Page 93 - Physiological based CPAP for preterm infants at birth Tessa Martherus

Introduction
High-CPAP does not impede cardiovascular changes at birth in preterm sheep
Respiratory support for preterm infants at birth has shifted from intubation and mechanical ventilation toward non-invasive strategies (1-4). However, when applied non-invasively, intermittent positive pressure ventilation (iPPV) is unable to ventilate the lung if the larynx is closed, which is known to occur in the fetus and newborn during apnea (5-8). As such, attention has now focused on stimulating and supporting spontaneous breathing at birth using continuous positive airway pressure (CPAP) (9-11). This has highlighted a knowledge gap regarding how CPAP should be applied in the delivery room. Currently, 4-8 cmH2O of CPAP is widely adopted, but this has been extrapolated from strategies used in the neonatal intensive care unit as there is little scientific evidence to support this pressure range at birth (12, 13).
To optimize CPAP support for preterm infants at birth, the underlying physiology of the infant
needs to be considered as it transitions to newborn life. During pregnancy, the airways are liquid-filled and pulmonary blood flow (PBF) is low and so at birth, the airways must be cleared
of liquid to allow the entry of air and PBF must increase to facilitate the onset of pulmonary
gas exchange (14-18). Lung aeration triggers a decrease in pulmonary vascular resistance
(PVR) and increase in PBF (19, 20), which is critical for the maintenance of cardiac output after 4 birth, as PBF must take over the role of providing preload for the left ventricle following cord
clamping (17).
As transpulmonary pressures generated by inspiration drive lung aeration after birth, increasing this pressure gradient could assist spontaneously breathing newborns aerate their lungs (18, 21, 22). This can be achieved by applying CPAP, but the optimal CPAP strategy is unknown. As airway resistance is initially high, due to the high viscosity of airway liquid (23, 24), theoretically, a high-CPAP will help overcome the initial high resistance of the liquid-filled airways. However, as the lungs aerate the resistance reduces and so the required CPAP level may also reduce (18, 22-25). Thus, a CPAP strategy that starts high and then decreases could reflect a changing physiological role for CPAP at birth. Initially CPAP may assist with lung aeration, but as the lung aerates and liquid is replaced by air, the role of CPAP could change to preventing liquid re-entry and alveolar collapse (18, 22-25). However, high airway pressures have been associated with pulmonary overexpansion, pneumothoraxes, reductions in cardiac output and PBF as well as elevated central venous pressures in (preterm) infants (26-28), adults (29-32), and animals (33-36).
Indeed, while high positive end-expiratory pressures (PEEP) enhance lung aeration and oxygenation and can reduce intubations and surfactant requirements in preterm infants (37), they also reduce PBF and increase the risk of pneumothoraxes in intubated and mechanically ventilated animals (38-42). As the application of CPAP during spontaneous breathing and PEEP during mechanical ventilation may have different effects on lung physiology, it is important to understand how high-CPAP levels affect lung physiology during spontaneous
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