亚麻醉剂量氯胺酮对肝移植围术期细胞因子的影响

Effects of subanesthetic dose of ketamine on perioperative serum cytokines in orthotopic liver transplantation

目的探讨原位肝移植围术期亚麻醉剂量氯胺酮对血清细胞因子水平的影响。方法将行经典式原位肝移植手术病人20例随机均分为氯胺酮组(于麻醉后手术前静脉注射氯胺酮0.25mg/kg·b.w.,继以每小时0.5mg/kg·b.w.持续静脉滴注,无肝期暂停,开放前10min重启至手术结束);对照组(给予同等容量生理盐水),并于麻醉后手术前、阻断前5min、开放前5min、开放后15min、开放后60min、术毕即刻、术后4h、术后24h采集动脉血,酶联法检测血清中TNF-α、IL-6、IL-10水平。结果无肝期两组病人血中3种细胞因子水平较术前均显著增加(P<0.05),以IL-6和IL-10更为明显,开放后进一步上升,并于开放后60min达高峰,术后24h降至较术前略高水平。氯胺酮组TNF-α水平从阻断前5min至术毕4h均显著低于对照组(P<0.05),IL-6水平从阻断前5min至开放后60min明显低于对照组(P<0.05),IL-10水平在各个时间点两组间均无影响(P>0.05)。结论肝移植术中由于缺血再灌注及手术应激,机体产生明显的炎症及抗炎反应,以IL6及IL-10更为灵敏。氯胺酮能够抑制TNF-α、IL-6的上升,对IL-10的作用不明确。

Objective To evaluate the effects of ketamine on perioperative serum cytokine levels in patients undergoing orthotopic liver transplantation （OLT）. Methods Twenty patients undergoing OLT were randomly divided into ketamine group （n=10） and control group （n=10）. Patients in ketamine group were given intravenous bolus injection of ketamine at 0.25 mg/kg followed by ketamine infusion at 0.5 mg.kg^-1·h^-1 until the end of operation except in the anhepatic phase, whereas the control group received saline of the same amount. Arterial blood samples were obtained at the start of surgery （T1）, 5 min before the anhepatic phase （T2）, 5 min before recirculation （T3）, 15 and 60 min aider recirculation （T4, T5）, and 0, 4 and 24 h after operation （T6, T7, T8）. Serum levels of tumor necrosis factor-α （TNF-α, interleukin-6 （IL-6） and IL-10 were measured by ELISA. Results Serum TNF-α, IL-6 and IL- 10 levels increased significantly during anhepatic phase as compared with the baseline level （T1） （P〈0.05）, and the changes were especially obvious in IL-6 and IL-10. The levels of the cytokines kept rising after recriculation and reached the peak level at Ts（P〈0.05）, followed then by rapid decline and still maintaining higher levels than the preoperative ones 24 h aider operation. The levels of TNF-α in ketamine group between T2 and T7 were significantly lower than that in the control group, and the IL-6 level between T2 and T5 were also significantly lower in ketamine group. Serum IL-10 level did not show any significant difference between the two groups. Conclusion Ischemia and reperfusion injury of the liver and surgical stress induce pro- and anti-inflammatory cytokine responses during liver transplantation, in which event IL-6 and IL- 10 are more sensitive than TNF-α. Ketamine can inhibit the production of TNF-α and IL-6 but not IL-10.