Respiratory drive heterogeneity associated with systemic inflammation and vascular permeability in acute respiratory distress syndrome.

BACKGROUND: In acute respiratory distress syndrome (ARDS), respiratory drive often differs among patients with similar clinical characteristics. Readily observable factors like acid-base state, oxygenation, mechanics, and sedation depth do not fully explain drive heterogeneity. This study evaluated the relationship of systemic inflammation and vascular permeability markers with respiratory drive and clinical outcomes in ARDS. METHODS: ARDS patients enrolled in the multicenter EPVent-2 trial with requisite data and plasma biomarkers were included. Neuromuscular blockade recipients were excluded. Respiratory drive was measured as PES0.1, the change in esophageal pressure during the first 0.1 s of inspiratory effort. Plasma angiopoietin-2, interleukin-6, and interleukin-8 were measured concomitantly, and 60-day clinical outcomes evaluated. RESULTS: 54.8% of 124 included patients had detectable respiratory drive (PES0.1 range of 0-5.1 cm H2O). Angiopoietin-2 and interleukin-8, but not interleukin-6, were associated with respiratory drive independently of acid-base, oxygenation, respiratory mechanics, and sedation depth. Sedation depth was not significantly associated with PES0.1 in an unadjusted model, or after adjusting for mechanics and chemoreceptor input. However, upon adding angiopoietin-2, interleukin-6, or interleukin-8 to models, lighter sedation was significantly associated with higher PES0.1. Risk of death was less with moderate drive (PES0.1 of 0.5-2.9 cm H2O) compared to either lower drive (hazard ratio 1.58, 95% CI 0.82-3.05) or higher drive (2.63, 95% CI 1.21-5.70) (p = 0.049). CONCLUSIONS: Among patients with ARDS, systemic inflammatory and vascular permeability markers were independently associated with higher respiratory drive. The heterogeneous response of respiratory drive to varying sedation depth may be explained in part by differences in inflammation and vascular permeability.

Switches in non-invasive respiratory support strategies during acute hypoxemic respiratory failure: Need to monitoring from a retrospective observational study

Objective To explore combined non-invasive-respiratory-support (NIRS) patterns, reasons for NIRS switching, and their potential impact on clinical outcomes in acute-hypoxemic-respiratory-failure (AHRF) patients. Design Retrospective, single-center observational study. Setting Intensive Care Medicine. Patients AHRF patients (cardiac origin and respiratory acidosis excluded) underwent combined NIRS therapies such as non-invasive-ventilation (NIV) and High-Flow-Nasal-Cannula (HFNC). Interventions Patients were classified based on the first NIRS switch performed (HFNC-to-NIV or NIV-to-HFNC), and further specific NIRS switching strategies (NIV trial-like vs. Non-NIV trial-like and single vs. multiples switches) were independently evaluated. Main variables of interest Reasons for switching, NIRS failure and mortality rates. Results A total of 63 patients with AHRF were included, receiving combined NIRS, 58.7% classified in the HFNC-to-NIV group and 41.3% in the NIV-to-HFNC group. Reason for switching from HFNC to NIV was AHRF worsening (100%), while from NIV to HFNC was respiratory improvement (76.9%). NIRS failure rates were higher in the HFNC-to-NIV than in NIV-to-HFNC group (81% vs. 35%, p < 0.001). Among HFNC-to-NIV patients, there was no difference in the failure rate between the NIV trial-like and non-NIV trial-like groups (86% vs. 78%, p = 0.575) but the mortality rate was significantly lower in NIV trial-like group (14% vs. 52%, p = 0.02). Among NIV to HFNC patients, NIV failure was lower in the single switch group compared to the multiple switches group (15% vs. 53%, p = 0.039), with a shorter length of stay (5 [2–8] vs. 12 [8–30] days, p = 0.001). Conclusions NIRS combination is used in real life and both switches’ strategies, HFNC to NIV and NIV to HFNC, are common in AHRF management. Transitioning from HFNC to NIV is suggested as a therapeutic escalation and in this context performance of a NIV-trial could be beneficial. ... (AU)

