Introduction

Rapacuronium (Raplon) is a new rapid-onset, short-acting, nondepolarizing neuromuscular blocking drug. It is the latest in the pancuroniun, vecuronium, pipecuronium, rocuronium series of amino-steroid drugs developed by Organon (West Orange, NJ). The purpose of this supplement is to put its pharmacological profile into perspective. The supplement will not present new studies or describe in detail the preclinical testing of the drug. Rather, it will present the general issues of onset and recovery of neuromuscular blocking, neuromuscular monitoring and reversal, pediatric differences, and cost and will discuss those areas in which the new drug’s activities differ from its predecessors. It may seem surprising that dose-response data for rapacuronium were not collected early in the evaluation process. With previous intermediate neuromuscular relaxants, such as rocuronium and cisatracurium, the 95% effective dose (ED95) was a useful variable because doses of twice the ED95 produced good intubating conditions in a reasonable period of time. The more rapid onset of rapacuronium makes such information unnecessary. Instead, dose-ranging studies were performed to determine the dose that produced good-excellent intubating conditions at 1 min. This was achieved, in adults, in a dose of 1.5 mg/kg, which is roughly equivalent to ED95 × 1.5. Another apparent difference is the ability to reverse the neuromuscular block by administering neostigmine 2 or 5 min after rapacuronium. This results in a train-of-four ratio approximately 16 min after 1.5 mg/kg rapacuronium. However, it is now recognized that such early reversal can also be achieved after rocuronium or vecuronium, but more slowly. The early reversal should be considered further evidence of the rapid recovery of rapacuronium. It will seldom be clinically useful except in those situations in which prompt restoration of ventilation is necessary. Clinicians will rapidly learn that early neostigmine administration will require careful patient observation until neuromuscular activity has been restored. Some questions remain to be answered concerning the new drug. It is metabolized to its 3-OH metabolite Org 9488 which is 2.5 times as potent a neuromuscular blocking agent than the parent compound and is cleared slowly by the kidney. Hence, there is the risk of a more prolonged block. At present, it is recommended that rapacuronium not be administered by continuous infusion or that more than 2–3 repeat doses be given. Early clinical testing reported a number of instances of “ bronchospasm” although, apparently, not accompanied by increased histamine concentrations. Further experience will be necessary to determine the true frequency and whether the response is directly the result of rapacuronium or a consequence of tracheal intubation in a lightly anesthetized, mildly paralyzed patient. The Food and Drug Administration has approved the use of rapacuronium to facilitate rapid sequence endotracheal intubation. However, anesthesiologists will require further proof of its efficacy in this situation before succinylcholine is abandoned. Nevertheless, rapacuronium appears to be the most promising nondepolarizing succinylcholine alternative to reach the clinician.

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