Exogenous surfactant reduces inflammation and redox imbalance in rats under prone or supine mechanical ventilation.

Mechanical ventilation (MV) is a lifesaving therapy for patients with acute or chronic respiratory failure. Despite, it can also cause lung injury by inducing or worsening inflammatory responses and oxidative stress. Several clinical approaches have protective effects on the lungs, including the prone position and exogenous surfactant; however, few studies have evaluated the association between the two strategies, especially in individuals without previous lung injury. We tested the hypothesis that the effects of the homogenization in lung aeration caused by the prone position in association with the anti-inflammatory properties of exogenous surfactant pre-treatment could have a cumulative protective effect against ventilator-induced lung injury. Therefore, Wistar rats were divided into four experimental groups: Mechanical Ventilation in Supine Position (MVSP), Mechanical Ventilation in Prone position (MVPP), Mechanical Ventilation in Supine Position + surfactant (MVSPS), and Mechanical Ventilation in Prone Position + Surfactant (MVPPS). The intranasal instillation of a porcine surfactant (Curosurf®) was performed in the animals of MVSPS and MVPPS 1 h before the MV, all the rats were subjected to MV for 1 h. The prone position in association with surfactant decreased mRNA expression levels of pro-inflammatory cytokines in ventilated animals compared to the supine position; in addition, the NfκB was lower in MVPP, MVSPS and MVPPS when compared to MVSP. However, it had no effects on oxidative stress caused by MV. Pre-treatment with exogenous surfactant was more efficient in promoting lung protection than the prone position, as it also reduced oxidative damage in the lung parenchyma. Nevertheless, the surfactant did not cause additional improvements in most parameters that were also improved by the prone position. Our results indicate that the pre-treatment with exogenous surfactant, regardless of the position adopted in mechanical ventilation, preserves the original lung histoarchitecture, reduces redox imbalance, and reduces acute inflammatory responses caused by mechanical ventilation in healthy adult Wistar rats.

Mechanical Ventilation in Sepsis

Sepsis can cause lung injury. Prior to the COVID-19 pandemic, sepsis was the main cause of acute respiratory distress syndrome (ARDS), associated with approximately >50% of cases. Mechanical ventilation (MV) may amplify the lung-specific inflammatory response in preinjured lungs by elevating cytokine release and augmenting damage to the alveolar integrity;in addition, sepsis per se constitutes a risk factor for mechanical ventilator-induced lung injury. Inadequate ventilator setting can contribute to increased infection-induced organ failure and uncontrolled systemic inflammatory response. Objectives of invasive MV are to maintain adequate gas exchange: maintain oxygenation goals and adequate ventilation. Regarding ventilatory modes, it has been proposed that volume control-continuous mandatory ventilation may be more protective than pressure control-continuous mandatory ventilation. It may be reasonable to maintain a target arterial partial pressure of oxygen of 60–80mm Hg (Young et al. 2022) or a saturation of peripheral oxygen of 92%–96% for most patients. Sepsis-induced diaphragmatic dysfunction is a major risk factor of weaning failure during MV. Diaphragmatic ultrasound had been a useful tool for predicting successful liberation from MV. Another important aspect of ventilation is the type of sedation to use. © 2023 Elsevier Inc. All rights reserved.

Ventilator-associated events: From surveillance to optimizing management

Mechanical ventilation (MV) is a life-support therapy that may predispose to morbid and lethal complications, with ventilator-associated pneumonia (VAP) being the most prevalent. In 2013, the Center for Disease Control (CDC) defined criteria for ventilator-associated events (VAE). Ten years later, a growing number of studies assessing or validating its clinical applicability and the potential benefits of its inclusion have been published. Surveillance with VAE criteria is retrospective and the focus is often on a subset of patients with higher than lower severity. To date, it is estimated that around 30% of ventilated patients in the intensive care unit (ICU) develop VAE. While surveillance enhances the detection of infectious and non-infectious MV-related complications that are severe enough to impact the patient's outcomes, there are still many gaps in its classification and management. In this review, we provide an update by discussing VAE etiologies, epidemiology, and classification. Preventive strategies on optimizing ventilation, sedative and neuromuscular blockade therapy, and restrictive fluid management are warranted. An ideal VAE bundle is likely to minimize the period of intubation. We believe that it is time to progress from just surveillance to clinical care. Therefore, with this review, we have aimed to provide a roadmap for future research on the subject.Copyright © 2022 The Author(s)

Mechanical power and 30-day mortality in mechanically ventilated, critically ill patients with and without Coronavirus Disease-2019: a hospital registry study.