Objetivo Explorar los patrones combinados de soporte-respiratorio-no-invasivo (SRNI), las razones para cambiar de SRNI y su potencial impacto en los resultados clínicos en pacientes con insuficiencia-respiratoria-aguda-hipoxémica (IRAH). Diseño Estudio observacional retrospectivo unicéntrico. Ámbito Cuidados Intensivos. Pacientes Pacientes con IRAH (excluyendo causa cardíaca y acidosis respiratoria) que recibieron tanto ventilación-no-invasiva (VNI) como cánula-nasal-de-alto-flujo (CNAF). Intervenciones Se categorizó a los pacientes según el primer cambio de SRNI realizado (CNAF-to-VNI o VNI-to-CNAF) y se evaluaron estrategias específicas de SRNI (VNI trial-like vs. Non-VNI trial-like y cambio único vs. múltiples cambios de NIRS) de manera independiente. Variables de interés principales Razones para el cambio, así como las tasas de fracaso de SRNI y la mortalidad. Resultados Un total de 63 pacientes recibieron SRNI combinado, 58,7% clasificados en el grupo CNAF-to-VNI y 41,3% en el grupo VNI-to-CNAF. Los cambios de CNAF a VNI ocurrieron por empeoramiento de la IRHA (100%) y de VNI a CNAF por mejora respiratoria (76.9%). Las tasas de fracaso de SRNI fueron mayores de CNAF a VNI que de VNI a CNAF (81% vs. 35%, p < 0.001). Dentro de los pacientes de CNAF a VNI, no hubo diferencia en las tasas de fracaso entre los grupos VNI trial-like y no-VNI trial-like (86% vs. 78%, p = 0.575), pero la mortalidad fue menor en el grupo VNI trial-like (14% vs. 52%, p = 0.02). Dentro de los pacientes de VNI a CNAF, el fracaso de VNI fue menor en grupo de cambio único vs. múltiple (15% vs. 53%, p = 0.039). Conclusiones Los cambios de estrategia de SRNI son comunes en el manejo clínico diario de la IRHA. El cambio de CNAF a VNI impresiona de ser una escalada terapéutica y en este contexto la realización de un VNI-trial puede ser beneficioso. Al contrario, cambiar de VNI a CNAF impresiona de ser una desescalada terapéutica y parece segura si no hay fracaso ... (AU)

Eficacia del protocolo Start to move en funcionalidad, DA-UCI y delirio: ensayo clínico aleatorizado / Efficacy of the «Start to move» protocol on functionality, ICU-acquired weakness and delirium: Randomized clinical trial

Objetivo Evaluar la eficacia del protocolo Start to move comparado con el tratamiento convencional en sujetos mayores de 15 años hospitalizados en la UCI sobre una mejoría en funcionalidad, disminución de debilidad adquirida en la UCI (DA-UCI), incidencia de delirio, días de ventilación mecánica (VM), estadía en la UCI y mortalidad a los 28 días. Diseño Ensayo clínico controlado aleatorizado. Ámbito Unidad de paciente crítico. Participantes Incluye adultos mayores a 15 años con VMI mayor a 48h, asignación aleatoria. Intervenciones Protocolo «Start to move» y tratamiento convencional. Variables de interés principales Se analizó funcionalidad, incidencia DA-UCI, incidencia delirio, días VM, estadía UCI y mortalidad-28 días, ClinicalTrials.gov número, NCT05053724. Resultados Sesenta y nueve sujetos fueron ingresados al estudio, 33 al grupo Start to move y 36 a tratamiento convencional, comparables clínico y sociodemograficamente. En el grupo Start to move la incidencia DAUCI al egreso de la UCI fue de 35,7 vs. 80,7% grupo tratamiento convencional (p=0,001). La funcionalidad (FSS-ICU) al egreso de la UCI corresponde a 26 vs. 17 puntos a favor del grupo Start to move (p=0,001). La diferencia en Barthel al egreso de la UCI fue del 20% a favor del grupo Start to move (p=0,006). No hubo diferencias significativas en incidencia de delirio, días de VM, estadía UCI y mortalidad-28 días. El estudio no reportó eventos adversos, ni suspensión de protocolo. Conclusiones La aplicación del protocolo Start to move en la UCI se asoció reducción en la incidencia DA-UCI, aumento en funcionalidad y menor caída en puntaje Barthel al egreso. (AU)

Objective To evaluate the efficacy of the Start to move protocol compared to conventional treatment in subjects over 15 years of age hospitalized in the ICU on an improvement in functionality, decrease in ICU-acquired weakness (IUCD), incidence of delirium, days of mechanical ventilation (MV), length of stay in ICU and mortality at 28 days. Design Randomized controlled clinical trial. Setting Intensive care unit. Participants Includes adults older than 15 years with invasive mechanical ventilation more than 48h, randomized allocation. Interventions Start to move protocol and conventional treatment. Main variables of interest Functionality, incidence of ICU-acquired weakness, incidence of delirium, days on mechanical ventilation, ICU stay and mortality-28 days, ClinicalTrials.gov number, NCT05053724. Results Sixty-nine subjects were admitted to the study, 33 to the Start to move group and 36 to conventional treatment, clinically and sociodemographic comparable. In the “Start to move” group, the incidence of IUCD at ICU discharge was 35.7% vs. 80.7% in the “conventional treatment” group (P=.001). Functionality (FSS-ICU) at ICU discharge corresponds to 26 vs. 17 points in favor of the “Start to move” group (P=.001). The difference in Barthel at ICU discharge was 20% in favor of the “Start to move” group (P=.006). There were no significant differences in the incidence of delirium, days of mechanical ventilation, ICU stay and 28-day mortality. The study did not report adverse events or protocol suspension. Conclusions The application of the “Start to move” protocol in ICU showed a reduction in the incidence of IUCD, an increase in functionality and a smaller decrease in Barthel score at discharge. (AU)

Differences of respiratory mechanics in mechanical ventilation of acute respiratory distress syndrome between patients with COVID-19 and Influenza A.

