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Background: Patients with severe coronavirus disease 2019 (COVID) pneumonia and acute respiratory distress syndrome (C-ARDS) on invasive mechanical ventilation (IMV) have been found to be prone to having other microbial findings than severe acute respiratory syndrome coronavirus 2 (SARS-2)-CoV-19 in the bronchoalveolar lavage (BAL) fluid at intubation causing a superinfection. These BAL results could guide empirical antibiotic treatment in complex clinical situations. However, there are limited data on the relationship between microbial findings in the initial BAL at intubation and later ventilator-associated pneumonia (VAP) diagnoses., Objective: To analyse the incidence of, and microorganisms responsible for, superinfections in C-ARDS patients at the time of first intubation through microbial findings in BAL fluid. To correlate these findings to markers of inflammation in plasma and later VAP development., Design: Retrospective single-centre study., Setting: One COVID-19 intensive care unit (ICU) at a County Hospital in Sweden during the first year of the pandemic., Patients: All patients with C-ARDS who were intubated in the ICU., Results: We analysed BAL fluid specimens from 112 patients at intubation, of whom 31 (28%) had superinfections. Blood levels of the C-reactive protein, procalcitonin, neutrophil granulocytes, and lymphocytes were indistinguishable between patients with and without a pulmonary superinfection. Ninety-eight (88%) of the patients were treated with IMV for more than 48 h and of these patients, 37% were diagnosed with VAP. The microorganisms identified in BAL at the time of intubation are normally found at the oral, pharyngeal, and airway sites. Only one patient had an indistinguishable bacterial strain responsible for both superinfection at intubation and in VAP., Conclusions: One fourth of the patients with C-ARDS had a pulmonary superinfection in the lungs that was caused by another microorganism identified at intubation. Routine serum inflammatory markers could not be used to identify this complication. Microorganisms located in BAL at intubation were rarely associated with later VAP development., (© 2024 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Introduction: Prone position ventilation (PPV) of patients with adult respiratory distress syndrome (ARDS) supported with veno-venous extracorporeal membrane oxygenation (V-V ECMO) may improve oxygenation and alveolar recruitment and is recommended when extensive dorsal consolidations are present, but only few data regarding adverse events (AE) related to PPV in this group of patients have been published., Methods: Nationwide retrospective analysis of 68 COVID-19 patients admitted from March 2020 - December 2021 with severe ARDS and need of V-V ECMO support. The number of patients treated with PPV, number of PPV-events, timing, the time spent in prone position, number and causes of AE are reported. Causes to stop the PPV regimen and risk factors for AE were explored., Results: 44 out of 68 patients were treated with PPV, and 220 PPV events are evaluated. AE were identified in 99 out of 220 (45%) PPV events and occurred among 31 patients (71%). 1 fatal PPV related AE was registered. Acute supination occurred in 19 events (9%). Causes to stop the PPV regimen were almost equally distributed between effect (weaned from ECMO), no effect, death (of other reasons) and AE. Frequent causes of AE were pressures sores and ulcers, hypoxia, airway related and ECMO circuit related. Most AE occurred during patients first or second PPV event., Conclusions: PPV treatment was found to carry a high incidence of PPV related AE in these patients. Causes and preventive measures to reduce occurrence of PPV related AE during V-V ECMO support need further exploration., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Lung ultrasound (LUS) is a known imaging modality employed for monitoring patients in an intensive care unit. This study evaluates, LUS in assessing disease severity and prognosis, by correlating its score with the three commonly used clinical severity scoring systems (CSSS), namely, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHE) II score, and simplified acute physiology score (SAPS) II., Methods: This single-center prospective observational study included 54 adult patients of primary lung disease-induced acute respiratory distress syndrome (ARDS), on invasive ventilation. The primary objective was to correlate LUS score with SOFA score. Secondary objectives were to correlate LUS score with APACHE II and SAPS II scores. LUS score was also correlated with the estimated mortality derived from the above-mentioned scores. A subgroup analysis on COVID-19-positive cases was also carried out. All scores were calculated on the initiation of mechanical ventilation, daily for 7 days or mortality, whichever was earlier., Results: A significant positive correlation ( P < 0.001) was found between LUS and all three severity scores, as well as their corresponding estimated mortality percentages, for all days of the study period, in both non-COVID-19 ARDS patients and in COVID-19 patients. The merit of all four scores in differentiating between the survivor and mortality group for the duration of study also showed significant ( P < 0.05) to very significant ( P < 0.001) results., Conclusion: Point-of-care LUS in conjunction with CSSS is a reliable tool for assessing the severity and progression of primary lung disease., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 International Journal of Critical Illness and Injury Science.)

Objective: This prospective observational study explored the effect of early onset hypoalbuminemia (EOH) on the development of adult respiratory distress syndrome (ARDS) in orthopedic trauma victims., Methods: Serum albumin levels were measured for the initial 7 days of injury for adult trauma patients (18-65 years). Patients were recruited into group A (any serum albumin value < 3.5 mg/dl) and group B (all serum albumin ≥ 3.5 mg/dl), based on serum albumin values. Patients were followed for the development of ARDS and outcome until 28 days. The primary outcome of the study was to explore the effects of EOH on ARDS., Results: EOH (any serum albumin value < 3.5 g/dl within 7 days of injury) was present in 205/386 (53.1%) patients. The majority of 174/205 (84.9%) patients had EOH by the fourth day after the injury, with the mean time for development of EOH being 2.15 ± 1.87 days. ARDS manifested in 87/205 (42.4%) and 15/181 (8.3%) patients in group A and group B, respectively (p < 0.001). EOH had 8.2 times greater odds of ARDS (OD 8.2 95% CL 4.7-14.0, p = 0.000). The mean time for the onset of ARDS was 5.63 ± 2.62 days. No statistically significant causal relationship occurred between the onset of EOH and the development of ARDS (Pearson's correlation coefficient = 0.14, p = 0.16). At serum albumin cutoff concentrations of 3.4 gm/dl on D1 (AUC 0.68, 95% CI: 0.61-0.74, p = 0.000), ARDS may be anticipated in 62.8% of patients. The commencement of ARDS was independently correlated with EOH (p = 0.000), Respiratory rate on admission (p = 0.000), inotrope use (p = 0.000), and soft tissue injury (p = 0.000) (R 2  = 0.466). The odds of 28-day all-cause death were 7.7 times higher in EOH (OD 7.7 95% CL 3.5-16.7, p = 0.00) and 9 times higher in ARDS (OD 9 95% CL 4.9-16.16, p = 0.00)., Conclusion: EOH is a frequent occurrence and has a strong influence development of ARDS and 28-day mortality in trauma patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Introduction: This bibliographic review is carried out in order to obtain answers about aspects related to techniques and treatments, as well as care associated with the critically ill patient diagnosed with COVID-19., Objective: To analyze the available scientific evidence on the effectiveness of the use of invasive mechanical ventilation together with other adjuvant techniques, in reducing the mortality rate in patients with acute respiratory distress syndrome and clinical trial of COVID-19 treated in intensive care units., Methodology: A systematized bibliographic review was carried out in the PubMed, CUIDEN, LILACS, Medline, CINAHL and Google Scholar databases, using MeSH terms (adult respiratory distress syndrome, mechanical ventilation, prone position, nitric oxide, extracorporeal membrane oxygenation, nursing care) and the corresponding Boolean operators. The selected studies underwent a critical reading carried out between December 6, 2020 and March 27, 2021 using the Critical Appraisal Skills Program tool in Spanish and a cross-sectional epidemiological studies evaluation instrument., Results: A total of 85 articles were selected. After performing the critical reading, a total of 7 articles were included in the review, 6 being descriptive studies and one a cohort study. After analyzing these studies, it appears that the technique that has obtained the best results is extracorporeal membrane oxygenation, with the care provided by qualified and trained nursing staff being very important., Conclusion: Mortality from COVID-19 increases in patients treated with invasive mechanical ventilation compared to patients treated with extracorporeal membrane oxygenation. Nursing care and specialization can have an impact on improving patient outcomes., (© 2022 Sociedad Española de Enfermería Intensiva y Unidades Coronarias (SEEIUC). Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: This bibliographic review is carried out in order to obtain answers about aspects related to techniques and treatments, as well as care associated with the critically ill patient diagnosed with Covid-19., Objective: To analyze the available scientific evidence on the effectiveness of the use of invasive mechanical ventilation together with other adjuvant techniques, in reducing the mortality rate in patients with Acute Respiratory Distress Syndrome and clinical trial of Covid-19 treated in intensive care units., Methodology: A systematized bibliographic review was carried out in the Pubmed, Cuiden, Lilacs, Medline, Cinahl and Google Scholar databases, using MeSH terms (Adult Respiratory Distress Syndrome, Mechanical Ventilation, Prone Position, Nitric Oxide, Extracorporeal Membrane Oxygenation, Nursing Care) and the corresponding Boolean operators. The selected studies underwent a critical reading carried out between December 6, 2020 and March 27, 2021 using the Critical Appraisal Skills Program tool in Spanish and a cross-sectional epidemiological studies evaluation instrument., Results: A total of 85 articles were selected. After performing the critical reading, a total of 7 articles were included in the review, 6 being descriptive studies and 1 cohort study. After analyzing these studies, it appears that the technique that has obtained the best results is ECMO, with the care provided by qualified and trained nursing staff being very important., Conclusion: Mortality from Covid-19 increases in patients treated with invasive mechanical ventilation compared to patients treated with extracorporeal membrane oxygenation. Nursing care and specialization can have an impact on improving patient outcomes., (Copyright © 2022 Sociedad Española de Enfermería Intensiva y Unidades Coronarias (SEEIUC). Published by Elsevier España, S.L.U. All rights reserved.)

