Abstract 4143599: Subpopulation Benefits and Adverse Events of Prophylactic Methylprednisolone for Infant Heart Surgery: An Analysis of the STRESS Trial

Background: The Steroids to Reduce Systemic Inflammation after Infant Heart Surgery (STRESS) trial randomized 1200 infants undergoing cardiac surgery with cardiopulmonary bypass to prophylactic intraoperative methylprednisolone (MP) versus placebo. Aims: Evaluate benefits and harms associated with MP in subset populations. Methods: STRESS participants were categorized based on STAT Mortality Category (1-3 and 4-5), age (neonate ≤ 30 days< non-neonate), prematurity (< 37 weeks gestation) and any chromosomal or syndromic diagnoses (CSD). Key postoperative outcomes included any steroid administration (< 72 hours after surgery), peak blood glucose (<72 hours), insulin use (< 24 hours), acute kidney injury (AKI), prolonged mechanical ventilation (>7 days), thrombosis, and infections. Results: The cohort consisted of 30% (364/1200) neonates, 16% (193/1197) premature, and 81% (969/1197) STAT 1-3 operations. Stratified analyses demonstrated notable beneficial effects with MP including reduced use of postoperative hydrocortisone in neonates (OR 0.39 [0.25-0.60]), those following STAT 1-3 (OR 0.65 [0.47-0.91]) and STAT 4-5 operations (OR 0.57 [0.34-0.97]), term infants (OR 0.62 [0.47-0.83]), and those without CSD (OR 0.63 [0.46-0.86]). MP associated with lower thrombosis occurrence among neonates (OR 0.37 [0.16-0.87]) and term infants (OR 0.38 [0.19-0.75]). Notable adverse associations with MP included increased postoperative peak blood glucose levels and insulin use (all subgroups, P<0.01), increased thrombosis events among premature infants (8/100 vs. 0/93, P=0.005), and increased AKI following STAT 1-3 operations (OR 1.35 [1.03-1.77]) and in neonates (OR 1.55 [1.02-2.37]). The AKI association was not significant after adjusting for preoperative renal dysfunction and peak blood glucose. No increase in overall infection or reduction in prolonged mechanical ventilation were detected in any subgroup with MP. Conclusion: Prophylactic intraoperative MP has beneficial and adverse effects in infants undergoing cardiac surgery. The reduction in hydrocortisone, a common treatment for low cardiac output syndrome, and absence of increased infection rates are arguments for prophylactic intraoperative MP. However, MP was associated with increased peak blood glucose levels and a neutral to harmful association with odds of AKI. Though the latter was not significant after adjusting for peak blood glucose, which suggests steroid induced hyperglycemia may contribute to AKI.