Ventilatory load reduction by combined mild hypothermia and ultraprotective mechanical ventilation strategy in severe COVID-19-related acute respiratory distress syndrome: A physiological study.

We report the feasibility of a combined approach of very low low tidal volume (VT) and mild therapeutic hypothermia (MTH) to decrease the ventilatory load in a severe COVID-19-related acute respiratory distress syndrome (ARDS) cohort. Inclusion criteria was patients ≥18-years-old, severe COVID-19-related ARDS, driving pressure ∆P >15 cmH2O despite low-VT strategy, and extracorporeal therapies not available. MTH was induced with a surface cooling device aiming at 34°C. MTH was maintained for 72 h, followed by rewarming of 1°C per day. Data were shown in median (interquartile range, 25%-75%). Mixed effects analysis and Dunnett's test were used for comparisons. Seven patients were reported. Ventilatory load decreased during the first 24 h, minute ventilation (VE) decreased from 173 (170-192) to 152 (137-170) mL/kg/min (P = 0.007), and mechanical power (MP) decreased from 37 (31-40) to 29 (26-34) J/min (P = 0.03). At the end of the MTH period, the VT, P, and plateau pressure remained consistently close to 3.9 mL/kg predicted body weight, 12 and 26 cmH2O, respectively. A combined strategy of MTH and ultraprotective mechanical ventilation (MV) decreased VE and MP in severe COVID-19-related ARDS. The decreasing of ventilatory load may allow maintaining MV within safety thresholds.

Mechanical and morphological characterization of the emphysematous lung tissue.

Irreversible alveolar airspace enlargement is the main characteristic of pulmonary emphysema, which has been extensively studied using animal models. While the alterations in lung mechanics associated with these morphological changes have been documented in the literature, the study of the mechanical behavior of parenchymal tissue from emphysematous lungs has been poorly investigated. In this work, we characterize the mechanical and morphological properties of lung tissue in elastase-induced emphysema rat models under varying severity conditions. We analyze the non-linear tissue behavior using suitable hyperelastic constitutive models that enable to compare different non-linear responses in terms of hyperelastic material parameters. We further analyze the effect of the elastase dose on alveolar morphology and tissue material parameters and study their connection with respiratory-system mechanical parameters. Our results show that while the lung mechanical function is not significantly influenced by the elastase treatment, the tissue mechanical behavior and alveolar morphology are markedly affected by it. We further show a strong association between alveolar enlargement and tissue softening, not evidenced by respiratory-system compliance. Our findings highlight the importance of understanding tissue mechanics in emphysematous lungs, as changes in tissue properties could detect the early stages of emphysema remodeling. STATEMENT OF SIGNIFICANCE: Gas exchange is vital for life and strongly relies on the mechanical function of the lungs. Pulmonary emphysema is a prevalent respiratory disease where alveolar walls are damaged, causing alveolar enlargement that induces harmful changes in the mechanical response of the lungs. In this work, we study how the mechanical properties of lung tissue change during emphysema. Our results from animal models show that tissue properties are more sensitive to alveolar enlargement due to emphysema than other mechanical properties that describe the function of the whole respiratory system.

Airway Management of Critically Ill Pediatric Patients with Suspected or Proven Coronavirus Disease 2019 Infection: An Intensivist Point of View.

Advanced airway management of critically ill children is crucial for novel coronavirus disease 2019 (COVID-19) management in the pediatric intensive care unit, whether due to shock and hemodynamic collapse or acute respiratory failure. In this article, intubation is challenging due to the particularities of children's physiology and the underlying disease's pathophysiology, especially when an airborne pathogen, like COVID-19, is present. Unfortunately, published recommendations and guidelines for COVID-19 in pediatrics do not address in-depth endotracheal intubation in acutely ill children. We discussed the caveats and pitfalls of intubation in critically ill children.

