J. R. Hood

The effect of residual receptor occupancy on sensitivity to repeated vecuronium

Cumulative dose‐response curves were obtained for vecuronium in 10 patients anaesthetised with thiopentone, enflurane and nitrous oxide using adductor pollicis mechanomyography. Five patients received vecuronium systemically, which was repeated at 100% twitch recovery to obtain initial and repeat curves. Another five patients received 0.3 mg vecuronium into an isolated forearm and at 100% recovery of this arm received vecuronium systemically to obtain simultaneous dose‐response curves in both the previously isolated and nonisolated arms. There was no significant difference between the calculated ED50 obtained after initial systemic administration [16.2 (1.7) μg.kg−1], after recovery in the previously isolated arm [14.8 (2.0) μg.kg−1] and simultaneously in the nonisolated arm [16.1 (2.9) μg.kg−1]. The ED50 obtained after repeated systemic administration was significantly reduced [8.2 (2.9) μ.kg−1]. These results suggest that the reduction in ED50 at 100% twitch recovery from systemic vecuronium is not due to residual drug at the biophase/receptor but to drug persisting in the plasma.

Sensitivity to second dose of mivacurium

The sensitivity of patients to a second dose of mivacurium has been studied following complete recovery of the twitch response after > 95% neuromuscular block produced by a systemic bolus of the drug. In further experiments we have excluded one arm from the effect of a systemic bolus ED95 dose of mivacurium for 100 s so as to obtain two different levels of neuromuscular block in the two arms of the same patient. Upon recovery from the block in the paralysed arm the dose response of both arms to a second dose of mivacurium was studied in order to investigate the effect of the amount and duration of block upon second dose sensitivity. An approximately 50% diminution in the ED95 dose requirement of mivacurium was found following complete recovery from an ED95 dose in spite of the rapid plasma clearance of this drug. A similar increase in sensitivity was observed in the arm that had been excluded for 100 s from the peak effect of the drug. It was concluded that the second dose sensitivity was not due to a receptor effect or to residual drug in plasma.

Recovery of mivacurium and doxacurium versus vecuronium in the isolated forearm

To assess rate of biophase recovery, the recovery from neuromuscular block with mivacurium in the isolated forearm was compared with that from vecuronium simultaneously administered into the other isolated forearm of six volunteers. In a second series of similar experiments, recovery from doxacurium was compared with that from vecuronium. Neuromuscular block was monitored using the adductor pollicis mechanomyographic response to ulnar nerve stimulation at 0.2 Hz. Comparable degrees of maximum twitch tension depression were obtained in each series. In the first series, mean (SD) 25–75% recovery index for mivacurium was 8.4 (1.5) min and 10.5 (1.9) min for vecuronium. In the second series, mean (SD) recovery index for doxacurium was 18.3 (4.2) min and 12.2 (5.0) min for vecuronium. The recovery index of doxacurium in the isolated forearm was significantly greater, and the recovery index of mivacurium significantly less, than the recovery index of simultaneously administered vecuronium. Mivacurium block in the isolated forearm recovers rapidly, although not faster than after systemic injection; this is consistent with a drug that is retained in the biophase despite rapid plasma metabolism. Doxacurium block in the isolated forearm is slow to recover, compared with vecuronium; this suggests that high affinity for the biophase may contribute to its long duration of action.

Extending a pipecurium neuromuscular block

[ I ] VANNER RG, PRYLE BJ. Regurgitation and oesophageal rupture with cricoid pressure-a cadaver study. Anaesthesia 1992; 47: 132-5. of anaesthesia. Proceedings of the First European Congress o j Anaesthesiology, Vienna 1962; 1: 89. [5] SALEM MR, WONG AY, Fizzom GF. Efficacy of cricoid pressure in preventing aspiration of gastric contents in paediatric patients. British Journal of Anaesthesia 1972; 44: 401-4. [6] SALEM R, JOSPEH NJ, HEYMAN HJ, BELANI B, PAULISSIAN R, FERRARA TP. Cricoid compression is effective in obliterating the esophageal lumen in the presence of a nasogastric tube. Anesthesiology 1985; 63: 443-6. [2] INGELFINGER FJ. Esophageal motility. Physiological Reviews 1958; 38: 533-84. [3] SELLICK BA. Cricoid pressure to control regurgitation of stomach contents during induction of anaesthesia. Lancet 1961; 2 404-6. [4] SELLICK BA. The prevention of regurgitation during induction

No effect of circulating drug upon isolated forearm block.

