Combining lung ultrasound and Wells score for diagnosing pulmonary embolism in critically ill COVID-19 patients.

Subpleural consolidations have been found in lung ultrasound in patients with COVID-19, possibly deriving from pulmonary embolism (PE). The diagnostic utility of impact of lung ultrasound in critical-ill patients with COVID-19 for PE diagnostics however is unclear. We retrospectively evaluated all SARS-CoV2-associated ARDS patients admitted to our ICU between March 8th and May 31th 2020. They were enrolled in this study, when a lung ultrasound and a computed tomography pulmonary angiography (CTPA) were documented. In addition, wells score was calculated to estimate the probability of PE. The CTPA was used as the gold standard for the detection of PE. Twenty out of 25 patients met the inclusion criteria. In 12/20 patients (60%) (sub-) segmental PE were detected by CT-angiography. Lung ultrasound found subpleural consolidations in 90% of patients. PE-typical large supleural consolidations with a size ≥ 1 cm were detectable in 65% of patients and were significant more frequent in patients with PE compared to those without (p = 0.035). Large consolidations predicted PE with a sensitivity of 77% and a specificity of 71%. The Wells score was significantly higher in patients with PE compared to those without (2.7 ± 0.8 and 1.7 ± 0.5, respectively, p = 0.042) and predicted PE with an AUC of 0.81. When combining the two modalities, comparing patients with considered/probable PE using LUS plus a Wells score ≥ 2 to patients with possible/unlikely PE in LUS plus a Wells score < 2, PE could be predicted with a sensitivity of 100% and a specificity of 80%. Large consolidations detected in lung ultrasound were found frequently in COVID-19 ARDS patients with pulmonary embolism. In combination with a Wells score > 2, this might indicate a high-risk for PE in COVID-19.

[How can an emergency department be strengthened against a pandemic?] / Was macht eine Notaufnahme schlagkräftig gegenüber einer Pandemie?

The emergency department (ED) is one of the crucial parts of the hospital infrastructure during all phases of the pandemic. The ED plays an important part in detecting an increasing number of new contagious diseases, which could potentially lead to an epidemic or pandemic.During a pandemic, the ED's main task is to detect infected individuals. These patients then need to be isolated and an adequate treatment is required. The ED must be prepared in order to perform well in such a situation. One major part for readiness is communication in an open manner to all partners within the department, as well as with emergency medical services and other departments of the hospital.The ED must be restructured to withstand the rising number of infected patients. These patients must be separated from other critically ill patients. Strategies for a diagnostic workup depending on the kind of infection have to be put in place. Pathways for the outpatient and inpatient management must be defined to avoid overcrowding in the ED. Depending on the number of patients, escalation and de-escalation strategies have to be set up within the hospital.Over the whole course of the pandemic, all staff members are the key resources for the ED and the entire hospital. The ED can only cope with a pandemic situation if staff are working together as a whole. This implies several important steps to get the staff prepared: Recurring, open conversations about fears, problems, and successes are critical for staff morale. Training must be continually provided, and protection strategies implemented. In the chronic phase of the pandemic the focus should shift more towards strategies on how to create possibilities for recuperation, domestic support measures, and mental health care for staff.

The Tissue Renin-Angiotensin System and Its Role in the Pathogenesis of Major Human Diseases: Quo Vadis?

Evidence has arisen in recent years suggesting that a tissue renin-angiotensin system (tRAS) is involved in the progression of various human diseases. This system contains two regulatory pathways: a pathological pro-inflammatory pathway containing the Angiotensin Converting Enzyme (ACE)/Angiotensin II (AngII)/Angiotensin II receptor type 1 (AGTR1) axis and a protective anti-inflammatory pathway involving the Angiotensin II receptor type 2 (AGTR2)/ACE2/Ang1-7/MasReceptor axis. Numerous studies reported the positive effects of pathologic tRAS pathway inhibition and protective tRAS pathway stimulation on the treatment of cardiovascular, inflammatory, and autoimmune disease and the progression of neuropathic pain. Cell senescence and aging are known to be related to RAS pathways. Further, this system directly interacts with SARS-CoV 2 and seems to be an important target of interest in the COVID-19 pandemic. This review focuses on the involvement of tRAS in the progression of the mentioned diseases from an interdisciplinary clinical perspective and highlights therapeutic strategies that might be of major clinical importance in the future.

Intensive Care Resources and 60-Day Survival of Critically-Ill COVID-19 Patients.