Factores asociados a ventilación mecánica prolongada en niños con fallo respiratorio de causa pulmonar: Estudio de cohortes del registro de LARed Network / Factors associated with prolonged mechanical ventilation in children with pulmonary failure: Cohort study from the LARed Network registry

Objetivos Identificar los factores asociados con la ventilación mecánica prolongada (pVMI) en pacientes pediátricos en la unidad de cuidados intensivos pediátricos (UCIP). Diseño Análisis secundario de una cohorte prospectiva. Ámbito UCIP en los centros que integran LARed Network entre abril del 2017 y enero del 2022. Participantes Pacientes pediátricos en ventilación mecánica (VMI) debido a causas respiratorias. Definimos pVMI como eventos con tiempo VMI mayor al percentil 75 global. Intervenciones Ninguna.Variables de interés principales Datos demográficos, diagnósticos, puntajes de gravedad, terapias, complicaciones, estancias y morbimortalidad. Resultados Se incluyó a 1.698 niños con VMI de 8 ± 7 días y se definió pVMI en 9 días. Los factores relacionados al ingreso fueron la edad menor de 6 meses (OR 1,61, IC del 95%, 1,17-2,22), la displasia broncopulmonar (OR 3,71, IC del 95%, 1,87-7,36) y las infecciones fúngicas (OR 6,66, IC del 95%, 1,87-23,74), mientras que los pacientes con asma tuvieron menor riesgo de pVMI (OR 0,30, IC del 95%, 0,12-0,78). En cuanto a la evolución y la estancia en UCIP, se relacionó a neumonía asociada a la ventilación mecánica (OR 4,27, IC del 95%, 1,79-10,20), necesidad de traqueostomía (OR 2,91, IC del 95%, 1,89-4,48), transfusiones (OR 2,94, IC del 95%, 2,18-3,96), bloqueo neuromuscular (OR 2,08, IC del 95%, 1,48-2,93) y ventilación de alta frecuencia (OR 2,91, IC del 95%, 1,89-4,48) y una mayor estadía en UCIP (OR 1,13, IC del 95%, 1,10-1,16). Además, la presión media aérea mayor a 13cmH2O se asoció a pVMI (OR 1,57, IC del 95%, 1,12-2,21). Conclusiones Se identificaron factores relacionados con VMI de duración mayor a 9 días en pacientes pediátricos en UCIP en cuanto a ingreso, evolución y estancia. (AU)

Objectives To identify factors associated with prolonged mechanical ventilation (pMV) in pediatric patients in pediatric intensive care units (PICUs). Design Secondary analysis of a prospective cohort.SettingPICUs in centers that are part of the LARed Network between April 2017 and January 2022. Participants Pediatric patients on mechanical ventilation (IMV) due to respiratory causes. We defined IMV time greater than the 75th percentile of the global cohort. Interventions None.Main variables of interestDemographic data, diagnoses, severity scores, therapies, complications, length of stay, morbidity, and mortality. Results One thousand 6hundred and ninety 8children with MV of 8±7 days were included, and pIMV was defined as 9 days. Factors related to admission were age under 6 months (OR 1.61, 95% CI 1.17–2.22), bronchopulmonary dysplasia (OR 3.71, 95% CI 1.87–7.36), and fungal infections (OR 6.66, 95% CI 1.87–23.74), while patients with asthma had a lower risk of pIMV (OR 0.30, 95% CI 0.12–0.78). Regarding evolution and length of stay in the PICU, it was related to ventilation-associated pneumonia (OR 4.27, 95% CI 1.79–10.20), need for tracheostomy (OR 2.91, 95% CI 1.89–4.48), transfusions (OR 2.94, 95% CI 2.18–3.96), neuromuscular blockade (OR 2.08, 95% CI 1.48–2.93), high-frequency ventilation (OR 2.91, 95% CI 1.89–4.48), and longer PICU stay (OR 1.13, 95% CI 1.10–1.16). In addition, mean airway pressure greater than 13cmH2O was associated with pIMV (OR 1.57, 95% CI 1.12–2.21). Conclusions Factors related to IMV duration greater than 9 days in pediatric patients in PICUs were identified in terms of admission, evolution, and length of stay. (AU)

Factors associated with prolonged mechanical ventilation in children with pulmonary failure: Cohort study from the LARed Network registry.

