The potential role of extracorporeal cytokine removal with CytoSorb® as an adjuvant therapy in Acute Respiratory Distress Syndrome.

Management of acute respiratory distress syndrome (ARDS) represents one of the greatest challenges in intensive care and despite all efforts mortality remains high. One common phenotype of ARDS is that of a secondary injury to a dysregulated inflammatory host response resulting in increased capillary congestion, interstitial lung edema, atelectasis, pulmonary embolism, muscle wasting, recurring infectious episodes, and multiple organ failure. In cases of hyperinflammation, immunomodulation by extracorporeal cytokine removal such as the CytoSorb hemoadsorption cartridge could conceptually enhance lung recovery during the early course of the disease. The aim of this narrative review is to summarize the currently available data in this field and to provide an overview of pathophysiology and rationale for the use of CytoSorb hemoadsorption in patients with hyperinflammatory ARDS.

Mortality and Pulmonary Embolism in Acute Respiratory Distress Syndrome From COVID-19 vs. Non-COVID-19.

Purpose: There may be a difference in respiratory mechanics, inflammatory markers, and pulmonary emboli in COVID-19 associated ARDS vs. ARDS from other etiologies. Our purpose was to determine differences in respiratory mechanics, inflammatory markers, and incidence of pulmonary embolism in patients with and without COVID-19 associated ARDS admitted in the same period and treated with a similar ventilation strategy. Methods: A cohort study of COVID-19 associated ARDS and non COVID-19 patients in a Saudi Arabian center between June 1 and 15, 2020. We measured respiratory mechanics (ventilatory ratio (VR), recruitability index (RI), markers of inflammation, and computed tomography pulmonary angiograms. Results: Forty-two patients with COVID-19 and 43 non-COVID patients with ARDS comprised the cohort. The incidence of "recruitable" patients using the recruitment/inflation ratio was slightly lower in COVID-19 patients (62 vs. 86%; p = 0.01). Fifteen COVID-19 ARDS patients (35.7%) developed a pulmonary embolism as compared to 4 (9.3%) in other ARDS patients (p = 0.003). In COVID-19 patients, a D-Dimer ≥ 5.0 mcg/ml had a 73% (95% CI 45-92%) sensitivity and 89% (95% CI 71-98%) specificity for predicting pulmonary embolism. Crude 60-day mortality was higher in COVID-19 patients (35 vs. 15%; p = 0.039) but three multivariate analysis showed that independent predictors of 60-day mortality included the ventilatory ratio (OR 3.67, 95% CI 1.61-8.35), PaO2/FIO2 ratio (OR 0.93; 95% CI 0.87-0.99), IL-6 (OR 1.02, 95% CI 1.00-1.03), and D-dimer (OR 7.26, 95% CI 1.11-47.30) but not COVID-19 infection. Conclusion: COVID-19 patients were slightly less recruitable and had a higher incidence of pulmonary embolism than those with ARDS from other etiologies. A high D-dimer was predictive of pulmonary embolism in COVID-19 patients. COVID-19 infection was not an independent predictor of 60-day mortality in the presence of ARDS.

Optic Nerve Sheath Diameter Ultrasound for Raised Intracranial Pressure: A Literature Review and Meta-analysis of its Diagnostic Accuracy.

Optic nerve sheath diameter (ONSD) ultrasound is becoming increasingly more popular for estimating raised intracranial pressure (ICP). We performed a systematic review and analysis of the diagnostic accuracy of ONSD when compared to the standard invasive ICP measurement. METHOD: We performed a systematic search of PUBMED and EMBASE for studies including adult patients with suspected elevated ICP and comparing sonographic ONSD measurement to a standard invasive method. Quality of studies was assessed using the QUADAS-2 tool by two independent authors. We used a bivariate model of random effects to summarize pooled sensitivity, specificity, and diagnostic odds ratio (DOR). Heterogeneity was investigated by meta-regression and sub-group analyses. RESULTS: We included 18 prospective studies (16 studies including 619 patients for primary outcome). Only one study was of low quality, and there was no apparent publication bias. Pooled sensitivity was 0.9 [95% confidence intervals (CI): 0.85-0.94], specificity was 0.85 (95% CI: 0.8-0.89), and DOR was 46.7 (95% CI: 26.2-83.2) with partial evidence of heterogeneity. The Area-Under-the-Curve of the summary Receiver-Operator-Curve was 0.93 (95% CI: 0.91-0.95, P < .05). No covariates were significant in the meta-regression. Subgroup analysis of severe traumatic brain injury and parenchymal ICP found no heterogeneity. ICP and ONSD had a correlation coefficient of 0.7 (95% CI: 0.63-0.76, P < .05). CONCLUSION: ONSD is a useful adjunct in ICP evaluation but is currently not a replacement for invasive methods where they are feasible.

