agents, such as halothane, the administration of DOI was fatal in 3 out of 5 animals. In genetically susceptible pigs, MH was also induced by 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), 0.5-1.8 mg/kg, and D-lysergic acid diethylamide (LSD), 60-110 micrograms/kg. Furthermore, 5-MeO-DMT and LSD induced head shakes in the animals, which had not been observed after DOI and could not be blocked by 5-HT2-antagonists, ketanserin (0.5-5 mg/kg) and ritanserin (1-2.5 mg/kg). The psychotomimetic effects of 5-MeO-DMT could be blocked by ketanserin or ritanserin, which, depending on the dose, also reduced or totally prevented the hyperthermia and metabolic changes induced by 5-MeO-DMT in pigs. Administration of 5-MeO-DMT, 1.8 mg/kg, was fatal in 4 of 5 MH-susceptible pigs, whereas pigs injected with this dosage after pretreatment with ketanserin (0.5-5 mg/kg) or ritanserin (1-2.5 mg/kg) did not die. In pigs from MH-resistant littermates, administration of 5-MeO-DMT was not fatal. Comparison of metabolic changes in susceptible and non-susceptible pigs suggested that the marked increase in plasma potassium, which arises principally from damaged muscle cells, is primarily responsible for the fatal effect of DOI and 5-MeO-DMT in genetically susceptible individuals. In MH-susceptible pigs, which were anesthetized, relaxed and artificially ventilated, 5-MeO-DMT did not induce hyperthermia, thus substantiating that the marked hyperthermia observed in conscious pigs was a result of muscle activation and not due to effects on thermoregulation or blood pressure. The results indicate that hallucinogenic drugs with 5-HT2 agonistic effects trigger a life-threatening syndrome, MH, in genetically susceptible pigs. 5-HT2 antagonists, such as ketanserin or ritanserin, are capable of counteracting the fatality of this syndrome.
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PMID:Pharmacodynamic effects of serotonin (5-HT) receptor ligands in pigs: stimulation of 5-HT2 receptors induces malignant hyperthermia. 211 35

A 7-year-old boy developed rhabdomyolysis with a peak creatine phosphokinase level of 261,400 IU/L after his appendectomy. These abnormalities occurred following a 2-3-day illness consisting of upper respiratory tract symptoms, fever, and abdominal pain mimicking acute appendicitis. At the time of operation, a normal appendix was removed, and mesenteric lymphadenitis was noted. The myoglobinuria and elevation of creatine phosphokinase were transient, and the patient remained asymptomatic. We review various causes of right lower quadrant pain and rhabdomyolysis and address the roles of malignant hyperthermia and infectious agents. The possible cause of the phenomena observed in this patient is discussed.
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PMID:Asymptomatic rhabdomyolysis of unknown etiology. 224 93

This study provides the first comprehensive characterisation of the calcium (Ca) homeostasis defects found in muscle and lymphocytes of a malignant hyperthermia (MH)-susceptible dog. Novel findings regarding this dog are reported, compared to controls. First, a canine stress syndrome occurs, analogous to the porcine stress syndrome; susceptibility can be identified by exercise challenge testing. Secondly, caffeine causes Ca release from muscle sarcoplasmic reticulum in a greater amount and at a greater rate. Thirdly, there is a compensatory increase in Ca sequestration by sarcoplasmic reticulum. Fourthly, lymphocytes have lower cytosolic-free Ca and a greater ability to prevent Ca increase. Halothane increases Ca by a greater amount and rate. Fifthly, muscle is more resistant to the contracture-producing effects of caffeine, as occurs in the non-rigid variant of MH susceptibility in man. This resistance, despite increased caffeine-induced release through the Ca channel, may be attributable to increased Ca sequestration by sarcoplasmic reticulum. Finally, erythrocyte osmotic fragility and creatine kinase tests fail to distinguish between the MH-susceptible dog and controls.
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PMID:Canine stress syndrome/malignant hyperthermia susceptibility: calcium-homeostasis defect in muscle and lymphocytes. 230 Jul 6

The anaesthetic records of 61 patients who had experienced adverse reactions thought to be malignant hyperthermia (MH) were reviewed retrospectively to evaluate the diagnostic importance of clinical symptoms. Using the in vitro contracture test, 38 (62%) patients were identified as MH susceptible (MHS), the remainder showing normal test results (MHN). Generalized rigidity, ventricular arrhythmias, cyanosis and postoperative myoglobinuria were observed significantly more often in MHS patients. Median values of body temperature and creatine kinase serum concentrations were significantly greater in the MHS group. Masseter spasm and sinus tachycardia were as common in MHS as in MHN individuals. Statistical models using generalized rigidity, ventricular arrhythmias, cyanosis and fever exceeding 38 degrees C for prediction of MH showed a maximum sensitivity and specificity of 78% and thus are not acceptable for clinical use. For definitive diagnosis of MH, the well established in vitro contracture test remains essential.
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PMID:Prediction of malignant hyperthermia susceptibility: statistical evaluation of clinical signs. 233 13

