乌司他丁早期干预对StanfordA型急性主动脉夹层围术期炎性细胞因子的影响

Effect of early intervention with ulinastatin on inflammatory cytokines in patients with Stanford A acute aortic dissection during perioperative period

目的探讨乌司他丁早期干预对Stanford A型急性主动脉夹层围术期炎性细胞因子水平的影响。方法选择2013年5月至2015年5月于首都医科大学附属北京安贞医院住院确诊的Stanford A型急性主动脉夹层患者88例。根据住院时间段将患者分为对照组（50例，2013年5月至2014年5月入院）和观察组（38例，2014年6月至2015年5月入院）。对照组术前按常规处理；观察组将1 000 000 IU乌司他丁溶入250 ml 0.9%氯化钠溶液中，术前6～8 h缓慢静脉滴注。2组患者均检测麻醉诱导后（T1）、离室前（T2）、术后6 h（T3）及术后24 h（T4）血浆炎性因子水平，包括肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）和IL-10。记录比较2组患者重症监护病房（ICU）机械通气时间、ICU停留时间、住院时间、术后呼吸系统并发症和病死率情况。结果组内比较，2组TNF-α水平在T2时明显高于T1时［对照组：76（12，323）μg/L比60（13，206）μg/L；观察组：57（18，87）μg/L比52（12，96）μg/L］，T3、T4时［对照组：54（15，245）μg/L、59（16，219）μg/L；观察组：40（15，87）μg/L、34（12，73）μg/L］明显低于T2时，差异均有统计学意义（均P＜0.05）；对照组TNF-α水平在T4时明显高于T3时，而观察组TNF-α水平在T4时明显低于T3时，差异均有统计学意义（均P＜0.05）；对照组IL-6水平在T2时明显高于T1时［57（13，106）μg/L比52（16，108）μg/L］，T3、T4时［48（23，94）μg/L、48（10，91）μg/L］明显低于T2时，差异均有统计学意义（均P＜0.05），观察组IL-6水平在T2、T3、T4时低于T1时［53（17，125）、48（26，64）、45（8，67）μg/L比79（38，128）μg/L］，T3、T4时明显低于T2时，T4时明显低于T3时，差异均有统计学意义（均P＜0.05）。组间比较，观察组TNF-α水平在T3、T4时明显低于对照组，差异均有统计学意义（均P＜0.05）；观察组IL-6水平在T1时高于对照组，差异有统计学意义（P＜0.05）。观察组IL-10水平在T1时低于对照组［60（9，169）μg/L比96（7，279）μg/L］，在T3、T4时明显高于对照组［83（39，119）μg/L比60（6，308）μg/L；90（29，239）μg/L比55（6，238）μg/L］，差异均有统计学意义（均P＜0.05）。观察组标准化IL-10的T4/T1高于T2/T1［1.49（0.31,2.26）比1.14（0.45,2.29）］，对照组标准化IL-10的T2/T1、T3/T1、T4/T1逐渐降低［0.95（0.58,1.46）、0.51（0.32,1.07）、0.42（0.24,0.78）］，组内差异均有统计学意义（均P＜0.05）。观察组ICU停留时间、住院时间明显短于对照组［65（16,480） h比78（8,486）h、14（9,25）d比18（14,21）d］，差异有统计学意义（P＜0.05）。结论Stanford A型急性主动脉夹层患者术前大剂量乌司他丁早期干预可抑制围术期炎性反应，对体外循环和外科手术导致的炎症放大效应有抑制作用，从而缩短患者ICU停留时间和住院时间。

ObjectiveTo evaluate the effect of early intervention with ulinastatin on inflammatory cytokines in patients with Stanford A acute aortic dissection during perioperative period. MethodsTotally 88 patients with Stanford A acute aortic dissection from May 2013 to May 2015 in Beijing Anzhen Hospital, Capital Medical University were divided into control group（50 cases） and observation group（38 cases） according to admission orders. The control group had routine treatment before operation. The observation group had intravenous infusion with 1 000 000 IU ulinastatin in 250 ml 0.9% sodium chloride solution 6-8 h before operation. Plasma inflammatory factors including tumor necrosis factor α（TNF-α）, serum interleukin 6（IL-6） and IL-10 were detected after anesthesia induction（T1）, at the end of operation（T2）, 6 h（T3） and 24 h（T4） after operation. Duration of mechanical ventilation, length of intensive care unit（ICU） stay, length of hospital stay, postoperative respiratory complications and mortality were analyzed. ResultsThe level of TNF-α at T2 was significantly higher than that at T1 in both groups[control group： 76（12, 323） μg/L vs 60（13, 206） μg/L; observation group： 57（18, 87） μg/L vs 52（12, 96） μg/L];levels of TNF-α at T3, T4[control group： 54（15, 245）μg/L, 59（16, 219）μg/L; observation group： 40（15, 87）μg/L, 34（12, 73）μg/L] were significantly lower than the level of TNF-α at T2（all P〈0.05）. The level of TNF-α in control group at T4 was significantly higher than that at T3; the level of TNF-α in observation group at T4 was significantly lower than that at T3（both P〈0.05）. The level of IL-6 in control group at T2 was significantly higher than that at T1[57（13, 106）μg/L vs 52（16, 108）μg/L]; levels of IL-6 at T3, T4[48（23, 94）μg/L, 48（10, 91）μg/L] were significantly lower than the level of IL-6 at T2（all P〈0.05）. Levels of IL-6 in observation group at T2, T3, T4 were significantly lower than the level of IL-6 at T1[53（17, 125）, 48（26, 64）, 45（8, 67）μg/L vs 79（38, 128）μg/L]; levels of IL-6 at T3, T4 were significantly lower than the level of IL-6 at T2; the level of IL-6 at T4 was significantly lower than that at T3（all P〈0.05）. Levels of TNF-α at T3, T4 in observation group were significantly lower than those in control group; the level of IL-6 at T1 in observation group was significantly higher than that in control group; the level of IL-10 at T1 in observation group was significantly lower than that in control group[60（9, 169）μg/L vs 96（7, 279）μg/L]; levels of IL-10 at T3, T4 in observation group were significantly higher than those in control group[83（39,119） μg/L vs 60（6,308） μg/L; 90（29,239）μg/L vs 55（6,238）μg/L]（all P〈0.05）. T4/T1 was significantly higher than T2/T1 on IL-10 after statistics in observation group[1.49（0.31, 2.26） vs 1.14（0.45, 2.29）] and decreased in control group[0.95（0.58,1.46）,0.51（0.32,1.07）,0.42（0.24,0.78）]（P〈0.05）. Lengths of ICU stay and hospital stay in observation group were significantly shorter than those in control group[65（16,480）h vs 78（8,486）h, 14（9,25）d vs 18（14,21）d]（P〈0.05）. ConclusionssEarly intervention with high dose of ulinastatin can inhibit inflammatory reaction after operation for Stanford A acute aortic dissection, shorten the length of ICU and hospital stay.