In patients receiving invasive ventilation, PPIs reduce upper GI bleeding but did not affect mortality at 90 d
An ACP Journal Club commentary said the results of the REVISE trial support the routine use of first-line proton-pump inhibitors (PPIs) for stress ulcer prophylaxis in high-risk, critically ill, ventilated patients but noted that the definition of “high risk” is uncertain.
A randomized international trial found that pantoprazole resulted in a significantly lower risk of clinically important upper GI bleeding than placebo but had no significant effect on mortality in critically ill adults undergoing invasive ventilation. Among a total of 4,821 patients randomized to receive IV pantoprazole, 40 mg/d, or matching placebo, 1.0% and 3.5%, respectively, had clinically important GI bleeding (hazard ratio [HR], 0.30 [95% CI, 0.19 to 0.47]; P<0.001) and 29.1% versus 30.9% had died (HR, 0.94 [95% CI, 0.85 to 1.04]; P=0.25).
The results were published June 14 by the New England Journal of Medicine. The following commentary by Melissa Carroll, MBBS, MHS, and Nicholas J. Talley, MD, PhD, FACP, was published in the ACP Journal Club section of Annals of Internal Medicine on Oct. 1.
A network meta-analysis ranked PPIs first for preventing GI bleeding in critically ill patients, followed by H2 receptor antagonists, and then sucralfate; no published trials have compared PPIs with each other. There is uncertainty around who is at high risk for bleeding and should receive ulcer prophylaxis, which PPI is the agent of choice, and whether the potential risks (e.g., pneumonia, Clostridioides difficile infection) outweigh any benefit of stress ulcer prophylaxis with a PPI.
The REVISE trial by Cook and colleagues rigorously evaluated pantoprazole, the most prescribed PPI for stress ulcer prophylaxis in the USA. Mirroring findings from a 2020 network meta-analysis, REVISE did not find an effect of PPIs on overall mortality at 90 days in ventilated patients. This result underscores the notion that, although PPIs mitigate a specific complication, this does not translate into improved survival outcomes for ventilated critically ill patients.
Previously raised safety concerns were addressed in REVISE, which found no increase in ventilator-associated pneumonia and only a small, nonsignificant increase in C difficile infections with PPIs.
Previous studies suggest that critically ill patients who are not at high risk for bleeding probably do not need stress ulcer prophylaxis. However, the definition of high risk is uncertain. In addition to patients receiving prolonged mechanical ventilation, other likely high-risk patients include those with bleeding diatheses, underlying chronic liver disease, or active sepsis; requiring high-dose steroids (if another risk factor is also present); and receiving antiplatelet agents. Patients with severe burns and brain or spinal injuries are also likely at high risk but are usually excluded from trials.
The REVISE trial supports the routine use of first-line PPIs for stress ulcer prophylaxis in high-risk, critically ill, ventilated patients to prevent upper GI bleeding, although this therapy does not reduce mortality. It emphasizes the importance of balancing potential benefits with risks associated with PPI use, such as infections, although the results of REVISE are reassuring.