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Efficacy and safety of gastrointestinal bleeding prophylaxis in critically ill patients: an updated systematic review and network meta-analysis of randomized trials

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Abstract

Purpose

Motivated by a new randomized trial (the PEPTIC trial) that raised the issue of an increase in mortality with proton pump inhibitors (PPIs) relative to histamine-2 receptor antagonists (H2RAs), we updated our prior systematic review and network meta-analysis (NMA) addressing the impact of pharmacological gastrointestinal bleeding prophylaxis in critically ill patients.

Methods

We searched for randomized controlled trials that examined the efficacy and safety of gastrointestinal bleeding prophylaxis with PPIs, H2RAs, or sucralfate versus one another or placebo or no prophylaxis in adult critically ill patients. We performed Bayesian random-effects NMA and conducted analyses using all PEPTIC data as well as a restricted analysis using only PEPTIC data from high compliance centers. We used the GRADE approach to quantify absolute effects and assess the certainty of evidence.

Results

Seventy-four trials enrolling 39 569 patients proved eligible. Both PPIs (risk ratio (RR) 1.03, 95% credible interval 0.93 to 1.14, moderate certainty) and H2RAs (RR 0.98, 0.89 to 1.08, moderate certainty) probably have little or no impact on mortality compared with no prophylaxis. There may be no important difference between PPIs and H2RAs on mortality (RR 1.05, 0.97 to 1.14, low certainty), the 95% credible interval of the complete analysis has not excluded an important increase in mortality with PPIs. Both PPIs (RR 0.46, 0.29 to 0.66) and H2RAs (RR 0.67, 0.48 to 0.94) probably reduce clinically important gastrointestinal bleeding; the magnitude of reduction is probably greater in PPIs than H2RAs (RR 0.69, 0.45 to 0.93), and the difference may be important in higher, but not lower bleeding risk patients. PPIs (RR 1.08, 0.88 to 1.45, low certainty) and H2RAs (RR 1.07, 0.85 to 1.37, low certainty) may have no important impact on pneumonia compared with no prophylaxis.

Conclusion

This updated NMA confirmed that PPIs and H2RAs are most likely to have a similar effect on mortality compared to each other and compared to no prophylaxis; however, the possibility that PPIs may slightly increase mortality cannot be excluded (low certainty evidence). PPIs and H2RAs probably achieve important reductions in clinically important gastrointestinal bleeding; for higher bleeding risk patients, the greater benefit of PPIs over H2RAs may be important. PPIs or H2RAs may not result in important increases in pneumonia but the certainty of evidence is low.

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References

  1. Cook D, Guyatt G (2018) Prophylaxis against upper gastrointestinal bleeding in hospitalized patients. N Engl J Med 378:2506–2516

    Article  CAS  PubMed  Google Scholar 

  2. Barletta JF, Kanji S, MacLaren R, Lat I, Erstad BL (2014) Pharmacoepidemiology of stress ulcer prophylaxis in the United States and Canada. J Crit Care 29:955–960

    Article  CAS  PubMed  Google Scholar 

  3. Krag M, Perner A, Wetterslev J et al (2015) Stress ulcer prophylaxis in the intensive care unit: an international survey of 97 units in 11 countries. Acta Anaesthesiol Scand 59:576–585

    Article  CAS  PubMed  Google Scholar 

  4. Wang Y, Ye Z, Ge L et al (2020) Efficacy and safety of gastrointestinal bleeding prophylaxis in critically ill patients: systematic review and network meta-analysis. BMJ 368:l6744

    Article  PubMed  PubMed Central  Google Scholar 

  5. Ye Z, Reintam Blaser A, Lytvyn L et al (2020) Gastrointestinal bleeding prophylaxis for critically ill patients: a clinical practice guideline. BMJ 368:l6722

