Prognostic value of right ventricular dilatation on computed tomography pulmonary angiogram for predicting adverse clinical events in severe COVID-19 pneumonia.

Background: Right ventricle dilatation (RVD) is a common complication of non-intubated COVID-19 pneumonia caused by pro-thrombotic pneumonitis, intra-pulmonary shunting, and pulmonary vascular dysfunction. In several pulmonary diseases, RVD is routinely measured on computed tomography pulmonary angiogram (CTPA) by the right ventricle-to-left ventricle (LV) diameter ratio > 1 for predicting adverse events. Objective: The aim of the study was to evaluate the association between RVD and the occurrence of adverse events in a cohort of critically ill non-intubated COVID-19 patients. Methods: Between February 2020 and February 2022, non-intubated patients admitted to the Amiens University Hospital intensive care unit for COVID-19 pneumonia with CTPA performed within 48 h of admission were included. RVD was defined by an RV/LV diameter ratio greater than one measured on CTPA. The primary outcome was the occurrence of an adverse event (renal replacement therapy, extracorporeal membrane oxygenation, 30-day mortality after ICU admission). Results: Among 181 patients, 62% (n = 112/181) presented RVD. The RV/LV ratio was 1.10 [1.05-1.18] in the RVD group and 0.88 [0.84-0.96] in the non-RVD group (p = 0.001). Adverse clinical events were 30% and identical in the two groups (p = 0.73). In Receiving operative curves (ROC) analysis, the RV/LV ratio measurement failed to identify patients with adverse events. On multivariable Cox analysis, RVD was not associated with adverse events to the contrary to chest tomography severity score > 10 (hazards ratio = 1.70, 95% CI [1.03-2.94]; p = 0.04) and cardiovascular component (> 2) of the SOFA score (HR = 2.93, 95% CI [1.44-5.95], p = 0.003). Conclusion: Right ventricle (RV) dilatation assessed by RV/LV ratio was a common CTPA finding in non-intubated critical patients with COVID-19 pneumonia and was not associated with the occurrence of clinical adverse events.

A norepinephrine weaning strategy using dynamic arterial elastance is associated with reduction of acute kidney injury in patients with vasoplegia after cardiac surgery: A post-hoc analysis of the randomized SNEAD study.

STUDY OBJECTIVE: To evaluate the impact of a dynamic arterial elastance guided norepinephrine weaning strategy on the occurrence of acute kidney injury (AKI) in patients with vasoplegia after cardiac surgery. DESIGN: A post-hoc analysis of a monocentric randomized controlled trial. SETTING: A tertiary care hospital in France. PARTICIPANTS: Vasoplegic cardiac surgical patients treated with norepinephrine. INTERVENTION: Patients were randomized to an algorithm-based norepinephrine weaning intervention (dynamic arterial elastance) group or a control group. MEASUREMENTS: The primary endpoint was the number of patients with AKI defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The secondary endpoint were major adverse cardiac post-operative events (new onset of atrial fibrillation or flutter, low cardiac output syndrome, and in-hospital death). End points were evaluated during the first seven post-operative days. RESULTS: 118 patients were analyzed. In the overall study population, the mean age was 70 (62-76) years, 65% were male and the median EuroSCORE was 7 (5-10). Overall, 46 (39%) patients developed AKI (30 KDIGO 1, 8 KDIGO 2, 8 KDIGO 3), and 6 patients required renal replacement therapy. The incidence of AKI was significantly lower in the intervention group than in the control group (16 patients (27%) vs 30 patients (51%), p = 0.12). Higher dose and longer duration of norepinephrine were associated with AKI severity. CONCLUSION: Decreasing norepinephrine exposure by using a dynamic arterial elastance guided norepinephrine weaning strategy was associated with a reduced incidence of acute kidney injury in patients with vasoplegia after cardiac surgery. Further prospective multicentric studies are needed to confirm these results.

Prognostic value of acute cor pulmonale in COVID-19-related pneumonia: A prospective study.

