王新宽等
[摘要] 目的 评价微型体外循环与传统体外循环对心脏手术术后死亡率与不良心血管事件的影响。方法 采用Cochrane系统评价方法,检索Pubmed、Embase、Cochrane database数据库,纳入心脏手术术中微型体外循环与传统体外循环对术后影响的随机对照试验,采用RevMan 5.2软件进行数据分析。 结果 共纳入24个研究共2770例患者。Meta分析结果显示,与传统体外循环比较,微型体外循环可减低术后死亡率(OR 0.40,95%CI 0.18,0.88),差异有统计学意义;与传统体外循环比较,微型体外循环可降低术后心肌梗死发病率(OR 0.33,95%CI 0.12,0.90)、降低输血率(OR 0.24,95%CI 0.16, 0.37)、降低心衰的发生率(OR 0.52,95%CI 0.32,0.84)、降低术后房颤的发生率(OR 0.66,95%CI 0.48,0.91)等不良心血管事件,差异均有统计学意义。 结论 心脏手术术中使用微型体外循环可降低术后的死亡率及不良心血管事件的发生率。
[关键词] 微型体外循环;心脏手术;Meta分析
[中图分类号] R608 [文献标识码] B [文章编号] 1673-9701(2014)33-0155-06
[Abstract] Objective To evaluate the impact of minimal extracorporeal circulation (MECC) compared to conventional extracorporeal circulation(CECC) on mortality and major adverse cardiovascular events in patients undergoing heart surgery. Methods Used Cochrane systemic review, we conducted systematic search of Pubmed, Embase and Cochrane databases to include randomized controlled trials(RCTs) of MECC vs. CECC in patients with heart surgery. RevMan 5.2 software was used for data analysis. Results Twenty-four prospective RCTs have been included (2770 patients). MECC significantly decrease mortality(OR 0.40,95%CI 0.18,0.88). And MECC significantly decrease postoperative myocardial infarction(OR 0.33,95%CI 0.12,0.90), need for red blood cell transfusion(OR 0.24,95%CI 0.16,0.37), need for inotropic support(OR 0.52,95%CI 0.32,0.84), and postoperative atrial fibrillation(OR 0.66,95%CI 0.48, 0.91). Conclusion Using of MECC in heart surgery resulted in improved short-term outcome as reflected by reduced mortality and morbidity compared with CECC.
[Key words] Minimal extracorporeal circulation; Heart surgery; Meta-analysis
随着医学的进步,心脏的各种手术量不断增多,如冠状动脉旁路移植术和心脏瓣膜置换术,均可以显著改善患者的预后,延长患者的预期寿命[1-3]。心脏的手术过程中尽管部分患者可采取不停跳冠状动脉旁路移植术,然而,由于解剖的特点、技术的水平、远期预后和特殊疾病的限制等原因,体外循环辅助仍然是必不可少的[4,5],可以在手术的过程中对血液和其他组织器官起到重要的保护作用[6-11]。然而,在体外循环之后,由于与外源性物品发生接触,常常会引起全身炎症反应综合征、凝血级联反应,最终导致手术发生严重的并发症[3,12,13]。随着微型体外循环技术在心脏外科手术过程中的应用,心脏手术术后预后有了进一步的提高[2,14]。但是,关于微型体外循环技术仍具有一定的争议性,临床疗效值得进一步探讨[4,5,15,16]。本研究拟采用系统评价的方法,评价微型体外循环技术对心脏手术术后死亡率和并发症的影响,以期为临床治疗方案的制定提供依据。
1 材料与方法
1.1 纳入标准
纳入的研究类型需为随机对照或半随机对照试验,语种不限;研究对象为心脏手术患者,所有患者在手术的过程中均需要辅助体外循环技术(传统体外循环/微型体外循环);观察组干预措施为心脏手术过程中辅助微型体外循环技术,对照组干预措施为心脏手术过程中辅助传统体外循环技术;结果指标为术后死亡率及术后的不良反应。
1.2文献检索
以“heart surgery AND extracorporeal circulation AND randomized trial”检索Pubmed(1966~2014年2月)、Embase(1970~2014年2月)和Cochrane database(1990~2014年2月)数据库。两个作者独立筛选所获取的文献,如遇不一致讨论解决。endprint
1.3数据提取与质量评价
主要提取以下资料:研究的基本情况、两组患者的基线资料和疾病状况、干预措施、对照措施、结果指标。纳入研究的质量据Cochrane 评价手册进行评价,主要评价以下条目:随机数字的产生、分配隐藏、盲法、结果数据完整性、选择性报告、其他偏倚。
