Ineffective aeration during the first inflations at birth creates regional aeration and ventilation defects, initiating injurious pathways. This study aimed to compare a sustained first inflation at birth or dynamic end-expiratory supported recruitment during tidal inflations against ventilation without intentional recruitment on gas exchange, lung mechanics, spatiotemporal regional aeration and tidal ventilation, and regional lung injury in preterm lambs. Lambs (127 ± 2 d gestation), instrumented at birth, were ventilated for 60 minutes from birth with either lung-protective positive pressure ventilation (control) or as per control after either an initial 30 seconds of 40 cm H2O sustained inflation (SI) or an initial stepwise end-expiratory pressure recruitment maneuver during tidal inflations (duration 180 s; open lung ventilation [OLV]). At study completion, molecular markers of lung injury were analyzed. The initial use of an OLV maneuver, but not SI, at birth resulted in improved lung compliance, oxygenation, end-expiratory lung volume, and reduced ventilatory needs compared with control, persisting throughout the study. These changes were due to more uniform inter- and intrasubject gravity-dependent spatiotemporal patterns of aeration (measured using electrical impedance tomography). Spatial distribution of tidal ventilation was more stable after either recruitment maneuver. All strategies caused regional lung injury patterns that mirrored associated regional volume states. Irrespective of strategy, spatiotemporal volume loss was consistently associated with up-regulation of early growth response-1 expression. Our results show that mechanical and molecular consequences of lung aeration at birth are not simply related to rapidity of fluid clearance; they are also related to spatiotemporal pressure-volume interactions within the lung during inflation and deflation.

A sustained first inflation (SI) at birth may aid lung liquid clearance and aeration, but the impact of SI duration relative to the volume-response of the lung is poorly understood. We compared three SI strategies: 1) variable duration defined by attaining volume equilibrium using real-time electrical impedance tomography (EIT; SI plat); 2) 30 s beyond equilibrium (SI long); 3) short 30-s SI (SI30); and 4) positive pressure ventilation without SI (no-SI) on spatiotemporal aeration and ventilation (EIT), gas exchange, lung mechanics, and regional early markers of injury in preterm lambs. Fifty-nine fetal-instrumented lambs were ventilated for 60 min after applying the allocated first inflation strategy. At study completion molecular and histological markers of lung injury were analyzed. The time to SI volume equilibrium, and resultant volume, were highly variable; mean (SD) 55 (34) s, coefficient of variability 59%. SI plat and SIlong resulted in better lung mechanics, gas exchange and lower ventilator settings than both no-SI and SI30. At 60 min, alveolar-arterial difference in oxygen was a mean (95% confidence interval) 130 (13, 249) higher in SI30 vs. SIlong group (two-way ANOVA). These differences were due to better spatiotemporal aeration and tidal ventilation, although all groups showed redistribution of aeration towards the nondependent lung by 60 min. Histological lung injury scores mirrored spatiotemporal change in aeration and were greatest in SI 30 group (P Ͻ 0.01, Kruskal-Wallis test). An individualized volume-response approach to SI was effective in optimizing aeration, homogeneous tidal ventilation, and respiratory outcomes, while an inadequate SI duration had no benefit over positive pressure ventilation alone. sustained inflation; neonatal resuscitation; lung mechanics; lung volume; variability; electrical impedance tomography; lung injury THE MAJORITY OF EXTREMELY preterm infants require respiratory assistance in the delivery room (41). In part this is because many of these infants do not have the ability to generate the initial prolonged high transpulmonary pressures required to drive lung fluid from the main airways, allow alveolar aeration, establish functional residual capacity (FRC), and then maintain it during tidal ventilation, essential processes for efficient gas exchange and lung protection (19,31). Recently, applying an initial sustained inflation (SI) at birth, consisting of an elevated pressure applied for longer than needed for usual tidal inflation, followed by sufficient positive end-expiratory pressure (PEEP), has been proposed as a method of generating the initial transpulmonary pressure needed at birth (10,18,20). SI has been extensively investigated in preterm animals (15,26,29,32,33,(35)(36)(37)(38) and humans (10, 18, 34) with conflicting results. 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 wi...

