Echocardiography Before Extracorporeal Membrane Oxygenation in Refractory Respiratory Failure: SARS-CoV-2 Infection Versus Other Etiologies.

OBJECTIVES: The study authors hypothesized that in patients with SARS-CoV-2, COVID-19-related refractory respiratory failure requiring extracorporeal membrane oxygenation (ECMO) support echocardiographic findings (just before ECMO implantation) would be different from those observed in patients with refractory respiratory failure from different etiologies. DESIGN: A single-center observational study. SETTING: At an intensive care unit (ICU). PARTICIPANTS: A total of 61 consecutive patients with refractory COVID-19-related respiratory failure (COVID-19 series) and 74 patients with refractory acute respiratory disease syndrome from other etiologies (no COVID-19 series), all needing ECMO support. INTERVENTIONS: Echocardiogram pre-ECMO. MEASUREMENTS AND MAIN RESULTS: Right ventricle dilatation and dysfunction were defined in the presence of the RV end-diastolic area and/or left ventricle end-diastolic area (LVEDA >0.6 and tricuspid annular plane systolic excursion [TAPSE] <15 mm. Patients in the COVID-19 series showed a higher body mass index (p < 0.001) and a lower Sequential Organ Failure Assessment score (p = 0.002). In-ICU mortality rates were comparable between the 2 subgroups. Echocardiograms performed in all patients before ECMO implantation revealed an incidence of RV dilatation that was higher in patients in the COVID-19 series (p < 0.001), and they also showed higher values of systolic pulmonary artery pressure (sPAP) (p < 0.001) and lower TAPSE and/or sPAP (p < 0.001). The multivariate logistic regression analysis showed that COVID-19-related respiratory failure was not associated with early mortality. The presence of RV dilatation and the uncoupling of RV function and pulmonary circulation were associated independently with COVID-19 respiratory failure. CONCLUSIONS: The presence of RV dilatation and an altered coupling between RVe function and pulmonary vasculature (as indicated by TAPSE and/or sPAP) are associated strictly with COVID-19-related refractory respiratory failure needing ECMO support.

Clinical Significance of Right Ventricle Echocardiographic Patterns in Critically-Ill COVID-Related Acute Respiratory Distress Syndrome "On Behalf of Protecting the Right Ventricle Network (PRORVnet)".

We assessed whether right ventricle (RV) alterations and their development may have clinical significance in critically-ill Coronavirus Disease (COVID) patients, as detected by serial echocardiograms during Intensive Care Unit (ICU) course. This observational single center study included 98 consecutive patients with COVID-related acute respiratory distress syndrome (ARDS). Three subgroups were considered: RV Dysfunction (Dys) on admission (10/98, 10%), developed RV Dys (17/98, 17%), and no RV Dys (71/98, 73%). Overall mortality at 3 months was 46.9%. The first subgroup was characterized by the highest need for Extracorporeal Membrane Oxygenation (ECMO) support (P < .001) and a systemic inflammatory activation (as indicated by increased D-dimer), the second one by the lowest PaO2/FiO2 (P/F). At multivariate regression analysis, age and Sequential Organ Failure Assessment score were independent predictors for mortality. Different RV echo patterns were observed in critically ill patients presenting with COVID-related ARDS during ICU stay. RV Dys on admission was characterized by a high inflammatory activation while patients who developed RV Dys during ICU stay showed lowest P/F. Both these two subgroups identify patients with a severe COVID disease which in a high percentage of cases was unresponsive to standard treatment and required the use of ECMO.

Coupling of right ventricular function to pulmonary circulation as an independent predictor for non invasive ventilation failure in SARSCoV 2-related acute respiratory distress syndrome.

Study objectives: To assess whether echocardiography, systematically performed, could help in risk stratifying patients with acute respiratory distress syndrome (ARDS) due to SARS-CoV2 (COVID) infection for non invasive ventilation (NIV) failure. Design: Observational single center investigation. Setting: Intensive care unit. Interventions: Echocardiography. Outcome measures: NIV failure. Main results: Seventy-five patients were included in our study. In respect to patients who did not need mechanical ventilation (NIV success), those in the NIV failure subgroup (31 patients, 41 %) were older, with more comorbidities and showed a higher SOFA score and LOS. Higher values of NTpro BNP, CRP and D-dimer were observed in the NIV failure subgroup who exhibited a higher ICU mortality rate. At echocardiographic examination, the NIV failure subgroup showed higher values of RV/LV ratio, systolic pulmonary arterial pressure (sPAP) and lower values of tricuspid annular plane systolic excursion (TAPSE)/SPAP, and PaO2/FiO2. At logistic regression analysis TAPSE/sPAP resulted an independent predictor of NIV failure. At receiving operating characteristic curve analysis, the TAPSE/SPAP cut-off of 0.575 mm/mm Hg showed a sensitivity of 97 % and a specificity of 48 %. Conclusions: Our results documented a marked uncoupling of right ventricular function from the pulmonary circulation (as indicated by TAPSE/sPAP) in COVID-related ARDS treated with non invasive ventilation and the measurement of this parameter, performed on ICU admission, provides independent prognostic relevance for NIV failure.

