Intravenous Paracetamol Treatment in the Management of Patent Ductus Arteriosus in Extremely Low Birth Weight Infants

Abstract

Background: Treatment options for the closure of a hemodynamically significant patent ductus arteriosus (hsPDA) include medical therapy such as ibuprofen and indomethacin and surgical ligation. Objective: To evaluate the efficacy of intravenous paracetamol in preterm infants with hsPDA whose feeding was contraindicated or had feeding intolerance. Methods: Preterm infants with hsPDA were started on intravenous paracetamol treatment with parental consent. Paracetamol was administered at a dose of 60 mg/kg/day, in four divided doses, for a period of 3 days. In the absence of closure of hsPDA, treatment was extended up to 6 days, after which echocardiographic examination was performed. Results: A total of 10 preterm infants were included in the study with a median gestational age of 27^4/7 weeks (minimum–maximum: 24–29) and a median birth weight of 775 g (590–990). The first dose of intravenous paracetamol was given after a median of 6 days (2–15). On echocardiographic examination, median internal ductal diameter was 2 mm (1.5–3), with a median left atrium-to-aortic root ratio of 1.95 (1.6–2.2). Intravenous paracetamol resulted in successful closure of hsPDA in all patients. Conclusions: This study is the first case series in the literature which used intravenous paracetamol treatment for hsPDA. We believe that intravenous paracetamol could be used as an alternative drug for infants. Further prospective randomized-controlled trials are needed to evaluate the efficacy of intravenous paracetamol for the closure of hsPDA.

IV Paracetamol for closure of patent ductus arteriosus in preterm neonates admitted to a tertiary care centre

“…25 Oncel et al reported the results of ramdomised contolled trial in preterm infants treated with oral paracetamol in whom closue of PDA was acheieved with no side effects. 29 According to Terrin et al a case series of neonates with hs-PDA treated with paracetamol because of contraindication to ibuprofen or indomethacin, ductal closure was noted in 70% of neonates with no adverse reactions likewise in our study ductal closure was noted in 75% neonates with IV paracetamol. 30 The mechanism by which paracetamol can close ibuprofen refractory PDA might lie in the different site of action on prostaglandin synthetase of the two drugs, that hypothetically might have also a synergistic effect.…”

Intravenous paracetamol and patent ductus arteriosus closure in preterm infants

“…[5][6][7][8][9][10][11][12][13][14][15] For case series using intravenous paracetamol, the proportion of successful PDA closure was between 75 and 100%.12-15 Our design was similar, but we had a larger sample size compared to previous case series. The proportion of successful PDA closure was lower at 65.5%, than in the four previous case series.…”

“…Paracetamol acts as a peroxidase inhibitor in prostaglandin synthesis. 4 In previous case series involving a limited number of subjects, both oral [5][6][7][8][9][10][11][12] and intravenous preparation [12][13][14][15] of paracetamol showed satisfactory results for PDA closure, with no liver toxicity. Moreover, two randomized, double-blind, control trials showed that oral paracetamol was better than oral ibuprofen.…”

Eficacia del paracetamol intravenoso para el cierre del conducto arterioso en recién nacidos prematuros

“…Estos datos reafirman la importancia de realizar el diagnóstico ecocardiográfico temprano de persistencia del conducto arterioso en todos los recién nacidos prematuros, ya que los signos clínicos típicos de persistencia del conducto arterioso no siempre son evidentes inicialmente; pueden presentarse tardíamente como se reporta en la literatura especializada: los criterios ecocardiográficos de un cortocircuito izquierda-derecha significativo habitualmente preceden a los síntomas clínicos por un intervalo de 2-3 días, 19 de modo que si se toman en cuenta sólo estos signos clínicos el diagnóstico podría retrasarse y el recién nacido prematuro estaría expuesto a una mayor frecuencia de complicaciones propias de la persistencia del conducto arterioso. 19,20 En nuestro estudio los hallazgos ecocardiográficos no tuvieron una correlación clínica adecuada ya que, si bien en la mayoría de los pacientes se identificó persistencia del conducto arterioso significativo por ecocardiografía, sólo en poco más de 50% de los pacientes el índice de Yeh fue mayor o igual a 3. Esta discordancia entre los hallazgos ecocardiográficos y clínicos se debe a que en el recién nacido prematuro las resistencias vasculares pulmonares están elevadas, por lo tanto existe poca diferencia de presión entre la aorta y la pulmonar, de modo que la velocidad de flujo transductal puede ser insuficiente para generar soplo u otros signos de persistencia del conducto arterioso.…”

“…En estudios con paracetamol intravenoso efectuados por Oncel y por Serafettin 20,21 el cierre del conducto arterioso fue de 100%. En el único paciente en el que no se consiguió el cierre del conducto arterioso se administró previamente ibuprofeno oral por falta de disponibilidad temporal de paracetamol intravenoso y se decidió, después de tres días de tratamiento con este fármaco, la administración de paracetamol intravenoso ante la falta de cierre del conducto arterioso.…”