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. This has prompted the derivation of simplified equations for calculating MP. OBJECTIVE: To validate the agreement between a simplified calculation of MP (MPSimple) and the true MP calculated using the geometric method (MPRef). METHODS: MPSimple and MPRef was calculated in mechanically ventilated preterm lambs (n = 71) and the agreement between both measures was determined using intraclass correlation coefficients (ICC), linear regression, and Bland-Altman analysis. RESULTS: A strong linear relationship (adjusted R2 = 0.98), and excellent agreement (ICC = 0.99, 95% CI = 0.98-0.99) between MPSimple and MPRef was demonstrated. Bland-Altman analysis demonstrated a negligible positive bias (mean difference = 0.131 J/min·kg). The 95% limits of agreement were -0.06 to 0.32 J/min·kg. CONCLUSIONS: In a controlled setting, there was excellent agreement between MPSimple and gold-standard calculations. MPSimple should be validated and explored in preterm neonates to assess the cause-effect relationship with VILI and neonatal outcomes. IMPACT STATEMENT: Mechanical power (MP) unifies the individual components of ventilator induced lung injury (VILI) and provides an estimate of total energy transferred to the respiratory system during mechanical ventilation. As gold-standard calculations of mechanical power at the bedside are not feasible, alternative simplified equations have been proposed. In this study, MP calculated using a simplified equation had excellent agreement with true MP in mechanically ventilated preterm lambs. These results lay foundations to explore the role of MP in neonatal VILI and determine its relationship with short and long term respiratory outcomes.

Top 10 research priorities for congenital diaphragmatic hernia in Australia: James Lind Alliance Priority Setting Partnership.

OBJECTIVES: The Gaps in the Congenital Diaphragmatic Hernia (CDH) Journey Priority Setting Partnership (PSP) was developed in collaboration with CDH Australia, James Lind Alliance (JLA) and the Murdoch Children's Research Institute to identify research priorities for people with CDH, their families and healthcare workers in Australasia. DESIGN: Research PSP in accordance with the JLA standardised methodology. SETTING: Australian community and institutions caring for patients with CDH and their families. PATIENTS: CDH survivors, families of children born with CDH (including bereaved) and healthcare professionals including critical care physicians and nurses (neonatal and paediatric), obstetric, surgical, allied health professionals (physiotherapists, speech pathologists and speech therapists) and general practitioners. MAIN OUTCOME MEASURE: Top 10 research priorities for CDH. RESULTS: 377 questions, from a community-based online survey, were categorised and collated into 50 research questions. Through a further prioritisation process, 21 questions were then discussed at a prioritisation workshop where they were ranked by 21 participants (CDH survivors, parents of children born with CDH (bereaved and not) and 11 multidisciplinary healthcare professionals) into their top 10 research priorities. CONCLUSION: Stakeholders' involvement identified the top 10 CDH-related research questions, spanning from antenatal care to long-term functional outcomes, that should be prioritised for future research to maximise meaningful outcomes for people with CDH and their families.

Endotracheal Tube Size Adjustments Within Seven Days of Neonatal Intubation.

BACKGROUND AND OBJECTIVES: Neonatal endotracheal tube (ETT) size recommendations are based on limited evidence. We sought to determine data-driven weight-based ETT sizes for infants undergoing tracheal intubation and to compare these with Neonatal Resuscitation Program (NRP) recommendations. METHODS: Retrospective multicenter cohort study from an international airway registry. We evaluated ETT size changes (downsizing to a smaller ETT during the procedure or upsizing to a larger ETT within 7 days) and risk of procedural adverse outcomes associated with first-attempt ETT size selection when stratifying the cohort into 200 g subgroups. RESULTS: Of 7293 intubations assessed, the initial ETT was downsized in 5.0% of encounters and upsized within 7 days in 1.5%. ETT downsizing was most common when NRP-recommended sizes were attempted in the following weight subgroups: 1000 to 1199 g with a 3.0 mm (12.6%) and 2000 to 2199 g with a 3.5 mm (17.1%). For infants in these 2 weight subgroups, selection of ETTs 0.5 mm smaller than NRP recommendations was independently associated with lower odds of adverse outcomes compared with NRP-recommended sizes. Among infants weighing 1000 to 1199 g: any tracheal intubation associated event, 20.8% with 2.5 mm versus 21.9% with 3.0 mm (adjusted OR [aOR] 0.62, 95% confidence interval [CI] 0.41-0.94); severe oxygen desaturation, 35.2% with 2.5 mm vs 52.9% with 3.0 mm (aOR 0.53, 95% CI 0.38-0.75). Among infants weighing 2000 to 2199 g: severe oxygen desaturation, 41% with 3.0 mm versus 56% with 3.5mm (aOR 0.55, 95% CI 0.34-0.89). CONCLUSIONS: For infants weighing 1000 to 1199 g and 2000 to 2199 g, the recommended ETT size was frequently downsized during the procedure, whereas 0.5 mm smaller ETT sizes were associated with fewer adverse events and were rarely upsized.

