title: Impact of empiric nesiritide or milrinone infusion on early postoperative recovery after Fontan surgery: a randomized, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  We sought to determine whether empirical nesiritide or milrinone would improve the early postoperative course after Fontan surgery. We hypothesized that compared with milrinone or placebo, patients assigned to receive nesiritide would have improved early postoperative outcomes.
  
  
  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 ≥12 hours and ≤5 days after cardiac intensive care unit 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 use, 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 [minimum to maximum, 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
  Compared with placebo, empirical perioperative nesiritide or milrinone infusions are not associated with improved early clinical outcomes after Fontan surgery.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT00543309.
authors.affiliation: From the Departments of Cardiology (J.M.C., C.D.-M., C.K.A., K.G., J.W.N., R.E.D., P.C.L.), Anesthesia (F.X.M.), and Cardiac Surgery (J.E.M.), Boston Children's Hospital, Harvard Medical School, MA; and Children's National Medical Center, George Washington University, Washington, DC (D.L.W.). jmcostello@luirechildrens.org.
authors.forename: John M
authors.initials: JM
authors.lastname: Costello
authors.affiliation: From the Departments of Cardiology (J.M.C., C.D.-M., C.K.A., K.G., J.W.N., R.E.D., P.C.L.), Anesthesia (F.X.M.), and Cardiac Surgery (J.E.M.), Boston Children's Hospital, Harvard Medical School, MA; and Children's National Medical Center, George Washington University, Washington, DC (D.L.W.).
authors.forename: Carolyn
authors.initials: C
authors.lastname: Dunbar-Masterson
authors.affiliation: From the Departments of Cardiology (J.M.C., C.D.-M., C.K.A., K.G., J.W.N., R.E.D., P.C.L.), Anesthesia (F.X.M.), and Cardiac Surgery (J.E.M.), Boston Children's Hospital, Harvard Medical School, MA; and Children's National Medical Center, George Washington University, Washington, DC (D.L.W.).
authors.forename: Catherine K
authors.initials: CK
authors.lastname: Allan
authors.affiliation: From the Departments of Cardiology (J.M.C., C.D.-M., C.K.A., K.G., J.W.N., R.E.D., P.C.L.), Anesthesia (F.X.M.), and Cardiac Surgery (J.E.M.), Boston Children's Hospital, Harvard Medical School, MA; and Children's National Medical Center, George Washington University, Washington, DC (D.L.W.).
authors.forename: Kimberlee
authors.initials: K
authors.lastname: Gauvreau
authors.affiliation: From the Departments of Cardiology (J.M.C., C.D.-M., C.K.A., K.G., J.W.N., R.E.D., P.C.L.), Anesthesia (F.X.M.), and Cardiac Surgery (J.E.M.), Boston Children's Hospital, Harvard Medical School, MA; and Children's National Medical Center, George Washington University, Washington, DC (D.L.W.).
authors.forename: Jane W
authors.initials: JW
authors.lastname: Newburger
authors.affiliation: From the Departments of Cardiology (J.M.C., C.D.-M., C.K.A., K.G., J.W.N., R.E.D., P.C.L.), Anesthesia (F.X.M.), and Cardiac Surgery (J.E.M.), Boston Children's Hospital, Harvard Medical School, MA; and Children's National Medical Center, George Washington University, Washington, DC (D.L.W.).
authors.forename: Francis X
authors.initials: FX
authors.lastname: McGowan
authors.affiliation: From the Departments of Cardiology (J.M.C., C.D.-M., C.K.A., K.G., J.W.N., R.E.D., P.C.L.), Anesthesia (F.X.M.), and Cardiac Surgery (J.E.M.), Boston Children's Hospital, Harvard Medical School, MA; and Children's National Medical Center, George Washington University, Washington, DC (D.L.W.).
authors.forename: David L
authors.initials: DL
authors.lastname: Wessel
authors.affiliation: From the Departments of Cardiology (J.M.C., C.D.-M., C.K.A., K.G., J.W.N., R.E.D., P.C.L.), Anesthesia (F.X.M.), and Cardiac Surgery (J.E.M.), Boston Children's Hospital, Harvard Medical School, MA; and Children's National Medical Center, George Washington University, Washington, DC (D.L.W.).
authors.forename: John E
authors.initials: JE
authors.lastname: Mayer
authors.affiliation: From the Departments of Cardiology (J.M.C., C.D.-M., C.K.A., K.G., J.W.N., R.E.D., P.C.L.), Anesthesia (F.X.M.), and Cardiac Surgery (J.E.M.), Boston Children's Hospital, Harvard Medical School, MA; and Children's National Medical Center, George Washington University, Washington, DC (D.L.W.).
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Salvin
authors.affiliation: From the Departments of Cardiology (J.M.C., C.D.-M., C.K.A., K.G., J.W.N., R.E.D., P.C.L.), Anesthesia (F.X.M.), and Cardiac Surgery (J.E.M.), Boston Children's Hospital, Harvard Medical School, MA; and Children's National Medical Center, George Washington University, Washington, DC (D.L.W.).
authors.forename: Roger E
authors.initials: RE
authors.lastname: Dionne
authors.affiliation: From the Departments of Cardiology (J.M.C., C.D.-M., C.K.A., K.G., J.W.N., R.E.D., P.C.L.), Anesthesia (F.X.M.), and Cardiac Surgery (J.E.M.), Boston Children's Hospital, Harvard Medical School, MA; and Children's National Medical Center, George Washington University, Washington, DC (D.L.W.).
authors.forename: Peter C
authors.initials: PC
authors.lastname: Laussen
mesh_terms: D000293:Adolescent; D002316:Cardiotonic Agents / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D018729:Fontan Procedure; D006330:Heart Defects, Congenital / Q000601:surgery; D006333:Heart Failure / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D007902:Length of Stay / Q000639:trends; D008297:Male; D020105:Milrinone / Q000008:administration & dosage*; D020097:Natriuretic Peptide, Brain / Q000008:administration & dosage*; D011182:Postoperative Care / Q000379:methods*; D020127:Recovery of Function / Q000187:drug effects*; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000502:physiology*
chemical_list: D002316:Cardiotonic Agents; D020097:Natriuretic Peptide, Brain; D020105:Milrinone
keywords: Fontan procedure; cardiopulmonary bypass; heart defects, congenital; milrinone; natriuretic peptides