Surfactant before the first inflation at birth improves spatial distribution of ventilation and reduces lung injury in preterm lambs

Abstract

The interrelationship between the role of surfactant and a sustained inflation (SI) to aid ex utero transition of the preterm lung is unknown. We compared the effect of surfactant administered before and after an initial SI on gas exchange, lung mechanics, spatial distribution of ventilation, and lung injury in preterm lambs. Gestational-age lambs (127 days; 9 per group) received 100 mg/kg of a surfactant (Curosurf) either prior (Surf+SI) or 10 min after birth (SI+Surf). At birth, a 20-s, 35 cmH2O SI was applied, followed by 70 min of positive pressure ventilation. Oxygenation, carbon dioxide removal, respiratory system compliance, end-expiratory thoracic volume (via respiratory inductive plethysmography), and distribution of end-expiratory volume and ventilation (via electrical impedance tomography) were measured throughout. Early markers of lung injury were analyzed using quantitative RT-PCR. During the first 15 min, oxygenation, carbon dioxide removal, and compliance were better in the Surf+SI group (all P < 0.05). End-expiratory volume on completion of the sustained inflation was higher in the Surf+SI group than the SI+Surf group; 11 ± 1 ml/kg vs. 7 ± 1 ml/kg (mean ± SE) (P = 0.043; t-test), but was not different at later time points. Although neither achieved homogenous aeration, spatial ventilation was more uniform in the Surf+SI group throughout; 50.1 ± 10.9% of total ventilation in the left hemithorax at 70 min vs. 42.6 ± 11.1% in the SI+Surf group. Surf+SI resulted in lower mRNA levels of CYR61 and EGR1 compared with SI+Surf (P < 0.001, one-way ANOVA). Surfactant status of the fetal preterm lung at birth influences the mechanical and injury response to a sustained inflation and ventilation by changing surface tension of the air/fluid interface.

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.…”

“…While many previous preclinical studies of lung recruitment administered surfactant before the first inflation (21,36), our current strategy is more clinically applicable. We have recently shown that there is considerable variability in the spatiotemporal behavior of lung mechanics at birth, even in controlled preclinical experiments (6,12,23). Although our choice of SI parameters is based on previous work (9,10,12,20,27,29), it is likely that some of our lambs required a longer SI duration.…”

“…A Florian Respiratory monitor (Acutronic Medical Systems AG, Hirzel, Switzerland) was used to continuously measure pressure (P AO ), gas flow, and tidal volume (V T ) at the airway opening (6,11,12). Arterial blood gases were performed at 5 min of age and every 15 min from birth.…”

“…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).…”

“…Clinical studies of SI have suggested a reduced need for surfactant replacement following a SI (24)(25)(26). However, in preterm lambs, pretreatment with surfactant improves the lung injury patterns and response to a SI compared with post-SI surfactant (12), suggesting a recruitment maneuver may also influence subsequent respiratory therapies (8). The interplay of Articles antenatal steroids with intentional recruitment maneuvers is even less well understood.…”