Global trial confirms antacids prevent bleeding in ventilated patients

A recent global study has found that a commonly available drug, pantoprazole, effectively prevents upper gastrointestinal bleeding in critically ill adults who are on mechanical ventilation. The research, led by a team at McMaster University, was published on June 14, 2024, in The New England Journal of Medicine and NEJM Evidence. The study specifically looked at the impacts of pantoprazole, a gastric acid suppressant primarily used to treat heartburn from gastroesophageal reflux disease (GERD), in preventing stress-induced ulcers in the stomach of ICU patients who require mechanical ventilation.

Critically ill patients in the ICU often receive pantoprazole to prevent upper gastrointestinal bleeding. However, there have been concerns regarding whether this complication has become less common over time and whether pantoprazole might have adverse side effects, such as an increased risk of death among the sickest patients. This new study provides much-needed clarity for healthcare professionals, helping them make informed decisions about the use of pantoprazole in critical care settings.

"This is the largest randomized trial on this topic globally, spearheaded by Canada," said Deborah Cook, the study’s lead author and principal investigator, and a professor in the Department of Medicine at McMaster University. "Physicians, nurses, and pharmacists working in ICUs can immediately apply this information in their practices. The trial results and the updated meta-analysis will also be integrated into international practice guidelines."

The Reevaluating the Inhibition of Stress Erosions (REVISE) Trial was a randomized control trial that compared the effects of pantoprazole to a placebo in critically ill adults on mechanical ventilation. Conducted across 68 centers in eight countries, the trial included over 4,800 patients. The results showed that pantoprazole significantly reduced the risk of clinically important upper gastrointestinal bleeding compared to the placebo, though it did not reduce the risk of death.

Specifically, clinically important upper gastrointestinal bleeding occurred in just 1% of the patients (25 out of 2,417) who received pantoprazole, compared to nearly 4% (84 out of 2,404) of those who received the placebo. At the 90-day mark, 29% of patients in the pantoprazole group (696 out of 2,390) had died, compared to 30% in the placebo group (734 out of 2,379).

In addition to the trial, researchers also conducted a meta-analysis of 12 randomized trials involving proton-pump inhibitors used for gastrointestinal bleeding prevention in 10,000 critically ill patients. This review summarized the current evidence on outcomes related to gastrointestinal bleeding, mortality, pneumonia, and C. difficile infection. The medications were found to reduce the incidence of clinically significant upper gastrointestinal bleeding and had little to no effect on mortality, pneumonia, and C. difficile infection.

Funding for the research was provided by several organizations, including the Canadian Institutes for Health Research, the Accelerating Clinical Trials Fund, Physicians Services Incorporated of Ontario, the Hamilton Association of Health Sciences Organization, and the National Health Medical Research Council of Australia.