OBJECTIVES: To identify factors associated with prolonged mechanical ventilation (pMV) in pediatric patients in pediatric intensive care units (PICUs). DESIGN: Secondary analysis of a prospective cohort. SETTING: PICUs in centers that are part of the LARed Network between April 2017 and January 2022. PARTICIPANTS: Pediatric patients on mechanical ventilation (IMV) due to respiratory causes. We defined IMV time greater than the 75th percentile of the global cohort. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Demographic data, diagnoses, severity scores, therapies, complications, length of stay, morbidity, and mortality. RESULTS: 1698 children with MV of 8±7 days were included, and pIMV was defined as 9 days. Factors related to admission were age under 6 months (OR 1.61, 95% CI 1.17-2.22), bronchopulmonary dysplasia (OR 3.71, 95% CI 1.87-7.36), and fungal infections (OR 6.66, 95% CI 1.87-23.74), while patients with asthma had a lower risk of pIMV (OR 0.30, 95% CI 0.12-0.78). Regarding evolution and length of stay in the PICU, it was related to ventilation-associated pneumonia (OR 4.27, 95% CI 1.79-10.20), need for tracheostomy (OR 2.91, 95% CI 1.89-4.48), transfusions (OR 2.94, 95% CI 2.18-3.96), neuromuscular blockade (OR 2.08, 95% CI 1.48-2.93), high-frequency ventilation (OR 2.91, 95% CI 1.89-4.48), and longer PICU stay (OR 1.13, 95% CI 1.10-1.16). In addition, mean airway pressure greater than 13cmH2O was associated with pIMV (OR 1.57, 95% CI 1.12-2.21). CONCLUSIONS: Factors related to IMV duration greater than 9 days in pediatric patients in PICUs were identified in terms of admission, evolution, and length of stay.

Lung mechanics in pediatric acute respiratory distress syndrome associated to acute COVID-19 and MIS-C: implications for therapies and outcomes. / Mecánica pulmonar en el síndrome de distrés respiratorio agudo pediátrico asociado a COVID-19 aguda y MIS-C.

OBJECTIVE: To describe lung mechanics in Pediatric Acute Respiratory Distress Syndrome (PARDS) associated with acute COVID-19 and MIS-C with respiratory failure. METHODS: A concurrent multicenter observational study was performed, analyzing clinical variables and pulmonary mechanics of PARDS associated with COVID-19 in 4 Pediatric intensive care units (PICU) in Peru. The subgroup analysis included PARDS associated with multisystem inflammatory syndrome in children (MIS-C), MIS-PARDS, and PARDS with COVID-19 primary respiratory infection, C-PARDS. In addition, receiver operating characteristic (ROC) curve analysis for mortality and lung mechanics was performed. RESULTS: 30 patients were included. The age was 7.5 (4-11) years, 60% were male, and mortality was 23%. 47% corresponded to MIS-PARDS and 53% to C-PARDS groups. C-PARDS had positive RT-PCR in 67% and MIS-PARDS none (p < 0.001). C-PARDS group had more profound hypoxemia (P/F ratio < 100, 86% vs. 38%, p < 0.01) and higher driving-pressure [14(10-22) vs 10(10-12) cmH2O], and lower compliance of the respiratory system (CRS) [0.5 (0.3-0.6) vs 0.7(0.6-0.8) ml/ kg/cmH2O] compared with MIS-PARDS (all p < 0.05). The ROC analysis for mortality showed that driving pressure had the best performance [AUC 0.91(95%CI0.81-1.00), with the best cut-off point of 15 cmH2O (100% sensitivity and 87% specificity). Mortality in C-PARDS was 38% and 7% in MIS-PARDS (p = 0.09). MV-free days were 12(0-23) in C-PARDS and 23(21-25) in MIS-PARDS (p = 0.02). CONCLUSION: Patients with C-PARDS have lung mechanics characteristics similar to classic moderate to severe PARDS. This was not observed in patients with MIS-C. As seen in other studies, a driving pressure ≥ 15 cmH2O was the best discriminator for mortality. These findings may help guide ventilatory management strategies for these two different presentations.

Capnometry after an inspiratory breath hold, PLAT CO2 , as a surrogate for P aCO 2 ${P}_{{\mathrm{aCO}}_{2}}$ in mild to moderate pediatric acute respiratory distress syndrome: A feasibility study.

