Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass: Randomized Controlled Trial

• Type of Material: Article
• Authors: Eric M. Graham, University of South Carolina; Renee H. Martin, University of South Carolina; Jason R. Buckley, University of South Carolina; Sinai C. Zyblewski, University of South Carolina; Minoo N. Kavarana, University of South Carolina; Scott M. Bradley, University of South Carolina; Bahaaldin Alsoufi, Emory University; William Mahle, Emory University; Marc Hassid, University of South Carolina; Andrew M. Atz, University of South Carolina
• Language: English
• Date: 2019-08-06
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 by the American College of Cardiology Foundation. Published by Elsevier.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jacc.2019.05.060
• Title of Journal or Parent Work: JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
• Volume: 74
• Issue: 5
• Start Page: 659
• End Page: 668
• Grant/Funding Information: This work was supported by grant HL112968 from the National Heart, Lung, and Blood Institute (NHLBI). This work is solely the responsibility of the authors and does not necessarily represent the official views of NHLBI or NIH.
• Keywords: congenital heart disease; cardiopulmonary bypass; pediatric

Abstract

Background The efficacy of intraoperative corticosteroids to improve outcomes following congenital cardiac operations remains controversial. Objective To determine whether intraoperative methylprednisolone improves postoperative recovery in neonates undergoing cardiac surgery. Methods Neonates undergoing cardiac surgery with cardiopulmonary bypass at 2 centers were enrolled in a double-blind randomized controlled trial of methylprednisolone (30 mg/kg) or placebo after the induction of anesthesia. The primary outcome was a previously validated morbidity-mortality composite that included any of the following events following surgery before discharge: death, mechanical circulatory support, cardiac arrest, hepatic injury, renal injury, or rising lactate level (>5 mmol/L). Results Of the 190 subjects enrolled, 176 (n=81 methylprednisolone, n=95 placebo) were included in this analysis. A total of 27 (33%) subjects in the methylprednisolone group and 40 (42%) in the placebo group reached the primary study endpoint (OR=0.63; 95% CI, 0.31–1.3; p=0.21). Methylprednisolone was associated with reductions in vasoactive inotropic requirements and in the incidence of the composite endpoint in subjects undergoing palliative operations (OR=0.38; 95% CI 0.15–0.99; p=0.048). There was a significant interaction between treatment effect and center. In this analysis, methylprednisolone was protective at 1 center with an OR=0.35 (95% CI, 0.15–0.84; p=0.02) and not so at the other center with OR=5.13 (95% CI, 0.85–30.9; p=0.07). Conclusions Intraoperative methylprednisolone failed to show an overall significant benefit on the incidence of the composite primary study endpoint. There was, however, a benefit in patients undergoing palliative procedures and a significant interaction between treatment effect and center suggesting there may be center or patient characteristics which make prophylactic methylprednisolone beneficial.