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Erschienen in:
01.07.2014 | Original
Predictors of insufficient amikacin peak concentration in critically ill patients receiving a 25 mg/kg total body weight regimen
Erschienen in: Intensive Care Medicine | Ausgabe 7/2014
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Purpose
Amikacin requires pharmacodynamic targets of peak serum concentration (C
max) of 8–10 times the minimal inhibitory concentration, corresponding to a target C
max of 60–80 mg/L for the less susceptible bacteria. Even with new dosing regimens of 25 mg/kg, 30 % of patients do not meet the pharmacodynamic target. We aimed to identify predictive factors for insufficient C
max in a population of critically ill patients.
Methods
Prospective observational monocentric study of patients admitted to a general ICU and requiring a loading dose of amikacin. Amikacin was administered intravenously at the dose of 25 mg/kg of total body weight. Independent determinants of C
max < 60 mg/L were identified by mixed model multivariate analysis.
Results
Over a 1-year period, 181 episodes in 146 patients (SAPS 2 = 51 [41–68]) were included. At inclusion, the SOFA score was 8 [6–12], 119 (66 %) episodes required vasopressors, 150 (83 %) mechanical ventilation, and 81 (45 %) renal replacement therapy. The amikacin C
max was 69 [54.9–84.4] mg/L. Overall, 60 (33 %) episodes had a C
max < 60 mg/L. The risk of C
max < 60 mg/L associated with BMI < 25 kg/m2 varied across quarters of inclusion. Independent risk factors for C
max < 60 mg/L were a BMI < 25 kg/m2 over the first quarter (odds ratio (OR) 15.95, 95 % confidence interval (CI) [3.68–69.20], p < 0.001) and positive 24-h fluid balance (OR per 250-mL increment 1.06, 95 % [CI 1.01–1.11], p = 0.018).
Conclusions
Despite an amikacin dose of 25 mg/kg of total body weight, 33 % of patients still had an amikacin C
max < 60 mg/L. Positive 24-h fluid balance was identified as a predictive factor of C
max < 60 mg/L. When total body weight is used, low BMI tended to be associated with amikacin underdosing. These results suggest the need for higher doses in patients with a positive 24-h fluid balance in order to reach adequate therapeutic targets.