H2RA for Prevention of Stress Ulcer Bleeding: A Systematic Review of Randomized Controlled Trials_Chinese Journal of Evidence-Based Medicine

Authors：

ZENG Chao ,  WANG Yiping

Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

WANG Yiping, Email: wyiping2006@yahoo.com.cn

Keywords：

Stress ulcer bleeding; H2RA; Systematic review; Meta-analysis

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Objective　 To assess the efficacy and safety of histamine H2 receptor antagonist (H2RA) for the prevention of stress ulcer bleeding (SUB) in critically ill patients.
Methods　 Trials were identified by searching Cochrane Controlled Trials (Issue 4, 2006), MEDLINE (1980 to October 2006),EMbase (1984 to October 2006) and the Chinese Biological Medicine Database (1978 to October), Chinese VIP Database (1989 to October 2006) and Chinese EBM Database. We also handsearched the proceedings of relevant conferences, 5 kinds of important Chinese journals and the references of all included trials. Two reviewers assessed the quality of studies and extracteddata independently. Disagreement was resolved by discussion . The primary outcomes included were incidence of SUB, incidence of nosocomial pneumonia (NP), mortality and adverse events. Secondary outcomes were gastric pH, length of hospital stayand length of ICU stay. RevMan4.2.7 software was used for meta-analyses.
Results　 Sixteen trials involving 2 014 patients were included. Most of the trials were of poor quality. Meta-analyses showed that H2RA significantly less SUB comparedwith patients in the placebo or non-prophylaxis group (RR 0.39, 95%CI 0.28 to 0.56; P lt;0.000 01, NNT=6), but but there was no significant difference in the incidence of clinically important bleeding (RR 0.51 , 95%CI 0.17 to 1.53; P=0.11). No significant difference was observed in the incidence of NP(RR 1.02, 95%CI 0.55 to 1.89,P=0.95). H2RA significantly decreased mortality in comparison with placebo or non-prophylaxis (RR 0.68, 95%CI 0.52 to 0.90; P=0.007, NNT=18). H2RA had a good safety profile. We did not perform meta-analysis for gastric pH due to the methodological limitations.
Conclusion　 H2RA may significantly reduce the incidence of SUB and mortality, but cannot reduce the incidence of clinically important bleeding. Due to the poor quality of included studies, the conclusion should be interpreted cautiously. More randomized controlled trials with sufficient sample size, uniform standards, higher quality and scientifically sound methodology should be performed.

Citation： ZENG Chao,WANG Yiping. H2RA for Prevention of Stress Ulcer Bleeding: A Systematic Review of Randomized Controlled Trials. Chinese Journal of Evidence-Based Medicine, 2007, 07(9): 658-668. doi: Copy

