• 四川大學(xué)華西醫(yī)院消化科(成都 610041);

目的 　評(píng)價(jià) H2受體拮抗劑（H2RA）對(duì)預(yù)防重危病人應(yīng)激性潰瘍出血（SUB）的有效性及安全性。
方法　 按既定的檢索策略，全面檢索 Cochrane 臨床對(duì)照試驗(yàn)數(shù)據(jù)庫(kù)（2006 年第 4 期）、MEDLINE 光盤數(shù)據(jù)庫(kù)（1980 ～ 2006 年 10月）、EMbase 光盤數(shù)據(jù)庫(kù)（1984 ～ 2006 年 10 月）、中國(guó)生物醫(yī)學(xué)文獻(xiàn)數(shù)據(jù)庫(kù)(1978 ～ 2006 年 10 月 )、維普中刊數(shù)據(jù)庫(kù)（1989 ～ 2006 年 10 月）和中文循證醫(yī)學(xué)隨機(jī)對(duì)照試驗(yàn)數(shù)據(jù)庫(kù)。手工檢索 5 種相關(guān)中文期刊、相關(guān)會(huì)議論文集及所有檢索到試驗(yàn)的參考文獻(xiàn)。納入H2RA 預(yù)防 SUB 的隨機(jī)對(duì)照試驗(yàn)。由兩位研究者獨(dú)立地對(duì)納入試驗(yàn)進(jìn)行質(zhì)量評(píng)價(jià)和資料提取，并交叉核對(duì)。如有分歧，通過討論解決。結(jié)局指標(biāo)包括 SUB 的發(fā)生率、醫(yī)源性肺炎 (nosocomial pneumonia，NP) 發(fā)生率、病死率、藥物不良反應(yīng)的發(fā)生率、胃液 pH 值等指標(biāo)評(píng)價(jià)藥物預(yù)防SUB 的效果和安全性。采用 RevMan4.2.7 軟件進(jìn)行 Meta 分析。
結(jié)果 　共檢索到 18 個(gè)可能符合納入標(biāo)準(zhǔn)的臨床試驗(yàn)，其中 16 個(gè)試驗(yàn)共包括 2 014 例病人符合納入標(biāo)準(zhǔn)，2 個(gè)試驗(yàn)被排除。納入試驗(yàn)的方法學(xué)質(zhì)量高低不齊。提取數(shù)據(jù)后，進(jìn)行 Meta分析或描述性分析。① H2RA能降低SUB的發(fā)生率［RR 0.39， 95%CI （0.28，0.56）； P lt;0.000 01，NNT=6］， H2RA（P=0.11），不能降低臨床大出血的發(fā)生率［RR 0.51， 95%CI（0.17， 1.53）； P=0.11］。② H2RA與安慰劑相比較， NP發(fā)生率差別無統(tǒng)計(jì)學(xué)意義［RR 1.02， 95%CI（0.55，1.89）； P=0.95］。③ H2RA 能降低病死率［RR 0.68， 95% CI（0.52， 0.90）； P=0.007，NNT=18］。④ H2RA的安全性好。⑤ 藥物預(yù)防 SUB 對(duì)胃內(nèi) pH 值的影響，由于所納入的試驗(yàn)在 pH 值的測(cè)量方法、測(cè)量時(shí)間上的差異，無法提取資料進(jìn)行合并分析。所有試驗(yàn)均未將住院時(shí)間作為觀察指標(biāo)。
結(jié)論　 現(xiàn)有的有限證據(jù)表明，預(yù)防性使用 H2RA 均能降低SUB 發(fā)生率、病死率但不能降低臨床大出血的發(fā)生率。因所發(fā)表的臨床研究方法學(xué)質(zhì)量普遍不高，存在多種方法學(xué)局限性。故應(yīng)謹(jǐn)慎看待以上結(jié)論。今后有必要進(jìn)一步開展大樣本、高質(zhì)量的臨床隨機(jī)對(duì)照試驗(yàn)，為 H2RA 預(yù)防SUB 提供更為可靠證據(jù)。

引用本文： 曾超,王一平. H2受體拮抗劑預(yù)防應(yīng)激性潰瘍出血的系統(tǒng)評(píng)價(jià). 中國(guó)循證醫(yī)學(xué)雜志, 2007, 07(9): 658-668. doi: 復(fù)制

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. 蕭樹東, 許國(guó)銘, 李兆申, 等. 應(yīng)激性潰瘍防治建議. 中國(guó)醫(yī)學(xué)雜志, 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. 劉厚鈺. 應(yīng)激性潰瘍. 現(xiàn)代胃腸病學(xué), 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. 劉鳴, 張世洪. 臨床試驗(yàn)中的意向處理分析. 英國(guó)醫(yī)學(xué)雜志中文版, 2001, 4(4): 223-224 .
