title: Edrophonium requirements for reversal of deep neuromuscular block following infusion of mivacurium.
abstract: Mivacurium is a new non-depolarizing muscle relaxant consisting of three stereoisomers. The two active isomers (cis-trans and trans-trans) undergo rapid metabolism by plasma cholinesterase (t1/2 beta < 2 min). Due to its rapid elimination, the need for reversal of mivacurium-induced neuromuscular block is controversial, and to date there have been no studies evaluating reversal of deep blocks. The object of the current investigation was to establish the lowest effective dose of edrophonium 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/alfentanil anaesthesia, a continuous infusion of mivacurium was adjusted to maintain between 5-10% of control T1 amplitude. Upon completion of surgery, neuromuscular block was reversed by injecting normal saline (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 T1 response of < 10% to a TOF ratio > or = 0.7, required 13.5 +/- 2.6 min (PLAC Group). In comparison, patients in the EDR-1 group required 9.2 +/- 2.6 min (P < 0.01). Higher doses of edrophonium conferred no advantage. Four patients (4%) had not achieved a TOF ratio of > or = 70%, 20 min after reversal, and required additional edrophonium. Two patients (PLAC group), had dibucaine numbers and cholinesterase levels consistent with an EUEA genotype, whereas the two patients with delayed recovery in the EDR-1 group had characteristics of a normal genotype. We conclude that a very low dose of edrophonium (0.125 mg.kg-1) hastens reversal of deep mivacurium-induced neuromuscular block by approximately four minutes, and that edrophonium doses exceeding 0.125 mg.kg-1 provide no additional benefit. Heterozygous patients with atypical plasma cholinesterase levels, as well as certain individuals with normal dibucaine numbers and plasma cholinesterase activity, are at risk for prolonged neuromuscular block, but the block is easily reversed with edrophonium.
authors.affiliation: Department of Anaesthesia, Ottawa General Hospital, Ontario.
authors.forename: D R
authors.initials: DR
authors.lastname: Miller
authors.forename: G
authors.initials: G
authors.lastname: Bryson
authors.forename: R J
authors.initials: RJ
authors.lastname: Martineau
authors.forename: J B
authors.initials: JB
authors.lastname: Kitts
authors.forename: M
authors.initials: M
authors.lastname: Curran
authors.forename: P
authors.initials: P
authors.lastname: Bragg
authors.forename: J B
authors.initials: JB
authors.lastname: Watson
authors.forename: K
authors.initials: K
authors.lastname: Hull
authors.forename: P
authors.initials: P
authors.lastname: Lindsay
mesh_terms: D000759:Adjuvants, Anesthesia / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D015760:Alfentanil / Q000008:administration & dosage; D000556:Ambulatory Surgical Procedures; D000768:Anesthesia, General; D018685:Anesthetics, Inhalation / Q000008:administration & dosage; D018686:Anesthetics, Intravenous / Q000008:administration & dosage; D001285:Atropine / Q000008:administration & dosage; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage*; D002802:Cholinesterases / Q000097:blood / Q000235:genetics / Q000378:metabolism; D004311:Double-Blind Method; D004491:Edrophonium / Q000008:administration & dosage*; D005260:Female; D005838:Genotype; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000077590:Mivacurium; D003473:Neuromuscular Nondepolarizing Agents / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009609:Nitrous Oxide / Q000008:administration & dosage; D010919:Placebos; D015742:Propofol / Q000008:administration & dosage; D013237:Stereoisomerism
chemical_list: D000759:Adjuvants, Anesthesia; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D002800:Cholinesterase Inhibitors; D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D010919:Placebos; D015760:Alfentanil; D004491:Edrophonium; D000077590:Mivacurium; D001285:Atropine; D002802:Cholinesterases; D009609:Nitrous Oxide; D015742:Propofol