Associated Acute Respiratory Distress Syndrome Research Articles

Meta-Analysis of Higher PEEP Strategies' Effects on Mortality Rates and Inflammatory Mediators in Patients with ARDS: A Perspective Review on Patients with Severe COVID-19-Associated ARDS

<strong>Background: </strong>Different strategies of positive end-expiratory pressure (PEEP) in mechanical ventilation are crucial for patients with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome (ARDS). PEEP acts as a “double-edged sword” for ARDS patients. PEEP could recover pulmonary atelectasis but can induce alveolar hyperinflation.<p><strong>Objective: </strong>This review aimed to evaluate the effect of higher PEEP in patients with severe COVID-19-associated ARDS.</p><p><strong>Method: </strong>This meta-analysis included randomized controlled trial (RCT) studies to assess the mortality rates, barotrauma events, and inflammatory mediators modulation due to higher PEEP strategies. The pooled effect of the mortality rates and barotrauma events were presented as risk ratios (RR) with 95% confidence of interval (CI) using random-effects model (REM) or fixed-effects model (FEM).</p><p><strong>Results: </strong>We identified twelve RCTs comparing higher versus lower PEEP in ARDS patients. There was unsignificant result in overall mortality rates group [RR=0.94,95%CI(85,1.03),p=0.21] but not in mortality after positive response of oxygenation group [RR=0.88,95%CI(0.81,0.95),p=0.002] in higher PEEP group. In terms of patients without positive response of oxygenation, higher PEEP group had significantly higher mortality rates [RR=1.07,95%CI(1.00,1.15),p=0.06]. Higher PEEP significantly reduced the mortality rates in ARDS patients with PaO<sub>2</sub>/FiO<sub>2</sub><150 mmHg [RR=0.867,95%CI(0.74,1.00),p=0.04] instead of patients with moderate ARDS (PaO<sub>2</sub>/FiO<sub>2 </sub>≥150 mmHg) [RR=1.12, 95%CI(0.85,1.47), p=0.44]. There were no differences in overall barotrauma events [RR=1.03,95%CI(0.78,1.36),p=0.85] between higher and lower PEEP group. The use of higher and lower PEEP also contribute to the modulation of inflammatory mediators including TNF-α, IL-6, IL-1RA, and IL-8.</p><p><strong>Conclusion: </strong>Higher PEEP could reduce the mortality of patients with ARDS who responded to the oxygenation. Higher PEEP does not increase the risk of overall barotrauma events. Higher PEEP can modulate the inflammatory mediators.</p>

Acute Respiratory Distress Syndrome due to Monkeypox Virus.

This is the first case of monkeypox virus associated ARDS in a young woman with no medical historyBiological follow-up showed disseminated MPXV and persistent viraemiaTecovirimat was well tolerated.

Days spent on non-invasive ventilation support: can it determine when to initiate VV- ECMO? Observational study in a cohort of Covid-19 patients

BackgroundThe study evaluates the impact of the time between commencing non-invasive ventilation (NIV) support and initiation of venovenous extracorporeal membrane oxygenation (VV-ECMO) in a cohort of critically ill patients with coronavirus disease 2019 (COVID-19) associated acute respiratory distress syndrome (ARDS).MethodsProspective observational study design in an intensive Care Unit (ICU) of a tertiary hospital in Barcelona (Spain). All patients requiring VV-ECMO support due to COVID-19 associated ARDS between March 2020 and January 2022 were analysed. Survival outcome was determined at 90 days after VV-ECMO initiation. Demographic data, comorbidities at ICU admission, RESP (respiratory ECMO survival prediction) score, antiviral and immunomodulatory treatments received, inflammatory biomarkers, the need for vasopressors, the thromboprophylaxis regimen received, and respiratory parameters including the length of intubation previous to ECMO and the length of each NIV support (high-flow nasal cannula, continuous positive airway pressure and bi-level positive airway pressure), were also collated in order to assess risk factors for day-90 mortality. The effect of the time lapse between NIV support and VV-ECMO on survival was evaluated using logistic regression and adjusting the association with all factors that were significant in the univariate analysis.ResultsSeventy-two patients finally received VV-ECMO support. At 90 days after commencing VV-ECMO 35 patients (48%) had died and 37 patients (52%) were alive. Multivariable analysis showed that at VV-ECMO initiation, age (p = 0.02), lactate (p = 0.001), and days from initiation of NIV support to starting VV-ECMO (p = 0.04) were all associated with day-90 mortality.ConclusionsIn our small cohort of VV-ECMO patients with COVID-19 associated ARDS, the time spent between initiation of NIV support and VV-ECMO (together with age and lactate) appeared to be a better predictor of mortality than the time between intubation and VV-ECMO.

