Subgroup analysis of the early paracetamol trial to preterm infants found haemodynamic changes and improved oxygenation. (June 2020)

• Record Type: Journal Article
• Authors: Härmä, Antti; Aikio, Outi; Härkin, Pia; Leskinen, Markku; Valkama, Marita; Saarela, Timo; Hallman, Mikko
• Is Part Of: Early human development. Volume 145(2020)
• Publication Date: 2020-06
• Subjects: cFTOE cerebral fractional tissue oxygen extraction -- MAP mean arterial pressure -- NIAPAS neonatal infant acute pain assessment score -- NICU neonatal intensive care unit -- NIRS near-infrared spectroscopy -- PDA patent ductus arteriosus -- rcSO2 regional cerebral oxygen saturation -- paCO2 partial pressure of arterial carbon dioxide -- PreParaS Premature infants' Paracetamol Study -- spO2 peripheral transcutaneous arterial oxygen saturation -- VLGA very low gestational age; Acetaminophen -- Blood pressure -- Near-infrared spectroscopy -- Patent ductus arteriosus -- Pain/drug therapy; Fetus -- Periodicals; Neonatology -- Periodicals; Prenatal influences -- Periodicals; 612.65
• DOI: 10.1016/j.earlhumdev.2020.105042
• Languages: English
• ISSNs: 0378-3782

Abstract

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. Highlights: In a previous trial, early intravenous paracetamol accelerated contraction of the ductus arteriosus in preterm infants. Shortly after premature birth, it caused an acute but modest decrease in blood pressure that remained stable during follow-up. During maintenance, cerebral oxygenation improved, possibly due to early ductal closure or effects into central nervous system.