Early ibuprofen administration to prevent patent ductus arteriosus in premature newborn infants
A. Varvarigou, C. L. Bardin, K. Beharry, S. Chemtob, A. Papageorgiou and J. V. Aranda
Department of Neonatology, Lady Davis Institute-SMBD Jewish General Hospital, Montreal, Quebec, Canada.
OBJECTIVE--To test whether early postnatal (0 to 3 hours) intravenous
administration of ibuprofen will prevent patent ductus arteriosus (PDA) in
preterm neonates. DESIGN--Prospective sequential controlled trial with
three treatment arms. SETTING--Level 3 perinatal-neonatal intensive care
nursery. PATIENTS--Thirty-four premature newborn infants born from February
to August 1993 with a mean birth weight of 913 g (range, 565 to 1460 g) and
gestational age of 26.9 weeks (range, 22.4 to 31.0). INTERVENTION--Infants
were consecutively assigned within 3 hours of age to treatment with either
one dose of ibuprofen lysine (10 mg/kg intravenously) followed by 5 mg/kg
per dose intravenously at 24 and 48 hours of age (n = 12), one dose of
ibuprofen lysine (10 mg/kg intravenously; n = 11), or saline (n = 11).
OUTCOME VARIABLES--Primary outcome variable was the presence of ductus
arteriosus by echocardiography and clinical assessments at 3, 7, and 21
days of life. Secondary outcome variables included presence of
intraventricular hemorrhage, renal function, ventilatory and oxygen needs,
hematologic changes, gastrointestinal function, time to full enteral
feeding, duration of hospitalization, and age at discharge. RESULTS--The
three groups of patients were comparable in birth weight, gestational age,
antenatal administration of betamethasone, and other perinatal
characteristics. Ibuprofen treatment significantly reduced plasma levels of
prostaglandins, and the levels remained low for 72 hours in newborns who
received three doses of the drug. The incidence of PDA and other variables
did not differ between patients who received a single dose of ibuprofen and
those given saline. However, compared with the saline-treated newborns,
babies who received three doses of ibuprofen had no PDA (0/12 vs 7/11 for
saline; P < .02), had lower daily mean airway pressures (mean +/- SD,
5.2 +/- 1.1 cm H2O vs 8.3 +/- 2.8 cm H2O for saline; P < .02) and better
oxygenation index (2.6 +/- 0.6 vs 4.7 +/- 1.8 for saline; P < .02) at
the end of the first week of life, and required fewer days of ventilation
(25 +/- 14 days vs 44 +/- 26 days for saline; P < .03). Babies given
three doses of ibuprofen tended to tolerate full oral feedings earlier (35
+/- 19 days vs 56 +/- 34 days for saline; P = .09), had shorter duration of
hospitalization (71.2 +/- 22.6 days vs 127.3 +/- 74.7 days for saline; P
< .05), and were discharged to home at an earlier postconceptional age
(37.8 +/- 2.0 weeks vs 44.8 +/- 9.8 weeks for saline; P < .05).
ibuprofen treatment in this phase I trial was not associated with any
apparent early neurological, intestinal, renal, hepatic, or hematologic
complications. CONCLUSIONS--Administration of three doses of ibuprofen
within 3 hours after birth in preterm neonates reduced the incidence of PDA
without causing notable early adverse drug reactions in this phase I trial.
Early closure of the ductus arteriosus was also associated with better
respiratory outcome and earlier discharge from the hospital.
Comparison of ibuprofen and indometacin for early-targeted treatment of patent ductus arteriosus in extremely premature infants: a randomised controlled trial
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ABSTRACT
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Calhoun et al.
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Aranda and Thomas
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Dani et al.
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Gregoire et al.
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Heyman et al.
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ABSTRACT
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Osborn et al.
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Sharma et al.
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ABSTRACT
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Narayanan-Sankar and Clyman
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Overmeire et al.
NEJM 2000;343:674-681.
ABSTRACT
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Ibuprofen and Patent Ductus Arteriosus
Clyman
NEJM 2000;343:728-730.
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Van Overmeire et al.
Arch. Dis. Child. Fetal Neonatal Ed. 1997;76:179F-184.
ABSTRACT
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IBUPROFEN MAY PREVENT PATENT DUCTUS ARTERIOSUS IN NEONATES
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