Abstract

Factors driving the development of neuromuscular blocking agents are discussed. The goal of recent development of neuromuscular blocking agents is to develop agents with fewer adverse effects than succinylcholine and greater control. Greater control can be achieved through a short duration of action and a fast onset, similar to that found with succinylcholine. Duration control can be achieved through rapid, reliable metabolism that is organ independent, as with cisatracurium, or that occurs in the liver, because this will fail only in patients with severe hepatic disease. Rapid onset can be achieved by giving higher doses of drugs that have a fast, reliable metabolism or a rapid distribution to tissue. This has been done with succinylcholine, cisatracurium, and mivacurium. It has been shown that a low-potency drug has a faster onset than a higher-potency drug, even at the same relative dose. Rocuronium was the first neuromuscular blocking agent marketed that was developed specifically as a low-potency drug for achieving a rapid onset. In a comparison with two other intermediate-duration neuromuscular blocking agents at equipotent doses, rocuronium's onset was about one minute, which was two minutes faster than that of either vecuronium or atracurium. Rapacuronium is an investigational intermediate-duration agent and is even less potent than rocuronium. Clinical studies have shown it to have a very rapid onset (about 50 seconds) and a short duration of action (15-25 minutes, depending on the dose). Its short duration of action will make it potentially useful for short surgical procedures and procedures in which nerve integrity must be monitored. At the same time, its onset time approaches that of succinylcholine. Recent advances have made the administration of neuromuscular blocking agents much easier because the newer nondepolarizing relaxants offer faster onset and greater control.

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