    Article  PubMed  Google Scholar 

  6. Young PJ, Bagshaw SM, Forbes AB et al (2020) Effect of stress ulcer prophylaxis with proton pump inhibitors vs histamine-2 receptor blockers on in-hospital mortality among ICU patients receiving invasive mechanical ventilation: the PEPTIC randomized clinical trial. JAMA 323:616–626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Hutton B, Salanti G, Caldwell DM et al (2015) The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med 162:777–784

    Article  PubMed  Google Scholar 

  8. Guyatt GH, Busse JW. Modification of cochrane tool to assess risk of bias in randomized trials. https://www.evidencepartners.com/resources/methodological-resources/

  9. Ades AE, Sculpher M, Sutton A et al (2006) Bayesian methods for evidence synthesis in cost-effectiveness analysis. PharmacoEconomics 24:1–19

    Article  CAS  PubMed  Google Scholar 

  10. Lumley T (2002) Network meta-analysis for indirect treatment comparisons. Stat Med 21:2313–2324

    Article  PubMed  Google Scholar 

  11. van Valkenhoef G, Dias S, Ades AE, Welton NJ (2016) Automated generation of node-splitting models for assessment of inconsistency in network meta-analysis. Res Synth Methods 7:80–93

    Article  PubMed  Google Scholar 

  12. Krag M, Marker S, Perner A et al (2018) Pantoprazole in patients at risk for gastrointestinal bleeding in the ICU. N Engl J Med 379:2199–2208

    Article  CAS  PubMed  Google Scholar 

  13. Granholm A, Zeng L, Dionne JC et al (2019) Predictors of gastrointestinal bleeding in adult ICU patients: a systematic review and meta-analysis. Intensive Care Med 45:1347–1359

    Article  PubMed  Google Scholar 

  14. Chaimani A, Higgins JP, Mavridis D, Spyridonos P, Salanti G (2013) Graphical tools for network meta-analysis in STATA. PLoS ONE 8:e76654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Balshem H, Helfand M, Schunemann HJ et al (2011) GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol 64:401–406

    Article  PubMed  Google Scholar 

  16. Brignardello-Petersen R, Bonner A, Alexander PE et al (2018) Advances in the GRADE approach to rate the certainty in estimates from a network meta-analysis. J Clin Epidemiol 93:36–44

    Article  PubMed  Google Scholar 

  17. Guyatt GH, Oxman AD, Kunz R et al (2011) GRADE guidelines 6. Rating the quality of evidence–imprecision. J Clin Epidemiol 64:1283–1293

    PubMed  Google Scholar 

  18. Guyatt GH, Oxman AD, Kunz R et al (2011) GRADE guidelines: 8. Rating the quality of evidence–indirectness. J Clin Epidemiol 64:1303–1310

    Article  PubMed  Google Scholar 

  19. Guyatt GH, Oxman AD, Kunz R et al (2011) GRADE guidelines: 7. Rating the quality of evidence–inconsistency. J Clin Epidemiol 64:1294–1302

    Article  PubMed  Google Scholar 

  20. Guyatt GH, Oxman AD, Montori V et al (2011) GRADE guidelines: 5. Rating the quality of evidence–publication bias. J Clin Epidemiol 64:1277–1282

    Article  PubMed  Google Scholar 

  21. Guyatt GH, Oxman AD, Vist G et al (2011) GRADE guidelines: 4. Rating the quality of evidence–study limitations (risk of bias). J Clin Epidemiol 64:407–415

    Article  PubMed  Google Scholar 

  22. Guyatt GH, Oxman AD, Vist GE et al (2008) GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 336:924–926

    Article  PubMed  PubMed Central  Google Scholar 

  23. Puhan MA, Schunemann HJ, Murad MH et al (2014) A GRADE Working Group approach for rating the quality of treatment effect estimates from network meta-analysis. BMJ 349:g5630