BACKGROUND: Whether COVID-19-induced acute respiratory distress syndrome (ARDS) should be approached differently in terms of mechanical ventilation therapy compared to other virus-induced ARDS is debatable. Therefore, we aimed to ascertain whether the respiratory mechanical characteristics of COVID-19-induced ARDS differ from those of influenza A induced ARDS, in order to establish a rationale for mechanical ventilation therapy in COVID-19-induced ARDS. METHODS: This was a retrospective cohort study comparing patients with COVID-19-induced ARDS and influenza A induced ARDS. We included intensive care unit (ICU) patients with COVID-19 or Influenza A aged ≥ 19, who were diagnosed with ARDS according to the Berlin definition between January 2015 and July 2021. Ventilation parameters for respiratory mechanics were collected at specific times on days one, three, and seven after intubation. RESULTS: The median age of the 87 participants was 71.0 (62.0-78.0) years old, and 63.2% were male. The ratio of partial pressure of oxygen in arterial blood to the fractional of inspiratory oxygen concentration in COVID-19-induced ARDS was lower than that in influenza A induced ARDS during the initial stages of mechanical ventilation (influenza A induced ARDS 216.1 vs. COVID-19-induced ARDS 167.9, p = 0.009, day 1). The positive end expiratory pressure remained consistently higher in the COVID-19 group throughout the follow-up period (7.0 vs. 10.0, p < 0.001, day 1). COVID-19 and influenza A initially showed different directions for peak inspiratory pressure and dynamic compliance; however, after day 3, both groups exhibited similar directions. Dynamic driving pressure exhibited opposite trends between the two groups during mechanical ventilation. CONCLUSIONS: Respiratory mechanics show clear differences between COVID-19-induced ARDS and influenza A induced ARDS. Based on these findings, we can consider future treatment strategies for COVID-19-induced ARDS.

A vagal reflex evoked by airway closure.

Airway integrity must be continuously maintained throughout life. Sensory neurons guard against airway obstruction and, on a moment-by-moment basis, enact vital reflexes to maintain respiratory function1,2. Decreased lung capacity is common and life-threatening across many respiratory diseases, and lung collapse can be acutely evoked by chest wall trauma, pneumothorax or airway compression. Here we characterize a neuronal reflex of the vagus nerve evoked by airway closure that leads to gasping. In vivo vagal ganglion imaging revealed dedicated sensory neurons that detect airway compression but not airway stretch. Vagal neurons expressing PVALB mediate airway closure responses and innervate clusters of lung epithelial cells called neuroepithelial bodies (NEBs). Stimulating NEBs or vagal PVALB neurons evoked gasping in the absence of airway threats, whereas ablating NEBs or vagal PVALB neurons eliminated gasping in response to airway closure. Single-cell RNA sequencing revealed that NEBs uniformly express the mechanoreceptor PIEZO2, and targeted knockout of Piezo2 in NEBs eliminated responses to airway closure. NEBs were dispensable for the Hering-Breuer inspiratory reflex, which indicated that discrete terminal structures detect airway closure and inflation. Similar to the involvement of Merkel cells in touch sensation3,4, NEBs are PIEZO2-expressing epithelial cells and, moreover, are crucial for an aspect of lung mechanosensation. These findings expand our understanding of neuronal diversity in the airways and reveal a dedicated vagal pathway that detects airway closure to help preserve respiratory function.

Lung microbiota composition, respiratory mechanics, and outcomes in COVID-19-related ARDS.

Few data are available on the lung microbiota composition of patients with coronavirus disease 2019-related acute respiratory distress syndrome (C-ARDS) receiving invasive mechanical ventilation (IMV). Moreover, it has never been investigated whether there is a potential correlation between lung microbiota communities and respiratory mechanics. We performed a prospective observational study in two intensive care units of a university hospital in Italy. Lung microbiota was investigated by bacterial 16S rRNA gene sequencing, performed on bronchoalveolar lavage fluid samples withdrawn after intubation. The lung bacterial communities were analyzed after stratification by respiratory system compliance/predicted body weight (Crs) and ventilatory ratio (VR). Weaning from IMV and hospital survival were assessed as secondary outcomes. In 70 C-ARDS patients requiring IMV from 1 April through 31 December 2020, the lung microbiota composition (phylum taxonomic level, permutational multivariate analysis of variance test) significantly differed between who had low Crs vs those with high Crs (P = 0.010), as well as in patients with low VR vs high VR (P = 0.012). As difference-driving taxa, Proteobacteria (P = 0.017) were more dominant and Firmicutes (P = 0.040) were less dominant in low- vs high-Crs patients. Similarly, Proteobacteria were more dominant in low- vs high-VR patients (P = 0.013). After multivariable regression analysis, we further observed lung microbiota diversity as a negative predictor of weaning from IMV and hospital survival (hazard ratio = 3.31; 95% confidence interval, 1.52-7.20, P = 0.048). C-ARDS patients with low Crs/low VR had a Proteobacteria-dominated lung microbiota. Whether patients with a more diverse lung bacterial community may have more chances to be weaned from IMV and discharged alive from the hospital warrants further large-scale investigations. IMPORTANCE: Lung microbiota characteristics were demonstrated to predict ventilator-free days and weaning from mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). In this study, we observed that in severe coronavirus disease 2019 patients with ARDS who require invasive mechanical ventilation, lung microbiota characteristics were associated with respiratory mechanics. Specifically, the lung microbiota of patients with low respiratory system compliance and low ventilatory ratio was characterized by Proteobacteria dominance. Moreover, after multivariable regression analysis, we also found an association between patients' microbiota diversity and a higher possibility of being weaned from mechanical ventilation and discharged alive from the hospital. For these reasons, lung microbiota characterization may help to stratify patient characteristics and orient the delivery of target interventions. (This study has been registered at ClinicalTrials.gov on 17 February 2020 under identifier NCT04271345.).Registered at ClinicalTrials.gov, 17 February 2020 (NCT0427135).