OBJECTIVE: Accurate and reliable noninvasive methods to estimate gas exchange are necessary to guide clinical decisions to avoid frequent blood samples in children with pediatric acute respiratory distress syndrome (PARDS). We aimed to investigate the correlation and agreement between end-tidal P CO 2 ${P}_{{\mathrm{CO}}_{2}}$ measured immediately after a 3-s inspiratory-hold (PLAT CO2 ) by capnometry and P aCO 2 ${P}_{{\mathrm{aCO}}_{2}}$ measured by arterial blood gases (ABG) in PARDS. DESIGN: Prospective cohort study. SETTING: Seven-bed Pediatric Intensive Care Unit, Hospital El Carmen de Maipú, Chile. PATIENTS: Thirteen mechanically ventilated patients aged ≤15 years old undergoing neuromuscular blockade as part of management for PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients were in volume-controlled ventilation mode. The regular end-tidal P CO 2 ( P ETCO 2 ) ${P}_{{\mathrm{CO}}_{2}}({P}_{{\mathrm{ETCO}}_{2}})$ (without the inspiratory hold) was registered immediately after the ABG sample. An inspiratory-hold of 3 s was performed for lung mechanics measurements, recording P ETCO 2 ${P}_{{\mathrm{ETCO}}_{2}}$ in the breath following the inspiratory-hold. (PLAT CO2 ). End-tidal alveolar dead space fraction (AVDSf) was calculated as [ ( P aCO 2 - P ETCO 2 ) / P aCO 2 ] $[({P}_{{\mathrm{aCO}}_{2}}\mbox{--}{P}_{{\mathrm{ETCO}}_{2}})/{P}_{{\mathrm{aCO}}_{2}}]$ and its surrogate (S)AVDSf as [ ( PLAT CO 2 - P ETCO 2 ) / PLAT CO 2 ] $[{(}_{\mathrm{PLAT}}{\mathrm{CO}}_{2}\mbox{--}{P}_{{\mathrm{ETCO}}_{2}}){/}_{\mathrm{PLAT}}{\mathrm{CO}}_{2}]$ . Measurements of P aCO 2 ${P}_{{\mathrm{aCO}}_{2}}$ were considered the gold standard. We performed concordance correlation coefficient (ρc), Spearman's correlation (rho), and Bland-Altmann's analysis (mean difference ± SD [limits of agreement, LoA]). Eleven patients were included, with a median (interquartile range) age of 5 (2-11) months. Tidal volume was 5.8 (5.7-6.3) mL/kg, PEEP 8 (6-8), driving pressure 10 (8-11), and plateau pressure 17 (17-19) cm H2 O. Forty-one paired measurements were analyzed. P aCO 2 ${P}_{{\mathrm{aCO}}_{2}}$ was higher than P ETCO 2 ${P}_{{\mathrm{ETCO}}_{2}}$ (52 mmHg [48-54] vs. 42 mmHg [38-45], p < 0.01), and there were no significant differences with PLAT CO2 (50 mmHg [46-55], p > 0.99). The concordance correlation coefficient and Spearman's correlation between P aCO 2 ${P}_{{\mathrm{aCO}}_{2}}$ and PLAT CO2 were robust (ρc = 0.80 [95% confidence interval [CI]: 0.67-0.90]; and rho = 0.80, p < 0.001.), and for P ETCO 2 ${P}_{{\mathrm{ETCO}}_{2}}$ were weak and strong (ρc = 0.27 [95% CI: 0.15-0.38]; and rho = 0.63, p < 0.01). The bias between PLAT CO2 and P aCO 2 ${P}_{{\mathrm{aCO}}_{2}}$ was -0.4 ± 3.5 mmHg (LoA -7.2 to 6.4), and between P ETCO 2 ${P}_{{\mathrm{ETCO}}_{2}}$ and P aCO 2 ${P}_{{\mathrm{aCO}}_{2}}$ was -8.5 ± 4.1 mmHg (LoA -16.6 to -0.5). The correlation between AVDSf and (S)AVDSf was moderate (rho = 0.55, p < 0.01), and the mean difference was -0.5 ± 5.6% (LoA -11.5 to 10.5). CONCLUSION: This pilot study showed the feasibility of measuring end-tidal CO2 after a 3-s end-inspiratory breath hole in pediatric patients undergoing controlled ventilation for ARDS. Encouraging preliminary results warrant further study of this technique.

Plateau Pressure and Driving Pressure in Volume- and Pressure-Controlled Ventilation: Comparison of Frictional and Viscoelastic Resistive Components in Pediatric Acute Respiratory Distress Syndrome.

