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End-stage renal failure reduces central clearance and prolongs the elimination half life of remifentanil

[L'insuffisance rénale terminale réduit la clairance centrale et prolonge la demi-vie d'élimination du rémifentanil]

Ashraf A. Dahaba, MD MSc^*, Karl Oettl, PhD, Fedor von Klobucar, MD^*, Gilbert Reibnegger, PhD and Werner F. List, MD^*

^* From the Departments of Anaesthesiology and Intensive Care Medicine, and
Medical Chemistry and Pregl Laboratory, Karl-Franzens University, Graz, Austria.

Dr. Ashraf Dahaba, Department of Anaesthesiology and Intensive Care Medicine, Karl-Franzens University, Auenbruggerplatz 29, A-8036, Graz, Austria. Phone: ++ 43-316-385-2829; Fax: ++ 43-316-385-3267; E-mail: Ashraf.Dahaba{at}kfunigraz.ac.at

Purpose: To evaluate the pharmacokinetics of remifentanil in 13 end-stage renal failure patients compared to matched control patients with normal renal function.

Methods: Remifentanil was infused for 20 min at a rate of 0.1 µg•kg^-1•min^-1. Serial arterial blood samples (3 mL) were drawn at the start of infusion (zero), five, ten, 15, 20, 22.5, 25, 27.5, 30, 35, 40, 45, 50, 55 and 60 min. Blood samples were immediately preserved with citric acid and chilled on ice. High performance liquid chromatography-tandem mass spectrometry concentration assay was performed using GI 95779B internal standard.

Results: A two-compartment pharmacokinetic model provided an adequate fit for individual patient data. There was no difference in the mean ± SD distribution half life (t ) between the renal failure group (1.65 ± 0.7 min) and the control group (1.58 ± 0.54 min). There was a significant difference in the central clearance (Cl_c) and elimination half life (t ß) between the renal failure group (28 ± 7 mL•kg^-1•min^-1 and 18.86 ± 2.06 min, respectively) and the control group (46.3 ± 13.8 mL•kg^-1•min^-1 and 16.35 ± 2.99 min, respectively). Remifentanil blood concentrations were significantly higher in the renal failure group than in the control group.

Conclusion: We have demonstrated a significant reduction in the Cl_c and a prolongation of t ß of remifentanil in end-stage renal failure patients. While statistically significant, these variations in the pharmacokinetics of remifentanil were clinically modest and may be explained by a reduced volume of distribution in the period following hemodialysis.

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