Drug Routinely Prescribed to Hospitalized Patients May Raise Risk of Dying

Michael O. Schroeder

About half of all patients who enter a U.S. hospital are prescribed an acid-reducing drug, called a proton-pump inhibitor. Many patients who were taking a PPI to manage a pre-existing condition are continued on PPIs upon admission, and roughly 1 in every 5 patients receives a new PPI prescription at the hospital.

As a matter of routine, doctors prescribe PPIs to prevent heartburn or bleeding in a patient's stomach or gut -- what's also generally referred to as gastrointestinal, or GI, bleeding -- a concern for many who are hospitalized, given the stress of health issues and undergoing treatment, like surgery. However, research has found that these common medications can increase a patient's risk of contracting serious infections that cannot only lengthen their hospital stay, but increase their likelihood of dying while there.

It's not known exactly why this is, but experts say it appears that the same ability PPIs have to suppress acid production -- a less acidic environment makes it easier for blood to clot normally and healing to take place -- also creates conditions ripe for potentially harmful bacteria to grow and infections to thrive, such as pneumonia or Clostridium difficile, a bacterium responsible for many hospital-acquired infections.

Using a model that simulates risk in large patient populations, Dr. Matthew Pappas and his colleagues at the University of Michigan Medical School and VA Ann Arbor Healthcare System found that for most patients, the overall effect of PPIs is to raise, rather than lower, the risk of dying in the hospital. (Pappas says he chose to do a simulation because it would have been virtually impossible to raise the necessary funds to conduct a study involving tens of thousands of people.)

"It's not a big effect, but it is a consistent effect," says Pappas, a clinical lecturer in internal medicine at the University of Michigan, a hospitalist and a research fellow at the VA Ann Arbor, who led the study published online last month in the Journal of General Internal Medicine. According to his team's estimates, for every 831 people newly prescribed a PPI in the hospital, approximately one patient would die before being discharged, and roughly 1 out of every 3,625 patients continued on a PPI in the hospital wouldn't make it home.

"There are over 35 million hospitalizations in the U.S. each year," he says. "So, even a small effect, as I found, could lead to several thousand unnecessary deaths in this country."

For the majority of hospitalized patients who aren't in the intensive care unit and don't have an active upper gastrointestinal bleeding, the researchers concluded that the potential harms of prescribing PPIs outweigh the benefits, and thus, should be discouraged.

Pappas says many hospitals, including those where he's employed, have taken initiative to reduce the unnecessary use of PPIs. But, he adds, he'd like to see more restrictions put in place to limit risk and better target their use to those patients who are most likely to benefit.

"I'm very aggressive about taking patients off PPIs if I don't think they need them," says Dr. Kyle Staller, a gastroenterologist at Massachusetts General Hospital, and an instructor of medicine at Harvard Medical School in Boston.

Because these drugs are very effective at reducing heartburn, peptic ulcers and bleeding, among other ailments, they have, over time, become overprescribed in outpatient settings as well as hospitals, he says.

"PPIs are a victim of their own success, because they've really revolutionized gastroenterology," Staller says, which has likely led to their being prescribed more broadly than they should be, he adds. The result has exposed more patients to short-term risks, like acquiring a C-diff infection or pneumonia, which can lengthen a hospital stay and increase the likelihood of dying in the hospital. What's more, he says, long-term use of these drugs can raise a person's risk of everything from low-bone density and vitamin B12 deficiency to GI infections. "Acid is an important barrier to bad bugs that you eat," Staller says.

Based on previous research showing the risks associated with PPIs, he says clinicians as at Mass General have moved away from more broadly prescribing PPIs to patients who aren't in the ICU, as a matter of routine. "So the only time that you see standardized prescription of these medications," he says, is for ICU patients on breathing machines; trauma patients; burn patients; or patients with pre-existing bleeding disorders.

While Pappas notes that many other medical centers are making similar moves, he predicts it will still be difficult to change clinical practice, since the measure is so ingrained.

For patients, experts say it's important to ask about the expected benefit of PPIs along with the risks before taking these medications, or continuing a prescription.

Not that all patients -- like those who are intubated -- find themselves in a position to talk about the nuances of everything prescribed, but Staller says physicians should be prepared to discuss the potential benefits and harms of PPIs with patients or their advocates.

"[They are] really one of the most widely prescribed medications out there," Staller says. "I think the evidence from this paper and from others as well is very clear that you should not be prescribed a proton-pump inhibitor, except in certain circumstances," Staller says. Those circumstances include when patients are admitted with GI bleeding or who come into the hospital with bleeding from the upper GI tract, and patients with major trauma or burns, for example. Those patients, he adds, see an "incredible benefit" from PPIs, which can also reduce blood loss, complications from treatment and speed healing.

So, while pressing concerns -- from treating a heart attack to prepping for surgery -- understandably take precedence during a hospitalization, experts say it's good to remember the big impact that relatively minor decisions can have on patients' outcomes.

"It's difficult because there are always, no doubt, more important issues in any given patient's hospital stay than a preventive PPI," Pappas says. "But it's important for physicians to try to get the details right, too, and it's important that patients are mindful of what is being given and why it's being given."

Michael Schroeder is a health editor at U.S. News. You can follow him on Twitter or email him at mschroeder@usnews.com.