OBJECTIVES: To examine frictional, viscoelastic, and elastic resistive components, as well threshold pressures, during volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) in pediatric patients with acute respiratory distress syndrome (ARDS). DESIGN: Prospective cohort study. SETTING: Seven-bed PICU, Hospital El Carmen de Maipú, Chile. PATIENTS: Eighteen mechanically ventilated patients less than or equal to 15 years old undergoing neuromuscular blockade as part of management for ARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients were in VCV mode during measurement of pulmonary mechanics, including: the first pressure drop (P1) upon reaching zero flow during the inspiratory hold, peak inspiratory pressure (PIP), plateau pressure (P PLAT ), and total positive end-expiratory pressure (tPEEP). We calculated the components of the working pressure, as defined by the following: frictional resistive = PIP-P1; viscoelastic resistive = P1-P PLAT ; purely elastic = driving pressure (ΔP) = P PLAT -tPEEP; and threshold = intrinsic PEEP. The procedures and calculations were repeated on PCV, keeping the same tidal volume and inspiratory time. Measurements in VCV were considered the gold standard. We performed Spearman correlation and Bland-Altman analysis. The median (interquartile range [IQR]) for patient age was 5 months (2-17 mo). Tidal volume was 5.7 mL/kg (5.3-6.1 mL/kg), PIP cm H 2 O 26 (23-27 cm H 2 O), P1 23 cm H 2 O (21-26 cm H 2 O), P PLAT 19 cm H 2 O (17-22 cm H 2 O), tPEEP 9 cm H 2 O (8-9 cm H 2 O), and ΔP 11 cm H 2 O (9-13 cm H 2 O) in VCV mode at baseline. There was a robust correlation (rho > 0.8) and agreement between frictional resistive, elastic, and threshold components of working pressure in both modes but not for the viscoelastic resistive component. The purely frictional resistive component was negligible. Median peak inspiratory flow with decelerating-flow was 21 (IQR, 15-26) and squared-shaped flow was 7 L/min (IQR, 6-10 L/min) ( p < 0.001). CONCLUSIONS: P PLAT , ΔP, and tPEEP can guide clinical decisions independent of the ventilatory mode. The modest purely frictional resistive component emphasizes the relevance of maintaining the same safety limits, regardless of the selected ventilatory mode. Therefore, peak inspiratory flow should be studied as a mechanism of ventilator-induced lung injury in pediatric ARDS.

Noninvasive Ventilation for Pediatric Acute Respiratory Distress Syndrome: Experience From the 2016/2017 Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Prospective Cohort Study.

OBJECTIVES: The worldwide practice and impact of noninvasive ventilation (NIV) in pediatric acute respiratory distress syndrome (PARDS) is unknown. We sought to describe NIV use and associated clinical outcomes in PARDS. DESIGN: Planned ancillary study to the 2016/2017 prospective Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology study. SETTING: One hundred five international PICUs. PATIENTS: Patients with newly diagnosed PARDS admitted during 10 study weeks. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Children were categorized by their respiratory support at PARDS diagnosis into NIV or invasive mechanical ventilation (IMV) groups. Of 708 subjects with PARDS, 160 patients (23%) received NIV at PARDS diagnosis (NIV group). NIV failure rate (defined as tracheal intubation or death) was 84 of 160 patients (53%). Higher nonrespiratory pediatric logistic organ dysfunction (PELOD-2) score, Pa o2 /F io2 was less than 100 at PARDS diagnosis, immunosuppression, and male sex were independently associated with NIV failure. NIV failure was 100% among patients with nonrespiratory PELOD-2 score greater than 2, Pa o2 /F io2 less than 100, and immunosuppression all present. Among patients with Pa o2 /F io2 greater than 100, children in the NIV group had shorter total duration of NIV and IMV, than the IMV at initial diagnosis group. We failed to identify associations between NIV use and PICU survival in a multivariable Cox regression analysis (hazard ratio 1.04 [95% CI, 0.61-1.80]) or mortality in a propensity score matched analysis ( p = 0.369). CONCLUSIONS: Use of NIV at PARDS diagnosis was associated with shorter exposure to IMV in children with mild to moderate hypoxemia. Even though risk of NIV failure was high in some children, we failed to identify greater hazard of mortality in these patients.

Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2).