Effects of rescue inhaled nitric oxide on right ventricle and pulmonary circulation in severe COVID-related acute respiratory distress syndrome.

PURPOSES: To assess the effects of inhaled Nitric Oxide (iNO) on right ventricle dimension and function and systolic pulmonary arterial pressures in severe Acute Respiratory Distress (ARDS) due to Sars-Cov2 (COVID) infection. MATERIALS AND METHODS: We assessed the effects of iNO on right ventricle dimension and function and systolic pulmonary arterial pressures in 12 consecutive COVID-related ARDS patients by means of serial echocardiographic exams (baseline, 12 and 24 h since iNO start). RESULTS: Inhaled NO administration did not influence systolic pulmonary arterial pressures nor RV dimension and function. No changes were detectable in ventilatory data with iNO administration. Considering the negligible effect on oxygenation, iNO use was discontinued in all cases. CONCLUSIONS: In COVID-related severe ARDS iNO administrated as rescue therapy is not able to ameliorate oxygenation nor pulmonary hypertension, as assessed by serial echocardiograms. This finding may be explained by the diffuse loss of hypoxic pulmonary vasoconstriction with increased perfusion around alveolar consolidations which characterizes COVID-related severe ARDS.

Persistent Right Ventricle Dilatation in SARS-CoV-2-Related Acute Respiratory Distress Syndrome on Extracorporeal Membrane Oxygenation Support.

OBJECTIVES: Venovenous extracorporeal membrane oxygenation (ECMO) support may be considered in experienced centers for patients with acute respiratory distress syndrome (ARDS) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection refractory to conventional treatment. In ECMO patients, echocardiography has emerged as a clinical tool for implantation and clinical management; but to date, little data are available on COVID-related ARDS patients requiring ECMO. The authors assessed the incidence of right ventricular dilatation and dysfunction (RvDys) in patients with COVID-related ARDS requiring ECMO. DESIGN: Single-center investigation. SETTING: Intensive care unit (ICU). PARTICIPANTS: A total of 35 patients with COVID-related ARDS requiring ECMO, consecutively admitted to the ICU (March 1, 2020, to February 28, 2021). INTERVENTIONS: Serial echocardiographic examinations. RvDys was defined as RV end-diastolic area/LV end-diastolic area >0.6 and tricuspid annular plane excursion <15 mm. MEASUREMENTS AND MAIN RESULTS: The incidence of RvDys was 15/35 (42%). RvDys patients underwent ECMO support after a longer period of mechanical ventilation (p = 0.006) and exhibited a higher mortality rate (p = 0.024) than those without RvDys. In nonsurvivors, RvDys was observed in all patients (n = nine) who died with unfavorable progression of COVID-related ARDS. In survivors, weaned from ECMO, a significant reduction in systolic pulmonary arterial pressures was detectable. CONCLUSIONS: According to the authors' data, in COVID-related ARDS requiring ECMO support, RvDys is common, associated with increased ICU mortality. Overall, the data underscored the clinical role of echocardiography in COVID-related ARDS supported by venovenous ECMO, because serial echocardiographic assessments (especially focused on RV changes) are able to reflect pulmonary COVID disease severity.

Electrodiagnostic findings in patients with non-COVID-19- and COVID-19-related acute respiratory distress syndrome.

