非选择性β受体阻滞剂对肝硬化合并食管-胃底静脉曲张患者血流动力学及肝肾综合征发生情况的影响
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摘要
背景非选择性β受体阻滞剂(NSBBs)可降低肝硬化失代偿期患者的门脉压力,因而在合并食管-胃底静脉曲张患者中应用广泛,但NSBBs对这些患者血流动力学及肝肾综合征(HRS)发生情况的影响却鲜有报道。目的探究NSBBs对肝硬化合并食管-胃底静脉曲张患者血流动力学及HRS发生情况的影响。方法收集2012—2016年于杭州市西溪医院重症肝病科住院的符合研究标准的215例肝硬化合并食管-胃底静脉曲张患者的临床资料。依据食管-胃底静脉曲张破裂出血情况分为仅静脉曲张组(A组,n=155)和有出血组(B组,n=60);两组再依据是否服用普萘洛尔分为仅静脉曲张未服用NSBBs亚组(A1亚组,n=56)、仅静脉曲张服用NSBBs亚组(A2亚组,n=99)和有出血未服用NSBBs亚组(B1亚组,n=25)、有出血服用NSBBs亚组(B2亚组,n=35)。比较A1亚组与A2亚组、B1亚组与B2亚组患者性别、年龄、实验室指标[总胆红素(TBiL)、清蛋白(ALB)、血小板计数(PLT)、国际标准化比值(INR)、肌酐(Cr)]、血流动力学指标[基础心率、动脉收缩压(SAP)、平均动脉压(MAP)]、HRS发生率。结果 A1亚组与A2亚组患者性别、年龄、TBiL、ALB、PLT、INR、Cr比较,差异无统计学意义(P>0.05);A1亚组患者基础心率、SAP、MAP高于A2亚组(P<0.05)。A1亚组HRS发生率为7.1%(4/56),A2亚组HRS发生率为2.0%(2/99);A1、A2亚组患者HRS发生率比较,差异无统计学意义(χ~2=1.334,P=0.248)。A组中发生HRS的6例患者在HRS首次诊断后90 d内均未死亡,其中Child-Pugh评分(CPS)C级患者3例(A1亚组中2例,A2亚组中1例)。B1、B2亚组患者性别、年龄、TBiL、PLT、INR、Cr、SAP、MAP比较,差异无统计学意义(P>0.05);B1亚组患者ALB低于B2亚组,基础心率高于B2亚组(P<0.05)。B1亚组HRS发生率为4.0%(1/25),B2亚组HRS发生率为5.7%(2/35);B1、B2亚组患者HRS发生率比较,差异无统计学意义(χ~2=0.090,P=0.754)。B组中发生HRS的3例患者在HRS首次诊断后90 d内均死亡,其中CPS C级患者2例(B1亚组中1例,B2亚组中1例)。结论 NSBBs会对肝硬化合并食管-胃底静脉曲张患者血流动力学产生一定程度的损害,但是否增加HRS发生率仍有待进一步研究和探讨。
Background Non-selective β receptor blockers(NSBBs) can reduce portal vein pressure in patients with decompensated cirrhosis,so they are widely used in cirrhosis patients with esophageal-gastric varices. However,the influence of NSBBs on hemodynamics and the incidence of hepatorenal syndrome(HRS) in these patients has rarely been reported.Objective To explore the effects of NSBBs on hemodynamics and the incidence of HRS in cirrhosis patients with esophageal-gastric varices.Methods Clinical data were collected from 215 cirrhosis patients with complications of esophagealgastric varices who were admitted to the Department of Hepatology of Xixi Hospital of Hangzhou between 2012 and 2016.According to esophageal-gastric variceal bleeding,the patients were divided into group A(only having varicose veins,n=155) and group B(having varicose veins with bleeding,n=60).Each group was further divided into two subgroups according to whether the subjects were taking propranolol:subgroup A1(not taking propranolol,n=56) and subgroup A2(taking propranolol,n=99),as well as subgroup B1(n=25) and subgroup B2(n=35).Indices including sex;age;laboratory tests including total bilirubin(TBiL),albumin(ALB),platelet count(PLT),international normalized ratio(INR) and creatinine(Cr);and hemodynamic parameters including basal heart rate,arterial systolic pressure(SAP),mean arterial pressure(MAP) and incidence of HRS among the above subgroups were compared.Results There were no significant differences in sex,age,TBiL,ALB,PLT,INR and Cr between subgroups A1 and A2(P>0.05).The basal heart rate,SAP and MAP were higher in subgroup A1 than in subgroup A2(P<0.05).The incidence of HRS in subgroup A1 was 7.1%(4/56),and that in subgroup A2 was 2.0%(2/99);this difference was not significant(χ~2=1.334,P=0.248).The six HRS cases in group A all survived 90 days after the first diagnosis of HRS;among them,three patients had a Child-Pugh score(CPS) of grade C(two patients in subgroup A1 and one in subgroup A2).There were no significant differences in sex,age,TBiL,PLT,INR,Cr,SAP and MAP between subgroups B1 and B2(P>0.05).ALB was lower and