PPIs for GI Bleeding Prophylaxis in Critically Ill ICU Patients: Benefits Vs Risks Results from the SUP-ICU trial

The use of Proton Pump Inhibitors (PPIs) for prophylaxis against gastrointestinal (GI) bleeding due to stress ulceration in critically ill patients admitted to the Intensive Care Unit (ICU) was not associated with improved mortality rate or fewer clinically important events, according to a new study published in the New England Journal of Medicine.

In an accompanying editorial, Dr. Alan Barkun (McGill University, Montreal) and Dr. Marc Bardou (Centre Hospitalier Universitaire de Dijon) found the review of this topic to be “timely” due to the following reasons: “First, contemporary observations suggested that stress-ulcer bleeding was less prevalent than it was in the past, probably as a result of improved care in the ICU. Second, the overall benefit from PPIs was reduced by adverse events that were associated with the use of these agents, including nosocomial pneumonia, Clostridium difficile enteritis, and myocardial ischemia. Third, administration of enteral feeding in parallel with bleeding prophylaxis reduced the risk of gastrointestinal bleeding, possibly obscuring the benefits of PPIs; conversely, the combination increased the risk of nosocomial pneumonia.” The randomized, blinded, placebo-controlled, multicenter trial assigned 3298 patients who were admitted to the ICU for acute conditions to receiving either pantoprazole 40 mg IV daily (n: 1645) or placebo (n: 1653). The primary outcome was death at 90 days of randomization.

“The take-home message from this trial is that, given the low incidence of clinically important upper gastrointestinal bleeding in the ICU, prophylaxis with a PPI, if initiated, should be reserved for seriously ill patients who are at high risk for this complication.” – Dr. Alan Barkun, M.D., C.M.

 

There was no significant difference in the mortality between the two arms after 90 days (relative risk [RR] 1.02; 95% confidence interval [CI] 0.91 to 1.13; P = 0.76). Moreover, there was no significant difference between the number of patients who had clinically important events (defined as (a composite of clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection, or myocardial ischemia) (RR 0.96; 95% C, 0.83 to 1.11). However, the pantoprazole group had fewer cases of clinically important GI bleeding as compared with the placebo group (2.5% vs 4.2% respectively). The results from the latter two outcomes were not adjusted for multiple comparisons. Dr. Barkun and Dr. Bardou commented, “The observed mortality rate was higher in the placebo group of the current trial than in cohorts that were used to calculate the sample size for this trial. It also remains unknown whether there could have been a survival benefit among patients in the ICU who were at especially high risk for death.”

PPIs are commonly used for the prophylaxis against stress ulcers in critically ill patients in the ICU. However, their use for stress ulcer prophylaxis is not approved by the FDA. Moreover, their use has been associated with adverse outcomes such as pneumonia and myocardial ischemia in previous studies. “The take-home message from this trial is that, given the low incidence of clinically important upper gastrointestinal bleeding in the ICU, prophylaxis with a PPI, if initiated, should be reserved for seriously ill patients who are at high risk for this complication,” Dr. Barkun and Dr. Bardou concluded.