1.4统计学分析
数据分析采用RevMan 5.2软件进行分析。对二分类变量的结果指标,采用比值比(OR)及其95%可信区间(95%CI)描述。采用I2检验进行异质性分析,若I2<50%,认为没有异质性,采用固定效应模型,反之则采用随机效应模型。检验水平为α=0.05。
2结果
2.1检索结果及纳入研究的一般特征
初步检索获得1634条文献,排除重复文献、综述、病例报告、动物实验等,最终纳入24个研究[1-3,6-9,12-14,17-30](图1)。纳入24个研究,共2770例心脏手术患者,1387例心脏手术患者接受微型体外循环辅助手术,1383例患者接受传统体外循环辅助手术。纳入研究的患者基线水平较一致,临床异质性较小。所有研究均报道了术后死亡率,6个研究关注了术后心肌梗死发生率,7个研究关注了术后输血率,7个研究关注了心衰需强心药物率,9个研究关注了术后房颤的发生率。所有研究都提及随机和盲法,但是均未描述随机的方法,所有研究均未提及分配隐藏,18个研究报道了失访。
2.2 Meta分析的结果
所有研究均关注了心脏手术术后死亡率,与传统体外循环相比较,微型体外循环的心脏术后的死亡率更低(OR 0.40,95%CI 0.18,0.88)(图2),结果有统计学意义。与传统体外循环比较,微型体外循环心脏手术组的各种不良事件发生率更低,包括心肌梗死的发病率(OR 0.33,95%CI 0.12,0.90)(图3)、降低输血率(OR 0.24,95%CI 0.16,0.37)(图4)、降低心衰的发生率(OR 0.52,95% CI 0.32,0.84)(图5)、降低术后房颤的发生率(OR 0.66,95% CI 0.48,0.91)(图6),结果均有统计学意义。
3 讨论
本研究是基于24个前瞻性随机对照试验的meta分析,共2770例患者。本研究结果显示,对于心脏手术术中辅助微型体外循环,可显著降低患者术后的死亡率,同时对减少术后不良反应包括心梗发生率、输血率、心衰率和房颤发生率及术后的恢复具有积极的作用。meta分析可以提高统计学精确性和统计学效能,可以增加样本量,减少假阳性的可能性,因此在评估干预措施的效果和安全性上具有独特的优势。本研究是国内第一个全面评估微型体外循环和传统体外循环的meta分析,通过全面检索,全面收集当前所有的随机对照试验,可对微型体外循环和传统体外循环效果和安全性差异进行全面分析、评价和比较。
研究显示,微型体外循环较传统体外循环可以减少术后死亡率、术后不良反应,这可能是由于微型体外循环较传统体外循环可以减少术后的炎症反应,同时避免术后凝血异常[14,22,24]。与传统的体外循环技术相比,微型体外循环系统为密闭式,避免了血液与空气接触面,使用肝素涂层管路,有效地减小血液在回路中的接触面积[5,15,31]。同时,其将术区血液经过处理后再回输体内,减少各种炎症因子的入血,可以避免全身炎症反应,同时可显著降低患者术后凝血紊乱和补体的激活,减少各种并发症的发生[11,32]。因微型体外循环可以减少术中失血,故其可以显著降低术后的输血率[6,9,12,23,25,26]。
本研究纳入24个研究,共2770例患者,纳入的研究较多,结果的可信度更高。但是本研究具有一定的局限性:第一:纳入的研究质量参差不齐。多数研究为报道具体的盲法及分配隐藏,研究的质量较低,说明研究可能存在较高的风险偏倚,进而影响研究的结果。随机对照试验采取一定的方法进行随机,是为了保证两组患者之间的可比性,但是目前所有的研究均提及随机,并没有详细描述随机方法,这意味着这些研究可能存在着风险偏倚。第二:本研究仅纳入英文文献,并没有纳入中文文献;同时,本研究只纳入发表的研究,并没有联系作者和相关机构,寻找未发表的研究或者正在进行的研究,这意味着本meta分析可能存在着选择偏倚。第三:大多数纳入研究的患者为轻中度患者,纳入的研究随访时间较短,这就意味着微型体外循环与传统体外循环在重度心脏病患者中的效果尚不可知,两者远期的效果并不清楚。患者的心脏病程度和随访时间限制了本meta分析的外部真实性及可推广性。
本研究表明,微型体外循环可以有效降低心脏手术术后的死亡率,同时减少术后不良事件的发生。本研究基于24个随机对照试验,总样本量2770例,因此本研究具有较高的统计效能和精确性,但是本研究纳入的患者为轻中度患者,随访时间段,这就意味着本研究的结果可适用于轻中度患者,对于重度患者,本研究的结果要慎重应用。本研究的结果局限于近期效果,因此两者的远期效果并不清楚。未来的研究应该评估两者在重度患者中的效果和安全性,同时对两者的远期效果应该进行评价。
由于本研究纳入研究质量普遍较低,因此未来的研究应该提高随机对照试验的质量,同时增加随访时间,详细报告完成的随机对照试验的具体细节。
本研究表明,微型体外循环可以有效降低心脏手术术后的死亡率,同时减少术后不良事件的发生。由于本研究纳入研究质量普遍较低,因此在未来的研究中应该采用高质量、大样本的随机对照试验,评估微型体外循环对心脏手术术后的影响。
[参考文献]
[1] Beghi C,Nicolini F,Agostinelli A,et al. Mini-cardiopulmonary bypass system:Results of a prospective randomized study[J]. Ann Thorac Surg,2006,81(4): 1396-1400.endprint
[2] Gunaydin S,Sari T,McCusker K,et al. Clinical evaluation of minimized extracorporeal circulation in high-risk coronary revascularization:Impact on air handling,inflammation,hemodilution and myocardial function[J]. Perfusion,2009,24(3): 153-162.
