Acids-Suppressive Drugs and Ventilator-Associated Pneumoni_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

 HUANG Wei , WAN Xianyao

General Intensive Care Unit, The First Affiliated Hospital, Dalian Medical University. Dalian , Liaoning , 116011, China;

Corresponding?author：

HUANG Wei, Email: huangwei9898@163.com

Keywords：

Acids-Suppressive Drugs; Ventilator-Associated Pneumoni

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為預防應激性潰瘍和消化道出血, 質子泵抑制劑( PPI) 、組胺H2 受體拮抗劑( H2 RA) 以及硫糖鋁在ICU中的應用非常普遍。既往的研究認為以PPI 或H2RA 為代表的抑酸劑( ASD) 可致胃液pH 值增高, 為細菌在胃腔內定植創造了條件, 并進而增加醫院獲得性肺炎( HAP) , 尤其是呼吸機相關性肺炎( VAP) 發生的風險。我們通過文獻復習發現,ASD 與VAP 的關聯性迄今仍無明確的證據, 已有的臨床研究結論互為矛盾; 另一方面, 既往研究多集中于硫糖鋁與H2RA 的比較, 有關PPI 和H2RA 導致VAP 的風險比較研究仍然缺乏, PPI 是否比H2 RA 更易發生VAP 也缺乏研究可資證明。為此我們將有關內容綜述如下, 以供同道參考。

Citation： HUANG Wei,WAN Xianyao. Acids-Suppressive Drugs and Ventilator-Associated Pneumoni. Chinese Journal of Respiratory and Critical Care Medicine, 2009, 09(6): 599-602. doi: Copy

