Predictors of insufficient amikacin peak concentration in critically ill patients receiving a 25 mg/kg total body weight regimen
Predictors of insufficient amikacin peak concentration in critically ill patients receiving a 25 mg/kg total body weight regimen
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DOI：
10.1007/s00134-014-3276-x
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发表时间：
2014-07-01
影响因子：
38.9
通讯作者：
Sonneville, Romain
中科院分区：
文献类型：
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作者：
de Montmollin, Etienne;Bouadma, Lila;Sonneville, Romain
阿米卡星要求药效学目标的峰值血清浓度（C (max)）为最低抑制浓度的8-10倍，对应于较不敏感菌的目标C （max）为60-80 mg/L。即使采用25mg /kg的新给药方案，30%的患者仍未达到药效学目标。我们的目的是确定危重患者人群中C （max）不足的预测因素。对普通ICU收治的需要阿米卡星负荷剂量的患者进行前瞻性单中心观察研究。阿米卡星静脉注射剂量为25mg /kg体重。通过混合模型多因素分析确定了C (max) < 60 mg/L的独立决定因素。在1年的时间里，纳入146例患者的181次发作（SAPS 2 = 51[41-68]）。纳入时，SOFA评分为8[6-12]，119次（66%）发作需要血管加压药物，150次（83%）需要机械通气，81次（45%）需要肾脏替代治疗。阿米卡星C （max）为69 [54.9 ~ 84.4]mg/L。总的来说，60次（33%）发作的C（最大）< 60 mg/L。C (max) < 60mg /L与BMI < 25kg /m(2)相关的风险在纳入的各个季度中有所不同。C (max) < 60 mg/L的独立危险因素是第一季度BMI < 25 kg/m(2)（优势比（OR） 15.95, 95%可信区间（CI） [3.68-69.20], p < 0.001）和24小时体液平衡阳性（OR每250-mL增加1.06,95% [CI 1.01-1.11], p = 0.018）。尽管阿米卡星剂量为25mg /kg总体重，33%的患者阿米卡星C（最大）仍< 60mg /L。24小时体液平衡阳性被认为是C (max) < 60 mg/L的预测因素。当使用总体重时，低BMI往往与阿米卡星剂量不足有关。这些结果表明，24小时体液平衡阳性的患者需要更高的剂量才能达到足够的治疗目标。
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.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.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/m(2) varied across quarters of inclusion. Independent risk factors for C (max) < 60 mg/L were a BMI < 25 kg/m(2) 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).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.