Proton Pump Inhibitor and H2RA Pharmacological Prevention of Stress Ulcer Bleeding in Stroke Patients: A Systematic Review of Randomized Controlled Trials_Chinese Journal of Evidence-Based Medicine

Authors：

WANG Yiping ¹ , ZENG Chao ² , WU Zongying ¹

1. Department of Emergency, West China Hospital, Sichuan University, Chengdu 610041, China2. The Digestive Department of the 3rd People＇s Hospital of Chengdu City, Chengdu 610041 China;

Corresponding author：

Keywords：

Stroke; Stress ulcer bleeding; Proton pump inbibitor; H2RA; Systematic review

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Objective 　To assess the clinical efficacy and safety of proton pump inhibitor （PPI） and H2RA for stress ulcer bleeding in stroke patients.
Methods　 Randomized controlled trials （RCT） were identified from MEDLINE （ 1966- Oct. 2005 ） ,EMBASE （ 1984- Oct. 2005 ）, The Cochrane Library （ Issue 4,2005 ）, CBMdisc （ 1980- Oct. 2005 ） and VIP（ 1980- Oct. 2005 ）. We handsearched the related published and unpublished data and their references. The quality of included trials was evaluated. Data were extracted by two reviewers independently with a designed extraction form. RevMan 4. 2.7 software was used for data analysis.
Results 　Twenty RCT were included with 2 624 patients. The results of meta-analysis were listed as follows：（1） stress ulcer bleeding （SUB）： PPI （ OR 0.14,95% CI 0.08 to 0.24, NNT = 3 ） and H2RA （OR 0.24,95% CI 0.15 to 0.39, NNT =5） significantly reduced the incidence of SUB in comparison with control group. PPI significantly reduced the incidence of SUB compared with H2R.A（P 〈0. 00001 ）. （2） Mortality： PPI （OR 0.22,95% CI 0. 11 to 0.47, NNT =8） and H2RA （OR 0.53,95% CI 0. 34 to 0.81, NNT =16） significantly decreased the mortality compared with non-prophylaxis group. PPI significantly decreased the mortality compared with H2RA （OR 0.28,95% CI 0.09 to 0. 89）. （3） Adverse effect： There were not evident adverse effects in both PPI and H2RA groups.
Conclusions 　PPI and H2RA may reduce the incidence and mortality of SUB in stroke patients, and PPls are better in reducing incidence of SUB than H2RA.

Citation： WANG Yiping,ZENG Chao,WU Zongying. Proton Pump Inhibitor and H2RA Pharmacological Prevention of Stress Ulcer Bleeding in Stroke Patients: A Systematic Review of Randomized Controlled Trials. Chinese Journal of Evidence-Based Medicine, 2006, 06(2): 107-116. doi: Copy