Effect of Tocilizumab on "Ventilator Free Days" Composite Outcome in SARS-CoV-2 Patients: A Retrospective Competing Risk Analysis.

Background: SARS-CoV-2 infection demonstrates a wide range of severity. More severe cases demonstrate a cytokine storm with elevated serum interleukin-6, hence IL-6 receptor antibody tocilizumab was tried for the management of severe cases. Aims: Effect of tocilizumab on ventilator-free days among critically ill SARS-CoV-2 patients. Method: Retrospective propensity score matching study, comparing mechanically ventilated patients who received tocilizumab to a control group. Results: 29 patients in the intervention group were compared to 29 controls. Matched groups were similar. Ventilator-free days were more numerous in the intervention group (SHR 2.7, 95% CI: 1.2 - 6.3; p = 0.02), ICU mortality rate was not different (37.9% versus 62%, p = 0.1), actual ventilator-free periods were significantly longer in tocilizumab group (mean difference 4.7 days; p = 0.02). Sensitivity analysis showed a significantly lower hazard ratio of death in tocilizumab group (HR 0.49, 95% CI: 0.25 - 0.97; p = 0.04). There was no difference in positive cultures among groups (55.2% in tocilizumab group versus 34.5% in the control; p = 0.1). Conclusion: Tocilizumab may improve the composite outcome of ventilator-free days at day 28 among mechanically ventilated SARS-CoV-2 patients; it is associated with significantly longer actual ventilator-free periods, and insignificantly lower mortality and higher superinfection.

Erratum: Profili et al. Overview of the User Experience for Snorkeling Mask Designs during the COVID-19 Pandemic. Healthcare 2021, 9, 204.

The authors would like to make the following corrections to the published paper [...].

Therapeutic plasma exchange in patients with life-threatening COVID-19: a randomised controlled clinical trial.

Assessment of efficacy of therapeutic plasma exchange (TPE) following life-threatening COVID-19. This was an open-label, randomised clinical trial of ICU patients with life-threatening COVID-19 (positive RT-qPCR plus ARDS, sepsis, organ failure, hyperinflammation). Study was terminated after 87/120 patients enrolled. Standard treatment plus TPE (n = 43) versus standard treatment (n = 44), and stratified by PaO2/FiO2 ratio (>150 vs. ≤150), were compared. Primary outcomes were 35-day mortality and TPE safety. Secondary outcomes were association between TPE and mortality, improvement in SOFA score, change in inflammatory biomarkers, days on mechanical ventilation (MV), and ICU length of stay (LOS). Eighty-seven patients [median age 49 (IQR 34-63) years; 82.8% male] were randomised (44 standard care; 43 standard care plus TPE). Days on MV (P = 0.007) and ICU LOS (P = 0.02) were lower in the TPE group. 35-Day mortality was non-significantly lower in the TPE group (20.9% vs. 34.1%; Kaplan-Meier, P = 0.582). TPE was associated with increased lymphocytes and ADAMTS-13 activity and decreased serum lactate, lactate dehydrogenase, ferritin, d-dimers and interleukin-6. Multivariable regression analysis provided several predictors of 35-day mortality: PaO2/FiO2 ratio (HR, 0.98, 95% CI 0.96-1.00; P = 0.02]; ADAMTS-13 activity (HR, 0.89, 95% CI 0.82-0.98; P = 0.01); pulmonary embolism (HR, 3.57, 95% CI 1.43-8.92; P = 0.007). Post-hoc analysis revealed a significant reduction in SOFA score for TPE patients (P < 0.05). In critically-ill COVID-19 patients, addition of TPE to standard ICU therapy was associated with faster clinical recovery and no increased 35-day mortality.