Background: Elderly patients are more susceptible to Coronavirus Disease-2019 (COVID-19) and are more likely to develop it in severe forms, (e.g., Acute Respiratory Distress Syndrome [ARDS]). Prone positioning is a treatment strategy for severe ARDS; however, its response in the elderly population remains poorly understood. The main objective was to evaluate the predictive response and mortality of elderly patients exposed to prone positioning due to ARDS-COVID-19., Methods: This retrospective multicenter cohort study involved 223 patients aged ≥ 65 years, who received prone position sessions for severe ARDS due to COVID-19, using invasive mechanical ventilation. The PaO 2 /FiO 2 ratio was used to assess the oxygenation response. The 20-point improvement in PaO 2 /FiO 2 after the first prone session was considered for good response. Data were collected from electronic medical records, including demographic data, laboratory/image exams, complications, comorbidities, SAPS III and SOFA scores, use of anticoagulants and vasopressors, ventilator settings, and respiratory system mechanics. Mortality was defined as deaths that occurred until hospital discharge., Results: Most patients were male, with arterial hypertension and diabetes mellitus as the most prevalent comorbidities. The non-responders group had higher SAPS III and SOFA scores, and a higher incidence of complications. There was no difference in mortality rate. A lower SAPS III score was a predictor of oxygenation response, and the male sex was a risk predictor of mortality., Conclusion: The present study suggests the oxygenation response to prone positioning in elderly patients with severe COVID-19-ARDS correlates with the SAPS III score. Furthermore, the male sex is a risk predictor of mortality., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2023 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Bioactive adrenomedullin (bio-ADM) is a vasoactive peptide with a key role in reducing vascular hyperpermeability and improving endothelial stability during infection, but it also has vasodilatory properties. Bioactive ADM has not been studied in conjunction with acute respiratory distress syndrome (ARDS), but it has recently been shown to correlate with outcomes after severe COVID-19. Therefore, this study investigated the association between circulating bio-ADM on intensive care unit (ICU) admission and ARDS. The secondary aim was the association between bio-ADM and ARDS mortality., Methods: We analysed bio-ADM levels and assessed the presence of ARDS in adult patients admitted to two general intensive care units in southern Sweden. Medical records were manually screened for the ARDS Berlin criteria. The association between bio-ADM levels and ARDS and mortality in ARDS patients was analysed using logistic regression and receiver-operating characteristics analysis. The primary outcome was an ARDS diagnosis within 72 h of ICU admission, and the secondary outcome was 30-day mortality., Results: Out of 1224 admissions, 11% (n = 132) developed ARDS within 72 h. We found that elevated admission bio-ADM level was associated with ARDS independently of sepsis status and of organ dysfunction as measured by the Sequential organ failure assessment (SOFA) score. Both lower levels (< 38 pg/L) and high (> 90 pg/L) levels of bio-ADM were independently (of the Simplified acute physiology score, SAPS-3) predictive of mortality. Patients with indirect mechanisms of lung injury had higher bio-ADM levels than those with a direct mechanism of injury, and bio-ADM increased with increasing ARDS severity., Conclusions: High levels of bio-ADM on admission are associated with ARDS, and bio-ADM levels significantly differ depending on the injury mechanism. In contrast, both high and low levels of bio-ADM are associated with mortality, possibly due to the dual action of bio-ADM in stabilising the endothelial barrier and causing vasodilation. These findings could lead to improved diagnostic accuracy of ARDS and potentially lead to new therapeutic strategies., (© 2023. The Author(s).)

Background: Arterial lactate is a recognized biomarker associated with death in critically ill patients. The prognostic role of arterial lactate in acute respiratory failure due to the novel coronavirus disease 2019 (COVID-19) is unclear., Objectives: We aimed to investigate the prognostic role of arterial lactate levels at admission in patients with COVID-19-related acute respiratory failure., Design and Methods: Cohorts of consecutive patients admitted to nonintensive care units (ICU) at study centers for COVID-19-related respiratory failure were merged into a collaborative database. The prognostic role of lactate levels at admission was assessed for continuous values and values ⩾2.0 mmol/l, and lactate clearance at 24 h through delta-lactate (ΔLac). The study outcome was 30-day in-hospital death. Cox proportional regression model was used to assess independent predictors of the study outcome., Results: At admission, 14.6% of patients had lactate levels ⩾2 mmol/l. In-hospital death at 30 days occurred in 57 out of 206 patients; 22.3% and 56.7% with normal or ⩾ 2 mmol/l lactate at admission, respectively. The median lactate level was 1.0 [interquartile range (IQR) 0.8-1.3] mmol/l and 1.3 (IQR 1.0-2.1) mmol/l in survivors and nonsurvivors, respectively ( p -value < 0.001). After adjusting for age, relevant comorbidities, acidemia, and the severity of respiratory failure, lactate ⩾2.0 mmol/l was associated with in-hospital death (HR 2.53, 95% CI 1.29-4.95, p -value 0.0066), while Δ Lac ⩾0 was not (HR 1.37, 95% CI 0.42-4.49). These results were confirmed in patients with a pO 2 /FiO 2 -ratio (P/F ratio) ⩽300 mmHg., Conclusions: In our study, increased arterial lactate at admission was independently associated with in-hospital death at 30 days in non-ICU patients with acute respiratory failure related to COVID-19.

