Nondialyzability of Fentanyl with High-Efficiency and High-Flux Membranes

To the Editor: Fentanyl is often used in intensive care units. Although elimination of fentanyl is mainly through hepatic metabolism, approximately 15%-20% of the drug is excreted by the kidneys [1]. Fentanyl is approximately 79% protein bound, and uremia has been shown not to influence its protein binding [2]. In a study of patients undergoing dialysis, there was an increase in the volume of distribution and systemic clearance of fentanyl [3]. Nevertheless, studies on fentanyl pharmacokinetics during anesthesia have found no difference between patients with renal failure and those with normal renal function [4]. Fentanyl has a molecular weight of 336.5 Daltons, a volume of distribution of 2-5 L/kg, and a serum half-life of 2.5-3.5 h in patients with normal renal function, as well as in patients with end-stage renal disease [5]. Because the liver is a major site for fentanyl elimination, no dose adjustment is required in patients with different degrees of renal insufficiency [5]. Currently, there is no information available regarding its dialyzability with hemodialysis (HD), peritoneal dialysis, continuous hemofiltration, or hemodiafiltration [5]. A 32-yr-old woman with end-stage renal disease secondary to primary hyperoxaluria type 1 received an orthotopic liver transplantation while receiving chronic HD. The patient received daily HD with different high-flux or high-efficiency membranes. Each HD session lasted for 4 h with an average ultrafiltration volume of 3.2 L (range 2.1-5.1 L). During this time, the patient was receiving intravenous fentanyl infusion at a rate of 60-90 micro g/h (0.02-0.03 micro g [center dot] kg-1 [center dot] min-1). The patient's weight was approximately 50 kg. The pertinent information regarding different dialyzers, fentanyl concentrations in the arterial (predialyzer) and venous (postdialyzer) lines, and the ultrafiltrate are shown in Table 1. Fentanyl concentration was undetectable in the ultrafiltrate, and there was no significant difference in the fentanyl concentrations between the arterial and venous lines, with the exception of the CT 190 dialyzer. In the latter, there was a 32% decline in the blood concentration of fentanyl between the arterial and venous lines (pre- and postdialyzer lines, respectively), despite a large volume of ultrafiltrate (5.1 L over 4 h), which should have resulted in hemoconcentration (approximately 7% hemoconcentration with blood flow rate of 200 mL/min). However, because these were single blood-level measurements, some inadvertent variability in the assay may have resulted in different blood levels. Nonetheless, if the decline is a true phenomenon, because fentanyl was not detectable in the ultrafiltrate, it would suggest that fentanyl had been adsorbed to the CT 190 dialyzer membrane.Table 1: Features of Different Dialyzers and Fentanyl Concentration in Different CompartmentsOur results suggest that fentanyl is not removed to any significant degree by the currently used high-efficiency or high-flux membranes, with the possible exception of CT 190. J. Joh, MD* M. K. Sila, MD dagger B. Bastani, MD* * Division of Nephrology and dagger Department of Anesthesiology; Saint Louis Health Sciences Center; St.