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. The aim was to determine whether LUS detects regional inhomogeneity identified by EIT in preterm lambs. METHODS: LUS and EIT were simultaneously performed on mechanically ventilated preterm lambs. LUS images from non-dependent and dependent regions were acquired and reported using a validated scoring system and computer-assisted quantitative LUS greyscale analysis (Q-LUSMGV). Regional inhomogeneity was calculated by observed over predicted aeration ratio from the EIT reconstructive model. LUS scores and Q-LUSMGV were compared with EIT aeration ratios using one-way ANOVA. RESULTS: LUS was performed in 32 lambs (~125d gestation, 128 images). LUS scores were greater in upper anterior (non-dependent) compared to lower lateral (dependent) regions of the left (3.4 vs 2.9, p = 0.1) and right (3.4 vs 2.7, p < 0.0087). The left and right upper regions also had greater LUS scores compared to right lower (3.4 vs 2.7, p < 0.0087) and left lower (3.7 vs 2.9, p = 0.1). Q-LUSMGV yielded similar results. All LUS findings corresponded with EIT regional differences. CONCLUSION: LUS may have potential in measuring regional aeration, which should be further explored in human studies. IMPACT: Inhomogeneous lung aeration is an important contributor to preterm lung injury, however, tools detecting inhomogeneous aeration at the bedside are limited. Currently, the only tool clinically available to detect this is electrical impedance tomography (EIT), however, its use is largely limited to research. Lung ultrasound (LUS) may play a role in monitoring lung aeration in preterm infants, however, whether it detects inhomogeneous lung aeration is unknown. Visual LUS scores and mean greyscale image analysis using computer assisted quantitative LUS (Q-LUSMGV) detects regional lung aeration differences when compared to EIT. This suggests LUS reliably detects aeration inhomogeneity warranting further investigation in human trials.

Factors that determine first intubation attempt success in high-risk neonates.

BACKGROUND: Approximately 50% of all neonatal endotracheal intubation attempts are unsuccessful and associated with airway injury and cardiorespiratory instability. The aim of this study was to describe intubation practice at a high-risk Neonatal Intensive Care Unit (NICU) and identify factors associated with successful intubation at the first attempt. METHODS: Retrospective cohort study of all infants requiring intubation within the Royal Children's Hospital NICU over three years. Data was collected from the National Emergency Airway Registry for Neonates (NEAR4NEOS). Outcomes were number of attempts, level of operator training, equipment used, difficult airway grade, and clinical factors. Univariate and multivariate analysis were performed to determine factors independently associated with first attempt success. RESULTS: Three hundred and sixty intubation courses, with 538 attempts, were identified. Two hundred and twenty-five (62.5%) were successful on first attempt, with similar rates at subsequent attempts. On multivariate analysis, increasing operator seniority increased the chance of first attempt success. Higher glottic airway grades were associated with lower chance of first attempt success, but neither a known difficult airway nor use of a stylet were associated with first attempt success. CONCLUSION: In a NICU with a high rate of difficult airways, operator experience rather than equipment was the greatest determinant of intubation success. IMPACT: Neonatal intubation is a high-risk lifesaving procedure, and this is the first report of intubation practices at a quaternary surgical NICU that provides regional referral services for complex medical and surgical admissions. Our results showed that increasing operator seniority and lower glottic airway grades were associated with increased first attempt intubation success rates, while factors such as gestational age, weight, stylet use, and known history of difficult airway were not. Operator factors rather than equipment factors were the greatest determinants of first attempt success, highlighting the importance of team selection for neonatal intubations in a high-risk cohort of infants.

Ratchet recruitment in the acute respiratory distress syndrome: lessons from the newborn cry.