The use of respiratory rate-oxygenation index to predict failure of high-flow nasal cannula in patients with coronavirus disease 2019-associated acute respiratory distress syndrome: A retrospective study.

Patients with mild-to-moderate coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome (ARDS) can be treated with a high-flow nasal cannula (HFNC). The use of the respiratory rate-oxygenation (ROX) index, calculated as the ratio of oxygen saturation (SpO2)/fractional oxygen (FiO2) to respiratory rate, in the first few hours after HFNC initiation can help identify patients who fail HFNC therapy later. However, few studies have documented the use of the ROX index during the period of HFNC therapy. Therefore, we aimed to demonstrate the diagnostic performance of the ROX index when calculated throughout the HFNC therapy period and to determine the best cut-off point for predicting HFNC failure. We conducted a retrospective study of patients with COVID-19-associated ARDS who commenced HFNC at the Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Thailand, between April 1 and August 30, 2021. We calculated the ROX index every 4 h throughout the HFNC therapy period and defined HFNC failure as a subsequent endotracheal tube intubation. The performance of the ROX index was analyzed using the area under the receiver operating characteristic curve (AUC). We applied the ROX index ≤ 4.88 to predict HFNC failure and obtained a new ROX cut-off point using Youden's method. In total, 212 patients with COVID-19 treated with HFNC were included in the study. Of these, 81 patients (38.2%) experienced HFNC failure. The ROX index ≤ 4.88 demonstrated a reasonable performance in predicting HFNC failure (AUC, 0.77; 95% confidence interval [CI], 0.72-0.83; p<0.001). However, compared with the original cut-off point of ≤ 4.88, the new ROX index cut-off point of ≤ 5.84 delivered optimal performance (AUC, 0.84; 95% CI, 0.79-0.88; p<0.001), with a significantly better discriminative ability (p = 0.007). In conclusion, a ROX index ≤ 5.84 was found to be optimal for predicting HFNC failure in patients with COVID-19-associated ARDS.

The effect of using iloprost on prognosis in COVID-19 patients with ARDS: a retrospective clinical study.

Epithelial damage together with endothelitis and microvascular thrombi are responsible for COVID-19 associated acute respiratory distress syndrome (ARDS). Iloprost, improves endothelial damage and reduces thrombotic complications with its vasodilator, anti-platelet, anti-inflammatory, and anti-fibrotic effects. In our study, we aimed to determine the effect of iloprost on oxygenation, hemodynamics, weaning, and mortality in severe COVID-19 ARDS. This was a retrospective study conducted in a pandemic hospital in the city of Istanbul, Turkey. Patients, with severe COVID-19 ARDS, who were receiving iloprost for seven days were included in the study. The demographic data, APACHE II, and SOFA (Sequential Organ Failure Assessment score) scores (at admission and discharge), pH, PaO2, PCO2, SatO2, lactate, PaO2/FiO2 (inspiratory fractionated oxygen), respiratory rate-oxygenation (ROX) index (peripheral oxygen saturation/fraction of inhaled oxygen), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressures (MAP), heart rate (HR) values were recorded before starting iloprost (T0), and on days of iloprost administration (2.0 nanograms/kg/minute/6 hours/day) (T1, T2, T3, T4, T5, T6, T7), and the day after last day of iloprost administration (Tfinal). Also, mortality was recorded in a retrospective manner. Two groups were formed according to mortality (Group M) and discharge (Group D). A total of 22 patients (16 men, 6 women) were evaluated. Age, APACHE II, SOFA scores were higher in Group M. The lactate value at T1-3-4-5-7 was lower than T0 in both groups. PaO2 value between T2-Tfinal was higher than T0. A statistically significant increase was found in PaO2/FiO2 levels in both groups. The PaO2/FiO2value between T5-Tfinal was significantly lower in Group M compared to Group D. ROX index was significantly higher between T4-Tfinal when compared with T0. Iloprost improves oxygenation but has no effect on mortality in COVID-19 ARDS.

Secondary Infections in Critical Patients with COVID-19 Associated ARDS in the ICU: Frequency, Microbiologic Characteristics and Risk Factors.