Delayed intensive care unit admission from the emergency department: impact on patient outcomes. A retrospective study. / Retardo na transferência do pronto-socorro para a unidade de terapia intensiva: impacto nos desfechos do paciente. Um estudo retrospectivo.

OBJECTIVE: To study the impact of delayed admission by more than 4 hours on the outcomes of critically ill patients. METHODS: This was a retrospective observational study in which adult patients admitted directly from the emergency department to the intensive care unit were divided into two groups: Timely Admission if they were admitted within 4 hours and Delayed Admission if admission was delayed for more than 4 hours. Intensive care unit length of stay and hospital/intensive care unit mortality were compared between the groups. Propensity score matching was performed to correct for imbalances. Logistic regression analysis was used to explore delayed admission as an independent risk factor for intensive care unit mortality. RESULTS: During the study period, 1,887 patients were admitted directly from the emergency department to the intensive care unit, with 42% being delayed admissions. Delayed patients had significantly longer intensive care unit lengths of stay and higher intensive care unit and hospital mortality. These results were persistent after propensity score matching of the groups. Delayed admission was an independent risk factor for intensive care unit mortality (OR = 2.6; 95%CI 1.9 - 3.5; p < 0.001). The association of delay and intensive care unit mortality emerged after a delay of 2 hours and was highest after a delay of 4 hours. CONCLUSION: Delayed admission to the intensive care unit from the emergency department is an independent risk factor for intensive care unit mortality, with the strongest association being after a delay of 4 hours.

OBJETIVO: Estudar o impacto do retardo na admissão à unidade de terapia intensiva em mais do que 4 horas nos desfechos de pacientes críticos. MÉTODOS: Este foi um estudo observacional retrospectivo, no qual pacientes adultos admitidos diretamente do pronto-socorro para a unidade de terapia intensiva foram divididos em dois grupos: Tempo Adequado, se admitidos dentro de 4 horas, e Admissão Retardada, nos casos em que a admissão demorou mais do que 4 horas para ocorrer. Compararam-se, entre os grupos, o tempo de permanência na unidade de terapia intensiva e a taxa de mortalidade na unidade de terapia intensiva e no hospital. Foi realizado pareamento por escore de propensão para correção de desequilíbrios. Utilizou-se uma análise de regressão logística para explorar retardo da admissão como fator independente de risco para mortalidade na unidade de terapia intensiva. RESULTADOS: Durante o período do estudo, 1.887 pacientes foram admitidos diretamente do pronto-socorro para a unidade de terapia intensiva, sendo que 42% dessas admissões foram retardadas. Os pacientes com retardo tiveram permanências na unidade de terapia intensiva significantemente mais longas e maior mortalidade na unidade de terapia intensiva e no hospital. Esses resultados persistiram após pareamento dos grupos por escore de propensão. O retardo da admissão foi fator independente de risco para mortalidade na unidade de terapia intensiva (RC = 2,6; IC95% 1,9 - 3,5; p < 0,001). A associação de retardo e mortalidade na unidade de terapia intensiva surgiu após período de retardo de 2 horas e foi mais alta após período de retardo de 4 horas. CONCLUSÃO: O retardo da admissão do pronto-socorro para a unidade de terapia intensiva é fator de risco independente para mortalidade na unidade de terapia intensiva, sendo a associação mais forte após retardo de 4 horas.

Overview of the User Experience for Snorkeling Mask Designs during the COVID-19 Pandemic.

During the first wave of the COVID-19 pandemic, industries and academic institutes have collaborated to resolve the worldwide medical supply shortage issues. Innovative designs of 3D-printed items were proposed and developed by the maker community as a temporary solution to address the lack of personal protective equipment. An overview of global ongoing and past initiatives during the COVID-19 pandemic along with their challenges on retrofitting full-face snorkeling masks for healthcare applications such as splash-proof face shields, respirator masks and non-invasive ventilation systems are reported in this contribution. This study reviews these global initiatives and challenges. From our analysis, the present situation highlights the need to build solid networks between healthcare institutes and the different rapid prototyping initiatives. A clear feedback system needs to be implemented to facilitate effective collaboration between engineering (maker) and healthcare teams, to optimize the available human resources, and to achieve adequate product developments responding to the needs of healthcare workers.

