OPCABG患者围手术期NT-ProBNP水平变化的临床意义

[关键词] 非体外循环冠状动脉旁路移植术;血浆脑钠肽前体;高龄

[摘要]目的 监测分析非体外循环冠状动脉旁路移植术(off-pump coronary artery bypass grafting ,OPCABG)患者围手术期血浆脑钠肽前体(N-terminal pro-brain natriureticpeptide,NT-proBNP)水平的变化规律,探讨影响其变化的因素及临床意义。方法 134例OPCABG患者,根据年龄分为高龄组(≥65岁)74例和对照组(<65岁)60例。比较分析两组患者围手术期临床资料,监测术前2d、术后1d、术后2d、术后4d和术后7d的NT-proBNP水平,术前因素与术前NT-proBNP水平相关性应用双变量相关分析。独立样本t检验比较两组NT-proBNP水平的变化。结果 患者术前2d NT-proBNP水平与术前EF(r=-0.443,P=0.000),心功能分级(r=0.181, P=0.036),冠心病分类(r=0.191, P=0.027)以及术后1d的NT-proBNP水平(r=0.557, P=0.000)等因素呈显著相关。围手术期血浆NT-proBNP水平呈现出一个先升高后降低的变化趋势(P=0.000)。与对照组相比,高龄组NT-proBNP水平在术前2d无显著性差异(637.34±805.184pg/ml vs. 445.27±717.384pg/ml,P=0.147),但在术后1d(1212.490±1198.282pg/ml vs. 819.630±1057.504pg/ml,P=0.046)、术后2d(1968.950±1683.499pg/ml vs. 1411.980±1091.622pg/ml,P=0.023)、术后4d(1726.450±1990.513pg/ml vs. 839.650±583.292pg/ml,P=0.001)和术后7d(1052.420±1319.620pg/ml vs. 643.500±684.959pg/ml,P=0.023)均较高,且有统计学差异。结论 患者OPCABG术后NT-proBNP水平出现先升高再下降的变化趋势,高龄患者术后NT-proBNP水平较对照组升高。术前NT-proBNP水平与术前EF、心功能分级、冠心病分类及术后NT-proBNP水平等因素相关,是预测OPCABG效果潜在有意义的指标。

The clinical significance of perioperative N-terminal pro-brain natriureticpeptide level changes in patients undergoing off-pump coronary artery bypass grafting

Gu Chang1, Zhang Weiran2, Zhuang Lingfang3, Xu Xiaohan4, Zhang Yangyang2

1. The first clinical medical college of Nanjing Medical University, Nanjing 210029, P. R. China.

2. Department of Thoracic and Cardiovascular Surgery, the First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, P. R. China

[Abstract]  Objective To monitor and analyze the regularities in the changes of perioperative plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients undergoing off-pump coronary artery bypass grafting (OPCABG) for exploring the influencing factors and clinical significance.  Methods 134 patients undergoing OPCABG were divided into 2 groups according to age. There were 74 patients in the elder group (age≥65) while the control group had 60. The preoperative and postoperative clinical data were analyzed and compared between the two groups; we monitored the NT-proBNP level respectively in 2 days before surgery and 1, 2, 4, 7 days after the surgery. We analyzed preoperative factors and preoperative NT - proBNP level by bivariate correlation analysis and compared perioperative NT - proBNP level changes in two groups by independent sample t test. Results The preoperative 2 day`s NT - proBNP level were significantly related with preoperative EF(r = 0.443, P = 0.443), heart function classification(r=0.181, P=0.036), coronary heart disease (CHD) classification(r=0.191, P=0.027), postoperative 1 day`s NT - proBNP level(r=0.557, P=0.000) and so on. The preoperative EF and preoperative NT - proBNP level has significant negative correlation in patients(r=-0.443, P=0.000). Perioperative NT - proBNP level present the change trend of lower after a rise. There was a statistical difference in the trend of perioperative NT - proBNP level changes between the two groups (P=0.000). Besides, a significant correlation was found in NT - proBNP levels between preoperative 1 day and postoperative 2 days(r=0.557, P=0.000). Compared with the control group, the elder group`s NT-proBNP level had no statistical difference 2 days before their surgery(637.34±805.184pg/ml vs. 445.27±717.384pg/ml, P=0.147), but the levels were higher after 1(1212.490±1198.282pg/ml vs. 819.630±819.630±1057.504pg/ml, P=0.046), 2(1968.950±1683.499pg/ml vs. 1411.980±1091.622pg/ml, P=0.023), 4(1726.450±1990.513pg/ml vs. 839.650±583.292pg/ml, P=0.001), 7(1052.420±1319.620pg/ml vs. 643.500±684.959pg/ml, P=0.023) days after their surgery and had statistical differences. Conclusion The postoperative NT-proBNP level presents the change trend of lower after a rise. There has a higher postoperative NT-proBNP level in elderly patients undergoing OPCABG. Preoperative NT - proBNP level is associated with preoperative EF, postoperative NT - proBNP level, heart function classification, coronary heart disease classification, and so forth. As a result, preoperative NT - proBNP level can act as a potential and meaningful indicator to anticipate the results of OPCABG.