To determine frequency, microbiologic characteristics and risks of secondary infections in patients with Coronavirus disease 2019 (COVID-19) associated acute respiratory distress syndrome (ARDS). An Observational study. COVID-19 intensive care unit (ICU), University of Health Sciences, Diskapı Yildirim Beyazit Research and Training Hospital, Turkey, from July 2020 to January 2021. Demographic data of the COVID-19 patients with ARDS, was collected with reference to (age, gender), comorbidities, illness scores, ICU management modalities, hospital, and ICU stay durations and ICU outcomes. Secondary infections [bloodstream infection (BSI), possible lower respiratory tract infection (pLRTI) or urinary tract infections (UTI)], microbiologic pathogens, and resistant patterns were recorded. A total of 205 COVID-19-related ARDS patients were included in this study. Out of them, 61 (29.8%) were diagnosed with secondary infection, 27 (13.1%) had at least one BSI, 20 (9.8%) had at least one pLRTI, and 34 (16.6%) had at least one UTI. Gram-negative pathogens were the most common cause of secondary infections (66/91, 72.5%). Klebsiella spp for BSI (10/19, 52.6%), Acinetobacter baumannii for pLRTI (10/18, 55.6%), and Escherichia coli for UTI (29/40, 72.5%) were the main causative agents. Among all Gram-negative bacteria, Carbapenem resistant was 62.1% (41/66) and extended-spectrum beta-lactamases positivity was 22.7% (15/66). At multivariable analysis, application of mechanical ventilation (MV) longer than 48 h, central catheterisation longer than 72 h, ICU stay longer than 10 days, and the time from hospitalisation to admission to the ICU longer than 48 h were associated with secondary infections. Patients with COVID-19 associated ARDS had a high rate of secondary infections. In order to reduce secondary infection in these patients, MV duration and ICU stay should be shortened and invasive catheters should be removed as soon as possible. SARS-CoV-2, COVID-19, Acute respiratory distress syndrome,Secondary infections.

Theimpact ofbacterial superinfections on theoutcome ofcritically ill patients with COVID-19 associated acute respiratory distress syndrome (ARDS) - asingle-centre, observational cohort study.

Bacterial superinfections are common in severely ill COVID-19 patients and could be associated with a significant increase in morbidity and mortality. We assessed 29 critically ill patients treated in a university hospital's intensive care unit (ICU). Each patient required mechanical ventilation due to COVID-19-induced acute respiratory distress syndrome (ARDS). Fifteen patients who required venovenous extracorporeal membrane oxygenation (VV-ECMO) support (ECMO group) were compared to a control group (CON group) of 14 individuals without ECMO. This study aimed to assess the prevalence of superinfection in both studied groups. Moreover, we evaluated mortality, length of stay in the ICU, positive culture results, antibiotics used during treatment, and the impact of immunomodulatory drugs on secondary infections. We did not find a difference in the number of superinfections between the ECMO and CON groups (11 vs. 10, P = 1.0). The mortality rate was 67% in the ECMO group and 64% in the CON group ( P = 1.0). The patients in both groups had similar numbers of positive culture results and days in the ICU prior to the detection of a positive culture. Antibiotics were administered to ten patients in the ECMO and eight patients in the CON group. The mortality rate was 81% in patients with superinfection versus 25% in those without co-infection ( P = 0.009). We found a negative impact of urea concentration on mortality in our cohort, with an odds ratio of 0.942 (0.891-0.996, P = 0.034). Our results suggest that bacterial superinfection in COVID-19 patients negatively impacted survival in the ICU. VV-ECMO support in COVID-19 patients does not seem to improve the outcomes of patients with severe ARDS.

Radiological Features and Outcomes of COVID-19 Associated ARDS Patients with Barotrauma

Objective: Barotrauma developing spontaneously or associated with positive pressure ventilation applied as respiratory support therapy is reported more frequently in patients with novel coronavirus 2019 (COVID-19). In this study, we aimed to determine the incidence of barotrauma in critically-ill patients with COVID-19 associated acute respiratory distress syndrome (ARDS) who received invasive mechanical ventilation (IMV), (non-invasive mechanical ventilation NIMV) or high flow nasal oxygen therapy (HFNO) and reveal clinical features, radiological findings and outcomes of these patients.&#x0D; Materials and Methods: In this two-center study, the frequency and clinical characteristics of patients who developed barotrauma while being followed up in the ICU due to COVID-19 were retrospectively investigated. &#x0D; Results: Barotrauma was detected in 29 (4.4%) of 660 patients. Nineteen (65.5%) patients developed pneumothorax, 5 (17.2%) patients developed pneumomediastinum, 5 (17.2%) patients developed subcutaneous emphysema; 18 (62.1%) patients underwent tube thoracostomy, 11 (37.9%) patients were followed conservatively. When barotrauma developed, 17 (58.6%) patients were receiving IMV, 11 (37.9%) patients were receiving NIMV, and 1 (3.4%) patient was receiving HFNO. The mean length of stay in the ICU was 15.3±10.8 days, 19 (65.5%) of the patients died. &#x0D; Conclusion: Barotrauma is not uncommon in COVID-19 ARDS patients; It is a complication that can increase mortality and length of stay in ICU.