    Article  PubMed  Google Scholar 

  24. Muzlovic I, Stubljar D (2019) Stress ulcer prophylaxis as a risk factor for tracheal colonization and hospital-acquired pneumonia in intensive care patients: impact on latency time for pneumonia. Acta Clinica Croatica 58:72–86

    PubMed  PubMed Central  Google Scholar 

  25. Alhazzani W, Guyatt G, Alshahrani M et al (2017) Withholding pantoprazole for stress ulcer prophylaxis in critically Ill patients: a pilot randomized clinical trial and meta-analysis. Crit Care Med 45:1121–1129

    Article  PubMed  Google Scholar 

  26. Apte NM, Karnad DR, Medhekar TP, Tilve GH, Morye S, Bhave GG (1992) Gastric colonization and pneumonia in intubated critically ill patients receiving stress ulcer prophylaxis: a randomized, controlled trial. Crit Care Med 20:590–593

    Article  CAS  PubMed  Google Scholar 

  27. Bashar FR, Manuchehrian N, Mahmoudabadi M, Hajiesmaeili MR, Torabian S (2013) Effects of ranitidine and pantoprazole on ventilator-associated pneumonia: a randomized double-blind clinical trial. Tanaffos 12:16–21

    PubMed  PubMed Central  Google Scholar 

  28. Ben-Menachem T, Fogel R, Patel RV et al (1994) Prophylaxis for stress-related gastric hemorrhage in the medical intensive care unit. A randomized, controlled, single-blind study. Ann Intern Med 121:568–575

    Article  CAS  PubMed  Google Scholar 

  29. Burgess P, Larson GM, Davidson P, Brown J, Metz CA (1995) Effect of ranitidine on intragastric pH and stress-related upper gastrointestinal bleeding in patients with severe head injury. Dig Dis Sci 40:645–650

    Article  CAS  PubMed  Google Scholar 

  30. Cannon LA, Heiselman D, Gardner W, Jones J (1987) Prophylaxis of upper gastrointestinal tract bleeding in mechanically ventilated patients. A randomized study comparing the efficacy of sucralfate, cimetidine, and antacids. Arch Intern Med 147:2101–2106

    Article  CAS  PubMed  Google Scholar 

  31. Chan KH, Lai EC, Tuen H et al (1995) Prospective double-blind placebo-controlled randomized trial on the use of ranitidine in preventing postoperative gastroduodenal complications in high-risk neurosurgical patients. J Neurosurg 82:413–417

    Article  CAS  PubMed  Google Scholar 

  32. Conrad SA, Gabrielli A, Margolis B et al (2005) Randomized, double-blind comparison of immediate-release omeprazole oral suspension versus intravenous cimetidine for the prevention of upper gastrointestinal bleeding in critically ill patients. Crit Care Med 33:760–765

    Article  CAS  PubMed  Google Scholar 

  33. Cook D, Guyatt G, Marshall J et al (1998) 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 J Med 338:791–797

    Article  CAS  PubMed  Google Scholar 

  34. De Azevedo JRA, Soares MDGA, Silva GAE, De Lima PG (2000) Prevention of stress ulcer bleeding in high risk patients. Comparison of three drugs. GED Gastrenterologia Endoscopia Digestiva 19:239–244

    Google Scholar 

  35. Eddleston JM, Pearson RC, Holland J, Tooth JA, Vohra A, Doran BH (1994) Prospective endoscopic study of stress erosions and ulcers in critically ill adult patients treated with either sucralfate or placebo. Crit Care Med 22:1949–1954

    Article  CAS  PubMed  Google Scholar 

  36. El-Kersh K, Jalil B, McClave SA et al (2018) Enteral nutrition as stress ulcer prophylaxis in critically ill patients: a randomized controlled exploratory study. J Crit Care 43:108–113

