Standardized preoperative corticosteroid treatment in neonates undergoing cardiac surgery: results from a randomized trial

Abstract

Objective: A heightened inflammatory response occurs after cardiac surgery. The perioperative use of glucocorticoids has been advocated as a method to improve postoperative outcomes. Randomized prospective studies to quantify the effect of methylprednisolone on perioperative outcomes in neonatal cardiac surgery have not been performed. We sought to determine whether preoperative methylprednisolone would improve postoperative recovery in neonates requiring cardiac surgery.

Methods: Neonates scheduled for cardiac surgery were randomly assigned to receive either 2-dose (8 hours preoperatively and operatively, n = 39) or single-dose (operatively, n = 37) methylprednisolone (30 mg/kg per dose) in a prospective double-blind trial. The primary outcome was the incidence of low cardiac output syndrome (standardized score) or death 36 hours postoperatively. Secondary outcomes were death at 30 days, interleukin-6 levels, inotropic score, fluid balance, serum creatinine, and intensive care unit and hospital stay.

Results: Preoperative plasma levels of the inflammatory cytokine interleukin-6 were reduced by 2-fold (P < .001) in the 2-dose methylprednisolone group, consistent with the anti-inflammatory effects of methylprednisolone. However, the incidence of low cardiac output syndrome was 46% (17/37) in the single-dose and 38% (15/39) in the 2-dose methylprednisolone groups (P = .51). Two-dose methylprednisolone was associated with a higher serum creatinine (0.61 ± 0.18 mg/dL vs 0.53 ± 0.12 mg/dL, P = .03) and poorer postoperative diuresis (-96 ± 49 mL, P = .05). Inotropic requirement, duration of mechanical ventilation, intensive care unit, and hospital stay did not differ between the 2 groups.

Conclusions: Combined preoperative and intraoperative use of glucocorticoids in neonatal cardiac surgery does not favorably affect early clinical outcomes and may exacerbate perioperative renal dysfunction.

Figure 1

Flow of Patients Through the Trial

Figure 2

Peri-operative Outcomes Top- Inotrope score was computed post-operatively in both the Single and Two Dose MP groups. There was an expected increase in inotrope score with respect to time (F_5,70 = 12.3, p < 0.001). While there was a slight reduction in inotrope score in the Two Dose MP group at 4 hours post-operatively, this did not reach statistical significance (p=0.08). At later post-operative time points, inotrope score was virtually equivalent between groups. Middle- Plasma creatinine values obtained pre-operatively, immediately post-operatively and at 36 hours post-operatively for the Single and Two Dose MP groups. Plasma creatinine was significantly higher in the Two Dose MP group immediately postoperatively (*p=0.03). Bottom- The pro-inflammatory cytokine, interleukin-6 (IL-6) was measured prior to randomization to the MP protocol (Pre-MP), immediately pre-operatively, and at 4, 12 and 24 hours post-operatively. The Two Dose MP group, in which MP was administered pre-operatively as well as intra-operatively, resulted in a significant reduction in IL-6 values in the immediate pre-operative period- consistent with an anti-inflammatory effect (*p<0.001). In the post-operative period, plasma IL-6 values significantly increased (F_3,66 = 34.7, p < 0.001), with no difference between the Single and Two Dose MP groups. All data presented as mean±SEM.