Amikacin in emergency surgery: How to dose it optimally?

Abstract

Amikacin is still a recommended option in emergency surgery. Current guidelines have suggested an amikacin dose of 15-20 mg/kg/24 h for intra-abdominal infections (IAI). Our objectives were to analyse amikacin pharmacokinetics (PK) and dosage requirements in patients who underwent emergency surgery, and to identify an optimal dosing approach. We performed a retrospective data analysis of patients who received amikacin for emergency surgery over 2.5 years, with measurement of both peak (C_max) and trough (C_min) concentration after the first dose. The BestDose software was used to analyse amikacin concentrations and simulate various alternative dosage regimens in each patient. We compared concentration estimates with target values: C_max > 64 mg/L and C_min < 2.5 mg/L at 24 h. Classification and regression tree analysis was used to identify determinants of C_max target attainment (TA) and optimal dose. Data from 84 patients, including 62 with IAI, were analysed. Despite a median initial dose of 25 mg/kg, 32% of patients did not achieve the C_max target. An amikacin dose ≤ 21.5 mg/kg was the primary predictor of failure to achieve the target. A dose of 30 mg kg of total or corrected body weight, as well as a fixed dose of 2500 mg would result in the highest TA. The primary determinants of the optimal dose were ideal body weight, age, and renal function. To conclude, recommended dosages of amikacin in emergency surgery are not optimal. A fixed initial dose of 2500 mg could simplify and optimise dosing in this setting.

Keywords: Amikacin; Emergency surgery; Intra-abdominal infections; Pharmacokinetics.