Methylprednisolone for Heart Surgery in Infants - A Randomized, Controlled Trial

Abstract

Background: Although perioperative prophylactic glucocorticoids have been used for decades, whether they improve outcomes in infants after heart surgery with cardiopulmonary bypass is unknown.

Methods: We conducted a multicenter, prospective, randomized, placebo-controlled, registry-based trial involving infants (<1 year of age) undergoing heart surgery with cardiopulmonary bypass at 24 sites participating in the Society of Thoracic Surgeons Congenital Heart Surgery Database. Registry data were used in the evaluation of outcomes. The infants were randomly assigned to receive prophylactic methylprednisolone (30 mg per kilogram of body weight) or placebo, which was administered into the cardiopulmonary-bypass pump-priming fluid. The primary end point was a ranked composite of death, heart transplantation, or any of 13 major complications. Patients without any of these events were assigned a ranked outcome based on postoperative length of stay. In the primary analysis, the ranked outcomes were compared between the trial groups with the use of odds ratios adjusted for prespecified risk factors. Secondary analyses included an unadjusted odds ratio, a win ratio, and safety outcomes.

Results: A total of 1263 infants underwent randomization, of whom 1200 received either methylprednisolone (599 infants) or placebo (601 infants). The likelihood of a worse outcome did not differ significantly between the methylprednisolone group and the placebo group (adjusted odds ratio, 0.86; 95% confidence interval [CI], 0.71 to 1.05; P = 0.14). Secondary analyses (unadjusted for risk factors) showed an odds ratio for a worse outcome of 0.82 (95% CI, 0.67 to 1.00) and a win ratio of 1.15 (95% CI, 1.00 to 1.32) in the methylprednisolone group as compared with the placebo group, findings suggestive of a benefit with methylprednisolone; however, patients in the methylprednisolone group were more likely than those in the placebo group to receive postoperative insulin for hyperglycemia (19.0% vs. 6.7%, P<0.001).

Conclusions: Among infants undergoing surgery with cardiopulmonary bypass, prophylactic use of methylprednisolone did not significantly reduce the likelihood of a worse outcome in an adjusted analysis and was associated with postoperative development of hyperglycemia warranting insulin in a higher percentage of infants than placebo. (Funded by the National Center for Advancing Translational Sciences and others; STRESS ClinicalTrials.gov number, NCT03229538.).

Figure 1.. Binary Components of the Primary End Point in the Trial Population.

Components of the primary end point are ranked according to level of clinical prioritization, with operative death (ranked as 97) being the worst outcome.

Figure 2.. Subgroup Analyses of Estimated Treatment Effects across Categories of Prespecified Baseline Risk Factors.

The adjusted odds ratios are for a worse outcome with respect to the primary composite end point. The odds ratios were adjusted for age, weight, prematurity status, and the 2020 Society of Thoracic Surgeons–European Association for Cardio-Thoracic Surgery (STAT) Mortality Category. Factors associated with relatively greater evidence of a treatment benefit included less complex operations (STAT Mortality Category 1 to 3 [on a scale of 1 to 5, with lower values indicating less complex operations]), longer duration of cardiopulmonary bypass, and no history of prematurity. The duration of cardiopulmonary bypass was analyzed as a continuous variable; the values of 60, 120, and 180 minutes are representative durations, and the adjusted odds ratios reflect the odds of a worse outcome at each of these time points in the continuous distribution. Race and ethnic group were reported by the patient’s family.