Background: It is known that acute cor pulmonale (ACP) worsens the prognosis of non-coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (NC-ARDS). The ACP risk score evaluates the risk of ACP occurrence in mechanically ventilated patients with NC-ARDS. There is less data on the risk factors and prognosis of ACP induced by COVID-19-related pneumonia. Objective: The objective of this study was to evaluate the prognostic value of ACP, assessed by transthoracic echocardiography (TTE) and clinical factors associated with ACP in a cohort of patients with COVID-19-related pneumonia. Materials and methods: Between February 2020 and June 2021, patients admitted to intensive care unit (ICU) at Amiens University Hospital for COVID-19-related pneumonia were assessed by TTE within 48 h of admission. ACP was defined as a right ventricle/left ventricle area ratio of >0.6 associated with septal dyskinesia. The primary outcome was mortality at 30 days. Results: Among 146 patients included, 36% (n = 52/156) developed ACP of which 38% (n = 20/52) were non-intubated patients. The classical risk factors of ACP (found in NC-ARDS) such as PaCO2 >48 mmHg, driving pressure >18 mmHg, and PaO2/FiO2 < 150 mmHg were not associated with ACP (all P-values > 0.1). The primary outcome occurred in 32 (22%) patients. More patients died in the ACP group (n = 20/52 (38%) vs. n = 12/94 (13%), P = 0.001). ACP [hazards ratio (HR) = 3.35, 95%CI [1.56-7.18], P = 0.002] and age >65 years (HR = 2.92, 95%CI [1.50-5.66], P = 0.002) were independent risk factors of 30-day mortality. Conclusion: ACP was a frequent complication in ICU patients admitted for COVID-19-related pneumonia. The 30-day-mortality was 38% in these patients. In COVID-19-related pneumonia, the classical risk factors of ACP did not seem relevant. These results need confirmation in further studies.

Mortality of COVID-19 Patients Requiring Extracorporeal Membrane Oxygenation During the Three Epidemic Waves.

Clinical presentation and mortality of patients treated with extracorporeal membrane oxygenation (ECMO) for COVID-19 acute respiratory distress syndrome (CARDS) were different during the French epidemic waves. The management of COVID-19 patients evolved through waves as much as knowledge on that new viral disease progressed. We aimed to compare the mortality rate through the first three waves of CARDS patients on ECMO and identify associated risk factors. Fifty-four consecutive ECMO for CARDS hospitalized at Amiens University Hospital during the three waves were included. Patients were divided into three groups according to their hospitalization date. Clinical characteristics and outcomes were compared between groups. Pre-ECMO risk factors predicting 90 day mortality were evaluated using multivariate Cox regression. Among 54 ECMO (median age of 61[48-65] years), 26% were hospitalized during the first wave (n = 14/54), 26% (n = 14/54) during the second wave, and 48% (n = 26/54) during the third wave. Time from first symptoms to ECMO was higher during the second wave than the first wave. (17 [12-23] days vs. 11 [9-15]; p < 0.05). Ninety day mortality was higher during the second wave (85% vs. 43%; p < 0.05) but less during the third wave (38% vs. 85%; P < 0.05). Respiratory ECMO survival prediction score and time from symptoms onset to ECMO (HR 1.12; 95% confidence interval [CI]: 1.05-1.20; p < 0.001) were independent factors of mortality. After adjustment, time from symptoms onset to ECMO was an independent factor of 90 day mortality. Changes in CARDS management from first to second wave-induced a later ECMO cannulation from symptoms onset with higher mortality during that wave. The duration of COVID-19 disease progression could be selection criteria for initiating ECMO.

Early hyperoxia and 28-day mortality in patients on venoarterial ECMO support for refractory cardiogenic shock: a bicenter retrospective propensity score-weighted analysis.

BACKGROUND: The mortality rate for a patient with a refractory cardiogenic shock on venoarterial (VA) extracorporeal membrane oxygenation (ECMO) remains high, and hyperoxia might worsen this prognosis. The objective of the present study was to evaluate the association between hyperoxia and 28-day mortality in this setting. METHODS: We conducted a retrospective bicenter study in two French academic centers. The study population comprised adult patients admitted for refractory cardiogenic shock. The following arterial partial pressure of oxygen (PaO2) variables were recorded for 48 h following admission: the absolute peak PaO2 (the single highest value measured during the 48 h), the mean daily peak PaO2 (the mean of each day's peak values), the overall mean PaO2 (the mean of all values over 48 h), and the severity of hyperoxia (mild: PaO2 < 200 mmHg, moderate: PaO2 = 200-299 mmHg, severe: PaO2 ≥ 300 mmHg). The main outcome was the 28-day all-cause mortality. Inverse probability weighting (IPW) derived from propensity scores was used to reduce imbalances in baseline characteristics. RESULTS: From January 2013 to January 2020, 430 patients were included and assessed. The 28-day mortality rate was 43%. The mean daily peak, absolute peak, and overall mean PaO2 values were significantly higher in non-survivors than in survivors. In a multivariate logistic regression analysis, the mean daily peak PaO2, absolute peak PaO2, and overall mean PaO2 were independent predictors of 28-day mortality (adjusted odds ratio [95% confidence interval per 10 mmHg increment: 2.65 [1.79-6.07], 2.36 [1.67-4.82], and 2.85 [1.12-7.37], respectively). After IPW, high level of oxygen remained significantly associated with 28-day mortality (OR = 1.41 [1.01-2.08]; P = 0.041). CONCLUSIONS: High oxygen levels were associated with 28-day mortality in patients on VA-ECMO support for refractory cardiogenic shock. Our results confirm the need for large randomized controlled trials on this topic.