1.	Cheng XM.Epidemiology of Cerebrovascular Disease.4th edition.Beijing:Chinese Science and Technique Publishing Company,1993; 11-13.程学铭.脑血管病的流行病学.第4版.北京:中国科学技术出版社,1993;11～13.
2.	Peng NS.Prognosis of 1000 cute brain hemorrhage cases.Chinese Journal of Emergency,1996;16(5):32-33.彭南生.急性脑出血1000例预后研究.中国急救医学杂志,1996;16(5):32～33.
3.	Lou JJ,Yan CJ,Chen H.Effect of cold constraint stress against microcirculation in big mouse.Microcircuology,1996 ; 6(4):8-10.楼继军,宴才杰,陈华.冷束缚应激对大鼠胃微循环的影响.微循环学,1996 ; 6(4):8～10.
4.	Yasue N,Guth PH.Role of exogenous acid and retransfusion in hemorrhagic shock-induced gastric lesions in he rat.Chinese Journal of Microcirculation,1988 ; 94 (5):1135-1143.
5.	Murakami M.Pathophysiology and pathogenesis of acute gastric mucosa lesions after hypothermic restraint stress in rats.Gastroenterology,1985 ; 88 (3):660-665.
6.	Kivilaakso E.Relationship between ulceration and intramural pH of gastric mucosa during hemorrhagic shock.Surgery,1987; 102:27.
7.	Priebe HJ.Antacid versus cimetidine in preventing acute gastrointestina bleeding.N EngI J Med,1980; 302 (8):426-427.
8.	Main points of dignosis of cerebrovascular disease.Chinese Journal of Neurology,1996; 29(6):379.各类脑血管疾病诊断要点(1995年中华医学会全国第四届脑血管病学术会议通过).中华神经科杂志,1996;29(6):379.
9.	Zhang FL,Zhao JH,Li Y.The clinical effective observation of Lansoprazole for stress ulcer bleeding in patients of cerebral stroke.Chinese Journal of Clinical Pharmacology and Therapeutics,2002;7(4):351-352.张凤兰,赵均和,李岩.兰索拉唑预防急性脑卒中后应激性溃疡出血的临床疗效观察.中国临床药理学与治疗学,2002;7(4):351～352.
10.	Liang J.Lansoprazole for stress ulcer bleeding in 30 patients of cerebral hemorrhage resulted of high pressure.New Medicine,1997;28(6):295-296.粱健.兰索拉唑对预防高血压性脑出血后应激性溃疡30例的作用.新医学,1997;28(6):295～296.
11.	Wei DS.Omeprazole and Cimetidine for acute cerebral vascular disease with stress ulcer bleeding.Journal of Modern Clinical Medical Bioengineering,2002;8(2):130-132.魏端生.洛赛克与西咪替丁预防急性脑血管病并应激性溃疡出血的临床研究.Journal of Modern Clinical Medical Bioengineering,2002;8(2):130～132.
12.	Huaug YF.Omeprazole for acute cerebral hemorrhage with stress ulcer bleeding.Medical Theory and Practice,2004;17(10):1166-1167.黄永锋.奥美拉唑预防急性脑出血并发应激性溃疡消化道出血的疗效观察.医学理论与实践,2004;17(10):1166～1167.
13.	Liu K.Pantoprazole for cerebral hemorrhage resulted of high pressure with stress ulcer bleeding.Medical Theory and Practice,2004;17(10):1166-1167.刘坤.潘托拉唑对预防高血压性脑出血后应激性溃疡的作用.医学理论与实践,2004;17(2):161～162.
14.	Wang QR,Pei GZ.Pantoprazole for stress ulcer in 43 severe cerebral hemorrhage patients.Chinese Society Physician,2003;5(8):21-22.王全让,裴广忠.泮妥拉唑钠对重度脑出血并发应激性溃疡43例的预防作用.中国社区医师,2003;5(8):21～22.
15.	Shang XW.The effect of omeprazole preventing severe cerebral hemorrhage with stress gastric lesions.Journal of Henan Employee Medical University,2004;16(3):271-272.尚现伟.洛赛克在预防重症脑出血并发应激性胃粘膜病变中的作用.河南职工医学院学报,2004;16(3):271～272.
16.	Gui JW.Cimetidine preventing cerebral hemorrhage with stress ulcer in old patients.Hengyang Journal of Medical University,1997;25(4):404-405.桂建伟.西咪替丁对老年人脑出血并发应激性溃疡的预防.衡阳医学院学报,1997;25(4):404～405.
17.	Peng XL,Tang BS,Yang QD et al.Clinical observation of prevention of cerebral hemorrhage with stress ulcer.Chinese Journal of Modern Medicine,1997;7(2):67-68.彭晓兰,唐北沙,杨期东等.脑出血应激性溃疡预防性治疗的临床观察.中国现代医学杂志,1997;7(2):67～68.
