Effectiveness of individualized lung recruitment strategies at birth: an experimental study in preterm lambs.

Respiratory transition at birth involves rapidly clearing fetal lung liquid and preventing efflux back into the lung while aeration is established. We have developed a sustained inflation (SIOPT) individualized to volume response and a dynamic tidal positive end-expiratory pressure (PEEP) (open lung volume, OLV) strategy that both enhance this process. We aimed to compare the effect of each with a group managed with PEEP of 8 cmH2O and no recruitment maneuver (No-RM), on gas exchange, lung mechanics, spatiotemporal aeration, and lung injury in 127 ± 1 day preterm lambs. Forty-eight fetal-instrumented lambs exposed to antenatal steroids were ventilated for 60 min after application of the allocated strategy. Spatiotemporal aeration and lung mechanics were measured with electrical impedance tomography and forced-oscillation, respectively. At study completion, molecular and histological markers of lung injury were analyzed. Mean (SD) aeration at the end of the SIOPT and OLV groups was 32 (22) and 38 (15) ml/kg, compared with 17 (10) ml/kg (180 s) in the No-RM (P = 0.024, 1-way ANOVA). This translated into better oxygenation at 60 min (P = 0.047; 2-way ANOVA) resulting from better distal lung tissue aeration in SIOPT and OLV. There was no difference in lung injury. Neither SIOPT nor OLV achieved homogeneous aeration. Histological injury and mRNA biomarker upregulation were more likely in the regions with better initial aeration, suggesting volutrauma. Tidal ventilation or an SI achieves similar aeration if optimized, suggesting that preventing fluid efflux after lung liquid clearance is at least as important as fluid clearance during the initial inflation at birth.

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

BACKGROUND: To describe the interrelationship between antenatal steroids, exogenous surfactant, and two approaches to lung recruitment at birth on oxygenation and respiratory system compliance (Cdyn) in preterm lambs. METHODS: Lambs (n = 63; gestational age 127 ± 1 d) received either surfactant at 10-min life (Surfactant), antenatal corticosteroids (Steroid), or neither (Control). Within each epoch lambs were randomly assigned to a 30-s 40 cmH2O sustained inflation (SI) or an initial stepwise positive end-expiratory pressure (PEEP) open lung ventilation (OLV) maneuver at birth. All lambs then received the same management for 60-min with alveolar-arterial oxygen difference (AaDO2) and Cdyn measured at regular time points. RESULTS: Overall, the OLV strategy improved Cdyn and AaDO2 (all epochs except Surfactant) compared to SI (all P < 0.05; two-way ANOVA). Irrespective of strategy, Cdyn was better in the Steroid group in the first 10 min (all P < 0.05). Thereafter, Cdyn was similar to Steroid epoch in the OLV + Surfactant, but not SI + Surfactant group. OLV influenced the effect of steroid and surfactant (P = 0.005) on AaDO2 more than SI (P = 0.235). CONCLUSIONS: The antenatal state of the lung influences the type and impact of a recruitment maneuver at birth. The effectiveness of surfactant maybe enhanced using PEEP-based time-dependent recruitment strategies rather than approaches solely aimed at initial lung liquid clearance.

An individualized approach to sustained inflation duration at birth improves outcomes in newborn preterm lambs.

A sustained first inflation (SI) at birth may aid lung liquid clearance and aeration, but the impact of SI duration relative to the volume-response of the lung is poorly understood. We compared three SI strategies: 1) variable duration defined by attaining volume equilibrium using real-time electrical impedance tomography (EIT; SIplat); 2) 30 s beyond equilibrium (SIlong); 3) short 30-s SI (SI30); and 4) positive pressure ventilation without SI (no-SI) on spatiotemporal aeration and ventilation (EIT), gas exchange, lung mechanics, and regional early markers of injury in preterm lambs. Fifty-nine fetal-instrumented lambs were ventilated for 60 min after applying the allocated first inflation strategy. At study completion molecular and histological markers of lung injury were analyzed. The time to SI volume equilibrium, and resultant volume, were highly variable; mean (SD) 55 (34) s, coefficient of variability 59%. SIplat and SIlong resulted in better lung mechanics, gas exchange and lower ventilator settings than both no-SI and SI30. At 60 min, alveolar-arterial difference in oxygen was a mean (95% confidence interval) 130 (13, 249) higher in SI30 vs. SIlong group (two-way ANOVA). These differences were due to better spatiotemporal aeration and tidal ventilation, although all groups showed redistribution of aeration towards the nondependent lung by 60 min. Histological lung injury scores mirrored spatiotemporal change in aeration and were greatest in SI30 group (P < 0.01, Kruskal-Wallis test). An individualized volume-response approach to SI was effective in optimizing aeration, homogeneous tidal ventilation, and respiratory outcomes, while an inadequate SI duration had no benefit over positive pressure ventilation alone.