OBJECTIVES: We sought to update our 2015 work in the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS), considering new evidence and topic areas that were not previously addressed. DESIGN: International consensus conference series involving 52 multidisciplinary international content experts in PARDS and four methodology experts from 15 countries, using consensus conference methodology, and implementation science. SETTING: Not applicable. PATIENTS: Patients with or at risk for PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eleven subgroups conducted systematic or scoping reviews addressing 11 topic areas: 1) definition, incidence, and epidemiology; 2) pathobiology, severity, and risk stratification; 3) ventilatory support; 4) pulmonary-specific ancillary treatment; 5) nonpulmonary treatment; 6) monitoring; 7) noninvasive respiratory support; 8) extracorporeal support; 9) morbidity and long-term outcomes; 10) clinical informatics and data science; and 11) resource-limited settings. The search included MEDLINE, EMBASE, and CINAHL Complete (EBSCOhost) and was updated in March 2022. Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to summarize evidence and develop the recommendations, which were discussed and voted on by all PALICC-2 experts. There were 146 recommendations and statements, including: 34 recommendations for clinical practice; 112 consensus-based statements with 18 on PARDS definition, 55 on good practice, seven on policy, and 32 on research. All recommendations and statements had agreement greater than 80%. CONCLUSIONS: PALICC-2 recommendations and consensus-based statements should facilitate the implementation and adherence to the best clinical practice in patients with PARDS. These results will also inform the development of future programs of research that are crucially needed to provide stronger evidence to guide the pediatric critical care teams managing these patients.

Monitoring in Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference.

OBJECTIVES: Monitoring is essential to assess changes in the lung condition, to identify heart-lung interactions, and to personalize and improve respiratory support and adjuvant therapies in pediatric acute respiratory distress syndrome (PARDS). The objective of this article is to report the rationale of the revised recommendations/statements on monitoring from the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2). DATA SOURCES: MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost). STUDY SELECTION: We included studies focused on respiratory or cardiovascular monitoring of children less than 18 years old with a diagnosis of PARDS. We excluded studies focused on neonates. DATA EXTRACTION: Title/abstract review, full-text review, and data extraction using a standardized data collection form. DATA SYNTHESIS: The Grading of Recommendations Assessment, Development and Evaluation approach was used to identify and summarize evidence and develop recommendations. We identified 342 studies for full-text review. Seventeen good practice statements were generated related to respiratory and cardiovascular monitoring. Four research statements were generated related to respiratory mechanics and imaging monitoring, hemodynamics monitoring, and extubation readiness monitoring. CONCLUSIONS: PALICC-2 monitoring good practice and research statements were developed to improve the care of patients with PARDS and were based on new knowledge generated in recent years in patients with PARDS, specifically in topics of general monitoring, respiratory system mechanics, gas exchange, weaning considerations, lung imaging, and hemodynamic monitoring.

Understanding clinical and biological heterogeneity to advance precision medicine in paediatric acute respiratory distress syndrome.

Paediatric acute respiratory distress syndrome (PARDS) is a heterogeneous clinical syndrome that is associated with high rates of mortality and long-term morbidity. Factors that distinguish PARDS from adult acute respiratory distress syndrome (ARDS) include changes in developmental stage and lung maturation with age, precipitating factors, and comorbidities. No specific treatment is available for PARDS and management is largely supportive, but methods to identify patients who would benefit from specific ventilation strategies or ancillary treatments, such as prone positioning, are needed. Understanding of the clinical and biological heterogeneity of PARDS, and of differences in clinical features and clinical course, pathobiology, response to treatment, and outcomes between PARDS and adult ARDS, will be key to the development of novel preventive and therapeutic strategies and a precision medicine approach to care. Studies in which clinical, biomarker, and transcriptomic data, as well as informatics, are used to unpack the biological and phenotypic heterogeneity of PARDS, and implementation of methods to better identify patients with PARDS, including methods to rapidly identify subphenotypes and endotypes at the point of care, will drive progress on the path to precision medicine.

Characteristics of Medically Transported Critically Ill Children with Respiratory Failure in Latin America: Implications for Outcomes.

Several challenges exist for referral and transport of critically ill children in resource-limited regions such as Latin America; however, little is known about factors associated with clinical outcomes. Thus, we aimed to describe the characteristics of critically ill children in Latin America transferred to pediatric intensive care units for acute respiratory failure to identify risk factors for mortality. We analyzed data from 2,692 patients admitted to 28 centers in the Pediatric Collaborative Network of Latin America Acute Respiratory Failure Registry. Among patients referred from another facility (773, 28%), nonurban transports were independently associated with mortality (adjusted odds ratio = 9.4; 95% confidence interval: 2.4-36.3).

