ENZYMATIC ANTAGONISM OF MIVACURIUM-INDUCED NEUROMUSCULAR BLOCKADE BY HUMAN PLASMA CHOLINESTERASE

Background: Mivacurium chloride is a bis-benzylisoquinolinium nondepol arizing neuromuscular blocking agent, hydrolyzed by butyrylcholinester ase (PCHE). The dose-response relationships for PCHE after mivacurium have not been studied. Therefore, this study was designed to establish dose-response relationships for PCHE as an antagonist of mivacurium-i nduced neuromuscular blockade. Methods: Forty-eight physical status 1 adults were given 0.15 mg/kg mivacurium during fentanyl-thiopental-nit rous oxide-isoflurane anesthesia. Train-of-four (TOF) stimulation was applied to the ulnar nerve every 12 s, and the force of contraction of the adductor pollicis muscle was recorded. When spontaneous recovery of first twitch height (T1) reached 10% of its initial control value, exogenous PCHE equivalent to activity present in 2.5, 5, 7.5, 15, or 2 5 ml/kg of human plasma was administered by random allocation to 40 pa tients. Neuromuscular function in another eight subjects was allowed t o recover spontaneously. Two blood samples were taken for determinatio n of plasma cholinesterase activity. The first sample was taken before induction of anesthesia, and the second sample was taken when the TOP ratio had recovered to 0.75. Dibucaine and fluoride numbers were dete rmined from the first assay. Results: Administration of PCHE produced significant increases in PCHE activity In all patients. The larger the dose, the greater was the resultant plasma activity. Human PCHE produ ced a dose-dependent antagonism of mivacurium-induced neuromuscular bl ockade and the recovery times correlated inversely with PCHE activity (P < 0.01). The recovery of T1 was greater (P < 0.01) and time to atta in a TOF ratio of 0.75 was shorter (P < 0.01) with any dose of PCHE th an that observed in the spontaneous recovery group. After the administ ration of exogenous PCHE equivalent to activity present in 25 ml/kg of human plasma, recovery of TOF ratio to 0.75 or more was observed in a ll patients in less than 10 min and time to attain a TOF ratio of 0.75 was 55% shorter than the spontaneous recovery group (8.4 [7.1-9.7] vs . 18.7 [15.4-22] min; mean and 95% confidence Intervals). Conclusions: Administration of exogenous PCHE equivalent to activity present in 25 ml/kg of human plasma (in a 65-kg patient, this dose is equivalent to PCHE activity of 1,625 ml of adult human plasma) resulted in reliable antagonism of mivacurium-induced neuromuscular blockade. Nevertheless , because of the prohibitive cost of this compound, this reversal moda lity is unlikely to have a routine practical application at this time.