1.	Morehead RS, Pinto SJ. Ventilator-Associated Pneumonia. Arch Intern Med, 2000, 160: 1926-1936.
2.	American Thoracic Society, Infectious Diseases Society of America.Guidelines for the management of adults with hospital-acquired,ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med, 2005, 171: 388-416.
3.	李華茵, 何禮賢, 胡必杰, 等. 胃腔定植菌在機械通氣相關性肺炎發病機制中的作用. 中華內科雜志, 2004, 43: 112-116.
4.	Daschner F, Reuschenbach K, Pfisterer J, et al. The effect of stress ulcer prevention on the incidence of pneumonia in artificial respiration. Anaesthesist, 1987 , 36 : 9-18 .
5.	代芊, 鄧宏, 黃漢朝, 等. GM-PFGE在院內肺炎逆行感染途徑研究中的應用. 中國公共衛生, 2000, 16: 236-238.
6.	Cheadle WG, Vitale GC, Mackie CR, et al. Prophylactic postoperative nasogastric decompression. A prospective study of its requirement and the influence of cimetidine in 200 patients. Ann Surg, 1985, 202: 361-366.
7.	Tryba M. Risk of acute stress bleeding and nosocomial pneumonia in ventilated intensive care unit patients: Sucralfate versus antacids. Am JMed, 1987, 83: 117-124.
8.	Reusser P, Zimmerli W, Scheidegger D, et al. Role of gastric colonization in nosocomial infections and endotoxemia: a prospective study in neurosurgical patients. J Infect Dis, 1989, 160: 414-421.
9.	Laggner AN, Lenz K, Base W, et al. Prevention of upper gastrointestinal bleeding in long-term ventilated patients. Sucralfate versus ranitidine. Am J Med, 1989 , 86 : 81-84.
10.	Kappstein I, Schulgen G, Friedrich T, et al. The effect of stress ulcer prevention on the incidence of pneumonia in artificial respiration. Am J Med, 1991 , 91: 125 S-131S.
11.	Eddleston JM, Vohra A, Scott P, et al. A comparison of the frequency of stress ulceration and secondary pneumonia in sucralfate- or ranitidine-treated intensive care unit patients. Crit Care Med, 1991, 19: 1491-1496.
12.	Apte NM, Karnad DR, Medhekar TP, et al. Gastric colonization and pneumonia in intubated critical ill patients receiving stress ulcer prophylaxis: a randomized, controlled trial. Crit Care Med, 1992 ,20: 590-593.
13.	Masterton RG, Galloway A, French G, et al. Guidelines for the management of hospital-acquired pneumonia in the UK: Report of the Working Party on Hospital-Acquired Pneumonia of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother,2008: 62: 5-34.
14.	Metz CA, Livingston DH, Smith JS, et al. Impact of multiple risk factors and ranitidine prophylaxis on the development of stressrelated upper gastrointestinal bleeding: a prospective, multicenter,double-blind, randomized trial. Crit Care Med, 1993, 21: 1844 -1849.
15.	Martin LF, Booth F, Karlstadt RG, et al. Continuous intravenous cimetidine decreases stress-related upper gastrointestinal hemorrhage without promoting pneumonia. Crit Care Med, 1993 , 21 : 19-30.
16.	Pickworth KK, Falcone RE, Hoogeboom JE, et al. Occurrence of nosocomial pneumonia in mechanically ventilated trauma patients: a comparison of sucralfate and ranitidine. Crit Care Med, 1993, 21 :1856-1862.
17.	Ben-Menachem T, Fogel R, Patel RV, et al. Prophylaxis for stressrelated gastric hemorrhage in the medical intensive care unit. Ann Intern Med, 1994, 121: 568-575.
18.	Prod′hom G, Leuenberger P, Koerfer J, et al. Nosocomial pneumonia in mechanically ventilated patients receiving antacid, ranitidine, or sucralfate as prophylaxis for stress ulcer. A randomized controlled trial. Ann Intern Med, 1994, 120: 653-662.
19.	Thomason MH, Payseur ES, Hakenewerth AM, et al. Nosocomial pneumonia in ventilated trauma patients during stress ulcer prophylaxis with sucralfate, antacid, and ranitidine. J Trauma,1996, 41: 503-508.
20.	Hanisch EW, Encke A, Naujoks F, et al. A randomized, doubleblind trial for stress ulcer prophylaxis shows no evidence of increased pneumonia. Am J Surg, 1998, 176: 453-457.
21.	Cook D, Guyatt G, Marshall J, et al. A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. N Engl JMed, 1998, 338: 791-797.
