Page 146 - Physiological based CPAP for preterm infants at birth Tessa Martherus

General discussion
then initiates a vagal reflex that facilitates a global pulmonary vasodilation and a subsequent increase in PBF and heart rate (43, 44).
The finding that PB-CPAP improves lung aeration is in line with previous studies (18, 24-28). However, it remains difficult to compare spontaneous breathing animal models with intubated animals. When intubated, pressures were immediately transmitted to the lungs, which is substantially different from non-invasive CPAP wherein the larynx and upper airway is included in the respiratory circuit. Indeed, in preterm sheep (Chapter 4) we observed that 15 cmH2O CPAP was partially (~75%) transmitted below the trachea, whereas 5-8 cmH2O CPAP was fully transmitted to the lungs. This suggest that the larynx regulates pressure transmission to the lungs during spontaneous breathing. We suspect that higher CPAP levels may provoke volume receptors in the lung that initiate a Hering-Breuer reflex (45, 46) that prevents over-expansion of the lung.
Oxygenation
We hypothesized that the increase in lung aeration would occur concomitantly with an increase in oxygenation and decrease in oxygen requirement, as oxygenation depends on the lung’s surface area available for gas exchange and the oxygen gradient for O2. In preterm lambs (Chapter 4), a static 15 cmH2O CPAP tended to increase SaO2 and reduce FiO2 when compared to 5 cmH2O. The decrease in CPAP levels always caused an increase in FiO2 requirement, which indicates that the timing when to decrease the CPAP level is crucial and in this experiment we may have decreased the CPAP level too soon. In our study in preterm infants (Chapter 5), it remains difficult to test whether CPAP affect SpO2, as the high FiO2 given to most preterm infants has a dominating effect on SpO2. However, it was possible to decrease FiO2 sooner in the BP-CPAP. While aeration is likely to positively affect SpO2, the relative contribution of lung aeration versus the gradient for oxygen diffusion is complex and influenced by other factors e.g. PBF, cardiac output. We speculate that in the clinical trial examining the benefits of PB-CPAP (Chapter 5), the use of high FiO2 levels may have masked the effect of PB-CPAP on SpO2.
Breathing effort
We evaluated the effect of CPAP levels on breathing effort, i.e. apnea, minute volume and/or rate of breathing. While we evaluated the occurrence of apnea (indicated by iPPV), the studies in this thesis were powered to detect differences in continuous outcomes and groups were too small to detect statistical differences in binary outcomes. In preterm rabbits (Chapter 3) we observed that higher CPAP levels reduce the incidence of apnoea, as this was more present in rabbits supported with initial CPAP pressures ≤ 8 cmH2O (36-46%) compared to those receiving 12-15 cmH2O (16-20%). Similarly, in our preterm lamb study the incidence of apnoea was higher with 5 cmH2O (83%) as compared to 15 (17%) cmH2O CPAP (Chapter 4). We concluded that initial higher CPAP levels decrease the risk of apnea. The limited number of included infants and unbalanced occurrence of hypoxia immediately at birth did not allow
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