Background: In translational animal studies both a sustained inflation (SI) and PEEP have been associated with better lung aeration at birth, but the role of each on lung injury is inconclusive. We aimed to determine the effect of different PEEP and SI strategies at birth on early development of lung injury pathways. Method: 70 antenatal-steroid exposed lambs (125d AE 1d) were instrumented during caesarean section. Lambs were randomly assigned to either 1) Positive Pressure Ventilation (PPV; n = 20) using volume targeted ventilation at PEEP 8 cmH 2 O (maximum PIP 35 cmH 2 O, V T 7 ml/kg), 2) Volumetric Sustained Inflation 1 at 35 cmH 2 O until full aeration was visualised using electrical impedance tomography (SI; n = 23), or 3) 3-min Dynamic PEEP strategy 1 guided by breath-to-breath compliance (n = 27). All lambs were treated at 10 min with surfactant 200 mg/kg, and then received PPV for 90 min, with measurement of mechanics and gas exchange throughout. Standardised samples from the gravity-dependent and non-dependent lung were analysed for early injury mRNA markers (EGR1, CYR61, CTGF, IL-6,-8,-1B) and histology. Results: All groups expressed injury in the non-dependent lung compared to unventilated fetal controls across all injury parameters (p < 0.0001 ANOVA). In the dependent lung, only SI resulted in higher EGR1, CYR61, CTGF, IL-6,-1B expression compared to PPV and dynamic PEEP (p < 0.0001 ANOVA), and both were not different from fetal controls. Dynamic PEEP had better oxygenation throughout (p < 0.0001, two-way ANOVA) Conclusions: This large preterm lamb study is the first to show significant injury differences between SI and PEEP starte-gies. Early lung injury was heterogeneous and greater in the dependent lung following a SI. This suggests that achieving aeration slowly using tidal inflations maybe more beneficial than a SI. Reference: 1. Tingay DG et al. Background: Volume targeted ventilation (VTV) is widely used and may reduce lung injury, but this assumes the clinically set V T (V Tset) is accurately delivered. The aims of this prospective observational study were to determine the relationship between V Tset , expiratory V T (V Te) and endotracheal tube leak in a modern neonatal VTV ventilator, and the resultant PaCO 2 relationship with and without VTV. Method: Continuous inflations were recorded for 24 hours in 100 infants receiving synchronised mechanical ventilation (SLE5000, SLE Ltd, UK) with VTV (n = 77 infants) or without, and either the manufacturer's V4 (n = 50) or newer V5 (n = 50) VTV algorithm. For every inflation the set V Tset , V Te and leak were determined (maximum 90000 inflations/infant). If PaCO 2 was sampled (maximum 2/infant), this was compared with the average V T data from the preceeding 15 minutes. Results: A total of 7,917,020 inflations were analysed. Using VTV the V Tset-V Te bias (95% CI) was 0.3 (−0.12, 0.19) mL/kg. Leak influenced V Tset-V Te bias with V4 algorithm (r 2 = −0.64, p < 0.0001; linear regression) but not V5 (r 2 = 0.04, p = 0.21). Overall 80% of V Te were AE...

Despite differing mechanisms for generating positive airway pressure, when compared at the same Prp, NCPAP and HHHFNC provide similar effects on all the outcomes explored.

BACKGROUND:The COVID-19 pandemic threatens global newborn health. We describe the current state of national and local protocols for managing neonates born to SARS-CoV-2-positive mothers. METHODS: Care providers from neonatal intensive care units on six continents exchanged and compared protocols on the management of neonates born to SARS-CoV-2-positive mothers. Data collection was between March 14 and 21, 2020. We focused on central protocol components, including triaging, hygiene precautions, management at delivery, feeding protocols, and visiting policies. RESULTS: Data from 20 countries were available. Disease burden varied between countries at the time of analysis. In most countries, asymptomatic infants were allowed to stay with the mother and breastfeed with hygiene precautions. We detected discrepancies between national guidance in particular regarding triaging, use of personal protection equipment, viral testing, and visitor policies. Local protocols deviated from national guidance. CONCLUSIONS: At the start of the pandemic, lack of evidence-based guidance on the management of neonates born to SARS-CoV-2positive mothers has led to ad hoc creation of national and local guidance. Compliance between collaborators to share and discuss protocols was excellent and may lead to more consensus on management, but future guidance should be built on high-level evidence, rather than expert consensus.