22.	O′Keefe GE, Gentilello LM, Maier RV. Incidence of infectious complications associated with the use of histamine2-receptor antagonists in critically ill trauma patients. Ann Surg, 1998, 227 :120-125.
23.	Bonten MJ, Gaillard CA, van Tiel FH, et al. The stomach is not a source for colonization of the upper respiratory tract and pneumonia in ICU patients. Chest, 1994, 105: 878-884.
24.	Markowicz P, Wolff M, Djedani K, et al. Multicenter Prospective Study of Ventilator Associated Pneumonia During Acute Respiratory Distress Syndrome. Incidence, prognosis, and Risk Factors. Am J Respir Crit Care Med, 2000, 161: 1942-1948.
25.	Bornstain C, Azoulay E, De Lassence A, et al. Sedation, sucralfate,and antibiotic use are potential means for protection against earlyonsetventilator-associated pneumonia. Clin Infect Dis, 2004, 38 :1401-1408.
26.	Cook DJ, Laine LA, Guyatt GH, et al. Nosocomial pneumonia and the role of gastric pH. A meta-analysis. Chest, 1991, 100: 7-13.
27.	Tryba M. Sucralfate versus antacids or H2 -antagonists for stress ulcer prophylaxis: a meta-analysis on efficacy and pneumonia rate.Crit Care Med, 1991, 19: 942-949.
28.	Cook DJ. Stress Ulcer Prophylaxis: Gastrointestinal Bleeding and Nosocomial Pneumonia. Best Evidence Synthesis. Scand J Gastroenterol Suppl, 1995, 210: 48-52.
29.	Tryba M, Cook DJ. Gastric alkalinization, pneumonia, and systemic infections: the controversy. Scand J Gastroenterol Suppl, 1995 ,210: 53-59.
30.	Cook DJ, Reeve BK, Guyatt GH, et al. Stress ulcer prophylaxis in critically ill patients. Resolving discordant meta-analyses. JAMA,1996, 275: 308-314.
31.	Messori A, Trippoli S, Vaiani M, et al. Bleeding and pneumonia in intensive care patients given ranitidine and sucralfate for prevention of stress ulcer: metaanalysis of randomised controlled trials. BMJ,2000: 321: 1-7.
32.	Lorente L, Blot S, Rello J. Evidence on measures for the prevention of ventilator-associated pneumonia. Eur Respir J, 2007, 30: 1193 -1207.
33.	CAG Clinical Affairs Committee. Community-acquired pneumonia and acid-suppressive drugs: position statement. Can J Gastroenterol, 2006, 20: 119-121, 123-125.
34.	Laheij RJ, Sturkenboom MC, Hassing RJ, et al. Risk of communityacquired pneumonia and use of gastric acid-suppressive drugs.JAMA, 2004, 292: 1955-1960.35 Thorens J, Froehlich F, Schwizer, W, et al. Bacterial overgrowth during treatment with cimetidine: a prospective randomised double blind study. Gut, 1996, 39: 54-59.
35.	Herzig SJ, Howell MD, Ngo LH, et al. Acid-suppressive medication use and the risk for hospital-acquired pneumonia. JAMA, 2009 ,301: 2120-2128.
36.	Conrad SA, Gabrielli A, Margolis B, et al. Randomized, doubleblind comparison of immediate-release omeprazole oral suspension versus intravenous cimetidine for the prevention of upper gastrointestinal bleeding in critically ill patients. Crit Care Med,2005, 33: 760-765.
37.	Levy MJ, Seelig CB, Robinson NJ, et al. Comparison of omeprazole and ranitidine for stress ulcer prophylaxis. Dig Dis Sci, 1997, 42 :1255-1259.
38.	Yildizdas D, Yapicioglu H, Yilmaz HL. Occurrence of ventilatorassociated pneumonia in mechanically ventilated pediatric intensive care patients during stress ulcer prophylaxis with sucralfate,ranitidine, and omeprazole. J Crit Care, 2002, 17: 240-245.
39.	Mallow S, Rebuck JA, Osler T, et al. Do Proton Pump Inhibitors Increase the Incidence of Nosocomial Pneumonia and Related Infectious Complications When Compared with Histamine-2 Receptor. Curr Surg, 2004, 61: 452-458.
40.	Beaulieu M, Williamson D, Sirois C, et al. Do proton-pump inhibitors increase the risk for nosocomial pneumonia in a medical intensive care unit? J Crit Care, 2008, 23: 513-518.
41.	Sultan N, Nazareno J, Gregor J. Association between proton pump inhibitors respiratory infection a systematic review and meta analysis. Can J Gastroenterol, 2008 , 22: 761 -766.
42.	Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock. Intensive Care Med, 2008, 34: 17-60.

