MALIGNANT HYPERPYREXIA AND ANAESTHESIA

Brit. J. Anaesth. (1970), 42, 1021

MALIGNANT HYPERPYREXIA AND ANAESTHESIA Two Case Reports BY P. M. E. DRURY AND A. A. GILBERTSON SUMMARY

Two cases of malignant hyperpyrexia during anaesthesia occurred in Liverpool during one month in 1969.

abscess less than 1 cm diameter in the adjacent temporal lobe, and the stomach contained fresh blood. Otherwise nothing abnormal was found. CASE REPORT N O . 2

CASE REPORT N O . 1

The patient was a 38-year-old policeman. In September 1966 he had a modified radical mastoidectomy for chronic suppurative otitis media. During his stay in hospital he had three anaesthetics; for examination of ears, for the mastoidectomy, and for a change of pack. The anaesthetic sequence on the first occasion is unknown. On the second occasion he received propanidid, suxamethonium, halothane, nitrous oxide, propartolol, and lignocaine (4 per cent spray), and on the third, propamdid alone. He remained well until April 196S when he developed erythema nodosum. This subsided in a few weeks and the ESR returned to normal. In May 1969 following two further episodes of his ear infection he was readmitted for radical mastoidectomy. Apart from his infected mastoid his general condition was excellent. The anaesthetic sequence on this occasion was: thiopentone 500 mg, suxamethonium 50 mg, nitrous oxide, oxygen and halothane, following premedication with pithidine and atropine. The operation lasted approximately 90 minutes and nothing unusual was noted until just before skin closure, when it was observed that he had a tachycardia (180 beats/mm) and was pjripherally cyanosed. At the end of the operation, breathing 100 p:r cent oxygen he was deeply unconscious, with pinpoint pupils and gasping respirations with a marked tracheal tug. He felt very hot and dry and the axillary temperature proved to be 109 °F. Surface cooling was started and 8.4 per cent sodium bicarbonate solution was given by intravenous drip. The e.og. was monitored. Fifteen minutes later the heart rate was seen to slow suddenly, and asystole quickly followed. External cardiac massage was started. Following intracardiac adrenaline and intravenous isoprenaline, palpable pulses returned but were maintained for only 3 minutes. There was no further response to drug therapy. The temperature, which had reached a maximum of 110°F, now fell to 107*F. Resuscitation was abandoned after 75 minutes. Muscular rigidity was not a feature of this case. At postmortem examination there was a small area of local meningitis at the operation site, a small cerebral

A 15-year-old boy sustained a compound fracture of his radius and ulna whilst playing football. Hi3 only previous illness had been a sinus infection for which he had had an antral wash-out under general anaesthesia. This anaesthetic had been uneventful. Anaesthesia had been induced with a barbiturate, and endotracheal intubation was aided by suxamethonium. Maintenance was by nitrous oxide, oxygen and halothane. Postoperatively the patient was noted to have b:en "wheezy" but a short period of oxygen inhalation was all that was required. An anaesthetic had also been administered for dental extractions. The method used is not known, but recovery was uneventful. General anaesthesia was administered for open reduction and fixation of his fractures. Premedication consisted of pethidine 25 mg and atropine 0.6 mg. Methohexitone 60 mg and suxamethoniuni 75 mg were used to induce anaesthesia and to aid intubation. Anaesthesia was maintained using nitrous oxide 6 l./min, oxygen 2 l./min and halothane 1 per cent. Cyanosis was noted immediately and after checking that both lungs were being inflated, the oxygen concentration was increased to 70 per cent which temporarily improved the patient's colour. Within 10 minutes cyanosis was again noted and a further 50-mg dose of suxamethonium was given so that the endotracheal rube could be replaced. This time the relaxant appeared ineffective and the patient was re-intubated with extreme difficulty. Spontaneous respiration returned after 5 minutes but peripheral oxygenation was again poor and the electrocardiogram showed supraventricular tachycardia (180 beats/min). At this stage, 20 minutes after induction, halothane was discontinued and tubocurarine (35 mg) was injected and intermittent positive pressure ventilation started using 50 per csnt oxygen with nitrous oxide. As oxygenation now appeared normal and the systolic blood pressure was 120 mm H g a tourniquet was applied and the operation started. P. M. E. DKURY, M.B., B.CHIR., F.F.A.R.C.S., United Liverpool Hospitals; A. A. GILBERTSON, M.B., CH.B.,

F.F.A.R.C.S., Sefton General Hospital, Liverpool.