18.	Xu ZQ.Effect of famotidine preventing cerebral stroke with stress ulcer bleeding.Chinese Journal of Clinical New Medicine,2002;2(12):1127-1128.许志强.法莫替丁预防脑卒中应激性溃疡出血的疗效观察.中华临床新医学,2002;2(12):1127～1128.
19.	Huang YF,Huang AZ,Wei HL.Effect of famotidine preventing cerebral stroke with stress ulcer bleeding.Huaxia Medicine,2003;16(3):315-316.黄永锋,黄爱珍,韦海玲.法莫替丁预防脑出血并发应激性溃疡出血的效果观察.华夏医学,2003;16(3):315～316.
20.	Lu YH.Cimetidine preventing for cerebral hemorrhage resulted of high pressure with stress ulcer.Chinese Emergency Disease Medicine,1998;10(7):446.陆亿华.泰胃美注射液预防高血压性脑出血后应激性溃疡.中国危重病急救医学,1998;10(7):446.
21.	Wang Y,Chen BH,Wu TF.Effect of cimetidine preventing stress ulcer of cerebral vascular disease.Chinese Clinical Medicine,2000;7(4):422-423.王英,陈百华,吴同发.泰胃美预防急性脑血管病性应激性溃疡的疗效观察.中国临床医学,2000;7(4):422～423.
22.	Miao JL,Geng LM,Xu JS et al.Prevention of stress ulcer in acute cerebral stroke.Practice of New Medicine,2001;3(2):116-117.苗今乐,耿黎明,徐建生等.急性脑卒中应激性溃疡的防治.实用新医学,2001;3(2):116～117.
23.	Liu XQ.Effect of Omeprazole preventing acute cerebral vascular disease with stress ulcer.Journal of NanHua University(Medical Edition),2002;30(1):55-56.刘雪晴.奥美拉唑对急性脑血管病应激性溃疡出血的预防作用.南华大学学报医学版,2002;30(1):55～56.
24.	Chen XD.Effect of Omeprazole combined with Cimetidine preventing severe cerebral vascular disease with stress ulcer.Journal of World Today Medicine,2003;4(4):279-280.陈新东.奥美拉唑与西咪替丁预防重症脑血管病应激性溃疡出血的疗效观察.世界今日医学杂志,2003;4(4):279～280.
25.	Zang WG.Pantoprazole preventing stree ulcer bleeding in 21 cerebral vascular disease.Shandong Medicine,2003;43(9):3.臧伟广.潘托拉唑预防脑出血并发应激性溃疡出血21例.山东医药,2003;43(9):3.
26.	Huang YD.Clinical study of pantopraloe combined withDahuang preventing acute cerebral vascular incidence with stress ulcer bleeding.Henan Medical Information,2002;10(3):52-53.黄永德.潘托拉唑与大黄预防急性脑血管意外合并发应激性溃疡出血的临床研究.河南医药信息,2002;10(3):52～53.
27.	Jin XY,Sun SZ,Cao X.Clinical observation of Omeprazole preventing cerebral hemorrhage coma combined with stress ulcer bleeding.Journal of Clinical Indigestive Disease,2001;13(2):58-59.金先银,孙素珍,曹侠.洛赛克预防脑出血昏迷并发应激性溃疡出血的临床观察.临床消化病杂志,2001;13(2):58～59.
28.	Xin JF,Zhang JT,Guo ML.Omeprazole combined with cimetidine preventing cerebral hemorrhage resulted of high pressure with stress ulcer bleeding.Journal of Practical Medical Technology,2004;11(9):1858.辛建峰,张江涛,郭美玲.洛赛克与西咪替丁对高血压脑出血并发应激性溃疡上消化道出血预防作用的研究.实用医技杂志,2004;11(9):1858.
29.	Mrrone GC,Silen W.Pathogenesis,diagnosis and treatment of acute gastric mucosal lesion.Clin Gastroenterol,1984 ; 13:635-650.
30.	Mitchell J,Spirt MD.Stress related mucosal disease:risk factors and prophylactic therapy.Clinical Therapeutics,2004 ; 26(2):197-231.
31.	Cook DJ,Fuller HD,Guyatt GH,et al.For the Canadian critical care trials group.Risk factors for gastrointestinal bleeding in critically ill patients.N Engl J Med,1994 ; 330 (6):377-381.
32.	Zuckerman GR,Shuman R.Therapeutic goals and treatmeat options for prevention of stress ulcer syndrom.Am J Med,1987 ; 83 (supple 6A):29-35.
33.	Phillips JO,Metzler MH,Palmieri MT,et al.A prospective study of simplified omeprazole suspension for the prophylaxis of stress-related mucosal damage.Crit Care Med,1996 ; 24:1793-1800.
34.	Asky MR,Metzler MH,Phillips JO.A prospective study of omeprazole suspension to prevent clinically significant gastrointestinal bleeding from stress ulcers in mechanically ventilated trauma patients.J Trauma,1998 ; 44 (3):527-533.

