In infants who are receiving a heart operation with cardiopulmonary bypass, prophylactic use of methylprednisolone is not linked to significant reductions in risk for poor outcomes and is associated with postoperative hyperglycemia needing insulin therapy. These findings were published in The New England Journal of Medicine.
The randomized, controlled STRESS (Steroids to Reduce Systemic Inflammation after Infant Heart Surgery; ClinicalTrials.gov Identifier: NCT03229538) trial was conducted to evaluate whether perioperative prophylactic glucocorticoids are associated with improvements in outcomes among infants following cardiac procedures. Investigators conducted a multicenter, prospective, placebo-controlled, registry-based study of infants aged younger than 1 year who were receiving a heart operation with cardiopulmonary bypass at 1 of 24 sites in the United States that participated in the Society of Thoracic Surgeons Congenital Heart Surgery Database. Registry data were utilized in the assessment of patient outcomes.
All of the participating infants were randomly assigned to receive either prophylactic methylprednisolone (30 mg/kg of body weight) or placebo, which was administered via cardiopulmonary-bypass pump-priming fluid. The primary study endpoint was a ranked composite of death, heart transplantation, or any of 13 different complications. Participants who did not experience any of these events were allocated to a ranked outcome based on their postoperative length of stay.
A total of 1263 patients received randomization, with 1200 of them treated with either methylprednisolone (n=599) or placebo (n=601). Results of the study showed that the likelihood of a worse outcome did not differ significantly between the methylprednisolone arm and the placebo arm (adjusted odds ratio [OR], 0.86; 95% CI, 0.71-1.05; P =.14).
Secondary analyses, which were unadjusted for risk factors, demonstrated an OR for a worse outcome of 0.82 (95% CI, 0.67-1.00) and a win ratio of 1.15 (95% CI, 1.00-1.32) in the methylprednisolone group vs the placebo group, which suggested a benefit with methylprednisolone. Infants in the methylprednisolone arm, however, were significantly more likely than those in the placebo arm to receive postoperative insulin for the development of hyperglycemia (19.0% vs 6.7%, respectively; P <.001).
Several limitations of the study include the possibility that the registry data are not as accurate as data that are collected and placed in a database from a traditional trial. Additionally, study enrollees were allowed to receive postoperative glucocorticoids. As hydrocortisone is occasionally administered to treat low cardiac output syndrome and was administered more often to patients in the placebo group, this might have limited the benefits of the active intervention.
The authors wrote, “Further study is needed to evaluate the role of postoperative glucocorticoids and whether a more targeted approach might offer benefit in select subpopulations.”
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Hill KD, Kannankeril PJ, Jacobs JP, et al; on behalf of the STRESS Network Investigators. Methylprednisolone for heart surgery in infants — a randomized, controlled trial. N Engl J Med. Published online November 6, 2022. doi:10.1056/NEJMoa2212667