Early closure mechanisms of the ductus arteriosus in immature infants

Aim According to experimental studies, cardiopulmonary distress decreases after closure of patent ductus arteriosus. However, early closure of the ductus using ibuprofen or indomethacin has failed to increase survival without serious morbidity. We review relevant data aiming to define optimal early management strategies that promote early closure of ductus arteriosus without serious adverse effects. Methods Literature in English was searched selectively focusing on the potential of using acetaminophen for early closure of the ductus. Results Prophylactic ibuprofen or indomethacin intended to close the ductus, predisposes infants to ischaemia, bleeding and immune dysfunction. Acetaminophen appears to have a similar efficacy as indomethacin or ibuprofen, and all three dose-dependently constrict the ductus. Ibuprofen and indomethacin cause non-specific inhibition of prostaglandin synthesis, while acetaminophen predominantly inhibits prostaglandin E synthesis. Owing to low CYP450 activity in infancy, acetaminophen toxicity has been rarely evident. However, increasing the dosage increases the oxidative stress. We review prophylactic treatments that may increase the safety and efficacy of acetaminophen. These include vitamin A, cysteine and glutamine, and low-dose corticosteroid supplementation. Conclusion The current challenge is to define a safe perinatal management practice that promotes cardiorespiratory adaptation in immature infants, particularly the seamless closure of the ductus before significant cardiopulmonary distress develops.

Automated summary

The aim is to find optimal management strategies for early closure of patent ductus arteriosus without serious adverse effects. Although acetaminophen shows similar efficacy as ibuprofen or indomethacin in constricting the ductus, careful dosage control is necessary to prevent toxicity. Prophylactic treatments such as vitamin A and low-dose corticosteroid supplementation may enhance the safety and efficacy of acetaminophen.