Excessive sedation is associated with poor outcome in critically ill acute respiratory distress syndrome (ARDS) patients. Whether this prognostic effect varies among ARDS patients with and without COVID-19 has yet to be determined. We compared the prognostic value of excessive sedation—in terms of delirium, length of stay in intensive care unit (ICU-LOS) and ICU mortality—between COVID-19 and non-COVID-19 critically ill ARDS patients. This was a second analysis of prospectively collected data in four European academic centers pertaining to 101 adult critically ill ARDS patients with and without COVID-19 disease. Depth of sedation (DOS) and delirium were monitored through processed electroencephalogram (EEG) and the Confusion Assessment Method for ICU (CAM-ICU). Our main exposure was excessive sedation and how it relates to the presence of delirium, ICU-LOS and ICU mortality. The criterion for excessive sedation was met in 73 (72.3%) patients; of these, 15 (82.2%) and 58 (69.1%) were in non-COVID-19 and COVID-19 ARDS groups, respectively. The criteria of delirium were met in 44 patients (60.3%). Moreover, excessive sedation was present in 38 (86.4%) patients with delirium (p < 0.001). ICU death was ascertained in 41 out of 101 (41.0%) patients; of these, 37 (90.2%) had excessive sedation (p < 0.001). The distribution of ICU-LOS among excessive-sedated and non-sedated patients was 22 (16−27) vs. 14 (10.5−19.5) days (p < 0.001), respectively. In a multivariable framework, excessive sedation was independently associated with the development of delirium (p = 0.001), increased ICU mortality (p = 0.009) and longer ICU-LOS (p = 0.000), but only in COVID-19 ARDS patients. Independent of age and gender, excessive sedation might represent a risk factor for delirium in COVID-19 ARDS patients. Similarly, excessive sedation shows to be an independent predictor of ICU-LOS and ICU mortality. The use of continuous EEG-based depth of sedation (DOS) monitoring and delirium assessment in critically ill COVID-19 patients is warranted.

Background: The use of extracorporeal membrane oxygenation (ECMO) has increased, although its survival benefit in trauma patients with severe adult respiratory distress syndrome (ARDS) remains controversial. We investigated the effect of veno-venous (VV)-ECMO on the clinical outcomes of trauma patients with severe ARDS., Methods: This was a retrospective study at a single center comprising trauma patients admitted between January 2013 and December 2017, diagnosed with severe ARDS using the Berlin definition (PaO2/FiO2 ratio ⩽100), in the 7 days following trauma. Patients were managed with VV-ECMO or conventional mechanical ventilation (CMV). The primary outcome was in-hospital mortality (mortality at 60 days); secondary outcomes comprised 28-day mortality, hospital length of stay (LOS), intensive care unit (ICU) LOS, ICU-free days, duration of mechanical ventilation (MV), and MV-free days. Propensity score matching was performed to adjust for the baseline differences., Results: Sixteen patients (22.5%) were managed with VV-ECMO and 55 were managed with CMV. After matching, the in-hospital mortality rate (43.8% vs 53.1%; p  = 0.760), 28-day mortality rate (37.5% vs 31.3%; p  = 0.750), median hospital LOS (39.5 vs 36.5 days; p  = 0.533), ICU-free days (0 vs 0 days; p  = 0.241), and MV-free days (0 vs 0 days; p  = 0.272) did not significantly differ between the VV-ECMO and CMV groups., Conclusion: In-hospital mortality (mortality at 60 days) did not differ significantly between the VV-ECMO and CMV groups. Although the safety of ECMO in trauma patients requires further investigation, VV-ECMO may be considered as a rescue therapy.

Background: Corticosteroids are one of the few drugs that have shown a reduction in mortality in coronavirus disease 2019 (COVID-19). In the RECOVERY trial, the use of dexamethasone reduced 28-day mortality compared to standard care in hospitalized patients with suspected or confirmed COVID-19 requiring supplemental oxygen or invasive mechanical ventilation. Evidence has shown that 30% of COVID-19 patients with mild symptoms at presentation will progress to acute respiratory distress syndrome (ARDS), particularly patients in whom laboratory inflammatory biomarkers associated with COVID-19 disease progression are detected. We postulated that dexamethasone treatment in hospitalized patients with COVID-19 pneumonia without additional oxygen requirements and at risk of progressing to severe disease might lead to a decrease in the development of ARDS and thereby reduce death., Methods/design: This is a multicenter, randomized, controlled, parallel, open-label trial testing dexamethasone in 252 adult patients with COVID-19 pneumonia who do not require supplementary oxygen on admission but are at risk factors for the development of ARDS. Risk for the development of ARDS is defined as levels of lactate dehydrogenase > 245 U/L, C-reactive protein > 100 mg/L, and lymphocyte count of < 0.80 × 10 9 /L. Eligible patients will be randomly assigned to receive either dexamethasone or standard of care. Patients in the dexamethasone group will receive a dose of 6 mg once daily during 7 days. The primary outcome is a composite of the development of moderate or more severe ARDS and all-cause mortality during the 30-day period following enrolment., Discussion: If our hypothesis is correct, the results of this study will provide additional insights into the management and progression of this specific subpopulation of patients with COVID-19 pneumonia without additional oxygen requirements and at risk of progressing to severe disease., Trial Registration: ClinicalTrials.gov NCT04836780. Registered on 8 April 2021 as EARLY-DEX COVID-19., (© 2022. The Author(s).)

Human metapneumovirus (hMPV) is a common cause of upper and lower respiratory tract infections in children. A few case reports have described hMPV encephalitis or encephalopathy. Neuroimaging data on patients with hMPV encephalitis are scarce. We report a patient with trisomy 13 who developed severe hMPV pneumonia, multifocal cerebral and cerebellar hemorrhagic infarctions and extensive cerebral white matter demyelination. Although adult respiratory distress syndrome and disseminated intravascular coagulation contributed to the devastating central nervous system (CNS) lesions, endothelial dysfunction of the CNS caused by hMPV infection probably also played a pathophysiological role in this case.

