Experience with a once-daily dosing program of aminoglycosides in critically ill patients
Experience with a once-daily dosing program of aminoglycosides in critically ill patients
复制标题
DOI：
10.1007/s00134-002-1313-7
复制
发表时间：
2002-07-01
影响因子：
38.9
通讯作者：
Bruining, HA
中科院分区：
文献类型：
--
作者：
Buijk, SE;Mouton, JW;Bruining, HA
背景：由于氨基糖苷类药物显示出浓度依赖性杀伤作用，因此已制定了每日一次的氨基糖苷类药物（ODA）方案。ODA方案治疗危重患者的经验数据有限。目的：1）评价危重患者的ODA方案; 2）描述氨基糖苷类药物（庆大霉素和妥布霉素）的药代动力学; 3）评估ODA方案相关肾毒性在这组患者中的发生率。设计：前瞻性、描述性研究。设置：转诊中心的18张外科病床和12张内科重症监护病房。患者：监测了89名疑似或确诊感染且需要使用庆大霉素或妥布霉素且肌酐清除率>30 ml/min的重症患者。收集了109份药代动力学曲线。干预措施：对每例患者给予第一剂7 mg/kg/24 h庆大霉素或妥布霉素，与肾功能无关。根据首次给药的药代动力学结果选择后续剂量。测量：在氨基糖苷类药物输注开始后1小时和6小时采集血清样品。所有样本均采用免疫荧光法进行检测。使用一室模型估计药代动力学参数。结果：重症感染性休克患者的氨基糖苷类药物分布容积明显高于无感染性休克患者。因此，感染性休克患者达到的最大浓度显著较低。在铜绿假单胞菌感染中，Cmax/MIC比值的平均（SD）估计值为10.3（3.3）。在n=17（49%）的患者中，治疗>24小时（n=35）。需要调整剂量或延长间隔。基于Hartford医院列线图和6 h单血清浓度的推荐给药间隔仅在62%的病例中正确。n=12（14%）例患者出现肾损害体征;所有存活者的肾功能完全恢复，无需血液滤过。结论：在我们人群中的大多数重症患者中，7 mg/kg的ODA方案产生的Cmax/MIC比值>10。感染性休克和肾功能不全导致这些患者氨基糖苷类药物的药代动力学特征异常。因此，个体治疗药物监测是必要的。肾损害体征在休克时常见，但似乎是可逆的。
Background: As aminoglycosides show concentration-dependent killing, once-daily aminoglycoside (ODA) regimens have been instituted. Data on experience with ODA regimens in critically ill patients are limited. Objectives: 1) To evaluate the ODA-program in critically ill patients; 2) to describe the pharmacokinetics of aminoglycosides (gentamicin and tobramycin); and 3) to assess the incidence of nephrotoxicity associated with an ODA regimen in this specific of group patients. Design: A prospective, descriptive study. Setting: Eighteen-bed surgical and 12-bed medical intensive care unit in a referral centre. Patients: Eighty-nine critically ill patients with a suspected or confirmed infection for which gentamicin or tobramycin was indicated and a creatinine clearance >30 ml/min were monitored. One hundred and nine pharmacokinetic profiles were gathered. Interventions: A first dose of 7 mg/kg/24 h of gentamicin or tobramycin was given to every patient independent of renal function. Subsequent doses were chosen on the basis of the pharmacokinetic results of the first dose. Measurements: Serum samples were collected I h and 6 h after start of the aminoglycoside infusion. All samples were assayed by using immunofluorescence. Pharmacokinetic parameters were estimated using a one-compartment model. Results: The volume of distribution of aminoglycosides was significantly higher in critical ill patients with septic shock than in those without. Consequently, the maximum concentration reached was significantly lower in patients with septic shock. In P. aeruginosa infections the mean (SD) estimated Cmax/MIC ratio was 10.3 (3.3). In n=17 (49%) of the patients treated >24 h (n=35). a dose adjustment or lengthening of interval was necessary. The recommended dosing interval based on the Hartford Hospital nomogram and one-serum concentration at 6 h was correct in only 62% of all cases. Signs of renal impairment occurred in n=12 (14%) of the patients; in all survivors renal function recovered completely and no haemofiltration was needed. Conclusions: An ODA-regimen of 7 mg/kg produced Cmax/MIC ratios >10 in the majority of critically ill patients in our population. Septic shock and renal dysfunction caused an aberrant pharmacokinetic profile of aminoglycosides in these patients. Therefore, individual therapeutic drug monitoring is warranted. Signs of renal impairment were common in the presence of shock, but appeared to be reversible.