Giles L J, Jennings A C, Thomson A H, Creed G, Beale R J, McLuckie A
Guy's and St. Thomas Hospital Trust, St. Thomas Hospital, London, UK.
Crit Care Med. 2000 Mar;28(3):632-7. doi: 10.1097/00003246-200003000-00005.
To evaluate an intravenous meropenem dosage regimen in adult intensive care patients with acute renal failure treated by continuous renal replacement therapy.
A prospective, clinical study.
General intensive care unit of a university hospital.
Ten critically ill adult patients being treated with meropenem and receiving continuous veno-venous hemofiltration (hemofiltration rates, 1-2 L/hr) (n = 5) or continuous venovenous hemodiafiltration (hemofiltration rates, 1-1.5 L/hr; dialysis rates, 1-1.5 L/hr) (n = 5) via a polyacrylonitrile hollow fiber 0.9-m2 filter.
Patients received a meropenem dose of 1 g iv every 12 hrs as a 5-min bolus.
Meropenem concentrations were measured by high-performance liquid chromatography in serum taken at timed intervals and in ultrafiltrate/dialysate to determine serum concentration-time profiles, derive pharmacokinetic variable estimates, and determine sieving coefficients and filter clearances. The serum concentrations were examined to see whether they were above the minimum inhibitory concentrations (MICs) for pathogens that may be encountered in intensive care patients. Serum concentrations exceeded 4 mg/L (MIC90 for Pseudomonas aeruginosa) during 67% of the dosage period in all patients. Sub-MIC90 concentrations were obtained in three patients immediately before treatment and in one patient 12 hrs after treatment. Mean (SD) (n = 10) pharmacokinetic variable estimates were as follows: elimination half-life, 5.16 hrs (1.83 hrs); volume of distribution, 0.35 L/kg (0.10 L/kg); and total clearance, 4.30 L/hr (1.38 L/hr). A sieving coefficient of 0.93 (0.06) (n = 9) indicated free flow across the filter. The fraction cleared by the extracorporeal route was 48% (13%) (n = 9), which is clinically important.
A meropenem dose of 1g iv every 12 hrs provides adequate serum concentrations in the majority of patients receiving continuous veno-venous hemofiltration or continuous venovenous hemofiltration with a 0.9-m2 polyacrylonitrile filter at combined ultrafiltrate/dialysate flow rates of up to 3 L/hr. A lower dose would not be sufficient for the empirical treatment of potentially life-threatening infections in all patients.
评估静脉注射美罗培南的给药方案在接受持续肾脏替代治疗的急性肾衰竭成年重症监护患者中的效果。
一项前瞻性临床研究。
一所大学医院的综合重症监护病房。
10例成年重症患者，正在接受美罗培南治疗，并通过聚丙烯腈中空纤维0.9平方米滤器接受持续静脉 - 静脉血液滤过（血液滤过率为1 - 2升/小时）（n = 5）或持续静脉 - 静脉血液透析滤过（血液滤过率为1 - 1.5升/小时；透析率为1 - 1.5升/小时）（n = 5）。
患者每12小时静脉注射1克美罗培南，推注时间为5分钟。
通过高效液相色谱法测量定时采集的血清以及超滤液/透析液中美罗培南的浓度，以确定血清浓度 - 时间曲线，推导药代动力学变量估计值，并确定筛系数和滤器清除率。检查血清浓度是否高于重症监护患者可能遇到的病原体的最低抑菌浓度（MIC）。在所有患者中，67%的给药期间血清浓度超过4毫克/升（铜绿假单胞菌的MIC90）。3例患者在治疗前即刻以及1例患者在治疗后12小时获得低于MIC90的浓度。平均（标准差）（n = 10）药代动力学变量估计值如下：消除半衰期为5.16小时（1.83小时）；分布容积为0.35升/千克（0.10升/千克）；总清除率为4.30升/小时（1.38升/小时）。筛系数为0.93（0.06）（n = 9）表明可自由通过滤器。体外途径清除的比例为48%（13%）（n = 9），这在临床上具有重要意义。
对于大多数接受持续静脉 - 静脉血液滤过或使用0.9平方米聚丙烯腈滤器的持续静脉 - 静脉血液透析滤过且超滤液/透析液联合流速高达3升/小时的患者，每12小时静脉注射1克美罗培南可提供足够的血清浓度。较低剂量对于所有患者潜在危及生命感染的经验性治疗是不够的。