1.	Xiao SD, Xu GM, Li ZS, et al.Suggest on prevention for stress ulcer. National Medical Journal of China, 2002, 82(14): 1000-1001.
2.	Liu HY. Stress ulcer. Modern Gastroenterology, 1994, 83: 951-95.
3.	Liu M, Zhang SH. Intention to treat in clinical trial. BMJ (Chinese edition), 2001, 4(4): 223-224.
4.	Hu YP, Chen MJ. Clinical research on Omeprazole and Ranitidine for postoperative of acute cerebral vascular disease with stress ulcer bleeding. New Chinese Medicine, 2001, 32(10): 598-599.
5.	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.
6.	Zhu T. The observation of omeprazole in prevention of upper gastrointestinal bleeding in severe head injury. Communication Medicine, 2003, 17(5): 530-534 .
7.	Xu M. The observation of Cimetidine in prevention of stress ulcer in respiratory failure. Practice Pharmaceutical Sciences of Zhejiang, 2001, 6(1): 14 .
8.	Gui JW. Cimetidine preventing cerebral hemorrhage with stress ulcer in old patients. Hengyang Journal of Medical University, 1997, 25(4): 404-405 .
9.	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 .
10.	Wang GQ, Chen TF, Lei PJ, et al. Clinical research on Cimetidine in prevention of stress ulcer in post-prostatectomy (103 reports). Clinical Medicine Magazine of China, 2003, 90: 8802-8803 .
11.	Xu ZQ. The observation of Famotidine in prevention of stress ulcer bleeding in stroke. Clinical New Medicine of China, 2002, 2(12): 1127-1128 .
12.	Huang YF, Huang AZ, Wei HL. Effect of famotidine preventing stroke with stress ulcer bleeding. Huaxia Medicine, 2003, 16(3): 315-316 .
13.	Fu XJ, Xu XL. Prevention of stress ulcer in postoperative of severe head injury. Emergency Medicine, 1999, 8(6): 432-433 .
14.	Lu YH. Cimetidine preventing for cerebral hemorrhage resulted of high pressure with stress ulcer. Chinese Emergency Disease Medicine, 1998, 10(7): 446 .
15.	Wang Y, Chen BH, Wu TF. The observation of Tagament effect on the prevention from stress ulcer in patients with acute cerebrovascular disease. Clinical Medicine Journal of China, 2000, 7(4): 422-423.
16.	萧树东, 许国铭, 李兆申, 等. 应激性溃疡防治建议. 中国医学杂志, 2002, 82(14): 1000-1001.
17.	Mitchell J, Spirt MD. Stress related mucosal disease: risk factors and prophylactic therapy. Clinical Therapeutics, 2004, 26(2): 197-231.
18.	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.
19.	Zuckerman GR, Shuman R. Therapeutic goals and treatmeat options for prevention of stress ulcer syndrom. Am J Med, 1987, 83(Supple 6A): 29-35.
20.	刘厚钰. 应激性溃疡. 现代胃肠病学, 1994, 83: 951-95.
21.	Beejay U, Wolfe MM. Acute gastrointestinal bleeding in the intensive care unit. The gastroenterologist’ s perspective. Gastroenterol Clin North Am, 2000, 29(2): 309-336.
22.	Haglund U. Stress ulcers. Scand J Gastroenterol, 1990, 35(Suppl 175): 27-33.
23.	Nardino RJ, Vender RJ, Herbert PN. Overuse of acid-suppressive therapy in hospitalized patients. Am J Gastroenterol, 2000, 95(11): 3118-3122.
24.	Andrew S, Jon I. Peptic ulcer disease: epidemiology , pathophyslology, clinical manifestations and diagnosis. Cecil Textbook of Medicine, 2003, Chapt126: 671-675.
25.	ASHP. Commission on therapeutic guidelines on stress ulcer prophylaxis. AM J Health Syst Pharm, 1999, 56(15): 347-379.
26.	ASHP. Stress ulcer prophylaxis in the postoperative period. AM J Health Syst Pharm, 2004, 61(15): 588-596.
27.	Kohka H, Nishibori M, Iwagaki H, et al. Histamine is a potent inducer of IL-18 and IFN-gamma in human peripheral blood mononuclear cells. J Immunol, 2000, 164(12): 6640-6646.
28.	Hellstrand K, Asea A, Hermodsson S. Role of histamine in natural killer cell-mediated resistance against tumor cells. J Immunol, 1990, 145(12): 4365-4370.
29.	Zantac [package insert]. Research Triangle park. NC GlaxoSmithKl ine, 2001.
30.	Cook DJ, Reeve BK, Guyatt GH, et al. Stress ulcer prophylaxis in critically ill patients: Resolving discordant meta-analyses. Journal of the American Medical Association, 1996, 275(4): 308-314 .
31.	Ernst W, Hanisch MD, Encke MD, et al. A randomized , double-blind trial for stress ulcer prophylaxis shows no evidence of increased pneumonia. American Journal of Surgery, 1998, 176(5): 453-457 .
32.	刘鸣, 张世洪. 临床试验中的意向处理分析. 英国医学杂志中文版, 2001, 4(4): 223-224 .
33.	胡义平, 陈明建. 奥美拉唑与雷尼替丁用于预防高血压并发脑出血术后应激性溃疡出血的临床研究. 新医学, 2001, 32(10): 598-599 .
34.	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. 现代临床医学生物工程学杂志, 2002, 8(2): 130-132 .
35.	朱涛. 奥美拉唑预防重型颅脑损伤后上消化道出血的疗效观察. 交通医学, 2003, 17(5): 530-534 .
36.	徐敏. 西咪替丁预防呼吸衰竭并发应激性溃疡疗效观察. 浙江实践药学, 2001, 6(1): 14 .
37.	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 .
38.	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 .
39.	王国强, 陈铁峰, 雷鹏举, 等. 甲氰咪呱预防前列腺术后并发应激性溃疡临床研究 (附103例报告). 中国临床医药研究杂志, 2003, 90: 8802-8803 .
40.	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 .
41.	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 .
42.	傅小君, 许信龙. 重型颅脑损伤术后应激性溃疡的预防. 急诊医学, 1999, 8(6): 432-433 .
43.	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 .
44.	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.
45.	Kantorova I, Svoboda P, Scheer P, et al. Stress ulcer prophylaxis in critically ill patients : a randomized controlled trial . Hepatogastroenterology, 2004, 51(57): 757-761 .
46.	Kaushal S, Midha V, Sood A, et al. A comparative study of the effects of famotidine and sucralfate in prevention of upper gastrointestinal bleeding in patients of head injury. Indian Journal of Pharmacology, 2000, 32(2): 246-249 .
47.	Halloran LG, Zfass AM, Gayle WE, et al. Prevention of acute gastrointestinal complications after severe head injury: A controlled trial of cimetidine propylaxis. American Journal of Surgery, 1980, 139(1): 44 -48.
48.	Priebe HJ, Skillman JJ, Bushnell LS, et al. Antacid versus cimetidine in preventing acute gastrointestina bleeding. N EngI J Med, 1980, 302(8): 426-427.

