持续肺动脉灌注含乌司他丁的氧合冷血对中高危瓣膜置换病人体外循环术后肺损伤的保护作用
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摘要
背景与目的
随着心脏外科技术的的不断改善和提高,以及体外循环材料的改进,例如肝素涂抹的体外循环管路的应用,血液滤过如动脉微栓滤器,白细胞滤器,改良超滤,无血预充,膜式氧合以及深低温保护,各型脑灌注方法的应用,体外循环术后各脏器损伤程度比以前明显减轻。但是体外循环术后由于各种炎症介质的释放和炎症细胞的激活,产生一系列的连续反应或“瀑布样效应”,最终导致全身炎症反应综合症会导致全身脏器的损伤,而肺是最早也是最容易受到累及的器官之一。体外循环术后肺部炎性因子的大量释放,导致肺泡和肺间质水肿,不均匀的充血、出血,微血栓的形成,局限性肺不张,弥慢性炎细胞浸润等引起的呼吸功能障碍仍时常发生,严重者可能发生急性呼吸窘迫综合症(ARDS)甚至导致死亡。如何选择更好的方法和途径来减轻和预防体外循环术后肺损伤已经成为当今心外科研究的重点之-。本研究立足临床,紧密围绕体外循环术后肺损伤的发生机制,旨在发现持续肺动脉灌注含乌司他丁的氧合血对中高危心脏瓣膜置换病人体外循环术后肺损伤保护作用的影响。
材料与方法
选取60例择期拟行心脏瓣膜置换心脏手术的中高危患者(山东大学齐鲁医院心脏外科手术危险因素评分EuroScore≥4随机分为2组：对照组(C组)和乌司他丁组(U组)。乌司他丁组(U组,n=30)给予乌司他丁3×10~4U／kg,于切皮后至CPB前缓慢静注半量,另半量加入预充液中随转机进入体内；对照组(C组,n=30)用等量生理盐水代替。记录各项临床参数,包括术中心脏复跳情况、体外循环时间、升主动脉阻闭时间、呼吸机辅助呼吸时间、ICU留观时间、并发症发生情况。于术前、手术结束后8h、1d、3d和5d测定血浆中肿瘤坏死因子(TNF-a),白细胞介素—6(IL—6),白细胞介素—8(IL—8),白细胞介素-10(IL—10)和丙二醛(MDA)的水平。并同时测定动脉血气,计算肺泡-动脉氧分压差(A-aDO2)和呼吸指数(RI)。
结果
术后住院和并发症的发生率两组间无显著差异,呼吸机辅助呼吸时间、ICU留观时间与术后住院时间无显著差异。与对照组相比,乌司他丁组术后8h血浆中TNF-α、IL-6.IL-8和MDA的水平均显著下降(P＜0.05)
结论
体外循环可造成肺损伤,应用乌司他丁可以有效抑制体外循环术后炎性细胞因子的释放,可以在一定程度上减轻体外循环术后肺功能的损伤。
Background And Objective
With the continue modification and development of cardiac surgical techniques and cardiopulmonary bypass material, such as heparin smear cardiopulmonary bypass piping, hemofiltration equipment such as arterial microthrombus filter,leukocyte filter, modified ultrafiltration, no blood prefilled,membrane oxygenator and deep hypothermia protection, as well as the application of various types of brain perfusion method. CPB-releated multiple organ injury have significantly reduced than before, but the release of various inflammatory mediators and activation of inflammatory cells due to cardiopulmonary bypass, resulting in a series of consecutive reactions or "waterfall-like effect", and eventually leading to a systemic inflammatory response syndrome, of all the organs of human body,lung is the earliest and the most vulnerable organs. the massive release of inflammatory cytokines after cardiopulmonary bypass may bring about alveolar and pulmonary interstitial edema, it may give rise to uneven hyperemia, hemorrhage, microthrombus formation, and also resulted in the limitations of atelectasis, diffuse inflammatory cell infiltration. As a consequence, it may lead to serious acute respiratory distress syndrome (ARDS) even cause death, how to find better approach to mitigate and prevent lung injury after cardiopulmonary bypass has become the focus of today's cardiac surgery field. based on clinical trial, we now focusing on the mechanism of lung injury after cardiopulmonary bypass, aimed at discovering the effect of continuous pulmonary artery perfusion with ulinastatin oxygenation cold-blooded in the moderate and high-risk valve replacement patients.
Methods
60patients undergoing cardiac surgery valve replacement with moderate and high-risk patient (EuroScore≥4) were randomly divided into2groups:control group (C group) and ulinastatin group (U group). Ulinastatin group (U group, n=30) was given half of the total amount of ulinastatin (2X10U/kg) after incision and before CPB, the other half the amount was given during the CPB; The control group (C group, n=30) was given normal saline instead, clinical parameters, including intraoperative cardiac resuscitation, cardiopulmonary bypass time, after the parallel time, ascending aortic occlusion time, mechanical ventilation time, ICU time, complications, and the number of patient deaths, plasma tumor necrosis factor (TNF a), interleukin-6(IL-6), interleukin-8(IL-8), and the level of malondialdehyde (MDA) were measured before surgery, after surgery for8h,1d,3d and5d, alveolar-arterial oxygen difference (A-aDO2) and respiratory index (RI) were also calculated.. The clinical results and prognosis were observed.
Results
Postoperative hospital deaths and no significant difference in the incidence of complications, mechanical ventilation time, ICU and postoperative hospital stay without significant differences. Compared with the control group, the ulinastatin group after8h plasma TNF-a a, IL6, IL-8and MDA significantly decreased (P <0.05).
Conclusion
Cardiopulmonary bypass can cause lung injury, ulinastatin can effectively inhibit the release of inflammatory cytokines during and after CPB, reduce lung injury, protect lung function in a certain extent.