BACKGROUND: Previous studies linked a high intensity of ventilation, measured as mechanical power, to mortality in patients suffering from "classic" ARDS. By contrast, mechanically ventilated patients with a diagnosis of COVID-19 may present with intact pulmonary mechanics while undergoing mechanical ventilation for longer periods of time. We investigated whether an association between higher mechanical power and mortality is modified by a diagnosis of COVID-19. METHODS: This retrospective study included critically ill, adult patients who were mechanically ventilated for at least 24 h between March 2020 and December 2021 at a tertiary healthcare facility in Boston, Massachusetts. The primary exposure was median mechanical power during the first 24 h of mechanical ventilation, calculated using a previously validated formula. The primary outcome was 30-day mortality. As co-primary analysis, we investigated whether a diagnosis of COVID-19 modified the primary association. We further investigated the association between mechanical power and days being alive and ventilator free and effect modification of this by a diagnosis of COVID-19. Multivariable logistic regression, effect modification and negative binomial regression analyses adjusted for baseline patient characteristics, severity of disease and in-hospital factors, were applied. RESULTS: 1,737 mechanically ventilated patients were included, 411 (23.7%) suffered from COVID-19. 509 (29.3%) died within 30 days. The median mechanical power during the first 24 h of ventilation was 19.3 [14.6-24.0] J/min in patients with and 13.2 [10.2-18.0] J/min in patients without COVID-19. A higher mechanical power was associated with 30-day mortality (ORadj 1.26 per 1-SD, 7.1J/min increase; 95% CI 1.09-1.46; p = 0.002). Effect modification and interaction analysis did not support that this association was modified by a diagnosis of COVID-19 (95% CI, 0.81-1.38; p-for-interaction = 0.68). A higher mechanical power was associated with a lower number of days alive and ventilator free until day 28 (IRRadj 0.83 per 7.1 J/min increase; 95% CI 0.75-0.91; p < 0.001, adjusted risk difference - 2.7 days per 7.1J/min increase; 95% CI - 4.1 to - 1.3). CONCLUSION: A higher mechanical power is associated with elevated 30-day mortality. While patients with COVID-19 received mechanical ventilation with higher mechanical power, this association was independent of a concomitant diagnosis of COVID-19.

What do we know about pathological mechanism and pattern of lung injury related to SARS-CoV-2 Omicron variant?

Pulmonary damage in SARS-CoV-2 is characterized pathologically by diffuse alveolar damage (DAD) and thrombosis. In addition, nosocomial bacterial superinfections and ventilator-induced lung injury (VILI) are likely to occur. The SARS-CoV-2 Omicron variant have manifested itself as a more diffusive virus which mainly affects the upper airways, such as the nose and pharynx. The mechanism leading to a lung injury with a complex clinical course for the Omicron SARS-CoV-2 variant remains unclear. A key question is whether the organ damage is due to direct organ targeting of the virus or downstream effects such as an altered immune response. An immune escape process of Omicron variant is being studied, which could lead to prolonged viral shedding and increase hospitalization times in patients with comorbidities, with an increased risk of pulmonary co-infections/superinfections and organ damage. This brief commentary reports the current knowledge on the Omicron variant and provides some useful suggestions to the scientific community.

Very Low Driving-Pressure Ventilation in Patients With COVID-19 Acute Respiratory Distress Syndrome on Extracorporeal Membrane Oxygenation: A Physiologic Study.

OBJECTIVES: To determine in patients with acute respiratory distress syndrome (ARDS) on venovenous extracorporeal membrane oxygenation (VV ECMO) whether reducing driving pressure (ΔP) would decrease plasma biomarkers of inflammation and lung injury (interleukin-6 [IL-6], IL-8, and the soluble receptor for advanced glycation end-products sRAGE). DESIGN: A single-center prospective physiologic study. SETTING: At a single university medical center. PARTICIPANTS: Adult patients with severe COVID-19 ARDS on VV ECMO. INTERVENTIONS: Participants on VV ECMO had the following biomarkers measured: (1) pre-ECMO with low-tidal-volume ventilation (LTVV), (2) post-ECMO with LTVV, (3) during low-driving-pressure ventilation (LDPV), (4) after 2 hours of very low driving-pressure ventilation (V-LDPV, main intervention ΔP = 1 cmH2O), and (5) 2 hours after returning to LDPV. MAIN MEASUREMENTS AND RESULTS: Twenty-six participants were enrolled; 21 underwent V-LDPV. There was no significant change in IL-6, IL-8, and sRAGE from LDPV to V-LDPV and from V-LDPV to LDPV. Only participants (9 of 21) with nonspontaneous breaths had significant change (p < 0.001) in their tidal volumes (Vt) (mean ± SD), 1.9 ± 0.5, 0.1 ± 0.2, and 2.0 ± 0.7 mL/kg predicted body weight (PBW). Participants with spontaneous breathing, Vt were unchanged-4.5 ± 3.1, 4.7 ± 3.1, and 5.6 ± 2.9 mL/kg PBW (p = 0.481 and p = 0.065, respectively). There was no relationship found when accounting for Vt changes and biomarkers. CONCLUSIONS: Biomarkers did not significantly change with decreased ΔPs or Vt changes during the first 24 hours post-ECMO. Despite deep sedation, reductions in Vt during V-LDPV were not reliably achieved due to spontaneous breaths. Thus, patients on VV ECMO for ARDS may have higher Vt (ie, transpulmonary pressure) than desired despite low ΔPs or Vt.