The influence of the post-hepatic septum and abdominal volume on breathing mechanics in the lizard Salvator merianae (Squamata: Teiidae).

Teiid lizards possess an incomplete post-hepatic septum (PHS) separating the lungs and liver from the remaining viscera, and within this group, Salvator merianae has the most complete PHS. In this study, we explored the combined effects of the presence of the PHS and alterations in abdominal volume on the mechanics of the respiratory system. The PHS is believed to act as a mechanical barrier, mitigating the impact of the viscera on the lungs. Using established protocols, we determined static (Cstat) and dynamic (Cdyn) compliance, lung volume and work of breathing for the respiratory system in tegu lizards with intact (PHS+) or removed (PHS-) PHS, combined with (balloon+) or without (balloon-) increased abdominal volume. The removal of the PHS significantly reduced resting lung volume and Cdyn, as well as significantly increasing the work of breathing. An increase in abdominal volume significantly reduced Cstat, Cdyn, and resting and maximum lung volume. However, the work of breathing increased less in the PHS+/balloon+ treatment than in the PHS- treatments. These results highlight the barrier function of the PHS within the tegu lizard's body cavity. The septum effectively reduces the impact of the viscera on the respiratory system, enabling the lungs to be ventilated at a low work level, even when abdominal volume is increased. The presence of the PHS in teiid lizards underscores how extrapulmonary structures, such as septal divisions of the body cavity, can profoundly affect pulmonary breathing mechanics.

Characteristics and risk factors associated with mortality during the first cycle of prone secondary to ARDS due to SARS-CoV-2 pneumonia / Características y factores de riesgo asociados a mortalidad durante el primer ciclo de prono por SDRA secundario a neumonía por SARS-CoV-2

Objective To analyze characteristics, changes in oxygenation, and pulmonary mechanics, in mechanically ventilated patients with ARDS due to SARS-CoV-2 treated with prone position and evaluate the response to this maneuver.Design Cohort study including patients with PaO2/FiO2 <150mmHg requiring prone position over 18 months. We classified patients according to PaO2/FiO2 changes from basal to 24h after the first prone cycle as: 1) no increase 2) increase <25%, 3) 25%–50% increase 4) increase >50%. Setting 33-bed medical-surgical Intensive Care Unit (ICU) in Argentina. Patients 273 patients. Interventions None. Main variables of interest Epidemiological characteristics, respiratory mechanics and oxygenation were compared between survivors and non-survivors. Independent factors associated with in-hospital mortality were identified. Results Baseline PaO2/FiO2 was 116 [97–135]mmHg (115 [94–136] in survivors vs. 117 [98–134] in non-survivors; p=0.50). After prone positioning, 22 patients (8%) had similar PaO2/FiO2 values; 46(16%) increased PaO2/FiO2 ≤25%; 55 (21%) increased it 25%–50%; and 150 (55%), >50%. Mortality was 86%, 87%, 72% and 50% respectively (p<0.001). Baseline PaO2/FiO2, <100mmHg did not imply that patients were refractory to prone position. Factors independently associated with mortality were age, percentage increase in PaO2/FiO2 after 24h being in prone, and number of prone cycles. Conclusions Older patients unable to improve PaO2/FiO2 after 24h in prone position and who require >1 cycle might early receive additional treatments for refractory hypoxemia. After the first 24h in the prone position, a low percentage of PaO2/FiO2 increase over baseline, beyond the initial value, was independently associated with higher mortality. (AU)

