Inflating Pressure and Not Expiratory Pressure Initiates Lung Injury at Birth in Preterm Lambs.

Rationale: Inflation is essential for aeration at birth, but current inflating pressure settings are without an evidence base. Objectives: To determine the role of inflating pressure (ΔP), and its relationship with positive end-expiratory pressure (PEEP), in initiating early lung injury pathways in the preterm lamb lung. Methods: Preterm (124 to 127 d) steroid-exposed lambs (n = 45) were randomly allocated (8-10 per group) to 15 minutes of respiratory support with placental circulation and 20 or 30 cm H2O ΔP, with an initial high PEEP (maximum, 20 cm H2O) recruitment maneuver known to facilitate aeration (dynamic PEEP), and compared with dynamic PEEP with no ΔP or 30 cm H2O ΔP and low (4 cm H2O) PEEP. Lung mechanics and aeration were measured throughout. After an additional 30 minutes of apneic placental support, lung tissue and bronchoalveolar fluid were analyzed for regional lung injury, including proteomics. Measurements and Main Results: The 30 cm H2O ΔP and dynamic PEEP strategies resulted in quicker aeration and better compliance but higher tidal volumes (often >8 ml/kg, all P < 0.0001; mixed effects) and injury. ΔP 20 cm H2O with dynamic PEEP resulted in the same lung mechanics and aeration, but less energy transmission (tidal mechanical power), as ΔP 30 cm H2O with low PEEP. Dynamic PEEP without any tidal inflations resulted in the least lung injury. Use of any tidal inflating pressures altered metabolic, coagulation and complement protein pathways within the lung. Conclusions: Inflating pressure is essential for the preterm lung at birth, but it is also the primary mediator of lung injury. Greater focus is needed on strategies that identify the safest application of pressure in the delivery room.

Dynamic positive end-expiratory pressure strategies using time and pressure recruitment at birth reduce early expression of lung injury in preterm lambs.

Positive end-expiratory pressure (PEEP) is critical to the preterm lung at birth, but the optimal PEEP level remains uncertain. The objective of this study was to determine the effect of maximum PEEP levels at birth on the physiological and injury response in preterm lambs. Steroid-exposed preterm lambs (124-127 days gestation; n = 65) were randomly assigned from birth to either 1) positive pressure ventilation (PPV) at 8 cmH2O PEEP or 3-min dynamic stepwise PEEP strategy (DynPEEP), with either 2) 20 cmH2O maximum PEEP (10 PEEP second steps) or 3) 14 cmH2O maximum PEEP (20-s steps), all followed by standardized PPV for 90 min. Lung mechanics, gas exchange, regional ventilation and aeration (electrical impedance tomography), and histological and molecular measures of lung injury were compared between groups. Dynamic compliance was greatest using a maximum 20 cmH2O (DynPEEP). There were no differences in gas exchange, end-expiratory volume, and ventilator requirements. Regional ventilation became more uniform with time following all PEEP strategies. For all groups, gene expression of markers of early lung injury was greater in the gravity nondependent lung, and inversely related to the magnitude of PEEP, being lowest in the 20 cmH2O DynPEEP group overall. PEEP levels had no impact on lung injury in the dependent lung. Transient high maximum PEEP levels using dynamic PEEP strategies may confer more lung protection at birth.

Synchronized Inflations Generate Greater Gravity-Dependent Lung Ventilation in Neonates.

OBJECTIVE: To describe the regional distribution patterns of tidal ventilation within the lung during mechanical ventilation that is synchronous or asynchronous with an infant's own breathing effort. STUDY DESIGN: Intubated infants receiving synchronized mechanical ventilation at The Royal Children's Hospital neonatal intensive care unit were studied. During four 10-minute periods of routine care, regional distribution of tidal volume (VT; electrical impedance tomography), delivered pressure, and airway flow (Florian Respiratory Monitor) were measured for every inflation. Post hoc, each inflation was then classified as synchronous or asynchronous from video data of the ventilator screen, and the distribution of absolute VT and delivered ventilation characteristics determined. RESULTS: In total, 2749 inflations (2462 synchronous) were analyzed in 19 infants; mean (SD) age 28 (30) days, gestational age 35 (5) weeks. Synchronous inflations were associated with a shorter respiratory cycle (P = .004) and more homogenous VT (center of ventilation) along the right (0%) to left (100%) lung plane; 45.3 (8.6)% vs 48.8 (9.4)% (uniform ventilation 46%). The gravity-dependent center of ventilation was a mean (95% CI) 2.1 (-0.5, 4.6)% toward the dependent lung during synchronous inflations. Tidal ventilation relative to anatomical lung size was more homogenous during synchronized inflations in the dependent lung. CONCLUSIONS: Synchronous mechanical ventilator lung inflations generate more gravity-dependent lung ventilation and more uniform right-to-left ventilation than asynchronous inflations.