[Key words] off-pump coronary artery bypass grafting; plasma N-terminal pro-brain natriuretic peptide; advanced age

   脑钠肽(brain natriureticpeptide,BNP)在冠心病(coronary artery disease, CAD)、心力衰竭等心血管疾病的诊断和预后评估有积极的作用[1-4]。脑钠肽前体(N-terminal pro-brain natriuretic peptide,NT-proBNP)与BNP相比在循环系统中更加稳定[5],半衰期更长,且分子量较大,做定量分析测定值高于BNP,测定方法较BNP更加简便,所以NT-proBNP在临床应用方面更具有优势[6]。NT-proBNP在心脏外科尤其是冠脉外科应用鲜有报道。本文通过监测分析NT-proBNP在非体外循环冠状动脉旁路移植术(off-pump coronary artery bypass grafting ,OPCABG)患者围手术期的血清水平,探讨影响其变化的因素及临床意义。

1  资料与方法

1.1  临床资料和分组

   江苏省人民医院2013年1月至2013年12月期间行OPCABG的289例患者中根据入选条件:大于40周岁,男女均可,首次单纯择期手术。排除标准:严重的肝肾功能不全,感染性疾病,不可控制的高血压、心脏衰竭,慢性阻塞性肺病,急诊手术,体外循环下手术,手术期间合并其他手术(如瓣膜手术),代谢疾病,恶性肿瘤等。共入选200例患者,均为严重CAD,术前的冠状动脉造影均显示为多支或(和)左主干病变。所有患者入选后均告知临床研究目的并签署知情同意书。66例患者因围手术期临床资料不全而中途退出研究,最终134例完成研究,其中男性106例,女性28例;年龄45~85岁,平均年龄65.46岁。根据年龄分为两组:年龄≥65岁为高龄组(n=74),年龄<65岁为对照组(n=60),两组患者性别、身高、体重、心功能分级、冠心病分类、高血压、高血脂、糖尿病、吸烟、术前EF等相关临床资料详见表1。

表1 术前因素与术前NT-proBNP相关性

Parameter

r

P

性别

-0.048

0.584

身高

-0.006

0.946

体重

-0.110

0.207

心功能分级

0.181

0.036

冠心病分类

0.191

0.027

高血压

0.046

0.596

高血脂

-0.049

0.572

糖尿病

-0.012

0.891

吸烟

-0015

0.860

术前EF

0.001

0.987

   两组患者分别于术前2d(PRD-2),术后1d(POD-1),术后2d(POD-2),术后4d(POD-4)以及术后7d(POD-7)等5个时间点检测血NT-proBNP。

1.2  手术方法

   全部患者术前5-7天停服抗血小板药物,手术均采用全身麻醉,胸骨正中切口,游离左侧乳内动脉,同时取大隐静脉和/或桡动脉备用。常规切开心包,肝素化,探查心脏,根据术前冠状动脉造影情况,暴露病变冠状动脉,用CTS心脏稳定器固定靶血管行OPCABG。所有患者先行左侧乳内动脉与左前降支吻合。对于其他移植血管则通常先吻合远心端,行单一端侧吻合或续贯式吻合,再将近心端吻合到升主动脉根部。

   记录两组患者的手术时间、术后机械通气时间、术后ICU停留时间、术后住院时间及出院时EF。

1.3  统计学分析

   SPSS17.0统计软件进行统计分析,计量资料采用均数±标准差表示,两组间比较采用独立样本t检验,术前因素(性别、身高、体重、心功能分级、冠心病分类、高血压、高血脂、糖尿病、吸烟、术前EF)与术前NT-proBNP相关性采用双变量相关分析,独立样本非参数秩和检验(Mann-Whitney U检验),计数资料以实际例数表示,对围手术期NT-proBNP水平变化趋势采用重复测量设计的方差分析,p<0.05提示差异有统计学意义。

