In this episode, I’ll discuss recent articles regarding stress ulcer prophylaxis.
The use of acid-suppressing agents to prevent the development of stress ulcers has been an area of intense research as the exact benefits and harms of this strategy in the context of modern ICU care is uncertain.
Several articles have recently been published in New England Journal of Medicine to provide clarity on this topic.
The first is a large randomized controlled multicenter trial of nearly 5000 critically ill adults who were undergoing invasive ventilation. Investigators randomized patients to receive either IV pantoprazole 40 mg daily or placebo. The primary efficacy outcome was clinically important upper gastrointestinal bleeding in the ICU at 90 days, and the primary safety outcome was death from any cause at 90 days.
Clinically important upper gastrointestinal bleeding occurred in just 1% of the pantoprazole group compared with 3.5% in the placebo group. At 90 days, mortality was numerically lower in the pantoprazole group at 29.1% vs 30.9% however this did not reach statistical significance.
Furthermore, the secondary end points of ventilator-associated pneumonia and C. difficile infection were similar in the two groups.
The authors concluded:
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.
Prior to this trial’s publication, the authors shared the data with another group of investigators that was conducting a systematic review and meta-analysis of randomized trials to examine the efficacy and safety of proton-pump inhibitors for stress ulcer prophylaxis in critically ill patients. This meta analysis included 12 trials and nearly 10000 patients. There was high certainty that proton-pump inhibitors were associated with a reduced incidence of clinically important upper gastrointestinal bleeding with a relative risk ratio of 0.51. The meta-analysis also concluded that proton-pump inhibitors had little or no effect on mortality, although subgroup analysis suggested the possibility that there was a decrease in mortality in less severely ill patients and an increase in mortality in more severely ill patients.
To put these articles into the context of clinical practice, the journal editors invited expert commentary in the form of an editorial titled “Uncertain Answers — Proton-Pump Inhibition in the ICU“. The editorialist reviews the meta-analysis and the newly published trial and synthesizes the data into a plan for their personal practice. The expert concludes they will prescribe prophylactic proton-pump inhibitors to patients during mechanical ventilation if they have an APACHE II score of less than 25 as a measure of less critically ill patients. For sicker patients, they state they would probably reserve the use of proton-pump inhibitors for those who are being treated with antiplatelet agents, especially in the presence of therapeutic anticoagulants.
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