PII-016 - CHARACTERIZATION AND PHARMACOKINETIC MODELLING OF VANCOMYCIN IN CRITICALLY ILL ICU PATIENTS UNDERGOING CVVHD

D. Quickfall¹, L. Awdishu², J. Koyner¹; ¹University of Chicago, Chicago, IL, United States, ²UCSD, University of California San Diego, United States.

Background: Sepsis is a leading cause of death in critically ill patients, with ~20% developing acute kidney injury requiring continuous renal replacement therapy (CRRT). Despite many studies on vancomycin dosing in CRRT, gaps remain due to technological changes, variable CRRT prescriptions, and limited data on transitions on and off CRRT. These gaps are notable in high-dose modalities like continuous veno-venous hemodialysis (CVVHD). This study aimed to characterize vancomycin dosing during CVVHD, assess drug concentrations, and develop a population pharmacokinetic (PopPK) model to improve dosing recommendations and patient outcomes.

Methods: A retrospective review of 390 ICU patients at the University of Chicago (April 2016 - March 2020) was conducted. All patients received ≥48 hours of CVVHD and had ≥2 vancomycin troughs recorded. Data included demographics (age, sex, comorbidities), serum creatinine, albumin, vancomycin doses, administration times, and CVVHD effluent flow rates (Qe). Statistical comparisons were made between CVVHD and non-CVVHD patients using Chi-squared and Wilcoxon signed-rank tests.

Results: The average (SD) age was 59.5 (15.2) years; 38.46% were female. Key comorbidities: chronic kidney disease (61.79%), heart failure (60.77%), and liver disease (56.15%). The median (IQR) CVVHD Qe was 30.7 [26.6 - 36.3] mL/kg/h, and CVVHD duration was 5.58 [3.42-12.21] days. Median (IQR) vancomycin dosing differed significantly on vs. off CVVHD 13.9 [10.14 - 17.13] vs. 8.9 [3.62 - 12.09] mg/kg (p < .001) respectively. Vancomycin concentrations were subtherapeutic in 58.2% of CVVHD patients, while 83.7% of non-CVVHD patients had supratherapeutic/toxic levels (p < 0.001). A PopPK model is being developed to estimate volume of distribution and clearance during CVVHD to refine dosing precision.

Conclusion: This study underscores dual risks: subtherapeutic vancomycin exposure in CVVHD patients, despite higher doses, and supratherapeutic/toxic exposure in non-CVVHD patients. These findings highlight the need for adaptable models that account for fluctuating dialysis parameters to guide dosing.