Delirium in Adults With COVID-19-Related Acute Respiratory Distress Syndrome: Comparison With Other Etiologies.

Neurologic complications have been associated with COVID-19, including delirium. Such complications have been reported to be frequent among intensive care unit (ICU)-admitted patients. We hypothesized that the rate of neurologic complications would be higher in COVID-19 associated acute respiratory distress syndrome (ARDS) than those who develop ARDS from a different cause. We conducted a retrospective cohort study in the adult ICU of Lausanne University Hospital, including all consecutive patients fulfilling the Berlin criteria for ARDS hospitalized between December 2017 and June 2021, stratifying exposure between COVID-19 or not. The primary outcome was delirium onset during ICU stay, defined by the confusion assessment method (CAM-ICU). Exploratory outcomes included development of neurologic complications of the central nervous system (stroke, hemorrhage, and vasculitis), critical illness weakness, and 30- and 180-day all-cause mortality. Three hundred eleven patients were included in the study (253 with COVID-19 and 58 with other causes) and CAM-ICU could be assessed in 231 (74.3% in COVID-19 vs 74.1% in non-COVID-19). The proportion of patients developing delirium was similar in patients with COVID-19 and controls in univariate comparison (69.1% vs 60.5%, p = 0.246). Yet, patients with COVID-19 had a higher body mass index, lower ICU severity, longer mechanical ventilation, and higher sedation doses (propofol and dexmedetomidine). After adjusting for these factors in a multivariable analysis, the risk of delirium remained comparable across groups (adjusted OR [95% CI]: 0.86 [0.35-2.1]). Similarly, COVID-19-related ARDS had no effect on all-cause mortality at 30 days (adjusted OR: 0.87 [0.39-1.92]) and 180 days (adjusted OR: 0.67 [0.33-1.35]). Finally, neurologic complications affecting the CNS (adjusted OR: 1.15 [0.25-5.29]) and critical illness weakness (adjusted OR: 2.99 [0.97-9.1]) were not higher in the COVID-19 group. Compared with other etiologies, patients with COVID-19 did not have higher incidence of delirium and other neurologic complications, after accounting for underlying disease severity in patients with ARDS. Management of COVID-19-associated ARDS needed longer invasive ventilation and higher sedation, which could explain higher rates of delirium in uncontrolled studies.

Hourly Analysis of Mechanical Ventilation Parameters in Critically Ill Adult Covid-19 Patients: Association with Mortality

Objective: There exists controversy about the pathophysiology and lung mechanics of COVID-19 associated acute respiratory distress syndrome (ARDS), because some report severe hypoxemia with preserved respiratory system mechanics, contrasting with “classic” ARDS. We performed a detailed hourly analysis of the characteristics and time course of lung mechanics and biochemical analysis of patients requiring invasive mechanical ventilation (IMV) for COVID-19-associated ARDS, comparing survivors and non-survivors. Methods: Retrospective analysis of the data stored in the ICU information system of patients admitted in our hospital ICU that required IMV due to confirmed SARS-CoV-2 pneumonia between March 5th and April 30th, 2020. We compare respiratory system mechanics and gas exchange during the first ten days of IMV, discriminating volume and pressure controlled modes, between ICU survivors and non-survivors. Results: 140 patients were included, analyzing 11 138 respiratory mechanics recordings. Global mortality was 38.6%. Multivariate analysis showed that age (OR 1.092, 95% (CI 1.014-1.176)) and need of renal replacement therapies (OR 10.15, (95% CI 1.58-65.11)) were associated with higher mortality. Previous use of Angiotensin Converting Enzyme inhibitor (ACEI)/angiotensin-receptor blockers (ARBs) also seemed to show an increased mortality (OR 4.612, (95% CI 1.19-17.84)) although this significance was lost when stratifying by age. Respiratory variables start to diverge significantly between survivors and non-survivors after the 96 to 120 hours (hs) from mechanical ventilation initiation, particularly respiratory system compliance. In non survivors, mechanical power at 24 and 96 hs was higher regardless ventilatory mode. Conclusions: In patients admitted for SARS-CoV-2 pneumonia and requiring mechanical ventilation, non survivors have different respiratory system mechanics than survivors in the first 10 days of ICU admission. We propose a checkpoint at 96–120 hs to assess patients improvement or worsening in order to consider escalating to extracorporeal therapies.

