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)

Malignant hyperthermia (MH) is an anesthetic agent-induced hypermetabolic state. Human beings and several other animal species, including dogs, have been described to be genetically predisposed to development of MH. The halothane-triggered MH syndrome was characterized in genetically predisposed dogs, and in vitro contracture sensitivity of biopsied gracilis muscle exposed to halothane and caffeine was quantitated. Within 1 hour of halothane administration, each MH-susceptible dog developed rapid increases in CO2 production and rectal temperature. Reversal of the hypermetabolic state was achieved when halothane was discontinued and dantrolene sodium was given i.v. Biopsied gracilis muscle from MH-susceptible dogs had abnormal in vitro contracture responses to halothane and caffeine. These findings were consistent with those observed for MH-susceptible human beings and pigs in which a loss in regulation of muscle cell Ca(+)+ is believed to be the primary etiologic event for induction of MH.
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PMID:Malignant hyperthermia in dogs. 203 26

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

Cardiac arrests (CA) occurring during anaesthesia and recovery can be classified into three groups: CA not related to anaesthesia (NACA), CA related to anaesthesia (ACA), whether partially (PACA) or totally (TACA). In the French survey, NACAs were three times more frequent than ACAs. Nearly 25% of ACAs occurred at induction and consisted mainly in TACAs. Another quarter of ACAs occurred during maintenance and consisted mainly in PACAs. About 50% of ACAs occurred after the end of anaesthesia and had the highest mortality rate. Cardiac arrest corresponds to the status of a heart unable to generate the minimum aortic blood flow required for functioning of vital organs. For the brain, a zero-blood flow of more than 4 seconds results in coma. Consequently CA exists when the time interval between two subsequent efficient systoles is greater than 4 seconds. Anaesthetic agents can result in CA by 1) overdose (absolute, relative), 2) anaphylactoid/anaphylactic reactions, 3) specific effects (acetylcholine-like effect, hyperkalaemia and malignant hyperthermia for succinylcholine; vagal effect of vecuronium and atracurium; cardiotoxicity of bupivacaine) and 4) drug interaction. In hypoxic CA, severe neurologic impairment often still exists at the time of onset of CA. The anaesthesia machine and controlled ventilation can induce CA by hypoxic ventilation, overdose of anaesthetic vapour, excessive CO2 reinhalation, hypoventilation, disconnection, excessive pressure in airways. Cardiac hypothermia can be a cause of CA as well as a cause of unsuccessful CPR. Massive infusion of unwarmed fluids and IPPV with unheated gases generate a temperature gradient within the heart which may result in severe arrhythmias and CA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Cardiac arrest during anesthesia and recovery period]. 214 88

The time course of changes in brain electrical activity during halothane anesthesia was examined in 12 malignant hyperthermia-susceptible (MHS) and 14 normal (nMHS) swine. Power densities in selected frequency bands were calculated from the electroen-cephalogram (EEG). EEG and systemic variables were determined over a period of 60 min after starting halothane (1% inspired). Malignant hyperthermia (MH) was triggered in all susceptible pigs. Initial changes in the EEG during development of MH consisted of a decrease in total power and a shift to lower frequencies (delta-theta activity) in all animals. These EEG alterations were noted when there was an increase in heart rate, but other systemic variables were still normal. EEG changes in all MHS animals started at an arterial oxygen tension (PaO2) greater than 90 mmHg and an arterial carbon dioxide tension (PaCO2) less than 50 mmHg. In 5 MHS animals EEG became isoelectric at a PaO2 of 61-82 mmHg and a PaCO2 of 53-68 mmHg. Mean arterial blood pressure at this time was 54-66 mmHg. To determine the effects of hypoxia on the EEG in 7 nMHS animals, oxygen was decreased over a period of 45-60 min to 7% inspired. In 7 other nMHS animals, hypercarbia was produced by admixture of carbon dioxide to the fresh gas supply to achieve incremental increases of PaCO2 to 110-120 mmHg. Significant EEG changes during hypoxia comparable to those seen at the onset of MH were noted at a PaO2 below 40 mmHg and during hypercarbia at a PaCO2 greater than 68 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations in brain electrical activity may indicate the onset of malignant hyperthermia in swine. 224

An automatic feed back controlled totally closed circuit system (Physioflex) has been developed for quantitative practice of inhalation anesthesia and ventilation. In the circuit system the gas is moved unidirectionally around by a blower at 70 l/min. In the system four membrane chambers are integrated for ventilation. Besides end-expiratory feed back control of inhalation anesthetics, and inspiratory closed loop control of oxygen, the system offers on-line registration of flow, volume and respiratory pressures as well as a capnogram and oxygen consumption. Alveolar ventilation and static compliance can easily be derived. On-line registration of oxygen consumption has proven to be of value for determination of any impairment of tissue oxygen supply when the oxygen delivery has dropped to critical values. Obstruction of the upper or lower airways are immediately detected and differentiated. Disregulations of metabolism, e.g. in malignant hyperthermia, are seen in a pre-crisis phase (increase of oxygen consumption and of CO2 production), and therapy can be started extremely early and before a disastrous condition has developed. Registration of compliance is only one of the continuously available parameters that guarantee a better and adequate control of lung function (e.g. atalectasis is early detected). The newly developed sophisticated anesthesia device enlarges tremendously the monitoring and respiratory diagnostic possibilities of artificial ventilation, gives new insights in the (patho)physiology and detects disturbances of respiratory parameters and metabolism in an early stage.
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PMID:Respiratory diagnostic possibilities during closed circuit anesthesia. 226 Apr 24

Two cases of malignant hyperthermia (MH) are presented. The first patient presented initially with tachyarrhythmia intraoperatively and rapid onset of MH crisis. Nasopharyngeal temperature of 43 degrees C was attained after 15-20 minutes of anaesthesia. The patient eventually died of myocardial failure despite external cardiac massage, inotropic support and ventricular pacing. The second patient presented with increasing endogenous hypercarbia following the administration of suxamethonium and isoflurane. The use of the end tidal carbon dioxide monitor led to an early diagnosis of MH. The early use of dantrolene may have contributed to the favourable outcome.
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PMID:Malignant hyperthermia. 239 48

Malignant hyperthermia (MH) is a pharmacogenetic disorder. It is classically described as a hypermetabolic state triggered by halogenated anaesthetics and/or depolarizing muscle relaxants. In fact, since Denborough and Lovel's case, it has been shown that MH has a great number of clinical forms. The overwhelming picture of muscular hypercatabolism with fulminating hyperthermia and generalized rigidity is becoming rare. A better knowledge of the first symptoms explains in part the better prognosis: masseter spasm after suxamethonium, an increase in expired CO2 concentration, unexplained tachycardia, ventricular arrhythmias. The use of dantrolene reduced the mortality of MH. The different types of clinical manifestations are due to genetic differences, the concentration of the anaesthetic agent, and the length of time of exposure to the drug. The severity of the episode is linked to environmental factors such as stress, physical exercise, ambient temperature, concomitant use of other drugs. Masseter spasm after suxamethonium is specific for MH, but not pathognomonic. It occurs in 1% of cases in children when using halothane with suxamethonium. However, in those patients who displayed such a spasm, more than 50% had a positive contracture test. Masseter spasm is often associated with severe rhabdomyolysis in patients with muscle dystrophy, especially Duchenne's dystrophy. In the latter case, major cardiac problems may occur at the time of anaesthetic induction. Even if there are no other signs of MH, all patients who have had a masseter spasm must be considered as open to doubt, and should be further explored. MH is often difficult to diagnose in medium severity types.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Clinical features of malignant hyperthermia crisis]. 251 11

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


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