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)

The purpose of the present investigation was to determine the normal perioperative variations in the serum concentration of creatine phosphokinase (CPK) and its isoenzymes MM, MB, and BB, and of lactic dehydrogenase (LDH) and its isoenzymes LDH1 to LDH5 to distinguish operation-induced changes in these enzymes from those due to acute myocardial infarction or malignant hyperthermia. In 30 patients, 52 to 75 years of age undergoing elective orthopedic operations, 10 serial blood samples were obtained in the perioperative period: two samples before skin incision and eight samples after the incision over a time span of 70 hours. The preinduction mean serum CPK level of 141 U/L increased gradually and significantly and reached a maximum mean concentration of 809 U/L 34 hours after incision (p less than 0.01). The CPK-MM percent increased after incision, whereas that of CPK-MB and CPK-BB decreased, although their absolute values in terms of U/L rose. The preinduction mean serum LDH value of 173 U/L increased gradually after incision and achieved peak levels at 34 hours (203 U/L) and 58 hours (210 U/L) after incision (p less than 0.05). The LDH1:LDH2 ratio did not change. The LDH5 percent increased and peaked 10 hours after incision (p less than 0.05). There was a significant correlation between severity of operation-induced tissue damage and the serum CPK concentration (p less than 0.001). The large increase in total CPK (primarily MM fraction) occurring after surgery may minimize the percentile effects caused by an increase in MB level due to myocardial infarction.
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PMID:Serum creatine phosphokinase, lactic dehydrogenase, and their isoenzymes in the perioperative period. 262 1

Striated musculature is considered unusually tolerant to all kinds of injuries, and rhabdomyolysis associated with drug overdose or chronic drug intake is a rare event. This may be because striated musculature, in contrast to other tissues such as liver and kidney, shows little affinity for most drugs. Several different types of drug-induced rhabdomyolysis may be distinguished, and the clinical features of the condition may vary widely, from moderate myalgia to involvement of groups of muscles to involvement of the total skeletal musculature. In clinically asymptomatic rhabdomyolysis, early diagnosis is only made if routine laboratory tests include determination of serum creatine kinase. Determination of myoglobin in serum and urine is more sensitive and allows earlier diagnosis of muscle necrosis. Myoglobinaemia may lead to toxin-induced tubular necrosis, and impairment of renal function or even acute renal failure. About 10% of all cases of acute renal failure are due to rhabdomyolysis. Fulminant rhabdomyolysis may be associated with excessive hyperkalaemia and hypocalcaemia which may induce further life-threatening complications. Therefore, early diagnosis of rhabdomyolysis is most important for prevention of its potentially life-threatening sequelae. Therapy of rhabdomyolysis consists of supportive and specific measures. Early diagnosis may help to prevent life-threatening sequelae like acute renal failure, electrolyte imbalance and shock. Withdrawal of the incriminated drug or detoxification in drug overdose should be followed by supportive measures including infusion therapy and correction of dehydration and electrolyte imbalances. Forced diuresis with sodium bicarbonate may protect the kidney function from acidosis and precipitation of myoglobin in tubules. Elimination of myoglobin from plasma may be enhanced by plasmapheresis. In patients with acute renal failure, haemodialysis is necessary. In malignant hyperthermia, immediate infusion of dantrolene sodium is required. This drug also seems to have a beneficial effect in neuroleptic malignant syndrome. The repair mechanisms of striated musculature function extremely well. The prognosis of muscular atrophy after the acute stage of rhabdomyolysis is excellent. The same is true for the prognosis of acute renal failure. However, the extent of complications or survival of the acute stage of rhabdomyolysis strongly depend on early diagnosis and start of adequate therapy.
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PMID:Clinical features, pathogenesis and management of drug-induced rhabdomyolysis. 265 42

