Neostigmine but not edrophonium prolongs the action of mivacurium

To examine the influence of anticholinesterase drugs neostigmine and edrophonium (which have different effects on plasma cholinesterase activity) administered for antagonism of neuromuscular block on the duration of action of mivacurium (a neuromuscular blocking drug metabolised by plasma cholinesterase). This was a randomized study where mivacurium 0.15 mg.kg-1 was administered to a control group or after administration of neostigmine 40 micrograms.kg-1 or edrophonium 1 mg.kg-1 (n = 10 for each group) administered 10 min earlier for antagonism of atracurium-induced neuromuscular block. Neuromuscular block was measured by stimulation of the ulnar nerve in a train-of-four mode (TOF) and measuring the force of contraction of the adductor pollicis muscle. Baseline plasma cholinesterase activity was estimated before drug administration in all the groups and following anticholinesterase administration. The times to recovery of T1 (first response in the TOF) to 25 and 90% of control and of the TOF ratio to 0.7 after 0.15 mg.kg-1 of mivacurium were 47, 65 and 70 min in the neostigmine group; 25, 36 and 36 min in the edrophonium group and 17, 29 and 27 min respectively in the control group (P < 0.01). The plasma cholinesterase activity (PCHE) after neostigmine decreased from 6596 to 1959 U.L-1 (P < 0.001) but there was no change after edrophonium (6140 to 6396 U.L-1). The duration of action of mivacurium is prolonged by previous administration of neostigmine and this is most likely to be due to inhibition of PCHE activity.