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体外循环心脏手术后洛索洛芬对肺炎症反应综合征的影响。

Effect of lornoxicam in lung inflammatory response syndrome after operations for cardiac surgery with cardiopulmonary bypass.

机构信息

1 Cardiothoracic Surgery Department, "Saint Luke" Private Hospital, Thessaloniki, Panorama, Greece ; 2 Pulmonary Department-Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece ; 3 Anesthisiology Department, University of Larisa, Larisa, Greece ; 4 Cardiothoracic Surgery Department, University General Hospital of Alexandroupolis, Alexandroupolis, Greece ; 5 Oncology Department, 6 Anesthisology Department, 7 Cardiology Department, "Saint Luke" Private Hospital, Thessaloniki, Panorama, Greece ; 8 Surgery Department (NHS), University General Hospital of Alexandroupolis, Alexandroupolis, Greece ; 9 Internal Medicine Department, "Thegeneio" Cancer Hospital, Thessaloniki, Greece ; 10 Cardiothoracic Surgery Department, University of Ioannina, Ioannina, Greece.

出版信息

J Thorac Dis. 2014 Mar;6 Suppl 1(Suppl 1):S7-S20. doi: 10.3978/j.issn.2072-1439.2013.12.30.

Abstract

BACKGROUND

The establishment of Extracorporeal Circulation (EC) significantly contributed to improvement of cardiac surgery, but this is accompanied by harmful side-effects. The most important of them is systemic inflammatory response syndrome. Many efforts have been undertaken to minimize this problem but unfortunately without satisfied solution to date.

MATERIALS AND METHODS

Lornoxicam is a non steroid anti-inflammatory drug which temporally inhibits the cycloxygenase. In this clinical trial we study the effect of lornoxicam in lung inflammatory response after operations for cardiac surgery with cardiopulmonary bypass. In our study we conclude 14 volunteers patients with ischemic coronary disease undergoing coronary artery bypass grafting with EC. In seven of them 16 mg lornoxicam was administered iv before the anesthesia induction and before the connection in heart-lung machine. In control group (7 patients) we administered the same amount of normal saline.

RESULTS

Both groups are equal regarding pro-operative and intra-operative parameters. The inflammatory markers were calculated by Elisa method. We measured the levels of cytokines (IL-6, IL-8, TNF-a), adhesion molecules (ICAM-1, e-Selectin, p-Selectin) and matrix metaloproteinase-3 (MMP-3) just after anesthesia induction, before and after cardiopulmonary bypass, just after the patients administration in ICU and after 8 and 24 hrs. In all patients we estimated the lung's inflammatory reaction with lung biopsy taken at the begging and at the end of the operation. We calculated hemodynamics parameters: Cardiac Index (CI), Systemic Vascular Resistance Index (SVRI), Pulmonary Vascular Resistance Index (PVRI), Left Ventricular Stroke Work Index (LVSWI), Right Ventricular Stroke Work Index (RVSWI), and the Pulmonary arterial pressure, and respiratory parameters too: alveolo-arterial oxygen difference D (A-a), intrapulmonary shunt (Qs/Qt) and pulmonary Compliance. IL-6 levels of lornoxicam group were statistical significant lower at 1st postoperative day compared to them of control group (113±49 and 177±20 respectively, P=0.008). ICAM-1 levels were statistical significant lower at the patient admission in ICU, compared to them of control group (177±29 and 217±22 respectively, P=0.014), and the 1st postoperative day compared to them in control group (281±134 and 489±206 respectively, P=0.045). P-selectin levels were statistical significant lower, compared to them in control group in four measurements (97±23 and 119±7 respectively, P=0.030, 77±19 and 101±20 respectively, P=0.044, 86±4 and 105±13 respectively, P=0.06, 116±13 and 158±17 respectively, P=0.000).

CONCLUSIONS

Hemodynamics and respiratory parameters were improved compared to control group, but these differences was not statistical significant. Eosinofil adhesion and sequestration in intermediate tissue of lung parenchyma were significantly lower compared to control group. Also, alveolar edema was not noted in lornoxicam's group. Lornoxicam reduce the inflammatory response in patients undergone coronary artery bypass grafting with extracorporeal circulation. This calculated from levels reduction of IL-6, ICAM-1 και p-Selectin, and from lung pathologoanatomic examination (absence of alveolar edema, reduce in eosinofil adhesion and sequestration in intermediate tissues). Despite the favorable effect of lornoxicam on the hemodinamics and respiratory parameters these improvement did not seem to be statistical significant.

摘要

背景

体外循环(EC)的建立显著改善了心脏手术,但随之而来的是有害的副作用。其中最重要的是全身炎症反应综合征。人们已经做出了许多努力来尽量减少这个问题,但不幸的是,到目前为止还没有令人满意的解决方案。

材料和方法

氯诺昔康是一种非甾体抗炎药,可暂时抑制环氧化酶。在这项临床试验中,我们研究了氯诺昔康对体外循环心脏手术后肺炎症反应的影响。在我们的研究中,我们总结了 14 名患有缺血性冠状动脉疾病的志愿者患者,他们正在进行冠状动脉旁路移植术和体外循环。在他们中的 7 人,在麻醉诱导前和心肺机连接前静脉注射 16 毫克氯诺昔康。在对照组(7 名患者)中,我们给予相同数量的生理盐水。

结果

两组在术前和术中参数方面是相等的。通过 Elisa 法测量炎症标志物。我们测量了细胞因子(IL-6、IL-8、TNF-a)、黏附分子(ICAM-1、e-Selectin、p-Selectin)和基质金属蛋白酶-3(MMP-3)的水平,这些标志物在麻醉诱导后、体外循环前后、患者进入 ICU 后以及 8 小时和 24 小时后进行测量。在所有患者中,我们通过在手术开始和结束时获取的肺活检来估计肺的炎症反应。我们计算了血流动力学参数:心指数(CI)、全身血管阻力指数(SVRI)、肺血管阻力指数(PVRI)、左心室每搏功指数(LVSWI)、右心室每搏功指数(RVSWI)和肺动脉压,以及呼吸参数:肺泡-动脉氧差 D(A-a)、肺内分流(Qs/Qt)和肺顺应性。氯诺昔康组的 IL-6 水平在术后第 1 天明显低于对照组(分别为 113±49 和 177±20,P=0.008)。ICAM-1 水平在患者入住 ICU 时明显低于对照组(分别为 177±29 和 217±22,P=0.014),且在术后第 1 天明显低于对照组(分别为 281±134 和 489±206,P=0.045)。与对照组相比,P-选择素水平在四个测量点明显降低(分别为 97±23 和 119±7,P=0.030,77±19 和 101±20,P=0.044,86±4 和 105±13,P=0.06,116±13 和 158±17,P=0.000)。

结论

与对照组相比,血流动力学和呼吸参数有所改善,但这些差异无统计学意义。与对照组相比,嗜酸性粒细胞在肺实质中间组织中的黏附和隔离明显减少。此外,氯诺昔康组未观察到肺泡水肿。氯诺昔康可降低体外循环下冠状动脉旁路移植术患者的炎症反应。这从 IL-6、ICAM-1 和 p-Selectin 水平的降低以及肺病理形态学检查(无肺泡水肿,嗜酸性粒细胞黏附和隔离在中间组织中的减少)中得到证实。尽管氯诺昔康对血液动力学和呼吸参数有有利影响,但这些改善似乎没有统计学意义。

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