Awad S S, Swaniker F, Magee J, Punch J, Bartlett R H
Department of Surgery, Division of Surgical Critical Care, University of Michigan Hospitals, Ann Arbor, USA.
Surgery. 2001 Aug;130(2):354-62. doi: 10.1067/msy.2001.116671.
We have previously reported the clearance of protein-bound and water-soluble hepatic toxins, in vitro and in an animal model, using albumin dialysis as an extracorporeal hepatic support (ECHS) device.
The objective of this study was to evaluate albumin dialysis through a phase I clinical trial. We hypothesized that albumin dialysis would (1) decrease elevated levels of hepatic toxins, (2) increase the Fischer ratio, and (3) decrease hepatic encephalopathy (HES) and intracranial pressure (ICP), while (4) maintaining stable hemodynamics.
Patients with acute liver failure were treated with an ECHS device utilizing continuous hemodiafiltration with continuous albumin dialysis. Mean arterial blood pressure (MAP), heart rate (HR), systemic venous oxygen saturation (Svo(2)), ICP, and HES were recorded. Blood samples were evaluated for hepatic toxins and factor VII levels.
Nine patients were enrolled (status I, n = 5; status IIA, n = 4). There was no significant change in MAP, HR, or Svo(2) (MAP: Pre = 81 +/- 5.6 mm Hg, Post = 79 +/- 5.9 mm Hg, P =.70; HR: Pre = 104 +/- 5.2 bpm, Post = 107 +/- 6.2 bpm, P =.62; Svo(2): Pre = 72 +/- 3.5, Post = 71 +/- 1.7, P =.77). There was a decrease in the ammonia and total bilirubin levels (NH(3): Pre = 129.8 +/- 23.8 mg/dL, Post = 63.9 +/- 16.1 mg/dL, P =.01; total bilirubin: Pre = 20.3 +/- 2.5 mg/dL, Post = 17.6 +/- 2.7 mg/dL, P =.4). There was a significant increase of the Fischer ratio and factor VII levels (Fischer ratio: Pre = 0.98 +/- 0.2, Post = 2.17 +/- 0.5, P =.038; factor VII: Pre = 13.9 +/- 4.9, Post = 23.2 +/- 4.8, P =.015). There was a significant decrease in the HES and ICP (HES: Pre = 3.8 +/- 0.1, Post = 2 +/- 0.7, P =.02; ICP: Pre = 37 +/- 3.9, Post = 13.3 +/- 2.8, P =.048). Of 5 status I patients, 1 recovered native hepatic function and 3 were bridged to transplantation.
This phase I study suggests that albumin dialysis as a liver support device is safe and effective in clearing hepatic toxins, with an associated decrease in the HES and ICP. This encouraging efficacy data warrant further investigation with a phase II/III trial.
我们之前曾报道过，在体外及动物模型中，使用白蛋白透析作为一种体外肝脏支持（ECHS）装置来清除与蛋白结合及水溶性的肝脏毒素。
本研究的目的是通过一项I期临床试验评估白蛋白透析。我们假设白蛋白透析将（1）降低肝脏毒素的升高水平，（2）提高费希尔比率，（3）降低肝性脑病（HES）和颅内压（ICP），同时（4）维持稳定的血流动力学。
急性肝衰竭患者使用一种ECHS装置进行治疗，该装置采用持续血液透析滤过联合持续白蛋白透析。记录平均动脉血压（MAP）、心率（HR）、全身静脉血氧饱和度（Svo₂）、ICP和HES。对血样进行肝脏毒素和凝血因子VII水平评估。
纳入9例患者（I期，n = 5；IIA期，n = 4）。MAP、HR或Svo₂无显著变化（MAP：术前 = 81 ± 5.6 mmHg，术后 = 79 ± 5.9 mmHg，P = 0.70；HR：术前 = 104 ± 5.2次/分钟，术后 = 107 ± 6.2次/分钟，P = 0.62；Svo₂：术前 = 72 ± 3.5，术后 = 71 ± 1.7，P = 0.77）。氨和总胆红素水平降低（NH₃：术前 = 129.8 ± 23.8 mg/dL，术后 = 63.9 ± 16.1 mg/dL，P = 0.01；总胆红素：术前 = 20.3 ± 2.5 mg/dL，术后 = 17.6 ± 2.7 mg/dL，P = 0.4）。费希尔比率和凝血因子VII水平显著升高（费希尔比率：术前 = 0.98 ± 0.2，术后 = 2.17 ± 0.5，P = 0.038；凝血因子VII：术前 = 13.9 ± 4.9，术后 = 23.2 ± 4.8，P = 0.015）。HES和ICP显著降低（HES：术前 = 3.8 ± 0.1，术后 = 2 ± 0.7，P = 0.02；ICP：术前 = 37 ± 3.9，术后 = 13.3 ± 2.8，P = 0.048）。5例I期患者中，1例恢复了肝脏自身功能，3例过渡到肝移植。
这项I期研究表明，白蛋白透析作为一种肝脏支持装置在清除肝脏毒素方面是安全有效的，同时伴有HES和ICP的降低。这些令人鼓舞的疗效数据值得通过II/III期试验进行进一步研究。
