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)

Death from malignant hyperthermia (MH) still occurs in France. However, anaesthesia of the MH susceptible (MhS) patient is quite possible without any more risk than for patients who are not MhS. Guidelines have been worked out: "trigger" drugs such as volatile anaesthetics (halothane, enflurane, isoflurane) and depolarizing muscle relaxants must be imperatively avoided; "non-trigger" drugs should be used, such as nitrous oxide, barbiturates, benzodiazepines, propofol, opiates, non-depolarizing muscle relaxants, amide or ester local anaesthetics at the usual doses without adrenaline. Moreover, dantrolene should be available in all hospitals, 12 bottles being a minimum at hand, or, better, 30 (about 10 mg.kg-1). In some cases, such as emergencies, an unprepared operating theatre, or an unprepared ventilator, the patient should be premedicated with 2.5 mg.kg-1 dantrolene intravenously. The ventilator, the circuit and the operating theatre should not contain any trace of halogenated vapour. The usual parameters, as well as temperature and expired CO2 concentration, should be closely monitored. MhS patients must also be given counselling. This includes explanations about MH, its genetic features, the main laboratory tests used to detect susceptibility, as well as advice about lifestyle, the use of drugs other than general and local anaesthetics, and a discussion concerning the association of MH with other diseases. This counselling is not always easy to provide, because many answers are not, as yet, definitive.
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PMID:[Management of a patient with malignant hyperthermia susceptibility during anesthesia and daily living]. 269 56

A review of the pharmacology of propofol, a new IV anesthetic agent, is presented. Solubilized in a soybean emulsion, propofol is one of a series of sterically hindered phenols that exhibit anesthetic activity. Induction of anesthesia with propofol may be associated with pain on injection, apnea, and a reduction in arterial blood pressure (BP) and cardiac output. Caution should be ascribed to its use in patients with coronary artery disease, where these effects may have the potential for producing myocardial ischemia. The hemodynamic responses to laryngoscopy and intubation are attenuated. The pharmacokinetic profile suggests suitability as an infusion for either maintenance of anesthesia or sedation. Use of propofol as an infusion during surgery may result in a further reduction in cardiac output, particularly with the concomitant administration of adjuvant increments of fentanyl. The ventilatory response to CO2 is depressed during such an infusion. The high clearance of propofol suggests that even after a prolonged infusion, recovery should be rapid. This finding has been confirmed in a series of studies establishing propofol as an ideal agent for use in a total IV anesthetic technique. Both the quality and speed of recovery, together with the absence of emetic sequelae, support the use of propofol in an outpatient setting. Propofol appears to have no long-term effect on adrenocortical function and appears safe for use in patients with acute intermittent porphyria and susceptibility to malignant hyperpyrexia.
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PMID:The pharmacology of propofol. 269 45

Malignant hyperthermia (MH) results from the presence of the halothane-sensitivity gene and is characterized by abnormalities in muscle function. Populations of genetically defined pigs were used to determine the in vivo and in vitro expression of this gene in both the homozygous and the heterozygous condition. On exposure to halothane, isolated muscle bundles from the homozygous halothane-sensitive pigs exhibited decreased tetanus tension and increased tetanus half-relaxation time and contracture and were clearly distinguished from homozygous normal muscles. The heterozygous and homozygous normal muscles were similar in contractile responses except for the occurrence of halothane-induced contractures in the heterozygotes. The heterozygous halothane-negative pigs did not exhibit the characteristic signs of an MH episode in response to halothane succinylcholine, although some metabolic responses were significantly altered (e.g., increased venous partial pressure of CO2 and arterial and venous K+ concentration). Thus the heterozygous pigs were not MH susceptible but did represent a phenotype distinct from the homozygous normal pigs both in vitro and in vivo. These data provide the first convincing evidence for the expression of the halothane-sensitivity gene in heterozygotes.
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PMID:Halothane-sensitivity gene and muscle contractile properties in malignant hyperthermia. 280 26