MO149: Effect of Plasma Exchange on COVID-19 Associated Excess of Von Willebrand Factor and Inflammation in Critically Ill Patients

BACKGROUND AND AIMSUbiquitous microthromboses in the pulmonary vasculature play a crucial role in the pathogenesis of COVID-19 associated acute respiratory distress syndrome (ARDS). Excess of von Willebrand factor (vWf) with intravascular multimer formation was identified as a key driver of this finding. Plasma exchange (PLEX) might be a therapeutic option to restore the disbalance between vWf and ADAMTS13. We report the effects of PLEX on vWf, ADAMTS13, inflammatory cytokines and parameters of ventilation.METHODWe investigated 25 patients, who were on mechanical ventilation for COVID-19 pneumonia with ARDS at two German university hospitals. All patients received PLEX as an ultima ratio measure for refractory ARDS. VWf antigen (vWf: Ag), ADAMTS13 activity, a cytokine panel mirroring the inflammatory situation and clinical parameters were assessed before and after three to six PLEX therapies with fresh frozen plasma.RESULTSBefore the PLEX sequence, there was an excessive release of vWf: Ag (425.4 ± 167.5%) and mildly reduced ADAMTS13 activity (49.7 ± 23.3%). After the PLEX series, there was a significant increase of ADAMTS13 activity to 62.4 ± 17.7% (P = .029) and a significant decrease of vWf: Ag to 336.1 ± 138.2% (P = .041) resulting in a 63% improvement of the ADAMT13/vWf: Ag ratio from 14.5 ± 10.0 to 23.7 ± 14.6 (P = .024). Comparison of parameters before and after individual PLEX sessions (n = 35) revealed a mean reduction of vWf from 387.8 ± 165.1% to 213.2 ± 62.3% (P = .001) and an increase of ADAMTS13 activity from 60.4 ± 20.1% to 70.5 ± 14.0% (P = .001). Parallelly, monocyte chemotactic protein-1 and interleukin-18 decreased significantly (P = .034 each). Along the PLEX sequence lactate dehydrogenase (P = .001), C-reactive protein (P = .001), and positive end expiratory pressure (P = .01) significantly decreased accompanied by an improvement of Horovitz index (P = .001).CONCLUSIONPLEX restores the disbalance between ADAMTS13 and vWf: Ag, a driver of immunothrombosis. Moreover, it reduces the inflammatory state and is associated with a benefit of ventilation parameters. These findings render a further rationale to regard PLEX as a therapeutic option in severe COVID-19.

Multi-omic approach to identify risk markers specific to COVID-19.

Coronavirus disease 2019 (COVID-19) has infected more than 470 million people and caused more than 6 million deaths worldwide. The high mortality mainly owes to the associated acute respiratory distress syndrome (ARDS), which is characterised by the sudden onset of noncardiogenic pulmonary oedema and hypoxemia.1 Recent studies have revealed that COVID-19 ARDS is a dysregulated host response of inflammation, immunity, and interferon signalling.2 Increasing evidence also suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exerts detrimental effects on the capillary endothelium, possibly by altering the integrity of the endothelial barrier or promoting a pro-coagulant state and the resulted endothelial inflammation.

Comparison of Clinical Features and Outcomes between SARS-CoV-2 and Non-SARS-CoV-2 Respiratory Viruses Associated Acute Respiratory Distress Syndrome: Retrospective Analysis.

Although a few studies comparing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and non-SARS-CoV-2 respiratory viruses have been reported, clinical features and outcomes comparing SARS-CoV-2 and non-SARS-CoV-2 respiratory viruses associated acute respiratory distress syndrome (ARDS) are still lacking. We retrospectively identified patients with SARS-CoV-2 (November 2020 to January 2022) and non-SARS-CoV-2 respiratory viruses associated ARDS (February 2015 to November 2020) at a single tertiary hospital. Their clinical data were obtained by medical record review. All viral infections were confirmed by RT-PCR. Thirty-one SARS-CoV-2 and seventy-one patients with non-SARS-CoV-2 respiratory viruses associated ARDS patients were identified. Influenza (62%) was the most common in non-SARS-CoV-2 respiratory viruses associated ARDS patients. Patients with SARS-CoV-2 were more likely to be female and had higher body mass index, lower clinical frailty, APACHE II, and SOFA score than those with non-SARS-CoV-2 respiratory viruses. All patients with SARS-CoV-2 were treated with corticosteroids and used more high-flow nasal oxygen than those with non-SARS-CoV-2 respiratory viruses. The concomitant respiratory bacterial infection was significantly higher in non-SARS-CoV-2 respiratory viruses than SARS-CoV-2. Although there were no significant differences in the 28-, 60-day, and in-hospital mortality rates between SARS-CoV-2 and non-SARS-CoV-2 respiratory viruses associated ARDS, the duration of mechanical ventilation and length of hospital stay were significantly longer in patients with SARS-CoV-2 than those with non-SARS-CoV-2 respiratory viruses. Although the severity of illness and the concomitant bacterial infection rate were lower in patients with SARS-CoV-2 associated ARDS, mortality rates did not differ from non-SARS-CoV-2 respiratory viruses associated ARDS.

