Pharmacokinetics and pharmacodynamics of rocuronium in patients with and without renal failure

Abstract

This study clarifies the relationship between the neuromuscular blocking effects of rocuronium 0.6 mg kg(-1) and its pharmacokinetics in patients with renal failure. Seventeen healthy patients and 17 patients with renal failure were studied under propofol anaesthesia in this prospective open label study. Rocuronium 0.6 mg kg(-1) was given after induction of anaesthesia. The train-of-four mechano-myographic response of the thumb to supramaximal stimulation of the ulnar nerve at 2 Hz every 12 s was measured. Venous blood samples (4 mL) were obtained at 0, 2, 4, 7, 10, 15, 20, 30, 60, 120, 180, 240 and 360 min after relaxant administration. Samples were centrifuged, separated and stored at -20 degrees C until plasma levels of rocuronium and its metabolites were measured. Two- and three-exponential equations were used to describe the pharmacokinetic data in each group and these were compared to each other using the Wilcoxon signed rank sum test as was the pharmacodynamic data. P < 0.05 was significant. Onset of block was similar in both groups. Clinical duration and the time to recovery of the train-of-four to 70% were prolonged in the renal failure group compared to control; 49 vs. 32 min (P < 0.004, 95% confidential, interval 17, difference 5-28) and 88 vs. 55 min (P < 0.001, 95% confidential interval 33, difference 17-50), respectively. Clearance of rocuronium was reduced by 39% in the renal failure patients compared to control, with an 84% increase in the mean residence time. The volume of distribution was unaffected by renal failure. The duration of action of a bolus dose of 0.6 mg kg(-1) rocuronium is increased significantly in patients with end-stage renal failure compared to healthy controls. This increase may be due to a decreased clearance of rocuronium, the disease process causing the renal failure and/or the medication which patients with renal failure need in their treatment.