Methylprednisolone for Infant Heart Surgery: Subpopulation Analyses of a Randomized Controlled Trial

Objectives: Evaluate benefits and harms of prophylactic intraoperative methylprednisolone in subpopulations undergoing infant heart surgery. Design: Subpopulation analyses of The Steroids to Reduce Systemic Inflammation after Infant Heart Surgery (STRESS) trial, a double-blind randomized placebo-controlled trial. Setting: Twenty-four congenital heart centers. Patients: Infants (< 1 yr old) undergoing heart surgery with cardiopulmonary bypass. Patients stratified by Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery (STAT) mortality category, age, gestational age, and presence of chromosomal or syndromic diagnosis (CSD). Interventions: Methylprednisolone (30 mg/kg) vs. placebo administered into cardiopulmonary bypass pump-priming fluid. Measurements and Main Results: Six postoperative outcomes: steroid use, acute kidney injury (AKI), thrombosis, infections, prolonged mechanical ventilation, peak blood glucose levels, and insulin exposure. One thousand two hundred patients received methylprednisolone or placebo. Beneficial effects associated with methylprednisolone included reduced use of postoperative hydrocortisone in neonates (odds ratio [OR], 0.39 [0.25-0.60]), both STAT category groups (1-3: OR, 0.64 [0.46-0.89]; 4-5: OR, 0.57 [0.34-0.97]), term infants (OR, 0.63 [0.47-0.83]), and those without CSD (OR, 0.63 [0.46-0.86]). Methylprednisolone was associated with lower thrombosis occurrence among neonates (OR, 0.37 [0.16-0.87]) and term infants (OR, 0.38 [0.19-0.75]). Adverse associations included increased thrombosis among premature infants (p = 0.005), increased AKI among neonates (OR, 1.55 [1.02-2.37]) and those following STAT category 1-3 operations (OR, 1.34 [1.02-1.75]), and increased peak blood glucose levels and insulin exposure (all subgroups; p < 0.001). No increase in overall infection or reduction in prolonged mechanical ventilation with methylprednisolone. Conclusions: Both beneficial and adverse associations were observed with prophylactic methylprednisolone. Reduction in postoperative hydrocortisone administration and absence of increased infection rates are arguments favoring prophylactic methylprednisolone use. Methylprednisolone was associated with increased peak blood glucose levels and a neutral to harmful association with odds of AKI. These data suggest certain subpopulations may benefit from prophylactic intraoperative methylprednisolone without significant harm.