Preoperative steroid treatment does not improve markers of inflammation after cardiac surgery in neonates: Results from a randomized trial

Abstract

Objective Neonatal cardiac surgery requiring cardiopulmonary bypass results in a heightened inflammatory response. Perioperative glucocorticoid administration is commonly utilized in attempt to reduce the inflammatory cascade, although characterization of the cytokine response to steroids in neonatal cardiac surgery remains elusive due to highly variable approaches in administration. This randomized trial was designed to prospectively evaluate the effect of specific glucocorticoid dosing protocols on inflammatory markers in neonatal cardiac surgery requiring cardiopulmonary bypass. Methods Neonates scheduled for cardiac surgery were randomly assigned to receive either two-dose (8 hours preoperatively and operatively, n=36) or single dose (operatively, n=32) methylprednisolone at 30mg/kg/dose in a prospective double-blind trial. The primary outcome was the effect of these steroid regimens on markers of inflammation. Secondary analyses evaluated the association of specific cytokine profiles with postoperative clinical outcomes. Results Patient demographics, perioperative variables and preoperative indices of inflammation were similar between the single and two-dose groups. Preoperative cytokine response after the two-dose methylprednisolone protocol was consistent with an anti-inflammatory effect, although this did not persist into the postoperative period. Pre-medication baseline levels of interleukin-6, interleukin-8, interleukin-10 and tumor necrosis factor alpha were predictive of postoperative intensive care unit and hospital length of stay. Only interleukin-8 demonstrated a postoperative response associated with duration of intensive care unit and hospital stay. Conclusions The addition of a preoperative dose of methylprednisolone to a standard intraoperative methylprednisolone dose does not improve markers of inflammation following neonatal cardiac surgery. The routine administration of preoperative glucocorticoids in neonatal cardiac surgery should be reconsidered. This is the largest pediatric and only exclusively neonatal randomized trial examining the anti-inflammatory effect of two different methylprednisolone dosing regimens for neonates requiring cardiac surgery. The addition of a preoperative dose of methylprednisolone to a standard intraoperative methylprednisolone dose does not improve markers of inflammation following neonatal cardiac surgery.

Vasoactive-Inotropic Score Is Associated With Outcome After Infant Cardiac Surgery

“…The metric we derived performs as well or better as a predictor of clinical outcome when compared to the IS or other derivations of an inotrope score. Maximum VIS in the first 24 hours has biologic plausibility as a measure of illness severity and predictor of outcome as previously literature demonstrates a nadir in cardiac output after bypass [1], higher risk of cardiac arrest [11], and peaking serum markers of inflammation [12] and myocardial injury [13, 14] during this time period.…”

Systemic Inflammation Increases Energy Expenditure Following Pediatric Cardiopulmonary Bypass

“…The role of IL-10 in the post-CPB inflammatory response remains unclear. Although often considered to have anti-inflammatory activity, plasma IL-10 concentrations are consistently elevated following CPB (27,28). This may reflect acute activation and dysregulation of all inflammatory pathways or alternate activity in this setting.…”

The Utility of Steroids in Pediatric Cardiac Operations*

“…Finally, in the largest randomized controlled pediatric trial, we prospectively enrolled 76 neonates undergoing cardiac surgery with cardiopulmonary bypass to either a single or two dose steroid groups(12;13). The single dose group received placebo 8 hours prior to surgery and methylprednisolone in the CPB prime.…”