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.

[1]  Steffen Leonhardt,et al.  Chest electrical impedance tomography examination, data analysis, terminology, clinical use and recommendations: consensus statement of the TRanslational EIT developmeNt stuDy group , 2016, Thorax.

[2]  D. Tingay,et al.  Selection of Reference Genes for Gene Expression Studies related to lung injury in a preterm lamb model , 2016, Scientific Reports.

[3]  F. Mosca,et al.  Intratracheal atomized surfactant provides similar outcomes as bolus surfactant in preterm lambs with respiratory distress syndrome , 2016, Pediatric Research.

[4]  D. Tingay,et al.  The proteomics of lung injury in childhood: challenges and opportunities , 2016, Clinical Proteomics.

[5]  P. Davis,et al.  The interrelationship of recruitment maneuver at birth, antenatal steroids, and exogenous surfactant on compliance and oxygenation in preterm lambs , 2016, Pediatric Research.

[6]  P. Davis,et al.  Spatiotemporal Aeration and Lung Injury Patterns Are Influenced by the First Inflation Strategy at Birth. , 2016, American journal of respiratory cell and molecular biology.

[7]  P. Davis,et al.  An individualized approach to sustained inflation duration at birth improves outcomes in newborn preterm lambs. , 2015, American journal of physiology. Lung cellular and molecular physiology.

[8]  S. Hooper,et al.  Respiratory transition in the newborn: a three-phase process , 2015, Archives of Disease in Childhood: Fetal and Neonatal Edition.

[9]  L. Owen,et al.  Sustained lung inflation at birth: what do we know, and what do we need to know? , 2015, Archives of Disease in Childhood: Fetal and Neonatal Edition.

[10]  J. Pillow,et al.  Pressure-limited sustained inflation vs. gradual tidal inflations for resuscitation in preterm lambs. , 2015, Journal of applied physiology.

[11]  L. Owen,et al.  Sustained Aeration of Infant Lungs (SAIL) trial: study protocol for a randomized controlled trial , 2015, Trials.

[12]  L. Boni,et al.  Sustained Lung Inflation at Birth for Preterm Infants: A Randomized Clinical Trial , 2015, Pediatrics.

[13]  M. Kumar,et al.  Sustained inflation versus positive pressure ventilation at birth: a systematic review and meta-analysis , 2014, Archives of Disease in Childhood: Fetal and Neonatal Edition.

[14]  D. Tingay,et al.  Optimal mean airway pressure during high-frequency oscillatory ventilation determined by measurement of respiratory system reactance , 2014, Pediatric Research.

[15]  J. Pillow,et al.  Pressure- versus volume-limited sustained inflations at resuscitation of premature newborn lambs , 2014, BMC Pediatrics.

[16]  P. Davis,et al.  Effect of sustained inflation vs. stepwise PEEP strategy at birth on gas exchange and lung mechanics in preterm lambs , 2014, Pediatric Research.

[17]  P. Davis,et al.  Surfactant before the first inflation at birth improves spatial distribution of ventilation and reduces lung injury in preterm lambs. , 2014, Journal of applied physiology.

[18]  A. Pedotti,et al.  Assessment of Dynamic Mechanical Properties of the Respiratory System During High-Frequency Oscillatory Ventilation* , 2013, Critical care medicine.

[19]  M. Kemp,et al.  Sustained inflation at birth did not protect preterm fetal sheep from lung injury. , 2013, American journal of physiology. Lung cellular and molecular physiology.

[20]  C. Morley,et al.  Indicators of Optimal Lung Volume During High-Frequency Oscillatory Ventilation in Infants* , 2013, Critical care medicine.

[21]  A. Pedotti,et al.  Optimizing positive end-expiratory pressure by oscillatory mechanics minimizes tidal recruitment and distension: an experimental study in a lavage model of lung injury , 2012, Critical Care.

[22]  Inez Frerichs,et al.  Changes in lung volume and ventilation during lung recruitment in high-frequency ventilated preterm infants with respiratory distress syndrome. , 2011, The Journal of pediatrics.

[23]  P. Davis,et al.  An Initial Sustained Inflation Improves the Respiratory and Cardiovascular Transition at Birth in Preterm Lambs , 2011, Pediatric Research.

[24]  A. Pedotti,et al.  Optimisation of positive end-expiratory pressure by forced oscillation technique in a lavage model of acute lung injury , 2011, Intensive Care Medicine.

[25]  I. Frerichs,et al.  Regional tidal ventilation and compliance during a stepwise vital capacity manoeuvre , 2010, Intensive Care Medicine.

[26]  Antonio Pedotti,et al.  Lung recruitment assessed by total respiratory system input reactance , 2009, Intensive Care Medicine.

[27]  C. Morley,et al.  Comparison of four methods of lung volume recruitment during high frequency oscillatory ventilation , 2009, Intensive Care Medicine.

[28]  P. Davis,et al.  Effect of Sustained Inflation Length on Establishing Functional Residual Capacity at Birth in Ventilated Premature Rabbits , 2009, Pediatric Research.

[29]  William R B Lionheart,et al.  GREIT: a unified approach to 2D linear EIT reconstruction of lung images , 2009, Physiological measurement.

[30]  P. Davis,et al.  Establishing Functional Residual Capacity at Birth: The Effect of Sustained Inflation and Positive End-Expiratory Pressure in a Preterm Rabbit Model , 2009, Pediatric Research.

[31]  P. Davis,et al.  Positive end-expiratory pressure enhances development of a functional residual capacity in preterm rabbits ventilated from birth. , 2009, Journal of applied physiology.

[32]  J. Pillow,et al.  Injury and Inflammation from Resuscitation of the Preterm Infant , 2008, Neonatology.

[33]  Kentaro Uesugi,et al.  Imaging lung aeration and lung liquid clearance at birth , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[34]  F. Walther,et al.  A Randomized, Controlled Trial of Delivery-Room Respiratory Management in Very Preterm Infants , 2007, Pediatrics.

[35]  C. Morley,et al.  The deflation limb of the pressure-volume relationship in infants during high-frequency ventilation. , 2006, American journal of respiratory and critical care medicine.

[36]  B. Lachmann,et al.  Open up the lung and keep the lung open , 1992, Intensive Care Medicine.

[37]  C. Morley,et al.  Positive End Expiratory Pressure during Resuscitation of Premature Lambs Rapidly Improves Blood Gases without Adversely Affecting Arterial Pressure , 2004, Pediatric Research.

[38]  A. Froese The incremental application of lung-protective high-frequency oscillatory ventilation. , 2002, American journal of respiratory and critical care medicine.

[39]  R. Soll,et al.  Prophylactic natural surfactant extract for preventing morbidity and mortality in preterm infants. , 2000, The Cochrane database of systematic reviews.

[40]  A Adler,et al.  Monitoring changes in lung air and liquid volumes with electrical impedance tomography. , 1997, Journal of applied physiology.

[41]  E. Özek,et al.  Prophylactic animal derived surfactant extract for preventing morbidity and mortality in preterm infants , 1997 .

[42]  A. Torresin,et al.  Relationships Between Lung Computed Tomographic Density, Gas Exchange, and PEEP in Acute Respiratory Failure , 1988, Anesthesiology.

[43]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.