Page 69 - Physiological based CPAP for preterm infants at birth Tessa Martherus

Background
Higher CPAP levels improve functional residual capacity at birth in preterm rabbits
Respiratory support for preterm infants at birth has recently shifted from intubation and mechanical ventilation towards non-invasive strategies (1-3). Although these strategies are less harmful, the larynx may close during apnoea, which prevents air from entering the lungs when intermittent positive pressure ventilation (IPPV) is applied non-invasively (4-8) This can be avoided by stimulating and supporting spontaneous breathing, which facilitates opening of the larynx (4). While breathing can be enhanced by tactile stimulation, caffeine and 100% oxygen (9-12) this does not necessarily enhance lung aeration (12). To further improve respiratory support at birth, approaches that optimize lung aeration should also be adopted.
The process of lung aeration has been described extensively (13). At birth, the liquid that fills
the airways during pregnancy must be cleared to allow the entry of air and the onset of pulmonary gas exchange. The process of liquid clearance is predominantly driven by transpulmonary pressures generated during spontaneous breathing (14-16). Each inspiration
provides a pressure gradient for the movement of liquid through the airways and across the 3 distal airway wall into lung tissue. As this airway liquid is replaced by air, a functional residual
capacity (FRC) increases stepwise with each inspiration and, in term rabbits, an FRC of 10-15 mL/kg can be established within 3-5 breaths (14, 15) As a result, during lung aeration, lung compliance markedly increases (~100-fold) and airway resistance markedly decreases, which greatly reduces the pressures required to inflate the lung. As this liquid accumulates within the interstitial tissue, it increases interstitial tissue pressures (17), which can result in liquid re-entry into the alveoli at end-expiration (15-19).
Most preterm infants breathe at birth (20, 21) and are supported with continuous positive airway pressure (CPAP). The underlying rationale for this approach is to maintain end-expiratory lung volumes or FRC, because a positive end-expiratory pressure (PEEP) has been shown to maintain FRC in intubated and mechanically ventilated very preterm newborns. Indeed, 5 cmH2O of PEEP improves lung aeration and prevents alveolar liquid re-entry in very preterm rabbits (28/32 days, ~26-28 weeks human gestation (GA)) (22-24). While this PEEP level lies within the pressure range (4-8 cmH2O) widely used for CPAP in the delivery room, it is unknown whether these pressures are optimal for assisting lung aeration in spontaneously breathing infants. For example, a PEEP level of 5 cmH2O is insufficient to maintain FRC in extremely preterm rabbits (27/32 days, ~24 weeks human GA) (24), whereas a PEEP of 10 cmH2O markedly improves FRC and the uniformity of air distribution within the lung (25). Furthermore, in intubated preterm sheep, 8 cmH2O of CPAP enhances lung function and oxygenation compared with 5 cmH2O CPAP (26) and a PEEP recruitment manoeuvre, which involves a stepwise increase and decrease in PEEP, has been shown to markedly improve lung function (27). However, while higher CPAP levels can improve lung function in preterm infants hours, and even up to days after birth (28-31), the use of CPAP in spontaneously breathing infants is markedly different from the use of PEEP during mechanical ventilation in intubated infants. Furthermore, as lung mechanics change dramatically during
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