Page 51 - Physiological based CPAP for preterm infants at birth Tessa Martherus

Comparison of two respiratory support strategies for stabilization of very preterm infants at birth
Introduction and rationale
Most very preterm infants require respiratory support in the delivery room, as they are unable
to adequately aerate their lungs (1-5). Historically, infants were intubated directly after birth
and respiratory support was given by mechanical ventilation with pure oxygen. In recent years
the focus of respiratory support has shifted toward a gentler approach, focusing on supporting spontaneous breathing and titrating the inspired oxygen content to reduce
hypoxia to quickly achieve target oxygen saturation values (6-8). A non-invasive approach is
now recommended that uses either continuous positive airway pressure (CPAP) and/or
positive pressure ventilation (PPV), combined with ambient or a blended air/oxygen gas
mixture (9-11). Yet, there is a wide diversity in clinical practice and very little data is available
on the most effective approach to support preterm infants during the cardiopulmonary 2 stabilization (12).
In preterm infants, the presence of breathing effort can often be missed during the initial evaluation, resulting in the application of PPV within the first minutes followed by CPAP once the infant is stabilized. CPAP pressures of 4-8 cmH2O are currently recommended in the delivery room (9, 10), although preclinical studies (13-18) have indicated that higher positive end-expiratory pressures (PEEP) may be beneficial during mechanical ventilation. Higher PEEP levels improve lung liquid clearance and lung aeration, thereby maintaining functional residual capacity (18). As such, higher CPAP levels may also improve liquid clearance and lung aeration, which may also improve pulmonary blood flow, heart rate and oxygenation and reduces the need of supplemental oxygen and PPV. On the other hand, high CPAP levels could over expand the lungs, thereby increasing the risk on pneumothoraxes (14, 15), reduce pulmonary blood flow (13, 15, 16) and breathing rate (19).
International guidelines (9-11) nowadays recommend commencing respiratory support with air or using a fraction of inspired oxygen (FiO2) content of 0.3, blended with air. The FiO2 can then be increased to achieve oxygen saturation (SpO2) values within the ranges depicted by the Dawson’s nomogram (20). Most infants (90-100%) with very low birth weight and preterm infants require an increase in FiO2 to increase oxygen saturation and avoid hypoxemia (21, 22) which has dangerous consequences. Indeed, data from eight randomized clinical trials showed that infants who did not reach an SpO2 of 80% at 5 min after birth, were more at risk to die before hospital discharge and to develop major intraventricular hemorrhages (23). However, supplemental oxygen increases the risk of hyperoxemia (22, 24). Due to the immaturity of the anti-oxidant defense systems, supplemental oxygen can lead to an excess of free oxygen radicals causing damage in multiple organs, thereby developing e.g., bronchopulmonary dysplasia and retinopathy of prematurity (25, 26). The control of oxygen during the neonatal stabilization should therefore be handled accurately to minimize the risk of hypoxemia while avoiding hyperoxemia. Several clinical trials have compared initiation of resuscitation with low vs. high oxygen levels, with a recent large clinical trial (27) finding a higher mortality rate when initiating resuscitation with FiO2 0.21, compared to FiO2
P
47
r