Right now, in any American hospital, about half of the patients have a prescription for an acid-reducing drug called proton-pump inhibitors (PPIs) to reduce heartburn or prevent bleeding in their stomach and gut. 

But that well-intentioned drug may actually boost their risk of dying during their hospital stay, a new study finds, by opening them up to infections that pose more risk than bleeding would. 

In fact, according to a computer simulation based on real-world risk and benefit data, around 90 percent of hospital inpatients who were first prescribed these drugs in the hospital have a higher risk of dying when they're taking them, compared with their risk if they hadn't gotten the prescription. And for around 80 percent of patients who were already on these common drugs, when they arrived at the hospital, staying on them also may lead to a small increase in the risk of dying.

The extra risk of death comes from the fact that reducing acid in the stomach can increase the risk of infections - especially pneumonia and Clostridium difficile, both of which pose a serious risk to hospitalized patients who develop them.

"Many patients who come into the hospital are on these medications, and we sometimes start them in the hospital to try to prevent gastrointestinal, or GI, bleeds," says lead author Matthew Pappas, M.D., MPH, of the University of Michigan Medical School. "But other researchers have shown that these drugs seem to increase the risk of pneumonia and C. diff, two serious and potentially life-threatening infections that hospitalized patients are also at risk for. Our new model allows us to compare that increased risk with the risk of upper GI bleeding. In general, it shows us that we're exposing many inpatients to higher risk of death than they would otherwise have - and though it's not a big effect, it is a consistent effect."

As a result of the new findings, he says, very few hospital patients should start taking or continue on PPIs as a preventive measure against gastrointestinal bleeding. 

Cutting PPI use to cut infection risk

Nationally, some efforts have already shown ways to reduce the rate of new PPI prescriptions to hospitalized patients - about 20 percent of whom receive such orders right now. But truly reducing PPI use in hospitals to the most appropriate patients - those with existing GI bleeding - will take more effort. That's because PPIs are built into many heuristics, or rules of thumb, that guide much hospital care. For instance, when a patient receives high-dose steroids in the hospital, the physician may automatically also prescribe a PPI to prevent the GI bleeding that steroids can cause.

"In fact, in running our simulation, we thought we would find some populations such as those on steroids or other medications often prescribed together with PPIs, who would not experience the increased mortality risk," Pappas says. "But that turned out not to be the case." GI bleeds are risky, it's true. But hospital-acquired pneumonia and C. diff are much more common.

Although research is still needed on why PPI use increases a patient's vulnerability to hospital-acquired pneumonia and C. diff infection, the effect of the acid-reducing drugs on gut bacteria likely has a direct impact. In the case of pneumonia, suppressing acid production may increase the amount of bacteria in the stomach and throat, which can then get into the lungs and cause pneumonia.

Published in the Journal of General Internal Medicine