Promoting improved healing: Lessons learned from the fetus

Background: It has long been known that the fetal response to skin injury is regenerative, with a lack of abnormal collagen deposition or scar, and restoration of normal dermal architecture. This response is associated with minimal inflammation.We have shown that the decreased inflammation is due to decreased production of pro-inflammatory cytokine production compared to the adult response. In addition, we have shown fetal tendon and the fetal heart can heal by regeneration, with restoration of structure and function, and is also associated with decreased proinflammatory cytokine production and decreased inflammation. We hypothesized that strategies targeting inflammation and associated oxidative stress could be used in adult diseases. We have identified diabetic wounds, acute lung injury, and colitis where inflammation and oxidative stress plays a central role in the pathogenesis the disease. Material(s) and Method(s): We have developed a novel strategy using nanotechnology to target inflammation and oxidative stress. We have conjugated novel cerium oxide nanoparticles, which act as potent scavengers of reactive oxygen species, to the anti-inflammatory microRNA miR146a, which suppresses the NFkB pathway and the production of the pro-inflammatory cytokines IL-6 and IL-8. Result(s): In diabetic wounds, impaired healing is associated with chronic inflammation and oxidative stress. We have demonstrated, in both small and large diabetic animals models, that CNP-miR146a can decrease inflammation and oxidative stress and correct the diabetic wound healing impairment and promote regeneration, similar to rates of healing in non-diabetic animals. We have also examined other disease states where inflammation and oxidative stress is pathogenic. Following acute lung injury, inflammation and oxidative stress leads to the development of adult respiratory distress syndrome or ARDS, the number one cause of mortality with COVID-19, and is associated with a 30-50% mortality. Inflammation and oxidative stress play a central role in the pathogenesis of ARDS. We have shown in models of acute lung injury, including bleomycin, LPS, MRSA, ventilator induced lung injury (VILI) and mustard gas, that CNP-miR146a decreases inflammation and oxidative stress, promotes regeneration and restoration of function, and decreased mortality. Finally, pathogenic inflammation plays a central role in the development of colitis or inflammatory bowel disease. We have shown that CNP-miR146a enemas can prevent progression of disease, restore weight gain, and lacks the adverse effects of systemic immunosuppression. Conclusion(s): We have used our understanding of the mechanisms of fetal regeneration following injury, which progresses with minimal inflammation and oxidative stress, to develop strategies targeting these processes to promote regeneration in adult disease.