Acute lymphatic leukemia (ALL) represents one of the most frequent malignancies in childhood. Central venous access ports or partly implanted silicone catheters are usually placed for high-dose chemotherapy in these children. We report two patients aged 7 and 3 years with acute lymphoblastic beta-cell leukemia (B-ALL), a less common subtype of ALL, which presented with hyperthermia (38.4 degrees C and 39 degrees C) during anesthesia with isoflurane for implantation of a central venous catheter. The hyperthermic reactions were accompanied by an increase in expired CO2 and acidosis as well as moderate elevation of heart rate and blood pressure. As in both patients the history and preoperative findings did not reveal signs of infection or other causes of fever, the observed alterations were interpreted as symptoms of malignant hyperthermia triggered either by succinylcholine or isoflurane, which were used in both children. In addition, the hyperthermia responded to administration of dantrolene sodium according to dose recommendations for treatment of malignant hyperthermia. In one of the patients, withdrawal of dantrolene during the initial postoperative hours was followed by a recurrent increase in body temperature, which once again could be suppressed by additional dantrolene infusion. According to the literature, malignant hyperthermia has occasionally been described in children with malignancies such as leukemia or Burkitt's lymphoma. Our observations indicate that children with B-ALL may be especially susceptible to malignant hyperthermia. Close monitoring of body temperature and expiratory CO2 are therefore indicated in these children, and dantrolene therapy should be started immediately in case of increased temperature during anesthesia.
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PMID:[Hyperthermic reaction in the perioperative phase in 2 children with acute lymphoblastic leukemia of B-cell type]. 292 70

Anesthesia in patients susceptible to malignant hyperthermia (MH) is generally considered to be very risky, although - with one notable exception - there are no prospective studies about anesthetic management in a large number of such patients. The prophylactic use of dantrolene has been recommended in MH patients, although there is no strong evidence supporting this - despite the fact that dantrolene may have serious side effects. We therefore decided to report the results of our own anesthetic technique for MH patients, as our technique does not include the prophylactic use of dantrolene. From 1981 to 1988, 19 operations on 16 MH-susceptible patients were performed. Patients 1-4 were pediatric survivors of an MH episode, where MH susceptibility was confirmed by muscle biopsy and in vitro contracture tests in at least one parent; patients 5-7 were survivors of an MH crisis, and they later underwent diagnostic muscle biopsies themselves; all other patients (nos. 8-16) were relatives of MH survivors with positive in vitro contracture tests. Diazepam, pentobarbital, pethidine, and chlorprothixene were used for premedication; no prophylactic dantrolene was given. Anesthesia was induced by thiopentone and was continued by nitrous oxide/oxygen, fentanyl, and droperidol; alcuronium, atracurium, and vecuronium were administered as necessary. Pyridostigmine, atropine, and naloxone were used if appropriate. New or disposable tubings were used for ventilation, and the vaporizers were removed from the anesthesia machines. ECG and body temperature were recorded in all patients; blood pressure was monitored invasively if indicated; end tidal CO2 was monitored whenever possible.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Malignant hyperthermia in Austria. III. Anesthesia in susceptible patients]. 317 78

Animals were identified as porcine malignant hyperthermia susceptible by halothane testing and were slaughtered at 90 kg of body weight. Coronary, renal and iliac arteries were isolated, dissected and 5 mm rings were mounted in 20 mL organ baths with modified Krebs solution maintained at 37 degrees C and oxygenated with 95% O2, 5% CO2. Halothane at 0%, 0.5%, 2% and 5% concentration was bubbled in the organ baths and mechanical responses were recorded over a period of 25 min. Halothane free arteries remained quiescent and the arteries from the halothane sensitive and from the halothane resistant groups reacted similarly. All arteries in the presence of halothane responded with an initial contraction of short duration followed by a relaxation and both phenomena occurred in a concentration-dependent fashion. The iliac artery was the most sensitive to halothane and responded to 0.5% concentration while coronary and renal arteries maintained the resting tension of 4 g. These results demonstrate that vascular smooth muscle, like skeletal muscle and unlike respiratory smooth muscle, has a direct pharmacological response to halothane. These observations led to the postulate that halothane by its transient but significant vasoconstrictive action could be a contributing factor to initiate the fulminant reactions occurring in malignant hyperthermia.
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PMID:Halothane induced vasomotion of coronary, renal and iliac arterial rings in malignant hyperthermia susceptible swine. 319 69

