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)

Clinical concentrations of anesthetics augment caffeine-induced contracture of frog sartorius muscle; however, anesthetics differ in this characteristic. The potentiation was quantitated using six paired sartorius muscles for each specified concentration of anesthetic and controls. At a concentration of 1 MAC, the greatest potentiation occurred with 2 mM caffeine for all anesthetics studied. Under these conditions the order of magnitude of augmentations was: chloroform (15 times); halothane (11 times); methoxyflurane (10 times); cyclopropane (5 times); enflurane (4 times); isoflurane (3 times); diethyl ether (2 times); Baxter 3224 (2 times); fluroxene (1.4 times); nitrous oxide (1.3 times). Halothane at .5 MAC augments the 2 mM caffeine-induced contracture almost seven times, and at 2 MAC almost 13 times, whereas 2 MAC isoflurane potentiates the caffeine-induced contracture only four times and 4 MAC diethyl ether only two and a half times. It is postulated that those anesthetics that most potentiate caffeine-induced contracture may be the most potent triggering agents of malignant hyperthermia.
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PMID:An in-vitro model of malignant hyperthermia: differential effects of inhalation anesthetics on caffeine-induced muscle contractures. 30 36

Isoflurane has a lesser ability than halothane to induce contracture in malignant hyperthermia (MH) muscle in vitro. This does not necessarily imply that isoflurane is not as potent an MH trigger as halothane in vivo. A hypothesis was tested that in vitro treatment with Bay K 8644, an activator of both the dihydropyridine receptors as well as the sodium channels of the T-tubules, potentiates isoflurane-induced MH-susceptible skeletal muscle contracture. In addition to the usual halothane-caffeine test, other muscle bundles were exposed to 10 microM Bay K 8644-halothane and equipotent anesthetic concentrations (expressed in multiple minimum alveolar concentration [MAC]) of isoflurane either alone or combined with Bay K 8644. In 14 MH-susceptible muscle bundles, the mean maximum contracture induced by 2 MAC isoflurane was 0.20 +/- 0.22 g (mean +/- SD), and this value was significantly less than that obtained with 2 MAC halothane (0.68 +/- 0.40 g). Bay K 8644 did not induce muscle contracture on its own but consistently enhanced both the 0.5 MAC isoflurane and halothane to the same maximal isometric tension (1.09 +/- 0.35 g and 1.11 +/- 0.37 g, respectively). Such an effect was not observed in the MH-nonsusceptible group. Under the conditions of this in vitro study, 0.5 MAC isoflurane appears to be as potent as halothane in inducing muscle contracture in skeletal muscle bundles from individuals susceptible to MH.
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PMID:Effect of Bay K 8644 on the magnitude of isoflurane and halothane contracture of skeletal muscle from patients susceptible to malignant hyperthermia. 137 90

The amounts of halothane and isoflurane trapped after exposure for up to 3 h at 2 MAC in commonly used anaesthesia circuit tubing were quantitated by gas chromatography. The decontaminating effects of procedures such as flushing with oxygen, thermal disinfection and/or routine storage were assessed in a similar way. After halothane exposure, anaesthetic content was highest in silicone (398 +/- 55 mg 100 g-1). Lower quantities were found in all other tubings investigated (electrically conductive latex: 64 +/- 4, conductive rubber: 62 +/- 4, polyethylene-vinyl-acetate (PEVA): 293 +/- 10 and 149 +/- 17 for non-conductive corrugated and spiral tubes, respectively, polysulfone (Hytrel): 155 +/- 10 mg 100 g-1). The isoflurane contents were substantially lower (silicone: 278 +/- 23; others: 55 +/- 7, 61 +/- 6, 163 +/- 9 and 86 +/- 8, 74 +/- 4 mg 100 g-1). The tubings' content did not correlate with the material's partition coefficient as full saturation was not achieved during exposure. Decontamination procedures reduced the content of volatile anaesthetics to a variable extent. Conductive latex and rubber showed the highest residual content, even after thermal disinfection and subsequent storage. Twenty-minute flushing with oxygen (8 l min-1) decreased effluent gas concentrations below 5 p.p.m. in all tubings. With silicone, after 1 h flushing, halothane concentrations still exceeded 10 p.p.m. (isoflurane: 8 p.p.m.). It is concluded that urgent decontamination by a 20-min flush warrants the safe re-use of previously 'contaminated' conductive rubber and latex as well as polysulfone tubings in critical situations, e.g. in malignant hyperthermia patients if disposable tubing is not immediately available.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anaesthetic uptake and washout characteristics of patient circuit tubing with special regard to current decontamination techniques. 144 61