ABDOMINAL COMPRESSION IN END-STAGE FIBROTIC INTERSTITIAL LUNG DISEASE (ILD) IMPROVES RESPIRATORY COMPLIANCE

SESSION TITLE: Critical Thinking SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 09:15 am - 10:15 am INTRODUCTION: Compressive therapies to improve respiratory mechanics, such as abdominal compression, have been described in literature in patients with COVID-19 induced acute respiratory distress syndrome (COVID-19 ARDS) 1–3. These compressive therapies minimize the risk of barotrauma by equal distribution of pressure across the alveoli. Hence, they help with lung protective ventilation. This phenomenon of paradoxical improvement in respiratory compliance with increase in intraabdominal pressure (IAP) has not been described in ILD population. We describe a case of end-stage fibrotic ILD, secondary to hypersensitivity pneumonitis (HP), exhibiting a paradoxical improvement in respiratory compliance with sustained abdominal compression. CASE PRESENTATION: 56-year-old female with history of NASH-related cirrhosis was transferred to our hospital for expedited work-up of lung transplant due to rapid progression of biopsy-proven steroid-unresponsive fibrotic HP. Due to worsening hypoxic respiratory failure, she was intubated on arrival to our hospital. Following intubation, she was sedated and paralyzed and was found to have high peak and plateau pressures in supine and reverse Trendelenburg positions. However, on application of abdominal pressure, her peak and plateau pressure showed a dramatic reduction in absolute values. This reduction was sustained during the entire duration of the maneuver. Overall, it reduced driving pressures and improved the static compliance of the respiratory system. We subsequently applied abdominal binder (table 1) and found a similar decrease in pressures (see images). Unfortunately, due to functional disability, patient was not deemed a candidate for lung and liver transplant and was transitioned to comfort measures. DISCUSSION: Paradoxical improvement in respiratory compliance has been demonstrated in late-stage COVID ARDS1,2. The mechanism behind this is unclear. In theory, increase in IAP increases intrapleural pressures, reduces end-expiratory volume and overdistention of aerated lung1,2. We hypothesize that patients with end-stage ILD behave similarly to patients with COVID-ARDS. However, this is purely exploratory as our observations are limited by lack of intrapleural measurements. Use of abdominal compression is a simple maneuver, which can be performed at the bedside to assess for the paradoxical phenomenon. Even though we postulate that long-term abdominal compression is well tolerated, we do not know the effects of sustained long-term abdominal compression on gas-exchange and chest wall dynamics. CONCLUSIONS: Patients with end-stage fibrotic lung disease, exhibiting high-driving pressures on mechanical ventilator in supine and reverse Trendelenburg positions, can be screened for reduction in peak and plateau pressures with abdominal compression. Use of this maneuver may help in lung-protective ventilation and minimize ventilator-induced lung injury. Reference #1: Elmufdi FS, Marini JJ. Dorsal Push and Abdominal Binding Improve Respiratory Compliance and Driving Pressure in Proned Coronavirus Disease 2019 Acute Respiratory Distress Syndrome. Crit Care Explor. 2021;3(11):e0593. doi:10.1097/cce.0000000000000593 Reference #2: Julia Cristina Coronado. Paradoxically Improved Respiratory Compliance With Abdominal Compression in COVID-19 ARDS. Is COVID-19 a risk factor Sev preeclampsia? Hosp Exp a Dev. 2020;(January):2020-2022. Reference #3: Stavi D, Goffi A, Shalabi M Al, et al. The Pressure Paradox: Abdominal Compression to Detect Lung Hyperinflation in COVID-19 Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2022;205(2):245-247. doi:10.1164/rccm.202104-1062IM DISCLOSURES: No relevant relationships by Abhishek Bhardwaj No relevant relationships by Brandon Francis no disclosure on file for Marina Freiberg;No relevant relationships by Simon Mucha No relevant relationships by Arsal Tharwani

Management of Hypoxia in Pediatric Population Affected with COVID-19

Pediatric acute respiratory distress syndrome (PARDS) is a life-threatening condition characterized by hypoxemia and is the most important cause of respiratory failure .It has been proposed that adult COVID-19 respiratory illness has two phenotypes: a low compliance ARDS- like phenotype and a normal compliance phenotype with low ventilation to perfusion ratio. The normal compliance phenotype is theorized to be due to a loss of hypoxic pulmonary vasoconstriction although the pediatric presentation in critical care has not been reported yet;the adult phenotype could be considered when managing pediatric patients with severe COVID-19. PARDS characterized by hypoxemia, radiographic haziness and decreased lung ,compliance per the criteria purposed by the pediatric acute lung injury consensus conference group (PALICC). High frequency nasal cannula or NIV by CPAP or BIPAP has been used successfully in pediatric patient with COVID-19 hypoxemia but increases risk of aerosolization and air born transmission that obligate strict airborne precautions. Management in ICU aims to maintain oxygenation while minimizing ventilation induced lung injury (VILI). For mechanical ventilation oxygen supplementation to maintain SPO2 > 92% and OI < 4 or OSI < 5 is recommended. Prone position and HFO ventilation (HFOV) are mostly utilized as rescue oxygenation. Prone position has been used as an adjunct therapy in adult patients with COVID 19 as chest computed tomography shows ground-glass appearance and depended lung injury. Pediatric evidence supp onorting prone position is scarce;however, there have been promising results with improved ventilation in dependent lung regions If HFOV is considered in patients with COVID-19, it should be used cautiously due to the high risk of aerosolization.