Clinical characteristics and outcomes of patients with COVID-19–associated acute respiratory distress syndrome

Aim. The aim was to analyze the results of intensive care for COVID-19 associated acute respiratory distress syndrome (ARDS) using optimized tactical aspects of respiratory support. Methods. In this prospective study, the comparison group included 436 consecutive patients admitted to the ICU of "A-block Zangiota-1" in the period from January 1, 2021 to June 30, 2021 (taking into account the representativeness of the main group), whose the therapeutic and tactical aspects of management were based on the first own experience with results analysis across organizational and therapeutic approaches. The main group included 288 patients admitted from July 1, 2021 to October 1, 2021, whose therapeutic and tactical aspects of management were developed on the basis of a fundamental revision of the differential diagnosis, pathomorphological classification and respiratory mechanics of COVID-19 associated ARDS, as well as taking into account the influence of risk factors for the severe course of the disease and various methods and technologies of respiratory support. Accordingly, adapted and optimized respiratory therapy standards have been applied in main group. Results. The frequency of intubations and transfers to mechanical ventilation had no statistical difference between the groups (p=0.362). In the main group, cases of tracheostomy (73.8%) were significantly (p&lt;0.001) more than the comparison group (14.5%). In the comparison group, the proportion of patients with severe ARDS decreased from 29.6% to 23.8% (p=0.067), and in the main group from 31.0% to 17.0% (p&lt;0.001). The average duration of treatment of patients in the ICU was 22 (from 7 to 32) days in the comparison group and 17 (from 9 to 27) days in the main group (p&lt;0.05). The frequency of deaths in COVID-19 associated ARDS was 11.1% in the main group, which was significantly lower (p=0.036) than the comparison group (16.7%). Among patients on invasive mechanical ventilation (intubation and tracheostomy), the mortality rate was 96.0% in the comparison group and 76.2% in the main group of patients (p = 0.003). Conclusion. Providing respiratory support for COVID-19 associated ARDS, taking into account the individual characteristics of respiratory mechanics, can improve the results of treatment of patients with an increase in the oxygenation index, a decrease in the proportion of cases of severe ARDS, and reduce the mortality rate and the length of stay of patients in the ICU.

"Pushing Geographic Boundaries: Interfacility transport and remote extracorporeal membrane oxygenation cannulation of patients during COVID-19 pandemic".

Amidst the pandemic, geographical boundaries presented challenges to those in need of higher levels of care from referral centers. Authors sought to evaluate potential predictors of treatment success; assess our transport and remote cannulation process; and identify transport associated complications.Retrospective series of critically ill adults with COVID-19 transferred by our Extracorporeal Membrane Oxygenation (ECMO) team 24 March 2020 through 8 June 2021. Descriptive statistics and associated interquartile ranges (IQR) were used to summarize the data.Sixty-three patients with COVID associated acute respiratory distress syndrome (ARDS) requiring ECMO support were admitted to our ECMO center. Mean age was 44 years old (SD 12; IQR 36–56). 59% (n = 37) of patients were male. Average body mass index was 39.7 (SD 11.3; IQR 31–48.5). Majority of patients (77.8%; n = 35) had severe ARDS. Predictors of treatment success were not observed.Transport distances ranged from 2.2 to 236 miles (median 22.5 miles; IQR 8.3–79); round trip times from 18 to 476 min (median 83 min; IQR 44–194). No transport associated complications occurred. Median duration of ECMO support was 17 days (IQR 9.5–34.5). Length of stay in the Intensive Care Unit (median 36 days; IQR 17–49) and hospital (median 39 days; IQR 25–57) varied. Amongst those discharged, 60% survived.

Effect of plasma exchange on COVID-19 associated excess of von Willebrand factor and inflammation in critically ill patients