Objetivo Analizar las características, cambios en la oxigenación y mecánica pulmonar, en pacientes ventilados mecánicamente con SDRA por SARS-CoV-2 tratados con posición prona, y evaluar la respuesta a esta maniobra. Diseño Estudio de cohorte que incluyó pacientes con PaO2/FiO2 <150mmHg que requirieron posición prona durante 18 meses. Se clasificaron los pacientes según los cambios de PaO2/FiO2 desde el basal y 24horas después del primer ciclo prono como: 1) Sin aumento 2) Aumento <25%, 3) 25–50% de aumento 4) Aumento >50%. Ambito Unidad de Cuidados Intensivos (UCI) médico-quirúrgica de 33 camas en Argentina. Pacientes 273 pacientes. Intervenciones Ninguna. Principales variables de interés Se compararon características epidemiológicas, mecánica respiratoria y oxigenación entre sobrevivientes y no sobrevivientes. Se identificaron factores independientes asociados a la mortalidad hospitalaria. Resultados La PaO2/FiO2 basal fue de 116 [97–135]mmHg (115 [94–136] en sobrevivientes vs. 117 [98–134] en no sobrevivientes; p=0,50). Después de la posición prona, 22 pacientes (8%) tenían valores similares de PaO2/FiO2; 46 (16%) aumentaron PaO2/FiO2 ≤25%; 55 (21%) lo aumentaron 25%–50%; y 150 (55%), >50%. La mortalidad fue de 86%, 87%, 72% y 50% respectivamente (p<0,001). La PaO2/FiO2 basal, <100mmHg no implicó que los pacientes fueran refractarios a la posición prona. Los factores asociados independientemente con la mortalidad fueron la edad, el aumento porcentual de PaO2/FiO2 después de 24horas en prona, y el número de ciclos prono. Conclusiones Los pacientes mayores que no pueden mejorar PaO2/FiO2 después de 24 horas en posición prona y que requieren más de 1 ciclo podrían recibir tratamientos adicionales para la hipoxemia refractaria. Después de las primeras 24horas en decúbito prono, un bajo porcentaje de aumento de PaO2/FiO2 sobre el valor basal, más allá del valor inicial, se asoció de forma independiente con una mayor mortalidad. (AU)

Comprehensive study of mechanical power in controlled mechanical ventilation: Prevalence of elevated mechanical power and component analysis / Estudio Integral de la Potencia Mecánica en la Ventilación Mecánica Controlada: Prevalencia de Potencia Mecánica Elevada y Análisis de Componentes

Objective To determine the prevalence of elevated mechanical power (MP) values (>17J/min) used in routine clinical practice. Design Observational, descriptive, cross-sectional, analytical, multicenter, international study conducted on November 21, 2019, from 8:00 AM to 3:00 PM. NCT03936231. Setting One hundred thirty-three Critical Care Units. Patients Patients receiving invasive mechanical ventilation for any cause. Interventions None. Main variables of interest Mechanical power. Results A population of 372 patients was analyzed. PM was significantly higher in patients under pressure-controlled ventilation (PC) compared to volume-controlled ventilation (VC) (19.20±8.44J/min vs. 16.01±6.88J/min; p<0.001), but the percentage of patients with PM>17J/min was not different (41% vs. 35%, respectively; p=0.382). The best models according to AICcw expressing PM for patients in VC are described as follows: Surrogate Strain (Driving Pressure) + PEEP+Surrogate Strain Rate (PEEP/Flow Ratio) + Respiratory Rate. For patients in PC, it is defined as: Surrogate Strain (Expiratory Tidal Volume/PEEP) + PEEP+Surrogate Strain Rate (Surrogate Strain/Ti) + Respiratory Rate+Expiratory Tidal Volume+Ti. Conclusions A substantial proportion of mechanically ventilated patients may be at risk of experiencing elevated levels of mechanical power. Despite observed differences in mechanical power values between VC and PC ventilation, they did not result in a significant disparity in the prevalence of high mechanical power values. (AU)

Objetivo Determinar la prevalencia de valores elevados de potencia mecánica (PM) (>17J/min) utilizados en la práctica clínica habitual. Diseño estudio observacional, descriptivo de corte transversal, analítico, multicéntrico e internacional, realizado el 21 de noviembre de 2019 en horario de 8 a 15 horas. NCT03936231. Ámbito Ciento treinta y tres Unidad de Cuidados Críticos. Pacientes pacientes que recibirán ventilación mecánica por cualquier causa. Intervenciones ninguna Variables de interés principales Potencia mecánica. Resultados se analizaron 372 enfermos. La PM fue significativamente mayor en pacientes en ventilación controlada por presión (PC) que en ventilación controlada por volumen (VC) (19,20+8,44J/min frente a 16,01+6,88J/min; p<0,001), pero el porcentaje de pacientes con PM>17J/min no fue diferente (41% frente a 35% respectivamente; p=0,382). Los mejores modelos según AICcw que expresan la PM para los enfermos en VC se decribe como: Strain subrogante (Presión de conducción) + PEEP+Strain Rate subrogante (PEEP/cociente de flujo) + Frecuencia respiratoria. Para los enfermos en PC se define como: Strain subrogante (Volumen tidal expiratorio/PEEP) + PEEP+Strain Rate subrogante (Strain subrogante/Ti) + Frecuencia respiratoria+Expiratory Tidal Volumen+Ti. Conclusiones Gran parte de los pacientes en ventilación mecánica en condiciones de práctica clínica habitual reciben niveles de potencia mecánica peligrosos. A pesar de las diferencias observadas en los valores de potencia mecánica entre la ventilación VC y PC, este porcentaje de riesgo fue similar en PC y VC. (AU)

Invasive Mechanical Ventilation.