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Two cases of malignant hyperpyrexia occurring during general anaesthesia are presented and some illustrative features discussed. Suxamethonium and halothane were both used, but bad been used on a previous occasion without incident. Support is given for the formation of a central investigating committee.

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However, 50 minutes after induction the heart arrested. Resuscitation was only temporarily successful. The temperature was found to be 109°F and there was marked hypertonicity of all muscles except those distal to the tourniquet Compliance was so poor that adequate inflation of the lungs was difficult. Resuscitation was finally abandoned 2 hours 40 minutes after induction of anaesthesia. By this time, in spite of attempts at cooling by ice and wet blankets, the rectal temperature was 110°F. Intestinal bleeding occurred terminally. The muscles of the right arm became rigid when the tourniquet was removed after death. DISCUSSION

REFERENCES

Britt, B. A., and Gordon, R. A. (1969). Three cases of malignant hyperpyrexia with special consideration of management. Caned. Anaesth. Soc. J.y 16, 99. Locher, W. G., and Kalow, W. (1969). Hereditary aspects of malignant hyperthermia. Canad. Anaesth. Soc. J., 16, 89. Davies, R. M , Packer, K. T., Titel, J., and Whitmarsh, V. (1969). Malignant hyperpyrexia: two case reports. Brit. J. Anaesth., 41, 703. Editorial (1966). Malignant hyperpyrexia during anaesthesia. Canad. Anaesth. Soc. J., 13, 415.

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Most of the reports of malignant hyperpyrexia associated with anaesthesia have come from North America; for example, Britt and Gordon (1969) reviewed 115 cases. There appear to be only five other cases reported from Britain (Hawthorne, Richardson and Whitfield, 1968; Murray and Williams, 1969; Davies et al., 1969). Our two cases occurred in Liverpool within one month. It is not known whether this reflects the true frequency of the condition. It may be that other cases have not been recognized or reported. The characteristic features of the condition have been summarized elsewhere (Editorial, 1966; Leading article, 1968), and are well demonstrated in these case reports. The excessively high temperature (reaching 110°F in both cases), accompanied by pronounced tachycardia and peripheral cyanosis, despite apparently adequate ventilation, is pathognomonic. The condition arises unexpectedly in apparently fit patients, often with a history of previous uneventful anaesthesia. Brit, Locher and Kalow (1969) in their review argue the case for an inherited tendency. The family history in the present cases was negative. It is known that three close relatives of the second case have experienced uneventful anaesthesia. Muscle rigidity is a frequent, though not invariable, finding in this condition. It was not noted in the first case. A noteworthy feature of the second case was the absence of rigidity in the arm distal to a tourniquet, the arm becoming rigid when the tourniquet was released. This has also been commented on by Satnick (1969). Suxamethonium and halothane were administered to both these patients. One or both of these drugs have been used in the majority of the reported cases. There is experimental evidence (Hall et al., 1966; Harrison et al., 1968) to sup-

port the theory that these drugs may trigger a hyperpyrexic response in susceptible subjects. Nevertheless, both patients received the combination on a previous occasion without incident. It is natural to search for common factors in the anaesthetic technique. A point that has not been emphasized previously is that the reported cases of malignant hyperpyrexia invariably received an antisialagogue drug as part of the premedication—usually atropine but sometimes hyoscine. It is known that large doses of these drugs can cause pyrexia, probably by suppression of sweating. Absence of sweating despite the very high temperature was a notable feature of both these cases. The results of treatment of this condition are disappointing and the mortality is high, except in small children who have a more favourable surface area for cooling. Surface cooling appears inadequate to lower the temperature, and it is not known whether other methods, such as gastric cooling or extracorporeal circulation, would be more effective. Nevertheless, in two cases where the temperature was successfully lowered (Hawthorne, Richardson and Whitfield, 1968; Britt and Gordon, 1969) the patients became hypothermic before death. It was not found possible to investigate these cases in any detail, so that we have nothing to contribute in the sphere of aetiology. Recently Isaacs and Barlow (1970) have reported abnormally high levels of serum creatine phosphokinase in relatives of affected patients over three generations. It may be that further investigations of this kind will throw more light on this mysterious condition. We would support the suggestion of Davies and associates (1969) that a central committee of reference should be set up to collect more evidence.

