Hyperpyrexia During Anaesthesia

Harrison, Gillian; Biebuyck, Julien F.; Terblanche, J.; Dent, D. M.; Hickman, Robert O.; Saunders, S. J.

doi:10.1136/bmj.3.5618.594

Cited by 70 publications

(13 citation statements)

References 8 publications

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“…In most of these unfortunate incidents the anaesthetics used were volatile fluorinated hydrocarbon agents, halothane or methoxyfluorane, but they have also occurred with other anaesthetics (Brown, 1954;Saidman, Havard & Eger, 1964;Cullen, 1966;Davies & Graves, 1966;Hogg & Renwick, 1966;Lavoie, 1966;Relton, Creighton, Johnston, Pelton & Conn, 1966;Thut & Davenport, 1966;Purkis, Horrelt, de Young, Fleming & Langley, 1967;Stephen, 1967;Wilson, Dent, Tralber, McCoy & Allen, 1967;Hawthorne, Richardson & Whitfield, 1968). Recently, lethal pyrexias have also been described in about 17% of pigs anaesthetized with halothane (Harrison, Biebuyck, Terblanche, Dent, Hickman & Saunders, 1968). In none of the present experiments on cats did halothane anaesthesia alone produce pyrexia.…”

Section: Discussionmentioning

confidence: 99%

Effects of monoamine oxidase inhibitors on the hypothermia produced in cats by halothane

Summers

1969

British J Pharmacology

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1. In cats, the effects of intraperitoneal injections of four monoamine oxidase (MAO) inhibitors, tranylcypromine, pheniprazine, pargyline, and nialamide, were examined on rectal temiperature and on the hypothermia during anaesthesia produced by a 2 hr period of halothane inhalation. 2. A 2 hr period of halothane inhalation produced a steady fall in temperature amounting to between 20 and 3.50 C. After discontinuation of halothane inhalation, temperature quickly returned to the pre-anaesthetic level but no pyrexia developed. A peculiar stiffness of the leg muscles occurred in several experiments either at the beginning of the inhalation or after its discontinuation.3. An injection of tranylcypromine (5 mg/kg) caused a rise in rectal temperature and prevented the hypothermia of halothane anaesthesia. This effect lasted for at least 4 hr; 20 hr after the injection, halothane again caused hypothermia.4. An injection of pheniprazine (10 mg/kg) usually caused a small rise in temperature which was not sustained. Pheniprazine not only prevented the hypothermia of halothane anaesthesia during the sulbsequent 20 hr, but during the first few hours after the injection halothane inhalation actually produced a steep rise in temperature.5. An injection of pargyline (50 mg/kg) had no effect on temperature but the hypothermia due to halothane inhalation was prevented 1 hr after the injection and attenuated after 20 hr. Injection of 200 mg/kg caused a steady rise in temperature which was accelerated when halothane was administered 1 hr later.6. An injection of nialamide (10, 25 or 50 mg/kg) had no immediate effect on temperature, but pyrexia developed overnight after the two larger doses. The effect on the hypothermia due to halothane inhalation was greater 20 hr after the injection than it was after 1 to 2 hr. Twenty hours after injection of the two larger doses, halothane no longer produced hypothermia but caused a lethal rise in temperature either during or after its inhalation. 7. In rabbits, the effect on temperature of halothane inhalation varied. Either temperature rose slightly or it fell, but not as much as in cats. In one rabbit in which the inhalation had produced a transient rise, pyrexia developed 40 min after discontinuation of halothane.

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Section: Discussionmentioning

confidence: 99%

Effects of monoamine oxidase inhibitors on the hypothermia produced in cats by halothane

Summers

1969

British J Pharmacology

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“…Our experiments used skeletal muscle from a well established porcine model of MH in which affected animals are homozygous for the RyR1 R615C mutation. 25,26 Using photon correlation spectroscopy, [ 3 H]ryanodine binding and mathematical modeling, 17,24,27,28 we demonstrate that the interaction between purified RyR1 R615C channels is greatly reduced relative to wild type RyR1 (RyR1 WT ), which may lead to leaky channels at the resting state and prolonged open duration following exposure to halothane, as occurs in MH-susceptible muscle. Our findings present the first model of a direct link between failed inter-receptor coupling and a severe disease.…”