basal heart rate was higher in subgroup B1 than in subgroup B2(P<0.05).The incidence of HRS in subgroup B1 was 4.0%(1/25),and that in subgroup B2 was 5.7%(2/35);this difference was not statistically significant(χ~2=0.090,P=0.754).Three patients with HRS in group B died within 90 days after the first diagnosis of HRS,of whom two had CPS grade C(one in subgroup B1 and one in B2).Conclusion NSBBs may have negative effects on hemodynamics in cirrhosis patients with esophageal-gastric varices,but whether the drugs increase the incidence of HRS still requires further study to verify.
Background Non-selective β receptor blockers(NSBBs) can reduce portal vein pressure in patients with decompensated cirrhosis,so they are widely used in cirrhosis patients with esophageal-gastric varices. However,the influence of NSBBs on hemodynamics and the incidence of hepatorenal syndrome(HRS) in these patients has rarely been reported.Objective To explore the effects of NSBBs on hemodynamics and the incidence of HRS in cirrhosis patients with esophageal-gastric varices.Methods Clinical data were collected from 215 cirrhosis patients with complications of esophagealgastric varices who were admitted to the Department of Hepatology of Xixi Hospital of Hangzhou between 2012 and 2016.According to esophageal-gastric variceal bleeding,the patients were divided into group A(only having varicose veins,n=155) and group B(having varicose veins with bleeding,n=60).Each group was further divided into two subgroups according to whether the subjects were taking propranolol:subgroup A1(not taking propranolol,n=56) and subgroup A2(taking propranolol,n=99),as well as subgroup B1(n=25) and subgroup B2(n=35).Indices including sex;age;laboratory tests including total bilirubin(TBiL),albumin(ALB),platelet count(PLT),international normalized ratio(INR) and creatinine(Cr);and hemodynamic parameters including basal heart rate,arterial systolic pressure(SAP),mean arterial pressure(MAP) and incidence of HRS among the above subgroups were compared.Results There were no significant differences in sex,age,TBiL,ALB,PLT,INR and Cr between subgroups A1 and A2(P>0.05).The basal heart rate,SAP and MAP were higher in subgroup A1 than in subgroup A2(P<0.05).The incidence of HRS in subgroup A1 was 7.1%(4/56),and that in subgroup A2 was 2.0%(2/99);this difference was not significant(χ~2=1.334,P=0.248).The six HRS cases in group A all survived 90 days after the first diagnosis of HRS;among them,three patients had a Child-Pugh score(CPS) of grade C(two patients in subgroup A1 and one in subgroup A2).There were no significant differences in sex,age,TBiL,PLT,INR,Cr,SAP and MAP between subgroups B1 and B2(P>0.05).ALB was lower and basal heart rate was higher in subgroup B1 than in subgroup B2(P<0.05).The incidence of HRS in subgroup B1 was 4.0%(1/25),and that in subgroup B2 was 5.7%(2/35);this difference was not statistically significant(χ~2=0.090,P=0.754).Three patients with HRS in group B died within 90 days after the first diagnosis of HRS,of whom two had CPS grade C(one in subgroup B1 and one in B2).Conclusion NSBBs may have negative effects on hemodynamics in cirrhosis patients with esophageal-gastric varices,but whether the drugs increase the incidence of HRS still requires further study to verify.
