Children who underwent cardiac surgery were less likely to develop acute kidney injury (AKI) if they had been treated with acetaminophen in the first 48 hours after their procedures, according to a Vanderbilt study recently published in JAMA Pediatrics. The research lays the groundwork for possibly establishing acetaminophen as a preventive agent for AKI.

AKI is a very common problem after such surgeries, and there previously have not been medications to treat or prevent it, said Sara Van Driest, M.D., an associate professor of medicine and pediatrics at Vanderbilt University Medical Center. Van Driest is the study’s lead author.

AKI a Significant Complication Across Pediatric Care

“Patients who have AKI are known to have increases in mortality during that hospital stay, and in morbidity”

At least 5 percent of all patients who are admitted to the pediatric floor and at least 25 percent of those who require intensive care develop AKI. Among children who have cardiac surgery, about half develop AKI.

“This is important because those patients who have AKI are known to have increases in mortality during that hospital stay, and in morbidity, meaning that they have worse kidney function in the months and years after,” said Van Driest. “They also have longer stays in the hospital, which is hard on patients and families.”

Research Design

The study was informed by years of research at Vanderbilt on the pathways targeted by acetaminophen. Researchers have found that the drug can prevent the damage that is done by free hemoglobin, one of the byproducts of the breaking up of red blood cells during cardiac bypass, Van Driest said. That prior research provided a hypothesis that could be tested: that acetaminophen could protect against AKI.

“We took measures to adjust for how sick the patients were, how long their cardiac surgery was, and how many risk factors they had for AKI… the protective effect of acetaminophen remained.”

The retrospective observational study found the lower rate of AKI in 999 pediatric surgery patients using acetaminophen, first with patients from Monroe Carell Jr. Children’s Hospital at Vanderbilt and then at Duke University. “We found that the more acetaminophen that they got, the less likely they were to have AKI,” Van Driest said. “Even after we took measures to adjust for how sick the patients were, how long their cardiac surgery was, and how many risk factors they had for AKI, the protective effect of acetaminophen remained.”

The study found an approximately 10 percent reduction in AKI risk for each additional 10 mg/kg of acetaminophen administered in the first 48 hours after surgery. Van Driest said that the next step is potentially a randomized trial to validate the findings. It is possible that the findings may also lead to randomized trials in other disease states that cause release of free hemoglobin, such as sickle cell disease and sepsis.

About the Expert

Sara Van Driest, M.D.

Sara Van Driest, M.D., is an associate professor of pediatrics at Vanderbilt University School of Medicine and Monroe Carell Jr. Children’s Hospital at Vanderbilt. Her research interests include leveraging large data sets to uncover strategies that improve patient responses to medication.