LAUSR

Introduction/Hypothesis: The pharmacokinetic (PK) and pharmacodynamic alterations in critically ill trauma patients may negatively impact therapeutic drug concentration attainment and compromise antibiotic efficacy. While no direct comparisons have been conducted between critically ill trauma and non-trauma patients, literature suggests that population PK algorithms should be used cautiously in trauma patients. A literature gap currently exists in addressing optimal aminoglycoside (AG) dosing among critically ill, trauma patients. Methods: This retrospective cohort study evaluated 103 critically ill patients who received IV AGs with two subsequent detectable concentrations. The primary objective was to compare AG dose (mg/kg) required to achieve extrapolated peak concentration above 20 mg/L between critically ill trauma and non-trauma patients. In addition to PK parameters (volume of distribution, elimination rate constant, half-life, clearance, drug-free interval) comparisons, this study investigated risk factors associated with subtherapeutic AG concentrations. Results: 58 trauma and 45 non-trauma patients were included for analysis. Median dose (mg/kg) required to achieve extrapolated peak concentration above 20 mg/L was 10.0 (7.8-14.7) vs. 11.8 (9.9-15.0) in trauma and non-trauma patients, respectively (p=0.189). Median volume of distribution (L/kg) was 0.5 (0.4-0.7) vs. 0.6 (0.5-0.8) in trauma and non-trauma patients, respectively (p=0.189). Median half-life (hours) was 3.9 (3.16.3) vs. 5.9 (5.1-8.2) in trauma and non-trauma patients, respectively (p<0.001). Multivariate logistic regression identified serum albumin as an independent risk factor associated with subtherapeutic peak AG concentrations within both the critically ill trauma and non-trauma patient population. Conclusions: No difference was demonstrated in volume of distribution or required AG dose to achieve peak concentration above 10 or 20 mg/L between critically ill trauma and nontrauma patients. Required AG dose in both critically ill trauma and non-trauma patients exceeds previously reported results. AG clearance is significantly higher in critically ill trauma patients compared to critically ill non-trauma patients. Low serum albumin is associated with subtherapeutic peak concentrations in both critically ill trauma and non-trauma patients.