引文
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[2]GE P S,RUNYON B A.The changing role of beta-blocker therapy in patients with cirrhosis[J].J Hepatol,2014,60(3):643-653.DOI:10.1016/j.jhep.2013.09.016.
[3]PECK-RADOSAVLJEVIC M,ANGERMAYR B,DATZ C,et al.Austrian consensus on the definition and treatment of portal hypertension and its complications(BillrothⅡ)[J].Wien Klin Wochenschr,2013,125(7/8):200-219.DOI:10.1007/s00508-013-0337-z.
[4]DE FRANCHIS R,BAVENO V F.Revising consensus in portal hypertension:report of the BavenoⅤconsensus workshop on methodology of diagnosis and therapy in portal hypertension[J].J Hepatology,2010,53(4):762-768.DOI:10.1016/j.jhep.2010.06.004.
[5]GARCIA-TSAO G,SANYAL A J,GRACE N D,et al.Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis[J].Hepatology,2007,102(9):922-938.
[6]LEBREC D,POYNARD T,HILLON P,et al.Propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis:a controlled study[J].N Engl J Med,1981,305(23):1371-1374.DOI:10.1056/NEJM198112033052302.
[7]KURT M.Deleterious effects of beta-blockers on survival in patients with cirrhosis and refractory ascites[J].Hepatology,2011,53(4):1411-1412.DOI:10.1002/hep.24051.
[8]KRAG A,WIEST R,ALBILLOS A,et al.The window hypothesis:haemodynamic and non-haemodynamic effects ofβ-blockers improve survival of patients with cirrhosis during a window in the disease[J].Gut,2012,61(7):967-969.DOI:10.1136/gutjnl-2011-301348.
[9]D'AMICO G,PAGLIARO L,BOSCH J.Pharmacological treatment of portal hypertension:an evidence-based approach[J].Semin Liver Dis,1999,19(4):475-505.DOI:10.1055/s-2007-1007133.
[10]FERLITSCH A,PLEINER J,MITTERMAYER F,et al.Vasoconstrictor hyporeactivity can be reversed by antioxidants in patients with advanced alcoholic cirrhosis of the liver and ascites[J].Crit Care Med,2005,33(9):2028-2033.DOI:10.1097/01.CCM.0000178173.27923.EB.
[11]RUIZ-DEL-ARBOL L,URMAN J,FERNáNDEZ J,et al.Systemic,renal,and hepatic hemodynamic derangement in cirrhotic patients with spontaneous bacterial peritonitis[J].Hepatology,2004,39(3):865-866.DOI:10.1053/jhep.2003.50447.
[12]KRAG A,M?LLER S,BURROUGHS A K,et al.Betablockers induce cardiac chronotropic incompetence[J].J Hepatol,2012,56(1):298-299.DOI:10.1016/j.jhep.2011.04.033.
[13]BENDTSEN F,HENRIKSEN J H,SORENSEN T I.Propranolol and haemodynamic response in cirrhosis[J].J Hepatol,1991,13(2):144-148.DOI:10.1016/0168-8278(91)90807-N.
[14]中华医学会肝病学分会中华医学会消化病学分会,中华医学会内镜学分会.肝硬化门静脉高压食管胃静脉曲张出血防治指南(2015)[J].中华胃肠内镜电子杂志,2015,2(4):1-21.DOI:10.3877/cma.j.issn.2095-7157.2015.04.001.
[15]BLACHIER M,LELEU H,PECKRADOSAVLJEVIC M,et al.The burden of liver disease in Europe:a review of available epidemiological data[J].J Hepatol,2013,58(3):593-608.DOI:10.1016/j.jhep.2012.12.005.
[16]ASRANI S K,LARSON J J,YAWN B,et al.Underestimation of liver-related mortality in the United States[J].Gastroenterology,2013,145(2):1-2.DOI:10.1053/j.gastro.2013.04.005.
[17]D'AMICO G,GARCIA-TSAO G,PAGLIARO L.Natural history and prognostic indicators of survival in cirrhosis:a systematic review of 118 studies[J].J Hepatol,2006,44(1):217-231.DOI:10.1016/j.jhep.2005.10.013.
