P27 Paracetamol levels following intravenous therapy for closure of patent ductus arteriosus

Introduction Paracetamol is increasingly used for the treatment of a haemodynamically significant patent ductus arteriosus (PDA) in preterm infants when ibuprofen is contraindicated.1 The local regimen consists of a 20 mg/kg loading dose, followed by an initial maintenance dose of 12.5 mg/kg or 15 mg/kg QDS, depending on gestation and age. The dose may be adjusted according to levels taken before each third maintenance dose. The target level is 15–25 mg/L, with dose reduction if > 25 mg/L and discontinuation if > 40 mg/L. This is the same regimen followed in other neonatal intensive care units (NICU), but not all NICUs monitor levels. The literature1 suggests there is doubt that the therapeutic drug concentration of paracetamol is a marker of its safety or efficacy. One study2 of paracetamol levels at a NICU using the above regimen found that all levels were within the target range, so no dose reductions were required. The aim of this study is to establish whether our levels are within the target range in order to guide the decision on whether to continue monitoring levels. Method Babies receiving intravenous paracetamol for PDA closure between November 2021 and May 2023 were identified using the BadgerNet EPR database. Their medical notes were obtained to review their paracetamol prescription chart, and paracetamol levels and plasma transaminases were viewed on the electronic reporting system. Results Thirty courses of intravenous paracetamol were administered to twenty-six babies. Median gestation at birth was 24+4 weeks (range 23+4–31+2). At initiation of paracetamol median corrected gestational age was 27+1 weeks (range 24+3–31+6). A total of 170 paracetamol levels were measured. The median paracetamol level was 21 mg/L (range 25 mg/L, 73(43%) were within the range of 15–25 mg/L and 34(20%) were 40 mg/L; therefore, paracetamol treatment was discontinued. Of the thirty courses of paracetamol, eight did not require any dose reduction, five required one dose reduction, seven required two dose reductions, eight required three dose reductions, and two required four dose reductions. In total, 51 dose reductions were performed. Following dose reduction, the paracetamol level continued to rise in 11 courses and remained static above 25 mg/L in two courses. Conclusion Overall, 51% of the paracetamol levels were outside the target range, with 31% > 25 mg/L and 20% 25 mg/L did not show clinical signs of toxicity or had significantly elevated plasma transaminase levels. The patient population was comparable to that in the study2 where levels were all within the target range. Therefore, further work needs to be done to establish why our levels are higher than those in the published study2 before we can decide to discontinue monitoring levels. References Gupta A, Mukherjee A. Do we know how to treat PDA with paracetamol? Current evidence on the pharmacokinetics and pharmacodynamics of paracetamol for hsPDA closure in extreme preterm infants. Infant 2021;17:186–193. Mulholland P, Heuchan A. Paracetamol levels following intravenous therapy in neonates less than 28 weeks gestation. Arch Dis Child 2018;103:e1.