Page 144 - Physiological based CPAP for preterm infants at birth Tessa Martherus

General discussion
There have been a few experimental studies investigating the effect of CPAP/PEEP in intubated preterm animals at birth. CPAP levels were investigated in intubated preterm lambs at birth, demonstrating that 8 cmH2O CPAP improves lung function and oxygenation when compared to 5 cmH2O (24). Studies in intubated and ventilated preterm rabbits demonstrated that with decreasing gestational age higher PEEP levels (10 cmH2O instead of 5 cmH2O) are needed for establishing lung aeration (18, 25-27). In intubated preterm sheep it was shown that increasing PEEP levels to max 20 cmH2O improves lung function when compared to a static PEEP levels of 5 cmH2O (28). In a clinical setting, increasing CPAP is known to positively affect lung function of preterm infants who are admitted to the NICU hours to days after birth (29-32). While there are no clinical studies on CPAP levels at birth, centres that use PEEP levels of 6-15 cmH2O during mask ventilation at birth have reported a reduction in intubation and mechanical ventilation in the DR when compared to a historical control where 4-5 cmH2O PEEP was used (33-35).
There were also concerns in using higher pressure levels at birth. When high intra-thoracic pressures are given to preterm infants on the NICU hours to days after birth, this can potentially over-expand the lungs and compromise cardiac output (36-38). Indeed, pulmonary blood flow (PBF) was reduced when 8-12 cmH2O CPAP/PEEP was applied to intubated preterm lambs during 10-20 min after birth and levels higher than 8 cmH2O increased the risk of pneumothoraxes (24, 39-42). There were however no adverse effects observed in preterm infants when 6-15 cmH2O PEEP was used in the DR (33-35). It is possible that CPAP/PEEP levels up to 15 cmH2O do not cause adverse events during the initial process of establishing aeration, but that maintaining pressures above 8 cmH2O after aeration has been established may lead to over-expansion of the lungs.
In Chapter 2 we reported our findings of a retrospective comparison study, in which we compared the CPAP strategies for preterm infants at birth of two neonatal centers. In this study we observed that oxygen saturation (SpO2) in the first minutes was not different when 12-35 cmH2O or 5-8 cmH2O CPAP was used. It is likely that other factors influenced oxygen saturation, such as breathing effort and that the larynx hampered the respiratory support (4-7). Once the fraction of inspired oxygen (FiO2) levels were increased in the 5-8 cmH2O group, these infants achieved higher SpO2 compared to those supported with 12-35 cmH2O CPAP. Because gas exchange (as reflected by SpO2/FiO2 ratios) remained similar between groups and FiO2 was increased in the 5-8 cmH2O but not in the 12-35 cmH2O group, we can assume that higher CPAP levels facilitated the increased in lung aeration that was needed to attain similar SpO2/FiO2 ratios.
We did not observe signs of over-expansion of the lungs leading to cardiac output compromise in the 12-35 mH2O CPAP cohort, as heart rate was similar in both groups the first ten minutes after birth. However, there was a non-significant increase in pneumothoraxes in the 12-35 cmH2O group (early 4 vs 11%; ns, during admission4 vs 19%; ns). When these pneumothoraxes occurred and the factors that may have contributed remains unclear. This
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