1. Cheng XM.Epidemiology of Cerebrovascular Disease.4th edition.Beijing:Chinese Science and Technique Publishing Company,1993; 11-13.程学铭.脑血管病的流行病学.第4版.北京:中国科学技术出版社,1993;11～13.
2. Peng NS.Prognosis of 1000 cute brain hemorrhage cases.Chinese Journal of Emergency,1996;16(5):32-33.彭南生.急性脑出血1000例预后研究.中国急救医学杂志,1996;16(5):32～33.
3. Lou JJ,Yan CJ,Chen H.Effect of cold constraint stress against microcirculation in big mouse.Microcircuology,1996 ; 6(4):8-10.楼继军,宴才杰,陈华.冷束缚应激对大鼠胃微循环的影响.微循环学,1996 ; 6(4):8～10.
4. Yasue N,Guth PH.Role of exogenous acid and retransfusion in hemorrhagic shock-induced gastric lesions in he rat.Chinese Journal of Microcirculation,1988 ; 94 (5):1135-1143.
5. Murakami M.Pathophysiology and pathogenesis of acute gastric mucosa lesions after hypothermic restraint stress in rats.Gastroenterology,1985 ; 88 (3):660-665.
6. Kivilaakso E.Relationship between ulceration and intramural pH of gastric mucosa during hemorrhagic shock.Surgery,1987; 102:27.
7. Priebe HJ.Antacid versus cimetidine in preventing acute gastrointestina bleeding.N EngI J Med,1980; 302 (8):426-427.
8. Main points of dignosis of cerebrovascular disease.Chinese Journal of Neurology,1996; 29(6):379.各类脑血管疾病诊断要点(1995年中华医学会全国第四届脑血管病学术会议通过).中华神经科杂志,1996;29(6):379.
9. Zhang FL,Zhao JH,Li Y.The clinical effective observation of Lansoprazole for stress ulcer bleeding in patients of cerebral stroke.Chinese Journal of Clinical Pharmacology and Therapeutics,2002;7(4):351-352.张凤兰,赵均和,李岩.兰索拉唑预防急性脑卒中后应激性溃疡出血的临床疗效观察.中国临床药理学与治疗学,2002;7(4):351～352.
10. Liang J.Lansoprazole for stress ulcer bleeding in 30 patients of cerebral hemorrhage resulted of high pressure.New Medicine,1997;28(6):295-296.粱健.兰索拉唑对预防高血压性脑出血后应激性溃疡30例的作用.新医学,1997;28(6):295～296.
11. Wei DS.Omeprazole and Cimetidine for acute cerebral vascular disease with stress ulcer bleeding.Journal of Modern Clinical Medical Bioengineering,2002;8(2):130-132.魏端生.洛赛克与西咪替丁预防急性脑血管病并应激性溃疡出血的临床研究.Journal of Modern Clinical Medical Bioengineering,2002;8(2):130～132.
12. Huaug YF.Omeprazole for acute cerebral hemorrhage with stress ulcer bleeding.Medical Theory and Practice,2004;17(10):1166-1167.黄永锋.奥美拉唑预防急性脑出血并发应激性溃疡消化道出血的疗效观察.医学理论与实践,2004;17(10):1166～1167.
13. Liu K.Pantoprazole for cerebral hemorrhage resulted of high pressure with stress ulcer bleeding.Medical Theory and Practice,2004;17(10):1166-1167.刘坤.潘托拉唑对预防高血压性脑出血后应激性溃疡的作用.医学理论与实践,2004;17(2):161～162.
14. Wang QR,Pei GZ.Pantoprazole for stress ulcer in 43 severe cerebral hemorrhage patients.Chinese Society Physician,2003;5(8):21-22.王全让,裴广忠.泮妥拉唑钠对重度脑出血并发应激性溃疡43例的预防作用.中国社区医师,2003;5(8):21～22.
15. Shang XW.The effect of omeprazole preventing severe cerebral hemorrhage with stress gastric lesions.Journal of Henan Employee Medical University,2004;16(3):271-272.尚现伟.洛赛克在预防重症脑出血并发应激性胃粘膜病变中的作用.河南职工医学院学报,2004;16(3):271～272.
16. Gui JW.Cimetidine preventing cerebral hemorrhage with stress ulcer in old patients.Hengyang Journal of Medical University,1997;25(4):404-405.桂建伟.西咪替丁对老年人脑出血并发应激性溃疡的预防.衡阳医学院学报,1997;25(4):404～405.
17. Peng XL,Tang BS,Yang QD et al.Clinical observation of prevention of cerebral hemorrhage with stress ulcer.Chinese Journal of Modern Medicine,1997;7(2):67-68.彭晓兰,唐北沙,杨期东等.脑出血应激性溃疡预防性治疗的临床观察.中国现代医学杂志,1997;7(2):67～68.
18. Xu ZQ.Effect of famotidine preventing cerebral stroke with stress ulcer bleeding.Chinese Journal of Clinical New Medicine,2002;2(12):1127-1128.许志强.法莫替丁预防脑卒中应激性溃疡出血的疗效观察.中华临床新医学,2002;2(12):1127～1128.