Objectives: The objectives of this study were to 1) in patients without pulmonary function, determine resting energy expenditure (REE) in venovenous extracorporeal membrane oxygenation (ECMO) acute respiratory distress syndrome (ARDS) patients by paralysis status and 2) determine the threshold tidal volume (TV) associated with meaningful gas exchange as determined by measurable end-tidal carbon dioxide elimination (etV̇co 2 )., Design: Retrospective observational study., Setting: A tertiary high ECMO volume academic institution., Patients/subjects: Ten adult ARDS patients on venovenous ECMO., Interventions: None., Measurements and Main Results: The modified Weir equation, Fick principle, Henderson-Hasselbalch equation, ECMO flow, hemoglobin, and pre and post oxygenator blood gases were used to determine ECMO carbon dioxide production (V̇co 2 ), ECMO oxygen consumption, and REE. REE values were matched to patients' paralysis status based on medication flowsheets and compared using a paired t test. Linear regression was performed to determine the threshold TV normalized to ideal body weight (IBW) associated with measurable ventilator etV̇co 2 , above which meaningful ventilation occurs. When lungs were not functioning, patients had significantly lower mean REE when paralyzed (23.4 ± 2.8 kcal/kg/d) than when not paralyzed (29.2 ± 5.8 kcal/kg/d) ( p = 0.02). Furthermore, mean REE was not similar between patients and varied as much as 1.7 times between patients when paralyzed and as much as 1.4 times when not paralyzed. Linear regression showed that ventilator V̇co 2 was measurable and increased linearly when TV was greater than or equal to 0.7 mL/kg., Conclusions: REE is patient-specific and varies significantly with and without patient paralysis. When TV exceeds 0.7 mL/kg IBW, ventilator V̇co 2 increases measurably and must be considered in determining total REE., Competing Interests: Dr. Ong was funded by the Hearts of extracorporeal membrane oxygenation (ECMO), a nonprofit organization funding ECMO research. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Extracorporeal membrane oxygenation (ECMO) is a potential option for the management of severe acute respiratory failure secondary to COVID-19. Conflicting the use of this therapy is the known coagulopathy within COVID-19, leading to an incidence of venous thrombotic events of 25% to 49%. To date, limited guidance is available on optimal anticoagulation strategies in this population., Objective: The purpose of this study was to evaluate the utilization of a pharmacist-driven bivalirudin dosing protocol for anticoagulation in the setting of ECMO for COVID-19-associated respiratory failure., Methods: This was a single-center retrospective chart review over a 9-month period of patients receiving bivalirudin while on ECMO. All patients with acute respiratory failure requiring ECMO with a positive SARS-CoV-2 polymerase chain reaction were included. Bivalirudin was dosed via aPTT monitoring after a starting dose of 0.2 or 0.3 mg/kg/h., Results: There were 33 patients included in this study, all receiving mechanical ventilation. The most common starting dose of bivalirudin was 0.2 mg/kg/h, with an average time to therapeutic range of 20 hours. Compared to previous reports, rates of bleeding were low at 15.1%, and 6.1% of patients developed a new venous thromboembolic event while on ECMO. ECMO survival was 51.5%, with an ICU mortality rate of 48.5%., Conclusion and Relevance: In the first published report of its use within this population, bivalirudin was found to be a viable choice for anticoagulation in those patients on ECMO for severe respiratory failure secondary to COVID-19.

Background: Severe hypoxic respiratory failure from COVID-19 pneumonia carries a high mortality risk. There is uncertainty surrounding which patients benefit from corticosteroids in combination with tocilizumab and the dosage and timing of these agents. The balance of controlling inflammation without increasing the risk of secondary infection is difficult. At present, dexamethasone 6 mg is the standard of care in COVID-19 hypoxia; whether this is the ideal choice of steroid or dosage remains to be proven., Objectives: The primary objective was to assess the impact on mortality of tocilizumab only, corticosteroids only, and combination therapy in patients with COVID-19 respiratory failure., Methods: A multihospital, retrospective study of adult patients with severe respiratory failure from COVID-19 who received supportive therapy, corticosteroids, tocilizumab, or combination therapy were assessed for 28-day mortality, biomarker improvement, and relative risk of infection. Propensity-matched analysis was performed between corticosteroid alone and combination therapies to further assess mortality benefit., Results: The steroid-only, tocilizumab-only, and combination groups showed hazard reduction in mortality at 28 days when compared with supportive therapy. In a propensity-matched analysis, the combination group (daily equivalent dexamethasone 10 mg and tocilizumab 400 mg) had an improved 28-day mortality compared with the steroid-only group (daily equivalent dexamethasone 10 mg; hazard ratio (95% CI) = 0.56 (0.38-0.84), P = 0.005] without increasing the risk of infection., Conclusion and Relevance: Combination of tocilizumab and corticosteroids was associated with improved 28-day survival when compared with corticosteroids alone. Modification of steroid dosing strategy as well as steroid type may further optimize therapeutic effect of the COVID-19 treatment.

Competing Interests: The authors are executive officers for Airway Therapeutics.

Corticosteroids are one of the few drugs that have shown a reduction in mortality in coronavirus disease 2019 (COVID-19). In the RECOVERY trial, the use of dexamethasone reduced 28-day mortality compared to standard care in hospitalized patients with suspected or confirmed COVID-19 requiring supplemental oxygen or invasive mechanical ventilation. No benefit in patients not requiring respiratory support at randomization was observed. However, we believe that the use of corticosteroids in patients with COVID-19 pneumonia might not be subject to a decision based solely on oxygen needs. Evidence has shown that 30% of COVID-19 patients in its initial phases will progress to acute respiratory distress syndrome, particularly patients in whom laboratory inflammatory biomarkers associated with COVID-19 disease progression are detected. We postulated that corticosteroids in patients with COVID-19 in its initial phases and risk of progressing to severe disease might lead to a decrease in the development of acute respiratory distress syndrome, and thereby reduce death.

Background: Findings from autopsies have provided evidence on systemic microvascular damage as one of the underlying mechanisms of Coronavirus disease 2019 (CO-VID-19). The aim of this study was to correlate autopsy-based cause of death in SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients with chest imaging and severity grade of pulmonary and systemic morphological vascular pathology., Methods: Fifteen SARS-CoV-2 positive autopsies with clinically distinct presentations (age 22-89 years) were retrospectively analyzed with focus on vascular, thromboembolic, and ischemic changes in pulmonary and in extrapulmonary sites. Eight patients died due to COVID-19 associated respiratory failure with diffuse alveolar damage in various stages and/or multi-organ failure, whereas other reasons such as cardiac decompensation, complication of malignant tumors, or septic shock were the cause of death in 7 further patients. The severity of gross and histopathological changes was semi-quantitatively scored as 0 (absent), 1 (mild), and 3 (severe). Severity scores between the 2 groups were correlated with selected clinical parameters, initial chest imaging, autopsy-based cause of death, and compared using Pearson χ2 and Mann-Whitney U tests., Results: Severe pulmonary endotheliitis (p = 0.031, p = 0.029) and multi-organ involvement (p = 0.026, p = 0.006) correlated significantly with COVID-19 associated death. Pulmonary microthrombi showed limited statistical correlation, while tissue necrosis, gross pulmonary embolism, and bacterial superinfection did not differentiate the 2 study groups. Chest imaging at hospital admission did not differ either., Conclusions: Extensive pulmonary endotheliitis and multi-organ involvement are characteristic autopsy features in fatal CO-VID-19 associated deaths. Thromboembolic and ischemic events and bacterial superinfections occur frequently in SARS-CoV-2 infection independently of outcome., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

The successful use of prolonged (ie, >28 days) veno-venous extracorporeal membrane oxygenation (V-V ECMO) is being increasingly reported. However, limited data are available on its outcomes. This study investigated the outcomes of acute respiratory distress syndrome (ARDS) patients on prolonged ECMO support. We retrospectively evaluated 57 patients requiring V-V ECMO for ARDS between 2015 and 2020. The patients were divided into two groups according to ECMO duration: (a) ≤28 days group (n = 43, 75%) or (b) >28 days (n = 14, 25%) group. Clinical characteristics, complications, and outcomes between these two groups were statistically compared. There were no significant differences in demographics, comorbidity, ARDS etiology, and severity scores between the two groups. However, the mechanical ventilation period before ECMO initiation was significantly longer in the >28 days group than in the ≤28 days group (10.5 days vs. 1 day; P < .05). The incidence of positive bacterial blood culture results during ECMO was significantly higher in the >28 days group than in the ≤28 days group (43% vs. 9%; P < .05). Additionally, the hospital survival rate was significantly lower in the >28 days group than in the ≤28 days ECMO group (21% vs. 60%; P < .05). Prolonged ECMO was associated with worse hospital survival outcomes. Early initiation of ECMO along with meticulous care and appropriate treatment against infection during ECMO could improve the hospital survival of ARDS patients on prolonged ECMO support., (© 2021 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Veno-venous extracorporeal membrane oxygenation is increasingly used for severe but potentially reversible acute respiratory failure in adults; however, there are limited data regarding long-term morbidity. At our institution, most patients requiring veno-venous extracorporeal membrane oxygenation have been followed up by a single physician. Our primary aim was to describe the serial long-term morbidity for respiratory, musculoskeletal and psychological functioning., A retrospective audit of inpatient and outpatient medical records was conducted. A total of 125 patients treated with veno-venous extracorporeal membrane oxygenation for primary respiratory failure were included. The patients were young (mean (standard deviation) age 43.7 (4.1) years), obese (mean (standard deviation) body mass index 30.8 (10.4) kg/m 2 ), and mostly were male (59%). Most patients (60%) had no comorbidities., The survival rate to discharge was 70%, with body mass index and the number of comorbidities being independent predictors of survival on multiple logistic regression analysis. Over half (57%) of the Australian survivors had regular outpatient follow-up. They had a median of three reviews (range 1-9) over a median of 11.8 months (range 1.5-79) months. Breathlessness and weakness resolved in most within six months, with lung function abnormalities taking longer to resolve. Over half (60%) returned to employment within six months of discharge. Over a quarter (29%) displayed symptoms of anxiety, depression or post-traumatic stress disorder.

