Methylprednisolone does not reduce odds of poor outcomes in infant heart surgery
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CHICAGO — In infants undergoing heart surgery with cardiopulmonary bypass, the use of the steroid methylprednisolone did not reduce odds of a worse outcome compared with placebo, according to the STRESS trial.
For the STRESS trial, Kevin D. Hill, MD, MSCI, professor of pediatrics and chief of the division of pediatric cardiology at Duke Children’s Hospital and Health Center, and colleagues enrolled 1,200 infants undergoing heart surgery with cardiopulmonary bypass (median age, 125 days; 54% male). Results were presented at the American Heart Association Scientific Sessions and simultaneously published in The New England Journal of Medicine.
Photo credit: Scott Buzby, Online Managing Editor
“Despite decades of use, we have no idea if steroids are safe or efficacious in children” undergoing heart surgery, Hill said during a press conference. Hill said 52% of such surgeries between 2011 and 2016 employed steroids before or during the procedures. “Clearly, there is clinical equipoise for this question,” Hill said.
Previous randomized trials exploring this question in children have been small.
“It is very difficult to conduct trials in children with heart disease, as it is a rare-disease patient population, trials are expensive and it is difficult to consent and enroll a patient, so our goal was to develop a new mechanism for trials,” Hill said during the press conference. “We envisioned a pragmatic trial built into an existing registry, the Society of Thoracic Surgeons Congenital Heart Surgery Database. This is a robust and rich registry that has been in existence for 20 years and includes demographic and outcomes data as well as operative data. Our patients were randomized within the registry to methylprednisolone 30 mg/kg vs. placebo. By leveraging the registry resources, we could dramatically decrease costs and improve efficiency of the trial.”
The primary outcome was a ranked composite of operative mortality, heart transplantation and 13 other complications, and the primary analysis was adjusted for covariates.
The primary outcome adjusted for covariates did not differ between the methylprednisolone and placebo groups (adjusted OR = 0.86; 95% CI, 0.71-1.05; P = .14), according to the researchers.
However, the unadjusted analysis of the primary outcome (OR = 0.82; 95% CI, 0.67-1; P = .047), the win ratio analysis of the primary outcome (OR = 1.15; 95% CI, 1-1.32; P = .046) and bleeding requiring reoperation (OR = 0.34; 95% CI, 0.14-0.81; P = .016) all favored the methylprednisolone group, Hill said.
Compared with patients in the placebo group, those in methylprednisolone group had higher postoperative blood glucose (P < .001) and were more likely to receive postoperative insulin (P < .001) but were less likely to receive postoperative hydrocortisone (P = .004), and there were no differences between the groups in any other complications, Hill and colleagues reported.
Generally, methylprednisolone was more favorable in infants with a Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) mortality category of 1, 2 or 3, but there was no difference in those with a STAT mortality category of 4 or 5, Hill said. He also said the results favored methylprednisolone in infants without prematurity but favored neither treatment in infants with prematurity.
“Future studies should evaluate mechanisms for risk stratification to determine whether a more targeted version might offer benefit in select subpopulations,” Hill said.
Reference:
Perspective
Back to TopTechnically, this is a negative trial. However, the trends are strong enough, and with the main secondary endpoints being positive, in context with relatively minor side effects of hyperglycemia, practice will shift toward more use of steroids in this situation.
Managing hyperglycemia is challenging in the ICU setting postoperatively, and we know that hyperglycemia not only has side effects but is associated with worse outcomes. But looking at the endpoints over time, it did not seem like the hyperglycemia was offsetting the trends toward potential benefit.
When you take everything in total, including the hyperglycemia, and look at what happened to these infants over time, they seemed to maybe do a little bit better with methylprednisolone.
Medical Director, Advanced Heart Failure
University of Colorado School of Medicine
Anschutz Medical Campus
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Hill KD, et al. LBS.03. Late-Breaking Science: High Impact Trials in Intervention and Surgery. Presented at: American Heart Association Scientific Sessions; Nov. 5-7, 2022; Chicago (hybrid meeting).
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