2  结果

   所有患者手术顺利,无手术中死亡,无重大手术并发症,无二次开胸止血。

2.1  术前相关因素与NT-proBNP的关系

   术前相关因素与NT-proBNP的相关性检验(表1):患者术前EF(r=-0.443,P=0.000),心功能分级(r=0.181, P=0.036),冠心病分类(r=0.191, P=0.027)与术前NT-proBNP水平呈显著相关。全组患者NT-proBNP重复测量方差分析的多变量分析显示,围手术期5次NT-proBNP水平测量值变化趋势存在差异(表2、图1)。组间交互效应方差分析NT-proBNP与年龄因素相关(P=0.003),NT-proBNP与术前EF因素相关(P=0.003)。

2 围手术期NT-proBNP水平变化对比

Parameter

全组

高龄组(N=74)

对照组(N=60)

*P value

NT-proBNP(pg/ml)

PRD-2

551.340±770.220

637.340±805.184

445.270±717.384

0.147

POD-1

1036.590±1150.069

1212.490±1198.282

819.630±1057.504

0.046

POD-2

1719.560±1470.205

1968.950±1683.499

1411.980±1091.622

0.023

POD-4

1329.370±1587.941

1726.450±1990.513

839.650±583.292

0.001

POD-7

869.320±1097.994

1052.420±1319.620

643.500±684.959

0.023

*高龄组与对照组相比

 


图1:围手术期NT-proBNP水平变化

2.2  围手术期两组临床资料及NT-proBNP水平变化

   两组患者在性别、身高、体重、肥胖、心功能、冠心病分类、高血压、高血脂、糖尿病、吸烟、术前EF、手术时间、术后机械通气时间、术后住院时间等临床资料均相似,无统计学意义(P>0.05)。与对照组相比,高龄组术后ICU时间(1894.660±1577.790pg/ml vs. 1348.920±673.050pg/ml, P=0.014)较长(表3)。

   两组NT-proBNP水平PRD-2无显著性差异(637.34±805.184pg/ml vs. 445.27±717.384pg/ml,P=0.147)。与对照组相比,高龄组NT-proBNP水平在POD-1,POD-2,POD-4,POD-7均较高,且有统计学差异(表1)。患者术前2d和术后1d的NT-proBNP水平有明显的相关性(r=0.557,P=0.000)。

3  讨论

   BNP最初是由Sudoh从猪脑中分离出[7],后来被证实其是由心脏产生的一种心脏激素。BNP存在于心室隔膜细胞中,主要由心室肌细胞产生。当受到刺激,尤其是心室壁张力变化的刺激可立即被释放出来[8]。NT-proBNP与BNP是由108个氨基酸的激素原(pro-brain natriuretic peptide, proBNP)被相关酶同比例分割生成。在循环系统中NT-proBNP比BNP更加稳定,故临床上有用NT-proBNP代替BNP的趋势[6]

   OPCABG与CABG手术相比具有更小的损伤,已成为治疗严重CAD的常规心脏术式并越来越多地应用于高危患者。OPCABG具有降低手术死亡率、减少围手术期心肌梗死、保持正常的肾功能以及减少住院时间等优点[9-14]。任何心脏手术都会对心脏及血流动力学产生的负面影响,OPCABG也不可避免地导致心室壁张力发生变化,引起NT-proBNP水平的升高[15]。Masuda M等报道利用心肌细胞酶泄露程度评估CABG与OPCABG的术中心肌损伤,后者心肌损伤减轻,相关心肌酶(CK-MB,Troponin T等)升高程度较CABG患者明显减轻,两者BNP水平在术后皆升高,但无差异,OPCABG患者术后BNP降低更加迅速[16]

   全组134例患者围手术期NT-proBNP水平呈现出一个先升高后降低的变化趋势,重复测量方差多变量分析提示这种变化趋势存在统计学差异,从图1可看出全组NT-proBNP的峰值出现在术后2d,之后逐渐降低。Kim H K等对18例OPCABG患者围手术期NT-proBNP水平监测发现术前NT-proBNP为235.0±167.8pg/ml,术后1d为1415.0±737.6pg/ml,术后第3d达到峰值2119.0±818.4pg/ml,术后7d降至522.0-334.0pg/ml[17]。文献报道与我们的临床观测结果基本相似,说明心脏手术引起患者NT-proBNP水平的一过性升高。由于条件限制,本研究仅检测到术后第7d的NT-proBNP水平。术后第7d的NT-proBNP水平并未恢复到术前基线,但回落的趋势是明显的。NT-proBNP水平何时恢复到术前基线以及是否会低于术前基线等问题还待进一步研究。

