Antacids are used commonly for symptoms such as heartburn, abdominal pain and nausea resulting from a number of conditions, such as inflammation or acid-peptic ulcers of the esophagus (esophagitis), stomach (gastritis) and duodenum (duodenitis). In almost any hospital in the United States, about half of the patients have a prescription for an acid-reducing drug to reduce heartburn or prevent bleeding in their stomach and gut.

However, according to new research in the Journal of General Internal Medicine, that well-intentioned drug may actually boost patients' risk of dying during their hospital stays by exposing them to infections that pose more risk than would bleeding.

Proton-pump inhibitors (PPIs) are commonly used among medical inpatients, both for prophylaxis against upper gastrointestinal (GI) bleeding, and they are often continued for outpatient use. However, PPIs also appear to increase the risk of hospital-acquired pneumonia and Clostridium difficile infection (CDI). Depending on the underlying risks of these conditions and the changes in those risks with PPIs, using PPIs may lead to a net benefit or net harm among medical inpatients.

This study, which used a computer model to achieve a result that would otherwise require an impractically large clinical trial, aimed to determine the net impact of PPIs on hospital mortality among medical inpatients.

The extra risk of death comes from the fact that reducing acid in the stomach can increase the risk of infections, especially pneumonia and CDI, both of which pose a serious risk to hospitalized patients. 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 taking them compared to their risk without them.

This new model allowed researchers to compare that increased risk with the risk of upper GI bleeding. In general, it showed many inpatients are being exposed to a higher risk of death than they would otherwise have been, and while not a big effect, it is a consistent effect.

The researchers used a computer model based on already existing statistics of inpatient hospital patients, finding new prescriptions of PPIs during a hospital stay led to an increased risk of death in 90 percent of simulated patients. Patients who continued to take PPIs they'd been prescribed before admission to the hospital had an increase of 79 percent.

As a result of these new findings, lead researcher Matt Pappas, M.D., of the University of Michigan, recommends that few hospital patients should start taking or continue on PPIs as a preventive measure against GI bleeding.

However, actually reducing PPI use in hospitals to the most appropriate patients — those with existing GI bleeding may require more effort because PPIs are built into many heuristics that guide much hospital care. For example, when a patient receives high-dose steroids in the hospital, the physician may automatically also prescribe a PPI to prevent steroid-induced GI bleeding.

Although research is still needed on why PPI use increases a patient's vulnerability to hospital-acquired pneumonia and CID, 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.

In his study, Pappas notes that the model he developed with fellow researcher Sandeep Vijan and recent U-M Ford School of Public Policy graduate Sanjay Jolly could be applied to many other situations where a common preventive or treatment measure in medicine also includes an increased risk of an unwanted effect. Using such models, based on data from observational studies, could answer important questions in medicine without the need for massive prospective clinical trials.