Background: The multifactorial etiology of acute respiratory failure (ARF) often complicates diagnosis at an early stage of clinical presentation. Despite being a common life-threatening disorder, accurate and timely diagnosis is hindered by bad quality of bedside radiographs and nonavailability of immediate computed tomography imaging. This study was an attempt to evaluate the diagnostic accuracy of ultrasound in diagnosing ARF., Methods: This hospital-based cross-sectional study investigated the underlying etiological factor in 130 patients presenting with ARF and admitted to the intensive care unit. Lung ultrasound was performed according to the Bedside Lung Ultrasound in Emergency (BLUE) protocol. The diagnostic accuracy of lung ultrasound by emergency protocol was measured against each final diagnosis., Results: The mean age observed was 49.28 ± 14.9 years among the cohort. Of the 130 patients, pneumonia was the most common cause of ARF, seen in 42 patients. Breathlessness (56.15%) and fever accompanied by cough (25.38%) were the chief complaints. Diagnostic accuracy of ultrasound lung emergency protocol was 95.38% in the diagnosis of pulmonary edema, 100% for pneumothorax, 93.85% for pneumonia, 96.92% for chronic obstructive pulmonary disease, 99.23% for pulmonary thromboembolism, and 95.38% for acute respiratory distress syndrome., Conclusion: Lung ultrasound is a reliable modality that provided accurate and timely diagnosis of ARF in this study. Therefore, BLUE protocol is feasible, easily implementable in the intensive care unit, and must be scaled up in respiratory health-care settings., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Medical Ultrasound.)

Objective Coronavirus disease 2019 (COVID-19) is associated with diffuse lung injury that can progress to acute respiratory distress syndrome, multisystem-organ failure, and death. The inflammatory storm seen in many COVID-19 patients closely resembles secondary hemophagocytic lymphohistiocytosis (sHLH) which has been described in other virus-associated severe sepsis. We sought to describe the incidence of sHLH in COVID-19 infected patients. Design In this retrospective study, we reviewed the records of critically ill COVID-19 positive patients to determine the incidence of sHLH. An H-score for sHLH diagnosis was determined for each study participant, with a score greater than 169 points needed for diagnosis. Setting A quaternary referral center in suburban Pennsylvania, USA. Patients All study participants had a positive COVID-19 test, and were deemed critically ill defined as receiving invasive mechanical ventilation and/or who expired. Measurements and Main Results Of the 246 records identified, 242 records met inclusion criteria and were reviewed. Eighty five patients were excluded from analysis due to missing H-score data parameters. Overall, 32 of 157 (20.38%, 95% CI:14.38-27.54%) patients met diagnostic criteria for sHLH. The average age was 69.42 years (standard deviation (SD) 14.81). Patients diagnosed with sHLH were more likely to be younger (61.09 years vs 69.38 years, P = 0.0036), male (71.88% vs 52.00%, P = 0.0433), and require mechanical ventilation (96.88% vs 72.80%, P = 0.0035). Conclusions Among critically ill COVID-19 positive patients, the incidence of sHLH is higher than previously reported in patients with non-COVID-19 related sepsis. Clinicians caring for COVID-19 patients should consider this secondary diagnosis and subsequent appropriate treatments, especially in those requiring mechanical ventilation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Allen et al.)

Background: In late 2019, the world saw a viral outbreak of unprecedented scale that sent a significant fraction of humankind into either quarantine or lockdown. Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which was first recognized in Wuhan, China, in December 2019., Methods: We created and administered a 17-item questionnaire for health care professionals (HCPs) to assess their level of knowledge towards this ongoing and evolving pandemic. It was disseminated through Web- and mobile-based social networks. The questions were sourced and created from various standard national and international guidelines available at the time of writing., Results: A total of 827 medical personnel participated in the study. Among them, 65.5% scored between 60% and 79%, indicating a moderate level of knowledge. There was no statistically significant difference in the scores of doctors, nursing officers and dental surgeons ( p  = 0.200). Participants had good knowledge regarding clinical symptoms, mode of transmission and preventive measures. But the study identified some gaps in knowledge in the implementation of management protocols, handling of dead bodies and biomedical waste management of COVID-19 cases., Conclusion: With this understanding, regular training, drills and knowledge dissemination along with skill development through learning correct practices focusing on HCP at all levels are the current needs., Competing Interests: The authors have none to declare., (© 2020 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd.)

Background Although commonly used inside hospitals, no previous case report has been published on high-flow nasal oxygen (HFNO) therapy in an adult in the prehospital setting. Case Report A 46-year-old nonsmoking man presented with a cough and fever. He deteriorated suddenly 5 days later. When the basic life support team arrived, his peripheral oxygen saturation (SpO 2 ) in ambient air was 56% and respiratory rate was 46 breaths/min. The man was weak with thoracoabdominal asynchrony. An emergency medical team with a physician was dispatched. As France was still under lockdown for the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic, COVID-19 (coronavirus disease 2019) was suspected. In spite of 15 L/min of oxygen delivered with a nonrebreathing mask, the patient's SpO 2 tended to drop below 90% at the slightest effort and during transport from home to the ambulance. It was therefore decided to start HFNO therapy. The patient was transferred to an intensive care unit, where HFNO was continued. Why Should an Emergency Physician Be Aware of This? As the trend in emergency medical services may move toward prehospital HFNO, this case report is an opportunity to question the feasibility of HFNO therapy in the prehospital setting., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This study's objective was to describe and validate flow index (flow rate × FiO 2 /weight) as a method to report the degree of respiratory support by high flow nasal cannula (HFNC) in children. We conducted a retrospective chart review of children managed with HFNC from January 1, 2015 to December 31, 2019. Variables included in the flow index (weight, fraction of inspired oxygen [FiO 2 ], flow rate) and outcomes (hospital and intensive care unit [ICU] length of stay [LOS], escalation to the ICU) were extracted from medical records. Max flow index was defined by the earliest timestamp when patients FiO 2  × flow rate was maximum. Step-wise regression was used to determine the relationship between outcome (LOS and escalation to ICU) and flow index. Fifteen hundred thirty-seven patients met the study criteria. The median first and maximum flow indexes of the population were 24.1 and 38.1. Both first and maximum flow indexes showed a significant correlation with the LOS ( r  = 0.25 and 0.31, p  < 0.001). Correlation for the index was stronger than that of the variables used to calculate them and remained significant after controlling for age, race, sex, and diagnoses. Mild, moderate, and severe categories of first and max flow index were derived using quartiles, and they showed significant age and diagnosis independent association with LOS. Patients with first flow index >20 and maximum flow index >59.5 had increased odds ratio of escalation to ICU (odds ratio: 2.39 and 8.08). The first flow index had a negative association with rapid response activation. Flow index is a valid measure for assessing the degree of respiratory support for children on HFNC., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Background: With pandemic of coronavirus disease 2019 (COVID-19), human coronaviruses (HCoVs) have recently attached worldwide attention as essential pathogens in respiratory infection. HCoV-229E has been described as a rare cause of lower respiratory infection in immunocompetent adults., Case Presentation: We reported a 72-year-old man infected by HCoV-229E with rapid progression to acute respiratory distress syndrome, in conjunction with new onset atrial fibrillation, intensive care unit acquired weakness, and recurrent hospital acquired pneumonia. Clinical and radiological data were continuously collected. The absolute number of peripheral T cells and the level of complement components diminished initially and recovered after 2 months. The patient was successfully treated under intensive support care and discharged from the hospital after 3 months and followed., Conclusion: HCoV-229E might an essential causative agent of pulmonary inflammation and extensive lung damage. Supportive treatment was essential to HCoVs infection on account of a long duration of immunological recovery in critical HCoV-229E infection.

