Page 22 - Physiological based CPAP for preterm infants at birth Tessa Martherus

General introduction
When lung aeration has improved and thus the area for gas exchange is expanded, preterm infants will likely sooner reach an increased oxygenation or require less supplemental oxygen. Promoting spontaneous breathing may also reduce the need for iPPV. When the initial high-CPAP is titrated to a lower level following lung aeration, lower CPAP pressures should be able to preserve aeration and sufficiently support spontaneous breathing.
Aim and outline of this thesis
The general aim of this thesis is to test the hypothesis that; (i) high-CPAP levels improve the neonatal transition of preterm infants at birth by enhancing lung aeration and supporting spontaneous breathing, and (ii) a PB-CPAP approach will prevent adverse events caused by pulmonary overexpansion. For this, we have performed studies investigating different CPAP strategies in spontaneous breathing preterm newborns at birth. This thesis includes a literature review of all available evidence, a bench test and retrospective analysis, preclinical studies that allow us to understand the underlying physiology and a single centre randomised controlled trial.
Although most preterm infants receive 4-8 cmH2O CPAP directly at birth via mask or prongs, there is a huge variability in CPAP protocols between centres due to the lack of scientific evidence (53, 65, 72). In Chapter 1 of this thesis, we provide an overview of the scientific evidence available in 2018 on the devices, interfaces and CPAP pressures that are commonly used in the delivery room. In Chapter 2 we describe a striking example of the huge variability in CPAP strategies currently used between centres in Europe. The difference in CPAP protocols (5-8 vs 12-35 cmH2O) allowed us to retrospectively perform a matched-pairs analysis comparing at oxygenation and heart rate, delivery room interventions and short- term clinical outcomes.
To understand the effect of different CPAP pressures on the neonatal transition at birth, we performed two preclinical studies in spontaneously breathing animals directly at birth. In the first experiment we explored the supposed main benefit of higher CPAP pressures, which is on lung aeration. We hypothesised that the application of high-CPAP levels would increase the transpulmonary pressure and enhance lung aeration. To test this hypothesis, we delivered rabbits preterm and provided them mask CPAP directly at birth. The preterm rabbits were assigned to different CPAP pressures (0 vs 5 vs 8 vs 12 vs 15 cmH2O) and CPAP strategies (15 cmH2O continuous vs titrated). By measuring intra-thoracic oesphageal pressure and imaging the preterm rabbits using phase contrast X-ray imaging, the breathing pattern and the degree of lung aeration were analysed. The results of this preclinical experiment can be found in Chapter 3.
18