[3] Mazzei V,Nasso G,Salamone G,et al. Prospective randomized comparison of coronary bypass grafting with minimal extracorporeal circulation system (MECC) versus off-pump coronary surgery[J]. Circulation,2007,116(16): 1761-1767.
[4] Donndorf P,Kuhn F,Vollmar B,et al. Comparing microvascular alterations during minimal extracorporeal circulation and conventional cardiopulmonary bypass in coronary artery bypass graft surgery:A prospective,randomized study[J]. J Thorac Cardiovasc Surg,2012,144(3): 677-683.
[5] Donndorf P,Park H,Vollmar B,et al. Impact of closed minimal extracorporeal circulation on microvascular tissue perfusion during surgical aortic valve replacement:Intravital imaging in a prospective randomized study[J]. Interact Cardiovasc Thorac Surg,2014.
[6] El-Essawi A,Hajek T,Skorpil J,et al. A prospective randomised multicentre clinical comparison of a minimised perfusion circuit versus conventional cardiopulmonary bypass[J]. Eur J Cardiothorac Surg,2010,38(1):91-97.
[7] Kofidis T,Baraki H,Singh H,et al. The minimized extracorporeal circulation system causes less inflammation and organ damage[J]. Perfusion,2008,23(3): 147-151.
[8] Perthel M,El-Ayoubi L,Bendisch A,et al. Clinical advantages of using mini-bypass systems in terms of blood product use,postoperative bleeding and air entrainment:An in vivo clinical perspective[J]. Eur J Cardiothorac Surg,2007,31(6):1070-1075.
[9] Skrabal CA,Steinhoff G,Liebold A. Minimizing cardiopulmonary bypass attenuates myocardial damage after cardiac surgery[J]. ASAIO J,2007,53(1): 32-35.
[10] Asteriou C,Antonitsis P,Argiriadou H,et al. Minimal extracorporeal circulation reduces the incidence of postoperative major adverse events after elective coronary artery bypass grafting in high-risk patients. A single-institutional prospective randomized study[J]. Perfusion,2013,28(4):350-356.
[11] Rajakaruna C,Webb G,Bennett M,et al. Minimal access aortic valve replacement using minimal extracorporeal circuit[J]. Asian Cardiovasc Thorac Ann,2012,20(3):358-360.
[12] Castiglioni A,Verzini A,Colangelo N,et al. Comparison of minimally invasive closed circuit versus standard extracorporeal circulation for aortic valve replacement:A randomized study[J]. Interact Cardiovasc Thorac Surg,2009,9(1):37-41.endprint
[13] Remadi JP,Rakotoarivelo Z,Marticho P,et al. Prospective randomized study comparing coronary artery bypass grafting with the new mini-extracorporeal circulation Jostra System or with a standard cardiopulmonary bypass[J]. Am Heart J,2006,151(1):198.
