Br. J. Anaesth. (1975), 47,419
CORRESPONDENCE Trimm and Woolf, 1972; Harrison, 1973) and has been used with satisfactory results in the anaesthesia of a Sir,—Suxamethonium is a depolarizing agent which patient with a history of hyperthermia (Judelman and results initially in muscle fasciculations followed by Pirie, 1974). We have investigated the effects of Althesin on the neuromuscular blockade. However, it has been observed in a family inheriting both dystichiasis and atypical development of MH in pigs of the Pietrain breed which esterase that the injection of suxamethonium in two have a reliable MH response to the triggering effects of atypical homozygote children was not followed by muscle suxamethonium with or without halothane. Anaesthesia fasciculations and rapidly resulted in a profound and was induced in five animals using Althesin 5 mg/kg Lv. The trachea was intubated; ventilation was with nitrous prolonged neuromuscular blockade (Baraka, 1975). This observation was noted also in three atypical oxide and oxygen. Halothane (3%) was introduced into homozygote adults from other families inheriting atypical the mixture within 20 min of induction of anaesthesia. esterase activity. The patients were undergoing different One pig developed MH immediately on exposure to surgical procedures, notably, cholecystectomy, Caesarean halothane and died. Another two showed a mild response section or exploratory laparotomy. The serum chol- with an increase in muscle temperature and heart rate inesterase activity in the five patients ranged from 10% and two did not react. These four animals were then to 16% of normal and the dibucaine numbers ranged given suxamethonium 50 mg. Three reacted and died after developing the characteristic metabolic changes seen from 20 to 30. in MH and rapid increases in temperature. On the Suxamethonium depolarizes the endplate. This initiates following day anaesthesia was induced widi halothane, repetitive action potentials which are manifest as muscle nitrous oxide oxygen in the surviving pig. It fasciculations. However, when depolarization exceeds a developed MH and within 5 min and died. Thus Althesin critical level, neuromuscular blockade results. The critical anaesthesia provided level of depolarization at which a muscle becomes electri- of the five animals. protection against MH in only one cally inexcitable is about —52 mV (Jenerick and Gerard, The two animals which showed no adverse response to 1953). In patients with homozygote atypical esterase activity, halothane had been fitted with indwelling jugular cannulae there is virtually no hydrolysis of suxamethonium (Kalow, under Althesin anaesthesia on the day before the experi1959) and the endplate will be flooded by suxamethonium. ment. This meant that induction of anaesthesia with It appears that in such cases, the critical level of Althesin on the day of the experiment was not associated depolarization necessary to produce block is reached very with the stress of restraint and venepuncture which the rapidly and that the stage of fasciculations is bypassed. other pigs suffered. Furthermore, halothane was given Since there are other factors which may inhibit muscle widiin 5 min of induction of anaesthesia when the animals fasciculations after suxamethonium, it can be concluded were still deeply anaesthetized with Althesin. It has been shown that Pietrain pigs are particularly that the absence of fasciculations provides only tentative evidence that the patient may be an atypical homozygote. sensitive to stress and respond with a massive release of However, the appearance of fasciculations excludes the catecholamines. This also occurs in MH and is of central importance in the reaction (Lister, Hall and Lucke, 1974). presence of this abnormality. Classically, anaesthetists were taught to give non- Any procedure, therefore, which reduces the release of depolarizing muscle relaxants only after witnessing the catecholamines or inhibits their effect on the adrenergic signs of recovery from suxamethonium blockade. However, receptors might be expected to provide some degree of this practice may result in the patient exhibiting a period protection. Unfortunately, we did not measure plasma of straining and coughing. For cliniml purposes, whenever catecholamines in the experiments reported here. It is the thiopentone-suxamethonium sequence is used for likely, however, that their concentration was very low inducing anaesthesia and is followed by muscle fascicula- in the animals in which anaesthesia was induced via tions, it is my belief that the non-depolarizing relaxant an indwelling cannula without the need for restraint. That Althesin may provide some degree of protection can be administered without waiting for signs of recovery from suxamethonium. This practice has been in use for is not disputed, particularly if it is given in the high 1 yr without any problems of reversal of neuromuscular doses recommended by Harrison (1973). However it is possible that deep barbiturate anaesthesia will produce a blockade. similar effect. ANIS BARAKA J. N. LUCKE Beirut, Lebanon ABSENCE OF SUXAMETHONIUM FASCICULATIONS IN PATIENTS WITH ATYPICAL PLASMA CHOLINESTERASE
Baraka, A. (1975). Potentiation of suxamethonium blockade by neostigmine in patients with atypical cholinesterase. Br. J. Anaesth., 47, 416. Jenerick, H. P., and Gerard, R. W. (1953). Membrane potential and threshold of single muscle fibers. J. Cell. Physiol., 42, 79. Kalow, W. (1959). The distribution, destruction and elimination of muscle relaxants. Anesthesiology, 20, 505.
