Original Paper Received: June 4, 2013 Accepted after revision: September 13, 2013 Published online: November 19, 2013
Neonatology 2014;105:46–54 DOI: 10.1159/000355679
Continuous Infusion of Ibuprofen for Treatment of Patent Ductus Arteriosus in Very Low Birth Weight Infants Paola Lago a Sabrina Salvadori a Francesca Opocher a Silvia Ricato a Lino Chiandetti a Anna Chiara Frigo b
a
Neonatal Intensive Care Unit, Department of Women’s and Children’s Health, Azienda Ospedaliera-University of Padua, and b Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy
Abstract Background: Ibuprofen (IBU) has proved as effective as indomethacin in the pharmacological closure of hemodynamically significant patent ductus arteriosus (HsPDA), with an efficacy inversely related to gestational age (57–89%). Objective: This study aimed to establish whether continuous infusions of IBU could be more effective in very low birth weight infants with no additional adverse effects and reduce the need for surgical ligation. Methods: A prospective, randomized, double-dummy study was conducted on 112 very low birth weight infants (mean gestational age 27.2 weeks, SD 2; birth weight 1,019 g, SD 330) with HsPDA, 56 of whom were given IBU in conventional 15-min intermittent boluses, while the other 56 were administered IBU as a 24-hour continuous infusion, both at standard doses (10/5/5 mg/kg). Extensive echocardiography was performed before and after treatment, and adverse effects were monitored. Results: Pharmacological PDA closure was achieved after 1 or 2 IBU courses in 36 of 56 infants (64.3%) after bolus administration and in 46 of 55 (83.6%) after continuous infusion (p = 0.020),
© 2013 S. Karger AG, Basel 1661–7800/14/1051–0046$39.50/0 E-Mail [email protected] www.karger.com/neo
and in 9 of 26 (34.6%) and 24 of 30 (80.0%), respectively, in the infants with a gestational age of 23–27 weeks (p = 0.006). Sustained pharmacological closure was observed in 38 of 56 infants (67.9%) after bolus IBU and in 47 of 55 (85.5%) after continuous infusion (p = 0.029). Surgical ligation was used less after continuous infusion than after bolus IBU (5.5 vs. 19.6%; p = 0.024). The continuous infusion group had fewer symptoms of necrotizing enterocolitis (NEC), especially in the more preterm infants, while other neonatal morbidity and mortality rates were similar. Conclusion: Continuous IBU infusion is more effective than standard boluses for sustained closure of HsPDA, with fewer NEC symptoms and less need for surgical ligation in very low birth weight infants. © 2013 S. Karger AG, Basel
Introduction
Patent ductus arteriosus (PDA) is common in preterm infants, affecting 37% of very low birth weight infants, almost 80% of whom receive pharmacological treatment, while 6.5% undergo surgical ligation (with a higher incidence in extremely premature infants) [1]. A persistent shunt through the ductus is associated with numerous morbidities relating to pulmonary overcircu-
Paola Lago, MD Neonatal Intensive Care Unit, Department of Women’s and Children’s Health Azienda Ospedaliera-University of Padua Via Giustiniani, 3, IT–35128 Padua (Italy) E-Mail lago @ pediatria.unipd.it
Downloaded by: University of Tokyo 157.82.153.40 - 5/25/2015 12:34:23 PM
Key Words Ibuprofen · Continuous infusion · Patent ductus arteriosus · Preterm infant · Efficacy · Safety
Methods Study Setting and Design This single-center, randomized, controlled, double-dummy study was conducted at the Neonatal Intensive Care Unit (NICU) of the Padua University Hospital, with approval of the local Ethics Committee (trial No. P 1549/2008). All inborn premature infants under 32 weeks of gestational age admitted with infant respiratory distress syndrome and ventilated were potential candidates for the study. Babies with renal impairment (creatinine >140 μmol/l) and/or urine output ≤1 ml/kg/h, thrombocytopenia (3 days) and CRIB score. In a secondary analysis, the efficacy and safety of the different modes of IBU administration were assessed in subgroups divided
48
