急性食管胃底静脉曲张破裂出血的控制及预后300例

摘要

目的: 探讨急性食管胃底静脉曲张破裂出血(bleeding esophageal varice, BEV)的治疗方法、控制时间及预后之间的关系, 找出预测控制出血无效的主要因素.

方法: 选取2008-01/2013-01入我院治疗的300例BEV患者, 回顾分析治疗后≤2 h、＞2 h但≤6 h、＞6 h但≤5 d、≥5 d的出血控制状况, 剖析控制出血时段与病死率的关系. 将单纯药物与药物联合内镜两种治疗措施在控制出血有效率与病死率间的差异进行对比. Logistic回归分析预测治疗无效的因素.

结果: 300例BEV患者内, 入院治疗时段出血控制无效者≤2 h、>2 h但≤6 h、>6 h但≤5 d时段内各自为75、25、27例, 病死依序为1、3、16例. ≤2 h时段出血未获控制病死率较高, ≤2 h时段出血控制可降低病死率, 支持>2 h出血未获控制须立即转换治疗的共识. 药物治疗控制出血有效率为57.67%(173/300), 病死率为9.67%(29/300). 药物治疗控制出血无效后, 组织黏合剂注射或套扎联合内镜治疗的控制出血有效率为90.00%(27/30), 死亡率为0. Logistic回归显示, 入院时收缩压≤90 mmHg、总胆红素表达加大、肝功能分级提升、有腹水为预测治疗无效的因素.

结论: 有腹水、总胆红素表达加大、入院时收缩压≤90 mmHg、肝功能Child-Pugh分级提升等状况也许为预测治疗无效的因素; 控制出血无效时段多发于≤2 h, 病死率随时间延长上升; >2 h出血未获控制须立即转换治疗; 药物联合内镜治疗控制出血有效率较高, 病死率较低.

关键词: 急性食管胃底静脉曲张破裂出血; 胃肠出血; 套扎术; 组织黏合剂; 垂体后叶素; 奥曲肽; 内镜检查; 治疗方法; 预后; 预测因素

核心提示: 此次回顾性剖析300例急性食管胃底静脉曲张破裂出血入院患者的临床资料, 对控制出血时间、治疗方法、预后关系进行分析, 找出治疗失败的预测因素.

Management and prognosis of acute esophageal variceal bleeding: Analysis of 300 cases

Yin-Hao Cai, Ya-Hua Zhang, Wan-Wei Chen, Sha-Sha Luo, En-Le He, Ming-Yao You

Yin-Hao Cai, Ya-Hua Zhang, Sha-Sha Luo, En-Le He, Department of Emergency Medicine, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, Guizhou Province, China

Wan-Wei Chen, Department of Gastroenterology, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, Guizhou Province, China

Ming-Yao You, Department of Neurology, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, Guizhou Province, China

Correspondence to: Ming-Yao You, Associate Chief Physician, Department of Neurology, Affiliated Hospital of Guiyang Medical College, 28 Guiyi Street, Guiyang 550004, Guizhou Province, China. caiyinhao110@163.com

Received: August 10, 2013
Revised: September 16, 2013
Accepted: September 30, 2013
Published online: October 28, 2013

Abstract

AIM: To analyze the treatment, management duration and prognosis of acute esophageal variceal bleeding and to identify predictive factors for treatment failure.

METHODS: Clinical data for 300 patients with acute esophageal variceal bleeding treated at our hospital from January 2008 to January 2013 were analyzed retrospectively. Bleeding control was analyzed ≤ 2 h, > 2 h but ≤ 6 h, > 6 h but ≤ 5 d, or ≥ 5 d after treatment to find the relationship between bleeding control time and mortality. The effective rate and mortality were compared between patients treated with simple drugs and those treated with drugs combined with endoscopic therapy. Logistic regression analysis was used to identify predictive factors for treatment failure.

RESULTS: The number of patients having ineffective bleeding management was 75, 25 and 27 in the ≤ 2 h, >2 h but ≤ 6 h, and >6 h but ≤ 5 d groups, respectively, and the number of dead patients was 1, 3 and 16, respectively. The percentage of patients having ineffective bleeding management was higher in the ≤ 2 h group. The effective rate of drug therapy in management of bleeding was 57.67% (173/300), and the mortality was 9.67% (29/300). The effective rate of tissue adhesive injection or ligation combined with endoscopic therapy in controlling bleeding in patients after ineffective drug therapy was 90.00% (27/30), and the mortality was 0. Logistic regression analysis showed that admission systolic blood pressure ≤ 90 mmHg, increased total bilirubin, high liver function classification, and ascites were predictive factors for treatment failure.