COVID-19 with spontaneous pneumothorax, pneumomediastinum, and subcutaneous emphysema in the intensive care unit: Two case reports.

Real-Time-reverse-transcription-Polymerase-Chain-Reaction from nasopharyngeal swabs and chest computed tomography (CT) depicting typically bilateral ground-glass opacities with a peripheral and/or posterior distribution are mandatory in the diagnosis of COVID-19. COVID-19 pneumonia may present though with atypical features such as pleural and pericardial effusions, lymphadenopathy, cavitations, and CT halo sign. In these two case-reports, COVID-19 presented as pneumothorax, pneumomediastinum and subcutaneous emphysema in critically ill patients. These disorders may require treatment or can be even self-limiting. Clinicians should be aware of their potential effects on the cardiorespiratory status of critically ill COVID-19 patients. Finally, pneumothorax can be promptly diagnosed by means of lung ultrasound. Although operator dependent, lung ultrasound is a useful bedside diagnostic tool that could alleviate the risk of cross-infection related to COVID-19 patient transport.

A Retrospective Analysis of Thromboembolic Phenomena in Mechanically Ventilated Patients with COVID-19.

BACKGROUND: Recent studies have shown an increased prevalence of thromboembolic disease in critically ill patients with the novel SARS-CoV-2 disease (COVID-19). However, the use of enhanced anticoagulation therapy in these patients remains controversial. OBJECTIVES: To determine the incidence of thromboembolic phenomena (TEP) and hemorrhagic events (HEs) in intensive care unit (ICU) COVID-19 patients. METHODS: One hundred and sixty ICU patients with COVID-19 were enrolled. Clinical examination results, laboratory data, and imaging studies (computed tomography/Doppler ultrasound scans) for these patients were retrospectively collected and analyzed. Outcome measures including days on mechanical ventilation, ICU length of stay, and day-28 mortality were recorded. RESULTS: Sixty patients (37.5%) developed TEP including thirty patients with deep vein thrombosis, 55 patients with pulmonary embolism, and 7 patients with arterial thromboembolism. Cardiac arrhythmias, lymphocytopenia, and increased D-dimers were more frequently observed in the TEP group compared to the non-TEP group of patients (all p < 0.05). The sensitivity, specificity, and positive and negative predictive values of a cutoff D-dimer level of 3.0 µg/mL for predicting PE were 74.5%, 95.1%, 86.8%, and 91.9%, respectively. Thirteen patients experienced HEs, which were more frequently observed in the TEP group (p < 0.05). Twenty-eight-day mortality was higher in the TEP group (60%) compared to the non-TEP group (30%) of patients (p=0.02). CONCLUSIONS: The rates of TEP and HEs in mechanically ventilated critically ill COVID-19 patients were 37. 5% and 8.1%. Twenty-eight-day mortality was higher in the TEP group (60%) compared to the non-TEP group (30%) of patients.

Radiological, epidemiological and clinical patterns of pulmonary viral infections.

Respiratory viruses are the most common causes of acute respiratory infections. However, identification of the underlying viral pathogen may not always be easy. Clinical presentations of respiratory viral infections usually overlap and may mimic those of diseases caused by bacteria. However, certain imaging morphologic patterns may suggest a particular viral pathogen as the cause of the infection. Although definitive diagnosis cannot be made on the basis of clinical or imaging features alone, the use of a combination of clinical and radiographic findings can substantially improve the accuracy of diagnosis. The purpose of this review is to present the clinical, epidemiological and radiological patterns of lower respiratory tract viral pathogens providing a comprehensive approach for their diagnosis and identification in hospitals and community outbreaks.

The COVID-19 Worsening Score (COWS)-a predictive bedside tool for critical illness.