Ubiquitous microthromboses in the pulmonary vasculature play a crucial role in the pathogenesis of COVID-19 associated acute respiratory distress syndrome (ARDS). Excess of Willebrand factor (vWf) with intravascular multimer formation was identified as a key driver of this finding. Plasma exchange (PLEX) might be a therapeutic option to restore the disbalance between vWf and ADAMTS13. We report the effects of PLEX on vWf, ADAMTS13, inflammatory cytokines and parameters of ventilation. We investigated 25 patients, who were on mechanical ventilation for COVID-19 pneumonia with ARDS at two German university hospitals. All patients received PLEX as an ultima ratio measure for refractory ARDS. VWf antigen (vWf:Ag), ADAMTS13 activity, a cytokine panel mirroring the inflammatory situation and clinical parameters were assessed before and after three to six PLEX therapies with fresh frozen plasma. Before the PLEX sequence there was an excessive release of vWf:Ag (425.4 ± 167.5%) and mildly reduced ADAMTS13 activity (49.7 ± 23.3%). After the PLEX series, there was a significant increase of ADAMTS13 activity to 62.4 ± 17.7% (p = 0.029) and a significant decrease of vWf:Ag to 336.1 ± 138.2% (p = 0.041) resulting in a 63% improvement of the ADAMT13/vWf:Ag ratio from 14.5 ± 10.0 to 23.7 ± 14.6, p = 0.024. Comparison of parameters before and after individual PLEX sessions (n = 35) revealed a mean reduction of vWf from 387.8 ± 165.1 to 213.2 ± 62.3% (p = 0.001) and an increase of ADAMTS13 activity from 60.4 ± 20.1 to 70.5 ± 14.0% (p = 0.001). Parallelly, monocyte chemotactic protein-1 and interleukin-18 decreased significantly (p = 0.034 each). Along the PLEX sequence lactate dehydrogenase (p = 0.001), C-reactive protein (p = 0.001), and positive end expiratory pressure (p = 0.01) significantly decreased accompanied by an improvement of Horovitz index (p = 0.001). PLEX restores the disbalance between ADAMTS13 and vWf:Ag, a driver of immunothrombosis. Moreover, it reduces the inflammatory state and is associated with a benefit of ventilation parameters. These findings render a further rationale to regard PLEX as a therapeutic option in severe COVID-19.

Clinical Characteristics and Outcomes of Patients With COVID-19–Associated Acute Respiratory Distress Syndrome Who Underwent Lung Transplant

Lung transplantation is a potentially lifesaving treatment for patients who are critically ill due to COVID-19-associated acute respiratory distress syndrome (ARDS), but there is limited information about the long-term outcome. To report the clinical characteristics and outcomes of patients who had COVID-19-associated ARDS and underwent a lung transplant at a single US hospital. Retrospective case series of 102 consecutive patients who underwent a lung transplant at Northwestern University Medical Center in Chicago, Illinois, between January 21, 2020, and September 30, 2021, including 30 patients who had COVID-19-associated ARDS. The date of final follow-up was November 15, 2021. Lung transplant. Demographic, clinical, laboratory, and treatment data were collected and analyzed. Outcomes of lung transplant, including postoperative complications, intensive care unit and hospital length of stay, and survival, were recorded. Among the 102 lung transplant recipients, 30 patients (median age, 53 years [range, 27 to 62]; 13 women [43%]) had COVID-19-associated ARDS and 72 patients (median age, 62 years [range, 22 to 74]; 32 women [44%]) had chronic end-stage lung disease without COVID-19. For lung transplant recipients with COVID-19 compared with those without COVID-19, the median lung allocation scores were 85.8 vs 46.7, the median time on the lung transplant waitlist was 11.5 vs 15 days, and preoperative venovenous extracorporeal membrane oxygenation (ECMO) was used in 56.7% vs 1.4%, respectively. During transplant, patients who had COVID-19-associated ARDS received transfusion of a median of 6.5 units of packed red blood cells vs 0 in those without COVID-19, 96.7% vs 62.5% underwent intraoperative venoarterial ECMO, and the median operative time was 8.5 vs 7.4 hours, respectively. Postoperatively, the rates of primary graft dysfunction (grades 1 to 3) within 72 hours were 70% in the COVID-19 cohort vs 20.8% in those without COVID-19, the median time receiving invasive mechanical ventilation was 6.5 vs 2.0 days, the median duration of intensive care unit stay was 18 vs 9 days, the median post-lung transplant hospitalization duration was 28.5 vs 16 days, and 13.3% vs 5.5% required permanent hemodialysis, respectively. None of the lung transplant recipients who had COVID-19-associated ARDS demonstrated antibody-mediated rejection compared with 12.5% in those without COVID-19. At follow-up, all 30 lung transplant recipients who had COVID-19-associated ARDS were alive (median follow-up, 351 days [IQR, 176-555] after transplant) vs 60 patients (83%) who were alive in the non-COVID-19 cohort (median follow-up, 488 days [IQR, 368-570] after lung transplant). In this single-center case series of 102 consecutive patients who underwent a lung transplant between January 21, 2020, and September 30, 2021, survival was 100% in the 30 patients who had COVID-19-associated ARDS as of November 15, 2021.

Sevoflurane in combination with esketamine is an effective sedation regimen in COVID-19 patients enabling assisted spontaneous breathing even during prone positioning.