BACKGROUND: Germany reported sufficient intensive care unit (ICU) resources throughout the first wave of coronavirus disease 2019 (COVID-19). The treatment of critically ill COVID-19 patients without rationing may improve the outcome. We therefore analyzed ICU resources allocated to COVID-19 patients with respiratory failure and their outcomes. METHODS: Retrospectively, we enrolled severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR)-positive patients with respiratory failure from 03/08/2020 to 04/08/2020 and followed until 05/28/2020 in the university hospital of Freiburg, Germany. RESULTS: In the defined interval, 34 COVID-19 patients were admitted to the ICU with median age of 67±13 (31-86) years. Six of 34 (17.6%) were female. All patients suffered from moderate or severe acute respiratory distress syndrome (ARDS), 91.2% of the patients were intubated and 23.5% required extracorporeal membrane oxygenation (ECMO). Proning was performed in 67.6%, renal replacement therapy (RRT) was required in 35.3%. Ninety-six percent required more than 20 nursing hours per day. Mean ICU stay was 21±19 (1-81) days. Sixty-day survival of critically ill COVID-19 patients was 50.0% (17/34). Causes of death were multi-organ failure (52.9%), refractory ARDS (17.6%) and intracerebral hemorrhage (17.6%). CONCLUSIONS: Treatment of critically ill COVID-19 patients is protracted and resource-intense. In a context without resources shortage, 50% of COVID-19 with respiratory failure survived up to 60 days.

Intracerebral Hemorrhage in COVID-19 Patients with Pulmonary Failure: A Propensity Score-Matched Registry Study.

BACKGROUND: Hypercoagulability in Coronavirus Disease 2019 (COVID-19) causes deep vein thrombosis and pulmonary embolism necessitating systemic anticoagulation. Case reports of intracerebral hemorrhages in ventilated COVID-19 patients warrant precaution. It is unclear, however, if COVID-19 patients with acute respiratory distress syndrome (ARDS) with or without veno-venous extracorporeal membrane oxygenation therapy (VV-ECMO) have more intracerebral hemorrhages (ICH) compared to other ARDS patients. METHODS: We conducted a retrospective observational single-center study enrolling all patients with ARDS from 01/2018 to 05/2020. PCR-positive SARS-CoV-2 patients with ARDS were allocated to the COVID-19 group. Propensity score matching was performed for age, VV-ECMO, and bleeding risk. RESULTS: A total of 163 patients with moderate or severe ARDS were identified, 47 (28.8%) in the COVID-19 group, and 116 (71.2%) in the non-COVID-19 group. In 63/163 cases (38.7%), VV-ECMO therapy was required. The ICU survival was 52.8%. COVID-19 patients were older, more often male, and exhibited a lower SOFA score, but the groups showed similar rates of VV-ECMO therapy. Treatments with antiplatelet agents (p = 0.043) and therapeutic anticoagulation (p = 0.028) were significantly more frequent in the COVID-19 patients. ICH was detected in 22 patients (13.5%) with no statistical difference between the groups (11.2 vs. 19.1% without and with SARS-CoV-2, respectively, p = 0.21). Propensity score matching confirmed similar rates of ICH in both groups (12.8 vs. 19.1% without and with SARS-CoV-2, respectively, p = 0.57), thus leveling out possible confounders. CONCLUSIONS: Intracerebral hemorrhage was detected in every tenth patient with ARDS. Despite statistically higher rates of antiplatelet therapy and therapeutic anticoagulation in COVID-19 patients, we found a similar rate of ICH in patients with ARDS due to COVID-19 compared to other causes of ARDS.

Lung ultrasound in the emergency department - a valuable tool in the management of patients presenting with respiratory symptoms during the SARS-CoV-2 pandemic.

BACKGROUND: Typical lung ultrasound (LUS) findings in patients with a COVID-19 infection were reported early on. During the global SARS-CoV-2 pandemic, LUS was propagated as a useful instrument in triage and monitoring. We evaluated LUS as a rapid diagnostic triage tool for the management of patients with suspected COVID-19 in the emergency department (ED). METHODS: The study retrospectively enrolled patients with suspected COVID-19, who were admitted from 1st April to 25th of April 2020 to the ED of a tertiary care center in Germany. During clinical work-up, patients underwent LUS and polymerase chain reaction (PCR) testing for SARS-CoV-2. The recorded ultrasound findings were analyzed and judged regarding typical signs of viral pneumonia, blinded for clinical information of the patients. The results were compared with PCR test and chest computed tomography (CT). RESULTS: 2236 patients were treated in the ED during the study period. 203 were tested for SARS-CoV-2 using PCR, 135 (66.5%) underwent LUS and 39 (28.9%) of the patients were examined by chest CT scan. 39 (28.9%) of the 135 patients were tested positive for SARS-CoV-2 with PCR. In 52 (38.5%) COVID-19 was suspected from the finding of the LUS, resulting in a sensitivity of 76.9% and a specificity of 77.1% compared with PCR results. The negative predictive value reached 89.2%. The findings of the LUS had - compared to a positive chest CT scan for COVID-19 - a sensitivity of 70.6% and a specificity of 72.7%. CONCLUSIONS: LUS is a rapid and useful triage tool in the work-up of patients with suspected COVID-19 infection during a pandemic scenario. Still, the results of the LUS depend on the physician's experience and skills.

COVID-19 in-hospital mortality and mode of death in a dynamic and non-restricted tertiary care model in Germany.

