Pain Treatment of Newborns: Paracetamol Rectal Versus Intravenous Administration, A Randomised Open Clinical Trial

Abstract

Background and aim: Early recognition and treatment of pain is of great importance in the neonatal period. Paracetamol is the most frequent prescribed medicine for pain treatment. Administration of rectal paracetamol has limitations and the effectiveness can be variable in neonates. This study is based on the hypothesis that intravenous (iv) paracetamol is well tolerated, less variable and therefore more reliable in preterm neonates compared to rectal paracetamol. We therefore compared the effectiveness of intravenous and rectal administration in (preterm) neonates during a period of sickness accompanied by pain. Methods: We included 21 neonates with pain, post menstrual age (PMA) of 28-44 weeks. They received paracetamol rectal or intravenous according to Dutch guidelines. Serum concentrations at steady state (t = 0, 0.5, 1, 2, 4, 6 hours) were determined. Results: Clearance was dependent of weight, not of PMA. Estimated mean serum concentrations after four administrations were 4,8 ± 0,7, 8,1 ± 1,9 and 10,2 ± 3,1 mg/L and after rectal administration 4,1 (n=1), 12,6 ± 6,0 and 14,0 ± 6,7 mg/L. Hepato- or renal dysfunction were not observed. Conclusion: Rectal and intravenous administration of paracetamol is well tolerated in (preterm) neonates. Rectal administration gives no paracetamol absorption or a major variation with inter- and intra-individual variation, which turns out to be unreliable especially in (pre)term neonates. Dosing of paracetamol (rectal and iv) should be based on weight instead of PMA. Further research is needed to define the exact dosing regime and target concentration of intravenous paracetamol in (preterm) neonates in comparison to the pain experience especially in preterm neonates.