EDROPHONIUM REQUIREMENTS FOR REVERSAL OF DEEP NEUROMUSCULAR BLOCK FOLLOWING INFUSION OF MIVACURIUM

Mivacurium is a new non-depolarizing muscle relaxant consisting of thr ee stereoisomers. The two active isomers (cis-trans and trans-trans) u ndergo rapid metabolism by plasma cholinesterase (t(1/2) beta<2 min). Due to its rapid elimination, the need for reversal of mivacurium-indu ced neuromuscular block is controversial, and to date there have been no studies evaluating reversal of deep blocks. The object of the curre nt investigation was to establish the lowest effective dose of edropho nium required to reverse deep mivacurium-induced neuromuscular block. One hundred ASA Class I and II patients undergoing outpatient surgery in two teaching institutions were studied in this randomized, placebo- controlled double-blind trial. Under balanced propofol/nitrous oxide/a lfentanil anaesthesia, a continuous infusion of mivacurium was adjuste d to maintain between 5-10% of control T-1 amplitude. Upon completion of surgery, neuromuscular block was reversed by injecting normal salin e (Group PLAC), edrophonium 0.125 mg . kg(-1) (Group EDR-1), 0.25 mg . kg(-1) (Group EDR-2), or 0.50 mg . kg(-1) (Group EDR-3), in addition to a corresponding dose of atropine. Spontaneous recovery, from a T-1 response of <10% to a TOF ratio greater than or equal to 0.7, required 13.5 +/- 2.6 min (PLAC Group). In comparison patients in the EDR-1 gr oup required 9.2 +/- 2.6 min (P < 0.01). Higher doses of edrophonium c onferred no advantage. Four patients (4%) had not achieved a TOF ratio of greater than or equal to 70%, 20 min after reversal, and required additional edrophonium. Two patients (PLAC group), had dibucaine numbe rs and cholinesterase levels consistent with an E(U)E(A) genotype, whe reas the two patients with delayed recovery in the EDR-1 group had cha racteristics of a normal genotype. We conclude that a very low dose of edrophonium (0.125 mg . kg(-1)) hastens reversal of deep mivacurium-i nduced neuromuscular block by approximately four minutes and that edro phonium doses exceeding 0.125 mg . kg(-1) provide no additional benefi t. Heterozygous patients with atypical plasma cholinesterase levels, a s well as certain individuals with normal dibucaine numbers and plasma cholinesterase activity, are at risk for prolonged neuromuscular bloc k, but the block is easily reversed with edrophonium.