Effective analgosedation for control of dyspnoea and for toleration of prone positioning (PP) in severe coronavirus disease 2019 (COVID-19) associated acute respiratory distress syndrome (ARDS) is difficult to adjust. This study was designed to evaluate the feasibility and safety of sedation with inhaled sevoflurane in combination with intravenous esketamine during PP in patients with COVID-19-ARDS (CARDS). All mechanically ventilated COVID-19 patients admitted to the departmental intensive care unit from March to June 2020 were included in this epidemiological cohort study. Patients were sedated with inhaled sevoflurane in combination with eske-tamine during PP and not or only lightly sedated during the supine position. Assisted spontaneous breathing was applied in both prone and supine position. Adverse events were documented prospectively, and routine ventilation parameters, hemodynamic parameters, Richmond Agitation and Sedation Scale (RASS) and sevoflurane consumption were monitored. Altogether, 146 episodes of PP in 15 patients were observed. No severe sedation-related event was observed during 2610 hours of PP. In 2498 hours (96%) patients were successfully converted to a pressure-supported spontaneous breathing mode. Inhaled sedation with the AnaConDa-S-System (Sedana Medical AB, Danderyd, Sweden) alone is insufficient as soon as minute volume exceeds 7-8 L min-1, most likely due to technical reasons. Inhaled sedation with sevoflurane in combination with esketamine, however, safely enables prolonged prone positioning in patients with CARDS. Moreover, sedation depth was light enough to enable assisted spontaneous breathing during prone positioning.

Factors Associated with Severe Acute Respiratory Infections Due to Rhinovirus/Enterovirus Complex in Children and Their Comparison with Those of Respiratory Syncytial Virus

Background: Acute respiratory tract infections (ARTIs) are one of the main causes of morbidity and mortality in children under the age of five worldwide. Objectives: The objective of this research was to describe the main characteristics of hospitalized patients with ARTI caused by the rhinovirus/enterovirus (RV/EV) complex and the risk factors associated with severe infection. Methods: This was a retrospective descriptive study in patients from one month to 18-years-old who had been hospitalized for ARTI between October 2015 and December 2019 at Fundación Cardioinfantil in Bogotá, Colombia, and had had an RT-PCR viral panel during their hospitalization. Rhinovirus/enterovirus infection was characterized to identify factors associated with disease severity as compared to respiratory syncytial virus (RSV). A multivariate analysis was performed, controlling for confounding factors, to identify groups at risk of developing associated acute respiratory distress syndrome (ARDS). Results: During the study period, 645 RT-PCRs were performed, with the two main etiological agents identified being RV/EV (n = 224) and RSV (n = 68). The median age of patients with the RV/EV complex was 27 months (IQR: 8 - 70), and seven months for those with RSV (IQR: 2 - 11). Severe RV/EV complex infections required more transfers to intensive care (47% vs. 11%), showed more viral coinfection (OR: 2.13, 95% CI: 1.42 - 4.64), and had less bacterial coinfection (OR: 0.55, 95% CI: 0.31 - 0.98) than RSV infections. The RV/EV group had a higher risk of developing ARDS (OR: 3.6, 95% CI: 1.07 - 12:18), especially in premature infants (P: 0.05; exp(B), 2.99; 95% CI = 1.01 - 8.82), those with heart disease (P: 0.047; exp(B), 2.99; 95% CI = 1.01 - 8.82), and those with inborn errors of metabolism (P: 0.032; exp(B), 5 - 01; 95% CI = 1.15 - 21.81). A total of 13 patients from both study groups died (4.5%), with no differences found between the groups (RV/EV 54% vs. RSV 46%; P = 0.3). Conclusions: Respiratory infection due to RV/EV in children can frequently be severe, requiring management with intensive care therapy. When compared to RSV, this complex is more frequently associated with the development of ARDS, especially in risk groups such as those with prematurity, heart disease, or inborn errors of metabolism.

Long COVID-19 Pulmonary Sequelae and Management Considerations.

The human coronavirus 2019 disease (COVID-19) and the associated acute respiratory distress syndrome (ARDS) are responsible for the worst global health crisis of the last century. Similarly, to previous coronaviruses leading to past pandemics, including severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS), a growing body of evidence support that a substantial minority of patients surviving the acute phase of the disease present with long-term sequelae lasting for up to 6 months following acute infection. The clinical spectrum of these manifestations is widespread across multiple organs and consists of the long-COVID-19 syndrome. The aim of the current review is to summarize the current state of knowledge on the pulmonary manifestations of the long COVID-19 syndrome including clinical symptoms, parenchymal, and functional abnormalities, as well as highlight epidemiology, risk factors, and follow-up strategies for early identification and timely therapeutic interventions. The literature data on management considerations including the role of corticosteroids and antifibrotic treatment, as well as the therapeutic potential of a structured and personalized pulmonary rehabilitation program are detailed and discussed.