Invasive mechanical ventilation allows clinicians to support gas exchange and work of breathing in patients with respiratory failure. However, there is also potential for iatrogenesis. By understanding the benefits and limitations of different modes of ventilation and goals for gas exchange, clinicians can choose a strategy that provides appropriate support while minimizing harm. The ventilator can also provide crucial diagnostic information in the form of respiratory mechanics. These, and the mechanical ventilation strategy, should be regularly reassessed.

Intra-breath changes in respiratory mechanics are sensitive to history of respiratory illness in preschool children: the SEPAGES cohort.

BACKGROUND: Intra-breath oscillometry has been proposed as a sensitive means of detecting airway obstruction in young children. We aimed to assess the impact of early life wheezing and lower respiratory tract illness on lung function, using both standard and intra-breath oscillometry in 3 year old children. METHODS: History of doctor-diagnosed asthma, wheezing, bronchiolitis and bronchitis and hospitalisation for respiratory problems were assessed by questionnaires in 384 population-based children. Association of respiratory history with standard and intra-breath oscillometry parameters, including resistance at 7 Hz (R7), frequency-dependence of resistance (R7 - 19), reactance at 7 Hz (X7), area of the reactance curve (AX), end-inspiratory and end-expiratory R (ReI, ReE) and X (XeI, XeE), and volume-dependence of resistance (ΔR = ReE-ReI) was estimated by linear regression adjusted on confounders. RESULTS: Among the 320 children who accepted the oscillometry test, 281 (88%) performed 3 technically acceptable and reproducible standard oscillometry measurements and 251 children also performed one intra-breath oscillometry measurement. Asthma was associated with higher ReI, ReE, ΔR and R7 and wheezing was associated with higher ΔR. Bronchiolitis was associated with higher R7 and AX and lower XeI and bronchitis with higher ReI. No statistically significant association was observed for hospitalisation. CONCLUSIONS: Our findings confirm the good success rate of oscillometry in 3-year-old children and indicate an association between a history of early-life wheezing and lower respiratory tract illness and lower lung function as assessed by both standard and intra-breath oscillometry. Our study supports the relevance of using intra-breath oscillometry parameters as sensitive outcome measures in preschool children in epidemiological cohorts.

Influence of the chest wall on respiratory function at birth in near-term lambs.

Airway liquid is cleared into lung tissue after birth, which becomes edematous and forces the chest wall to expand to accommodate both the cleared liquid and incoming air. This study investigated how changing chest wall mechanics affects respiratory function after birth in near-term lambs with different airway liquid volumes. Surgically instrumented near-term lambs (139 ± 2 days) were randomized into Control (n = 7) or Elevated Liquid (EL; n = 6) groups. Control lambs had lung liquid drained to simulate expected volumes following vaginal delivery. EL lambs had airway liquid drained and 30 mL/kg liquid returned to simulate expected airway liquid volumes after elective cesarean section. Lambs were delivered, transferred to a Perspex box, and ventilated (30 min). Pressure in the box was adjusted to apply positive (7-8 cmH2O above atmospheric pressure) or negative (7-8 cmH2O below atmospheric pressure) pressures for 30 min before pressures were reversed. External negative pressures expanded the chest wall, reduced chest wall compliance (CCW) and increased lung compliance (CL) in Control and EL lambs. External positive pressures compressed the chest wall, increased CCW and reduced CL in Control and EL lambs. External negative pressure improved pulmonary oxygen exchange, reducing the alveolar-arterial difference in oxygen (AaDO2) by 69 mmHg (95% CI [13, 125]; P = 0.016) in Control lambs and by 300 mmHg (95% CI [233, 367]; P < 0.001) in EL lambs. In contrast, external positive pressures impaired pulmonary gas exchange, increasing the AaDO2 by 179 mmHg (95% CI [73, 285]; P = 0.002) in Control and by 215 mmHg (95% CI [89, 343]; P < 0.001) in EL lambs. The application of external thoracic pressures influences respiratory function after birth.NEW & NOTEWORTHY This study investigated how changes in chest wall mechanics influence respiratory function after birth. Our data indicate that the application of continuous external subatmospheric pressure greatly improves respiratory function in near-term lambs with respiratory distress, whereas external positive pressures impair respiratory function. Our findings indicate that, during neonatal resuscitation at birth, the forces applied to the chest wall should not be ignored as they can have a major impact on neonatal respiratory function.

Evaluation of Optimal Esophageal Catheter Balloon Inflation Volume in Mechanically Ventilated Children.

