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

Published online by Cambridge University Press:  13 April 2005

E. N. Robertson ,
J. J. Driessen  and
L. H. D. J. Booij
E. N. Robertson
Affiliation:
University Medical Center, Department of Anesthesiology, Nijmegen, The Netherlands
J. J. Driessen
Affiliation:
University Medical Center, Department of Anesthesiology, Nijmegen, The Netherlands
L. H. D. J. Booij
Affiliation:
University Medical Center, Department of Anesthesiology, Nijmegen, The Netherlands
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Extract

Summary

Background and objective: 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.

Methods: 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°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.

Results: 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.

Conclusions: 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.

Keywords

NEUROMUSCULAR NON-DEPOLARIZING AGENTS, rocuroniumKIDNEY FAILURE, CHRONICPHARMACOKINETICS, rocuronium, metabolites
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 22 , Issue 1 , January 2005 , pp. 4 - 10
Copyright
© 2005 European Society of Anaesthesiology

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References

Mirakhur RK, Cooper R, McCarthy G, Elliot P. Comparison of the intubating conditions and some neuromuscular effects following administration of Org 9426 and succinylcholine. Anesth Analg 1992; 74: S210.Google Scholar
Mirakhur RK. Safety aspects on non-depolarizing neuromuscular blocking agents with special reference to rocuronium bromide. Eur J Anaesth 1994; 11 (Suppl 9): 133–140.Google Scholar
Wierda JMKH, Kleef UW, Lambalk LM, Kloppenburg WD, Agoston S. The pharmacodynamics and pharmacokinetics of Org 9426, a new non-depolarizing neuromuscular blocking agent, in patients anaesthetized with nitrous oxide, halothane and fentanyl. Can J Anaesth 1991; 38: 430–435.Google Scholar
Wierda JMKH, Proost JH, Schiere S, Hommes FDM. Pharmacokinetics and pharmacokinetic/dynamic relationship of rocuronium bromide in humans. Eur J Anaesth 1994; 11: 66–74.Google Scholar
Khuenl-Brady KS, Pomaroli A, Pühringer F, Mitterschiffthaler G, Koller J. The use of rocuronium in patients with chronic renal failure. Anaesthesia 1993; 48: 873–875.Google Scholar
Cooper RA, Maddineni VR, Mirakhur RK, Wierda JMKH, Brady M, Fitzpatrick KTJ. Time course of neuromuscular effects and pharmacokinetics of rocuronium bromide during isoflurane anaesthesia in patients with and without renal failure. Br J Anaesth 1993; 71: 222–226.Google Scholar
Szenohradszky J, Fisher DM, Segredo V, et al. Pharmacokinetics of rocuronium bromide in patients with normal renal function or patients undergoing cadaver renal transplantation. Anesthesiology 1992; 77: 899–904.Google Scholar
Cooper AR, Wierda JMKH, Mirakhur RK, Maddineni VR. Pharmacodynamics and pharmacokinetics of rocuronium bromide in patients with and without renal failure. Eur J Anaesth 1994; 11 (Suppl 9): 82–84.Google Scholar
Kleef UW, Proost JH, Roggeveld J, Wierda JMKH. Determination of rocuronium and its putative metabolites in body fluids and tissue homogenates. J Chromatogr 1993; 621; 65–76.Google Scholar
Press WH, Flannery BP, Teukolsky SA, Vetterling WT (eds). Numerical Recipes. Cambridge: Cambridge University Press, 1986.
Wagner JG. Fundamentals of Clinical Pharmacokinetics. Hamilton: Drug Intelligence Publications, 1975.
Driessen JJ, Robertson EN, Booij LHDJ, Vree TB. Accelerated recovery and disposition from rocuronium in an end-stage renal failure patient on chronic anticonvulsant therapy with sodium valproate and primidone. Br J Anaesth 1998; 80: 386–388.Google Scholar
McCoy EP, Mirakhur RK, Maddineni VR, Wierda JMKH, Proost JH. Pharmacokinetics of rocuronium after bolus and continuous infusion during halothane anaesthesia. Br J Anaesth 1996; 76: 29–33.Google Scholar
Van den Broek L, Wierda JMKH, Smeulers NJ, Van Santen GJ, Leclerc MGL, Hennis PJ. Clinical pharmacology of rocuronium: study of the time course of action, dose requirement, reversibility and pharmacokinetics. J Clin Anesth 1994; 6: 288–296.Google Scholar
Kheunl-Brady K, Castagnoli KP, Canfell PC, Caldwell JE, Agoston S, Miller RD. The neuromuscular blocking effects and pharmacokinetics of Org 9426 and Org 9616 in the cat. Anesthesiology 1990; 72: 669–674.Google Scholar
Driessen JJ, Robertson EN, VanEgmond J, Booij LHDJ. Time-course of action of rocuronium 0.3 mg kg−1 in children with and without endstage renal failure. Paediatr Anaesth 2002; 12: 507–510.Google Scholar