Neuroleptic malignant syndrome is an uncommon, idiosyncratic, and sometimes life-threatening disorder associated with the use of neuroleptic drugs. The pathogenesis of neuroleptic malignant syndrome is uncertain, but it may be similar to that of malignant hyperthermia (MH). Some of the symptoms of neuroleptic malignant syndrome are similar to those of MH. We anesthetized a 17-year-old man with this syndrome multiple times for electroconvulsive therapy (ECT) using a variety of anesthetic techniques. In this patient, dantrolene pretreatment and the use of nondepolarizing muscle relaxants did not relieve symptoms of the syndrome, including fever and creatine phosphokinase (CPK) increases.
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PMID:Anesthetic management of a patient with neuroleptic malignant syndrome. 235 60

Erythrocyte osmotic fragility, serum creatine kinase (CK) and its isoenzymes (CK-MM, CK-MB and CK-BB) were determined in pigs susceptible (SMH) and resistant (RMH) to malignant hyperthermia at three different body weights (Group 1, 10 to 25 kg; Group 2, 26 to 55 kg; Group 3, 56 to 95 kg). The halothane challenge test was used for determining susceptibility to malignant hyperthermia (MH). Significantly (P less than 0.05) greater erythrocyte haemolysis at saline concentrations of 80 to 100 mM NaCl occurred only between SMH and RMH pigs for body weight group 2. The determination of blood enzyme activities revealed also a significant (P less than 0.001) increase for total CK, CK-MM and CK-BB in SMH and RMH pigs of body weight Group 2. Furthermore in SMH pigs, total CK, CK-MM and CK-MB activities were significantly (P less than 0.05) greater in the animals of body weight Group 2. It was concluded that, in SMH pigs, weighing between 26 and 55 kg, there is a relationship between erythrocyte osmotic fragility, plasma CK, CK isoenzyme activities and muscle development.
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PMID:Erythrocyte osmotic fragility, serum creatine kinase and its isoenzymes related to body weight in porcine malignant hyperthermia. 236 58

A 6 month old domestic shorthaired cat died of suspected malignant hyperthermia. Anesthesia was induced and maintained with halothane vaporized in oxygen and nitrous oxide, after acepromazine premedication. Before an incision was made, the cat's heart rate dropped from 140 to 90 beats/min concomitant with a drop in blood pressure. Glycopyrrolate administration resulted in severe ventricular tachycardia (340 beats/min). Halothane and nitrous oxide were discontinued and the surgery was abandoned. Lidocaine administration resulted in a normal sinus rhythm. In recovery, the cat was tachypneic and struggling, with a rectal temperature of 40.1 degrees C that quickly increased to 41.4 degrees C. While the cat was being cooled, cardiac dysrhythmias progressed to ventricular fibrillation that was not responsive to cardiorespiratory resuscitation. Blood specimens obtained while the cat was being cooled showed hyperkalemia (10.0 mEq/L) and increased serum creatine kinase activity (780 IU/L). There was extreme extensor rigidity (rigor mortis) within 5 min of cardiac arrest. Results of microscopic and electron microscopic examination of muscle showed occasional perivascular infiltrates of lymphocytes with infrequent perimysial and epimysial neutrophils and a few sarcomeres with streaming of Z-bands (suggesting a contracted state). Histochemical evaluation of skeletal muscle showed no significant difference between type I and type II fibers.
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PMID:Suspected malignant hyperthermia after halothane anesthesia in a cat. 260 80

Signs of malignant hyperthermia, including progressive increases in PaCO2, skin temperature and heart rate, and elevated serum levels of potassium, inorganic phosphate, and creatine kinase, were identified in a halothane-anesthetized horse. Treatment was discontinuing halothane administration, applying ice and cold fluids, and hyperventilating with 100% oxygen. After an initial recovery, bilateral hindlimb myopathy and pigmenturia developed. The myopathy resolved after treatment with oral dantrolene, IV fluids, and hydrocortisone. Results of caffeine-halothane challenge, using semimembranosus muscle collected 2 weeks after the episode, were considered within normal limits for horses. The intraoperative abnormalities were evidently predictive of postanesthetic myopathy but the cause in this horse remained unclear.
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PMID:Postanesthetic equine myopathy suggestive of malignant hyperthermia. A case report. 260 79


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