Association of Ventilator Settings and Lung Mechanics During VV-ECMO Treatment with Short Term Pulmonary Function and Lung Imaging Outcomes in COVID-19 Survivors, a Retrospective Cohort Study

Background: Lung protective ventilation plays a crucial role in the management of patients with COVID-19 ARDS treated with VV-ECMO. We hypothesized that increasingly protective ventilator settings may be associated with improved lung recovery by reducing ventilator induced lung injury. Method(s): We performed a retrospective cohort study of all patients treated with VV-ECMO for COVID-19 at NYU Langone Medical Center from March 2020 to June 2020. Ventilator data including tidal volume (cc/ kg predicted body weight), peak airway pressure, PEEP, Driving pressure (DP), Respiratory Rate, FiO2, lung compliance, and mechanical power were obtained. Pulmonary function test (PFT) results, 6-minute walk test results, and quantitative chest CT scores were obtained from the first outpatient follow up assessment. Bivariate and multivariate analysis correlating ventilator data with lung function and CT outcomes was performed. Result(s): 30 COVID-19 patients were treated with VV-ECMO during the study period, of which 26 survived without lung transplantation and 12 completed follow up assessment at a median of 106 days post ECMO decannulation. Multivariate LASSO regression model results;FEV1: DP (beta=-5.535), Respiratory Rate (beta=-0.370), compliance (beta=0.467), FVC: DP (beta=-4.08), compliance (beta=0.875), preECMO tidal volume (beta=-0.0008), TLC: DP (beta=-4.518), ECMO sweep (beta=-0.598), DLCO: peak airway presure (beta=-1.836), 6MWT distance: compliance (beta=1.436), Chest CT total opacity score: DP(beta=-0.60), preECMO tidal volume(beta=-0.0033). Conclusion(s): Driving pressure and peak airway pressure during VV-ECMO had the strongest associations with improved short-term follow up lung volumes, DLCO, and chest CT outcomes in VV-ECMO treated COVID-19 survivors.

Effect of invasive mechanical ventilation on the diversity of the pulmonary microbiota.

Pulmonary microbial diversity may be influenced by biotic or abiotic conditions (e.g., disease, smoking, invasive mechanical ventilation (MV), etc.). Specially, invasive MV may trigger structural and physiological changes in both tissue and microbiota of lung, due to gastric and oral microaspiration, altered body posture, high O2 inhalation-induced O2 toxicity in hypoxemic patients, impaired airway clearance and ventilator-induced lung injury (VILI), which in turn reduce the diversity of the pulmonary microbiota and may ultimately lead to poor prognosis. Furthermore, changes in (local) O2 concentration can reduce the diversity of the pulmonary microbiota by affecting the local immune microenvironment of lung. In conclusion, systematic literature studies have found that invasive MV reduces pulmonary microbiota diversity, and future rational regulation of pulmonary microbiota diversity by existing or novel clinical tools (e.g., lung probiotics, drugs) may improve the prognosis of invasive MV treatment and lead to more effective treatment of lung diseases with precision.

Proning on Veno-venous ExtraCorporeal Membrane Oxygenation in Treatment of Severe ARDS in COVID-19: A Retrospective Case Series

Aim and background: Infection due to SARS-CoV-2 may lead to an atypical ARDS, requiring in the most severe cases VV ECMO. The management of persistent severe hypoxemia under VV ECMO requires a multistep clinical approach including prone positioning which could improve oxygenation. Objective: To assess the synergistic effect of prone ventilation and VV-ECMO in addition to lung-protective ventilation to improve patient outcomes in severe ARDS. Materials and methods: Fortis hospital has been an established ECMO center prior to the COVID-19 pandemic but has now become a primary referral center for ECMO retrieval of critically ill patients. In the past 10 months, we had 19 ECMO patients. All patients who underwent ECMO insertion had CT imaging done on the day of ECMO insertion. Patients with inhomogeneous lung opacities on imaging were postulated to potentially benefit from proning on ECMO. We would like to present a case series of 3 patients (2 retrievals and 1 in-house) subjected to prone ventilation immediately after initiation of VV ECMO in view of ARDS with refractory hypoxia, high driving pressures, and Murray score of >3. Femoro-jugular configuration of VV ECMO was used with adequate anticoagulation. All patients were subjected to proning and supining with a dedicated team of 8-10 members including a senior intensivist and airway expert at the head end and perfusionist taking care of the ECMO circuit along with 6 support staff on side of the patient and 1-2 staff for placing/removing the head support, chest, and pelvic bolsters. All patients received immunomodulation with methylprednisolone for the persistent maladaptive hyperinflammatory states. Ventilatory parameters on conventional lung-protective ventilation were compared to parameters on ECMO at the initiation of proning and after completion of prone sessions. Any complications associated with proning were noted. Results: We describe 3 patients with severe COVID-19 bronchopneumonia with refractory hypoxemia who received prone ventilation on VV ECMO. The median age of patients was 40 years with 1 male and 2 female patients. The median time from symptom onset to mechanical ventilation was 7 days and from mechanical ventilation to VV ECMO initiation was 1.5 days. The median duration on VV-ECMO was 5 days with a duration of prone sessions lasting 18 hours. The mean driving pressure has reduced by 17.6% with an improvement in compliance by 26.3%. The paO2 and P/F ratio improved by 63.2% and 260%, respectively, on ECMO support and these changes were sustained post-ECMO decannulation. None of the patients had any major complications associated with proning. The median duration of hospital stay was 30 days. Days to discharge were prolonged due to sepsis from secondary infection. All 3 patients survived to hospital discharge with minimal to no oxygen requirement, mobilized to an adequate functional capacity to perform activities of daily living. Conclusion: ECMO is often used in patients with severe ARDS and refractory hypoxemia to improve oxygenation and survival. Prone positioning concurrently with ECMO in selected patients can further aid in optimizing alveolar recruitment and reducing ventilator-induced lung injury, which ultimately may be associated with a reduction in-hospital mortality.