BACKGROUND: Accuracy of esophageal pressure measured by an air-filled esophageal balloon catheter is dependent on balloon filling volume. However, this has been understudied in mechanically ventilated children. We sought to study the optimal filling volume in children receiving ventilation by using previously reported calibration methods. Secondary objectives included to examine the difference in pressure measurements at individualized optimal filling volume versus a standardized inflation volume and to study if a static hold during calibration is required to identify the optimal filling volume. METHODS: An incremental inflation calibration procedure was performed in children receiving ventilation, <18 y, instrumented with commercially available catheters (6 or 8 French) who were not breathing spontaneously. The balloon was manually inflated by 0.2 to 1.6 mL (6 French) or 2.6 mL (8 French). Esophageal pressure (Pes) and airway pressure tracings were recorded during the procedure. Data were analyzed offline by using 2 methods: visual determination of filling range with the calculation of the highest difference between expiratory and inspiratory Pes and determination of a correctly filled balloon by calculating the esophageal elastance. RESULTS: We enrolled 40 subjects with median (interquartile range [IQR]) age 6.8 (2-25) months. The optimal filling volume ranged from 0.2 to 1.2 mL (median [IQR] 0.6 [0.2-1.0] mL) in the subjects with a 6 French catheter and 0.2-2.0 mL (median [IQR] 0.7 [0.5-1.2] mL) for 8 French catheters. Inflating the balloon with 0.6 mL (median computed from the whole cohort) gave an absolute difference in transpulmonary pressure that ranged from -4 to 7 cm H2O compared with the personalized volume. Pes calculated over 5 consecutives breaths differed with a maximum of 1 cm H2O compared to Pes calculated during a single inspiratory hold. The esophageal elastance was correlated with weight, age, and sex. CONCLUSIONS: The optimal balloon inflation volume was highly variable, which indicated the need for an individual calibration procedure. Pes was not overestimated when an inspiratory hold was not applied.

Driving pressure of respiratory system and lung stress in mechanically ventilated patients with active breathing.

BACKGROUND: During control mechanical ventilation (CMV), the driving pressure of the respiratory system (ΔPrs) serves as a surrogate of transpulmonary driving pressure (ΔPlung). Expiratory muscle activity that decreases end-expiratory lung volume may impair the validity of ΔPrs to reflect ΔPlung. This prospective observational study in patients with acute respiratory distress syndrome (ARDS) ventilated with proportional assist ventilation (PAV+), aimed to investigate: (1) the prevalence of elevated ΔPlung, (2) the ΔPrs-ΔPlung relationship, and (3) whether dynamic transpulmonary pressure (Plungsw) and effort indices (transdiaphragmatic and respiratory muscle pressure swings) remain within safe limits. METHODS: Thirty-one patients instrumented with esophageal and gastric catheters (n = 22) were switched from CMV to PAV+ and respiratory variables were recorded, over a maximum of 24 h. To decrease the contribution of random breaths with irregular characteristics, a 7-breath moving average technique was applied. In each patient, measurements were also analyzed per deciles of increasing lung elastance (Elung). Patients were divided into Group A, if end-inspiratory transpulmonary pressure (PLEI) increased as Elung increased, and Group B, which showed a decrease or no change in PLEI with Elung increase. RESULTS: In 44,836 occluded breaths, ΔPlung ≥ 12 cmH2O was infrequently observed [0.0% (0.0-16.9%) of measurements]. End-expiratory lung volume decrease, due to active expiration, was associated with underestimation of ΔPlung by ΔPrs, as suggested by a negative linear relationship between transpulmonary pressure at end-expiration (PLEE) and ΔPlung/ΔPrs. Group A included 17 and Group B 14 patients. As Elung increased, ΔPlung increased mainly due to PLEI increase in Group A, and PLEE decrease in Group B. Although ΔPrs had an area receiver operating characteristic curve (AUC) of 0.87 (95% confidence intervals 0.82-0.92, P < 0.001) for ΔPlung ≥ 12 cmH2O, this was due exclusively to Group A [0.91 (0.86-0.95), P < 0.001]. In Group B, ΔPrs showed no predictive capacity for detecting ΔPlung ≥ 12 cmH2O [0.65 (0.52-0.78), P > 0.05]. Most of the time Plungsw and effort indices remained within safe range. CONCLUSION: In patients with ARDS ventilated with PAV+, injurious tidal lung stress and effort were infrequent. In the presence of expiratory muscle activity, ΔPrs underestimated ΔPlung. This phenomenon limits the usefulness of ΔPrs as a surrogate of tidal lung stress, regardless of the mode of support.

Pulmonary response prediction through personalized basis functions in a virtual patient model.

