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“高剂量”抑肽酶与肝素涂层体外循环管路:临床疗效及炎症反应

'High dose' aprotinin and heparin-coated circuits: clinical efficacy and inflammatory response.

作者信息

Parolari A, Alamanni F, Gherli T, Salis S, Spirito R, Foieni F, Rossi F, Bertera A, Oddono P, Biglioli P

机构信息

Department of Cardiac Surgery, University of Milan, Centro Cardiologico, Fondazione I Monzino IRCCS, Milano, Italy.

出版信息

Cardiovasc Surg. 1999 Jan;7(1):117-27. doi: 10.1016/s0967-2109(98)00016-7.

DOI:10.1016/s0967-2109(98)00016-7
PMID:10073771
Abstract

Heparin-coated cardiopulmonary bypass circuits reduce the inflammatory response to cardiopulmonary bypass circuit, improve biocompatibility and may protect the postoperative hemostasic mechanisms in routine coronary bypass operations. 'High-dose' aprotinin reduces bloodloss, transfusion needs, and re-explorations as a result of bleeding, and may have an additional role in reducing the inflammatory response of the body to cardiopulmonary bypass circuit. It has not been established, however, if the addition of a heparin-coated circuit to the intraoperative administration of 'high dose' aprotinin further reduces the whole-body inflammatory response to cardiopulmonary bypass circuit and improves the postoperative clinical course of the patients who are undergoing coronary surgery. Thirty patients undergoing primary elective coronary artery bypass grafting were studied. All the patients received, intraoperatively, the serine-protease inhibitor aprotinin according to the 'Hammersmith' protocol and full heparin dose. Patients were randomly allocated to be treated either with a circuit completely coated with surface-bound heparin (n = 15) or with an uncoated, but otherwise identical, circuit (n = 15). Differences in the clinical course of the two groups of patients, as well as differences in the behavior of hematological and inflammatory (interleukin-6 (IL-6) and C-reactive protein) factors before, during and after bypass, were analyzed. There were no significant differences between the two groups in terms of bleeding and transfusional requirements, the time spent on a ventilator, or in duration of stay in the intensive care unit (ICU). In all patients, a significant increase in the total white blood cell count, neutrophils, serum IL-6 and C-reactive protein occurred in relation to cardiopulmonary bypass. This was not influenced by heparin precoating of the circuit. In addition, there was an increase in the monocyte count during follow-up, and there was a trend towards higher monocyte counts in the patients who were treated with heparin-coated circuits. These results suggest that the addition of a heparin-coated circuit to the intraoperative 'high-dose' aprotinin therapy probably had little influence on the clinical course and on the time-course of the inflammatory parameters of the adult patients undergoing primary coronary surgery with a full heparinization protocol.

摘要

肝素涂层体外循环回路可减轻对体外循环回路的炎症反应,提高生物相容性,并可能保护常规冠状动脉搭桥手术中的术后止血机制。“高剂量”抑肽酶可减少因出血导致的失血量、输血需求和再次手术探查,并且在减轻机体对体外循环回路的炎症反应方面可能具有额外作用。然而,术中给予“高剂量”抑肽酶时添加肝素涂层回路是否能进一步减轻对体外循环回路的全身炎症反应并改善接受冠状动脉手术患者的术后临床病程,目前尚未明确。对30例接受初次择期冠状动脉搭桥术的患者进行了研究。所有患者术中均按照“哈默史密斯”方案接受丝氨酸蛋白酶抑制剂抑肽酶和全剂量肝素治疗。患者被随机分为两组,一组使用完全涂有表面结合肝素的回路(n = 15),另一组使用未涂层但其他方面相同的回路(n = 15)。分析了两组患者临床病程的差异,以及体外循环前、中、后血液学和炎症(白细胞介素-6(IL-6)和C反应蛋白)因子行为的差异。两组在出血和输血需求、呼吸机使用时间或重症监护病房(ICU)住院时间方面无显著差异。在所有患者中,与体外循环相关的总白细胞计数、中性粒细胞、血清IL-6和C反应蛋白均显著增加。这不受回路肝素预涂层的影响。此外,随访期间单核细胞计数增加,使用肝素涂层回路治疗的患者单核细胞计数有升高趋势。这些结果表明,在术中“高剂量”抑肽酶治疗基础上添加肝素涂层回路可能对接受全肝素化方案的初次冠状动脉手术成年患者的临床病程和炎症参数的时间进程影响不大。

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'High dose' aprotinin and heparin-coated circuits: clinical efficacy and inflammatory response.“高剂量”抑肽酶与肝素涂层体外循环管路:临床疗效及炎症反应
Cardiovasc Surg. 1999 Jan;7(1):117-27. doi: 10.1016/s0967-2109(98)00016-7.
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Cytokine release and neutrophil activation are not prevented by heparin-coated circuits and aprotinin administration.肝素涂层管路和使用抑肽酶并不能阻止细胞因子释放和中性粒细胞激活。
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Heparinized cardiopulmonary bypass and full heparin dose marginally improve clinical performance.肝素化体外循环和全量肝素剂量仅略微改善临床效果。
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The impact of aprotinin on blood loss and blood transfusion in off-pump coronary artery bypass grafting.抑肽酶对非体外循环冠状动脉旁路移植术中失血及输血的影响。
Ann Thorac Surg. 2008 May;85(5):1662-8. doi: 10.1016/j.athoracsur.2008.01.087.

引用本文的文献

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Effects of interventions targeting the systemic inflammatory response to cardiac surgery on clinical outcomes in adults.针对心脏手术全身炎症反应的干预措施对成人临床结局的影响。
Cochrane Database Syst Rev. 2023 Oct 24;10(10):CD013584. doi: 10.1002/14651858.CD013584.pub2.
2
Anti-Inflammatory Effects of Heparin and Its Derivatives: A Systematic Review.肝素及其衍生物的抗炎作用:一项系统评价
Adv Pharmacol Sci. 2015;2015:507151. doi: 10.1155/2015/507151. Epub 2015 May 12.