OBJECTIVES: To evaluate the accuracy of a new COVID-19 prognostic score based on lung ultrasound (LUS) and previously validated variables in predicting critical illness. METHODS: We conducted a single-center retrospective cohort development and internal validation study of the COVID-19 Worsening Score (COWS), based on a combination of the previously validated COVID-GRAM score (GRAM) variables and LUS. Adult COVID-19 patients admitted to the emergency department (ED) were enrolled. Ten variables previously identified by GRAM, days from symptom onset, LUS findings, and peripheral oxygen saturation/fraction of inspired oxygen (P/F) ratio were analyzed. LUS score as a single predictor was assessed. We evaluated GRAM model's performance, the impact of adding LUS, and then developed a new model based on the most predictive variables. RESULTS: Among 274 COVID-19 patients enrolled, 174 developed critical illness. The GRAM score identified 51 patients at high risk of developing critical illness and 132 at low risk. LUS score over 15 (range 0 to 36) was associated with a higher risk ratio of critical illness (RR, 2.05; 95% confidence interval [CI], 1.52-2.77; area under the curve [AUC], 0.63; 95% CI 0.676-0.634). The newly developed COVID-19 Worsening Score relies on five variables to classify high- and low-risk patients with an overall accuracy of 80% and negative predictive value of 93% (95% CI, 87%-98%). Patients scoring more than 0.183 on COWS showed a RR of developing critical illness of 8.07 (95% CI, 4.97-11.1). CONCLUSIONS: COWS accurately identify patients who are unlikely to need intensive care unit (ICU) admission, preserving resources for the remaining high-risk patients.

Retardo na transferência do pronto-socorro para a unidade de terapia intensiva: impacto nos desfechos do paciente. Um estudo retrospectivo / Delayed intensive care unit admission from the emergency department: impact on patient outcomes. A retrospective study

RESUMO Objetivo: Estudar o impacto do retardo na admissão à unidade de terapia intensiva em mais do que 4 horas nos desfechos de pacientes críticos. Métodos: Este foi um estudo observacional retrospectivo, no qual pacientes adultos admitidos diretamente do pronto-socorro para a unidade de terapia intensiva foram divididos em dois grupos: Tempo Adequado, se admitidos dentro de 4 horas, e Admissão Retardada, nos casos em que a admissão demorou mais do que 4 horas para ocorrer. Compararam-se, entre os grupos, o tempo de permanência na unidade de terapia intensiva e a taxa de mortalidade na unidade de terapia intensiva e no hospital. Foi realizado pareamento por escore de propensão para correção de desequilíbrios. Utilizou-se uma análise de regressão logística para explorar retardo da admissão como fator independente de risco para mortalidade na unidade de terapia intensiva. Resultados: Durante o período do estudo, 1.887 pacientes foram admitidos diretamente do pronto-socorro para a unidade de terapia intensiva, sendo que 42% dessas admissões foram retardadas. Os pacientes com retardo tiveram permanências na unidade de terapia intensiva significantemente mais longas e maior mortalidade na unidade de terapia intensiva e no hospital. Esses resultados persistiram após pareamento dos grupos por escore de propensão. O retardo da admissão foi fator independente de risco para mortalidade na unidade de terapia intensiva (RC = 2,6; IC95% 1,9 - 3,5; p < 0,001). A associação de retardo e mortalidade na unidade de terapia intensiva surgiu após período de retardo de 2 horas e foi mais alta após período de retardo de 4 horas. Conclusão: O retardo da admissão do pronto-socorro para a unidade de terapia intensiva é fator de risco independente para mortalidade na unidade de terapia intensiva, sendo a associação mais forte após retardo de 4 horas.