Malignant hyperthermia (MH) is a pharmacogenetic disease in man and animals. It primarily involves skeletal muscle tissue, but other tissues might be affected to a lesser degree. Calcium homeostasis in muscle cells is upset in susceptible individuals, so that various agents and circumstances can increase the free, ionised intracellular calcium concentration to damaging levels. The primary defect is not known at present, but is believed to involve an abnormally sensitive calcium-induced calcium release mechanism. Thus small, localised increases in calcium concentration releases more calcium so that a vicious cycle is triggered. The increased calcium concentration causes multiple effects in the muscles by stimulating contraction and a hypermetabolic state, clinically observed as rigidity and fever. If demands on the homeostatic mechanisms to lower the calcium concentration become exhausted, and metabolism is insufficient to supply enough phosphocreatine and ATP, membrane potentials cannot be maintained, and permeability of the cell membranes increase. This causes loss of phosphate and H+ as well as K+ and Mg++, and later myoglobin and creatine kinase. Thereby oxidative metabolism is further impeded with formation of lactate as a result. The ensuing acidosis stimulates sympathetic innervation, resulting in tachycardia, high blood pressure, and vasoconstriction. Hyperkalemia causes arrhythmia. Dantrolene inhibits the release of calcium and can halt the process if given before depletion of the energy rich phosphates is too advanced.
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PMID:Pathophysiology of malignant hyperthermia. 269 55

We report on a patient with neuroleptic malignant syndrome (NMS) caused by a therapy for endogenous depression. The symptoms were hyperpyrexia (39.2 degrees C), rigidity, elevated creatine kinase (CK: 594 U/l) and coma. After transfer from an outside hospital, he was treated, at first without effect with dantrolene p.o. (80 mg q.i.d.) and i.v. (1 mg/kg-1/h-1). Clinical improvement and temperature reduction were noted when the levels of neuroleptic drugs fell during unspecific intensive care with mechanical ventilation, sedation (flunitrazepam, barbiturates), relaxation (pancuronium), and hydration. After uncomplicated weaning from the ventilator the patient became more cooperative and was returned to the psychiatric ward. Further treatment took the form of combined drug therapy with biperiden and flunitrazepam and in addition a series of 12 electroconvulsive therapies (ECT). The elevated CK levels initially decreased, serum potassium levels were found to be within normal limits, and myoglobinuria was not detected during the further course. Trigger agents for NMS are antipsychotic drugs such as thioxanthenes, phenothiazines and butyrophenones. Because the signs and symptoms are so similar to those of malignant hyperthermia (MH), it has been suggested that NMS and MH are related diseases. The postulated mechanisms of NMS become apparent in the CNS, whereas those of MH affect the muscle cell itself. An abnormal in vitro contraction test after NMS should suggest to triggering of MH crisis after succinylcholine administration in anaesthesia for ECT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The malignant neuroleptic syndrome and malignant hyperthermia]. 272 40

The occurrence of masseteric muscle spasm (MMS) in children is thought to be frequent and to be associated usually with malignant hyperpyrexia (MH). We have found a lower incidence of MMS in children and 50% had no muscle abnormality. Clinical features that support a diagnosis of MH include high serum creatine kinase (CK) concentration and the presence of myoglobinuria. There is evidence to suggest that suxamethonium does increase jaw tone in adults and children, and an exaggerated response may be taken clinically to be MMS. However, MMS should still be regarded as an early warning sign of MH.
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PMID:Is there a relationship between masseteric muscle spasm and malignant hyperpyrexia? 273 Aug 25

A 33 year old woman, with myotonia atrophica and a known susceptibility to malignant hyperthermia, presented during her second pregnancy with multiple episodes of hyperthermia. They were associated with a rapid rise in the serum creatine phosphokinase (CPK) level, and not with infection or a myotonic crisis. Because of the obstetric conditions, caesarean section was planned. Preoperative oral dantrolene was used as prophylaxis. Six days after the start of this treatment, CPK and serum myoglobin levels were back within the normal range. There were no side-effects for the mother nor for the foetus. There were no further increases in either CPK or serum myoglobin levels during surgery or afterwards, but the rectal temperature remained markedly raised for 48 h after the delivery. Oral dantrolene was given during the first nine postoperative days. The occurrence of episodes of high fever during pregnancy linked to MHS and myotonia atrophica is discussed, as well as the anaesthetic management of such a patient. Side-effects of dantrolene for the mother or the foetus are also considered, especially as foetal levels of this drug would seem not to reach therapeutic levels. It would appear interesting to measure maternal dantrolene blood levels, especially if high doses are administered, to avoid reaching therapeutic levels in the foetus.
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PMID:[Oral dantrolene in a parturient with myotonic dystrophy and susceptibility to malignant hyperthermia]. 320 29