    Article  PubMed  Google Scholar 

  37. Fink M, Karlstadt RG, Maroko RT, Field B (2003) Intravenous pantoprazole (IVP) and continuous infusion cimetidine (C) prevent upper gastrointestinal bleeding (UGIB) regardless of APSII score (APACHE II) in high risk intensive care unit (ICU) patients. Gastroenterology 124:A625–A626

    Article  Google Scholar 

  38. Groll A, Simon JB, Wigle RD, Taguchi K, Todd RJ, Depew WT (1986) Cimetidine prophylaxis for gastrointestinal bleeding in an intensive care unit. Gut 27:135–140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Gursoy O, Memis D, Sut N (2008) Effect of proton pump inhibitors on gastric juice volume, gastric pH and gastric intramucosal pH in critically ill patients : a randomized, double-blind, placebo-controlled study. Clin Drug Investig 28:777–782

    Article  CAS  PubMed  Google Scholar 

  40. Halloran LG, Zfass AM, Gayle WE, Wheeler CB, Miller JD (1980) Prevention of acute gastrointestinal complications after severe head injury: a controlled trial of cimetidine prophylaxis. Am J Surg 139:44–48

    Article  CAS  PubMed  Google Scholar 

  41. Hanisch EW, Encke A, Naujoks F, Windolf J (1998) A randomized, double-blind trial for stress ulcer prophylaxis shows no evidence of increased pneumonia. Am J Surg 176:453–457

    Article  CAS  PubMed  Google Scholar 

  42. Harlaftis N, Basdanis G, Papapolychroniadis C et al (1997) Nosocomial pneumonia in mechanically ventilated patients during stress ulcer prophylaxis with sucralfate and ranitidine. Hell J Gastroenterol 10:230–235

    Google Scholar 

  43. Jakob SM, Parviainen I, Ruokonen E, Uusaro A, Takala J (2005) Lack of effect of ranitidine on gastric luminal pH and mucosal PCO2 during the first day in the ICU. Acta Anaesthesiol Scand 49:390–396

    Article  CAS  PubMed  Google Scholar 

  44. Kantorova I, Svoboda P, Scheer P et al (2004) Stress ulcer prophylaxis in critically ill patients: a randomized controlled trial. Hepatogastroenterology 51:757–761

    PubMed  Google Scholar 

  45. Karlstadt RG, Iberti TJ, Silverstein J et al (1990) Comparison of cimetidine and placebo for the prophylaxis of upper gastrointestinal bleeding due to stress-related gastric mucosal damage in the intensive care unit. J Intensive Care Med 5:26–32

    Article  Google Scholar 

  46. Kaushal S, Midha V, Sood A, Chopra SC, Gupta C (2000) A comparative study of the effects of famotidine and sucralfate in prevention of upper gastro-intestinal bleeding in patients of head injury. Indian J Pharmacol 32:246–249

    CAS  Google Scholar 

  47. Khorvash F, Abbasi S, Meidani M, Dehdashti F, Ataei B (2014) The comparison between proton pump inhibitors and sucralfate in incidence of ventilator associated pneumonia in critically ill patients. Adv Biomed Res 3:52

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Labattut AG, Santolalla PM, De Andres AP et al (1992) Efficacy of sucralfate in the prevention of upper gastrointestinal stress bleeding in intensive care patients: comparison vs a control group. Clin Intensive Care 3:S19–S25

    Google Scholar 

  49. Laggner AN, Lenz K, Base W, Druml W, Schneeweiss B, Grimm G (1989) Prevention of upper gastrointestinal bleeding in long-term ventilated patients. Sucralfate versus ranitidine. Am J Med 86:81–84

    Article  CAS  PubMed  Google Scholar 

  50. Laggner AN, Lenz K, Graninger W et al (1988) Stress ulcer prophylaxis in a general intensive care unit: sucralfate versus ranitidine. Der Anaesthesist 37:704–710

    CAS  PubMed  Google Scholar 

  51. Lee TH, Hung FM, Yang LH (2014) Comparison of the efficacy of esomeprazole and famotidine against stress ulcers in a neurosurgical intensive care unit. Adv Digest Med 1:50–53

