Annual Scientific Meeting, Belfast; November 2000.

K C McCourt

The ‘Holy Grail’ of muscle relaxant research remains the discovery of an ultra-short acting nondepolarising neuromuscular blocking drug of rapid onset, the properties required of the so-called ‘ideal’ relaxant . This review sets out to discuss how new agents may compare to that ideal.

Although not yet licensed for general use in Europe, rapacuronium bromide (Org 9487), the 16-N-allyl-17-ß-propionate analogue of vecuronium, has been available in the USA for approximately one year (RaplonÔ , Organon Inc.). The formulation available in the USA consists of 5 and 10 ml vials of lyophilised cake to be reconstituted in water to a final concentration of 20 mg ml^-1 and pH 4.0.

Rapacuronium is less potent than other available aminosteroid neuromuscular blocking agents. Initial work suggested a 90% effective dose (ED₉₀) of 1.15 mg kg^-1 (equivalent to ED₉₅ of 1.35 mg kg^-1, recalculated to 1.19 mg kg^-1 to take into account active drug moiety only) , but more recent work has suggested that it may be more potent than this, with an ED₉₅ of 0.75 mg kg^-1 . This is still, however, considerably less potent than other aminosteroid agents such as rocuronium (ED₉₅ ~0.3 mg kg^-1) and vecuronium (ED₉₅ ~0.05 mg kg^-1).

The recommended intubating dose of rapacuronium is 1.5 mg kg^-1. This dose will give complete onset of block in 55-70s . Following succinylcholine 1.0 mg kg^-1 or rapacuronium 1.5 mg kg^-1, clinically acceptable intubating conditions at 50-60s occur in 95-97% of the former and about 90% of the latter . Rapacuronium 1.5 mg kg^-1 has a more rapid onset, similar intubating conditions at 60s, and a shorter recovery time than rocuronium 0.6 mg kg^-1 .

Following the administration of rapacuronium 1.5 mg kg^-1, spontaneous recovery to the endpoint T₁25% (first twitch height 25% of control) takes ~14 min (cf. succinylcholine ~8 min), and interval T₁25%-TOF 0.8 takes ~19 min . Repeat administration of rapacuronium, or administration by continuous infusion, is associated with more prolonged block, possibly due in part to cumulation of active metabolites .

Initial work suggested that neostigmine administered 2 min after an intubating dose of rapacuronium would shorten recovery times to those of succinylcholine – so called ‘rescue reversal’ . Although such rapid recovery has not subsequently been shown, administration of either neostigmine or edrophonium 2 min after rapacuronium 1.5 mg kg^-1 shortens recovery time to T₁25% to approximately 10 min .

Rapacuronium causes dose-dependent increases in heart rate and decreases in arterial blood pressure . Although its administration has been associated with histamine release, these cardiovascular changes do not appear to correlate directly with histamine levels, at least in the dose range 1-3 mg kg^-1, and other factors may be involved . In addition, erythema, bronchospasm and/or increased airway pressure have been reported after the use of this drug .

Other agents, such as G-1-64 and GW 280430A are at various stages of development and may offer alternatives to our current armamentarium of benzylisoquinolinium or aminosteroid series of drugs . It is however, too early to say whether any will reach clinical use.

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