19. Huang YF,Huang AZ,Wei HL.Effect of famotidine preventing cerebral stroke with stress ulcer bleeding.Huaxia Medicine,2003;16(3):315-316.黄永锋,黄爱珍,韦海玲.法莫替丁预防脑出血并发应激性溃疡出血的效果观察.华夏医学,2003;16(3):315～316.
20. Lu YH.Cimetidine preventing for cerebral hemorrhage resulted of high pressure with stress ulcer.Chinese Emergency Disease Medicine,1998;10(7):446.陆亿华.泰胃美注射液预防高血压性脑出血后应激性溃疡.中国危重病急救医学,1998;10(7):446.
21. Wang Y,Chen BH,Wu TF.Effect of cimetidine preventing stress ulcer of cerebral vascular disease.Chinese Clinical Medicine,2000;7(4):422-423.王英,陈百华,吴同发.泰胃美预防急性脑血管病性应激性溃疡的疗效观察.中国临床医学,2000;7(4):422～423.
22. Miao JL,Geng LM,Xu JS et al.Prevention of stress ulcer in acute cerebral stroke.Practice of New Medicine,2001;3(2):116-117.苗今乐,耿黎明,徐建生等.急性脑卒中应激性溃疡的防治.实用新医学,2001;3(2):116～117.
23. Liu XQ.Effect of Omeprazole preventing acute cerebral vascular disease with stress ulcer.Journal of NanHua University(Medical Edition),2002;30(1):55-56.刘雪晴.奥美拉唑对急性脑血管病应激性溃疡出血的预防作用.南华大学学报医学版,2002;30(1):55～56.
24. Chen XD.Effect of Omeprazole combined with Cimetidine preventing severe cerebral vascular disease with stress ulcer.Journal of World Today Medicine,2003;4(4):279-280.陈新东.奥美拉唑与西咪替丁预防重症脑血管病应激性溃疡出血的疗效观察.世界今日医学杂志,2003;4(4):279～280.
25. Zang WG.Pantoprazole preventing stree ulcer bleeding in 21 cerebral vascular disease.Shandong Medicine,2003;43(9):3.臧伟广.潘托拉唑预防脑出血并发应激性溃疡出血21例.山东医药,2003;43(9):3.
26. Huang YD.Clinical study of pantopraloe combined withDahuang preventing acute cerebral vascular incidence with stress ulcer bleeding.Henan Medical Information,2002;10(3):52-53.黄永德.潘托拉唑与大黄预防急性脑血管意外合并发应激性溃疡出血的临床研究.河南医药信息,2002;10(3):52～53.
27. Jin XY,Sun SZ,Cao X.Clinical observation of Omeprazole preventing cerebral hemorrhage coma combined with stress ulcer bleeding.Journal of Clinical Indigestive Disease,2001;13(2):58-59.金先银,孙素珍,曹侠.洛赛克预防脑出血昏迷并发应激性溃疡出血的临床观察.临床消化病杂志,2001;13(2):58～59.
28. Xin JF,Zhang JT,Guo ML.Omeprazole combined with cimetidine preventing cerebral hemorrhage resulted of high pressure with stress ulcer bleeding.Journal of Practical Medical Technology,2004;11(9):1858.辛建峰,张江涛,郭美玲.洛赛克与西咪替丁对高血压脑出血并发应激性溃疡上消化道出血预防作用的研究.实用医技杂志,2004;11(9):1858.
29. Mrrone GC,Silen W.Pathogenesis,diagnosis and treatment of acute gastric mucosal lesion.Clin Gastroenterol,1984 ; 13:635-650.
30. Mitchell J,Spirt MD.Stress related mucosal disease:risk factors and prophylactic therapy.Clinical Therapeutics,2004 ; 26(2):197-231.
31. Cook DJ,Fuller HD,Guyatt GH,et al.For the Canadian critical care trials group.Risk factors for gastrointestinal bleeding in critically ill patients.N Engl J Med,1994 ; 330 (6):377-381.
32. Zuckerman GR,Shuman R.Therapeutic goals and treatmeat options for prevention of stress ulcer syndrom.Am J Med,1987 ; 83 (supple 6A):29-35.
33. Phillips JO,Metzler MH,Palmieri MT,et al.A prospective study of simplified omeprazole suspension for the prophylaxis of stress-related mucosal damage.Crit Care Med,1996 ; 24:1793-1800.
34. Asky MR,Metzler MH,Phillips JO.A prospective study of omeprazole suspension to prevent clinically significant gastrointestinal bleeding from stress ulcers in mechanically ventilated trauma patients.J Trauma,1998 ; 44 (3):527-533.

Chinese Journal of Evidence-Based Medicine

Proton Pump Inhibitor and H2RA Pharmacological Prevention of Stress Ulcer Bleeding in Stroke Patients: A Systematic Review of Randomized Controlled Trials

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