Revisiting the loading dose of amikacin for patients with severe sepsis and septic shock 英文参考文献.docVIP

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Revisiting the loading dose of amikacin for patients with severe sepsis and septic shock 英文参考文献.doc

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Revisiting the loading dose of amikacin for patients with severe sepsis and septic shock 英文参考文献

Taccone et al. Critical Care 2010, 14:R53 /content/14/2/R53 RESEARCH Open Access Revisiting the loading dose of amikacin for patients Research with severe sepsis and septic shock Fabio Silvio Taccone1, Pierre-Fran?ois Laterre2, Herbert Spapen3, Thierry Dugernier4, Isabelle Delattre5, Brice Layeux6, Daniel De Backer1, Xavier Wittebole2, Pierre Wallemacq5, Jean-Louis Vincent1 and Frédérique Jacobs*6 Abstract Introduction: It has been proposed that doses of amikacin of 15 mg/kg should be used in conditions associated with an increased volume of distribution (Vd), such as severe sepsis and septic shock. The primary aim of this study was to determine whether 25 mg/kg (total body weight) of amikacin is an adequate loading dose for these patients. Methods: This was an open, prospective, multicenter study in four Belgian intensive care units (ICUs). All consecutive patients with a diagnosis of severe sepsis or septic shock, in whom amikacin treatment was indicated, were included in the study. Results: In 74 patients, serum samples were collected before (t = 0 h) and 1 hour (peak), 1 hour 30 minutes, 4 hours 30 minutes, 8 hours, and 24 hours after the first dose of amikacin. Blood amikacin levels were measured by using a validated fluorescence polarization immunoassay method, and an open two-compartment model with first-order elimination was fitted to concentrations-versus-time data for amikacin (WinNonlin). In 52 (70%) patients, peak serum concentrations were 64 μg/ml, which corresponds to 8 times the clinical minimal inhibitory concentration (MIC) breakpoints defined by EUCAST for Enterobacteriaceae and Pseudomonas aeruginosa (S8, R16 μg/ml). Vd was 0.41 (0.29 to 0.51) L/kg; elimination half-life, 4.6 (3.2 to 7.8) hours; and total clearance, 1.98 (1.28 to 3.54) ml/min/kg. No correlation was found between the amikacin peak and any clinical or hemodynamic variable. Conclusions: As patients with severe sepsis and septic shock have an increased Vd, a first dose o