BACKGROUND: Reported mortality of hospitalised Coronavirus Disease-2019 (COVID-19) patients varies substantially, particularly in critically ill patients. So far COVID-19 in-hospital mortality and modes of death under state of the art care have not been systematically studied. METHODS: This retrospective observational monocenter cohort study was performed after implementation of a non-restricted, dynamic tertiary care model at the University Medical Center Freiburg, an experienced acute respiratory distress syndrome (ARDS) and extracorporeal membrane-oxygenation (ECMO) referral center. All hospitalised patients with PCR-confirmed SARS-CoV-2 infection were included. The primary endpoint was in-hospital mortality, secondary endpoints included major complications and modes of death. A multistate analysis and a Cox regression analysis for competing risk models were performed. Modes of death were determined by two independent reviewers. RESULTS: Between February 25, and May 8, 213 patients were included in the analysis. The median age was 65 years, 129 patients (61%) were male. 70 patients (33%) were admitted to the intensive care unit (ICU), of which 57 patients (81%) received mechanical ventilation and 23 patients (33%) ECMO support. Using multistate methodology, the estimated probability to die within 90 days after COVID-19 onset was 24% in the whole cohort. If the levels of care at time of study entry were accounted for, the probabilities to die were 16% if the patient was initially on a regular ward, 47% if in the intensive care unit (ICU) and 57% if mechanical ventilation was required at study entry. Age ≥65 years and male sex were predictors for in-hospital death. Predominant complications-as judged by two independent reviewers-determining modes of death were multi-organ failure, septic shock and thromboembolic and hemorrhagic complications. CONCLUSION: In a dynamic care model COVID-19-related in-hospital mortality remained very high. In the absence of potent antiviral agents, strategies to alleviate or prevent the identified complications should be investigated. In this context, multistate analyses enable comparison of models-of-care and treatment strategies and allow estimation and allocation of health care resources.

Incidence of Barotrauma in Patients With COVID-19 Pneumonia During Prolonged Invasive Mechanical Ventilation - A Case-Control Study.

BACKGROUND: SARS-CoV2 can cause pulmonary failure requiring prolonged invasive mechanical ventilation (MV). Lung protective ventilation strategies are recommended in order to minimize ventilator induced lung injury. Whether patients with COVID-19 have the same risk for complications including barotrauma is still unknown. Therefore, we investigated barotrauma in patients with COVID-19 pneumonia requiring prolonged MV. METHODS: All patients meeting diagnosis criteria for ARDS according to the Berlin Definition, with PCR positive SARS-CoV2 infection and prolonged mechanical ventilation, defined as ≥2 days, treated at our ARDS referral center between March and April 2020 were included in a retrospective registry analysis. Complications were detected by manual review of all patient data including respiratory data, imaging studies, and patient files. RESULTS: A total of 20 patients with severe COVID-19 pulmonary failure (Overall characteristics: median age: 61 years, female gender 6, median duration of MV 22 days) were analyzed. Eight patients (40%) developed severe barotrauma during MV (after median 18 days, range: 1-32) including pneumothorax (5/20), pneumomediastinum (5/20), pneumopericard (1/20), and extended subcutaneous emphysema (5/20). Median respirator settings 24 hours before barotrauma were: Peak inspiratory pressure (Ppeak) 29 cm H2O (range: 27-35), positive end-expiratory pressure (PEEP) 14 cm H2O (range: 5-24), tidal volume (VT) 5.4ml/kg predicted body weight (range 0.4-8.6), plateau pressure (Pplateau) 27 cm H2O (range: 19-30). Mechanical ventilation was significantly more invasive on several occasions in patients without barotrauma. CONCLUSION: Barotrauma in COVID-19 induced respiratory failure requiring mechanical ventilation was found in 40% of patients included in this registry. Our data suggest that barotrauma in COVID-19 may occur even when following recommendations for lung protective MV.

Pulmonary artery thrombi are co-located with opacifications in SARS-CoV2 induced ARDS.

PURPOSE: Patients hospitalized for infection with SARS-CoV-2 typically present with pneumonia. The respiratory failure is frequently complicated by pulmonary embolism in segmental pulmonary arteries. The distribution of pulmonary embolism in regard to lung parenchymal opacifications has not been investigated yet. METHODS: All patients with COVID-19 treated at a medical intensive care unit between March 8th and April 15th, 2020 undergoing computed tomography pulmonary angiography (CTPA) were included. All CTPA were assessed by two radiologists independently in respect to parenchymal changes and pulmonary embolism on a lung segment basis. RESULTS: Out of 22 patients with severe COVID-19 treated within the observed time period, 16 (age 60.4 ± 10.2 years, 6 female SAPS2 score 49.2 ± 13.9) underwent CT. A total of 288 lung segment were analyzed. Thrombi were detectable in 9/16 (56.3%) patients, with 4.4 ± 2.9 segments occluded per patient and 40/288 (13.9%) segments affected in the whole cohort. Patients with thrombi had significantly worse segmental opacifications in CT (p < 0.05) and all thrombi were located in opacitated segments. There was no correlation between d-dimer level and number of occluded segmental arteries. CONCLUSIONS: Thrombi in segmental pulmonary arteries are common in COVID-19 and are located in opacitated lung segments. This might suggest local clot formation.