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Stress Ulcer Prophylaxis during Invasive Mechanical Ventilation

A critical care clinician’s role involves administering timely and appropriate antibiotics, expediting necessary surgeries, supporting patients' physical and mental recovery, and preventing complications. Despite the protocolized nature of the work, it remains demanding. A significant concern in ICU settings is the use of gastric acid suppression among mechanically ventilated patients.

Previous randomized trials and meta-analyses of proton-pump inhibitors (PPIs) in critically ill patients have been inconclusive regarding their effect on mortality, with observational data suggesting a potential risk of pneumonia and Clostridioides difficile infection. The SUP-ICU and PEPTIC trials indicated that PPIs might be less safe for more severely ill patients.

The REVISE trial, evaluating pantoprazole for preventing gastrointestinal bleeding in 4821 mechanically ventilated patients, showed a small reduction in bleeding risk with no significant differences in mortality, pneumonia, or C. difficile infection between the pantoprazole and placebo groups. A concurrent meta-analysis combining REVISE and SUP-ICU data confirmed pantoprazole’s benefit in reducing gastrointestinal bleeding and suggested decreased mortality among less severely ill patients but not among more severely ill ones.

Which agent do you use for stress ulcer prophylaxis in your ICU?

  • 0%PPI

  • 0%H2 blocker

  • 0%Other

These findings indicate that while PPIs can reduce gastrointestinal bleeding and possibly mortality in less severely ill patients, they do not significantly impact mortality or safety events in more severely ill patients. Given these insights, clinicians might consider prophylactic PPIs for less severely ill ventilated patients and reserve their use for more severely ill patients with specific risk factors like antiplatelet or anticoagulant therapy



  1. Cook. Stress Ulcer Prophylaxis during Invasive Mechanical Ventilation. N Engl J Med 2024;epublished June 14th

  2. Krag M, Marker S, Perner A, et al. Pantoprazole in patients at risk for gastrointestinal bleeding in the ICU. N Engl J Med 2018;379:2199-2208. [PubMed]

  3. PEPTIC Investigators for the Australian and New Zealand Intensive Care Society Clinical Trials Group, Alberta Health Services Critical Care Strategic Clinical Network, Irish Critical Care Trials Group. 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 2020;323:616-626.

  4. Cook D, Deane A, Lauzier F, et al. Stress ulcer prophylaxis during invasive mechanical ventilation. N Engl J Med 2024.

  5. Wang Y, Parpia S, Ge L, et al. Proton pump inhibitors to prevent gastrointestinal bleeding — an updated meta-analysis. NEJM Evid 2024;3(7). EVIDoa2400134.

  6. Kent DM, Rothwell PM, Ioannidis JP, Altman DG, Hayward RA. Assessing and reporting heterogeneity in treatment effects in clinical trials: a proposal. Trials 2010;11:85-85.

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