1. Xiao SD, Xu GM, Li ZS, et al.Suggest on prevention for stress ulcer. National Medical Journal of China, 2002, 82(14): 1000-1001.
2. Liu HY. Stress ulcer. Modern Gastroenterology, 1994, 83: 951-95.
3. Liu M, Zhang SH. Intention to treat in clinical trial. BMJ (Chinese edition), 2001, 4(4): 223-224.
4. Hu YP, Chen MJ. Clinical research on Omeprazole and Ranitidine for postoperative of acute cerebral vascular disease with stress ulcer bleeding. New Chinese Medicine, 2001, 32(10): 598-599.
5. 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.
6. Zhu T. The observation of omeprazole in prevention of upper gastrointestinal bleeding in severe head injury. Communication Medicine, 2003, 17(5): 530-534 .
7. Xu M. The observation of Cimetidine in prevention of stress ulcer in respiratory failure. Practice Pharmaceutical Sciences of Zhejiang, 2001, 6(1): 14 .
8. Gui JW. Cimetidine preventing cerebral hemorrhage with stress ulcer in old patients. Hengyang Journal of Medical University, 1997, 25(4): 404-405 .
9. 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 .
10. Wang GQ, Chen TF, Lei PJ, et al. Clinical research on Cimetidine in prevention of stress ulcer in post-prostatectomy (103 reports). Clinical Medicine Magazine of China, 2003, 90: 8802-8803 .
11. Xu ZQ. The observation of Famotidine in prevention of stress ulcer bleeding in stroke. Clinical New Medicine of China, 2002, 2(12): 1127-1128 .
12. Huang YF, Huang AZ, Wei HL. Effect of famotidine preventing stroke with stress ulcer bleeding. Huaxia Medicine, 2003, 16(3): 315-316 .
13. Fu XJ, Xu XL. Prevention of stress ulcer in postoperative of severe head injury. Emergency Medicine, 1999, 8(6): 432-433 .
14. Lu YH. Cimetidine preventing for cerebral hemorrhage resulted of high pressure with stress ulcer. Chinese Emergency Disease Medicine, 1998, 10(7): 446 .
15. Wang Y, Chen BH, Wu TF. The observation of Tagament effect on the prevention from stress ulcer in patients with acute cerebrovascular disease. Clinical Medicine Journal of China, 2000, 7(4): 422-423.
16. 萧树东, 许国铭, 李兆申, 等. 应激性溃疡防治建议. 中国医学杂志, 2002, 82(14): 1000-1001.
17. Mitchell J, Spirt MD. Stress related mucosal disease: risk factors and prophylactic therapy. Clinical Therapeutics, 2004, 26(2): 197-231.
18. 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.
19. Zuckerman GR, Shuman R. Therapeutic goals and treatmeat options for prevention of stress ulcer syndrom. Am J Med, 1987, 83(Supple 6A): 29-35.
20. 刘厚钰. 应激性溃疡. 现代胃肠病学, 1994, 83: 951-95.
21. Beejay U, Wolfe MM. Acute gastrointestinal bleeding in the intensive care unit. The gastroenterologist’ s perspective. Gastroenterol Clin North Am, 2000, 29(2): 309-336.
22. Haglund U. Stress ulcers. Scand J Gastroenterol, 1990, 35(Suppl 175): 27-33.
23. Nardino RJ, Vender RJ, Herbert PN. Overuse of acid-suppressive therapy in hospitalized patients. Am J Gastroenterol, 2000, 95(11): 3118-3122.
24. Andrew S, Jon I. Peptic ulcer disease: epidemiology , pathophyslology, clinical manifestations and diagnosis. Cecil Textbook of Medicine, 2003, Chapt126: 671-675.
