Steroids are commonly given to infants during open-heart surgery to reduce inflammation, but whether the drugs significantly improve patient outcomes has not been settled — until now.
Results of the STeroids to REduce Systemic Inflammation After Infant Heart Surgery (STRESS) trial, co-led by investigators from Vanderbilt University Medical Center, were published Nov. 6 in The New England Journal of Medicine, and presented Nov. 8 at the American Heart Association Scientific Sessions 2022 in Chicago.
Approximately 40,000 operations for congenital heart disease are performed annually in the United States, the majority in infants younger than 1 year of age. Congenital heart disease surgery in infants is a high-risk procedure, with death and complications often directly related to severe systemic inflammatory response syndrome after cardiopulmonary bypass.
The randomized STRESS study, the largest prospective clinical trial ever conducted in the field of pediatric cardiology, compared methylprednisolone to inactive placebo in 1,200 infants under 1 year of age who underwent elective cardiac surgery with cardiopulmonary bypass at 24 U.S. congenital heart disease centers, including VUMC.
Compared to placebo, methylprednisolone did not reduce the likelihood of “worse outcomes,” including death during hospitalization or within 30 days after surgery, heart transplantation during the hospitalization, and a long postoperative hospital stay. Steroid use also was associated with a higher likelihood of hyperglycemia (high blood glucose) requiring insulin treatment.
However, the odds of postoperative bleeding requiring a second operation were lower in the methylprednisolone group, and patients undergoing less-complex operations were more likely to benefit from steroid administration.
These findings are particularly relevant to congenital heart surgery centers, said Scott Baldwin, MD, director of the Division of Pediatric Cardiology at Vanderbilt, and the study’s co-principal investigator. Roughly half of these centers give steroids during surgery, he said.
“This unprecedented study has settled an important question in the surgical treatment of congenital heart defects,” said Prince Kannankeril, MD, MSCI, who directs the Vanderbilt Center for Pediatric Precision Medicine. “While the results are nuanced, they suggest that further study and patient stratification could lead to a more personalized medicine approach to this difficult problem.”
Kannankeril, who holds the Richard B. Johnston Jr. MD, Chair in Pediatric Research, and Baldwin, the Katrina Overall McDonald Professor of Pediatrics, were among three co-authors from VUMC. The third was David Bichell, MD, chief of Pediatric Cardiac Surgery and William S. Stoney Jr. Professor of Cardiac and Thoracic Surgery.
Clinical trials, particularly those involving young children, have been hampered by the limited number of patients at a single institution and the high cost of patient recruitment.
STRESS utilized the Society for Thoracic Surgeons database, which includes 98% of congenital heart disease surgeries performed in the United States and Canada. By identifying patients through registries, the cost of conducting this study was cut by about two-thirds, compared to traditional clinical trials with similar enrollment.
“Using the ‘trial within a registry’ model, it was the cheapest per patient cost,” Baldwin said. “This is important because even though our final end point showed no definitive benefit, we could figure that out without a spending a fortune.”
Kevin Hill, MD, MS, chief of Pediatric Cardiology at Duke University Medical Center, and a former Pediatric Cardiology fellow and graduate of the Master of Science in Clinical Investigation program at Vanderbilt, is the paper’s first and corresponding author.
The trial was co-sponsored by the Duke University/Vanderbilt University Trial Innovation Center and supported in part through the Pediatric Trials Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.