Paracetamol in Patent Ductus Arteriosus Treatment: Efficacious and Safe?

Abstract

In preterm infants, failure or delay in spontaneous closure of Ductus Arteriosus (DA), resulting in the condition of Patent Ductus Arteriosus (PDA), represents a significant issue. A prolonged situation of PDA can be associated with several short- and long-term complications. Despite years of researches and clinical experience on PDA management, unresolved questions about the treatment and heterogeneity of clinical practices in different centers still remain, in particular regarding timing and modality of intervention. Nowadays, the most reasonable strategy seems to be reserving the treatment only to hemodynamically significant PDA. The first-line therapy is medical, and ibuprofen, related to several side effects especially in terms of nephrotoxicity, is the drug of choice. Administration of oral or intravenous paracetamol (acetaminophen) recently gained attention, appearing effective as traditional nonsteroidal anti-inflammatory drugs (NSAIDs) in PDA closure, with lower toxicity. The results of the studies analyzed in this review mostly support paracetamol efficacy in ductal closure, with inconstant low and transient elevation of liver enzymes as reported side effect. However, more studies are needed to confirm if this therapy shows a real safety profile and to evaluate its long-term outcomes, before considering paracetamol as first-choice drug in PDA treatment.

Is high dose intravenous acetaminophen affect liver function in premature neonates with patent ductus arteriosus?

“…week would reduce to 2%, 65% and 87%. (2,3) Hypoxia, acidosis, raised pulmonary pressure and increasing prostaglandin level are risk factors that contributing to ductal patency. Shunt of blood from the aorta into the pulmonary artery can promote pulmonary over circulation that lead to significant clinical consequence such as vital organ perfusion impairment for example pulmonary hypertension, heart failure, intra ventricular hemorrhage and respiratory disease, periventricular leukomalacia, cerebral palsy or death.…”

“…Shunt of blood from the aorta into the pulmonary artery can promote pulmonary over circulation that lead to significant clinical consequence such as vital organ perfusion impairment for example pulmonary hypertension, heart failure, intra ventricular hemorrhage and respiratory disease, periventricular leukomalacia, cerebral palsy or death. (2,(4)(5)(6)(7) PDA intervention is controversial, and there is limitation of evidence to guide treatment. There is 3 strategies for closure of PDA in prelatures: Prophylactic management, treatment of clinically detected asymptomatic PDA, and treatment when the PDA is symptomatic neonates.…”

Pharmacological treatment strategies for neonates with patent ductus arteriosus: a systematic review

“…These treatments include indomethacin, ibuprofen, and paracetamol. 3,6 Indomethacin is an NSAID that was first introduced to treat PDA due to its potent vasoconstrictor properties. It is also recommended for prophylaxis, but is associated with side effects due to excessive vasoconstriction, such as impaired renal function, white matter damage, and intestinal perforation.…”

“…It is also recommended for prophylaxis, but is associated with side effects due to excessive vasoconstriction, such as impaired renal function, white matter damage, and intestinal perforation. 6 Ibuprofen is another NSAID that has milder side effects compared to indomethacin due to its weaker vasoconstrictor capacity. However, both NSAIDs have been implicated in nephrotoxicity due to prostaglandin suppression, which is requisite for neonatal renal adaptation and development.6 In addition, various contraindications for NSAID use, such as hematuria, blood in stool, sepsis, pulmonary hemorrhage, and renal dysfunction, limit the use of these NSAIDs for PDA, leaving physicians with surgical ligation as a last resort.…”

“…However, both NSAIDs have been implicated in nephrotoxicity due to prostaglandin suppression, which is requisite for neonatal renal adaptation and development.6 In addition, various contraindications for NSAID use, such as hematuria, blood in stool, sepsis, pulmonary hemorrhage, and renal dysfunction, limit the use of these NSAIDs for PDA, leaving physicians with surgical ligation as a last resort. 6 Recently, paracetamol, a non-classic NSAID, was shown to be safer and associated with fewer side effects compared to the former two medications. One study reported that paracetamol administration was associated with lower urinary PGE2 reduction and incidence of oliguria, indicating less nephrotoxicity.…”