    Article  Google Scholar 

  52. Levy MJ, Seelig CB, Robinson NJ, Ranney JE (1997) Comparison of omeprazole and ranitidine for stress ulcer prophylaxis. Dig Dis Sci 42:1255–1259

    Article  CAS  PubMed  Google Scholar 

  53. Lin CC, Hsu YL, Chung CS, Lee TH (2016) Stress ulcer prophylaxis in patients being weaned from the ventilator in a respiratory care center: a randomized control trial. J Formos Med Assoc 115:19–24

    Article  PubMed  Google Scholar 

  54. Liu BL, Li B, Zhang X et al (2013) A randomized controlled study comparing omeprazole and cimetidine for the prophylaxis of stress-related upper gastrointestinal bleeding in patients with intracerebral hemorrhage. J Neurosurg 118:115–120

    Article  CAS  PubMed  Google Scholar 

  55. Lou W, Xia Y, Xiang P et al (2018) Prevention of upper gastrointestinal bleeding in critically ill Chinese patients: a randomized, double-blind study evaluating esomeprazole and cimetidine. Curr Med Res Opin 34:1449–1455

    Article  CAS  PubMed  Google Scholar 

  56. Macdougall BR, Bailey RJ, Williams R (1977) H2-receptor antagonists and antacids in the prevention of acute gastrointestinal haemorrhage in fulminant hepatic failure. Two controlled trials. Lancet (London, England) 1:617–619

    Article  CAS  Google Scholar 

  57. Martin LF, Booth FV, Karlstadt RG et al (1993) Continuous intravenous cimetidine decreases stress-related upper gastrointestinal hemorrhage without promoting pneumonia. Crit Care Med 21:19–30

    Article  CAS  PubMed  Google Scholar 

  58. Nielsen HJ, Witt K, Moesgaard F, Kehlet H (1989) Ranitidine for improvement of delayed hypersensitivity response in patients with sepsis. Acta Chir Scand 155:445–449

    CAS  PubMed  Google Scholar 

  59. Nourian A, Mohammadi M, Beigmohammadi MT et al (2018) Comparing efficacy of enteral nutrition plus ranitidine and enteral nutrition alone as stress ulcer prophylaxis. J Comp Effect Res 7:493–501

    Article  Google Scholar 

  60. Peura DA, Johnson LF (1985) Cimetidine for prevention and treatment of gastroduodenal mucosal lesions in patients in an intensive care unit. Ann Intern Med 103:173–177

    Article  CAS  PubMed  Google Scholar 

  61. Pickworth KK, Falcone RE, Hoogeboom JE, Santanello SA (1993) Occurrence of nosocomial pneumonia in mechanically ventilated trauma patients: a comparison of sucralfate and ranitidine. Crit Care Med 21:1856–1862

    Article  CAS  PubMed  Google Scholar 

  62. Powell H, Morgan M, Li SK, Baron JH (1993) Inhibition of gastric acid secretion in the intensive care unit after coronary artery bypass graft. A pilot control study of intravenous omeprazole by bolus and infusion, ranitidine and placebo. Theor Surg 8:125–130

    Google Scholar 

  63. Prakash S, Rai A, Gogia AR, Prakash S (2008) Nosocomial pneumonia in mechanically ventilated patients receiving ranitidine or sucralfate as stress ulcer prophylaxis. Indian J Anaesth 52:179–184

    Google Scholar 

  64. Prod'hom G, Leuenberger P, Koerfer J et al (1994) Nosocomial pneumonia in mechanically ventilated patients receiving antacid, ranitidine, or sucralfate as prophylaxis for stress ulcer. A randomized controlled trial. Ann Intern Med 120:653–662

