Patent Ductus Arteriosus in Preterm Infants Clinical Trial
Official title:
Comparison of The Effect of Continuous and Standard Intermittent Boluses Paracetamol Infusion on Patent Ductus Arteriosus
The aim of this study was to evaluate the effect of paracetamol on patent ductus arteriosus (PDA) closure and clinical outcomes in preterm infants when used as standard intermittent bolus and continuous intravenous (IV) infusion. Preterm neonates with birth weight (BW) ≤1500 g and gestational age (GA) ≤32 weeks were included in this study. During the study period, IV paracetamol therapy was given to all infants with hemodynamically significant patent ductus arteriosus (hsPDA). The patients were divided into the standard IV intermittent bolus infusion group and the continuous IV infusion group.
Demographic and clinical features Perinatal variables were recorded for all infants,
including GA, BW, sex, APGAR scores (at 1 and 5 minutes), prenatal steroids, pre- and
post-treatment alanine aminotransferase (ALT)/aspartate aminotransferase (AST), second and
third courses of paracetamol, PDA ligation, clinical variables including respiratory distress
syndrome (RDS), IVH (grade ≥3), NEC (grade≥2), moderate or severe BPD, ROP requiring laser
therapy, early-onset neonatal sepsis (EOS), late-onset sepsis (LOS), duration of non-invasive
ventilation (NIV), mechanical ventilation (MV) and oxygen (O2) supplementation, day of full
enteral feeding achievement, length of hospital stay, and mortality.
Sepsis with onset at ≤72 hours was defined as EOS and at >72 hours as LOS in infants
hospitalized in the NICU. RDS was defined as the need for surfactant administration [5]. IVH
was diagnosed by cranial ultrasound in the first 7 days of life (intraparenchymal hemorrhage
+ IVH, large IVH). NEC diagnosis and staging were implemented by using Bell's criteria.
Neonates that received positive pressure or ≥30% oxygen without pressure after a
postmenstrual age of 36 weeks were diagnosed as having moderate or severe BPD [8]. ROP
screening was done by ophthalmologists according to the International Classification of
Retinopathy of Prematurity Revisited [9].
Hemodynamically Significant Patent Ductus Arteriosus All neonates underwent Doppler
echocardiography (ECHO) at postnatal 72 hours. Diagnosis of hsPDA was based on clinical and
ECHO features [10]. ECHO evaluation was repeated at regular intervals. IV paracetamol was
used as primary rescue therapy for hsDPA. If hsPDA persisted despite 3 courses of paracetamol
therapy, surgical ligation was performed. The non-hsPDA group comprised non-hsPDA preterm
infants selected using the same exclusion criteria. Infants with non-hsPDA were excluded from
the study.
Continuous and Standard Intermittent Bolus Infusion of Paracetamol IV paracetamol therapy was
delivered as primary rescue pharmacological treatment to all neonates who had hsPDA during
the study period. Standard IV intermittent bolus paracetamol therapy was administered in the
form of 15 mg/kg doses as 1-hour infusions every 6 hours for 5 days, while continuous IV
paracetamol infusion therapy was administered as a 60 mg/kg/day dose continuously for 5 days
(Parol, Atabay Ilac Kimya San., Istanbul, Turkey). ALT and AST levels were analyzed before
and after treatment . Infants received standard IV intermittent bolus paracetamol between
January 1 and April 31, 2018, and continuous IV infusion paracetamol between May 1 - August
31, 2018 for hsPDA medical treatment. Therefore, eligible infants were divided into two
groups as the standard IV intermittent bolus infusion group and the continuous IV infusion
group.
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