Estimation of theophylline clearance during continuous arteriovenous hemofiltration

Pharmacologic agents and other non-protein-bound compounds smaller than 5,000 daltons have the potential to be removed by continuous arteriovenous hemofiltration (CAVH). A proposed method for estimating drug clearance by CAVH (ClCAVH) equates ultrafiltrate clearance to the product of the sieving coefficient and the average ultrafiltration rate. This simplified approach for estimating ClCAVH would be a clinically useful method for calculating replacement doses, as it economizes on the sampling and analytical requirements associated with the conventional method. Presented are some theoretical considerations and a brief evaluation of the accuracy of this proposed method. The evaluation was conducted using an animal model whereby CAVH was performed in four male beagles. During the hemofiltration period, an i.v. bolus of theophylline, 6 mg/kg, was administered over 15 s. Samples for analysis of theophylline were collected from the arterial, venous, and ultrafiltrate ports at 0, 5, 15, 30, 45, 60, 90, 120, 180, 240, 360, and 480 min following dosage administration. The volume of ultrafiltrate produced during each collection interval was measured. Theophylline serum concentrations were determined by a high performance liquid chromatography assay. Statistically, the simplified method was found to result in significantly (p less than 0.05) larger estimates of ultrafiltrate clearance when compared to the conventional method. However, the average magnitude of difference was only 9% and does not constitute a clinically significant margin between the two methods.