Mivacurium. A review of its pharmacology and therapeutic potential in general anaesthesia.
Mivacurium is a potent nondepolarising neuromuscular blocking agent which is structurally related to the benzylisoquinolinium compound, atracurium. Mivacurium has a short duration of action due to its rapid elimination by plasma cholinesterase. When administered to essentially healthy adult patients receiving nitrous oxide-narcotic anaesthesia, the recommended intubating dose (2 x ED95) usually provides clinically effective neuromuscular block for approximately 15 to 20 minutes and spontaneous recovery is 95% complete within about 25 to 30 minutes. When administered to paediatric patients aged 2 to 12 years, the recommended intubating dose of mivacurium produces approximately 10 minutes of clinically effective neuromuscular block. The clinical duration of action of mivacurium is shorter than that of the other nondepolarising blockers atracurium and vecuronium, although it is still longer than that of the depolarising blocker suxamthonium (succinylcholine). The recommended intubating dose usually produces good or excellent conditions for tracheal intubation within 2 to 2.5 minutes in adult patients, although intubation times are longer than those for a standard intubating dose of suxamethonium. Thus far, mivacurium has not demonstrated a cumulative neuromuscular blockade when administered to patients with normal plasma cholinesterase activity. Furthermore, due to the intrinsically faster rate of recovery, pharmacological reversal with anticholinesterases is less likely to be indicated with mivacurium than for other, longer-acting, nondepolarising blockers. Benzylisoquinolinium compounds such as mivacurium have the potential to release histamine and cause cardiovascular instability. Interpatient variability in the susceptibility to histamine release is to be expected, although the recommended intubating dose has produced minimal haemodynamic effects in clinical trials to date. Prolonged neuromuscular block is likely in patients with markedly reduced plasma cholinesterase activity. In particular, patients homozygous for the atypical plasma cholinesterase gene are extremely sensitive to the neuromuscular blocking effects of mivacurium and should not receive the drug. In summary, a single bolus dose of mivacurium can be recommended for use in adult and paediatric patients undergoing nonemergency tracheal intubation and/or during short surgical procedures. For maintenance of neuromuscular block, mivacurium can be administered as multiple bolus doses or as a continuous infusion. In particular, the lack of a significant cumulative effect renders the drug suitable for the maintenance of neuromuscular blockade during extended surgical procedures of unpredictable length.
Frampton
James E
JE
Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand.
McTavish
Donna
D
Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D000768:Anesthesia, General; D002648:Child; D002675:Child, Preschool; D002802:Cholinesterases / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D007442:Intubation, Intratracheal; D007546:Isoquinolines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D000077590:Mivacurium; D009469:Neuromuscular Junction / Q000187:drug effects*; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology / Q000627:therapeutic use*
D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D000077590:Mivacurium; D002802:Cholinesterases