BACKGROUND: Critical illness polyneuropathy and myopathy (CIPNM) is a frequent neurological manifestation in patients with acute respiratory distress syndrome (ARDS) from coronavirus disease 2019 (COVID-19) infection. CIPNM diagnosis is usually limited to clinical evaluation. We compared patients with ARDS from COVID-19 and other aetiologies, in whom a neurophysiological evaluation for the detection of CIPNM was performed. The aim was to determine if there were any differences between these two groups in frequency of CINPM and outcome at discharge from the intensive care unit (ICU). MATERIALS AND METHODS: This was a single-centre retrospective study performed on mechanically ventilated patients consecutively admitted (January 2016-June 2020) to the ICU of Careggi Hospital, Florence, Italy, with ARDS of different aetiologies. Neurophysiological evaluation was performed on patients with stable ventilation parameters, but marked widespread hyposthenia (Medical Research Council score <48). Creatine phosphokinase (CPK), lactic dehydrogenase (LDH) and mean morning glycaemic values were collected. RESULTS: From a total of 148 patients, 23 with COVID-19 infection and 21 with ARDS due to other aetiologies, underwent electroneurography/electromyography (ENG/EMG) recording. Incidence of CIPNM was similar in the two groups, 65% (15 of 23) in COVID-19 patients and 71% (15 of 21) in patients affected by ARDS of other aetiologies. At ICU discharge, subjects with CIPNM more frequently required ventilatory support, regardless the aetiology of ARDS. CONCLUSION: ENG/EMG represents a useful tool in the identification of the neuromuscular causes underlying ventilator wean failure and patient stratification. A high incidence of CIPNM, with a similar percentage, has been observed in ARDS patients of all aetiologies.

The prognostic role of hyperglycemia and glucose variability in covid-related acute respiratory distress Syndrome.

AIMS: Due to heterogeneity on the prognostic role of glucose values and glucose variability in Novel Coronavirus (COVID) disease, we aimed at assessing the prognostic role for Intensive Care Unit (ICU) death of admission hyperglycaemia, peak glycemia and glucose variability in critically ill COVID patients: METHODS: 83 patients consecutively admitted for COVID-related Acute Respiratory Distress Syndrome (ARDS) from from 1st March to 1st October 2020. RESULTS: Non survivors were older, with more comorbidities and a more severe disease. Corticosteroids were used in the majority of patients (54/83, 65%) with no difference between survivors and non survivors. Mean blood glucose values, (during the first 24 and 48 h, respectively), were comparable between the two subgroups, as well as SD 24 and CV 24. During the first 48 h, survivors showed significantly lower values of SD 48 (p < 0.001) and CV 48, respectively (p < 0.001) than non survivors. CONCLUSIONS: in consecutive COVID-related ARDS patients admitted to ICU hyperglycemia (>180 mg/dl) is more common in non survivors who also showed a significantly higher glucose variability in the first 48 h since ICU admission. Our findings point to the clinical significance of in-ICU glucose control in severe COVID patients.

Combined lung and cardiac ultrasound in COVID-related acute respiratory distress syndrome.

BACKGROUND: Lung ultrasound (LU) is a useful tool for monitoring lung involvement in novel coronavirus (COVID) disease, while information on echocardiographic findings in COVID disease is to date scarce and heterogeneous. We hypothesized that lung and cardiac ultrasound examinations, serially and simultaneously performed, could monitor disease severity in COVID-related ARDS. METHODS: We enrolled 47 consecutive patients with COVID-related ARDS (1st March-31st May 2020). Lung and cardiac ultrasounds were performed on admission, at discharged and when clinically needed. RESULTS: Most patients were mechanically ventilated (75%) and veno-venous extracorporeal membrane oxygenation was needed in ten patients (21.2%). The in-ICU mortality rate was 27%%. On admission, not survivors showed a higher LUS score (p = 0.006) and a higher incidence of consolidations (p = 0.003), lower values of LVEF (p = 0.027) and a higher RV/LV ratio (0.008). At discharge, a significant reduction in the incidence of subpleural consolidations (p < 0.001) and, thus, in LUS score (p < 0.001) and an increase in patter A findings (p < 0.001) together with reduced systolic pulmonary arterial pressures were detectable. In not survivors at final examination, an increased in LUS score (p < 0.001), and in RV/LV ratio (p < 0.001) associated with a reduction in TAPSE (p = 0.013) were observed. A significant correlation was observed between LUS and systolic pulmonary arterial pressure (p = 0.04). LUS and RV/LV resulted independent predictors of in-ICU death. CONCLUSIONS: In COVID-related ARDS, the combined lung and cardiac ultrasound proved to be an useful clinical tool in monitoring disease progression and in identifying parameters (LU score and RV/LV ratio) able to risk stratifying these patients.

Echocardiographic assessment of the right ventricle in COVID -related acute respiratory syndrome.