Section: Introductionmentioning

confidence: 97%

Impaired interaction between skeletal ryanodine receptors in malignant hyperthermia

et al. 2009

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Functional coupling between clustered membrane receptors has been identified as a novel mechanism to improve signaling performance in a number of physiological processes. The potential role of defective inter-receptor coupling in the pathogenesis of disease, however, has not previously been explored. Ryanodine receptors (RyRs), the primary calcium release channel of muscle, usually form ordered two-dimensional arrays in the sarcoplasmic reticulum membranes. Mutations in RyRs are known to cause a number of severe diseases both in skeletal muscle and in heart. Here we present a model demonstrating how impaired functional coupling between neighboring mutant RyR1(R615C) channels may contribute to the pharmacogenetic skeletal muscle sensitivity, malignant hyperthermia (MH). We find that purified RyR1(R615C) from MH susceptible porcine skeletal muscle shows significantly reduced oligomerization when compared to RyR1(WT), indicating a potential loss of intrinsic intermolecular control. The MH-triggering volatile anesthetic, halothane, activates RyR1(R615C) and RyR1(WT) to a similar extent, using [(3)H]ryanodine binding as a measure of activation. Modeling RyR1 array function with parameters modified to simulate the loss of functional inter-RyR coupling recapitulates the MH molecular phenotype-RyR1 channels leaky to Ca(2+) at rest and long open-times following exposure to halothane. Our work suggests that a defect in inter-RyR1 coupling is a novel direction for research into the pathogenesis of MH.

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“…In many instances an abnormal response to suxamethonium has been reported, but this has not been invariable (Cullen, 1966), and Harrison et al (1968) recorded the frequent development of hyperpyrexia in pigs without administration of this drug. In our case the response to suxamethonium was apparently normal.…”

Section: Commentmentioning

confidence: 99%

Malignant hyperpyrexia during anaesthesia for colectomy.

Murray¹,

Williams²

1969

BMJ

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Malignant hyperpyrexia associated with anaesthesia is a condition which is increasingly attracting the attention of anaesthetists and surgeons. Initially most reports came from the North American Continent (Canad. Anaesth. Soc. 7., 1966;Stephen, 1967), but it now appears that a number of cases have occurred in Britain (Brit. med. 7., 1968). The following report illustrates such a case. CASE REPORTThe patient, a 20-year-old man, was a routine list case for total colectomy and ileorectal anastomosis. He had a history of two severe attacks of typical ulcerative colitis which had responded adequately but not completely to medical treatment. Two squint operations at the age of 4 years had been performed without incident, and two siblings and both parents had operations under general anaesthesia quite uneventfully. Immediately before operation his temperature was normal and his resting pulse rate was 90.After premedication with papaveretum 20 mg. and hyoscine 0 4 mg. he was conscious and co-operative. Induction of anaesthesia at 8.50 a.m. (0 hours) with methohexitone 100 mg. and suxamethonium 75 mg. was normal and uneventful, and an endotracheal tube was passed. The action and duration of the suxamethonium were normal and the patient was allowed to breathe spontaneously while sigmoidoscopy was performed. At 20 minutes tubocurarine 45 mg. and pethidine 30 mg. were given, and his respirations were completely controlled on the East-Radcliffe ventilator with a mixture of oxygen 3 l., nitrous oxide 5 1., and halothane 0-25 %. Relaxation was complete and the operation was begun. The systolic blood pressure stabilized at 120 mm. Hg and the pulse rate at 120. An intravenous infusion of Ringer lactate solution was started.Operation and anaesthesia proceeded quite normally and uneventfully, and regular monitoring of pulse and blood pressure showed no change from the original measurements. The tachycardia was attributed to the nature of the patient's disease. At 1 hour 30 minutes the first bottle of blood (group Q rhesus-negative) was set up.At 1 hour 55 minutes the soda lime canister on the ventilator was noticed to be warmer than normal. The patient was also observed to be sweating slightly around the mouth. The pulse and blood pressure remained as before. His lips were then noted to be slightly cyanosed, and the anaesthetic equipment, tubing, and endotracheal tube were at once checked. His colour then deteriorated more generally and ventilation was continued with pure oxygen, which quickly improved his colour. He was then seen to be sweating more freely, and was for the first time felt to be quite hot.

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Hyperpyrexia During Anaesthesia

Abstract: Work in pigs has shown that malignant hyperpyrexia during anaesthesia may occur without suxamethonium having been given. A virtually constant feature in reported cases and in our own observations is that all subjects developing hyperpyrexia had received nitrous oxide and halothane.

Cited by 70 publications

References 8 publications

Effects of monoamine oxidase inhibitors on the hypothermia produced in cats by halothane

Effects of monoamine oxidase inhibitors on the hypothermia produced in cats by halothane

Impaired interaction between skeletal ryanodine receptors in malignant hyperthermia

Malignant hyperpyrexia during anaesthesia for colectomy.

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