CONCLUSION: Ascites, increased total bilirubin, admission systolic blood pressure ≤ 90 mmHg, and high Child-Pugh classification can predict treatment failure in patients with acute esophageal variceal bleeding. Invalid bleeding control is more common during ≤ 2 h after treatment. Mortality increases with time. If bleeding can not be controlled effectively 2 h after treatment, treatment conversion should be considered. Drugs in combination with endoscopic therapy are associated with higher efficacy and lower mortality in controlling bleeding.

Key Words: Acute esophageal variceal bleeding; Gastrointestinal bleeding; Ligation; Tissue adhesive; Vasopressin; Octreotide; Endoscopy; Treatment; Prognosis; Predictive factors

0 引言

急性食管胃底静脉曲张破裂出血(bleeding esophageal varice, BEV), 为肝硬化门脉高压病的危重并发症[1,2]. 因其来势凶、出血大、病情险的特点, 病死率>40%, 若治疗不及时, 将造成严重后果[3,4]. 治疗急性BEV的关键是快速有效止血、抗休克、防并发症等. 控血时限国内外皆以超过6 h为失败, 近来皆将药物及内镜治疗2 h后未能实现控血则表明失败[5]. 此次回顾性剖析300例BEV入院患者的临床资料, 对控制出血时间、治疗方法、预后关系进行分析, 找出治疗失败的预测因素.

1 材料和方法

1.1 材料

选取2008-01/2013-01于我院治疗的300例急性BEV患者资料展开回顾性分析. 其中, 男188例, 女112例, 平均年龄55.86岁±13.98岁, 首次出血89例, 为总比率的29.67%, 再次出血111例, 为总比率的70.33%. 入选标准: 依内镜下BEV诊断标准, 确诊为急性BEV的患者; 依Baveno Ⅳ共识意见[6], 于血容量恢复前提下, 药物治疗初选生长抑素、垂体后叶素、普奈洛尔或奥曲肽的患者.

1.2 方法

1.2.1 分析方法: 详细记录年龄、性别、病因、病程, 出血史、内镜治疗史、本次出血状况, 入院时收缩压、心率, 肝功能Child-Pugh分级、食管静脉曲张美国分级、腹水状况, 血浆总胆红素(total bilirubin, TBIL)、血红蛋白(hemoglobin, HB)、肌酐(creatinine, Cr)、血尿素氮(blood urea nitrogen, BUN)、血小板(blood platelet, BP)水平, 患者输血量, 感染状况, 合并胃底静脉曲张、肝性脑病、肝癌状况, 药物治疗状况. 食管静脉曲张程度分级: 轻度(A): 曲张静脉略隆起自食管黏膜表面, 直径<5 mm; 中度(B): 曲张静脉直径≥5 mm、<食管腔直径1/3; 重度(C): 曲张静脉直径≥5 mm、≥食管腔直径的1/3[7]. 统计治疗时段: ≤2 h; >2 h但≤6 h; ＞6 h但≤5 d; ≥5 d.

1.2.2 疗效判定标准: 于观察时段内, 鼻胃管吸出新鲜血液、持续或再次呕吐新鲜血液、失血性休克及/或死亡发生, 则为急诊出血控制无效[8,9].

统计学处理 采取SPSS16.0软件进行数据统计处理. 计量资料以mean±SD表示, 两组单因素对比分析采取独立样本t检验. χ²检验计数资料. 控制出血失败的预测因素, 采取多因素Logistic回归模型分析. P<0.05为差异具有统计学意义.

2 结果

2.1 急性BEV控制状况

300例急性BEV患者, ≤5 d出血未获控制者为127例(42.33%), 死亡29例(9.67%), 其中, 重症感染1例, 并发失血性体休克3例、肝性脑病25例; 控制出血失败率≤2 h最高为75例, 占控血失败总数的59.06%, 病死率随时间延长而上升. 2 h时段为控制出血失败界限. 分析显示, ≤2 h出血未能控制者后续病死率较高[30.67%(23/75) vs 11.54%(6/52), χ² = 5.18, P = 0.019](表1).

表1 急性BEV患者控制出血失败时限与死因分析 (n).

时段	n	控制出血失败	肝性脑病	失血性休克	死亡	其他因素
≤2 h	300	75	1	0	1	0
>2 h、≤6 h	298	25	4	0	3	0
>6 h、≤5 d	293	27	14	2	16	0
≥5 d	287	未统计	6	1	8	11

¹重症感染死亡. BEV: 食管胃底静脉曲张破裂出血.

2.2 治疗方法与控制出血关系的分析

300例患者, 药物治疗控制出血有效率为57.67%(173/300), 病死率为9.67%(29/300). 药物治疗控制出血无效后, 组织黏合剂注射或套扎联合内镜治疗的控制出血成功率为90.00%(27/30), 病死率为0.