Bristol
ALTHESm AND MALIGNANT HYPERTHERMIA
Sir,—Althesin has been reported to have a protective effect against malignant hyperthermia (MH) in pigs (Hall,
REFERENCES
Hall, L. W., Trimm, C. M., and Woolf, N. (1972). Further studies of porcine malignant hyperthennia. Br. Med. J., 2, 145. Harrison, G. G. (1973). Althesin and malignant hyperpyrexia. Br. J. Anaesth., 45, 1010. Judelman, H., and Pirie, D. H. (1974). Anaesthesia of a patient with previous malignant hyperthermia. Br. J. Anaesth., 46, 519. Lister, D., Hall, G. M., and Lucke, J. N. (1974). Catecholamines in suxamethonium induced hyperthermia in Pietrain pigs. Br. J. Anaesth., 46, 803.
Downloaded from http://bja.oxfordjournals.org/ at Simon Fraser University on June 4, 2015
D. LISTER REFERENCES
CORRESPONDENCE Trimm and Woolf, 1972; Harrison, 1973) and has been used with satisfactory results in the anaesthesia of a Sir,—Suxamethonium is a depolarizing agent which patient with a history of hyperthermia (Judelman and results initially in muscle fasciculations followed by Pirie, 1974). We have investigated the effects of Althesin on the neuromuscular blockade. However, it has been observed in a family inheriting both dystichiasis and atypical development of MH in pigs of the Pietrain breed which esterase that the injection of suxamethonium in two have a reliable MH response to the triggering effects of atypical homozygote children was not followed by muscle suxamethonium with or without halothane. Anaesthesia fasciculations and rapidly resulted in a profound and was induced in five animals using Althesin 5 mg/kg Lv. The trachea was intubated; ventilation was with nitrous prolonged neuromuscular blockade (Baraka, 1975). This observation was noted also in three atypical oxide and oxygen. Halothane (3%) was introduced into homozygote adults from other families inheriting atypical the mixture within 20 min of induction of anaesthesia. esterase activity. The patients were undergoing different One pig developed MH immediately on exposure to surgical procedures, notably, cholecystectomy, Caesarean halothane and died. Another two showed a mild response section or exploratory laparotomy. The serum chol- with an increase in muscle temperature and heart rate inesterase activity in the five patients ranged from 10% and two did not react. These four animals were then to 16% of normal and the dibucaine numbers ranged given suxamethonium 50 mg. Three reacted and died after developing the characteristic metabolic changes seen from 20 to 30. in MH and rapid increases in temperature. On the Suxamethonium depolarizes the endplate. This initiates following day anaesthesia was induced widi halothane, repetitive action potentials which are manifest as muscle nitrous oxide oxygen in the surviving pig. It fasciculations. However, when depolarization exceeds a developed MH and within 5 min and died. Thus Althesin critical level, neuromuscular blockade results. The critical anaesthesia provided level of depolarization at which a muscle becomes electri- of the five animals. protection against MH in only one cally inexcitable is about —52 mV (Jenerick and Gerard, The two animals which showed no adverse response to 1953). In patients with homozygote atypical esterase activity, halothane had been fitted with indwelling jugular cannulae there is virtually no hydrolysis of suxamethonium (Kalow, under Althesin anaesthesia on the day before the experi1959) and the endplate will be flooded by suxamethonium. ment. This meant that induction of anaesthesia with It