COVID-19 and Non-mucor Invasive Fungal Infections and Colonisation in Critically Ill Patients

Aim and background: Mechanical Power in ARDS has predictive value for both VILI and mortality. Driving pressure and mechanical power are two new targets in the mechanical ventilation of ARDS patients. COVID-19 pneumonia has two different phenotypes H type and L type which have different lung compliance, elasticity, and recrutability with different ventilatory strategies. We want to observe how Mechanical Power behaves in H type COVID-19 ARDS and its correlation with compliance and driving pressure. Objective: To study the correlation of Mechanical Power with Driving Pressure and Compliance in H type of COVID-19 pneumonia. Materials and methods: It is a prospective observational study conducted in COVID-19 patients admitted to the Medical Intensive Care unit. We included 65 adult COVID-19 patients aged between 18 and 70 years requiring invasive mechanical ventilation for at least 24 hours. Patients who developed spontaneous pneumothorax and pneumomediastinum before initiation of mechanical ventilation were excluded. Patients were categorised to H type based on lung compliance (<40 mL/cmH2O), recrutability, and lung weight. The Mechanical Power was calculated using the following equation, MP = 0.098 × TV × RR (Paw-1/2 ΔP). Paw-peak airway pressure, ΔP-driving pressure, TV-tidal volume, RR-respiratory rate. The variables are taken at 3 different time intervals in the first 24 hours of invasive mechanical ventilation. All patients are ventilated according to ARDSNET protocol. The Driving pressure and compliance were recorded. The correlation of Mechanical Power with Driving pressure and Compliance were analysed using Pearson Correlation. Results: The mean age of the patients was 57.04 ± 13.96 years (mean ± SD), gender distribution 75% were males and 25% were females. A positive correlation was observed between Mechanical power and Driving pressure (Pearson correlation 0.245) which is statistically significant p = 0.049. A negative correlation was observed between Mechanical power and Compliance (Pearson correlation 0.183) which is not statistically significant. Conclusion: The Mechanical Power and Driving pressure the new targets of Ventilator-Induced Lung Injury (VILI) and also predictors of mortality in ARDS patients. The positive correlation between Mechanical Power and Driving pressure was observed in H type of COVID-19 patients which behaves similar to other ARDS and independent risk factors of mortality in H type of COVID-19 ARDS too.

Mechanical Power in H Type COVID-19 Pneumonia: A Prospective Observational Study

Aim and background: Mechanical Power in ARDS has predictive value for both VILI and mortality. Driving pressure and mechanical power are two new targets in the mechanical ventilation of ARDS patients. COVID-19 pneumonia has two different phenotypes H type and L type which have different lung compliance, elasticity, and recrutability with different ventilatory strategies. We want to observe how Mechanical Power behaves in H type COVID-19 ARDS and its correlation with compliance and driving pressure. Objective: To study the correlation of Mechanical Power with Driving Pressure and Compliance in H type of COVID-19 pneumonia. Materials and methods: It is a prospective observational study conducted in COVID-19 patients admitted to the Medical Intensive Care unit. We included 65 adult COVID-19 patients aged between 18 and 70 years requiring invasive mechanical ventilation for at least 24 hours. Patients who developed spontaneous pneumothorax and pneumomediastinum before initiation of mechanical ventilation were excluded. Patients were categorised to H type based on lung compliance (<40 mL/cmH2O), recrutability, and lung weight. The Mechanical Power was calculated using the following equation, MP = 0.098 ∼ TV ∼ RR (Paw-1/2 for). Paw-peak airway pressure, for-driving pressure, TV-tidal volume, RR-respiratory rate. The variables are taken at 3 different time intervals in the first 24 hours of invasive mechanical ventilation. All patients are ventilated according to ARDSNET protocol. The Driving pressure and compliance were recorded. The correlation of Mechanical Power with Driving pressure and Compliance were analysed using Pearson Correlation. Results: The mean age of the patients was 57.04 ) 13.96 years (mean ) SD), gender distribution 75% were males and 25% were females. A positive correlation was observed between Mechanical power and Driving pressure (Pearson correlation 0.245) which is statistically significant p = 0.049. A negative correlation was observed between Mechanical power and Compliance (Pearson correlation 0.183) which is not statistically significant. Conclusion: The Mechanical Power and Driving pressure the new targets of Ventilator-Induced Lung Injury (VILI) and also predictors of mortality in ARDS patients. The positive correlation between Mechanical Power and Driving pressure was observed in H type of COVID-19 patients which behaves similar to other ARDS and independent risk factors of mortality in H type of COVID-19 ARDS too.

