Speed of lung inflation at birth influences the initiation of lung injury in preterm lambs.

Gas flow is fundamental for driving tidal ventilation and, thus, the speed of lung motion, but current bias flow settings to support the preterm lung after birth do not have an evidence base. We aimed to determine the role of gas bias flow rates to generate positive pressure ventilation in initiating early lung injury pathways in the preterm lamb. Using slower speeds to inflate the lung during tidal ventilation (gas flow rates 4-6 L/min) did not affect lung mechanics, mechanical power, or gas exchange compared with those currently used in clinical practice (8-10 L/min).

Plasma Proteome Profiles Associated with Early Development of Lung Injury in Extremely Preterm Infants.

The biological mediators that initiate lung injury in extremely preterm infants during early postnatal life remain largely unidentified, limiting opportunities for early treatment and diagnosis. In this exploratory study, we used sequential window acquisition of all theoretical mass spectra mass spectrometry to identify bronchopulmonary dysplasia (BPD)-specific changes in protein abundance in plasma samples obtained in the first 72 hours of life from extremely preterm infants and bioinformatic analysis to identify BPD-related biological categories and pathways. Last, binary logistic regression analysis was used to test the BPD predictive potential of a base model alone (gestational age, birth weight, sex) and with the protein biomarker added, with bootstrap resampling used to internally validate protein predictors and adjust for overoptimism.

Mechanical power made simple: validating a simplified calculation of mechanical power in preterm lungs.

Background: The incidence of chronic lung disease is increasing, suggesting a need to explore novel ways to understand ventilator induced lung injury (VILI) in preterm infants. Mechanical power (MP) is a unifying measure of energy transferred to the respiratory system and a proposed determinant of VILI. The gold-standard method for calculating MP (geometric method) is not feasible in the clinical setting.

Impact of tidal volume strategy at birth on initiating lung injury in preterm lambs.

Tidal ventilation is essential in supporting the transition to air-breathing at birth, but excessive tidal volume (V) is an important factor in preterm lung injury. Few studies have assessed the impact of specific V levels on injury development. Here, we used a lamb model of preterm birth to investigate the role of different levels of V during positive pressure ventilation (PPV) in promoting aeration and initiating early lung injury pathways.

Lung ultrasound detects regional aeration inhomogeneity in ventilated preterm lambs.

Background: Inhomogeneous lung aeration is a significant contributor to preterm lung injury. EIT detects inhomogeneous aeration in the research setting. Whether LUS detects inhomogeneous aeration is unknown.

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

Inflation is essential for aeration at birth, but current inflating pressure settings are without an evidence base. 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. Preterm (124 to 127 d) steroid-exposed lambs ( = 45) were randomly allocated (8-10 per group) to 15 minutes of respiratory support with placental circulation and 20 or 30 cm HO ΔP, with an initial high PEEP (maximum, 20 cm HO) recruitment maneuver known to facilitate aeration (dynamic PEEP), and compared with dynamic PEEP with no ΔP or 30 cm HO ΔP and low (4 cm HO) PEEP.

Is mechanical power an under-recognised entity within the preterm lung?

Background: Mechanical power is a major contributor to lung injury and mortality in adults receiving mechanical ventilation. Recent advances in our understanding of mechanical power have allowed the different mechanical components to be isolated. The preterm lung shares many of the same similarities that would indicate mechanical power may be relevant in this group.

Respiratory strategy at birth initiates distinct lung injury phenotypes in the preterm lamb lung.

Background: A lack of clear trial evidence often hampers clinical decision-making during support of the preterm lung at birth. Protein biomarkers have been used to define acute lung injury phenotypes and improve patient selection for specific interventions in adult respiratory distress syndrome. The objective of the study was to use proteomics to provide a deeper biological understanding of acute lung injury phenotypes resulting from different aeration strategies at birth in the preterm lung.

Quantitative lung ultrasound detects dynamic changes in lung recruitment in the preterm lamb.

Background: Lung ultrasound (LUS) may not detect small, dynamic changes in lung volume. Mean greyscale measurement using computer-assisted image analysis (Q-LUS) may improve the precision of these measurements.

Methods: Preterm lambs (n = 40) underwent LUS of the dependent or non-dependent lung during static pressure-volume curve mapping.

Aeration strategy at birth does not impact carotid haemodynamics in preterm lambs.

Background: The impact of different respiratory strategies at birth on the preterm lung is well understood; however, concerns have been raised that lung recruitment may impede cerebral haemodynamics. This study aims to examine the effect of three different ventilation strategies on carotid blood flow, carotid artery oxygen content and carotid oxygen delivery.