appears that in such cases, the critical level of Althesin on the day of the experiment was not associated depolarization necessary to produce block is reached very with the stress of restraint and venepuncture which the rapidly and that the stage of fasciculations is bypassed. other pigs suffered. Furthermore, halothane was given Since there are other factors which may inhibit muscle widiin 5 min of induction of anaesthesia when the animals fasciculations after suxamethonium, it can be concluded were still deeply anaesthetized with Althesin. It has been shown that Pietrain pigs are particularly that the absence of fasciculations provides only tentative evidence that the patient may be an atypical homozygote. sensitive to stress and respond with a massive release of However, the appearance of fasciculations excludes the catecholamines. This also occurs in MH and is of central importance in the reaction (Lister, Hall and Lucke, 1974). presence of this abnormality. Classically, anaesthetists were taught to give non- Any procedure, therefore, which reduces the release of depolarizing muscle relaxants only after witnessing the catecholamines or inhibits their effect on the adrenergic signs of recovery from suxamethonium blockade. However, receptors might be expected to provide some degree of this practice may result in the patient exhibiting a period protection. Unfortunately, we did not measure plasma of straining and coughing. For cliniml purposes, whenever catecholamines in the experiments reported here. It is the thiopentone-suxamethonium sequence is used for likely, however, that their concentration was very low inducing anaesthesia and is followed by muscle fascicula- in the animals in which anaesthesia was induced via tions, it is my belief that the non-depolarizing relaxant an indwelling cannula without the need for restraint. That Althesin may provide some degree of protection can be administered without waiting for signs of recovery from suxamethonium. This practice has been in use for is not disputed, particularly if it is given in the high 1 yr without any problems of reversal of neuromuscular doses recommended by Harrison (1973). However it is possible that deep barbiturate anaesthesia will produce a blockade. similar effect. ANIS BARAKA J. N. LUCKE Beirut, Lebanon ABSENCE OF SUXAMETHONIUM FASCICULATIONS IN PATIENTS WITH ATYPICAL PLASMA CHOLINESTERASE
Baraka, A. (1975). Potentiation of suxamethonium blockade by neostigmine in patients with atypical cholinesterase. Br. J. Anaesth., 47, 416. Jenerick, H. P., and Gerard, R. W. (1953). Membrane potential and threshold of single muscle fibers. J. Cell. Physiol., 42, 79. Kalow, W. (1959). The distribution, destruction and elimination of muscle relaxants. Anesthesiology, 20, 505.
Bristol
ALTHESm AND MALIGNANT HYPERTHERMIA
Sir,—Althesin has been reported to have a protective effect against malignant hyperthermia (MH) in pigs (Hall,
REFERENCES
Hall, L. W., Trimm, C. M., and Woolf, N. (1972). Further studies of porcine malignant hyperthennia. Br. Med. J., 2, 145. Harrison, G. G. (1973). Althesin and malignant hyperpyrexia. Br. J. Anaesth., 45, 1010. Judelman, H., and Pirie, D. H. (1974). Anaesthesia of a patient with previous malignant hyperthermia. Br. J. Anaesth., 46, 519. Lister, D., Hall, G. M., and Lucke, J. N. (1974). Catecholamines in suxamethonium induced hyperthermia in Pietrain pigs. Br. J. Anaesth., 46, 803.
Downloaded from http://bja.oxfordjournals.org/ at Simon Fraser University on June 4, 2015
D. LISTER REFERENCES
