Malignant hyperpyrexia in the cat.
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Decamethonium and succinylcholine were used to study the effects of depolarizing muscle relaxants on serum potassium in 60 patinets, free of neuromuscular disease, during major orthopedic surgery. Significant increases in serum K+ were found after administration of decamethonium or succinylcholine in the usual clinical doses. The abnormal elevations of serum K+ found in patients with burns, massive trauma, or muscle denervation are thus accentuations of the process that occurs in normal man following use of these depolarizing drugs. The administration of any depolarizing agent to these abnormal patient groups would, therefore, appear contraindicated.
The effects of repeated doses of decamethonium or succinylcholine in muscles of the cat, dog, and rabbit have been examined. In particular, the relation of degree of neuromuscular block to intensity of the electrical change at the end-plate region has been found to be more consistent when the peak spatial gradient of depolarization is used as a measure of electrical effect than when the peak depolarization is used; the reason for this difference is discussed. A plot of twitch height against electrical change provides a convenient frame of reference for following the development of phase II block quantiatively. Examples presented show that the extent and kinetics of phase II block can vary considerably among species or among muscles in a given species.
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The effects of lithium carbonate on the responses to five neuromuscular blocking agents were evaluated in dogs anesthetized with halothane (1 per cent) and N2O (60 per cent) in O2. Latency (time from first twitch-height depression to maximal blockade), maximal twitch-height depression, and times to return to 50 per cent and 100 per cent control twitch tension were measured before and after intravenous infusion of lithium carbonate (1 mg/kg/min for one hour) during neuromuscular blockades produced by succinylcholine, decamethonium, gallamine, d-tubocurarine, or pancuronium. Lithium prolonged the latencies of neuromuscular blockades produced by 0.1 mg/kg succinylcholine and 0.1 mg/kg decamethonium by 248.1 per cent and 49.0 per cent, respectively, but had no effect on latency produced by 0.02 mg/kg pancuronium. The times for return to 50 per cent of control twitch height were prolonged by 69.5, 40.0, and 120.1 per cent, respectively. Lithium had no effect on latency or duration of blockades produced by 0.15 mg/kg d-tubocurarine and 0.6 mg/kg gallamine, but enhanced maximal twitch-height depressions produced by 0.9 mg/kg gallamine and 0.02 mg/kg pancuronium by 22.9 and 9.9 per cent, respectively. Twitch tensions decreased 5-10 per cent over three hours in three dogs receiving lithium infusion without relaxants. Twitch tension was depressed 0-2 per cent in three dogs after five hours of anesthesia in the absence of lithium or relaxants. Lithium prolonged the time required for neostigmine to reverse neuromuscular blockade produced by pancuronium in two of three dogs from a mean of 60 seconds to 135 seconds.
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The Arrhenius hypothesis suggests that change in temperature has a less marked effect on the rate of physical processes than on biological reactions. We have investigated the process underlying recovery from neuromuscular block in man by studying the effect of cooling on the rate of recovery from depolarising and non-depolarising block. Vecuronium, rocuronium and decamethonium (C10) neuromuscular block were investigated using the isolated forearm technique on awake human volunteers. In these experiments, one arm was cooled whilst the other was used as control. Moderate hypothermia decreased the rate of recovery from all three agents, but this was significantly less marked with the depolarising drug. The mean Q10 (the anticipated change in rate of a reaction across of 10 degrees C temperature gradient) of the rate of recovery for vecuronium was 3.21, rocuronium 2.86 and decamethonium 1.29. This suggests a different process in the recovery of these two types of drug. According to the Arrhenius hypothesis this would suggest that the recovery from non-depolarising drugs is likely to involve a biochemical mechanism and that recovery from decamethonium is controlled by a physical process.
1 The tetanic and single twitch responses to the adductor pollicis muscle were used to study the neuromuscular effects of repeated dosage of decamethonium in nine anaesthetized patients. 2 In two of three patients who received the same total dose of decamethonium in three separate series of injections, blockade of the tetanic response was less after the third administration. In the third patient tachyphylaxis was evident after the second series of injections. 3 In three other patients, tachyphylaxis occurred after the second series of injections when the total dose of decamethonium administered was at least twice that given on the first occasion. 4 In terms of tachyphylaxis the single twitch response followed a similar pattern to that of the tetanic response. 5 Once tachyphylaxis had developed, neuromuscular block of the tetanic response by decamethonium was antagonised by neostigmine (2.5 mg) and enhanced by 2% halothane. 6 In contrast, in three patients who were not exposed to more than one series of injections of decamethonium, and presumably therefore before tachyphylaxis had developed, neuromuscular block of the tetanic response was potentiated by neostigmine. Under these circumstances recovery was unaffected by halothane. 7 Thus, when tachyphylaxis occurs with decamethonium the characteristics of the block change to resemble those of the competitive neuromuscular blocking agents; these findings could be of importance in clinical anaesthesia.
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