Purpose: This study aims to determine the incidence and outcome of COVID-19 patients who required positive pressure ventilation (PPV) and subsequently developed pulmonary barotrauma (PBT). Also, to investigate the risk factors and predictors of these complications to better understand the disease pathogenesis., Patients and Methods: This retrospective analysis enrolled all adult COVID-19 patients admitted through the period from October 1, 2020, to December 31, 2020. All patients who received any form of PPV were included. Patients were then divided into two groups based on PBT development, including subcutaneous emphysema, pneumothorax, and pneumomediastinum. Medical records of all patients were reviewed. Patients' demographics, laboratory data on admission, respiratory support modes, surgical interventions, and outcomes were collected and analyzed., Results: In the specified period, 1095 patients were hospitalized due to COVID-19 illness. A total of 239 (21.8%) of all admitted patients received PPV. PBT accounted for 21.3% (51/239) of the study cohort. While both groups were equally exposed to the same modes of PPV, receiving invasive ventilation significantly correlated with decreased PBT odds (OR = 0.891; 95% CI, 0.803-0.988; p =0.029). PBT patients were significantly younger ( p <0.001). Diabetes mellitus was found to have a protective effect on developing PBT (OR = 0.867; 95% CI, 0.782-0.962), while PO 2 /FIO 2 ratio was inversely associated with higher odds of developing PBT in both univariate and multivariate analyses ( p =0.03 and p =0.019, respectively)., Conclusion: COVID-19-infected patients are at a higher risk of developing PBT. Invasive positive pressure ventilation was associated with less PBT compared to noninvasive ventilation and delaying intubation does not seem to reduce the risk of pulmonary barotrauma., Competing Interests: The authors declare that they have no conflicts of interest and no financial disclosures., (© 2021 Hamouri et al.)

This clinical review paper discusses the pathophysiology of the pulmonary and cardiovascular manifestations of a SARS-CoV-2 infection and the ensuing implications on acute cardiovascular care in patients presenting with a severe COVID-19 syndrome admitted to an intensive acute cardiac care unit. The high prevalence of old age, obesity, diabetes, hypertension, heart failure, and ischaemic heart disease in patients who develop a severe to critical COVID-19 syndrome suggests shared pathophysiological mechanisms. Pre-existing endothelial dysfunction and an impaired innate immune response promote the development by the viral infection of an acute endothelialitis in the pulmonary microcirculation complicated by abnormal vasoconstrictor responses, luminal plugging by inflammatory cells, and intravascular thrombosis. This endothelialitis extends into the systemic circulation what may lead to acute myocardial injury, myocarditis, and thromboembolic complications both in the arterial and venous circulation.

Background: Mortality rates in COVID-19 patients in need of mechanical ventilation are high, with wide variations between countries. Most studies were retrospective, and results may not be generalizable due to differences in demographics, healthcare organization and surge capacity. We present a cohort of mechanically ventilated COVID-19 patients from a resource-rich, publicly financed healthcare system., Methods: Prospective study from a tertiary hospital. Consecutive SARS-CoV-2 positive adult patients admitted to the ICU for mechanical ventilation from 10 March 2020 to 04 May 2020 were included. Triage and treatment were protocolized. High-dose dalteparin was adjusted by D-dimer. Demographics, treatments and high-resolution physiological variables were collected. Outcomes were 30-day and hospital mortality. Data are medians (quartiles)., Results: Of the 1484 persons in the hospital catchment area testing positive for SARS-CoV-2, 201 (13.5%) were hospitalized. Thirty-eight (19%) patients were mechanically ventilated, of whom five (13%) died. Of the 163 patients treated with supplemental oxygen, eight (5%) died. In ventilated patients (75% males, age 61 (53-70) years), severe, moderate and mild ARDS was present in 25%, 70% and 5%. Tidal volume ≤8 mL/kg ideal bodyweight was achieved in 34 (94%) patients. Proning and neuromuscular blockers were used in 19 (54%) and 20 (61%) patients. Duration of ventilation was 12 days (8-23). D-dimer peaked at 3.8 mg/L (2.1-5.3), and maximum dalteparin dose was 15 000 IU/24 h (10 000-15 000). Despite organizational changes, a high degree of adherence to treatment protocols was achieved., Conclusion: In a prospective cohort study of mechanically ventilated COVID-19 patients treated in a resource-rich, publicly financed healthcare system, mortality was considerably lower than previously reported in retrospective studies., (© 2020 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Introduction: In March and April 2020 of the coronavirus disease 2019 pandemic, site clinical practice guidelines were implemented for prone positioning of patients with suspected coronavirus disease 2019 in hypoxic respiratory distress who are awake, alert, and spontaneously breathing. The purpose of this pandemic disaster practice improvement project was to measure changes in pulse oximetry associated with prone positioning of patients with coronavirus disease 2019 infection in adult acute respiratory distress or adult respiratory distress syndrome, who are awake, alert, spontaneously breathing, and nonintubated., Methods: A retrospective chart review of patients who were coronavirus disease 2019 positive in the emergency department from March 30, 2020 to April 30, 2020 was conducted for patients with a room air pulse oximetry <90% and a preprone position pulse oximetry ≤94% who tolerated prone positioning for at least 30 minutes. The primary outcome was the change in pulse oximetry associated with prone positioning, measured on room air, with supplemental oxygen, and approximately 30 minutes after initiating prone positioning. Median and mean differences were compared with the Wilcoxon signed-rank test and paired t-test., Results: Of the 440 patients with coronavirus disease 2019, 31 met inclusion criteria. Median pulse oximetry increased as 83% (interquartile range, 75%-86%) on room air, 90% (interquartile range, 89%-93%) with supplemental oxygen, and 96% (interquartile range, 94%-98%) with prone positioning (z = -4.48, P < .001). A total of 45% (n = 14) were intubated during their hospital stay, and 26% (n = 8) of the included patients died., Discussion: In patients with coronavirus disease 2019 who are awake, alert, and spontaneously breathing, an initially low pulse oximetry reading improved with prone positioning. Future studies are needed to determine the association of prone positioning with subsequent endotracheal intubation and mortality., (Copyright © 2020 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.)