   患者术前EF与术前NT-proBNP水平呈显著负相关(r=-0.443, P=0.000)。术前心功能分级(r=0.181, P=0.036)和冠心病分类(r=0.191, P=0.027)与术前NT-proBNP水平呈显著正相关。心脏病患者如出现心功能不全,心功能级数升高,心肌缺血症状等,可引起射血分数减低,心室壁张力变化,导致NT-proBNP水平升高[18]。术前NT-proBNP水平可以很好地反映患者心脏功能状态。有趣的是患者术前2d和术后1d的NT-proBNP水平呈明显正相关(r=0.557, P=0.000)。高龄患者全身脏器储备能力下降,手术创伤耐受力下降,术后并发症应当引起足够重视。有报道指出血清 NT-proBNP水平是预测心脏手术结果的良好指标[19-20]。Eliasdottir S B等发现各种心脏术后ICU滞留时间大于2d或术后28d内死亡、应用主动脉内球囊反搏以及术后新发肾功能衰竭的患者术前NT-proBNP水平显著升高[20]。因此术前NT-proBNP水平对评估心脏手术预后可能具有一定的价值。

   高龄因素是心脏手术死亡率和并发症发生率增加的独立因素[21]。高龄患者全身脏器储备能力下降,合并高血压、高血脂、糖尿病、肾功能不全等并发症的比例较年轻患者高。本研究表明,高龄患者术后NT-proBNP水平均高于对照组。由于NT-proBNP几乎完全通过肾脏排泄[22],老年人随着年龄的增长而出现生理性肾功能下降,肾小球滤过率下降,可能是高龄患者术后NT-proBNP水平显著增高的原因之一[23]。而术前NT-proBNP水平在两组中并没有显著差异(P=0.147),可能因为高龄患者虽然全身脏器储备能力下降,但是术前机体处于代偿状态,由于手术对心脏、肾脏等的创伤引起术后代偿不足,使得高龄组与对照组相比术后NT-proBNP水平显著增高。

   OPCABG患者围手术期NT-proBNP水平呈先上升后下降的变化趋势,峰值出现在术后2d。术前NT-proBNP水平与患者术前EF、心功能分级、冠心病分类及术后NT-proBNP水平相关,是预测OPCABG结果潜在有意义的指标;高龄患者OPCABG术后NT-proBNP水平较高。本临床研究中也存在一些不足:例如样本量较小可能造成统计结果的误差;观测的指标太少,没有具体考虑除年龄外影响NT-proBNP水平的因素等。随着临床研究的深入,NT-proBNP作为新一代心脏功能标志物,将对OPCABG术前评价患者病情及预后提供帮助。

   参考文献

[1]McDonagh T A, Holmer S, Raymond I, et al. NT-proBNP and the diagnosis of heart failure: a pooled analysis of three European epidemiological studies[J]. European Journal of Heart Failure, 2004, 6(3): 269-273.

[2]Steiner J, Guglin M. BNP or NTproBNP? A clinician´s perspective[J]. International journal of cardiology, 2008, 129(1): 5-14.

[3]Dückelmann C, Mittermayer F, Haider D G, et al. Asymmetric dimethylarginine enhances cardiovascular risk prediction in patients with chronic heart failure[J]. Arteriosclerosis, thrombosis, and vascular biology, 2007, 27(9): 2037-2042.

[4] Ndrepepa G, Braun S, Mehilli J, et al.N-terminal pro-brain natriuretic peptide on admission in patients with acute myocardial infarction and correlation with scintigraphic infarct size, efficacy of reperfusion,and prognosis[J].Am J Cardiol,2006, 97(8):1151-1156.

[5]HuntpJ,RichardsaM,NichollsmG,etal.Immunore active amino-terminal probrain natriuretic peptide(NT-proBNP):a new marker of cardiac impairment[J].ClinEndocrinol,1997,47(3);287-296.

[6]Reyes G, Forés G, Rodríguez-Abella R H, et al. NT-proBNP in cardiac surgery: a new tool for the management of our patients?[J]. Interactive CardioVascular and Thoracic Surgery, 2005, 4(3): 242-247

[7]Mukoyama M, Nakao K, Saito Y, et al. Human brain natriuretic peptide, a novel cardiac hormone[J]. The Lancet, 1990, 335(8692): 801-802.