BACKGROUND AND OBJECTIVE: Recruitment maneuvers with subsequent positive-end-expiratory-pressure (PEEP) have proven effective in recruiting lung volume and preventing alveoli collapse. However, determining a safe, effective, and patient-specific PEEP is not standardized, and this more optimal PEEP level evolves with patient condition, requiring personalised monitoring and care approaches to maintain optimal ventilation settings. METHODS: This research examines 3 physiologically relevant basis function sets (exponential, parabolic, cumulative) to enable better prediction of elastance evolution for a virtual patient or digital twin model of MV lung mechanics, including novel elements to model and predict distension elastance. Prediction accuracy and robustness are validated against recruitment maneuver data from 18 volume-controlled ventilation (VCV) patients at 7 different baseline PEEP levels (0 to 12 cmH2O) and 14 pressure-controlled ventilation (PCV) patients at 4 different baseline PEEP levels (6 to 12 cmH2O), yielding 623 and 294 prediction cases, respectively. Predictions were made up to 12 cmH2O of added PEEP ahead, covering 6 × 2 cmH2O PEEP steps. RESULTS: The 3 basis function sets yield median absolute peak inspiratory pressure (PIP) prediction error of 1.63 cmH2O for VCV patients, and median peak inspiratory volume (PIV) prediction error of 0.028 L for PCV patients. The exponential basis function set yields a better trade-off of overall performance across VCV and PCV prediction than parabolic and cumulative basis function sets from other studies. Comparing predicted and clinically measured distension prediction in VCV demonstrated consistent, robust high accuracy with R2 = 0.90-0.95. CONCLUSIONS: The results demonstrate recruitment mechanics are best captured by an exponential basis function across different mechanical ventilation modes, matching physiological expectations, and accurately capture, for the first time, distension mechanics to within 5-10 % accuracy. Enabling the risk of lung injury to be predicted before changing ventilator settings. The overall outcomes significantly extend and more fully validate this digital twin or virtual mechanical ventilation patient model.

A Comparative Study of Ex-Vivo Murine Pulmonary Mechanics Under Positive- and Negative-Pressure Ventilation.

Increased ventilator use during the COVID-19 pandemic resurrected persistent questions regarding mechanical ventilation including the difference between physiological and artificial breathing induced by ventilators (i.e., positive- versus negative-pressure ventilation, PPV vs NPV). To address this controversy, we compare murine specimens subjected to PPV and NPV in ex vivo quasi-static loading and quantify pulmonary mechanics via measures of quasi-static and dynamic compliances, transpulmonary pressure, and energetics when varying inflation frequency and volume. Each investigated mechanical parameter yields instance(s) of significant variability between ventilation modes. Most notably, inflation compliance, percent relaxation, and peak pressure are found to be consistently dependent on the ventilation mode. Maximum inflation volume and frequency note varied dependencies contingent on the ventilation mode. Contradictory to limited previous clinical investigations of oxygenation and end-inspiratory measures, the mechanics-focused comprehensive findings presented here indicate lung properties are dependent on loading mode, and importantly, these dependencies differ between smaller versus larger mammalian species despite identical custom-designed PPV/NPV ventilator usage. Results indicate that past contradictory findings regarding ventilation mode comparisons in the field may be linked to the chosen animal model. Understanding the differing fundamental mechanics between PPV and NPV may provide insights for improving ventilation strategies and design to prevent associated lung injuries.

An Initial Investigation of Diaphragm Neurostimulation in Patients with Acute Respiratory Distress Syndrome.

BACKGROUND: Lung protective ventilation aims at limiting lung stress and strain. By reducing the amount of pressure transmitted by the ventilator into the lungs, diaphragm neurostimulation offers a promising approach to minimize ventilator-induced lung injury. This study investigates the physiologic effects of diaphragm neurostimulation in acute respiratory distress syndrome (ARDS) patients. The hypothesis was that diaphragm neurostimulation would improve oxygenation, would limit the distending pressures of the lungs, and would improve cardiac output. METHODS: Patients with moderate ARDS were included after 48 h of invasive mechanical ventilation and had a left subclavian catheter placed to deliver bilateral transvenous phrenic nerve stimulation. Two 60-min volume-controlled mechanical ventilation (control) sessions were interspersed by two 60-min diaphragm neurostimulation sessions delivered continually, in synchrony with the ventilator. Gas exchange, lung mechanics, chest electrical impedance tomography, and cardiac index were continuously monitored and compared across four sessions. The primary endpoint was the Pao2/fraction of inspired oxygen (Fio2) ratio at the end of each session, and the secondary endpoints were lung mechanics and hemodynamics. RESULTS: Thirteen patients were enrolled but the catheter could not be inserted in one, leaving 12 patients for analysis. All sessions were conducted without interruption and well tolerated. The Pao2/Fio2 ratio did not change during the four sessions. Median (interquartile range) plateau pressure was 23 (20 to 31) cm H2O and 21 (17 to 25) cm H2O, driving pressure was 14 (12 to 18) cm H2O and 11 (10 to 13) cm H2O, and end-inspiratory transpulmonary pressure was 9 (5 to 11) cm H2O and 7 (4 to 11) cm H2O during mechanical ventilation alone and during mechanical ventilation + neurostimulation session, respectively. The dorsal/ventral ventilation surface ratio was 0.70 (0.54 to 0.91) when on mechanical ventilation and 1.20 (0.76 to 1.33) during the mechanical ventilation + neurostimulation session. The cardiac index was 2.7 (2.3 to 3.5) l · min-1 · m-2 on mechanical ventilation and 3.0 (2.4 to 3.9) l · min-1 · m-2 on mechanical ventilation + neurostimulation. CONCLUSIONS: This proof-of-concept study showed the feasibility of short-term diaphragm neurostimulation in conjunction with mechanical ventilation in ARDS patients. Diaphragm neurostimulation was associated with positive effects on lung mechanics and on hemodynamics.