In patients with the novel coronavirus (COVID-19) infection, the echocardiographic assessment of the right ventricle (RV) represents a pivotal element in the understanding of current disease status and in monitoring disease progression. The present manuscript is aimed at specifically describing the echocardiographic assessment of the right ventricle, mainly focusing on the most useful parameters and the time of examination. The RV direct involvement happens quite often due to preferential lung tropism of COVID-19 infection, which is responsible for an interstitial pneumonia characterized also by pulmonary hypoxic vasoconstriction (and thus an RV afterload increase), often evolving in acute respiratory distress syndrome (ARDS). The indirect RV involvement may be due to the systemic inflammatory activation, caused by COVID-19, which may affect the overall cardiovascular system mainly by inducing an increase in troponin values and in the sympathetic tone and altering the volemic status (mainly by affecting renal function). Echocardiographic parameters, specifically focused on RV (dimensions and function) and pulmonary circulation (systolic pulmonary arterial pressures, RV wall thickness), are to be measured in a COVID-19 patient with respiratory failure and ARDS. They have been selected on the basis of their feasibility (that is easy to be measured, even in short time) and usefulness for clinical monitoring. It is advisable to measure the same parameters in the single patient (based also on the availability of valid acoustic windows) which are identified in the first examination and repeated in the following ones, to guarantee a reliable monitoring. Information gained from a clinically-guided echocardiographic assessment holds a clinical utility in the single patients when integrated with biohumoral data (indicating systemic activation), blood gas analysis (reflecting COVID-19-induced lung damage) and data on ongoing therapies (in primis ventilatory settings).

Cardiac Involvment in COVID-19-Related Acute Respiratory Distress Syndrome.

The cardiac involvement in Coronavirus disease (COVID-19) is still under evaluation, especially in severe COVID-19-related Acute Respiratory Distress Syndrome (ARDS). The cardiac involvement was assessed by serial troponin levels and echocardiograms in 28 consecutive patients with COVID-19 ARDS consecutively admitted to our Intensive Care Unit from March 1 to March 31. Twenty-eight COVID-19 patients (aged 61.7 ± 10 years, males 79%). The majority was mechanically ventilated (86%) and 4 patients (14%) required veno-venous extracorporeal membrane oxygenation. As of March 31, the Intensive Care Unit mortality rate was 7%, whereas 7 patients were discharged (25%) with a length of stay of 8.2 ±5 days. At echocardiographic assessment on admission, acute core pulmonale was detected in 2 patients who required extracorporeal membrane oxygenation support. Increased systolic arterial pressure was detected in all patients. Increased Troponin T levels were detectable in 11 patients (39%) on admission. At linear regression analysis, troponin T showed a direct relationship with C-reactive Protein (R square: 0.082, F: 5.95, p = 0.017). In conclusions, in COVID-19-related ARDS, increased in Tn levels was common but not associated with alterations in wall motion kinesis, thus suggesting that troponin T elevation is likely to be multifactorial, mainly linked to disease severely (as inferred by the relation between Tn and C-reactive Protein). The increase in systolic pulmonary arterial pressures observed in all patients may be related to hypoxic vasoconstriction. Further studies are needed to confirm our findings in larger cohorts.

Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent.

BACKGROUNDCoronavirus disease 19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2. Antiviral immune response is crucial to achieve pathogen clearance; however, in some patients an excessive and aberrant host immune response can lead to an acute respiratory distress syndrome. The comprehension of the mechanisms that regulate pathogen elimination, immunity, and pathology is essential to better characterize disease progression and widen the spectrum of therapeutic options.METHODSWe performed a flow cytometric characterization of immune cell subsets from 30 patients with COVID-19 and correlated these data with clinical outcomes.RESULTSPatients with COVID-19 showed decreased numbers of circulating T, B, and NK cells and exhibited a skewing of CD8+ T cells toward a terminally differentiated/senescent phenotype. In agreement, CD4+ T and CD8+ T, but also NK cells, displayed reduced antiviral cytokine production capability. Moreover, a reduced cytotoxic potential was identified in patients with COVID-19, particularly in those who required intensive care. The latter group of patients also showed increased serum IL-6 levels that inversely correlated to the frequency of granzyme A-expressing NK cells. Off-label treatment with tocilizumab restored the cytotoxic potential of NK cells.CONCLUSIONThe association between IL-6 serum levels and the impairment of cytotoxic activity suggests the possibility that targeting this cytokine may restore antiviral mechanisms.FUNDINGThis study was supported by funds from the Department of Experimental and Clinical Medicine of University of Florence (the ex-60% fund and the "Excellence Departments 2018-2022 Project") derived from Ministero dell'Istruzione, dell'Università e della Ricerca (Italy).