33. 胡義平, 陳明建. 奧美拉唑與雷尼替丁用于預(yù)防高血壓并發(fā)腦出血術(shù)后應(yīng)激性潰瘍出血的臨床研究. 新醫(yī)學(xué), 2001, 32(10): 598-599 .
34. 魏端生. 洛賽克與西咪替丁預(yù)防急性腦血管病并應(yīng)激性潰瘍出血的臨床研究. 現(xiàn)代臨床醫(yī)學(xué)生物工程學(xué)雜志, 2002, 8(2): 130-132 .
35. 朱濤. 奧美拉唑預(yù)防重型顱腦損傷后上消化道出血的療效觀察. 交通醫(yī)學(xué), 2003, 17(5): 530-534 .
36. 徐敏. 西咪替丁預(yù)防呼吸衰竭并發(fā)應(yīng)激性潰瘍療效觀察. 浙江實(shí)踐藥學(xué), 2001, 6(1): 14 .
37. 桂建偉. 西咪替丁對(duì)老年人腦出血并發(fā)應(yīng)激性潰瘍的預(yù)防. 衡陽(yáng)醫(yī)學(xué)院學(xué)報(bào), 1997, 25(4): 404-405 .
38. 彭曉蘭, 唐北沙, 楊期東, 等. 腦出血應(yīng)激性潰瘍預(yù)防性治療的臨床觀察. 中國(guó)現(xiàn)代醫(yī)學(xué)雜志, 1997, 7(2): 67-68 .
39. 王國(guó)強(qiáng), 陳鐵峰, 雷鵬舉, 等. 甲氰咪呱預(yù)防前列腺術(shù)后并發(fā)應(yīng)激性潰瘍臨床研究 (附103例報(bào)告). 中國(guó)臨床醫(yī)藥研究雜志, 2003, 90: 8802-8803 .
40. 許志強(qiáng). 法莫替丁預(yù)防腦卒中應(yīng)激性潰瘍出血的療效觀察. 中華臨床新醫(yī)學(xué), 2002, 2(12): 1127-1128 .
41. 黃永鋒, 黃愛珍, 韋海玲. 法莫替丁預(yù)防腦出血并發(fā)應(yīng)激性潰瘍出血的效果觀察. 華夏醫(yī)學(xué), 2003, 16(3): 315-316 .
42. 傅小君, 許信龍. 重型顱腦損傷術(shù)后應(yīng)激性潰瘍的預(yù)防. 急診醫(yī)學(xué), 1999, 8(6): 432-433 .
43. 陸億華. 泰胃美注射液預(yù)防高血壓性腦出血后應(yīng)激性潰瘍. 中國(guó)危重病急救醫(yī)學(xué), 1998, 10(7): 446 .
44. 王英, 陳百華, 吳同發(fā). 泰胃美預(yù)防急性腦血管病性應(yīng)激性潰瘍的療效觀察. 中國(guó)臨床醫(yī)學(xué), 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. 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. 2. Liu HY. Stress ulcer. Modern Gastroenterology, 1994, 83: 951-95.
  3. 3. Liu M, Zhang SH. Intention to treat in clinical trial. BMJ (Chinese edition), 2001, 4(4): 223-224.
  4. 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. 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. 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. 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. 8. Gui JW. Cimetidine preventing cerebral hemorrhage with stress ulcer in old patients. Hengyang Journal of Medical University, 1997, 25(4): 404-405 .
  9. 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. 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. 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. 12. Huang YF, Huang AZ, Wei HL. Effect of famotidine preventing stroke with stress ulcer bleeding. Huaxia Medicine, 2003, 16(3): 315-316 .
  13. 13. Fu XJ, Xu XL. Prevention of stress ulcer in postoperative of severe head injury. Emergency Medicine, 1999, 8(6): 432-433 .
  14. 14. Lu YH. Cimetidine preventing for cerebral hemorrhage resulted of high pressure with stress ulcer. Chinese Emergency Disease Medicine, 1998, 10(7): 446 .
  15. 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. 16. 蕭樹東, 許國(guó)銘, 李兆申, 等. 應(yīng)激性潰瘍防治建議. 中國(guó)醫(yī)學(xué)雜志, 2002, 82(14): 1000-1001.
  17. 17. Mitchell J, Spirt MD. Stress related mucosal disease: risk factors and prophylactic therapy. Clinical Therapeutics, 2004, 26(2): 197-231.