2.3 治疗失败影响因素分析

2.3.1 治疗失败影响因素的单因素分析: 控制出血有效、无效两组入院时收缩压(χ² = 29.98, P<0.01)、TBIL(t = 3.89, P<0.01)、肝功能分级(χ² = 26. 01, P<0.01)、是否呕血(χ² = 5.68, P = 0.02)、Cr(t = 2.06, P = 0.04)、有无腹水(χ² = 7.59, P = 0.01)、有无肝性脑病(χ² = 5.19, P = 0.02)状况皆差异显著(P<0.05); HB(t = 1.99, P = 0.05)、年龄(t = 0.36, P = 0.69)、性别(χ² = 0.23, P = 0.59)、病程(t = 1.39, P = 0.14)、入院时心率(χ² = 1.06, P = 0.29)、BP(t = 0.66, P = 0.49)、BUN(t = 0.95, P = 0.33)、凝血酶原活动度(t = 1.36, P = 0.16)、肝硬化病因(χ² = 0.72, P = 0.39)、是否首次出血(χ² = 1.53, P = 0.21)、内镜治疗史(χ² = 0.67, P = 0.39)、食管静脉曲张程度分级(χ² = 0.01, P = 1.00)、有无感染(χ² = 0.01, P = 0.90)、有无脾大(χ² = 2.51, P = 0.l0)、有无合并胃底静脉曲张(χ² = 0.22, P = 0.62)状况差异皆无统计学意义.

2.3.2 治疗失败影响因素的Logistic回归分析: 入院时收缩压≤90 mmHg(l mmHg = 0.133 kPa)、TBIL表达加大、肝功能分级提升、有腹水为预测治疗失败的因素(表2).

表2 治疗失败影响因素的Logistic回归分析结果.

变量	回归系数	标准差	自由度	χ2值	P值	OR	95%CI
入院时收缩压≤90 mmHg	-0.71	0.31	1	5.09	0.02	0.48	0.25-0.90
总胆红素表达加大	0.02	0.01	1	6.20	0.01	1.01	0.99-1.02
肝功能分级提升	0.60	0.20	1	4.53	0.04	1.83	1.21-2.75
有腹水	-0.91	0.28	1	10.43	<0.01	0.39	0.22-0.69

3 讨论

BEV具有突发性、出血量大, 止血困难、复发率、病死率高等特点, 治疗中的紧急处理、转换治疗时段至关重要[10]. 国外相关研究表明, 经药物、内镜治疗>2 h出血未获控制需采取转换治疗[11], 可临床观察资料的证据尚欠缺. 此次研究, 急性BEV患者≤5 d出血未获控制率达42.33%, 入院BEV患者病死率为9.67%, 死因主要为出血过多循环衰竭所致. 此次研究入院治疗时段出血未获控制者≤2 h、>2 h但≤6 h、>6 h但≤5 d时段内各自为75、25、27例, 随出血时间延长, 死亡加大. 出血未获控制与死亡加大呈线性相关. 此次研究≤2 h时段出血未获控制病死率较高, ≤2 h时段出血控制可降低病死率, 支持>2 h出血未获控制须立即转换治疗的共识.

诸多研究证实, 预测出血未获控制的独立危险因素为内镜下活动性出血与较高的肝静脉压力梯度(hepatic venous pressure gradient, HVPG)[12]. 可目前临床实践中, 不能所有急性BEV患者可于≤2 h获内镜检测及HVPG测定, 有待更加便捷、迅速的出血未获控制的预测因素及评估指标[13]. 本研究中, 控制出血成功、失败两组入院时的收缩压、TBIL、肝功能分级、Cr、有无肝性脑病、有无呕血及腹水差异显著(P<0.05), 即入院时的生命体征、肝功能状况、出血程度、有无合并肝性脑病为控制出血的主要影响因素. Logistic回归分析表明, 入院时收缩压≤90 mmHg、TBIL水平增高、肝功能分级上升及有腹水为预测出血控制失败的关键要素. TBIL与腹水为肝功能分级关键指准. 肝功能分级为BEV预后有价值的判定指标. 国外相关研究表明, 以血流动收缩压及舒张压力学状态与所需输血量为判定指标, BEV再出血组与非再出血组的出血严重程度不具统计学意义, 提示血流动力学状态并非预测治疗失败的可靠指标[3]. 此次研究提示, 入院时收缩压≤90 mmHg可作为预测出血控制失败因素. 血流动力学状态对出血控制成败有影响, 入院时收缩压表达低下可间接体现患者出血量较大, 循环血容量缺失.

入院时收缩压≤90 mmHg、TBIL表达加大、肝功能Child-Pugh分级上升、有腹水也许为预测治疗无效的因素[14,15]. 急性BEV患者控制出血无效时段多于≤2 h, 病死率随时间延长提升. 药物联合内镜治疗止血有效率高, 病死率低.

