title: Phase 1 study of two inodilators in neonates undergoing cardiovascular surgery.
abstract: BACKGROUND
  Inodilators are routinely used in cardiovascular surgery with cardiopulmonary bypass (CPB). Information regarding safety and tolerability of the novel molecule, levosimendan (LEVO), in newborns is anecdotal; no pharmacokinetic data in this population are available.
  
  
  METHODS
  This was a phase I, randomized, and blinded study. Neonates undergoing surgical repair for congenital heart defects received stepwise dose increases of milrinone (MR; 0.5-1 μg/kg/min, n = 9) or LEVO (0.1-0.2 μg/kg/min, n = 11) as an i.v. continuous infusion, starting before CPB. Infants had continuous, time-locked, physiological, and near-infrared spectroscopy (NIRS) (cerebral and peripheral) recordings during the first 24 h, and at 48 and 96 h postsurgery. Serial biochemistry and pharmacokinetic studies were performed.
  
  
  RESULTS
  During the first 24 h postsurgery, patients showed time-related, group-independent increased cerebral tissue oxygenation and decreased diastolic blood pressure; in addition, group-dependent differences in heart rate and peripheral perfusion were found. Early postsurgery, MR-treated infants showed lower pH, higher glycemia, and higher inotrope score. The groups differed in cerebral NIRS-derived variables from 24 to 96 h. Study drug withdrawal at 96 h was more frequent with LEVO. LEVO intermediate metabolites were detected in plasma at day 14 after surgery.
  
  
  CONCLUSIONS
  LEVO is well tolerated in critically ill neonates. LEVO may have advantages over MR in terms of the dosing regimen.
authors.affiliation: Department of Neonatology, La Paz University Hospital, Madrid, Spain. apellicer.hulp@salud.madrid.org
authors.forename: Adelina
authors.initials: A
authors.lastname: Pellicer
authors.forename: Joan
authors.initials: J
authors.lastname: Riera
authors.forename: Paloma
authors.initials: P
authors.lastname: Lopez-Ortego
authors.forename: María Carmen
authors.initials: MC
authors.lastname: Bravo
authors.forename: Rosario
authors.initials: R
authors.lastname: Madero
authors.forename: Jesús
authors.initials: J
authors.lastname: Perez-Rodriguez
authors.forename: Carlos
authors.initials: C
authors.lastname: Labrandero
authors.forename: Jose
authors.initials: J
authors.lastname: Quero
authors.forename: Antonio
authors.initials: A
authors.lastname: Buño
authors.forename: Luis
authors.initials: L
authors.lastname: Castro
authors.forename: Rubin
authors.initials: R
authors.lastname: Lubomirov
authors.forename: Fernando
authors.initials: F
authors.lastname: Cabañas
mesh_terms: D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013504:Cardiovascular Surgical Procedures / Q000379:methods*; D054022:Cerebrum / Q000378:metabolism; D006330:Heart Defects, Congenital / Q000601:surgery*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006835:Hydrazones; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D010100:Oxygen / Q000378:metabolism; D011724:Pyridazines; D000077464:Simendan; D019265:Spectroscopy, Near-Infrared; D013997:Time Factors; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D014665:Vasodilator Agents; D000077464:Simendan; D010100:Oxygen