Establishing Functional Residual Capacity at Birth: The Effect of Sustained Inflation and Positive End-Expiratory Pressure in a Preterm Rabbit Model

Abstract

The effect of a 20 s sustained inflation (SI) and positive end-expiratory pressure (PEEP) on functional residual capacity (FRC) formation at birth were investigated. Preterm rabbit pups (28 d) were randomized at birth into four groups (n = 6 for each): 1) SI, PEEP 5 cm H2O, 2) no SI, PEEP 5 cm H2O, 3) no SI + no PEEP, 4) SI + no PEEP. FRC and tidal volume (Vt) were measured by plethysmography and uniformity of lung aeration by phase contrast x-ray imaging. Ventilation with a SI and PEEP uniformly aerated the lung and Vt and FRC were recruited by the first tidal inflation. Ventilation without a SI, with PEEP, gradually recruited Vt and FRC with each inflation but aeration was not uniform. Ventilation without a SI or PEEP, gradually recruited Vt, but no FRC. Ventilation with a SI, without PEEP, uniformly aerated the lung and recruited Vt but no FRC. FRC was greater with SI (p = 0.006) during the first minute, but was larger with PEEP than without PEEP throughout the first 7 min (p < 0.0005). Effects of PEEP and SI were additive. In ventilated preterm rabbits at birth, combining a SI and PEEP improved FRC formation and uniformity of lung aeration, but PEEP had the greatest influence.

The interrelationship of recruitment maneuver at birth, antenatal steroids, and exogenous surfactant on compliance and oxygenation in preterm lambs

“…A SI focuses on the initial fluid clearance and aeration but its value depends on subsequent respiratory management maintaining aeration. PEEP is essential in the preterm lung (5,14). In our study, we used a PEEP (8 cmH 2 O) previously shown to be appropriate in preterm lambs (6,11,16,17), and higher than that used in similar animal studies (5,9,10,14,15,20,29), suggesting our results are due to differences in recruitment strategy and not subsequent ventilator management.…”

“…To achieve lung aeration at birth, and then maintain recruitment and tidal ventilation, a recruitment strategy needs to overcome specific the mechanical and time constant constraints of the respiratory system (1,6,23). Practically, this requires an adequate inflating pressure and/or PEEP to be applied for a sufficient duration to achieve volume change (5,9,23). The preterm lamb is known to require a longer and higher inflating pressure to achieve lung aeration (10,13,20,23) than has been advocated in human trials (19,25).…”

“…The most widely examined intentional recruitment maneuver at birth is the use of an initial sustained inflation (SI) to clear fetal lung liquid from the airways (18,19). Preclinical experimental studies of SI have been mixed (5,6,(9)(10)(11)20), with an increase in lung injury reported in some studies (21-23). Improved short-term respiratory outcomes have been reported in some clinical trials (24,25), although without long-term benefits, and an increased risk of patent ductus arteriosus (19).…”

“…During this period, the infant must rapidly clear lung liquid, aerate the lung, establish a functional residual capacity, and commence tidal ventilation, processes influenced by the intrinsic mechanical properties of the lung as well as the applied respiratory strategy (5,6,(9)(10)(11)(12)(13). The optimal approach in preterm infants remains unclear but broadly requires an inflating pressure to drive fetal lung fluid into the alveoli and allow lung aeration, and positive end-expiratory pressure (PEEP) to maintain aeration and prevent fluid efflux back into the airways (14)(15)(16)(17).…”

Establishing lung gas volumes at birth: interaction between positive end-expiratory pressures and tidal volumes in preterm rabbits

“…This creates a pressure gradient that facilitates the movement of liquid across the distal airways into the surrounding tissue (19), from where it is cleared (13,20). Because hydrostatic pressure gradients facilitate lung aeration, we investigated the effect of PEEP and sustained inflations on lung aeration at birth in preterm rabbits (9,21,22) using synchrotron-based imaging techniques (23). These studies demonstrated that both pressure and the time over which the pressure is applied (pressure-time integral) are important for facilitating and maintaining FRC immediately after birth.…”