Spatiotemporal Aeration and Lung Injury Patterns Are Influenced by the First Inflation Strategy at Birth

Abstract

Ineffective aeration during the first inflations at birth creates regional aeration and ventilation defects, initiating injurious pathways. This study aimed to compare a sustained first inflation at birth or dynamic end-expiratory supported recruitment during tidal inflations against ventilation without intentional recruitment on gas exchange, lung mechanics, spatiotemporal regional aeration and tidal ventilation, and regional lung injury in preterm lambs. Lambs (127 ± 2 d gestation), instrumented at birth, were ventilated for 60 minutes from birth with either lung-protective positive pressure ventilation (control) or as per control after either an initial 30 seconds of 40 cm H2O sustained inflation (SI) or an initial stepwise end-expiratory pressure recruitment maneuver during tidal inflations (duration 180 s; open lung ventilation [OLV]). At study completion, molecular markers of lung injury were analyzed. The initial use of an OLV maneuver, but not SI, at birth resulted in improved lung compliance, oxygenation, end-expiratory lung volume, and reduced ventilatory needs compared with control, persisting throughout the study. These changes were due to more uniform inter- and intrasubject gravity-dependent spatiotemporal patterns of aeration (measured using electrical impedance tomography). Spatial distribution of tidal ventilation was more stable after either recruitment maneuver. All strategies caused regional lung injury patterns that mirrored associated regional volume states. Irrespective of strategy, spatiotemporal volume loss was consistently associated with up-regulation of early growth response-1 expression. Our results show that mechanical and molecular consequences of lung aeration at birth are not simply related to rapidity of fluid clearance; they are also related to spatiotemporal pressure-volume interactions within the lung during inflation and deflation.

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

“…In our study using intubated preterm lambs, we systematically describe the interrelationship between the use of antenatal corticosteroids, exogenous surfactant therapy, and two distinct recruitment strategies applied Unlike previous animal studies of respiratory care at birth (6,(10)(11)(12)15,16,(20)(21)(22)(27)(28)(29)(30), our study involved a large sample size. Pooling all epochs, the use of an OLV stepwise PEEP approach significantly improved C dyn and oxygenation compared to a 30-s 40 cmH 2 O SI.…”

“…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).…”

“…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). In preterm animals, using an initial stepwise PEEP or open lung ventilation (OLV) approach during tidal ventilation from birth improves aeration and short-term respiratory outcomes in preterm animals via utilizing hysteresis and time dependency (6,11). However, clinical trials at birth are lacking.…”

“…This study was a priori designed as part of a 3-y program of nested studies examining the role of inflating pressure (SI) and stepwise PEEP approaches (OLV) on regional aeration, lung mechanics, and lung injury. Some of the detailed individual injury and physiological data have been reported separately (6,11).…”