1. Morehead RS, Pinto SJ. Ventilator-Associated Pneumonia. Arch Intern Med, 2000, 160: 1926-1936.
2. American Thoracic Society, Infectious Diseases Society of America.Guidelines for the management of adults with hospital-acquired,ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med, 2005, 171: 388-416.
3. 李華茵, 何禮賢, 胡必杰, 等. 胃腔定植菌在機械通氣相關性肺炎發病機制中的作用. 中華內科雜志, 2004, 43: 112-116.
4. Daschner F, Reuschenbach K, Pfisterer J, et al. The effect of stress ulcer prevention on the incidence of pneumonia in artificial respiration. Anaesthesist, 1987 , 36 : 9-18 .
5. 代芊, 鄧宏, 黃漢朝, 等. GM-PFGE在院內肺炎逆行感染途徑研究中的應用. 中國公共衛生, 2000, 16: 236-238.
6. Cheadle WG, Vitale GC, Mackie CR, et al. Prophylactic postoperative nasogastric decompression. A prospective study of its requirement and the influence of cimetidine in 200 patients. Ann Surg, 1985, 202: 361-366.
7. Tryba M. Risk of acute stress bleeding and nosocomial pneumonia in ventilated intensive care unit patients: Sucralfate versus antacids. Am JMed, 1987, 83: 117-124.
8. Reusser P, Zimmerli W, Scheidegger D, et al. Role of gastric colonization in nosocomial infections and endotoxemia: a prospective study in neurosurgical patients. J Infect Dis, 1989, 160: 414-421.
9. Laggner AN, Lenz K, Base W, et al. Prevention of upper gastrointestinal bleeding in long-term ventilated patients. Sucralfate versus ranitidine. Am J Med, 1989 , 86 : 81-84.
10. Kappstein I, Schulgen G, Friedrich T, et al. The effect of stress ulcer prevention on the incidence of pneumonia in artificial respiration. Am J Med, 1991 , 91: 125 S-131S.
11. Eddleston JM, Vohra A, Scott P, et al. A comparison of the frequency of stress ulceration and secondary pneumonia in sucralfate- or ranitidine-treated intensive care unit patients. Crit Care Med, 1991, 19: 1491-1496.
12. Apte NM, Karnad DR, Medhekar TP, et al. Gastric colonization and pneumonia in intubated critical ill patients receiving stress ulcer prophylaxis: a randomized, controlled trial. Crit Care Med, 1992 ,20: 590-593.
13. Masterton RG, Galloway A, French G, et al. Guidelines for the management of hospital-acquired pneumonia in the UK: Report of the Working Party on Hospital-Acquired Pneumonia of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother,2008: 62: 5-34.
14. Metz CA, Livingston DH, Smith JS, et al. Impact of multiple risk factors and ranitidine prophylaxis on the development of stressrelated upper gastrointestinal bleeding: a prospective, multicenter,double-blind, randomized trial. Crit Care Med, 1993, 21: 1844 -1849.
15. Martin LF, Booth F, Karlstadt RG, et al. Continuous intravenous cimetidine decreases stress-related upper gastrointestinal hemorrhage without promoting pneumonia. Crit Care Med, 1993 , 21 : 19-30.
16. Pickworth KK, Falcone RE, Hoogeboom JE, et al. Occurrence of nosocomial pneumonia in mechanically ventilated trauma patients: a comparison of sucralfate and ranitidine. Crit Care Med, 1993, 21 :1856-1862.
17. Ben-Menachem T, Fogel R, Patel RV, et al. Prophylaxis for stressrelated gastric hemorrhage in the medical intensive care unit. Ann Intern Med, 1994, 121: 568-575.
18. Prod′hom G, Leuenberger P, Koerfer J, et al. Nosocomial pneumonia in mechanically ventilated patients receiving antacid, ranitidine, or sucralfate as prophylaxis for stress ulcer. A randomized controlled trial. Ann Intern Med, 1994, 120: 653-662.
19. Thomason MH, Payseur ES, Hakenewerth AM, et al. Nosocomial pneumonia in ventilated trauma patients during stress ulcer prophylaxis with sucralfate, antacid, and ranitidine. J Trauma,1996, 41: 503-508.
20. Hanisch EW, Encke A, Naujoks F, et al. A randomized, doubleblind trial for stress ulcer prophylaxis shows no evidence of increased pneumonia. Am J Surg, 1998, 176: 453-457.
21. Cook D, Guyatt G, Marshall J, et al. A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. N Engl JMed, 1998, 338: 791-797.
