Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, Bruxelles, Belgium.
Crit Care. 2010;14(2):R53. doi: 10.1186/cc8945. Epub 2010 Apr 6.
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.
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.
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 microg/ml, which corresponds to 8 times the clinical minimal inhibitory concentration (MIC) breakpoints defined by EUCAST for Enterobacteriaceae and Pseudomonas aeruginosa (S<8, R>16 microg/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.
As patients with severe sepsis and septic shock have an increased Vd, a first dose of >or= 25 mg/kg (total body weight) of amikacin is required to reach therapeutic peak concentrations. However, even with this higher amikacin dose, the peak concentration remained below therapeutic target levels in about one third of these patients. Optimizing aminoglycoside therapy should be achieved by tight serum-concentration monitoring because of the wide interindividual variability of pharmacokinetic abnormalities.
有人提出，在分布容积（Vd）增加的情况下（如严重脓毒症和感染性休克），应使用大于 15 毫克/公斤的阿米卡星剂量。本研究的主要目的是确定 25 毫克/公斤（体重）的阿米卡星是否为这些患者的合适负荷剂量。
这是一项在比利时四个重症监护病房（ICU）进行的开放、前瞻性、多中心研究。所有被诊断为严重脓毒症或感染性休克并需要接受阿米卡星治疗的连续患者均纳入研究。
在 74 例患者中，在给予阿米卡星第一剂前（t=0 小时）和 1 小时（峰值）、1 小时 30 分钟、4 小时 30 分钟、8 小时和 24 小时采集血清样本。采用经验证的荧光偏振免疫测定法测量血阿米卡星水平，并采用开放式单室模型和一级消除拟合阿米卡星（WinNonlin）的浓度-时间数据。在 52 例（70%）患者中，峰值血清浓度>64 微克/毫升，这对应于 EUCAST 为肠杆菌科和铜绿假单胞菌定义的临床最小抑菌浓度（MIC）断点的 8 倍（S<8，R>16 微克/毫升）。Vd 为 0.41（0.29 至 0.51）L/kg；消除半衰期为 4.6（3.2 至 7.8）小时；总清除率为 1.98（1.28 至 3.54）毫升/分钟/公斤。未发现阿米卡星峰值与任何临床或血流动力学变量之间存在相关性。
由于严重脓毒症和感染性休克患者的 Vd 增加，需要给予>或=25 毫克/公斤（体重）的阿米卡星首剂，以达到治疗性峰值浓度。然而，即使使用这种更高剂量的阿米卡星，在大约三分之一的这些患者中，峰值浓度仍低于治疗目标水平。由于药代动力学异常的个体间变异性很大，应通过严格的血清浓度监测来优化氨基糖苷类药物治疗。
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