revisiting the loading dose of amikacin for patients with severe sepsis and septic shock重新加载剂量阿米卡星的严重脓毒症和脓毒性休克患者.pdfVIP

Taccone et al. Critical Care 2010, 14:R53 /content/14/2/R53 R E S E A R C H Open Access Research Revisiting the loading dose of amikacin for patients with severe sepsis and septic shock 1 2 3 4 5 6 Fabio Silvio Taccone , Pierre-François Laterre , Herbert Spapen , Thierry Dugernier , Isabelle Delattre , Brice Layeux , 1 2 5 1 6 Daniel De Backer , Xavier Wittebole , Pierre Wallemacq , Jean-Louis Vincent and Frédérique Jacobs* 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 fo ur 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 concent