Methods: 124-127-day gestation apnoeic intubated preterm lambs studied as part of a larger programme primarily assessing lung injury were randomised to positive pressure ventilation with positive end-expiratory pressure (PEEP) 8 cmHO (No-RM; n = 12), sustained inflation (SI; n = 15) or dynamic PEEP strategy (DynPEEP; maximum PEEP 14 or 20 cmHO, n = 41) at birth, followed by 90 min of standardised ventilation.

Lung ultrasound of the dependent lung detects real-time changes in lung volume in the preterm lamb.

Background: Effective lung protective ventilation requires reliable, real-time estimation of lung volume at the bedside. Neonatal clinicians lack a readily available imaging tool for this purpose.

Objective: To determine the ability of lung ultrasound (LUS) of the dependent region to detect real-time changes in lung volume, identify opening and closing pressures of the lung, and detect pulmonary hysteresis.

Imaging the Respiratory Transition at Birth: Unraveling the Complexities of the First Breaths of Life.

The transition to air breathing at birth is a seminal respiratory event common to all humans, but the intrathoracic processes remain poorly understood. The objectives of this prospective, observational study were to describe the spatiotemporal gas flow, aeration, and ventilation patterns within the lung in term neonates undergoing successful respiratory transition. Electrical impedance tomography was used to image intrathoracic volume patterns for every breath until 6 minutes from birth in neonates born by elective cesearean section and not needing resuscitation.

Regional ventilation characteristics during non-invasive respiratory support in preterm infants.

Objectives: To determine the regional ventilation characteristics during non-invasive ventilation (NIV) in stable preterm infants. The secondary aim was to explore the relationship between indicators of ventilation homogeneity and other clinical measures of respiratory status.

Design: Prospective observational study.

Proteomics reveals region-specific hemostatic alterations in response to mechanical ventilation in a preterm lamb model of lung injury.

Introduction: Preterm infants often require assisted ventilation, however ventilation when applied to the immature lung can initiate ventilator-induced lung injury (VILI). The biotrauma which underscores VILI is largely undefined, and is likely to involve vascular injury responses, including hemostasis. We aimed to use a ventilated, preterm lamb model to: (1) characterize regional alterations in hemostatic mediators within the lung and (2) assess the functional impact of protein alterations on hemostasis by analyzing temporal thrombin generation.

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 (V; electrical impedance tomography), delivered pressure, and airway flow (Florian Respiratory Monitor) were measured for every inflation.

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.

Respiratory mechanics during initial lung aeration at birth in the preterm lamb.

Despite recent insights into the dynamic processes during lung aeration at birth, several aspects remain poorly understood. We aimed to characterize changes in lung mechanics during the first inflation at birth and their relationship to changes in lung volume. Intubated preterm lambs (gestational age, 124-127 days; = 17) were studied at birth.

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 cmHO; dynamic PEEP (DynPEEP)), followed by PPV for 60 min using a standardised protocol.

Gestational Age Influences the Early Microarchitectural Changes in Response to Mechanical Ventilation in the Preterm Lamb Lung.

Preterm birth is associated with abnormal lung architecture, and a reduction in pulmonary function related to the degree of prematurity. A thorough understanding of the impact of gestational age on lung microarchitecture requires reproducible quantitative analysis of lung structure abnormalities. The objectives of this study were (1) to use quantitative histological software (ImageJ) to map morphological patterns of injury resulting from delivery of an identical ventilation strategy to the lung at varying gestational ages and (2) to identify associations between gestational age-specific morphological alterations and key functional outcomes.

A dedicated respiratory function monitor to improve tidal volume delivery during neonatal anesthesia.

Background: Tight control of tidal volume using accurate monitoring may improve neonatal outcomes. However, respiratory function monitors incorporated in current anesthetic workstations are generally inaccurate at tidal volumes used for infants.

Aims: To determine if a specific respiratory function monitor for neonatal infants improved expired tidal volume delivery during anesthesia.

Preterm Lung Exhibits Distinct Spatiotemporal Proteome Expression at Initiation of Lung Injury.

The development of regional lung injury in the preterm lung is not well understood. This study aimed to characterize time-dependent and regionally specific injury patterns associated with early ventilation of the preterm lung using a mass spectrometry-based proteomic approach. Preterm lambs delivered at 124-127 days gestation received 15 or 90 minutes of mechanical ventilation (positive end-expiratory pressure = 8 cm HO, Vt = 6-8 ml/kg) and were compared with unventilated control lambs.