IMPORTANCE Heated, humidified high-flow nasal cannula (HHHFNC) has gained increasing popularity as respiratory support for newborn infants thanks to ease of use and improved patient comfort. However, its role as primary therapy for respiratory distress syndrome (RDS) of prematurity needs to be further elucidated by large, randomized clinical trials. OBJECTIVE To determine whether HHHFNC provides respiratory support noninferior to nasal continuous positive airway pressure (nCPAP) or bilevel nCPAP (BiPAP) as a primary approach to RDS in infants older than 28 weeks' gestational age (GA). DESIGN, SETTING, AND PARTICIPANTS An unblinded, monocentric, randomized clinical noninferiority trial at a tertiary neonatal intensive care unit. Inborn infants at 29 weeks 0 days to 36 weeks 6 days of GA were eligible if presenting with mild to moderate RDS requiring noninvasive respiratory support. Criteria for starting noninvasive respiratory support were a Silverman score of 5 or higher or a fraction of inspired oxygen higher than 0.3 for a target saturation of peripheral oxygen of 88% to 93%. Infants were ineligible if they had major congenital anomalies or severe RDS requiring early intubation. Infants were enrolled between

Among an experienced group of nHFT clinical researchers, there was general consensus in the approach to neonatal nHFT. Additional randomized studies are indicated to provide better evidence related to several aspects of nHFT, as well as to identify other clinical conditions where nHFT may provide safe, effective noninvasive support.

BackgroundMalaria caused by Plasmodium falciparum is one of the leading causes of human morbidity and mortality from infectious diseases, predominantly in tropical and sub-tropical countries. As genetic variations in the toll-like receptors (TLRs)-signalling pathway have been associated with either susceptibility or resistance to several infectious and inflammatory diseases, the supposition is that single nucleotide polymorphisms (SNPs) of TLR2, TLR4, TLR9, Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) and FCGR2A could modulate malaria susceptibility and severity.MethodsThis study was planned to make a further contribution to solving the problem of the real role of the most common polymorphisms of TLR4, TLR9, TIRAP and FCGR2A genes in modulating the risk of malaria and disease severity in children from Burundi, Central Africa. All the paediatric patients aged six months to 10 years admitted to the hospital of Kiremba, Burundi, between February 2011 and September 2011, for fever and suspicion of acute malaria were screened for malaria parasitaemia by light microscopy of thick and thin blood smears. In children with malaria and in uninfected controls enrolled during the study period in the same hospital, blood samples were obtained on filter paper and TLR4 Asp299Gly rs4986790, TLR9 G1174A rs352139, T-1486 C rs187084 TLR9 T-1237 C rs5743836, TIRAP Ser180Leu rs8177374 and the FCGR2A His131Arg rs1801274 polymorphisms were studied using an ABI PRISM 7900 HT Fast Real-time instrument.ResultsA total of 602 patients and 337 controls were enrolled. Among the malaria cases, 553 (91.9 %) were considered as suffering from uncomplicated and 49 (8.1 %) from severe malaria. TLR9 T1237C rs5743836CC was associated with an increased risk of developing malaria (p = 0.03), although it was found with the same frequency in uncomplicated and severe malaria cases. No other differences were found in all alleles studied and in genotype frequencies between malaria cases and uninfected controls as well as between uncomplicated and severe malaria cases.ConclusionsTLR9 T1237C seems to condition susceptibility to malaria in Burundian children but not its severity, whereas none of the assessed SNPs of TLR4, TIRAP and FCGR2A seem to influence susceptibility to malaria and disease severity in this population.