Desflurane (difluoromethyl 1-fluoro 2,2,2-trifluoroethyl ether: CF2-H-O-CFH-CF3) is a potent inhalation anesthetic agent being investigated for possible clinical use. The authors examined the effects of this agent on normal swine and those from a special breeding program that were considered purebred for susceptibility to malignant hyperthermia (MH). Animals were exposed to 1 or 2 MAC or both doses of desflurane and observed for changes in end-tidal CO2, arterial blood gases, lactate, catecholamines, core temperature, blood pressure, and heart rate. All normal swine tolerated exposure to desflurane without clinical signs of MH, but significant changes in heart rate and blood pressure were noted. In contrast, of six MH susceptible swine tested, two had unequivocal MH reactions to deflurane, defined by significant increases of end-tidal CO2 (greater than 50 mmHg), an increase in PaCO2 (greater than 70 mmHg), a decrease in blood pH (less than 7.30), an increase in blood lactate concentration, and an increase in core temperature. Two other susceptible swine showed equivocal signs of MH but not until desflurane had been administered for 40-60 min. Finally, two other susceptible swine showed no signs of MH after 60 min of exposure to 2 MAC desflurane. These latter four animals all developed episodes of MH immediately after intravenous succinylcholine (2 mg/kg). The increased PaCO2, blood lactate concentrations, and temperature, and the decrease in pH induced by desflurane, were successfully treated with dantrolene and supportive measures. All surviving animals were biopsied 1 to 2 weeks after the exposure to desflurane for in vitro contracture testing to confirm MH susceptibility.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Desflurane is a trigger of malignant hyperthermia in susceptible swine. 190 Mar 98

Clinical uses of calcium channel blockers are expanding. In addition to the established uses in patients with arrhythmias, angina pectoris or hypertension, newer and to some extent investigational uses indicate widespread application. For instance, their use has been reported in hypertrophic cardiomyopathy and cold cardioplegia, as well as in pulmonary hypertension, antiplatelet therapy, asthma, achalasia and oesophageal spasm, increased intraocular pressure and in cerebral vasospasm. Their use in obstetrical practice has been proposed. Thus, the presentation of a patient who is treated with calcium channel blockers and who requires anaesthesia will become more common. Calcium channel blockers may, under certain circumstances, potentiate haemodynamic and MAC depressive effects of inhalation agents. There is also evidence that the effects of neuromuscular blocking agents may be potentiated. The anaesthetist should be aware that the potential for interactions exists with digoxin, propranolol, quinidine, theophylline or dantrolene. Of interest and some significance are the anaesthetic implications of pathophysiological alterations that can be induced by calcium channel blockers, by affecting lower oesophageal tone, intracranial hypertension, bronchomotor tone (asthma), muscular dystrophy, neuromuscular function, hypoxic pulmonary vasoconstriction, malignant hyperthermia, inhibition of platelet aggregation and hyperkalemia. Despite these significant potential anaesthetic implications and because, at this time, in some instances withdrawal has clearly demonstrated increase in the signs of myocardial ischaemia, it would not seem necessary to recommend preoperative discontinuation of calcium channel blocker medication in patients presenting for anaesthesia. It is, however, appropriate that there is a high index of awareness of potential problems, unless there is some modification in inhalation anaesthetic concentrations and neuromuscular blocker dosage. Monitoring of cardiovascular and neuromuscular functions is essential. Calcium channel blockers would appear to be currently the drugs of choice for angina pectoris, arrhythmias or hypertension in patients with associated chronic obstructive pulmonary disease.
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PMID:Anaesthetic implications of calcium channel blockers. 286 80

