Impact of Empiric Nesiritide or Milrinone Infusion on Early Postoperative Recovery following Fontan Surgery: A Randomized, Double-blind, Placebo-Controlled Trial
Background—We sought to determine whether empiric nesiritide or milrinone would improve the early postoperative course after Fontan surgery. We hypothesized that when compared to milrinone or placebo, patients assigned to receive nesiritide would have improved early postoperative outcomes.
Methods and Results—In a single center, randomized, double-blinded, placebo-controlled, multi-arm parallel-group clinical trial, patients undergoing primary Fontan surgery were assigned to receive nesiritide, milrinone or placebo. A loading dose of study drug was administered on cardiopulmonary bypass followed by a continuous infusion for at least 12 hours, and up to five days, after CICU admission. The primary outcome was days alive and out of the hospital within 30 days of surgery. Secondary outcomes included measures of cardiovascular function, renal function, resource utilization, and adverse events. Among 106 enrolled subjects, 35, 36 and 35 were randomized to the nesiritide, milrinone, and placebo groups, respectively, and all were analyzed based on intention to treat. Demographics, patient characteristics and operative factors were similar among treatment groups. No significant treatment-group differences were found for median days alive and out of the hospital within 30 days of surgery [nesiritide, 20 (min -to- max, 0-24); milrinone, 18 (0-23); placebo, 20 (0-23); p = 0.38]. Treatment groups did not significantly differ in cardiac index, arrhythmias, peak lactate, inotropic scores, urine output, duration of mechanical ventilation, intensive care or chest tube drainage, or adverse events.
Conclusions—When compared to placebo, empiric perioperative nesiritide or milrinone infusions are not associated with improved early clinical outcomes following Fontan surgery.
Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00543309.
- Received November 30, 2013.
- Accepted June 5, 2014.