[14] Formica F,Broccolo F,Martino A,et al. Myocardial revascularization with miniaturized extracorporeal circulation versus off pump: Evaluation of systemic and myocardial inflammatory response in a prospective randomized study[J]. J Thorac Cardiovasc Surg,2009,137(5):1206-1212.
[15] Anastasiadis K,Antonitsis P,Haidich AB,et al. Use of minimal extracorporeal circulation improves outcome after heart surgery;A systematic review and meta-analysis of randomized controlled trials[J]. Int J Cardiol,2013,164(2):158-169.
[16] Anastasiadis K,Fragoulakis V,Antonitsis P,et al. Coronary artery bypass grafting with minimal versus conventional extracorporeal circulation,An economic analysis[J]. Int J Cardiol,2013,168(6):5336-5343.
[17] Abdel Aal M,ElNahal N,Bakir BM,et al. Mini-cardiopulmonary bypass impact on blood conservation strategy in coronary artery bypass grafting[J]. Interact Cardiovasc Thorac Surg,2011,12(4):600-604.
[18] Abdel-Rahman U,Ozaslan F,Risteski PS,et al. Initial experience with a minimized extracorporeal bypass system:Is there a clinical benefit?[J]. Ann Thorac Surg,2005,80(1):238-243.
[19] Anastasiadis K,Asteriou C,Deliopoulos A,et al. Haematological effects of minimized compared to conventional extracorporeal circulation after coronary revascularization procedures[J]. Perfusion,2010,25(4):197-203.
[20] Bauer A,Diez C,Schubel J,et al. Evaluation of hemodynamic and regional tissue perfusion effects of minimized extracorporeal circulation (MECC)[J]. J Extra Corpor Technol,2010,42(1):30-39.
[21] Bical OM,Fromes Y,Gaillard D,et al. Comparison of the inflammatory response between miniaturized and standard CPB circuits in aortic valve surgery[J]. Eur J Cardiothorac Surg,2006,29(5):699-702.
[22] Camboni D,Schmidt S,Philipp A,et al. Microbubble activity in miniaturized and in conventional extracorporeal circulation[J]. ASAIO J,2009,55(1): 58-62.
[23] Fromes Y,Gaillard D,Ponzio O,et al. Reduction of the inflammatory response following coronary bypass grafting with total minimal extracorporeal circulation[J]. Eur J Cardiothorac Surg,2002,22(4):527-533.
[24] Huybregts RA,Morariu AM,Rakhorst G,et al. Attenuated renal and intestinal injury after use of a mini-cardiopulmonary bypass system[J].Ann Thorac Surg,2007,83(5):1760-1766.endprint
[25] Kutschka I,Skorpil J,El Essawi A,et al. Beneficial effects of modern perfusion concepts in aortic valve and aortic root surgery[J]. Perfusion,2009,24(1):37-44.
[26] Ohata T,Mitsuno M,Yamamura M,et al. Beneficial effects of mini-cardiopulmonary bypass on hemostasis in coronary artery bypass grafting:Analysis of inflammatory response and hemodilution[J]. ASAIO J,2008,54(2): 207-209.
[27] Remadi JP,Rakotoarivello Z,Marticho P,et al. Aortic valve replacement with the minimal extracorporeal circulation (Jostra MECC System) versus standard cardiopulmonary bypass:A randomized prospective trial[J]. J Thorac Cardiovasc Surg,2004,128(3):436-441.
[28] Valtonen M,Vahasilta T,Kaila-Keinanen T,et al. New mini-extracorporeal circulation system(ECC.O) is a safe technique in coronary surgery[J]. Scand Cardiovasc J,2007,41(5):345-350.
[29] Benedetto U,Luciani R,Goracci M,et al. Miniaturized cardiopulmonary bypass and acute kidney injury in coronary artery bypass graft surgery[J]. Ann Thorac Surg,2009,88(2):529-535.
[30] Wippermann J,Albes JM,Hartrumpf M,et al. Comparison of minimally invasive closed circuit extracorporeal circulation with conventional cardiopulmonary bypass and with off-pump technique in CABG patients: Selected parameters of coagulation and inflammatory system[J]. Eur J Cardiothorac Surg,2005,28(1):127-132.
[31] Anastasiadis K,Asteriou C,Antonitsis P,et al. Enhanced recovery after elective coronary revascularization surgery with minimal versus conventional extracorporeal circulation:A prospective randomized study[J]. J Cardiothorac Vasc Anesth,2013,27(5):859-864.