Neonatology 2014;105:46–54 DOI: 10.1159/000355679
according to gestational age (
Neonatology 2014;105:46–54 DOI: 10.1159/000355679
Continuous Infusion of Ibuprofen for Treatment of Patent Ductus Arteriosus in Very Low Birth Weight Infants Paola Lago a Sabrina Salvadori a Francesca Opocher a Silvia Ricato a Lino Chiandetti a Anna Chiara Frigo b
a
Neonatal Intensive Care Unit, Department of Women’s and Children’s Health, Azienda Ospedaliera-University of Padua, and b Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy
Abstract Background: Ibuprofen (IBU) has proved as effective as indomethacin in the pharmacological closure of hemodynamically significant patent ductus arteriosus (HsPDA), with an efficacy inversely related to gestational age (57–89%). Objective: This study aimed to establish whether continuous infusions of IBU could be more effective in very low birth weight infants with no additional adverse effects and reduce the need for surgical ligation. Methods: A prospective, randomized, double-dummy study was conducted on 112 very low birth weight infants (mean gestational age 27.2 weeks, SD 2; birth weight 1,019 g, SD 330) with HsPDA, 56 of whom were given IBU in conventional 15-min intermittent boluses, while the other 56 were administered IBU as a 24-hour continuous infusion, both at standard doses (10/5/5 mg/kg). Extensive echocardiography was performed before and after treatment, and adverse effects were monitored. Results: Pharmacological PDA closure was achieved after 1 or 2 IBU courses in 36 of 56 infants (64.3%) after bolus administration and in 46 of 55 (83.6%) after continuous infusion (p = 0.020),
© 2013 S. Karger AG, Basel 1661–7800/14/1051–0046$39.50/0 E-Mail [email protected] www.karger.com/neo
and in 9 of 26 (34.6%) and 24 of 30 (80.0%), respectively, in the infants with a gestational age of 23–27 weeks (p = 0.006). Sustained pharmacological closure was observed in 38 of 56 infants (67.9%) after bolus IBU and in 47 of 55 (85.5%) after continuous infusion (p = 0.029). Surgical ligation was used less after continuous infusion than after bolus IBU (5.5 vs. 19.6%; p = 0.024). The continuous infusion group had fewer symptoms of necrotizing enterocolitis (NEC), especially in the more preterm infants, while other neonatal morbidity and mortality rates were similar. Conclusion: Continuous IBU infusion is more effective than standard boluses for sustained closure of HsPDA, with fewer NEC symptoms and less need for surgical ligation in very low birth weight infants. © 2013 S. Karger AG, Basel
Introduction
Patent ductus arteriosus (PDA) is common in preterm infants, affecting 37% of very low birth weight infants, almost 80% of whom receive pharmacological treatment, while 6.5% undergo surgical ligation (with a higher incidence in extremely premature infants) [1]. A persistent shunt through the ductus is associated with numerous morbidities relating to pulmonary overcircu-
Paola Lago, MD Neonatal Intensive Care Unit, Department of Women’s and Children’s Health Azienda Ospedaliera-University of Padua Via Giustiniani, 3, IT–35128 Padua (Italy) E-Mail lago @ pediatria.unipd.it
Downloaded by: University of Tokyo 157.82.153.40 - 5/25/2015 12:34:23 PM
Key Words Ibuprofen · Continuous infusion · Patent ductus arteriosus · Preterm infant · Efficacy · Safety
Methods Study Setting and Design This single-center, randomized, controlled, double-dummy study was conducted at the Neonatal Intensive Care Unit (NICU) of the Padua University Hospital, with approval of the local Ethics Committee (trial No. P 1549/2008). All inborn premature infants under 32 weeks of gestational age admitted with infant respiratory distress syndrome and ventilated were potential candidates for the study. Babies with renal impairment (creatinine >140 μmol/l) and/or urine output ≤1 ml/kg/h, thrombocytopenia (3 days) and CRIB score. In a secondary analysis, the efficacy and safety of the different modes of IBU administration were assessed in subgroups divided
48
Neonatology 2014;105:46–54 DOI: 10.1159/000355679
according to gestational age (