随着心脏外科技术的的不断改善和提高,以及体外循环材料的改进,例如肝素涂抹的体外循环管路的应用,血液滤过如动脉微栓滤器,白细胞滤器,改良超滤,无血预充,膜式氧合以及深低温保护,各型脑灌注方法的应用,体外循环术后各脏器损伤程度比以前明显减轻。但是体外循环术后由于各种炎症介质的释放和炎症细胞的激活,产生一系列的连续反应或“瀑布样效应”,最终导致全身炎症反应综合症会导致全身脏器的损伤,而肺是最早也是最容易受到累及的器官之一。体外循环术后肺部炎性因子的大量释放,导致肺泡和肺间质水肿,不均匀的充血、出血,微血栓的形成,局限性肺不张,弥慢性炎细胞浸润等引起的呼吸功能障碍仍时常发生,严重者可能发生急性呼吸窘迫综合症(ARDS)甚至导致死亡。如何选择更好的方法和途径来减轻和预防体外循环术后肺损伤已经成为当今心外科研究的重点之-。本研究立足临床,紧密围绕体外循环术后肺损伤的发生机制,旨在发现持续肺动脉灌注含乌司他丁的氧合血对中高危心脏瓣膜置换病人体外循环术后肺损伤保护作用的影响。
材料与方法
选取60例择期拟行心脏瓣膜置换心脏手术的中高危患者(山东大学齐鲁医院心脏外科手术危险因素评分EuroScore≥4随机分为2组：对照组(C组)和乌司他丁组(U组)。乌司他丁组(U组,n=30)给予乌司他丁3×10~4U／kg,于切皮后至CPB前缓慢静注半量,另半量加入预充液中随转机进入体内；对照组(C组,n=30)用等量生理盐水代替。记录各项临床参数,包括术中心脏复跳情况、体外循环时间、升主动脉阻闭时间、呼吸机辅助呼吸时间、ICU留观时间、并发症发生情况。于术前、手术结束后8h、1d、3d和5d测定血浆中肿瘤坏死因子(TNF-a),白细胞介素—6(IL—6),白细胞介素—8(IL—8),白细胞介素-10(IL—10)和丙二醛(MDA)的水平。并同时测定动脉血气,计算肺泡-动脉氧分压差(A-aDO2)和呼吸指数(RI)。
结果
术后住院和并发症的发生率两组间无显著差异,呼吸机辅助呼吸时间、ICU留观时间与术后住院时间无显著差异。与对照组相比,乌司他丁组术后8h血浆中TNF-α、IL-6.IL-8和MDA的水平均显著下降(P＜0.05)
结论
体外循环可造成肺损伤,应用乌司他丁可以有效抑制体外循环术后炎性细胞因子的释放,可以在一定程度上减轻体外循环术后肺功能的损伤。
Background And Objective
With the continue modification and development of cardiac surgical techniques and cardiopulmonary bypass material, such as heparin smear cardiopulmonary bypass piping, hemofiltration equipment such as arterial microthrombus filter,leukocyte filter, modified ultrafiltration, no blood prefilled,membrane oxygenator and deep hypothermia protection, as well as the application of various types of brain perfusion method. CPB-releated multiple organ injury have significantly reduced than before, but the release of various inflammatory mediators and activation of inflammatory cells due to cardiopulmonary bypass, resulting in a series of consecutive reactions or "waterfall-like effect", and eventually leading to a systemic inflammatory response syndrome, of all the organs of human body,lung is the earliest and the most vulnerable organs. the massive release of inflammatory cytokines after cardiopulmonary bypass may bring about alveolar and pulmonary interstitial edema, it may give rise to uneven hyperemia, hemorrhage, microthrombus formation, and also resulted in the limitations of atelectasis, diffuse inflammatory cell infiltration. As a consequence, it may lead to serious acute respiratory distress syndrome (ARDS) even cause death, how to find better approach to mitigate and prevent lung injury after cardiopulmonary bypass has become the focus of today's cardiac surgery field. based on clinical trial, we now focusing on the mechanism of lung injury after cardiopulmonary bypass, aimed at discovering the effect of continuous pulmonary artery perfusion with ulinastatin oxygenation cold-blooded in the moderate and high-risk valve replacement patients.
Methods
60patients undergoing cardiac surgery valve replacement with moderate and high-risk patient (EuroScore≥4) were randomly divided into2groups:control group (C group) and ulinastatin group (U group). Ulinastatin group (U group, n=30) was given half of the total amount of ulinastatin (2X10U/kg) after incision and before CPB, the other half the amount was given during the CPB; The control group (C group, n=30) was given normal saline instead, clinical parameters, including intraoperative cardiac resuscitation, cardiopulmonary bypass time, after the parallel time, ascending aortic occlusion time, mechanical ventilation time, ICU time, complications, and the number of patient deaths, plasma tumor necrosis factor (TNF a), interleukin-6(IL-6), interleukin-8(IL-8), and the level of malondialdehyde (MDA) were measured before surgery, after surgery for8h,1d,3d and5d, alveolar-arterial oxygen difference (A-aDO2) and respiratory index (RI) were also calculated.. The clinical results and prognosis were observed.
Results
Postoperative hospital deaths and no significant difference in the incidence of complications, mechanical ventilation time, ICU and postoperative hospital stay without significant differences. Compared with the control group, the ulinastatin group after8h plasma TNF-a a, IL6, IL-8and MDA significantly decreased (P <0.05).
Conclusion
Cardiopulmonary bypass can cause lung injury, ulinastatin can effectively inhibit the release of inflammatory cytokines during and after CPB, reduce lung injury, protect lung function in a certain extent.
引文
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