Patients with acute respiratory distress syndrome (ARDS) have few treatment options other than supportive mechanical ventilation. The mortality associated with ARDS remains unacceptably high, and mechanical ventilation itself has the potential to increase mortality further by unintended ventilator-induced lung injury (VILI). Thus, there is motivation to improve management of ventilation in patients with ARDS. The immediate goal of mechanical ventilation in ARDS should be to prevent atelectrauma resulting from repetitive alveolar collapse and reopening. However, a long-term goal should be to re-open collapsed and edematous regions of the lung and reduce regions of high mechanical stress that lead to regional volutrauma. In this paper, we consider the proposed strategy used by the full-term newborn to open the fluid-filled lung during the initial breaths of life, by ratcheting tissues opened over a series of initial breaths with brief expirations. The newborn's cry after birth shares key similarities with the Airway Pressure Release Ventilation (APRV) modality, in which the expiratory duration is sufficiently short to minimize end-expiratory derecruitment. Using a simple computational model of the injured lung, we demonstrate that APRV can slowly open even the most recalcitrant alveoli with extended periods of high inspiratory pressure, while reducing alveolar re-collapse with brief expirations. These processes together comprise a ratchet mechanism by which the lung is progressively recruited, similar to the manner in which the newborn lung is aerated during a series of cries, albeit over longer time scales.

The neonatal airway.

Safe and effective management of the neonatal airway requires knowledge, teamwork, preparation and experience. At baseline, the neonatal airway can present significant challenges to experienced neonatologists and paediatric anaesthesiologists, and increased difficulty can be due to anatomical abnormalities, physiological instability or increased situational stress. Neonatal airway obstruction is under recognised, and should be considered an emergency until the diagnosis and physiological implications are understood. When multiple types of difficulties are present or there are multiple levels of anatomical obstruction, the challenge increases exponentially. In these situations, preparation, multi-disciplinary teamwork and a consistent hospital-wide approach will help to reduce errors and morbidity.

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 (VT) is an important factor in preterm lung injury. Few studies have assessed the impact of specific VT levels on injury development. Here, we used a lamb model of preterm birth to investigate the role of different levels of VT during positive pressure ventilation (PPV) in promoting aeration and initiating early lung injury pathways. VT was delivered as 1) 7 mL/kg throughout (VTstatic), 2) begun at 3 mL/kg and increased to a final VT of 7 mL/kg over 3 min (VTinc), or 3) commenced at 7 mL/kg, decreased to 3 mL/kg, and then returned to 7 mL/kg (VTalt). VT, inflating pressure, lung compliance, and aeration were similar in all groups from 4 min, as was postmortem histology and lung lavage protein concentration. However, transient decrease in VT in the VTalt group caused increased ventilation heterogeneity. Following TMT-based quantitative mass spectrometry proteomics, 1,610 proteins were identified in the lung. Threefold more proteins were significantly altered with VTalt compared with VTstatic or VTinc strategies. Gene set enrichment analysis identified VTalt specific enrichment of immune and angiogenesis pathways and VTstatic enrichment of metabolic processes. Our finding of comparable lung physiology and volutrauma across VT groups challenges the paradigm that there is a need to rapidly aerate the preterm lung at birth. Increased lung injury and ventilation heterogeneity were identified when initial VT was suddenly decreased during respiratory support at birth, further supporting the benefit of a gentle VT approach.NEW & NOTEWORTHY There is little evidence to guide the best tidal volume (VT) strategy at birth. In this study, comparable aeration, lung mechanics, and lung morphology were observed using static, incremental, and alternating VT strategies. However, transient reduction in VT was associated with ventilation heterogeneity and inflammation. Our results suggest that rapidly aerating the preterm lung may not be as clinically critical as previously thought, providing clinicians with reassurance that gently supporting the preterm lung maybe permissible at birth.

Community Versus Vertically Acquired Neonatal SARS-CoV-2 Infection: The EPICENTRE Cohort Study.

Neonatal Severe Acute Respiratory Syndrome-CoronaVirus-2 infections can be community-acquired or vertically-acquired. The analysis of neonatal patients requiring hospitalization reported in the EPICENTRE worldwide registry shows that community-acquired cases have clinical features (fever, respiratory signs, feeding difficulties, P < 0.0001) and received antibiotics (P = 0.014) more frequently than vertically-acquired patients. Severe Acute Respiratory Syndrome-CoronaVirus-2 infections should be considered in the clinical workout of neonatal infections.

