Santiago F M, Bueno P, Olmedo C, Muffak-Granero K, Comino A, Serradilla M, Mansilla A, Villar J M, Garrote D, Ferrón J A
Anesthesiology Service, Virgen de las Nieves University Hospital, Granada, Spain.
Transplant Proc. 2008 Nov;40(9):2978-80. doi: 10.1016/j.transproceed.2008.08.103.
We investigated whether intraoperative administration of N-acetylcysteine (NAC) in liver transplant recipients ameliorated their inflammatory responses by increasing intraoperative plasma levels of interleukin (IL)-4 and IL-10. This prospective, randomized, double-blind clinical trial included liver transplant recipients randomly assigned to the NAC-treated (n = 25) or the placebo (n = 25) group. The NAC-treated group received 100 mg/kg dissolved in 5% dextrose over 15 minutes during the anhepatic phase, followed by a continuous infusion of 50 mg/kg in 5% dextrose over the next 24 hours, whereas the placebo group received equal amounts of 5% dextrose solution during the same time. Peripheral blood samples were drawn in EDTA-containing tubes after induction of anesthesia (I-1); at 15 minutes into the anhepatic phase (I-2) prior to the administration of NAC or placebo; at 5 minutes before reperfusion (I-3); at 10 minutes after reperfusion (I-4); at 20 minutes after reperfusion (I-5); at 60 minutes after reperfusion (I-6); and at 1 hour after completion of the liver transplantation (I-7). Cytokine levels were determined using a technique which combined enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Plasma IL-4 levels were significantly higher among the NAC-treated group than the placebo group at I-3 (P = .046) and I-4 (P = .041). Plasma IL-10 levels showed significant enhancement in the NAC-treated group at 5 minutes before reperfusion (I-3; P = .007). We concluded that intraoperative NAC administration during the anhepatic phase of liver transplantation significantly increased recipient IL-4 plasma levels before and after reperfusion, and IL-10 plasma values before reperfusion (I-3). These enhancements seemed to be associated with a protective effect against reperfusion injury.
我们研究了肝移植受者术中给予N-乙酰半胱氨酸(NAC)是否通过提高术中血浆白细胞介素(IL)-4和IL-10水平来改善其炎症反应。这项前瞻性、随机、双盲临床试验纳入了随机分配至NAC治疗组(n = 25)或安慰剂组(n = 25)的肝移植受者。NAC治疗组在无肝期15分钟内静脉输注溶解于5%葡萄糖溶液中的100 mg/kg NAC,随后在接下来的24小时内持续输注溶解于5%葡萄糖溶液中的50 mg/kg,而安慰剂组在相同时间内输注等量的5%葡萄糖溶液。在麻醉诱导后(I-1);在无肝期给予NAC或安慰剂前15分钟(I-2);再灌注前5分钟(I-3);再灌注后10分钟(I-4);再灌注后20分钟(I-5);再灌注后60分钟(I-6);以及肝移植完成后1小时(I-7),采集含乙二胺四乙酸(EDTA)的外周血样本。采用酶联免疫吸附测定(ELISA)和流式细胞术相结合的技术测定细胞因子水平。在I-3(P = .046)和I-4(P = .041)时,NAC治疗组的血浆IL-4水平显著高于安慰剂组。在再灌注前5分钟(I-3;P = .007),NAC治疗组的血浆IL-10水平显著升高。我们得出结论,肝移植无肝期术中给予NAC可显著提高受者再灌注前后的IL-4血浆水平以及再灌注前(I-3)的IL-10血浆水平。这些升高似乎与对再灌注损伤的保护作用有关。