Effect of renal failure and cirrhosis on the pharmacokinetics and neuromuscular effects of rapacuronium administered by bolus followed by infusion

Background: Recent trials indicate that rapacuronium's pharmacokinetic char acteristics are influenced by both renal failure and cirrhosis but the time course of a single bolus dose of 1.5 mg/kg is affected minimally. The auth ors reassessed these pharmacokinetic findings and examined the time course of the same bolus dose followed by a 30-min infusion. Methods: During nitrous oxide-isoflurane anesthesia, patients with normal r enal and hepatic function (n = 25), those with renal failure (n = 28), and those with cirrhosis (n = 6) received a bolus dose of rapacuronium (1.5 mg/ kg) followed by a 30-min infusion adjusted to maintain 90-95% twitch depres sion. At 25% recovery, neostigmine was administered. Blood was sampled unti l 8 h after the infusion to determine concentrations of rapacuronium and it s active metabolite ORG9488. Rapacuronium's pharmacokinetic parameters were determined using mixed-effects modeling. Results Onset and facilitated recovery of twitch depression were similar in the three groups. Patients with renal failure required 22% less rapacuroni um to maintain target twitch depression during the infusion. Rapacuronium's plasma clearance was 24% smaller in renal failure and decreased 0.5%/yr of age; rapid distribution clearance was 51% smaller in men than in women. Af ter the infusion, ORG9488 concentrations decreased markedly more slowly in patients with renal failure. Cirrhosis did not alter the pharmacokinetics o f rapacuronium, Conclusion: Rapacuronium's plasma clearance and infusion requirement were d ecreased by renal failure. By dosing to maintain target twitch depression, recovery was not prolonged. Cirrhosis does not affect the pharmacokinetics or neuromuscular effects of rapacuronium. Persistence of ORG9488 in patient s with renal failure might prolong recovery after rapacuronium if target tw itch depression is not maintained or with administration of rapacuronium fo r more than 30 min.