Sevoflurane may be an interesting substance for paediatric anaesthesia due to its combination of a very low blood-gas partition coefficient and non-pungency. This review discusses the status of sevoflurane in paediatric anaesthesia on the basis of studies published so far. The blood-gas partition coefficient of sevoflurane in children is 0.66, and hence markedly lower than those of isoflurane (1.25) and halothane (2.26) [15]. Induction of anaesthesia with sevoflurane/N2O is slightly shorter compared to halothane/N2O (Table 1) [4]. During induction of anaesthesia, sevoflurane/O2 is more often associated with excitement (35%) than sevoflurane/N2O (5%) and halothane/N2O (5%) [25]. Seizure-like movements in one case [1] and electrically generalised but clinically silent seizure activity in two cases [12] may raise the question of seizure-inducing effects of sevoflurane. However, up to now there is no clinical evidence of epileptogenic effects of sevoflurane. The MAC50 in neonates and infants 1-6 months of age is 3.3 vol% [14]; in infants 6-12 months and children 1-12 years of age it is 2.5 vol.% [14]. Sixty per cent N2O decreases the MAC50 of sevoflurane and desflurane by only 20%-25% [3, 14]. In contrast, 60% N2O decreases the MAC50 of halothane in children by 60% [16]. Thus, the MAC-reducing effect of N2O in children appears to be attenuated in the presence of less soluble inhalation anaesthetics. Sevoflurane has a similar low incidence of airway irritation as halothane and provides a smooth induction (Fig. 2) [4]. Haemodynamics during sevoflurane anaesthesia may be somewhat more stable compared to halothane. Serum fluoride levels increase rapidly when sevoflurane is administered, but decrease shortly after discontinuation [4]. Mean maximum levels reported are about 20 mumol/l and are of no concern for renal function. A study with mivacurium indicates more pronounced muscle relaxation by sevoflurane compared to halothane [9]. Sevoflurane may induce malignant hyperthermia. Emergence from sevoflurane anaesthesia is significantly more rapid than after halothane anaesthesia (Table 1); however, it is associated with more restlessness and agitation, probably due to the earlier perception of pain [4]. The incidence of postoperative nausea and vomiting after sevoflurane anaesthesia is comparable to that after halothane (Table 2). Sevoflurane may be a user-friendly alternative to halothane and is more preferred by children than halothane [32]. The status of sevoflurane in paediatric anaesthesia will depend on several factors: its own benefit/risk-ratio, a possible re-evaluation of the known risks of halothane and the financial limitations of the hospitals.
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PMID:[Sevoflurane in pediatric anesthesia]. 877 99

Inhalational anaesthesia is the most common anaesthesia technique in paediatric anaesthesia worldwide. Up to now the standard anaesthetic used is halothane. Because halothane is tolerated in the upper airways without side effects it is well suited for the inhalational induction of anaesthesia. However, halothane exerts side effects on the hepatic and the cardiovascular system. This review focuses on the replacement of halothane by sevoflurane in paediatric anaesthesia. Apart from its favorable pharmacological properties sevoflurane is also superior because of economical considerations. The following conclusions are drawn: (1) Halothane and sevoflurane do not cause irritations of the airways and are thus suitable for an inhalational induction. Sevoflurane should be administered in oxygen/nitrous oxide during induction of anaesthesia to reduce excitation. (2) The MAC values of sevoflurane are age dependent. In contrast to adult patients the MAC values of sevoflurane are only decreased by 20 to 25% in paediatric patients. The end-tidal concentration of sevoflurane necessary for intubation or insertion of a laryngeal mask is 2 to 4 Vol.%. (3) The blood/gas partition coefficient of sevoflurane is low, resulting in shorter induction times with sevoflurane compared to halothane. The so called priming technique with 8 Vol.% of sevoflurane results in shorter induction times. Consequently, times to recovery and psycho-motor functions are favourable for sevoflurane compared to halothane in paediatric patients. However, shorter recovery times lead to earlier perception of postoperative pain, requiring adequate pain management. (4) The hemodynamic stability after administration of sevoflurane is favourable to that after halothane in paediatric patients, leading to significantly less bradycardia. (5) In paediatric patients no negative effects on kidney function have been observed after administration of sevoflurane. There is no scientific basis for organotoxic effects, thus sevoflurane is suitable for low-flow and minimal-flow anaesthesia. (6) The duration of the action of muscle relaxants is increased to a greater extent in presence of sevoflurane compared to halothane. Consequently, the total dose of muscle relaxants can be reduced using sevoflurane. (7) Similar to the established inhalational anaesthetics sevoflurane triggers malignant hyperthermia (MH) and must not be used in patients in which MH is suspected or in which a predisposition for MH is known.
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PMID:[Sevoflurane in pediatric anesthesia. Malignant hyperthermia]. 989 80