[8]Yasue H, Yoshimura M, Sumida H, et al. Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure[J]. Circulation, 1994, 90(1): 195-203.

[9]Athanasiou T, Al-Ruzzeh S, Kumar P, et al. Off-pump myocardial revascularization is associated with less incidence of stroke in elderly patients[J]. The Annals of thoracic surgery, 2004, 77(2): 745-753.

[10]Lancey R A, Soller B R, Vander Salm T J. Off-Pump Versus On-Pump Coronary Artery Bypass Surgery: A Case-Matched Comparison of Clinical Outcomes and Cost[C]//Heart Surgery Forum. FORUM MULTIMEDIA PUBLISHING, 2000, 3: 277-281.

[11]Calafiore A M, Di Giammarco G, Teodori G, et al. Recent advances in multivessel coronary grafting without cardiopulmonary bypass[C]//Heart Surg Forum. 1998, 1(1): 20-25.

[12]Bouchard D, Cartier R. Off-pump revascularization of multivessel coronary artery disease has a decreased myocardial infarction rate[J]. European journal of cardio-thoracic surgery, 1998, 14(Supplement 1): S20-S24.

[13]Ascione R, Lloyd C T, Underwood M J, et al. On-pump versus off-pump coronary revascularization: evaluation of renal function[J]. The Annals of Thoracic Surgery, 1999, 68(2): 493-498.

[14] Khan N E, De Souza A, Mister R, et al. A randomized comparison of off-pump and on-pump multivessel coronary-artery bypass surgery[J]. New England Journal of Medicine, 2004, 350(1): 21-28.

[15]Youn Y N, Chang B C, Hong Y S, et al. Early and mid-term impacts of cardiopulmonary bypass on coronary artery bypass grafting in patients with poor left ventricular dysfunction: a propensity score analysis[J]. Circulation journal: official journal of the Japanese Circulation Society, 2007, 71(9): 1387-1394.

[16]Masuda M, Morita S, Tomita H, et al. Off-pump CABG attenuates myocardial enzyme leakage but not postoperative brain natriuretic peptide secretion[J]. Annals of Thoracic and Cardiovascular Surgery, 2002, 8(3): 139-144.

[17] Kim H K, Kim H J, Kim J W, et al. Changes in N-terminal Pro B-type Natriuretic Peptide Concentration: Comparative Study of Percutaneous Transluminal Coronary Angioplasty and Off-Pump Coronary Artery Bypass Graft[J]. Journal of Korean medical science, 2007, 22(1): 16-19.

[18] Raymond I, Groenning B A, Hildebrandt P R, et al. The influence of age, sex and other variables on the plasma level of N-terminal pro brain natriuretic peptide in a large sample of the general population[J]. Heart, 2003, 89(7): 745-751.

[19]Hutfless R, Kazanegra R, Madani M, et al. Utility of B-type natriuretic peptide in predicting postoperative complications and outcomes in patients undergoing heart surgery[J]. Journal of the American College of Cardiology, 2004, 43(10): 1873-1879.

[20]Eliasdottir S B,Klemenzson G, Torfason B, et al. Brain natriuretic peptide is a good predictor for outcome in cardiac surgery[J]. ActaanaesthesiologicaScandinavica, 2008, 52(2): 182-187.

[21]Parsonnet V, Dean D, Bernstein A D. A met, , hod of uniform stratification of risk for evaluating the results of surgery in acquired adult heart disease[J]. Circulation, 1989, 79(6 Pt 2): I3.

[22] Hall C. Essential biochemistry and physiology of (NT-pro) BNP.Eur J Heart Fail 2004;6:257–260.

[23]McCullough P A, Duc P, Omland T, et al. B-type natriuretic peptide and renal function in the diagnosis of heart failure: an analysis from the Breathing Not Properly Multinational Study[J]. American Journal of Kidney Diseases, 2003, 41(3): 571-579.


    2014/8/7 10:49:30     访问数:1259
    转载请注明:内容转载自365医学网

大家都在说       发表留言

客服中心 4000680365  service@365yixue.com
编辑部   editor@365yixue.com

365医学网 版权所有 © 365heart All Rights Reserved.

京ICP备12009013号-1
京卫网审[2013]第0056号
京公网安备110106006462号
京ICP证041347号
互联网药品信息服务资格证书(京)-经营性-2018-0016  
搜专家
搜医院
搜会议
搜资源
 
先点击
再选择添加到主屏