    Article  CAS  PubMed  Google Scholar 

  65. Reusser P, Gyr K, Scheidegger D, Buchmann B, Buser M, Zimmerli W (1990) Prospective endoscopic study of stress erosions and ulcers in critically ill neurosurgical patients: current incidence and effect of acid-reducing prophylaxis. Crit Care Med 18:270–274

    Article  CAS  PubMed  Google Scholar 

  66. Ruiz-Santana S, Ortiz E, Gonzalez B, Bolanos J, Ruiz-Santana AJ, Manzano JL (1991) Stress-induced gastroduodenal lesions and total parenteral nutrition in critically ill patients: frequency, complications, and the value of prophylactic treatment. A prospective, randomized study. Crit Care Med 19:887–891

    Article  CAS  PubMed  Google Scholar 

  67. Ryan P, Dawson J, Teres D, Celoria G, Navab F (1993) Nosocomial pneumonia during stress ulcer prophylaxis with cimetidine and sucralfate. Arch Surg 128:1353–1357

    Article  CAS  PubMed  Google Scholar 

  68. Selvanderan SP, Summers MJ, Finnis ME et al (2016) Pantoprazole or placebo for stress ulcer prophylaxis (POP-UP): randomized double-blind exploratory study. Crit Care Med 44:1842–1850

    Article  CAS  PubMed  Google Scholar 

  69. Solouki M, Mar'ashian SM, Koochak M, Nasiri A, Mokhtari M, Amirpour A (2009) Ventilator-associated pneumonia among ICU patients receiving mechanical ventilation and prophylaxis of gastrointestinal bleeding. Iran J Clin Infect Dis 4:177–180

    Google Scholar 

  70. Solouki M, Marashian SM, Kouchak M, Mokhtari M, Nasiri E (2009) Comparison between the preventive effects of ranitidine and omeprazole on upper gastrointestinal bleeding among ICU patients. Tanaffos 8:37–42

    Google Scholar 

  71. Somberg L, Morris J, Fantus R et al (2008) Intermittent intravenous pantoprazole and continuous cimetidine infusion: effect on gastric pH control in critically ill patients at risk of developing stress-related mucosal disease. J Trauma 64:1202–1210

    CAS  PubMed  Google Scholar 

  72. Spapen H, Diltoer M, Nguyen DN, Ingels G, Ramet J, Huyghens L (1995) One week treatment with cimetidine does not attenuate the cortisol response to a short corticotropin test in stable intensive care patients: a prospective, randomized, and controlled study. Acta Anaesthesiol Belg 46:133–140

    CAS  PubMed  Google Scholar 

  73. Thomason MH, Payseur ES, Hakenewerth AM et al (1996) Nosocomial pneumonia in ventilated trauma patients during stress ulcer prophylaxis with sucralfate, antacid, and ranitidine. J Trauma 41:503–508

    Article  CAS  PubMed  Google Scholar 

  74. Tryba M, Zevounou F, Torok M, Zenz M (1985) Prevention of acute stress bleeding with sucralfate, antacids, or cimetidine. A controlled study with pirenzepine as a basic medication. Am J Med 79:55–61

    Article  CAS  PubMed  Google Scholar 

  75. Zinner MJ, Zuidema GD, Smith P, Mignosa M (1981) The prevention of upper gastrointestinal tract bleeding in patients in an intensive care unit. Surg Gynecol Obstet 153:214–220

    CAS  PubMed  Google Scholar 

  76. Schandelmaier S, Briel M, Varadhan R, Schmid CH, Devasenapathy N, Hayward RA. A new instrument to assess the credibility of effect modification analyses (ICEMAN) in randomized controlled trials and meta-analyses (in submission)

  77. Darlong V, Jayalakhsmi TS, Kaul HL, Tandon R (2003) Stress ulcer prophylaxis in patients on ventilator. Trop Gastroenterol 24:124–128

