Neuromuscular block and relative concentrations of mivacurium isomers under isoflurane versus propofol anaesthesia

The augmentation of the effect of neuromuscular blocking drugs with volatile anaesthetics is well documented, but the mechanism remains unclear. The pharmacological interaction and relative plasma concentrations of mivacurium isomers were investigated during either propofol- or isoflurane-maintained anaesthesia.

Forty-four patients were randomly assigned to one of two groups: isoflurane or propofol. All patients received an initial dose of mivacurium 0.1 mg kg(-1). After recovery of the first twitch (T1) response measured by acceleromyography to 5%, a T1 depression of 90-99% was maintained by infusion. After a steady state was reached, blood samples were taken after 10 and 30 min for analysis of mivacurium isomers. Recovery times for T1 to 251/50/75/90% (TW25-90), train-of-four ratio 25/70% and recovery index (time TW25-75) were recorded after stop of infusion.

In the isoflurane group, lower infusion rates were needed (3.0 +/- 1.6 versus 3.6 +/- 1.6 microg kg(-1) min(-1)) and there was a slower recovery (significant for train-of-four ratio 70%: 21.9 versus 17.9 min). The plasma concentrations of mivacurium and its trans-trans isomer (in percentage of the total) were significantly higher in the isoflurane group (10 min: 52.6 versus 25.8%; 30 min: 49.6 versus 23.2%).

For mivacurium, the phenomenon of 'potentiation' of the effect of muscle relaxants by volatile anaesthetics could be due to an increase in the plasma concentration of the potent trans-trans isomer.