During the last 4 years different diagnostic procedures for the detection of malignant hyperthermia (MH) susceptibility have been used at the authors' clinical unit; this study was designed to compare the results of these tests. PATIENTS AND METHODS. Since March 1983, 158 patients have been referred for the following reasons: group A: probands (n = 17) who had had symptoms of MH during anesthesia; group B: patients of probands (n = 48) if the latter were not tested because of age (n = 24) or death (n = 2); group C: relatives from MH families (n = 86); group D: patients (n = 5) who developed fever during stress and/or physical activity (n = 3), had myotonia (n = 1), or developed rhabdomyolysis during intensive care (n = 1); group E: controls (n = 2). Two static halothane and two static caffeine tests according to the European protocol were performed in all patients (n = 158). Histological examinations of skeletal muscle (fixed in glutaraldehyde, stained with hematoxylin-eosin, Gieson, and toluidine blue) were done in the first 100 patients; all specimens were scored by the same investigator (E.S.). Score 0: normal; 1: increased number of sarcolemma cores; 2: 1+cores forming groups; 3: 1+2+fiber degeneration; 4: specific changes-myopathies. Plasma levels of creatine kinase (CK) were determined in the first 50 patients. Complete neurological examinations, including electromyography (EMG), were done in ten patients who had increased CK levels as well as histological scores of 3 or 4 (Table 1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Malignant hyperthermia in Austria. II. A comparison of the results of diagnostic test procedures]. 341 55

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

A healthy, 15-year-old male received a thiopental, nitrous oxide, oxygen, enflurane anesthetic for appendectomy. Cardiac arrest, following succinylcholine administration, was associated with marked hyperkalemia (potassium levels 8.7 to 11.6 meq), hemolysis (hematocrit fall from 41.7 to 26.6%, plasma hemoglobin 27 mg/dL), and creatine phosphokinase (CPK) elevation (8900 units). Vigorous resuscitative therapy including dantrolene was unsuccessful. The diagnosis of malignant hyperthermia was made by the marked CPK elevation on blood samples drawn during resuscitation and analyzed by the Medical Examiner's Office.
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PMID:Hemolysis and hyperkalemia complicate malignant hyperpyrexia during anesthetic death. 371 29

Ten susceptible and ten resistant pigs to malignant hyperthermia were used to observe the effects of exercise and ambient temperature on selected physiological parameters. Pigs were submitted to a ten minute exercise on a treadmill operating at a speed of 1.8 km/h and inclined to 11 degrees. Exercise in the first group was at an ambient temperature of 14 degrees C, and in the second at 29 degrees C. The right carotid artery was previously cannulated for blood pressure measurements and for repeated blood sampling during exercise. Arterial pressure, heart rate, rectal and cutaneous temperatures were recorded. Levels of cortisol, creatine kinase and its isoenzymes were measured. At 14 degrees C, exercise caused some physiological adjustments in susceptible animals; heart rate, skin temperature and cortisol levels increased (P less than 0.05). In resistant pigs, only the heart rate was elevated significantly following exertional stress at 14 degrees C. Exercise at 29 degrees C produced severe stress and marked physiological changes: heart rate, rectal and skin temperatures and cortisol levels increased significantly in both susceptible and resistant swine. At 29 degrees C, susceptible pigs also had higher levels of serum cortisol, total creatine kinase and MM isoenzyme (P less than 0.05) compared to resistant pigs. The results indicate that, following exertional or thermal stress, susceptible pigs undergo more extensive physiological changes than do resistant pigs. Similar levels of stress prior to slaughter may trigger physiological changes which in the susceptible pigs would likely result in pale, soft exudative myopathy.
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PMID:Physiological responses to treadmill exercise and ambient temperature in normal and malignant hyperthermia susceptible pigs. 374 62


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