25. ASHP. Commission on therapeutic guidelines on stress ulcer prophylaxis. AM J Health Syst Pharm, 1999, 56(15): 347-379.
26. ASHP. Stress ulcer prophylaxis in the postoperative period. AM J Health Syst Pharm, 2004, 61(15): 588-596.
27. Kohka H, Nishibori M, Iwagaki H, et al. Histamine is a potent inducer of IL-18 and IFN-gamma in human peripheral blood mononuclear cells. J Immunol, 2000, 164(12): 6640-6646.
28. Hellstrand K, Asea A, Hermodsson S. Role of histamine in natural killer cell-mediated resistance against tumor cells. J Immunol, 1990, 145(12): 4365-4370.
29. Zantac [package insert]. Research Triangle park. NC GlaxoSmithKl ine, 2001.
30. Cook DJ, Reeve BK, Guyatt GH, et al. Stress ulcer prophylaxis in critically ill patients: Resolving discordant meta-analyses. Journal of the American Medical Association, 1996, 275(4): 308-314 .
31. Ernst W, Hanisch MD, Encke MD, et al. A randomized , double-blind trial for stress ulcer prophylaxis shows no evidence of increased pneumonia. American Journal of Surgery, 1998, 176(5): 453-457 .
32. 刘鸣, 张世洪. 临床试验中的意向处理分析. 英国医学杂志中文版, 2001, 4(4): 223-224 .
33. 胡义平, 陈明建. 奥美拉唑与雷尼替丁用于预防高血压并发脑出血术后应激性溃疡出血的临床研究. 新医学, 2001, 32(10): 598-599 .
34. 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. 现代临床医学生物工程学杂志, 2002, 8(2): 130-132 .
35. 朱涛. 奥美拉唑预防重型颅脑损伤后上消化道出血的疗效观察. 交通医学, 2003, 17(5): 530-534 .
36. 徐敏. 西咪替丁预防呼吸衰竭并发应激性溃疡疗效观察. 浙江实践药学, 2001, 6(1): 14 .
37. 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 .
38. 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 .
39. 王国强, 陈铁峰, 雷鹏举, 等. 甲氰咪呱预防前列腺术后并发应激性溃疡临床研究 (附103例报告). 中国临床医药研究杂志, 2003, 90: 8802-8803 .
40. 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 .
41. 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 .
42. 傅小君, 许信龙. 重型颅脑损伤术后应激性溃疡的预防. 急诊医学, 1999, 8(6): 432-433 .
43. 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 .
44. 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.
45. Kantorova I, Svoboda P, Scheer P, et al. Stress ulcer prophylaxis in critically ill patients : a randomized controlled trial . Hepatogastroenterology, 2004, 51(57): 757-761 .
46. Kaushal S, Midha V, Sood A, et al. A comparative study of the effects of famotidine and sucralfate in prevention of upper gastrointestinal bleeding in patients of head injury. Indian Journal of Pharmacology, 2000, 32(2): 246-249 .
47. Halloran LG, Zfass AM, Gayle WE, et al. Prevention of acute gastrointestinal complications after severe head injury: A controlled trial of cimetidine propylaxis. American Journal of Surgery, 1980, 139(1): 44 -48.
48. Priebe HJ, Skillman JJ, Bushnell LS, et al. Antacid versus cimetidine in preventing acute gastrointestina bleeding. N EngI J Med, 1980, 302(8): 426-427.

Chinese Journal of Evidence-Based Medicine

H2RA for Prevention of Stress Ulcer Bleeding: A Systematic Review of Randomized Controlled Trials

Abstract Full text Figures/Tables Video References Cited by

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