ARDS in the time of corona: context and perspective.

For more than 2 years, COVID-19 has been holding the world at awe with new waves of infections, novel mutants, and still limited (albeit improved) means to combat SARS-CoV-2-induced respiratory failure, the most common and fatal presentation of severe COVID-19. In the present perspective, we draw from the successes and-mostly-failures in previous acute respiratory distress syndrome (ARDS) work and the experiences from COVID-19 to define conceptual barriers that have so far hindered therapeutic breakthroughs in this deadly disease, and to open up new avenues of thinking and thus, ultimately of therapy.

Invasive mechanical ventilation in patients with acute respiratory distress syndrome receiving extracorporeal support: a narrative review of strategies to mitigate lung injury.

Veno-venous extracorporeal membrane oxygenation is indicated in patients with acute respiratory distress syndrome and severely impaired gas exchange despite evidence-based lung protective ventilation, prone positioning and other parts of the standard algorithm for treating such patients. Extracorporeal support can facilitate ultra-lung-protective ventilation, meaning even lower volumes and pressures than standard lung-protective ventilation, by directly removing carbon dioxide in patients needing injurious ventilator settings to maintain sufficient gas exchange. Injurious ventilation results in ventilator-induced lung injury, which is one of the main determinants of mortality in acute respiratory distress syndrome. Marked reductions in the intensity of ventilation to the lowest tolerable levels under extracorporeal support may be achieved and could thereby potentially mitigate ventilator-induced lung injury and theoretically patient self-inflicted lung injury in spontaneously breathing patients with high respiratory drive. However, the benefits of this strategy may be counterbalanced by the use of continuous deep sedation and even neuromuscular blocking drugs, which may impair physical rehabilitation and impact long-term outcomes. There are currently a lack of large-scale prospective data to inform optimal invasive ventilation practices and how to best apply a holistic approach to patients receiving veno-venous extracorporeal membrane oxygenation, while minimising ventilator-induced and patient self-inflicted lung injury. We aimed to review the literature relating to invasive ventilation strategies in patients with acute respiratory distress syndrome receiving extracorporeal support and discuss personalised ventilation approaches and the potential role of adjunctive therapies in facilitating lung protection.

Utilizing Machine Learning and Esophageal Pressure to Detect Ventilator Dyssynchrony and Delineate the Potential for Ventilator Induced Lung Injury

Rationale: It is recognized that ventilator dyssynchrony (VD) may propagate ventilator induced lung injury (VILI). Yet some VD cannot be detected without advanced monitoring like measuring esophageal pressure (Pes) and it is unknown which types of VD propagate VILI. We describe the automated detection of VD using machine learning (ML) in patients with esophageal manometry to quantify the frequency and association between VD, tidal volume (VT) and transpulmonary driving pressure (ΔPdyn.tp). Methods: We enrolled 42 patients with ARDS or ARDS risk factors, including COVID-19. XGBoost, a ML algorithm, was trained to identify 7 types of breaths using a one-vs-all strategy, from a training set of 3500 random breaths. We compared the models' sensitivity and specificity with and without features derived from Pes. Finally, the association between each VD type and VT or ΔPdyn.tp was calculated using separate linear mixed-effect models. Temporally related breaths were nested by patient and modeled as random effects, accounting for repeat measures and changing pulmonary mechanics in each patient. Breaths without an adequate Pes signal were excluded from analysis Results: Patients were 37.5% female, 52±15 years old, had an initial P:F ratio of 140±64, and 24.2% of the 480, 976 breaths were dyssynchronous. Normal passive (Nlp), normal spontaneous (Nls), late reverse triggered (RTl), reverse triggered double triggered (DTr), mild flow limited (FLm), severe flow limited (FLs), and early ventilator terminated (EVT) account for 47.0%, 28.7%, 4.8%, 3.7%, 8.9%, 4.2%, and 2.5% of all breaths, respectively. ML training, VT and ΔPdyn.tp results are show in the table (∗p<0.001). Conclusion: ML algorithms can be trained using Pes to identify types of VD that traditionally need Pes measurements, although without Pes sensitivity may decrease. VD is frequent and DTr is associated with an increase in VT, while FLm and FLs are associated with an increased in ΔPdyn.tp. These data suggest that double triggered breaths and flow limited breaths have the potential to propagate VILI, while other types of VD may not be as deleterious. (Table Presented).