[2]GE P S,RUNYON B A.The changing role of beta-blocker therapy in patients with cirrhosis[J].J Hepatol,2014,60(3):643-653.DOI:10.1016/j.jhep.2013.09.016.
[3]PECK-RADOSAVLJEVIC M,ANGERMAYR B,DATZ C,et al.Austrian consensus on the definition and treatment of portal hypertension and its complications(BillrothⅡ)[J].Wien Klin Wochenschr,2013,125(7/8):200-219.DOI:10.1007/s00508-013-0337-z.
[4]DE FRANCHIS R,BAVENO V F.Revising consensus in portal hypertension:report of the BavenoⅤconsensus workshop on methodology of diagnosis and therapy in portal hypertension[J].J Hepatology,2010,53(4):762-768.DOI:10.1016/j.jhep.2010.06.004.
[5]GARCIA-TSAO G,SANYAL A J,GRACE N D,et al.Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis[J].Hepatology,2007,102(9):922-938.
[6]LEBREC D,POYNARD T,HILLON P,et al.Propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis:a controlled study[J].N Engl J Med,1981,305(23):1371-1374.DOI:10.1056/NEJM198112033052302.
[7]KURT M.Deleterious effects of beta-blockers on survival in patients with cirrhosis and refractory ascites[J].Hepatology,2011,53(4):1411-1412.DOI:10.1002/hep.24051.
[8]KRAG A,WIEST R,ALBILLOS A,et al.The window hypothesis:haemodynamic and non-haemodynamic effects ofβ-blockers improve survival of patients with cirrhosis during a window in the disease[J].Gut,2012,61(7):967-969.DOI:10.1136/gutjnl-2011-301348.
[9]D'AMICO G,PAGLIARO L,BOSCH J.Pharmacological treatment of portal hypertension:an evidence-based approach[J].Semin Liver Dis,1999,19(4):475-505.DOI:10.1055/s-2007-1007133.
[10]FERLITSCH A,PLEINER J,MITTERMAYER F,et al.Vasoconstrictor hyporeactivity can be reversed by antioxidants in patients with advanced alcoholic cirrhosis of the liver and ascites[J].Crit Care Med,2005,33(9):2028-2033.DOI:10.1097/01.CCM.0000178173.27923.EB.
[11]RUIZ-DEL-ARBOL L,URMAN J,FERNáNDEZ J,et al.Systemic,renal,and hepatic hemodynamic derangement in cirrhotic patients with spontaneous bacterial peritonitis[J].Hepatology,2004,39(3):865-866.DOI:10.1053/jhep.2003.50447.
[12]KRAG A,M?LLER S,BURROUGHS A K,et al.Betablockers induce cardiac chronotropic incompetence[J].J Hepatol,2012,56(1):298-299.DOI:10.1016/j.jhep.2011.04.033.
[13]BENDTSEN F,HENRIKSEN J H,SORENSEN T I.Propranolol and haemodynamic response in cirrhosis[J].J Hepatol,1991,13(2):144-148.DOI:10.1016/0168-8278(91)90807-N.
[14]中华医学会肝病学分会中华医学会消化病学分会,中华医学会内镜学分会.肝硬化门静脉高压食管胃静脉曲张出血防治指南(2015)[J].中华胃肠内镜电子杂志,2015,2(4):1-21.DOI:10.3877/cma.j.issn.2095-7157.2015.04.001.
[15]BLACHIER M,LELEU H,PECKRADOSAVLJEVIC M,et al.The burden of liver disease in Europe:a review of available epidemiological data[J].J Hepatol,2013,58(3):593-608.DOI:10.1016/j.jhep.2012.12.005.
[16]ASRANI S K,LARSON J J,YAWN B,et al.Underestimation of liver-related mortality in the United States[J].Gastroenterology,2013,145(2):1-2.DOI:10.1053/j.gastro.2013.04.005.
[17]D'AMICO G,GARCIA-TSAO G,PAGLIARO L.Natural history and prognostic indicators of survival in cirrhosis:a systematic review of 118 studies[J].J Hepatol,2006,44(1):217-231.DOI:10.1016/j.jhep.2005.10.013.