title: Safety of milrinone use in neonatal intensive care units.
abstract: BACKGROUND
  Milrinone use in the neonatal intensive care unit has increased over the last 10 years despite a paucity of published safety data in infants. We sought to determine the safety of milrinone therapy among infants in the neonatal intensive care unit.
  
  
  METHODS
  We conducted a retrospective data analysis, identifying all infants who were exposed to milrinone and discharged from 322 neonatal intensive care units managed by the Pediatrix Medical Group from 1997-2010. We identified adverse events (AEs) during milrinone exposure. The unit of observation for clinical AEs was the first course of milrinone and for laboratory AEs it was an infant-day of exposure to milrinone.
  
  
  RESULTS
  Overall, 1446 of 716,821 (0.2%) infants received milrinone for a total of 6894 infant-days. The proportion of infants exposed to milrinone increased from 0 in 1997 to 4/1000 infant cases in 2010. Persistent pulmonary hypertension (40%) was the most commonly reported diagnosis at the start of milrinone administration. Overall, 606/1446 (42%) of infants had at least 1 clinical AE recorded during milrinone therapy. Hypotension requiring pressors and thrombocytopenia (<100,000/mm(3)) were the most commonly reported clinical and laboratory AEs, respectively. Death was reported in 8% of infants during the first course of milrinone therapy.
  
  
  CONCLUSIONS
  Among infants hospitalized in the neonatal intensive care unit, there was an increase in the use of milrinone over the past 13 years. The safety, dosing, and efficacy of milrinone in infants should be determined in prospective clinical trials.
authors.affiliation: Center for Translational Science, Children's National Medical Center, Washington, DC, United States; Division of Clinical Pharmacology, Children's National Medical Center, Washington, DC, United States; Division of Neonatology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Samira
authors.initials: S
authors.lastname: Samiee-Zafarghandy
authors.affiliation: Duke Clinical Research Institute, Duke University, Durham, NC, United States.
authors.forename: Sudha R
authors.initials: SR
authors.lastname: Raman
authors.affiliation: Center for Translational Science, Children's National Medical Center, Washington, DC, United States; Division of Clinical Pharmacology, Children's National Medical Center, Washington, DC, United States; Intensive Care, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands; Department of Paediatric Pharmacology, University Children's Hospital Basel, Switzerland.
authors.forename: John N
authors.initials: JN
authors.lastname: van den Anker
authors.affiliation: Duke Clinical Research Institute, Duke University, Durham, NC, United States.
authors.forename: Kerstin
authors.initials: K
authors.lastname: McHutchison
authors.affiliation: Duke Clinical Research Institute, Duke University, Durham, NC, United States; Department of Pediatrics, Duke University, Durham, NC, United States.
authors.forename: Christoph P
authors.initials: CP
authors.lastname: Hornik
authors.affiliation: Pediatrix-Obstetrix Center for Research and Education, Sunrise, FL, United States.
authors.forename: Reese H
authors.initials: RH
authors.lastname: Clark
authors.affiliation: Duke Clinical Research Institute, Duke University, Durham, NC, United States; Department of Pediatrics, Duke University, Durham, NC, United States.
authors.forename: P
authors.initials: P
authors.lastname: Brian Smith
mesh_terms: D002316:Cardiotonic Agents / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007022:Hypotension / Q000209:etiology*; D007231:Infant, Newborn; D007234:Infant, Premature; D007363:Intensive Care Units, Neonatal / Q000706:statistics & numerical data*; D008297:Male; D020105:Milrinone / Q000009:adverse effects*; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000209:etiology*
chemical_list: D002316:Cardiotonic Agents; D020105:Milrinone
keywords: Adverse events; Infants; Milrinone; Neonatal intensive care unit; Persistent pulmonary hypertension; Safety