    CAS  PubMed  Google Scholar 

  78. Fabian TC, Boucher BA, Croce MA et al (1993) Pneumonia and stress ulceration in severely injured patients. A prospective evaluation of the effects of stress ulcer prophylaxis. Arch Surg 128:185–191

    Article  CAS  PubMed  Google Scholar 

  79. Fogas JF, Kiss KK, Gyura FG, Tóbiás ZT, Molnár ZM (2013) Effects of proton pump inhibitor versus H2-receptor antagonist stress ulcer prophylaxis on ventilator-associated pneumonia: a pilot study. Crit Care 17:S150–S151

    Article  Google Scholar 

  80. Gundogan K, Karakoc E, Teke T, Zerman A, Coruh A, Sungur M (2017) Effects of enteral nutrition on stress ulcer hemorrhage in critically ill patients: multicenter randomized controlled trial. Intensive Care Medicine Experimental Conference:30th Annual Congress of the European Society of Intensive Care Medicine, ESICM 2017. Austria. 2015 (2012 Supplement 2011) (no pagination)

  81. Hummer-Sigiel M, Jacquier A, Girard A, Garric J, Laxenaire MC, Mandorla JY (1986) Ranitidine pour la prophylaxie de l'ulcére de stress chexz les traumatisés crâniens graves. Ann Med Nancy l'Est 25:101–103

    Google Scholar 

  82. Kotlyanskaya A, Luka B, Mukherji R, Shukla M, Vajinder V, Cohen H (2007) A comparison trial of lansoprazole disintegrating tablet, lansoprazole suspension or ranitidine for stress ulcer prophylaxis in critically ill patients. Crit Care Med 35:A194–A194

    Google Scholar 

  83. Phillips J, Metzler M, Huckfeldt R, Olsen K (1998) A multicenter, prospective, randomized clinical trial of continuous infusion i.v. ranitidine vs omeprazole suspension in the prophylaxis of stress ulcers. Crit Care Med 26:101A

    Google Scholar 

  84. Simms HH, DeMaria E, McDonald L, Peterson D, Robinson A, Burchard KW (1991) Role of gastric colonization in the development of pneumonia in critically ill trauma patients: results of a prospective randomized trial. J Trauma 31:531–536

    Article  CAS  PubMed  Google Scholar 

  85. Wee B, Liu CH, Cohen H, Kravchuk S, Reddy K, Mukherji R (2013) IV famotidine vs IV pantoprazole for stress ulcer prevention in the ICU: a prospective study. Crit Care Med 41:A181

    Article  Google Scholar 

  86. Bhanot RD (2010) Nosocomial pneumonia in mechanically ventilated patients receiving ranitidine, omeprazole or sucralfate as stress ulcer prophylaxis. Am J Respir Crit Care Med 181:A6039

    Google Scholar 

  87. Metz CA, Livingston DH, Smith JS, Larson GM, Wilson TH (1993) Impact of multiple risk factors and ranitidine prophylaxis on the development of stress-related upper gastrointestinal bleeding: a prospective, multicenter, double-blind, randomized trial. The Ranitidine Head Injury Study Group. Crit Care Med 21:1844–1849

    Article  CAS  PubMed  Google Scholar 

  88. Mustafa NA, Akturk G, Ozen I, Koksal I, Erciyes N, Solak M (1995) Acute stress bleeding prophylaxis with sucralfate versus ranitidine and incidence of secondary pneumonia in intensive care unit patients. Intensive Care Med 21:287

    Article  CAS  PubMed  Google Scholar 

  89. Basso N, Bagarani M, Materia A, Fiorani S, Lunardi P, Speranza V (1981) Cimetidine and antacid prophylaxis of acute upper gastrointestinal bleeding in high risk patients. Controlled, randomized trial. Am J Surg 141:339–341

    Article  CAS  PubMed  Google Scholar 

  90. Brophy GM, Brackbill ML, Bidwell KL, Brophy DF (2010) Prospective, randomized comparison of lansoprazole suspension, and intermittent intravenous famotidine on gastric pH and acid production in critically ill neurosurgical patients. Neurocrit Care 13:176–181

