Aminoglycoside Dosing and Volume of Distribution in Critically Ill Surgery Patients

Background: At a tertiary referral and Level I trauma center, current institutional guidelines suggest initial aminoglycoside doses of gentamicin or tobramycin 4 mg/kg and amikacin 16 mg/kg for patients admitted to surgical intensive care units (SICUs) with suspected gram-negative infection. The objective of this study was to evaluate initial aminoglycoside dosing and peak serum drug concentrations in critically ill surgery patients to characterize the aminoglycoside volume of distribution (V-d) and determine an optimal standardized dosing strategy. Methods: This retrospective, observational, single-center study included adult SICU patients who received an aminoglycoside for additional gram-negative coverage. Descriptive statistics were used to evaluate the patient population, aminoglycoside dosing, and V-d. Multivariable linear regression was applied to determine variables associated with greater aminoglycoside V-d. The mortality rate was compared in patients who achieved adequate initial peak concentrations versus those who did not. Results: One hundred seventeen patients received an aminoglycoside in the SICUs, of whom 58 had an appropriately timed peak concentration measurement. The mean Acute Physiology, Age, and Chronic Health Evaluation (APACHE) II score was 27.8 +/- 8.9. The V-d in patients receiving gentamicin, tobramycin, and amikacin was 0.49 +/- 0.10, 0.41 +/- 0.09, and 0.53 +/- 0.13 L/kg, respectively. Together, the mean aminoglycoside V-d was 0.50 +/- 0.12 L/kg. Gentamicin or tobramycin 5 mg/kg achieved goal peak concentrations in 24 patients (63.2%), and amikacin 20 mg/kg achieved the desired concentrations in nine patients (50.0%). Net fluid status, Body Mass Index, and vasopressor use were not predictive of V-d. There was no difference in the in-hospital mortality rate in patients who achieved adequate peak concentrations versus those who did not (26.8% versus 26.7%; p = 0.99). Conclusion: High aminoglycoside doses are needed in critically ill surgery patients to achieve adequate initial peak concentrations because of the high V-d. Goal peak concentrations were optimized at doses of gentamicin or tobramycin 5 mg/kg, and amikacin 20 mg/kg.