Spontaneous breathing promotes lung injury in an experimental model of alveolar collapse.

Vigorous spontaneous breathing has emerged as a promotor of lung damage in acute lung injury, an entity known as "patient self-inflicted lung injury". Mechanical ventilation may prevent this second injury by decreasing intrathoracic pressure swings and improving regional air distribution. Therefore, we aimed to determine the effects of spontaneous breathing during the early stage of acute respiratory failure on lung injury and determine whether early and late controlled mechanical ventilation may avoid or revert these harmful effects. A model of partial surfactant depletion and lung collapse was induced in eighteen intubated pigs of 32 ±4 kg. Then, animals were randomized to (1) SB-group: spontaneous breathing with very low levels of pressure support for the whole experiment (eight hours), (2) Early MV-group: controlled mechanical ventilation for eight hours, or (3) Late MV-group: first half of the experiment on spontaneous breathing (four hours) and the second half on controlled mechanical ventilation (four hours). Respiratory, hemodynamic, and electric impedance tomography data were collected. After the protocol, animals were euthanized, and lungs were extracted for histologic tissue analysis and cytokines quantification. SB-group presented larger esophageal pressure swings, progressive hypoxemia, lung injury, and more dorsal and inhomogeneous ventilation compared to the early MV-group. In the late MV-group switch to controlled mechanical ventilation improved the lung inhomogeneity and esophageal pressure swings but failed to prevent hypoxemia and lung injury. In a lung collapse model, spontaneous breathing is associated to large esophageal pressure swings and lung inhomogeneity, resulting in progressive hypoxemia and lung injury. Mechanical ventilation prevents these mechanisms of patient self-inflicted lung injury if applied early, before spontaneous breathing occurs, but not when applied late.

Distribution and Magnitude of Regional Volumetric Lung Strain and Its Modification by PEEP in Healthy Anesthetized and Mechanically Ventilated Dogs.

The present study describes the magnitude and spatial distribution of lung strain in healthy anesthetized, mechanically ventilated dogs with and without positive end-expiratory pressure (PEEP). Total lung strain (LSTOTAL) has a dynamic (LSDYNAMIC) and a static (LSSTATIC) component. Due to lung heterogeneity, global lung strain may not accurately represent regional total tissue lung strain (TSTOTAL), which may also be described by a regional dynamic (TSDYNAMIC) and static (TSSTATIC) component. Six healthy anesthetized beagles (12.4 ± 1.4 kg body weight) were placed in dorsal recumbency and ventilated with a tidal volume of 15 ml/kg, respiratory rate of 15 bpm, and zero end-expiratory pressure (ZEEP). Respiratory system mechanics and full thoracic end-expiratory and end-inspiratory CT scan images were obtained at ZEEP. Thereafter, a PEEP of 5 cmH2O was set and respiratory system mechanics measurements and end-expiratory and end-inspiratory images were repeated. Computed lung volumes from CT scans were used to evaluate the global LSTOTAL, LSDYNAMIC, and LSSTATIC during PEEP. During ZEEP, LSSTATIC was assumed zero; therefore, LSTOTAL was the same as LSDYNAMIC. Image segmentation was applied to CT images to obtain maps of regional TSTOTAL, TSDYNAMIC, and TSSTATIC during PEEP, and TSDYNAMIC during ZEEP. Compliance increased (p = 0.013) and driving pressure decreased (p = 0.043) during PEEP. PEEP increased the end-expiratory lung volume (p < 0.001) and significantly reduced global LSDYNAMIC (33.4 ± 6.4% during ZEEP, 24.0 ± 4.6% during PEEP, p = 0.032). LSSTATIC by PEEP was larger than the reduction in LSDYNAMIC; therefore, LSTOTAL at PEEP was larger than LSDYNAMIC at ZEEP (p = 0.005). There was marked topographic heterogeneity of regional strains. PEEP induced a significant reduction in TSDYNAMIC in all lung regions (p < 0.05). Similar to global findings, PEEP-induced TSSTATIC was larger than the reduction in TSDYNAMIC; therefore, PEEP-induced TSTOTAL was larger than TSDYNAMIC at ZEEP. In conclusion, PEEP reduced both global and regional estimates of dynamic strain, but induced a large static strain. Given that lung injury has been mostly associated with tidal deformation, limiting dynamic strain may be an important clinical target in healthy and diseased lungs, but this requires further study.