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 We handsearched the related published and unpublished data and their references.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.程學銘.腦血管病的流行病學.第4版.北京:中國科學技術出版社,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.急性腦出血1000例預后研究.中國急救醫學雜志,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.樓繼軍,宴才杰,陳華.冷束縛應激對大鼠胃微循環的影響.微循環學,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.各類腦血管疾病診斷要點(1995年中華醫學會全國第四屆腦血管病學術會議通過).中華神經科雜志,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.張鳳蘭,趙均和,李巖.蘭索拉唑預防急性腦卒中后應激性潰瘍出血的臨床療效觀察.中國臨床藥理學與治療學,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.蘭索拉唑對預防高血壓性腦出血后應激性潰瘍30例的作用.新醫學,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.洛賽克與西咪替丁預防急性腦血管病并應激性潰瘍出血的臨床研究.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.黃永鋒.奧美拉唑預防急性腦出血并發應激性潰瘍消化道出血的療效觀察.醫學理論與實踐,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.劉坤.潘托拉唑對預防高血壓性腦出血后應激性潰瘍的作用.醫學理論與實踐,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.王全讓,裴廣忠.泮妥拉唑鈉對重度腦出血并發應激性潰瘍43例的預防作用.中國社區醫師,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.尚現偉.洛賽克在預防重癥腦出血并發應激性胃粘膜病變中的作用.河南職工醫學院學報,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.桂建偉.西咪替丁對老年人腦出血并發應激性潰瘍的預防.衡陽醫學院學報,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.彭曉蘭,唐北沙,楊期東等.腦出血應激性潰瘍預防性治療的臨床觀察.中國現代醫學雜志,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.許志強.法莫替丁預防腦卒中應激性潰瘍出血的療效觀察.中華臨床新醫學,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.黃永鋒,黃愛珍,韋海玲.法莫替丁預防腦出血并發應激性潰瘍出血的效果觀察.華夏醫學,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):446.陸億華.泰胃美注射液預防高血壓性腦出血后應激性潰瘍.中國危重病急救醫學,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,陳百華,吳同發.泰胃美預防急性腦血管病性應激性潰瘍的療效觀察.中國臨床醫學,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.苗今樂,耿黎明,徐建生等.急性腦卒中應激性潰瘍的防治.實用新醫學,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.劉雪晴.奧美拉唑對急性腦血管病應激性潰瘍出血的預防作用.南華大學學報醫學版,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.陳新東.奧美拉唑與西咪替丁預防重癥腦血管病應激性潰瘍出血的療效觀察.世界今日醫學雜志,2003;4(4):279～280.
25.	Zang WG.Pantoprazole preventing stree ulcer bleeding in 21 cerebral vascular disease.Shandong Medicine,2003;43(9):3.臧偉廣.潘托拉唑預防腦出血并發應激性潰瘍出血21例.山東醫藥,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.黃永德.潘托拉唑與大黃預防急性腦血管意外合并發應激性潰瘍出血的臨床研究.河南醫藥信息,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.金先銀,孫素珍,曹俠.洛賽克預防腦出血昏迷并發應激性潰瘍出血的臨床觀察.臨床消化病雜志,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,張江濤,郭美玲.洛賽克與西咪替丁對高血壓腦出血并發應激性潰瘍上消化道出血預防作用的研究.實用醫技雜志,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.程學銘.腦血管病的流行病學.第4版.北京:中國科學技術出版社,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.急性腦出血1000例預后研究.中國急救醫學雜志,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.樓繼軍,宴才杰,陳華.冷束縛應激對大鼠胃微循環的影響.微循環學,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.各類腦血管疾病診斷要點(1995年中華醫學會全國第四屆腦血管病學術會議通過).中華神經科雜志,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.張鳳蘭,趙均和,李巖.蘭索拉唑預防急性腦卒中后應激性潰瘍出血的臨床療效觀察.中國臨床藥理學與治療學,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.蘭索拉唑對預防高血壓性腦出血后應激性潰瘍30例的作用.新醫學,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.洛賽克與西咪替丁預防急性腦血管病并應激性潰瘍出血的臨床研究.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.黃永鋒.奧美拉唑預防急性腦出血并發應激性潰瘍消化道出血的療效觀察.醫學理論與實踐,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.劉坤.潘托拉唑對預防高血壓性腦出血后應激性潰瘍的作用.醫學理論與實踐,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.王全讓,裴廣忠.泮妥拉唑鈉對重度腦出血并發應激性潰瘍43例的預防作用.中國社區醫師,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.尚現偉.洛賽克在預防重癥腦出血并發應激性胃粘膜病變中的作用.河南職工醫學院學報,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.桂建偉.西咪替丁對老年人腦出血并發應激性潰瘍的預防.衡陽醫學院學報,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.彭曉蘭,唐北沙,楊期東等.腦出血應激性潰瘍預防性治療的臨床觀察.中國現代醫學雜志,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.許志強.法莫替丁預防腦卒中應激性潰瘍出血的療效觀察.中華臨床新醫學,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.黃永鋒,黃愛珍,韋海玲.法莫替丁預防腦出血并發應激性潰瘍出血的效果觀察.華夏醫學,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):446.陸億華.泰胃美注射液預防高血壓性腦出血后應激性潰瘍.中國危重病急救醫學,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,陳百華,吳同發.泰胃美預防急性腦血管病性應激性潰瘍的療效觀察.中國臨床醫學,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.苗今樂,耿黎明,徐建生等.急性腦卒中應激性潰瘍的防治.實用新醫學,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.劉雪晴.奧美拉唑對急性腦血管病應激性潰瘍出血的預防作用.南華大學學報醫學版,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.陳新東.奧美拉唑與西咪替丁預防重癥腦血管病應激性潰瘍出血的療效觀察.世界今日醫學雜志,2003;4(4):279～280.
25. Zang WG.Pantoprazole preventing stree ulcer bleeding in 21 cerebral vascular disease.Shandong Medicine,2003;43(9):3.臧偉廣.潘托拉唑預防腦出血并發應激性潰瘍出血21例.山東醫藥,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.黃永德.潘托拉唑與大黃預防急性腦血管意外合并發應激性潰瘍出血的臨床研究.河南醫藥信息,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.金先銀,孫素珍,曹俠.洛賽克預防腦出血昏迷并發應激性潰瘍出血的臨床觀察.臨床消化病雜志,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,張江濤,郭美玲.洛賽克與西咪替丁對高血壓腦出血并發應激性潰瘍上消化道出血預防作用的研究.實用醫技雜志,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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