Although considerable uncertainty remains, the inferences from SUP-ICU and PEPTIC are consistent with the hypothesis that proton pump inhibitors (PPIs) increase the risk of death in patients with higher illness severity.

While, the overall evidence that PPIs reduce upper GI bleeding in the critically ill is unequivocal, it appears that most upper gastrointestinal (GI) bleeds are not fatal, and the attributable mortality from such bleeds appears to be low. Therefore, we suspect that most patients would exchange the small increased risk of upper GI bleeding to avoid a therapy that might increase their risk of death, despite the uncertainty.

These data are not definitive and further research is warranted, but for now, they are likely to be sufficient to prompt a shift by many clinicians away from the routine use of PPIs for stress ulcer prophylaxis in patients with high illness severity.

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