Skin-to-skin care alters regional ventilation in stable neonates.

OBJECTIVE: Skin-to-skin care (SSC) has proven psychological benefits; however, the physiological effects are less clearly defined. Regional ventilation patterns during SSC have not previously been reported. This study aimed to compare regional ventilation indices and other cardiorespiratory parameters during prone SSC with supine and prone position cot-nursing. DESIGN: Prospective observational study. SETTING: Single quaternary neonatal intensive care unit in Australia. PATIENTS: 20 infants spontaneously breathing (n=17) or on non-invasive ventilation (n=3), with mean (SD) gestational age at birth of 33 (5) weeks. INTERVENTIONS: Thirty-minute episodes of care in each position: supine cot care, prone SSC and prone cot care preceding a 10 min period of continuous electrical impedance tomography measurements of regional ventilation. MAIN OUTCOME MEASURES: In each position, ventral-dorsal and right-left centre of ventilation (CoV), percentage of whole lung ventilation by region and percentage of apparent unventilated lung regions were determined. Heart and respiratory rates, oxygen saturation and axillary temperature were also measured. RESULTS: Heart and respiratory rates, oxygen saturation, temperature and right-left lung ventilation did not differ between the three positions (mixed-effects model). Ventilation generally favoured the dorsal lung, but the mean (95% CI) ventrodorsal CoV was -2.0 (-0.4 to -3.6)% more dorsal during SSC compared with prone. Supine position resulted in 5.0 (1.5 to 5.3)% and 4.5 (3.9 to 5.1)% less apparently unventilated lung regions compared with SSC and prone, respectively. CONCLUSIONS: In clinically stable infants, SSC generates a distinct regional ventilation pattern that is independent of prone position and results in greater distribution of ventilation towards the dorsal lung.

Aeration strategy at birth influences the physiological response to surfactant in preterm lambs.

BACKGROUND: The influence of pressure strategies to promote lung aeration at birth on the subsequent physiological response to exogenous surfactant therapy has not been investigated. OBJECTIVES: To compare the effect of sustained inflation (SI) and a dynamic positive end-expiratory pressure (PEEP) manoeuvre at birth on the subsequent physiological response to exogenous surfactant therapy in preterm lambs. METHODS: Steroid-exposed preterm lambs (124-127 days' gestation; n=71) were randomly assigned from birth to either (1) positive-pressure ventilation (PPV) with no recruitment manoeuvre; (2) SI until stable aeration; or (3) 3 min dynamic stepwise PEEP strategy (maximum 14-20 cmH2O; dynamic PEEP (DynPEEP)), followed by PPV for 60 min using a standardised protocol. Surfactant (200 mg/kg poractant alfa) was administered at 10 min. Dynamic compliance, gas exchange and regional ventilation and aeration characteristics (electrical impedance tomography) were measured throughout and compared between groups, and with a historical group (n=38) managed using the same strategies without surfactant. RESULTS: Compliance increased after surfactant only in the DynPEEP group (p<0.0001, repeated measures analysis of variance), being 0.17 (0.10, 0.23) mL/kg/cmH2O higher at 60 min than the SI group. An SI resulted in the least uniform aeration, and unlike the no-recruitment and DynPEEP groups, the distribution of aeration and tidal ventilation did not improve with surfactant. All groups had similar improvements in oxygenation post-surfactant compared with the corresponding groups not treated with surfactant. CONCLUSIONS: A DynPEEP strategy at birth may improve the response to early surfactant therapy, whereas rapid lung inflation with SI creates non-uniform aeration that appears to inhibit surfactant efficacy.