MALIGNANT HYPERPYREXIA AND ANAESTHESIA

L'HYPERPYREXIE MALJGNE ET L'ANESTHESIE: DESCRIPTION DE DEUX CAS SOMMAIRE

Les auteurs presentent deux cas d'hyperpyrexie maligne, survenue au cours d'une anesthesie gene'rale et discutent quelques caracteristiqucs illustratives. Le suxamethonium et rhalothane ont tous deux 6vi utilises, mais il en fut de meme a une occasion prec&iente sans incidents. Un comity central d'investigation est propose. MALIGNE HYPERPYREXIE UND ANASTHESIE: ZWEI FALLBERICHTE ZUSAMMENFASSUNG

Zwei Falle von maligner Hyperpyrexie, die unter der AnSsthesie auftraten, werden prasentiert und einige bezeichnende Merkmale diskutiert. In beiden Fallen wurd:n Suxamethonium und Halotban verabfolgt, die jedoch bei einer fruheren Gelegenheit bereits ohne Zwischenfall angewendet worden waren. Die Bildung eines zentralen Untersuchungskommittees wird angeregt.

BOOK REVIEW Techniques in Clinical Physiology: a survey of measurements in anesthesiology. Edited by J. Weldon Bellville, M.D., and Charles S. Weaver PH.D. Published by Collier-Macmillan Ltd., London. Pp. 532; indexed; illus. Price £10. Since the introduction of the third part into the primary examination for the Fellowship in Anaesthesia, potential candidates have complained about the difficulty of obtaining information about clinical measurement. This difficulty no longer exists. In Techniques m Clinical Physiology Dr Weldon Bellville and his associate editor Dr Weaver have produced an outstanding book which will undoubtedly serve as a standard text and reference for many years to come. In this connection perhaps editors of such books should reflect on the fact that many readers do not have ready access to medical libraries and that as in this case the problem of viewing the many special reports cited in the bibliography is serious. Since most bibliographies are already highly selective it is surely only a matter of directing the selection. To assist them in the preparation of the text the editors have enlisted a panel of contributors nearly all of whom are or have been directly associated with the Department of Anesthesiology in Stanford University School of Medicine and their contributions illustrate the wide range of that department's activities. The book is subtitled "A survey of measurements in anesthesiology" and it is therefore rather disappointing to find that many aspects of clinical measurement use-

ful in anaesthetic practice have been omitted. The measurement of neuromuscular activity is ignored; venous occlusion plethysmography is not mentioned nor is central venous pressure; methods of measuring oxygen consumption are not described and the absence of any information on electroencephalography is an unfortunate omission. In fairness, the editors have not claimed that the book is comprehensive but with a volume in this price range and with such a subtitle the reader might have expected a fuller survey. On the credit side, what is done is well done. It is perhaps unfair to select individual chapters for comment but the introductory chapter on basic electronics sets the tone for the whole book and the chapters on gas analysis and gas chromatography are particularly clear and concise. It is a matter of conjecture whether or not a book of this type should devote nearly 25 per cent of the text to the application of computers to anaesthesia, but it does serve to emphasize the extent to which they have become an integral part of Hinirai measurement in the United States. The failure to follow suit on this side of the Atlantic may well cost us dear in the years to follow. The book is beautifully produced and a delight to handle; the print is dear and the illustrations are excellent Despite its limitations this is compulsory reading for all concerned with clinical measurement and certainly is not restricted to the examination candidate; it should be on every anaesthetist's bookshelf. J. P. Payne

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Hall, I. W., Woolf, N., Bradley, J. W. P., and Jolly, D. W. (1966). Unusual reaction to suxamethonium chloride. Brit. med. J., 2, 1305. Harrison, G. G., Biebuyck, J. F., Terblanche, J., Dent, D. M., Hickman, R., and Saunders, S. J. (1968). Hyperpyrexia during anaesthesia. Brit. med. J., 3, 594. Hawthorne, A. T., Richardson, M. E., and Whitfield, G. T. (1968). Fulminating hyperthermia and general anaesthesia. Brit. med. J., 4, 750. Isaacs, H., and Barlow, D. B. (1970). Malignant hyperpyrexia during anaesthesia: possible association with subclinkal myopathy. Brit. med. J., 1, 275. Leading article (1968). Malignant hyperpyrexia. Brit, med. J., 3, 69. Murray, B. R. P., and Williams, P. A. D. (1969). Malignant hyperpyrexia during anaesthesia for colectomy. Brit. med. J., 1, 488. Satnick, J. H. (1969). Hyperthermia under anesthesia with regional muscle flaccidity. Anesthesiology, 30, 472.

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