[32] Baikoussis NG,Papakonstantinou NA,Apostolakis E. The "benefits" of the mini-extracorporeal circulation in the minimal invasive cardiac surgery era[J]. J Cardiol,2014,63(6):391-396.
(收稿日期:2014-06-06)endprint
[25] Kutschka I,Skorpil J,El Essawi A,et al. Beneficial effects of modern perfusion concepts in aortic valve and aortic root surgery[J]. Perfusion,2009,24(1):37-44.
[26] Ohata T,Mitsuno M,Yamamura M,et al. Beneficial effects of mini-cardiopulmonary bypass on hemostasis in coronary artery bypass grafting:Analysis of inflammatory response and hemodilution[J]. ASAIO J,2008,54(2): 207-209.
[27] Remadi JP,Rakotoarivello Z,Marticho P,et al. Aortic valve replacement with the minimal extracorporeal circulation (Jostra MECC System) versus standard cardiopulmonary bypass:A randomized prospective trial[J]. J Thorac Cardiovasc Surg,2004,128(3):436-441.
[28] Valtonen M,Vahasilta T,Kaila-Keinanen T,et al. New mini-extracorporeal circulation system(ECC.O) is a safe technique in coronary surgery[J]. Scand Cardiovasc J,2007,41(5):345-350.
[29] Benedetto U,Luciani R,Goracci M,et al. Miniaturized cardiopulmonary bypass and acute kidney injury in coronary artery bypass graft surgery[J]. Ann Thorac Surg,2009,88(2):529-535.
[30] Wippermann J,Albes JM,Hartrumpf M,et al. Comparison of minimally invasive closed circuit extracorporeal circulation with conventional cardiopulmonary bypass and with off-pump technique in CABG patients: Selected parameters of coagulation and inflammatory system[J]. Eur J Cardiothorac Surg,2005,28(1):127-132.
[31] Anastasiadis K,Asteriou C,Antonitsis P,et al. Enhanced recovery after elective coronary revascularization surgery with minimal versus conventional extracorporeal circulation:A prospective randomized study[J]. J Cardiothorac Vasc Anesth,2013,27(5):859-864.
[32] Baikoussis NG,Papakonstantinou NA,Apostolakis E. The "benefits" of the mini-extracorporeal circulation in the minimal invasive cardiac surgery era[J]. J Cardiol,2014,63(6):391-396.
(收稿日期:2014-06-06)endprint
[25] Kutschka I,Skorpil J,El Essawi A,et al. Beneficial effects of modern perfusion concepts in aortic valve and aortic root surgery[J]. Perfusion,2009,24(1):37-44.
[26] Ohata T,Mitsuno M,Yamamura M,et al. Beneficial effects of mini-cardiopulmonary bypass on hemostasis in coronary artery bypass grafting:Analysis of inflammatory response and hemodilution[J]. ASAIO J,2008,54(2): 207-209.
[27] Remadi JP,Rakotoarivello Z,Marticho P,et al. Aortic valve replacement with the minimal extracorporeal circulation (Jostra MECC System) versus standard cardiopulmonary bypass:A randomized prospective trial[J]. J Thorac Cardiovasc Surg,2004,128(3):436-441.
[28] Valtonen M,Vahasilta T,Kaila-Keinanen T,et al. New mini-extracorporeal circulation system(ECC.O) is a safe technique in coronary surgery[J]. Scand Cardiovasc J,2007,41(5):345-350.
[29] Benedetto U,Luciani R,Goracci M,et al. Miniaturized cardiopulmonary bypass and acute kidney injury in coronary artery bypass graft surgery[J]. Ann Thorac Surg,2009,88(2):529-535.
[30] Wippermann J,Albes JM,Hartrumpf M,et al. Comparison of minimally invasive closed circuit extracorporeal circulation with conventional cardiopulmonary bypass and with off-pump technique in CABG patients: Selected parameters of coagulation and inflammatory system[J]. Eur J Cardiothorac Surg,2005,28(1):127-132.
[31] Anastasiadis K,Asteriou C,Antonitsis P,et al. Enhanced recovery after elective coronary revascularization surgery with minimal versus conventional extracorporeal circulation:A prospective randomized study[J]. J Cardiothorac Vasc Anesth,2013,27(5):859-864.
[32] Baikoussis NG,Papakonstantinou NA,Apostolakis E. The "benefits" of the mini-extracorporeal circulation in the minimal invasive cardiac surgery era[J]. J Cardiol,2014,63(6):391-396.
(收稿日期:2014-06-06)endprint