Authors: Roy G. Soto, M.D. et al
ASA Monitor 05 2017, Vol.81, 30-31.
Mivacurium is a benzylisoquinolinium nondepolarizing neuromuscular-blocking drug that was developed in the early 1980s and disappeared from the U.S. market in 2006.
It was reintroduced in December 2016, and many have asked what the appropriate niche is for this seemingly resurrected medication.
Since the successful introduction of succinylcholine in the mid-20th century, there have been many attempts to duplicate its quick onset and short duration of action without the negative effects of depolarizing paralytics. Mivacurium has an onset time similar to most other intermediate-acting neuromuscular blocking agents (NMBAs), but a shorter duration of action. While it was available, many used the drug for short cases or for cases when reversal was not wanted. Others avoided the drug due to untoward side effects, notably histamine release.
In 2006, due to manufacturing problems, possibly related to an intermediary product’s availability, the supply of the drug to the U.S. ended. In part due to the imminent introduction of sugammadex in 2008, the decision was made to not pursue relicensing of mivacurium in the U.S. market. Sugammadex was not approved at that time, however, and three factors led to the reintroduction of mivacurium in 2016: sugammadex was introduced at a price higher than anticipated, neostigmine price increased dramatically, and cases continued to get shorter in duration.
Mivacurium’s short duration of action is attributed to the drug’s rapid elimination via plasma cholinesterase. At a recommended induction dose of 0.15mg/kg (twice the ED95). the drug has an onset time of three minutes and duration (as measured by return of 25 percent of first twitch height on train of four/TOF monitoring) of 12-20 minutes.1 This onset time is similar to most other intermediate-acting NMBAs, and its duration of action is approximately twice that of succinylcholine but 60-75 percent as long as vecuronium and rocuronium (time to return of 25 percent of first twitch: 20-35 minutes, for both vecuronium and rocuronium).2
For maintenance of paralysis, boluses of the drug can be administered, although given its pharmacokinetics, it would ideally be used as a continuous infusion (2-14mcg/kg/min, titrated to TOF). The 5 percent to 95 percent spontaneous recovery time after infusion discontinuation is 14.5 +/- 0.4 minutes.3
Side Effects and Patient Considerations
As mentioned, mivacurium administration can result in histamine release with resultant bronchospasm and hypotension. If larger doses of mivacurium are used (0.2-0.25mg/kg is supported in the literature to speed onset), it should be administered slowly to diminish the degree of hypotension.4 Due to the histamine-mediated hypotension and tachycardia, mivacurium should be used with caution in cardiac patients. Also, due to the increased risk of bronchoconstriction, mivacurium should be used judiciously with smokers or with patients with reactive airway disease.
Since mivacurium is metabolized by plasma cholinesterase, mivacurium should be avoided in patients with atypical or decreased levels of plasma cholinesterase. In such patients, the rate of hydrolysis of mivacurium is decreased, which results in an increased duration of action.2 Consequently, one can expect longer durations of action in patients with end-stage renal disease or liver failure.
Clinical Indications for Mivacurium
Succinylcholine, due to its short duration of action, is the paralytic of choice for short cases that require paralysis. Succinylcholine, however, has several undesirable side effects and is contraindicated in some patient populations. In very short cases, when succinylcholine is contraindicated or undesirable, mivacurium might be indicated over other NMBAs.1 However, the comparatively similar reversal times with other agents make the window of advantage very small. Specifically, mivacurium could be advantageous for cases lasting 30 minutes or less. Given well documented concerns for residual paralysis, we cannot recommend avoiding reversal agents for patients treated with mivacurium.
The costs of residual neuromuscular blockade and resultant reintubation or pulmonary complications are high. Mivacurium, at $30/vial, is significantly more expensive than rocuronium at approximately $2.50/vial. Since we cannot recommend using mivacurium without reversal (for the short cases in which it is clearly indicated), the cost of reversal agents should be considered in any pharmacoeconomic analysis. Sugammadex has also recently been introduced into clinical practice, and its efficacy and safety are clearly better than that of neostigmine. Given the incrementally higher cost of sugammadex versus neostigmine/glycopyrrolate (around $15 for most accounts), it seems prudent to use rocuronium/sugammadex for short cases, as it would be less expensive than mivacurium/neostigmine/glycopyrrolate.
Although the reintroduction of any medication into clinical practice can be advantageous in some circumstances, the indications for mivacurium are narrow. For those institutions that do not yet have sugammadex on formulary, we would recommend the use of mivacurium only for patients undergoing short cases who can tolerate its side effect profile.
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