22. O′Keefe GE, Gentilello LM, Maier RV. Incidence of infectious complications associated with the use of histamine2-receptor antagonists in critically ill trauma patients. Ann Surg, 1998, 227 :120-125.
23. Bonten MJ, Gaillard CA, van Tiel FH, et al. The stomach is not a source for colonization of the upper respiratory tract and pneumonia in ICU patients. Chest, 1994, 105: 878-884.
24. Markowicz P, Wolff M, Djedani K, et al. Multicenter Prospective Study of Ventilator Associated Pneumonia During Acute Respiratory Distress Syndrome. Incidence, prognosis, and Risk Factors. Am J Respir Crit Care Med, 2000, 161: 1942-1948.
25. Bornstain C, Azoulay E, De Lassence A, et al. Sedation, sucralfate,and antibiotic use are potential means for protection against earlyonsetventilator-associated pneumonia. Clin Infect Dis, 2004, 38 :1401-1408.
26. Cook DJ, Laine LA, Guyatt GH, et al. Nosocomial pneumonia and the role of gastric pH. A meta-analysis. Chest, 1991, 100: 7-13.
27. Tryba M. Sucralfate versus antacids or H2 -antagonists for stress ulcer prophylaxis: a meta-analysis on efficacy and pneumonia rate.Crit Care Med, 1991, 19: 942-949.
28. Cook DJ. Stress Ulcer Prophylaxis: Gastrointestinal Bleeding and Nosocomial Pneumonia. Best Evidence Synthesis. Scand J Gastroenterol Suppl, 1995, 210: 48-52.
29. Tryba M, Cook DJ. Gastric alkalinization, pneumonia, and systemic infections: the controversy. Scand J Gastroenterol Suppl, 1995 ,210: 53-59.
30. Cook DJ, Reeve BK, Guyatt GH, et al. Stress ulcer prophylaxis in critically ill patients. Resolving discordant meta-analyses. JAMA,1996, 275: 308-314.
31. Messori A, Trippoli S, Vaiani M, et al. Bleeding and pneumonia in intensive care patients given ranitidine and sucralfate for prevention of stress ulcer: metaanalysis of randomised controlled trials. BMJ,2000: 321: 1-7.
32. Lorente L, Blot S, Rello J. Evidence on measures for the prevention of ventilator-associated pneumonia. Eur Respir J, 2007, 30: 1193 -1207.
33. CAG Clinical Affairs Committee. Community-acquired pneumonia and acid-suppressive drugs: position statement. Can J Gastroenterol, 2006, 20: 119-121, 123-125.
34. Laheij RJ, Sturkenboom MC, Hassing RJ, et al. Risk of communityacquired pneumonia and use of gastric acid-suppressive drugs.JAMA, 2004, 292: 1955-1960.35 Thorens J, Froehlich F, Schwizer, W, et al. Bacterial overgrowth during treatment with cimetidine: a prospective randomised double blind study. Gut, 1996, 39: 54-59.
35. Herzig SJ, Howell MD, Ngo LH, et al. Acid-suppressive medication use and the risk for hospital-acquired pneumonia. JAMA, 2009 ,301: 2120-2128.
36. Conrad SA, Gabrielli A, Margolis B, et al. Randomized, doubleblind comparison of immediate-release omeprazole oral suspension versus intravenous cimetidine for the prevention of upper gastrointestinal bleeding in critically ill patients. Crit Care Med,2005, 33: 760-765.
37. Levy MJ, Seelig CB, Robinson NJ, et al. Comparison of omeprazole and ranitidine for stress ulcer prophylaxis. Dig Dis Sci, 1997, 42 :1255-1259.
38. Yildizdas D, Yapicioglu H, Yilmaz HL. Occurrence of ventilatorassociated pneumonia in mechanically ventilated pediatric intensive care patients during stress ulcer prophylaxis with sucralfate,ranitidine, and omeprazole. J Crit Care, 2002, 17: 240-245.
39. Mallow S, Rebuck JA, Osler T, et al. Do Proton Pump Inhibitors Increase the Incidence of Nosocomial Pneumonia and Related Infectious Complications When Compared with Histamine-2 Receptor. Curr Surg, 2004, 61: 452-458.
40. Beaulieu M, Williamson D, Sirois C, et al. Do proton-pump inhibitors increase the risk for nosocomial pneumonia in a medical intensive care unit? J Crit Care, 2008, 23: 513-518.
41. Sultan N, Nazareno J, Gregor J. Association between proton pump inhibitors respiratory infection a systematic review and meta analysis. Can J Gastroenterol, 2008 , 22: 761 -766.
42. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock. Intensive Care Med, 2008, 34: 17-60.

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