Prophylactic low-dose paracetamol administration associated with lowered rate of patent ductus arteriosus in preterm infants – Impact on outcome and pain perception

Abstract

Background: To determine the rate of patent ductus arteriosus after prophylactic low-dose paracetamol administration, the impact on outcome parameters, possible treatment side-effects and the influence on pain perception. Methods: We report retrospective single-centre outcome data of premature infants ≤ 32 weeks of gestation (n = 476). The intervention group received intravenous paracetamol, the control group obtained no preventive therapy. Ductal closure rate and outcome parameters were compared between the two groups. Adverse effects were determined by laboratory parameters. For the assessment of pain the Bernese Pain Scale for Neonates was used. Results: The rate of patent ductus arteriosus was significantly lower in the paracetamol-treated group compared to the control group (13.6% vs. 38.2%, p < 0.001). With regard to secondary outcome parameters, severe and moderate bronchopulmonary dysplasia (2.7% vs. 7.4%, p = 0.023), severe retinopathy of prematurity (0% vs. 4.4%, p = 0.002) and late onset sepsis (2.7% vs. 8.3%, p = 0.009) were significantly less frequent in the paracetamol group. Except for a 1.5-fold increased risk for hyperbilirubinemia (86.0% vs. 77.6%, p = 0.035) in the paracetamol group following treatment, no significant differences in laboratory parameters were found. Relating to pain, the administration of Glucose 33% was significantly more often necessary in the control group compared to the paracetamol-treated group (mean 13.48 vs. 8.71, p < 0.001), just as the need for additional treatment with systemic analgesics, which was more frequent in the control group (mean 0.72 vs. 0.57, p = 0.361). Conclusion: In our study we were able to show a significantly lower rate of patent ductus arteriosus after prophylactic paracetamol administration without serious adverse effect, but a beneficial influence of this regime on the patient's pain perception. Key Words: paracetamol, patent ductus arteriosus, preterm infants, outcome