Ductus paracetamol

Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low birth weight infants (Review)

Effect on cerebral oxygenation of paracetamol for patent ductus arteriosus in preterm infants

Paracetamol seems to have similar success rates compared with indomethacin and ibuprofen in closing patent ductus arteriosus (PDA) in preterm infants, but with a better safety profile. The aim of our study was to evaluate the possible effects of paracetamol on cerebral oxygenation and cerebral blood flow velocity (CBFV). Infants with gestational age < 32 weeks with hemodynamically significant PDA (hsPDA) were prospectively studied by near infrared spectroscopy (NIRS) after the first dose of paracetamol (15 mg/kg) or ibuprofen (10 mg/kg).

Our patients were treated with ibuprofen (10 mg/kg i.v.followed by 5 mg/kg each, after 24 and 48 h) as first choice drug for hsPDA, while paracetamol (15 mg / kg i.v. every 6 h for 3 days) was used in presence of contraindications to ibuprofen: urine output < 1 mL/kg/h during the preceding 12 h (with the exception of the first dose); a serum creatinine concentration > 1.5 mg/dL; platelet count < 50,000/mm3; a tendency to bleed, as revealed by hematuria, blood in the endotracheal aspirate, gastric aspirate, or stools, and oozing from puncture sites. The medication was infused continuously over a period of 15 min.

Cerebral regional oxygenation (rSO2C) and fractional oxygen extraction ratio (FOEC) were recorded 30 min before (T0) and 60 ± 20 min (T1), 180 ± 30 min (T2), and 360 ± 30 min (T3) after the beginning of drug infusion. Moreover, mean flow velocity (Vmean) and resistance index (RI = PSV-DV/PSV) measured with Doppler ultrasound in pericallosal artery were recorded at the same times. Significant changes in rSO2C and FOEC were not found during the study period within and between the groups. Similarly, Vmean did not vary in infants treated with paracetamol or ibuprofen, while RI decreased in the ibuprofen group.

Conclusion: The treatment of hsPDAwith paracetamol does not affect cerebral oxygenation in very preterminfants; there were no differences in cerebral oxygenation in infants treated with paracetamol or ibuprofen, although in the ibuprofen group, the possible closure progression of PDA was associated to changes of RI.

Acetaminophen for Patent Ductus Arteriosus in Extremely Low-Birth-Weight Neonates

OBJECTIVE Although non-steroidal anti-inflammatory drugs (NSAIDs) are the current standard therapy for the treatment of patent ductus arteriosus (PDA), many neonates have contraindications to receiving or may fail NSAID therapy. To avoid surgical ligation, these patients may benefit from an alternative therapy. The objective of this research is to report the efficacy and safety of acetaminophen for the treatment of PDA in a cohort of premature neonates.

METHODS Demographics and clinical course were retrospectively evaluated for all neonates admitted during the study period who received acetaminophen for the treatment of PDA. Initial acetaminophen dosing was 15 mg/kg every 6 hours (88% intravenous). Efficacy was analyzed from ductal constriction on echocardiogram as well as need for further PDA treatment. Markers of hepatic and renal function as well as respiratory support and neonatal morbidities were evaluated to describe the safety of acetaminophen.

RESULTS Forty-one neonates were identified with a median birth weight of 760 g (IQR 614– 948 g) and median gestational age of 25 weeks (IQR 24–27 weeks). Treatment was initiated at a median postnatal age of 15 days (IQR 8–19 days) for a median duration of 7 days (IQR 6–10 days). Twenty-seven neonates (66%) required no further PDA treatment, with echocardiographic PDA closure documented in 10 neonates (24%) and reduced ductal size in 15 neonates (37%). No clinically significant adverse effects attributable to acetaminophen therapy were detected.

CONCLUSIONS Most patients in this study responded to acetaminophen treatment for PDA, indicating that this therapy may be an option for extremely low-birth-weight neonates in order to avoid surgical ligation.