Abstract Objective: To study the impact of delayed admission by more than 4 hours on the outcomes of critically ill patients. Methods: This was a retrospective observational study in which adult patients admitted directly from the emergency department to the intensive care unit were divided into two groups: Timely Admission if they were admitted within 4 hours and Delayed Admission if admission was delayed for more than 4 hours. Intensive care unit length of stay and hospital/intensive care unit mortality were compared between the groups. Propensity score matching was performed to correct for imbalances. Logistic regression analysis was used to explore delayed admission as an independent risk factor for intensive care unit mortality. Results: During the study period, 1,887 patients were admitted directly from the emergency department to the intensive care unit, with 42% being delayed admissions. Delayed patients had significantly longer intensive care unit lengths of stay and higher intensive care unit and hospital mortality. These results were persistent after propensity score matching of the groups. Delayed admission was an independent risk factor for intensive care unit mortality (OR = 2.6; 95%CI 1.9 - 3.5; p < 0.001). The association of delay and intensive care unit mortality emerged after a delay of 2 hours and was highest after a delay of 4 hours. Conclusion: Delayed admission to the intensive care unit from the emergency department is an independent risk factor for intensive care unit mortality, with the strongest association being after a delay of 4 hours.

Plasma exchange in the treatment of complex COVID-19-related critical illness: controversies and perspectives.

COVID-19 (coronavirus disease 2019), caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), emerged in Wuhan, China, and has spread worldwide, resulting in over 73 million cases and more than 1 600 000 deaths as of December 2020. Although the disease is asymptomatic in most cases, some patients develop life-threatening disease characterised by acute respiratory distress syndrome, sepsis, multisystem organ failure (MSOF), extrapulmonary manifestations, thromboembolic disease and associated cytokine release syndrome. The rationale for applying therapeutic plasma exchange (TPE) early in the course of fulminant COVID-19 is the suppression of thromboinflammation and amelioration of microangiopathy, thus preventing the ensuing MSOF. In the course of complicated critical illness due to COVID-19, immune dysregulation may be as important as viral replication itself. Moreover, the natural course of SARS-CoV-2 infection remains obscure, as re-infections and/or recurrently positive real-time PCR results have been reported. Although concerns still exist regarding its potential immunosuppressive effects and safety, TPE shows promise in the management of life-threatening COVID-19 as documented by various pilot studies, which remain to be confirmed by future randomised controlled trials. However, current data suggest that TPE could be an adjunctive rescue therapy in complex COVID-19 critical illness.

Residual Lung Injury in Patients Recovering From COVID-19 Critical Illness: A Prospective Longitudinal Point-of-Care Lung Ultrasound Study.

Scarce data exist regarding the natural history of lung lesions detected on ultrasound in those who survive severe COVID-19 pneumonia. OBJECTIVE: We performed a prospective analysis of point-of-care ultrasound (POCUS) findings in critically ill COVID-19 patients during and after hospitalization. METHODS: We enrolled 171 COVID-19 intensive care unit patients. POCUS of the lungs was performed with phased array (2-4 MHz), convex (2-6 MHz) and linear (10-15 MHz) transducers, scanning 12 lung areas. Chest computed tomography angiography was performed to exclude suspected pulmonary embolism. Survivors were clinically and sonographically evaluated during a 4 month period for evidence of residual lung injury. Chest computed tomography angiography and echocardiography were used to exclude pulmonary hypertension (PH) and chest high-resolution-computed-tomography to exclude interstitial lung disease (ILD) in symptomatic survivors. RESULTS: Cox regression analysis showed that lymphocytopenia (hazard ratio [HR]: 0.88, 95% confidence intervals [CI]: 0.68-0.96, p = .048), increased lactate (HR: 1.17, 95% CI: 0.94-1.46, p = 0.049), and D-dimers (HR: 1.21, 95% CI: 1.03-1.44, p = .03) were mortality predictors. Non-survivors had increased incidence of pulmonary abnormalities (B-lines, pleural line irregularities, and consolidations) compared to survivors (p < .05). During follow-up, POCUS with clinical and laboratory parameters integrated in the semi-quantitative Riyadh-Residual-Lung-Injury scale had sensitivity of 0.82 (95% CI: 0.76-0.89) and specificity of 0.91 (95% CI: 0.94-0.95) in predicting ILD. The prevalence of PH and ILD (non-specific-interstitial-pneumonia) was 7% and 11.8%, respectively. CONCLUSION: POCUS showed ability to monitor the evolution of severe COVID-19 pneumonia after hospital discharge, supporting its integration in clinical predictive models of residual lung injury.