Invasive mechanical ventilation (IMV) is the standard treatment in critically ill COVID-19 patients with acute severe respiratory distress syndrome (ARDS). When IMV setting is extremely aggressive, especially through the application of high positive-end-expiratory respiration (PEEP) values, lung damage can occur. Until today, in COVID-19 patients, two types of ARDS were identified (L- and H-type); for the L-type, a lower PEEP strategy was supposed to be preferred, but data are still missing. The aim of this study was to evaluate if a clinical management with lower PEEP values in critically ill L-type COVID-19 patients was safe and efficient in comparison to usual standard of care. A retrospective analysis was conducted on consecutive patients with COVID-19 ARDS admitted to the ICU and treated with IMV. Patients were treated with a lower PEEP strategy adapted to BMI: PEEP 10 cmH 2 O if BMI < 30 kg m -2 , PEEP 12 cmH 2 O if BMI 30-50 kg m -2 , PEEP 15 cmH 2 O if BMI > 50 kg m -2 . Primary endpoint was the PaO 2 /FiO 2 ratio evolution during the first 3 IMV days; secondary endpoints were to analyze ICU length of stay (LOS) and IMV length. From March 2 to January 15, 2021, 79 patients underwent IMV. Average applied PEEP was 11 ± 2.9 cmH 2 O for BMI < 30 kg m -2 and 16 ± 3.18 cmH 2 O for BMI > 30 kg m -2 . During the first 24 h of IMV, patients' PaO 2 /FiO 2 ratio presented an improvement ( p <0.001; CI 99%) that continued daily up to 72 h ( p <0.001; CI 99%). Median ICU LOS was 15 days (10-28); median duration of IMV was 12 days (8-26). The ICU mortality rate was 31.6%. Lower PEEP strategy treatment in L-type COVID-19 ARDS resulted in a PaO 2 /FiO 2 ratio persistent daily improvement during the first 72 h of IMV. A lower PEEP strategy could be beneficial in the first phase of ARDS in critically ill COVID-19 patients., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s) 2021.)

Introduction: Coronavirus disease 2019 (COVID-19) is a viral respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This novel virus was discovered in Wuhan City, Hubei Province, China, in December 2019. As of September 6, 2020, confirmed cases have risen to more than 27,000,000 worldwide and more than 885,000 people have died. Currently, no cure or standard treatment for COVID-19 exists. We conducted a prospective single-arm open-label phase II clinical trial assessing the safety and efficacy of convalescent plasma in hospitalized patients with COVID-19., Methods: Convalescent plasma with sufficient total anti-SARS-CoV-2 IgG titer (1:320) obtained from recovered donors was administered to adult patients with either severe or critical COVID-19 illness. Primary outcomes were adverse events in association with plasma administration, and hospital mortality. Secondary outcomes included disease progression, recovery, length of stay, and hospital discharge., Results: Of the 38 patients included in the analysis, 24 (63%) recovered and were discharged, and 14 (37%) died. Patients who received convalescent plasma early in the disease course (severe illness group) as compared to the patients that received convalescent plasma later in the disease progression (critical illness group) had significantly lower hospital mortality 13% vs 55% (p < 0.02) and shorter mean hospital length of stay 15.4 vs 33 days (p < 0.01). One patient experienced a transient transfusion reaction. No other adverse effects of convalescent plasma infusion were observed., Conclusions: Our results suggest that convalescent plasma with adequate anti-SARS-CoV-2 antibody titer is safe and has the potential for positive impact on clinical outcomes including recovery and survival if given to patients early in the course of COVID-19 disease., Trial Registration: ClinicalTrials.gov. Identifier, NCT04343261, IND #19805.

Since the appearance of the novel coronavirus (severe acute respiratory syndrome-coronavirus-2) and related coronavirus disease 2019 (COVID-19) in China in December 2019, a very high number of small and large patient series have been published in literature from around the world. Even though the classical presentation of COVID-19 is one with respiratory symptoms with or without pneumonia that can be self-limiting or evolve into severe respiratory distress syndrome with multiple organ failure, and secondary bacterial sepsis, a large body of evidence suggests a plethora of other types of clinical presentation. In this exhaustive review, we reviewed all of the published literature on COVID-19 to identify different types of clinical presentations affecting various organ systems, to provide an in-depth analysis that may prove useful for clinicians and health-workers on the frontline, battling the severe pandemic., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interests for this article., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The incidence of acute complications and mortality associated with COVID-19 remains poorly characterized. The aims of this systematic review and meta-analysis were to summarize the evidence on clinically relevant outcomes in hospitalized patients with COVID-19., Methods: MEDLINE, EMBASE, PubMed, and medRxiv were searched up to April 20, 2020, for studies including hospitalized symptomatic adult patients with laboratory-confirmed COVID-19. The primary outcomes were all-cause mortality and acute respiratory distress syndrome (ARDS). The secondary outcomes included acute cardiac or kidney injury, shock, coagulopathy, and venous thromboembolism. The main analysis was based on data from peer-reviewed studies. Summary estimates and the corresponding 95% prediction intervals (PIs) were obtained through meta-analyses., Results: A total of 44 peer-reviewed studies with 14,866 COVID-19 patients were included. In general, risk of bias was high. All-cause mortality was 10% overall (95% PI, 2 to 39%; 1687/14203 patients; 43 studies), 34% in patients admitted to intensive care units (95% PI, 8 to 76%; 659/2368 patients; 10 studies), 83% in patients requiring invasive ventilation (95% PI, 1 to 100%; 180/220 patients; 6 studies), and 75% in patients who developed ARDS (95% PI, 35 to 94%; 339/455 patients; 11 studies). On average, ARDS occurred in 14% of patients (95% PI, 2 to 59%; 999/6322 patients; 23 studies), acute cardiac injury in 15% (95% PI, 5 to 38%; 452/2389 patients; 10 studies), venous thromboembolism in 15% (95% PI, 0 to 100%; patients; 3 studies), acute kidney injury in 6% (95% PI, 1 to 41%; 318/4682 patients; 15 studies), coagulopathy in 6% (95% PI, 1 to 39%; 223/3370 patients; 9 studies), and shock in 3% (95% PI, 0 to 61%; 203/4309 patients; 13 studies)., Conclusions: Mortality was very high in critically ill patients based on very low-quality evidence due to striking heterogeneity and risk of bias. The incidence of clinically relevant outcomes was substantial, although reported by only one third of the studies suggesting considerable underreporting., Trial Registration: PROSPERO registration ID for this study is CRD42020177243 ( https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=177243 ).

COVID-19, a new viral disease affecting primarily the respiratory system and the lung, has caused a pandemic posing serious challenges to healthcare systems around the world. In about 20% of patients, severe symptoms occur after a mean incubation period of 5 - 6 days; 5% of patients need intensive care therapy. Mortality is about 1 - 2%. Protecting healthcare workers is of paramount importance in order to prevent hospital-acquired infections. Therefore, during all procedures associated with aerosol production, personal protective equipment consisting of a FFP2/FFP3 (N95) respiratory mask, gloves, safety glasses and a waterproof overall should be used. Therapy is based on established recommendations issued for patients with acute lung injury (ARDS). Lung protective ventilation, prone position, restrictive fluid management and adequate management of organ failure are the mainstays of therapy. In case of fulminant lung failure, veno-venous extracorporeal membrane oxygenation may be used as a rescue in experienced centres. New, experimental therapies are evolving with ever increasing frequency; currently, however, no evidence-based recommendation is possible. If off-label and compassionate use of these drugs is considered, an individual benefit-risk assessment is necessary, since serious side effects have been reported., Competing Interests: Conflict of Interest/Interessenkonflikt Prof. Bein received honoraria for consulting and giving lectures from Pulsion/Maquet, Edwards Life Sciences and Cytosorbents. The other authors state that they have no conflict of interest./ Prof. Bein hat Honorare für Vorträge und Beratertätigkeit von Pulsion/Maquet, Edwards Life Sciences und Cytosorbents erhalten. Die anderen Autorinnen/Autoren geben an, dass keine Interessenkonflikte bestehen.