    Article  CAS  PubMed  Google Scholar 

  91. Cartier F, Gauthier-Lafaye P, Lareng L, Mottin J, Cara M, Passelecq J (1980) Cimetideine in patients at risk of stress ulcers: a multi-centre controlled trial. Intensive Care Med 6:54

    Google Scholar 

  92. Friedman CJ, Oblinger MJ, Suratt PM et al (1982) Prophylaxis of upper gastrointestinal hemorrhage in patients requiring mechanical ventilation. Crit Care Med 10:316–319

    CAS  PubMed  Google Scholar 

  93. Larson GM, Davidson P, Brown J, Wilson T, Bishop A (1989) Comparison of ranitidine versus placebo on 24-hour gastric Ph and upper gastrointestinal (UGI) bleeding in head injury patients. Am J Gastroenterol 84:1165

    Google Scholar 

  94. Luk GD, Summer WR, Messersmith JF (1982) Cimetidine and antacid in prophylaxis of acute gastrointestinal bleeding: a randomized, doubleblind, controlled study. Gastroenterology 82:1121

    Google Scholar 

  95. Pan X, Zhang W, Li Z et al (2004) The preventive effects of rabeprazole on upper gastrointestinal tract hemorrhage in patients with severe acute pancreatitis. Chin J Gastroenterol 9:30–32

    Google Scholar 

  96. van den Berg B, van Blankenstein M (1985) Prevention of stress-induced upper gastrointestinal bleeding by cimetidine in patients on assisted ventilation. Digestion 31:1–8

    Article  PubMed  Google Scholar 

  97. McGinn T, Wyer P, McCullagh P, Wisnivesky J, Devereaux PJ, Stiell I, Richardson S, Agoritsas T, Guyatt G. Clinical Prediction Rules. In: Users' Guides to the Medical Literature. Chapt. 19.4

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Acknowledgements

We thank Rachel Couban for her help with the search strategy and running the search. We thank Diane Heels-Ansdell for the support and suggestions for the statistical analysis for subgroup analysis.

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Authors and Affiliations

  1. Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada

    Ying Wang, Zhikang Ye, Reed A. Siemieniuk, Waleed Alhazzani, Deborah Cook & Gordon H. Guyatt

  2. Evidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, China

    Long Ge

  3. Department of Medicine, University of Toronto, Toronto, Canada

    Reed A. Siemieniuk

  4. Department of Intensive Care Medicine, Lucerne Cantonal Hospital, Lucerne, Switzerland

    Annika Reintam Blaser

  5. Department of Anaesthesiology and Intensive Care, University of Tartu, Tartu, Estonia

    Annika Reintam Blaser

  6. Department of Pharmacy, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

    Xin Wang

  7. Department of Intensive Care, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    Anders Perner & Morten H. Møller

  8. Department of Medicine, McMaster University, Hamilton, Canada

    Waleed Alhazzani, Deborah Cook & Gordon H. Guyatt

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  1. Ying Wang
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Correspondence to Gordon H. Guyatt.

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Conflicts of interest

YW, ZKY, RAS, ARB and GHG are the co-authors of the BMJ rapid recommendation for gastrointestinal bleeding prophylaxis (https://doi.org/10.1136/bmj.l6722). AP and MHM are the co-authors of the SUP-ICU trial (https://doi.org/10.1056/NEJMoa1714919); WA, DC and GHG are the investigators of the REVISE trial (NCT03374800).

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Wang, Y., Ge, L., Ye, Z. et al. Efficacy and safety of gastrointestinal bleeding prophylaxis in critically ill patients: an updated systematic review and network meta-analysis of randomized trials. Intensive Care Med 46, 1987–2000 (2020). https://doi.org/10.1007/s00134-020-06209-w

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