The pathogenesis of the malignant hyperthermia syndrome is not yet completely understood. There is evidence of involvement of the sympathoadrenergic system. We describe the anesthetic management of two patients considered to be MH-susceptible. Management in the theater included an infusion of dantrolene 2.5 mg/kg prior to induction of anesthesia. In addition, the first patient was given a peroral prophylaxis with dantrolene; in subsequent cases this route of administration was abandoned. Anesthesia was performed with a drug combination devoid of sympathomimetic effects (diazepam, flunitrazepam, midazolam,--methohexital,--fentanyl, alfentanil,--vecuronium). Monitoring should include ECG, blood pressure, body temperature and end-tidal CO2-concentration.
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PMID:Malignant hyperthermia susceptibility--successful management with a "stressfree" technique. 359 Dec 64

The safety of etomidate for induction of anesthesia in malignant hyperthermia-susceptible (MHS) pigs was evaluated in a two-phase experiment. Two litters of Purebred Poland China pigs, one MHS (n = 4) and the other malignant hyperthermia-resistant (MHR) (n = 4) were used. Phase I compared MHS vs MHR animals in terms of cardiovascular, metabolic, and skeletal muscle rigidity responses to etomidate and fentanyl anesthesia and to a subsequent malignant hyperthermia (MH) challenge with halothane-succinylcholine. When three of the four criteria for the diagnosis of MH occurred (rigidity, tachycardia, or increases in temperature or end-tidal CO2) in an animal, phase I was terminated. In phase II, only the MHS animals were used and experimental procedures were as in phase I except thiopental replaced etomidate. In phase I, evidence was inadequate to support the diagnosis of MH based upon responses of MHS pigs to the infusion of etomidate even though the infusion of etomidate in MHS pigs was associated with statistically significant increases in body temperature and plasma lactate levels above those observed in MHR pigs. Heart rate and bicarbonate levels were lower in MHS than in MHR pigs during etomidate infusion. With discontinuation of etomidate and a subsequent challenge with halothane-succinylcholine, all four pigs developed the MH syndrome within 15-30 min. Thiopental replacement of etomidate in the phase II experiment resulted in a twofold greater time (45-75 min) for halothane-succinylcholine to trigger MH in the susceptible pigs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Malignant hyperthermia: is etomidate safe? 398 91

Two cases of malignant hyperthermia are described where the earliest sign was a rise in the end-tidal CO2 concentration. This led to nearly immediate detection and adequate treatment with sodium dantrolene. These cases demonstrate the efficacy of monitoring end-expired CO2 concentrations in patients at risk from malignant hyperthermia, as well as a means for following the adequacy of treatment.
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PMID:End-tidal CO2 monitoring. Its use in the diagnosis and management of malignant hyperthermia. 643 67

The effects of an induced malignant hyperthermia (MH) crisis have been studied in the intact pig. Both physiological and biochemical changes in skeletal muscle were studied. MH was induced with 3% halothane plus a bolus injection of succinylcholine. In the prechallenge period a significant difference was observed in the concentration of certain muscle metabolites, comparing the MH-susceptible (MH+) with the non-susceptible (MH-) pigs. A lower level was measured for phosphocreatine (PCr), inosine monophosphate (IMP) and an increased level of lactate and creatine (Cr) in the susceptible pigs (MH+). The challenge caused a significant reduction of the level of PCr and adenosine in MH+ pigs, compared to the prechallenge period. After administration of dantrolene sodium, a significant decrease was measured in the level of lactate, compared to the prechallenge period as well as during the challenge. In contrast, in the control pigs no significant changes were observed in muscle metabolites, either after induction of MH or after the administration of dantrolene sodium. Enzyme activity determinations of muscle adenylate kinase and adenosine monophosphate (AMP)-deaminase did not show any difference in activity either before or during the MH crisis or after treatment with dantrolene sodium. The earliest physiological change during an induced MH crisis in our study was the rapid increase of the end-tidal CO2. Within 5 min after MH induction, end-tidal CO2 was doubled. It is concluded that the monitoring of the end-tidal CO2 is essential to diagnose MH at a very early stage.
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PMID:In vivo induced malignant hyperthermia in pigs. I. Physiological and biochemical changes and the influence of dantrolene sodium. 671 Dec 53


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