Subgroup analysis of the early paracetamol trial to preterm infants found haemodynamic changes and improved oxygenation

Abstract

Background: We previously reported in a randomised trial that early intravenous paracetamol accelerated contraction of ductus arteriosus in very preterm infants (<32 gestation weeks).

Aims: To monitor sequentially paracetamol effects on the blood pressure and brain tissue oxygenation in the infants participating the trial.

Methods: In a double-blind trial, intravenous paracetamol or placebo was infused to 48 very premature infants starting within 24 h of birth for four days. Besides the ductus arteriosus, we systematically measured blood pressure, peripheral (spO₂) and regional cerebral oxygen saturation (rcSO₂), and cerebral fractional tissue oxygen extraction (cFTOE) during the study period.

Results: Compared to the placebo, the paracetamol loading dose transiently decreased the arterial blood pressure. During treatment, the paracetamol-treated infants had higher spO₂ (p = .042) and rcSO₂ (p = .036) values than the placebo group infants. Additionally, the cFTOE values were lower in the paracetamol group during the study without statistical significance. All infants with closed ductus had higher tissue oxygenation and a lower cFTOE than infants with open ductus.

Conclusions: Paracetamol caused modest haemodynamic effects and increased cerebral oxygenation. They were mostly due to early contraction of ductus. Additional direct drug-effects in brain are not ruled-out.

Keywords: Acetaminophen; Blood pressure; Near-infrared spectroscopy; Pain/drug therapy; Patent ductus arteriosus.