574 - Early intravenous paracetamol for pain treatment in very preterm infants: A randomized clinical trial.

Publication Number: 574.4876

Tiina M. Ukkonen, Oulu University Hospital, Oulu, Pohjois-Pohjanmaa, Finland; Outi Aikio, Oulu Univeristy Hospital, Oulu, Pohjois-Pohjanmaa, Finland; Mikko Hallman, University of Oulu, Oulu, Pohjois-Pohjanmaa, Finland; Antti Härmä, Lapland Central hospital, Rovaniemi, Lappi, Finland

Background: Very low gestational age infants’ (gestation < 32wk, VLGA) early intensive care may require painful and invasive treatments. The standard pain medication in VLGA infants, morphine, was shown to cause severe adverse effects in premature infants (Anand, 2004). Previously, intravenous (iv) paracetamol was found to be safe, but no prospective evidence of its efficacy as pain medication in preterm infants is available (Härmä, 2016). We hypothesized that early iv paracetamol decreases the need for morphine and lowers pain scale scorings in VLGA infants.

Objective: To study the efficacy and safety of iv paracetamol for pain treatment in intubated VLGA infants.

Design/Methods: In the present Premature infants’ Paracetamol Study (PreParaS, EudraCT 2013-001842-33, NCT01938261), intubated VLGA infants were randomly assigned to iv paracetamol (loading dose 20mg/kg, maintenance 7.5mg/kg q6h) or placebo (0.45% NaCl) within 24h from birth for 4d. Morphine was given as needed, based on infants’ pain scale scorings and clinical symptoms. The primary outcome was the decrease in the need for morphine medication. Secondary outcomes included pain scale scorings, duration of mechanical ventilation, paracetamol adverse effects, long-term morbidities, and mortality.

Results: From IX/2013 to VIII/2024, 129 infants were randomized, 67 to paracetamol and 62 to placebo, in the Neonatal Intensive Care Unit of Oulu University Hospital, Oulu, Finland. Baseline data were similar between the two groups (Table). After randomization, one infant was excluded due to chromosomal anomaly and one died early, both from the placebo group. During the study drug, 50 (80.1%) infants in the paracetamol group and 49 (73.1%) infants in the placebo group received morphine (Table). Paracetamol group infants received fewer doses and smaller dosages of morphine, although no statistical difference was reached. However, after the four-days study drug period, the paracetamol group had significantly lower cumulative sum of morphine doses compared to the placebo group, n=238 vs. n=283, P=.032 (Kaplan-Meier Hazard function; Figure). No harmful paracetamol effects were detected. Long-term morbidities and mortality did not differ. The pain scale scoring analysis is continuing.

Conclusion(s): In present randomized, placebo-controlled trial, paracetamol decreased the need for morphine medication in intubated VLGA infants during the early neonatal intensive care. No adverse effects were observed. Larger studies are needed to show the efficacy on the individual patients.

Table: Baseline data and outcomes by study groups
241104_Table.pdf

Figure: Cumulative sum of morphine doses during the study drug
241104_Figure.pdf