Capellier G, Cornette C, Boillot A, Guinchard C, Jacques T, Blasco G, Barale F
Centre Hospitalier Universitaire Jean Minjoz, Faculté de Pharmacie, Besançon, France.
Crit Care Med. 1998 Jan;26(1):88-91. doi: 10.1097/00003246-199801000-00021.
Continuous hemofiltration is now widely used in the intensive care unit. Our study aimed to assess the removal of piperacillin under continuous hemofiltration and to define a suitable dosage regimen of administration.
Prospective study of blood and ultrafiltrate concentrations of piperacillin to assess the pharmacokinetics of the antibiotic.
The medical intensive care unit of a teaching hospital.
Ten patients were included in the study. Six patients were receiving their first dose of piperacillin (group 1) and four had already been treated for 2 to 6 days (group 2). The mean Simplified Acute Physiology II score was 74 +/- 6 (SEM), and the number of organ failures was 3.6 +/- 0.3 (range 3 to 5). Renal failure was related to septic shock in seven patients and to cardiogenic shock in three patients. Seven patients were anuric. Hepatic dysfunction was present in four of the ten patients.
Patients were treated with continuous venovenous hemofiltration using a hollow polysulfone capillary fiber. Piperacillin (4 g) was injected intravenously over 20 mins. Arterial blood and ultrafiltrate were sampled immediately before the injection and then every hour until 8 hrs after injection time. Piperacillin concentrations were assayed using high performance liquid chromatography.
In group 1, the mean serum peak concentration of piperacillin was in the normal range (125 +/- 21 mg/L), but trough values were higher (48 +/- 8 mg/L) than in normal subjects. In group 2, trough values before the injection were increased in all patients (188 +/- 71 mg/L). At T1, blood peak concentration reached 470 +/- 127 mg/L. A small amount of piperacillin was retrieved from the ultrafiltrate. The elimination half-life was 5.1 +/- 1.4 and 4.8 +/- 1.4 hrs in groups 1 and 2, respectively.
Piperacillin was not removed to a significant extent during continuous hemofiltration. Further, in the intensive care unit, patients in shock with multiple organ failure such as liver failure might behave differently from patients with stable end-stage renal disease. A 4-g dose of piperacillin twice a day is recommended in such patients.
持续血液滤过目前在重症监护病房中广泛应用。我们的研究旨在评估持续血液滤过对哌拉西林的清除作用,并确定合适的给药剂量方案。
对哌拉西林的血液和超滤液浓度进行前瞻性研究,以评估该抗生素的药代动力学。
一家教学医院的内科重症监护病房。
10名患者纳入研究。6名患者接受哌拉西林首剂治疗(第1组),4名患者已接受2至6天治疗(第2组)。简化急性生理学II评分均值为74±6(标准误),器官功能衰竭数为3.6±0.3(范围3至5)。7名患者肾衰竭与感染性休克有关,3名患者与心源性休克有关。7名患者无尿。10名患者中有4名存在肝功能障碍。
患者采用中空聚砜毛细管纤维进行持续静静脉血液滤过治疗。哌拉西林(4g)在20分钟内静脉注射。在注射前即刻采集动脉血和超滤液样本,然后每小时采集一次,直至注射后8小时。采用高效液相色谱法测定哌拉西林浓度。
在第1组中,哌拉西林的血清平均峰浓度在正常范围内(125±21mg/L),但谷值高于正常受试者(48±8mg/L)。在第2组中,所有患者注射前的谷值均升高(188±71mg/L)。在T1时,血液峰浓度达到470±127mg/L。从超滤液中回收了少量哌拉西林。第1组和第2组的消除半衰期分别为5.1±1.4小时和4.8±1.4小时。
持续血液滤过期间哌拉西林清除程度不显著。此外,在重症监护病房中,伴有多器官功能衰竭如肝衰竭的休克患者与稳定的终末期肾病患者的表现可能不同。建议此类患者每日两次给予4g哌拉西林。