Driving pressure-guided ventilation decreases the mechanical power compared to predicted body weight-guided ventilation in the Acute Respiratory Distress Syndrome.

BACKGROUND: Whether targeting the driving pressure (∆P) when adjusting the tidal volume in mechanically ventilated patients with the acute respiratory distress syndrome (ARDS) may decrease the risk of ventilator-induced lung injury remains a matter of research. In this study, we assessed the effect of a ∆P-guided ventilation on the mechanical power. METHODS: We prospectively included adult patients with moderate-to-severe ARDS. Positive end expiratory pressure was set by the attending physician and kept constant during the study. Tidal volume was first adjusted to target 6 ml/kg of predicted body weight (PBW-guided ventilation) and subsequently modified within a range from 4 to 10 ml/kg PBW to target a ∆P between 12 and 14 cm H2O. The respiratory rate was then re-adjusted within a range from 12 to 40 breaths/min until EtCO2 returned to its baseline value (∆P-guided ventilation). Mechanical power was computed at each step. RESULTS: Fifty-one patients were included between December 2019 and May 2021. ∆P-guided ventilation was feasible in all but one patient. The ∆P during PBW-guided ventilation was already within the target range of ∆P-guided ventilation in five (10%) patients, above in nine (18%) and below in 36 (72%). The change from PBW- to ∆P-guided ventilation was thus accompanied by an overall increase in tidal volume from 6.1 mL/kg PBW [5.9-6.2] to 7.7 ml/kg PBW [6.2-8.7], while respiratory rate was decreased from 29 breaths/min [26-32] to 21 breaths/min [16-28] (p < 0.001 for all comparisons). ∆P-guided ventilation was accompanied by a significant decrease in mechanical power from 31.5 J/min [28-35.7] to 28.8 J/min [24.6-32.6] (p < 0.001), representing a relative decrease of 7% [0-16]. With ∆P-guided ventilation, the PaO2/FiO2 ratio increased and the ventilatory ratio decreased. CONCLUSION: As compared to a conventional PBW-guided ventilation, a ∆P-guided ventilation strategy targeting a ∆P between 12 and 14 cm H2O required to change the tidal volume in 90% of the patients. Such ∆P-guided ventilation significantly reduced the mechanical power. Whether this physiological observation could be associated with clinical benefit should be assessed in clinical trials.

Venovenous extracorporeal CO2 removal to support ultraprotective ventilation in moderate-severe acute respiratory distress syndrome: A systematic review and meta-analysis of the literature.

BACKGROUND: A strategy that limits tidal volumes and inspiratory pressures, improves outcomes in patients with the acute respiratory distress syndrome (ARDS). Extracorporeal carbon dioxide removal (ECCO2R) may facilitate ultra-protective ventilation. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of venovenous ECCO2R in supporting ultra-protective ventilation in moderate-to-severe ARDS. METHODS: MEDLINE and EMBASE were interrogated for studies (2000-2021) reporting venovenous ECCO2R use in patients with moderate-to-severe ARDS. Studies reporting ≥10 adult patients in English language journals were included. Ventilatory parameters after 24 h of initiating ECCO2R, device characteristics, and safety outcomes were collected. The primary outcome measure was the change in driving pressure at 24 h of ECCO2R therapy in relation to baseline. Secondary outcomes included change in tidal volume, gas exchange, and safety data. RESULTS: Ten studies reporting 421 patients (PaO2:FiO2 141.03 mmHg) were included. Extracorporeal blood flow rates ranged from 0.35-1.5 L/min. Random effects modelling indicated a 3.56 cmH2O reduction (95%-CI: 3.22-3.91) in driving pressure from baseline (p < .001) and a 1.89 mL/kg (95%-CI: 1.75-2.02, p < .001) reduction in tidal volume. Oxygenation, respiratory rate and PEEP remained unchanged. No significant interactions between driving pressure reduction and baseline driving pressure, partial pressure of arterial carbon dioxide or PaO2:FiO2 ratio were identified in metaregression analysis. Bleeding and haemolysis were the commonest complications of therapy. CONCLUSIONS: Venovenous ECCO2R permitted significant reductions in ∆P in patients with moderate-to-severe ARDS. Heterogeneity amongst studies and devices, a paucity of randomised controlled trials, and variable safety reporting calls for standardisation of outcome reporting. Prospective evaluation of optimal device operation and anticoagulation in high quality studies is required before further recommendations can be made.