Beck-Schimmer Beatrice, Breitenstein Stefan, Urech Severin, De Conno Elisena, Wittlinger Moritz, Puhan Milo, Jochum Wolfram, Spahn Donat R, Graf Rolf, Clavien Pierre-Alain
Swiss HPB (Hepato-Pancreatico-Biliary) Center, University of Zurich, Zurich, Switzerland.
Ann Surg. 2008 Dec;248(6):909-18. doi: 10.1097/SLA.0b013e31818f3dda.
To evaluate the effects of pharmacological preconditioning with a volatile anesthetic in patients undergoing liver resection with inflow occlusion.
In liver surgery, ischemic preconditioning and intermittent clamping are the only established protective strategies to reduce tissue damage due to ischemia during inflow occlusion. Preconditioning with volatile anesthetics has provided protection against cardiac and renal ischemic injury in several animal models through NO and HO-1 pathways. But pharmacological preconditioning has never been tested in patients undergoing liver surgery in a randomized trial.
Sixty-four patients undergoing liver surgery with inflow occlusion were randomized intraoperatively for preconditioning with sevoflurane or not (ClinicalTrials.gov NCT00516711). Anesthesia was performed intravenously with propofol. Thirty minutes before inflow occlusion propofol was replaced by sevoflurane in the preconditioning group. Primary endpoint was postoperative liver injury assessed by peak values of liver transaminases. Postoperative complications were recorded according to an established scoring system.
Sevoflurane preconditioning significantly limited the postoperative increase of serum transaminase levels by 261 U/L (95% CI, 65 to 458; P = 0.01) for the ALT and by 239 (95% CI, -2 to 480; P = 0.05) for the AST corresponding to decreases of baseline levels of 35% and 31%, respectively. Patients with steatosis had an even better benefit than patients without steatosis. The rates of any complication (risk ratio 0.46; 95% CI, 0.25 to 0.85; P = 0.006) and of severe complications requiring invasive procedures (risk ratio 0.25; 95% CI, 0.06 to 1.08; P = 0.05) were also lowered by preconditioning.
This first randomized trial of pharmacological preconditioning in liver surgery in humans showed a protective effect of preconditioning with volatile anesthetics. This strategy may provide a new and easily applicable therapeutic option to protect the liver and to lower complication rates.
评估挥发性麻醉药进行药理学预处理对行入肝血流阻断肝切除术患者的影响。
在肝脏手术中，缺血预处理和间歇性阻断是目前仅有的已确立的可减少入肝血流阻断期间缺血所致组织损伤的保护策略。在多种动物模型中，挥发性麻醉药预处理已通过一氧化氮（NO）和血红素氧合酶-1（HO-1）途径为心脏和肾脏缺血性损伤提供保护。但药理学预处理从未在肝脏手术患者中进行过随机试验。
64例行入肝血流阻断肝切除术的患者术中随机分为七氟醚预处理组和非预处理组（ClinicalTrials.gov NCT00516711）。采用丙泊酚静脉麻醉。预处理组在入肝血流阻断前30分钟将丙泊酚替换为七氟醚。主要终点是通过肝转氨酶峰值评估的术后肝损伤。根据既定评分系统记录术后并发症。
七氟醚预处理显著限制了术后血清转氨酶水平的升高，谷丙转氨酶（ALT）升高261 U/L（95%CI，65至458；P = 0.01），谷草转氨酶（AST）升高239（95%CI，-2至480；P = 0.05），分别相当于基线水平降低35%和31%。脂肪变性患者比无脂肪变性患者获益更大。预处理还降低了任何并发症发生率（风险比0.46；95%CI，0.25至0.85；P = 0.006）以及需要侵入性操作的严重并发症发生率（风险比0.25；95%CI，0.06至1.08；P = 0.05）。
这项人类肝脏手术药理学预处理的首次随机试验显示了挥发性麻醉药预处理的保护作用。该策略可能为保护肝脏和降低并发症发生率提供一种新的、易于应用的治疗选择。