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.

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. To date, the role of mechanical power in neonatal lung injury is unknown. We hypothesise that mechanical power maybe useful in expanding our understanding of preterm lung disease. Specifically, that mechanical power measures may account for gaps in knowledge in how lung injury is initiated. HYPOTHESIS-GENERATING DATA SET: To provide a justification for our hypothesis, data in a repository at the Murdoch Children's Research Institute, Melbourne (Australia) were re-analysed. 16 preterm lambs 124-127d gestation (term 145d) who received 90 min of standardised positive pressure ventilation from birth via a cuffed endotracheal tube were chosen as each was exposed to three distinct and clinically relevant respiratory states with unique mechanics. These were (1) the respiratory transition to air-breathing from an entirely fluid-filled lung (rapid aeration and fall in resistance); (2) commencement of tidal ventilation in an acutely surfactant-deficient state (low compliance) and (3) exogenous surfactant therapy (improved aeration and compliance). Total, tidal, resistive and elastic-dynamic mechanical power were calculated from the flow, pressure and volume signals (200 Hz) for each inflation. RESULTS: All components of mechanical power behaved as expected for each state. Mechanical power increased during lung aeration from birth to 5 min, before again falling immediately after surfactant therapy. Before surfactant therapy tidal power contributed 70% of total mechanical power, and 53.7% after. The contribution of resistive power was greatest at birth, demonstrating the initial high respiratory system resistance at birth. CONCLUSIONS: In our hypothesis-generating dataset, changes in mechanical power were evident during clinically important states for the preterm lung, specifically transition to air-breathing, changes in aeration and surfactant administration. Future preclinical studies using ventilation strategies designed to highlight different types of lung injury, including volu-, baro- and ergotrauma, are needed to test our hypothesis.

Estimating Preterm Lung Volume: A Comparison of Lung Ultrasound, Chest Radiography, and Oxygenation.

OBJECTIVE: To determine the relationship between lung ultrasound (LUS) examination, chest radiograph (CXR), and radiographic and clinical evaluations in the assessment of lung volume in preterm infants. STUDY DESIGN: In this prospective cohort study LUS was performed before CXR on 70 preterm infants and graded using (1) a LUS score, (2) an atelectasis score, and (3) measurement of atelectasis depth. Radiographic diaphragm position and radio-opacification were used to determine global and regional radiographic atelectasis. The relationship between LUS, CXR, and oxygenation was assessed using receiver operator characteristic and correlation analysis. RESULTS: LUS scores, atelectasis scores, and atelectasis depth did not correspond with radiographic global atelectasis (area under receiver operator characteristics curves, 0.54 [95% CI, 0.36-0.71], 0.49 [95% CI, 0.34-0.64], and 0.47 [95% CI, 0.31-0.64], respectively). Radiographic atelectasis of the right upper, right lower, left upper, and left lower quadrants was predicted by LUS scores (0.75 [95% CI, 0.59-0.92], 0.75 [95% CI, 0.62-0.89], 0.69 [95% CI, 0.56-0.82], and 0.63 [95% CI, 0.508-0.751]) and atelectasis depth (0.66 [95% CI, 0.54-0.78], 0.65 [95% CI, 0.53-0.77], 0.63 [95% CI, 0.50-0.76], and 0.56 [95% CI, 0.44-0.70]). LUS findings were moderately correlated with oxygen saturation index (ρ = 0.52 [95% CI, 0.30-0.70]) and saturation to fraction of inspired oxygen ratio (ρ = -0.63 [95% CI, -0.76 to -0.46]). The correlation between radiographic diaphragm position, the oxygenation saturation index, and peripheral oxygen saturation to fraction of inspired oxygen ratio was very weak (ρ = 0.36 [95% CI, 0.11-0.59] and ρ = -0.32 [95% CI, -0.53 to -0.07], respectively). CONCLUSIONS: LUS assessment of lung volume does not correspond with radiographic diaphragm position preterm infants. However, LUS predicted radiographic regional atelectasis and correlated with oxygenation. The relationship between radiographic diaphragm position and oxygenation was very weak. Although LUS may not replace all radiographic measures of lung volume, LUS more accurately reflects respiratory status in preterm infants. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12621001119886.