  18. 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. 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. 20. 劉厚鈺. 應(yīng)激性潰瘍. 現(xiàn)代胃腸病學(xué), 1994, 83: 951-95.
  21. 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. 22. Haglund U. Stress ulcers. Scand J Gastroenterol, 1990, 35(Suppl 175): 27-33.
  23. 23. Nardino RJ, Vender RJ, Herbert PN. Overuse of acid-suppressive therapy in hospitalized patients. Am J Gastroenterol, 2000, 95(11): 3118-3122.
  24. 24. Andrew S, Jon I. Peptic ulcer disease: epidemiology , pathophyslology, clinical manifestations and diagnosis. Cecil Textbook of Medicine, 2003, Chapt126: 671-675.
  25. 25. ASHP. Commission on therapeutic guidelines on stress ulcer prophylaxis. AM J Health Syst Pharm, 1999, 56(15): 347-379.
  26. 26. ASHP. Stress ulcer prophylaxis in the postoperative period. AM J Health Syst Pharm, 2004, 61(15): 588-596.
  27. 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. 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. 29. Zantac [package insert]. Research Triangle park. NC GlaxoSmithKl ine, 2001.
  30. 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. 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. 32. 劉鳴, 張世洪. 臨床試驗(yàn)中的意向處理分析. 英國(guó)醫(yī)學(xué)雜志中文版, 2001, 4(4): 223-224 .
  33. 33. 胡義平, 陳明建. 奧美拉唑與雷尼替丁用于預(yù)防高血壓并發(fā)腦出血術(shù)后應(yīng)激性潰瘍出血的臨床研究. 新醫(yī)學(xué), 2001, 32(10): 598-599 .
  34. 34. 魏端生. 洛賽克與西咪替丁預(yù)防急性腦血管病并應(yīng)激性潰瘍出血的臨床研究. 現(xiàn)代臨床醫(yī)學(xué)生物工程學(xué)雜志, 2002, 8(2): 130-132 .
  35. 35. 朱濤. 奧美拉唑預(yù)防重型顱腦損傷后上消化道出血的療效觀察. 交通醫(yī)學(xué), 2003, 17(5): 530-534 .
  36. 36. 徐敏. 西咪替丁預(yù)防呼吸衰竭并發(fā)應(yīng)激性潰瘍療效觀察. 浙江實(shí)踐藥學(xué), 2001, 6(1): 14 .
  37. 37. 桂建偉. 西咪替丁對(duì)老年人腦出血并發(fā)應(yīng)激性潰瘍的預(yù)防. 衡陽(yáng)醫(yī)學(xué)院學(xué)報(bào), 1997, 25(4): 404-405 .
  38. 38. 彭曉蘭, 唐北沙, 楊期東, 等. 腦出血應(yīng)激性潰瘍預(yù)防性治療的臨床觀察. 中國(guó)現(xiàn)代醫(yī)學(xué)雜志, 1997, 7(2): 67-68 .
  39. 39. 王國(guó)強(qiáng), 陳鐵峰, 雷鵬舉, 等. 甲氰咪呱預(yù)防前列腺術(shù)后并發(fā)應(yīng)激性潰瘍臨床研究 (附103例報(bào)告). 中國(guó)臨床醫(yī)藥研究雜志, 2003, 90: 8802-8803 .
  40. 40. 許志強(qiáng). 法莫替丁預(yù)防腦卒中應(yīng)激性潰瘍出血的療效觀察. 中華臨床新醫(yī)學(xué), 2002, 2(12): 1127-1128 .
  41. 41. 黃永鋒, 黃愛珍, 韋海玲. 法莫替丁預(yù)防腦出血并發(fā)應(yīng)激性潰瘍出血的效果觀察. 華夏醫(yī)學(xué), 2003, 16(3): 315-316 .
  42. 42. 傅小君, 許信龍. 重型顱腦損傷術(shù)后應(yīng)激性潰瘍的預(yù)防. 急診醫(yī)學(xué), 1999, 8(6): 432-433 .
  43. 43. 陸億華. 泰胃美注射液預(yù)防高血壓性腦出血后應(yīng)激性潰瘍. 中國(guó)危重病急救醫(yī)學(xué), 1998, 10(7): 446 .
  44. 44. 王英, 陳百華, 吳同發(fā). 泰胃美預(yù)防急性腦血管病性應(yīng)激性潰瘍的療效觀察. 中國(guó)臨床醫(yī)學(xué), 2000, 7(4): 422-423.
  45. 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 .
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