264 - Acetaminophen for Patent Ductus Arteriosus in the Neonatal Intensive Care Unit

Patent Ductus Arteriosus (PDA) is the most common cardiovascular abnormality in preterm neonates. The association of PDA with long-term morbidity and mortality is not well defined, resulting in lack of uniform approach in medical and surgical management including timing, mode, dose and duration of therapy. Significant toxicities from widely used drugs, like indomethacin, have resulted in increased usage of acetaminophen in recent years.

Objective:

To examine the effectiveness of acetaminophen therapy in treating PDA and to assess whether the ductal response is related to the serum concentration of acetaminophen, postnatal age of treatment, route and duration of therapy.

Design/Methods:

In this single tertiary center study, we retrospectively evaluated a large cohort of preterm neonates treated with acetaminophen for PDA either as first or second line therapy from 2014 to 2021. Efficacy of acetaminophen therapy was defined as a lack of further need for medical or surgical intervention based on PDA that was closed or trivial. Safety of acetaminophen was evaluated by examining markers of hepatic and renal injury. Correlation between ductal response and serum acetaminophen concentration, route and duration of therapy as well as postnatal age of treatment were evaluated using chi-squared and t-tests.

Results:

Our cohort included 84 neonates with a median gestational age of 26.3 weeks and a median birth weight of 815 grams. 73% babies (n=61)received acetaminophen as first line therapy. Responders to treatment in this group had a mean gestational age, birth weight (BW) and postnatal age of 26.9 weeks, 900g and 7 days respectively compared to non-responders whose mean gestational age, BW and postnatal age were 25 weeks, 685g and 3.5 days respectively.  The median serum acetaminophen concentration was 16.9 mcg/mL in responders and 21.4 mcg/mL in non-responders. Responders received a median of 7 days treatment compared to 14 days treatment in non-responders. 47 neonates (77%) in first line treatment group and 16 neonates (70%) in second line group required no further medical or surgical intervention. Markers of hepatic or renal injury were within normal range. 

Conclusion(s):

Acetaminophen was an effective and safe therapy for PDA both when used as first line medication and as second line medication after drugs like indomethacin failed to close the PDA. When used as first line medication, responders to treatment were significantly heavier, more mature, older in postnatal age, received shorter duration of treatment, and had lower serum acetaminophen concentrations compared to non-responders.