Aminoglycoside Pharmacokinetics in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy

Abstract

Background: There are few studies describing aminoglycoside pharmacokinetics during continuous renal replacement therapy (CRRT). Objective: To characterize the effect of CRRT on aminoglycoside clearance and volume of distribution ( Vd). Methods: Retrospective observational pharmacokinetic study of adult critically ill oncologic patients who received a first dose of amikacin or tobramycin during CRRT between February 2012 and May 2017. Study outcomes included aminoglycoside clearance, Vd, and attainment of the target peak: MIC (minimum inhibitory concentration) ratio as a surrogate for dosing appropriateness. Results: In total, 80 patients were included, sustained low-efficiency dialysis (SLED), n = 49; continuous venovenous hemodialysis (CVVHD), n = 19; continuous venovenous hemofiltration (CVVH), n = 12. Fifty-one patients received amikacin at a median dose of 14.5 mg/kg per actual body weight and achieved a median peak level of 26.7 mg/L. Twenty-nine patients received tobramycin at a median dose of 6.5 mg/kg actual body weight and achieved a median peak level of 10.3 mg/L. The median aminoglycoside clearance was 63.1 mL/min and was similar between CRRT modality groups ( P = 0.97). The median Vd was 0.47 L/kg and was different between the SLED and CVVH groups ( P = 0.007). Attainment of target peak: MIC occurred in 29% in the total study population and 44% in the subgroup of 23 patients with isolates tested for aminoglycoside susceptibility. Conclusion and Relevance: Critically ill oncology patients undergoing CRRT exhibited reduced clearance and expanded Vd that was not significantly different between CRRT modalities. Current dosing regimens led to low peak concentrations and poor attainment of pharmacokinetic targets.