Related Experiment Videos
Comparative tolerability of pharmacological treatments for patent ductus arteriosus
1Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel. cathy@cc.huji.ac.il
Insights
The ductus arteriosus normally closes after birth, but premature infants often experience delayed closure (patent ductus arteriosus). This review examines pharmacological treatments like indomethacin and ibuprofen for managing this condition.
Area of Science:
- Neonatal Physiology
- Pharmacology
- Cardiovascular Medicine
Background:
- The ductus arteriosus is crucial for fetal circulation but must close postnatally.
- Premature infants frequently exhibit delayed or ineffective ductal closure, leading to patent ductus arteriosus (PDA).
- Understanding the biochemical control of normal ductal closure is key to managing PDA.
Purpose of the Study:
- To review current knowledge on the control of normal ductal closure.
- To focus on pharmacological strategies for preventing and treating patent ductus arteriosus in premature infants.
- To compare the efficacy and side effects of indomethacin and ibuprofen for PDA treatment.
Main Methods:
- Review of existing literature on ductal closure mechanisms and pharmacological interventions.
- Analysis of indomethacin's role, including antenatal tocolytic use and prophylactic administration.
- Examination of novel therapeutic approaches and newer agents like ibuprofen for PDA.
Main Results:
- Antenatal indomethacin can transiently constrict the ductus arteriosus, potentially hindering later closure.
- Prophylactic indomethacin may reduce PDA risk while primarily preventing intraventricular hemorrhages.
- Continuous infusions and prolonged maintenance doses of indomethacin are explored to minimize side effects and prevent recurrence.
- Ibuprofen shows promise as an alternative with potentially fewer vasoconstrictive adverse effects compared to indomethacin.
Conclusions:
- Pharmacological interventions are essential for managing patent ductus arteriosus in premature neonates.
- Indomethacin remains a standard treatment, but its use requires careful consideration of timing and administration.
- Ibuprofen represents a promising alternative with a potentially improved safety profile for treating PDA.
Abstract:
The ductus arteriosus is a vascular channel which, although vital to the fetal circulation, rapidly becomes unnecessary and even deleterious after birth. As such, it is 'preprogrammed' to constrict within the first few hours of life. In infants born prematurely this natural closure is often delayed and/or ineffective. In this review, we summarise the current knowledge of the delicately orchestrated control of normal ductal closure, with emphasis on the role of various biochemical mediators. The major focus of this review, however, is on pharmacological approaches designed to prevent and/or treat the persistently patent ductus arteriosus (PDA) which often fails to constrict spontaneously in the premature infant. The standard treatment regimen is based on the administration of 3 doses of the nonselective cyclo-oxygenase inhibitor, indomethacin. We begin by examining, from the vantage point of the ductus, the use of this indomethacin as a tocolytic. It seems that antenatal administration of indomethacin can cause transient, reversible ductus constriction which renders the post-treatment ductus resistant to subsequent closure, both natural and therapeutic. We then review some of the pros and cons associated with the prophylactic administration of indomethacin. Although prophylactic indomethacin is aimed primarily at preventing intraventricular haemorrhages in premature neonates, it does tend to reduce the risk of PDA as well. We then describe some novel therapeutic approaches to effect ductal closure with indomethacin, including the use of continuous infusions to minimise toxic vasoconstrictive phenomena and the use of prolonged maintenance dose to prevent PDA recurrences. Finally we discuss some of the newer agents described more recently which play a role in closing the persistently patent ductus over the next decade. Most prominent of these is ibuprofen which some studies have shown to have less undesirable vasoconstrictive adverse effects. Studies which compare the use of ibuprofen to indomethacin are summarised.