评论

背景资料

治疗急性食管胃底静脉曲张破裂出血的关键是快速有效止血、抗休克、防并发症等. 控血时限国内外皆以超过6 h为失败, 近来皆将药物及内镜治疗2 h后未能实现控血则表明失败.

同行评议者

王文跃, 主任医师, 中日友好医院普通外科

研发前沿

急性食管胃底静脉曲张破裂出血具有突发性、出血量大, 止血困难、复发率、病死率高等特点, 治疗中的紧急处理、转换治疗时段至关重要.

相关报道

国外相关研究表明, 经药物、内镜治疗>2 h出血未获控制需采取转换治疗, 可临床观察资料的证据尚欠缺.

同行评价

本文研究急性急性食管胃底静脉曲张破裂出血的治疗方法、控制时间及预后的关系, 设计合理, 样本比较大, 有一定的学术价值.

备注

编辑:郭鹏 电编:闫晋利

参考文献

1.	杨 拯, 李 晓娇, 呙 金海, 陈 建敏, 荣 成, 张 晓. 国产醋酸奥曲肽治疗食管胃底静脉曲张破裂出血的系统评价. 世界华人消化杂志. 2010;18:2365-2369.  [PubMed]  [DOI]

2.	de Franchis R. Updating consensus in portal hypertension: report of the Baveno III Consensus Workshop on definitions, methodology and therapeutic strategies in portal hypertension. J Hepatol. 2000;33:846-852.  [PubMed]  [DOI]

3.	Majid S, Azam Z, Shah HA, Salih M, Hamid S, Abid S, Jafri W. Factors determining the clinical outcome of acute variceal bleed in cirrhotic patients. Indian J Gastroenterol. 2009;28:93-95.  [PubMed]  [DOI]

4.	朱 长清, 董 胜翔, 茅 益民, 曾 民德, 蒋 义斌, 许 建明, 田 德安, 刘 吉勇, 徐 三平, 孙 樱. 奥曲肽治疗肝硬化门静脉高压食管胃底静脉曲张急性出血的多中心对照研究. 世界华人消化杂志. 2009;17:2570-2573.  [PubMed]  [DOI]

5.	de Franchis R. Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol. 2010;53:762-768.  [PubMed]  [DOI]

6.	de Franchis R. Evolving consensus in portal hypertension. Report of the Baveno IV consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol. 2005;43:167-176.  [PubMed]  [DOI]

7.	Lay CS, Tsai YT, Lee FY, Lai YL, Yu CJ, Chen CB, Peng CY. Endoscopic variceal ligation versus propranolol in prophylaxis of first variceal bleeding in patients with cirrhosis. J Gastroenterol Hepatol. 2006;21:413-419.  [PubMed]  [DOI]

8.	Javvaji S, Kumar A, Madan K, Garg PK, Acharya SK. Management of gastric variceal bleeding. Trop Gastroenterol. 2007;28:51-57.  [PubMed]  [DOI]

9.	Sarin SK, Wadhawan M, Agarwal SR, Tyagi P, Sharma BC. Endoscopic variceal ligation plus propranolol versus endoscopic variceal ligation alone in primary prophylaxis of variceal bleeding. Am J Gastroenterol. 2005;100:797-804.  [PubMed]  [DOI]

10.	Dhiman RK, Chawla Y, Taneja S, Biswas R, Sharma TR, Dilawari JB. Endoscopic sclerotherapy of gastric variceal bleeding with N-butyl-2-cyanoacrylate. J Clin Gastroenterol. 2002;35:222-227.  [PubMed]  [DOI]

11.	Garcia-Tsao G, Sanyal AJ, Grace ND, Carey WD. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Am J Gastroenterol. 2007;102:2086-2102.  [PubMed]  [DOI]

12.	Abraldes JG, Villanueva C, Bañares R, Aracil C, Catalina MV, Garci A-Pagán JC, Bosch J. Hepatic venous pressure gradient and prognosis in patients with acute variceal bleeding treated with pharmacologic and endoscopic therapy. J Hepatol. 2008;48:229-236.  [PubMed]  [DOI]

13.	Augustin S, González A, Genescà J. Acute esophageal variceal bleeding: Current strategies and new perspectives. World J Hepatol. 2010;2:261-274.  [PubMed]  [DOI]

14.	Burroughs AK, Triantos CK. Predicting failure to control bleeding and mortality in acute variceal bleeding. J Hepatol. 2008;48:185-188.  [PubMed]  [DOI]

15.	Zoli M, Merkel C, Magalotti D, Gueli C, Grimaldi M, Gatta A, Bernardi M. Natural history of cirrhotic patients with small esophageal varices: a prospective study. Am J Gastroenterol. 2000;95:503-508.  [PubMed]  [DOI]