PMID- 25460254
OWN - NLM
STAT- MEDLINE
DCOM- 20151026
LR  - 20240407
IS  - 1872-6232 (Electronic)
IS  - 0378-3782 (Print)
IS  - 0378-3782 (Linking)
VI  - 91
IP  - 1
DP  - 2015 Jan
TI  - Safety of milrinone use in neonatal intensive care units.
PG  - 31-5
LID - S0378-3782(14)00272-2 [pii]
LID - 10.1016/j.earlhumdev.2014.10.007 [doi]
AB  - 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. CONCLUSION: 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.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - Samiee-Zafarghandy, Samira
AU  - Samiee-Zafarghandy S
AD  - 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.
FAU - Raman, Sudha R
AU  - Raman SR
AD  - Duke Clinical Research Institute, Duke University, Durham, NC, United States.
FAU - van den Anker, John N
AU  - van den Anker JN
AD  - 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.
FAU - McHutchison, Kerstin
AU  - McHutchison K
AD  - Duke Clinical Research Institute, Duke University, Durham, NC, United States.
FAU - Hornik, Christoph P
AU  - Hornik CP
AD  - Duke Clinical Research Institute, Duke University, Durham, NC, United States; 
      Department of Pediatrics, Duke University, Durham, NC, United States.
FAU - Clark, Reese H
AU  - Clark RH
AD  - Pediatrix-Obstetrix Center for Research and Education, Sunrise, FL, United 
      States.
FAU - Brian Smith, P
AU  - Brian Smith P
AD  - Duke Clinical Research Institute, Duke University, Durham, NC, United States; 
      Department of Pediatrics, Duke University, Durham, NC, United States.
CN  - Best Pharmaceuticals for Children Act-Pediatric Trials Network Administrative 
      Core Committee
LA  - eng
GR  - HHSN267200700051C/HD/NICHD NIH HHS/United States
GR  - R01 HD060543/HD/NICHD NIH HHS/United States
GR  - UL1TR001117/TR/NCATS NIH HHS/United States
GR  - HHSN275201000003I/HD/NICHD NIH HHS/United States
GR  - HHSN267200700051C/DK/NIDDK NIH HHS/United States
GR  - HHSN275201000003C/AA/NIAAA NIH HHS/United States
GR  - UL1 TR001117/TR/NCATS NIH HHS/United States
GR  - U54 HD071601/HD/NICHD NIH HHS/United States
GR  - K24 DA027992/DA/NIDA NIH HHS/United States
GR  - R01 HD048689/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20141126
PL  - Ireland
TA  - Early Hum Dev
JT  - Early human development
JID - 7708381
RN  - 0 (Cardiotonic Agents)
RN  - JU9YAX04C7 (Milrinone)
SB  - IM
CIN - Early Hum Dev. 2015 Feb;91(2):109. PMID: 25584458
MH  - Cardiotonic Agents/*adverse effects
MH  - Female
MH  - Humans
MH  - Hypotension/*etiology
MH  - Infant, Newborn
MH  - Infant, Premature
MH  - Intensive Care Units, Neonatal/*statistics & numerical data
MH  - Male
MH  - Milrinone/*adverse effects
MH  - Retrospective Studies
MH  - Thrombocytopenia/*etiology
PMC - PMC4302030
MID - NIHMS640848
OTO - NOTNLM
OT  - Adverse events
OT  - Infants
OT  - Milrinone
OT  - Neonatal intensive care unit
OT  - Persistent pulmonary hypertension
OT  - Safety
COIS- Conflict-of-interest statement Dr. Smith receives salary support for research 
      from the NIH, the U.S. Department of Health and Human Services, and the National 
      Center for Advancing Translational Sciences of the NIH (HHSN267200700051C, 
      HHSN275201000003I, and UL1TR001117); he also receives research support from 
      industry for neonatal and pediatric drug development 
      (www.dcri.duke.edu/research/coi.jsp). Dr. van den Anker receives salary support 
      for research from the NIH (5K24DA027992, 5U54HD071601, 5R01HD048689, and 
      5R01HD060543). Dr. Hornik receives salary support for research from the National 
      Center for Advancing Translational Sciences of the National Institutes of Health 
      (UL1TR001117). The remaining authors have no potential conflicts to disclose.
FIR - Benjamin, Daniel K Jr
IR  - Benjamin DK Jr
FIR - Berezny, Katherine
IR  - Berezny K
FIR - Barrett, Jeffrey
IR  - Barrett J
FIR - Capparelli, Edmund
IR  - Capparelli E
FIR - Cohen-Wolkowiez, Michael
IR  - Cohen-Wolkowiez M
FIR - Kearns, Gregory L
IR  - Kearns GL
FIR - Laughon, Matthew
IR  - Laughon M
FIR - Muelenaer, Andre
IR  - Muelenaer A
FIR - O'Shea, T Michael
IR  - O'Shea T
FIR - Paul, Ian M
IR  - Paul IM
FIR - Wade, Kelly
IR  - Wade K
FIR - Walsh, Thomas J
IR  - Walsh TJ
FIR - Siegel, David
IR  - Siegel D
FIR - Taylor-Zapata, Perdita
IR  - Taylor-Zapata P
FIR - Zajicek, Anne
IR  - Zajicek A
FIR - Pagan, Alice
IR  - Pagan A
FIR - Anand, Ravinder
IR  - Anand R
FIR - Clemons, Traci
IR  - Clemons T
FIR - Simone, Gina
IR  - Simone G
EDAT- 2014/12/03 06:00
MHDA- 2015/10/27 06:00
PMCR- 2016/01/01
CRDT- 2014/12/03 06:00
PHST- 2014/04/07 00:00 [received]
PHST- 2014/10/21 00:00 [revised]
PHST- 2014/10/27 00:00 [accepted]
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2015/10/27 06:00 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - S0378-3782(14)00272-2 [pii]
AID - 10.1016/j.earlhumdev.2014.10.007 [doi]
PST - ppublish
SO  - Early Hum Dev. 2015 Jan;91(1):31-5. doi: 10.1016/j.earlhumdev.2014.10.007. Epub 
      2014 Nov 26.