Background: No previous studies exist examining 2 inhaled epoprostenol formulations in an acute respiratory distress syndrome (ARDS) patient population. Objective: The study aim was to evaluate a formulary conversion from inhaled Flolan to Veletri to determine the impact on effectiveness, safety, and cost in patients with ARDS. Methods: This was a single-center, retrospective, matched cohort observational study at a tertiary care academic medical center. Patients included were mechanically ventilated, adult patients with ARDS receiving inhaled Flolan or Veletri for ≥1 hour in the intensive care unit. Results: A total of 132 patients were included in the matched cohort. There was no difference detected in change in partial pressure of arterial O 2 /fraction of inspired O 2 (PaO 2 /FiO 2 ) ratio after 1 hour of therapy between the inhaled Flolan and Veletri groups (27.2 ± 46.2 vs 30 ± 68 mm Hg, P = 0.78). Significant differences in secondary outcomes included incidence of hypotension (83% vs 95.5%, P = 0.04) and thrombocytopenia (9.1% vs 29.5%, P < 0.01) in the inhaled Flolan and Veletri groups, respectively, with no difference in cost per duration of therapy ( P = 0.29). Conclusions and Relevance: There was no difference in the change in PaO 2 /FiO 2 ratio after 1 hour of therapy between inhaled Flolan and Veletri in an ARDS patient population. The formulary conversion from inhaled Flolan to Veletri was likely justified.

We report our initial experience with the management of a mixed group of patients with COVID-19 infection, admitted and treated in a designated COVID-19 centre in the Athens Metropolitan area over a 4-week period. The SARS-CoV-2 pandemic presented a huge challenge to the Greek National Healthcare System and healthcare workers. Their response so far has been miraculously effective. Since there are essentially no therapeutic guidelines yet for this disease, we relied mainly on our medical intuition, our empathy for our patients and team work to do the best possible for 49 people with this infection. We present the therapeutic algorithm we gradually developed (on the job) and applied in our patients, based on continuous creative brainstorming and monitoring of the literature., (© Springer Nature Switzerland AG 2020.)

To better describe the outcomes of acute respiratory distress syndrome in mechanically ventilated patients with cirrhosis., Design: Single-center, retrospective study of mechanically ventilated patients with cirrhosis between 2008 and 2015., Setting: ICU at a large academic medical and transplant center., Patients: One hundred eighty-one mechanically ventilated patients with cirrhosis., Interventions: Demographic and clinical data were reviewed, and acute respiratory distress syndrome was identified per Berlin criteria. We compared demographic and clinical characteristics on ICU admission in patients with and without acute respiratory distress syndrome. The primary endpoint was hospital mortality (including discharge to hospice). Mortality risk was stratified by Chronic Liver Failure-Sequential Organ Failure Assessment and Model for End-Stage Liver Disease., Measurements and Main Results: The mean age in 181 eligible patients was 53 ± 11 years; 67% were male; and 91% were Caucasian. In all, n = 35 (19%) of mechanically ventilated patients had acute respiratory distress syndrome. They were more frequently female (46% vs 30%; p = 0.08), with suspected infection (86% vs 53%; p < 0.001), and had higher mean Model for End-Stage Liver Disease (32 vs 24; p < 0.001) and Chronic Liver Failure-Sequential Organ Failure Assessment (15 vs 11; p < 0.001) than patients without acute respiratory distress syndrome. Hospital mortality was higher in patients with (40%) versus without (22%) acute respiratory distress syndrome ( p = 0.03). In the risk-adjusted analysis (for Model for End-Stage Liver Disease, Chronic Liver Failure-Sequential Organ Failure Assessment and age), acute respiratory distress syndrome was not independently associated with hospital mortality (odds ratio, 0.80; CI, 0.3-2.5; p = 0.7)., Conclusions: Acute respiratory distress syndrome is common in mechanically ventilated patients with cirrhosis but is not independently associated with increased mortality., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background/aim: Blunt chest trauma is one of the major injuries in multiply injured patients and is associated with an increased risk of acute respiratory distress syndrome (ARDS) and ventilator-associated pneumonia (VAP). Accidental hypothermia is a common accompaniment of multiply injured patients. The objective of this study was to analyze the influence of accidental hypothermia on pulmonary complications in multiply injured patients with blunt chest trauma., Patients and Methods: Multiply injured patients [injury severity score (ISS) ≥16] with severe blunt chest trauma [abbreviated injury scale of the chest (AISchest) ≥3] were analyzed. Hypothermia was defined as body core temperature <35°C. The primary endpoint was the development of ARDS and VAP. Propensity score matching was performed., Results: Data were analyzed for 238 patients, with a median ISS of 26 (interquartile range=12). A total of 67 patients (28%) were hypothermic on admission. Hypothermic patients were injured more severely (median ISS 34 vs. 24, p<0.001) and had a higher transfusion requirement (p<0.001). Their mortality rate was consequently increased (10% vs. 1%, p=0.002); After propensity score matching, the mortality rate was still higher (10% vs. 2%, p=0.046). However, hypothermia was not an independent predictor of mortality. Hypothermic patients had to be ventilated longer (p=0.02). However, there were no differences in occurrence of ARDS and VAP. Hypothermia was not identified as an independent predictor of ARDS and VAP., Conclusion: Among multiply injured patients with severe blunt chest trauma, accidental hypothermia is not an independent predictor of ARDS and VAP and is more likely to be an accompaniment of injury severity and hemorrhage., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Legionella community-acquired pneumonia necessitating veno-venous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome has been reported in adults. However, few options remain in cases of refractory hypoxemia on veno-venous extracorporeal membrane oxygenation. Herein, we describe adjunctive extended therapeutic hypothermia for refractory hypoxemia despite veno-venous extracorporeal membrane oxygenation for successful management of severe acute respiratory distress syndrome secondary to Legionella.

Objective: Extracorporeal membrane oxygenation (ECMO) is used to provide support for patients with cardiopulmonary failure. Best available medical management often fails in these patients and referring hospitals have no further recourse for escalating care apart from transfer to a tertiary facility. In severely unstable patients, the only option might be to use ECMO to facilitate safe transport. This study aimed to examine the characteristics and outcomes of patients transported while receiving ECMO., Methods: Statistical analysis was performed on data gathered retrospectively from the electronic medical records of adult patients transported while receiving ECMO to Columbia University Medical Center between January 1, 2008, and December 31, 2017., Results: Two hundred sixty five adult patients were safely transported while receiving ECMO with no transport-related complications that adversely affected outcomes. Transport distance ranged from 0.2 to 7084 miles with a median distance of 16.9 miles. One hundred eighty-three (69%) received on veno-venous, 72 (27%) veno-arterial, and 10 (3.8%) veno-venous arterial or veno-arterial venous configurations. Two hundred ten (79%) cannulations were performed at our institution at the referring hospital. Sixty-four percent of patients transported while receiving ECMO survived to hospital discharge., Conclusions: Interfacility transport during ECMO was shown to be safe and effective with minimal complications and favorable outcomes when performed at an experienced referral center using stringently applied protocols., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)