Differential effects of ibuprofen and indomethacin on cerebral oxygen kinetics in the very preterm baby.

Background: Ibuprofen is preferred to indomethacin for treatment of a significant patent ductus arteriosus (PDA) in preterm babies despite indomethacin being associated with a lower risk of intraventricular haemorrhage. This difference is thought to relate to the discrepant effects of each medication on cerebral oxygen kinetics yet the effect of ibuprofen on cerebral perfusion is uncertain. Methods: Forty-eight babies < 30 weeks with a significant PDA, defined by echocardiography, were randomly assigned to either indomethacin or ibuprofen (n = 24 per group) and stratified by gestation and chronologic age. Cerebral blood flow [total internal carotid blood flow (TICF)] and oxygen physiology [oxygen delivery (modCerbDO2) and consumption (modCerbVO2)] were measured using cranial Doppler ultrasound and near-infrared spectroscopy, and cerebral oxygen extraction (cFTOE) calculated, immediately before and following administration. Temporal and treatment related changes were analysed. Results: A fixed effect of time was seen for TICF (p = 0.03) and therefore modCerbDO2 (p = 0.046) and cFTOE (p = 0.04) for indomethacin alone. In the indomethacin group, TICF and modCerbDO2 fell from baseline to 5 and 30 min respectively (TICF p < 0.01, cDO2 p = 0.01) before increasing from 5 min to 24 h (p < 0.01) and 30 min and 24 h (p < 0.01) timepoints. cFTOE peaked at 30 min (p = 0.02) returning to baseline at 24 h. There was a parallel increase in arterial lactate. Conclusion: Indomethacin significantly reduces cerebral blood flow soon after administration, resulting in a parallel increase in oxygen extraction and arterial lactate. This implies that the balance of oxygen kinetics at the time of treatment may be critical in very preterm babies with significant PDA.

Determining the venous oxygen reservoir: A novel, hypothetical approach to titration of supplemental oxygen in preterm newborns.

While normal oxygen saturation is commonly thought to be a marker of normal oxygenation, cutaneous saturation does not account for the sufficiency of oxygen within each cell or that of the system overall. Rather, cutaneous oximetry simply defines the saturation of haemoglobin (Hb) with oxygen in a pulsatile vessel. Assessment of sufficiency is best determined by measurement of the amount of oxygen left over following aerobic respiration. This left over oxygen is 'stored' on Hb in the venous compartment and can be calculated as the venous oxygen content. We hypothesize that the development of a venous oxygen content or saturation reference range in a group of well, uninjured very preterm newborns and subsequent application, in a randomised trial, with a structural, functional and molecular outcome will resolve the method for assessment of oxygen sufficiency in preterms by demonstrating both clinical safety and effectiveness. This method could be subsequently used for titration of supplemental oxygen.