Article first published online: October 28, 2014; Issue published: February 1, 2015

Objective: To evaluate the literature describing acetaminophen use in treatment of patent ductus arteriosus (PDA).

Data Sources: Searches were conducted in MEDLINE with full text (EBSCOhost; 1946 to September 2014) using the search terms acetaminophen, paracetamol, and patent ductus arteriosus. The references of identified articles were reviewed to identify other relevant articles.

Study Selection and Data Extraction: Human clinical trials and case reports limited to the English language were reviewed. In all, 12 case reports and 2 randomized, controlled clinical trials explored the use of acetaminophen in treating PDA.

Data Synthesis: The case reports described the use of oral or intravenous acetaminophen in patients with contraindications to or who had previously failed nonsteroidal anti-inflammatory drug therapy for PDA. More than 76% of patients achieved successful PDA closure in reported cases. The clinical trials compared the efficacy of oral acetaminophen versus oral ibuprofen in preterm infants. Acetaminophen was noninferior to ibuprofen, with closure rates from 72.5% to 81.2%. The acetaminophen dose used in most case series and trials was 15 mg/kg dose every 6 hours for 3 days. Acetaminophen therapy was well tolerated, with only a few incidents of elevated liver enzymes being reported.

Conclusion: Oral acetaminophen is an alternative to PDA therapy in preterm infants when indomethacin/ibuprofen is not effective or is contraindicated, and it may be considered before surgical ligation.

Acetaminophen for Patent Ductus Arteriosus in Extremely Low-Birth-Weight Neonates

Caitlyn M. Luecke

Department of Pharmacy (CML, CJL, BNZ, CM), St. Louis Children's Hospital, St Louis, Missouri, Department of Pediatrics (ZAV, CM), Washington University School of Medicine, St Louis, Missouri

The Journal of Pediatric Pharmacology and Therapeutics

https://doi.org/10.5863/1551-6776-22.6.461

RESULTS Forty-one neonates were identified with a median birth weight of 760 g (IQR 614–948 g) and median gestational age of 25 weeks (IQR 24–27 weeks). Treatment was initiated at a median postnatal age of 15 days (IQR 8–19 days) for a median duration of 7 days (IQR 6–10 days). Twenty-seven neonates (66%) required no further PDA treatment, with echocardiographic PDA closure documented in 10 neonates (24%) and reduced ductal size in 15 neonates (37%). No clinically significant adverse effects attributable to acetaminophen therapy were detected.

Oral Paracetamol for Patent Ductus Arteriosus Rescue Closure

Pramod Pharande

Pediatr Cardiolog 2017

DOI 10.1007/s00246-017-1745-z

Abstract

The objective of this study was to ascertain the efficacy of oral paracetamol in closing a symptomatic patent ductus arteriosus (PDA) when used as ‘rescue’ option. After obtaining ethics approval, a retrospective appraisal of the data from April 2014 to July 2015 was performed. Infants who were administered oral paracetamol either after unsuccessful therapy with ibuprofen or where it was considered contraindicated were included. A previously published echocardiographic scoring schema to stratify for ductal disease severity was used. Using univariate analysis, characteristics of infants with successful closure were compared with partial (a priori reduction in composite score by C 50% of pretreatment) or no closure. Twenty infants with gestation age and birthweight of 25.7 ± 1.5 weeks and 724.1 ± 143 g, respectively, were studied. Complete closure was noted in 10 (50%) infants with additional four infants showing a significant reduction in haemodynamic shunting. Gestational age at birth and at therapy, chronological age at therapy, birthweight and total fluid intake were comparable between the two groups.

The pre-therapy composite score had a significant association with successful closure (the higher the echocardiographic score, the lesser the closure). Concomitant furosemide therapy and late-onset sepsis had a high likelihood ratio of unsuccessful closure (11.01 [2-tailed, p = 0.005] and 5.3 [2-tailed, p = 0.07]), respectively.

