Population Pharmacokinetics of Vancomycin in Intensive Care Patients with the Time-Varying Status of Temporary Mechanical Circulatory Support or Continuous Renal Replacement Therapy

Abstract

Abstract Introduction This study characterized the population pharmacokinetics (PK) of vancomycin in patients treated with and without continuous renal replacement therapy (CRRT) or temporary mechanical circulatory support (tMCS), including extracorporeal membrane oxygenation or extracorporeal ventricular assist device. Methods Critically ill adults with and without tMCS or CRRT prescribed vancomycin were enrolled for population PK modeling. Monte Carlo simulation provided dosing recommendations based on the probability of target attainment (PTA), achieving a 24-h area under curve (AUC24h) of 400–600 mg*h/L. Results Twenty-five patients with 184 plasma samples were analyzed. The median age was 61.0 years. The final model was a two-compartment PK model. CRRT, serum creatinine, and body weight were significant predictors of clearance. CRRT was a covariate on the central volume of distribution. tMCS significantly decreased the intercompartmental clearance. The simulated mean trough levels at the 48th hour were lower in the tMCS group (13.4 versus 14.2 mg/dL in non-tMCS, p < 0.001) in a 70-kg subject with a creatinine of 1 mg/dL and a daily dose of 20 mg/kg, but the PTA was similar (61.8% versus 62.2%). A reduction of maintenance dose from 30 to 10 mg/kg/day with loading dose from 25 to 15 mg/kg is recommended while serum creatinine progresses from 0.5 to 4.0 mg/dL. For CRRT, the optimal regimen consists of 20–25 mg/kg loading and maintenance of 15 mg/kg/day. Conclusions The dosing strategy of vancomycin can be based on body weight or renal function, regardless of tMCS. Intercompartmental clearance decreases under tMCS, which can mislead a dosing adjustment based on trough level.

Keywords

• Vancomycin
• ECMO
• Temporary mechanical circulatory support
• Continuous renal replacement therapy
• Population pharmacokinetics