Controversy exists as to whether the recovery of isolated arm blockade is primarily determined by resultant plasma drug concentrations, or by the affinity of the drug for the biophase. We have investigated the effect of the circulating drug produced by the isolated forearm experiment upon its recovery profile. Paralysis from retrograde spread of drug after the intravenous injection of 20 ml saline containing vecuronium 0.3 mg into a forearm isolated from the circulation was achieved in three groups of five experiments. Group 1 were used as controls, the tourniquet being released after 3–4 min and the recovery of block observed. In group 2 the tourniquet was similarly released but a repeat dose of vecuronium 0.3 mg was administered into the systemic circulation at 10% recovery. In group 3 the tourniquet was released at 50% twitch depression and the repeat dose of vecuronium 0.3 mg given when the twitch height had recovered to that level. The mean (SD) 25% to 75% recovery indices of groups 1, 2 and 3 were: 9.2 (2.4), 8.7 (1.2) and 9.9 (1.9) min. There was no noticeable effect on the recovery slope of any of the traces when the second dose of myoneural blocker was given systemically in groups 2 and 3. The findings indicate that the main determinant of recovery of the isolated forearm experiment is not its plasma drug concentration but a mechanism which maintains the drug in the effect compartment.

Curare modification of suxamethonium blockade.

Tubocurare (0.125 mg.kg‐1 or 0.25 mg.kg‐1) was injected 10 s before 1 mg.kg‐1 suxamethonium in patients anaesthetised with enflurane 1–1.5%. Measurement of electromyographic response was recorded using a 0.2 Hz train‐of‐four every 20 s. The modified blocks were slower in onset, of lesser intensity, and of shorter duration than that of suxamethonium alone, but were much closer to those of suxamethonium than of tubocurare. However, the train‐of‐four fade observed during onset of the modified blocks were similar to that of their tubocurare controls and significantly different from the suxamethonium group. We conclude that effective amounts of tubocurare are present in the neuromuscular junction within the 30 s following intravenous injection of the drugs, and this affects the onset of action of the suxamethonium block. The presence of train‐of‐four fade during a predominantly agonist block is difficult to explain on the basis of diminished acetylcholine release and a postsynaptic site of action of suxamethonium.

A modified bonded strain gauge for adductor pollicis mechanomyography

Routine monitoring of neuromuscular function during anaesthesia provides valuable information about the effects of neuromuscular blocking drugs. In procedures where access to the limbs is difficult, such monitoring can be accomplished by stimulating the temporal branch of the facial nerve and observing the motor response of the frontalis muscle [I]. However, in the writers experience this method frequently gives equivocal results due to direct stimulation of the underlying muscle. Recently, I have obtained better results by stimulating the accessory nerve and observing the response of the sternomastoid and trapezius muscles.-This can readily be accomplished by placing the stimulating electrodes over the depression between the ramus of the mandible and the mastoid process/sternomastoid muscle (Fig. I) . In this position the accessory nerve is stimulated as it passes deep to the styloid process and the posterior belly of the digastric muscle [2]. Clear surface landmarks facilitate accurate electrode placement and the occurrence of muscle artifacts in minimal.

Effect of voluntary tetanus on recovery of vecuronium block in the isolated forearm

This study was conducted to investigate the effect of voluntary tetanus on the recovery from neuromuscular block produced by a nondepolarising drug, vecuronium, in the isolated forearm. We have studied the recovery indices and train of four fade at different levels of recovery following vecuronium in both isolated forearms simultaneously, in six sets of experiments. In one hand the volunteer performed a maximum contraction of his thumb repeatedly at fixed intervals. We found that following voluntary tetanus there is an increased rate of recovery from nondepolarising neuromuscular block; mean Recovery Index (7.4, SD 0.97) compared to control Recovery Index (10.55, SD 2.58), p < 0.05. The train‐of‐four fade also showed a sustained reduction in the isolated forearm which underwent voluntary tetanus. During the later phase of recovery the train‐of‐four fade showed significant difference statistically (p < 0.01). The findings of this study supports the hypothesis that more rapid recovery associated with voluntary tetanus is due to a reduction in the presynaptic block thus resulting in an increased rate of transmitter release.