Sustained inflation at birth did not protect preterm fetal sheep from lung injury

Abstract

Hillman NH, Kemp MW, Noble PB, Kallapur SG, Jobe AH. Sustained inflation at birth did not protect preterm fetal sheep from lung injury. Am J Physiol Lung Cell Mol Physiol 305: L446 -L453, 2013. First published July 19, 2013 doi:10.1152/ajplung.00162.2013.-Sustained lung inflations (SI) at birth may recruit functional residual capacity (FRC). Clinically, SI increase oxygenation and decrease need for intubation in preterm infants. We tested whether a SI to recruit FRC would decrease lung injury from subsequent ventilation of fetal, preterm lambs. The preterm fetus (128 Ϯ 1 day gestation) was exteriorized from the uterus, a tracheostomy was performed, and fetal lung fluid was removed. While maintaining placental circulation, fetuses were randomized to one of four 15-min interventions: 1) positive endexpiratory pressure (PEEP) 8 cmH 2O (n ϭ 4), 2) 20 s SI to 50 cmH2O then PEEP 8 cmH 2O (n ϭ 10), 3) mechanical ventilation at tidal volume (V T) 7 ml/kg (n ϭ 13), or 4) 20 s SI then ventilation at VT 7 ml/kg (n ϭ 13). Lambs were ventilated with 95% N 2/5% CO2 and PEEP 8 cmH 2O. Volume recruitment was measured during SI, and fetal tissues were collected after an additional 30 min on placental support. SI achieved a mean FRC recruitment of 15 ml/kg (range 8 -27). Fifty percent of final FRC was achieved by 2 s, 65% by 5 s, and 90% by 15 s, demonstrating prolonged SI times are needed to recruit FRC. SI alone released acute-phase proteins into the fetal lung fluid and increased mRNA expression of proinflammatory cytokines and acute-phase response genes in the lung. Mechanical ventilation further increased all markers of lung injury. SI before ventilation, regardless of the volume of FRC recruited, did not alter the acutephase and proinflammatory responses to mechanical ventilation at birth.

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

“…This was intentional to allow isolation of the inflammatory events occurring in early life from those of the injurious cycle of ongoing mechanical ventilation, but the relatively short study duration, although still longer than many previous SI animal studies (26,29,32,33,36), was unlikely to be sufficient to result in posttranscription protein changes within the lung and correlation with the histology findings. We chose accepted markers of preterm lung injury known to be upregulated within 30 min of injurious ventilation (11,12,14,40), but clear patterns for specific mechanisms of injury were not apparent. This may have been influenced by the sample size of each treatment group and the large variability in mRNA expression due to the multiple influences beyond those variables controlled in our study.…”

“…Some studies suggested SI improved aeration, FRC, and cerebral oxygen delivery (29,32,33), while others failed to demonstrate any benefit over standard respiratory support with sufficient PEEP (26,(35)(36)(37). SI was associated with increased lung injury in two studies (11,12). These data suggest the optimal SI strategy still needs to be elucidated.…”

“…All studies of SI have used predefined pressure, duration, and/or inflating volume goals (11,12,18,26,29,32,33,(35)(36)(37)(38). These approaches assume that the lungs of preterm infants will behave in a consistent, predictable and uniform manner.…”

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)(22)(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).…”