Paracetamol was administered orally at a dose of 15 mg/kg/dose every 6 h for 3 days.

Compared to COX inhibitors, paracetamol acts via the peroxidase component of the enzyme (which is activated at lower arachidonic acid levels) [14].

Oral paracetamol may be a possible therapeutic option in premature infants where therapy with first-line agents is unsuccessful or contraindicated. Concomitant sepsis and furosemide administration may affect successful therapy.

Further Experience with Oral Paracetamol as a Rescue Therapy for Patent Ductus Arteriosus in Preterm Infants

Hannes Sallmon y Cols

Pediatric Cardiology https://doi.org/10.1007/s00246-017-1791-6

Received: 20 November 2017 / Accepted: 1 December 2017 © Springer Science+Business Media, LLC, part of Springer Nature 2017

To the Editor :

Con gran interés hemos leído el reciente artículo de Pharande y cols sobre el uso de paracetamol oral como terapia de rescate para ductus arterioso persistente (DAP) en neonatos prematuros ¹. Los autores encontraron que el paracetamol tiene éxito en cierre de DAP en aproximadamente 50% de los pacientes. Estos resultados son prometedores; sin embargo, los autores solo investigaron los resultados del tratamiento de 20 pacientes.

Nosotros, en este documento, informamos resultados adicionales de 19 recién nacidos prematuros que recibieron paracetamol oral después de fracaso de tratamiento con ibuprofeno. Incluimos a todos los bebés que recibieron paracetamol entre 2014 y 2016 en nuestra institución. Algunos bebés recibieron indometacina profiláctica durante las primeras 72 h de vida con el objetivo de reducir la tasa de hemorragia intracraneal ². A todos los neonatos con MBPN se les realizó screening con ecocardiografía para DAP hemodinámicamente significativo entre los 3 - 5 días de vida y recibieron ibuprofeno (10-5-5 mg / kg / dosis PO) si estaba indicado (una descripción detallada de la ecocardiografía y los protocolos de tratamiento han sido previamente reportados). ³

Paracetamol se administró como terapia de rescate a dosis de 15 mg / kg / dosis PO cada 6 h.

La mediana del peso de nacimiento y de la edad gestacional de los recién nacidos incluídos fueron 745 g (± 202 g) y 25 5/7 semanas (± 1 2/7 semanas), respectivamente. Observamos cierre completo después del paracetamol en 4/19 pacientes y cierre parcial (es decir, sin repercusión hemodinámica) en 7/19 pacientes. En total, 11/19 (58%) de los pacientes no requirieron tratamiento adicional de DAP después del tratamiento de rescate con paracetamol, mientras que 8/19 niños se sometieron a cierre quirúrgico o intervencional de DAP o mostraron signos de repercusión hemodinámica al alta.

Desde la primera observación del cierre de DAP inducido por paracetamol, varios estudios han abordado el efecto de paracetamol (PO o IV) como terapia de primera línea y como una alternativa potencial a las terapias establecidas . Recientemente, El-Kuffash y cols demostraron un rol para paracetamol IV en cierre médico tardío de DAP.

El valor de la investigación actual por Pharande et al. radica en la investigación de paracetamol oral como terapia de rescate después del fracaso de tratamiento estándar o como un enfoque no invasivo en presencia de contraindicaciones para el tratamiento con inhibidores de la ciclooxigenasa estándar (insuficiencia renal, trombocitopenia, etc.).

En estas circunstancias, además del paracetamol, solo están disponibles como alternativa intervenciones quirúrgicas o basadas en catéteres, que están asociadas con complicaciones significativas, como la anestesia, la parálisis de las cuerdas vocales o la infección. Por lo tanto, el Paracetamol proporciona un enfoque alternativo razonable frente al cierre ductal invasivo en los recién nacidos prematuros de mayor edad antes de la intervención quirúrgica o por catéter.

Sin embargo, las indicaciones y los enfoques de tratamiento deben seleccionarse cuidadosamente de forma individual .