Cook D, Deane A, Lauzier F, et al. Stress Ulcer Prophylaxis during Invasive Mechanical Ventilation. N Engl J Med. 2024 Jul 4;391(1):9-20. doi: 10.1056/NEJMoa2404245. Epub 2024 Jun 14.
Abstract

BACKGROUND: Whether proton-pump inhibitors are beneficial or harmful for stress ulcer prophylaxis in critically ill patients undergoing invasive ventilation is unclear.

METHODS: In this international, randomized trial, we assigned critically ill adults who were undergoing invasive ventilation to receive intravenous pantoprazole (at a dose of 40 mg daily) or matching placebo. The primary efficacy outcome was clinically important upper gastrointestinal bleeding in the intensive care unit (ICU) at 90 days, and the primary safety outcome was death from any cause at 90 days. Multiplicity-adjusted secondary outcomes included ventilator-associated pneumonia, Clostridioides difficile infection, and patient-important bleeding.

RESULTS: A total of 4821 patients underwent randomization in 68 ICUs. Clinically important upper gastrointestinal bleeding occurred in 25 of 2385 patients (1.0%) receiving pantoprazole and in 84 of 2377 patients (3.5%) receiving placebo (hazard ratio, 0.30; 95% confidence interval [CI], 0.19 to 0.47; P<0.001). At 90 days, death was reported in 696 of 2390 patients (29.1%) in the pantoprazole group and in 734 of 2379 patients (30.9%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.85 to 1.04; P = 0.25). Patient-important bleeding was reduced with pantoprazole; all other secondary outcomes were similar in the two groups.

CONCLUSIONS: Among patients undergoing invasive ventilation, pantoprazole resulted in a significantly lower risk of clinically important upper gastrointestinal bleeding than placebo, with no significant effect on mortality. (Funded by the Canadian Institutes of Health Research and others; REVISE ClinicalTrials.gov number, NCT03374800.).

Ratings by Clinicians (at least 3 per Specialty)
Specialty Score
Respirology/Pulmonology
Gastroenterology
Intensivist/Critical Care
Internal Medicine
Comments from MORE raters

Intensivist/Critical Care rater

This robust international trial confirms the efficacy of pantoprazole for preventing GI bleeding in mechanically ventilated patients, without signs of increased mortality or C diff infection.

Intensivist/Critical Care rater

A well designed study addressing a common ICU question. This gives wide support and reassurance to continued use of PPI in patients on mechanical ventilation. Definitely relevant in the field, and a timely reminder of good-quality data for patient care.

Respirology/Pulmonology rater

Useful evidence to help in the clinical management of mechanically ventilated patients.

Respirology/Pulmonology rater

GI bleed prophylaxis with proton pump inhibitors or H2 blockers is part of our "mechanical ventilation bundle." This study underscores the benefits of GI bleed prophylaxis with pantoprazole and gives reassurance that treatment does not increase the chance of infection or mortality. The question remains whether or not prophylaxis is cost-effective.

Respirology/Pulmonology rater

It is reassuring that stress ulcer prophylaxis with the proton pump inhibitor (PPI) pantoprazole during mechanical ventilation did not increase the risk for pneumonia or Clostridium infection in this large RCT involving 4,821 participants. The accompanying editorial suggests withholding stress ulcer prophylaxis with a PPI when the APACHE II score is 25 or greater, according to a subgroup analysis of an updated meta-analysis that included this study. This recommendation should likely be verified with further studies focusing on that population.