Initial vancomycin dosing recommendations for critically ill patients undergoing continuous venovenous hemodialysis.

BACKGROUND Delaying appropriate antimicrobial therapy for critically ill patients increases the risk of death. Currently, there are insufficient data to guide initial vancomycin dosing for patients undergoing continuous venovenous hemodialysis (CVVHD). OBJECTIVE To develop practical recommendations for initial dosing of vancomycin, based on the pharmacokinetics of this drug in critically ill patients undergoing CVVHD. METHODS A chart review was conducted for 24 critically ill adult patients who had undergone concurrent CVVHD and vancomycin therapy. Mean pharmacokinetic parameters were determined, along with practical recommendations for initial vancomycin dosing that targeted steady-state trough concentrations for patients receiving intermittent infusions and steady-state levels for those receiving continuous infusions between 15 and 20 mg/L. Monte Carlo simulation was used to develop the initial vancomycin dosing recommendations. RESULTS The mean (95% confidence interval) pharmacokinetic parameters for vancomycin (elimination rate constant 0.0315 [0.0254-0.0391], half-life 22.0 h [17.72-27.24 h], volume of distribution 0.96 L/kg [0.77-1.20 L/kg], and clearance 2.4 L/h [1.97-2.92 L/h]) indicated that initial intermittent IV dosing of 1.25-1.5 g q24h or 15 mg/kg q24h would be suitable. For continuous infusion, a 1.5-g IV loading dose followed by continuous infusion of 1-1.5 g IV over 24 h (42-62 mg/h) would be recommended. However, Monte Carlo simulation revealed that the probability of achieving desired concentrations between 15 and 20 mg/L with any of these initial regimens is low. CONCLUSIONS There was considerable variation in vancomycin pharmacokinetics in this patient population. The observations reported here raise concerns about the reliability of numerous empiric dosing recommendations derived from small pharmacokinetic studies in heterogeneous populations. Follow-up therapeutic drug monitoring is essential to ensure that concentrations remain within the target range.