Association between acute kidney injury and norepinephrine use following cardiac surgery: a retrospective propensity score-weighted analysis.

BACKGROUND: Excess exposure to norepinephrine can compromise microcirculation and organ function. We aimed to assess the association between norepinephrine exposure and acute kidney injury (AKI) and intensive care unit (ICU) mortality after cardiac surgery. METHODS: This retrospective observational study included adult patients who underwent cardiac surgery under cardiopulmonary bypass from January 1, 2008, to December 31, 2017, at the Amiens University Hospital in France. The primary exposure variable was postoperative norepinephrine during the ICU stay and the primary endpoint was the presence of AKI. The secondary endpoint was in-ICU mortality. As the cohort was nonrandom, inverse probability weighting (IPW) derived from propensity scores was used to reduce imbalances in the pre- and intra-operative characteristics. RESULTS: Among a population of 5053 patients, 1605 (32%) were exposed to norepinephrine following cardiac surgery. Before weighting, the prevalence of AKI was 25% and ICU mortality 10% for patients exposed to norepinephrine. Exposure to norepinephrine was estimated to be significantly associated with AKI by a factor of 1.95 (95% confidence interval, 1.63-2.34%; P < 0.001) in the IPW cohort and with in-ICU mortality by a factor of 1.54 (95% confidence interval, 1.19-1.99%; P < 0.001). CONCLUSION: Norepinephrine was associated with AKI and in-ICU mortality following cardiac surgery. While these results discourage norepinephrine use for vasoplegic syndrome in cardiac surgery, prospective investigations are needed to substantiate findings and to suggest alternative strategies for organ protection.

Feasibility, Prediction and Association of Right Ventricular Free Wall Longitudinal Strain with 30-Day Mortality in Severe COVID-19 Pneumonia: A Prospective Study.

Introduction: Right ventricular (RV) systolic dysfunction (RVsD) is a common complication of coronavirus infection 2019 disease (COVID-19). The right ventricular free wall longitudinal strain parameter (RV-FWLS) is a powerful predictor of mortality. We explored the performance of RVsD parameters for predicting 30-day mortality and the association between RV-FWLS and 30-day mortality. Methods: COVID-19 patients hospitalized at Amiens University Hospital in the critical care unit with transthoracic echocardiography were included. We measured tricuspid annular plane systolic excursion (TAPSE), the RV S' wave, RV fractional area change (RV-FAC), and RV-FWLS. The diagnostic performance of RVsD parameters as predictors for 30-day mortality was evaluated by the area under the receiver operating characteristic (ROC) curve (AUC). RVsD was defined by an RV-FWLS < 21% to explore the association between RVsD and 30-day mortality. Results: Of the 116 patients included, 20% (n = 23/116) died and 47 had a RVsD. ROC curve analysis showed that RV-FWLS failed to predict 30-day mortality, as did conventional RV parameters (all p > 0.05). TAPSE (21 (19−26) mm vs. 24 (21−27) mm; p = 0.024) and RV-FAC (40 (35−47)% vs. 47 (41−55)%; p = 0.006) were lowered in the RVsD group. In Cox analysis, RVsD was not associated with 30-day mortality (hazard ratio = 1.12, CI 95% (0.49−2.55), p = 0.78). Conclusion: In severe COVID-19 pneumonia, RV-FWLS was not associated with 30-day mortality.

Association between the Right Ventricular Longitudinal Shortening Fraction and Mortality in Acute Respiratory Distress Syndrome Related to COVID-19 Infection: A Prospective Study.

Introduction: Right ventricular systolic dysfunction (RVsD) increases acute respiratory distress syndrome mortality in COVID-19 infection (CARDS). The RV longitudinal shortening fraction (RV-LSF) is an angle-independent and automatically calculated speckle-tracking parameter. We explored the association between RV-LSF and 30-day mortality in CARDS patients. Methods: Moderate-to-severe CARDS patients hospitalized at Amiens University Hospital with transesophageal echocardiography performed within 48 h of intensive care unit admission were included. RVsD was defined by an RV-LSF of <20%. The patients were divided into two groups according to the presence of RVsD. Using multivariate Cox regression, clinical and echocardiographic risk factors predicting 30-day mortality were evaluated. Results: Between 28 February 2020 and 1 December 2021, 86 patients were included. A total of 43% (n = 37/86) of the patients showed RVsD and 22% (n = 19/86) of the patients died. RV-LSF was observed in 26 (23.1−29.7)% of the no-RVsD function group and 16.5 (13.7−19.4)% (p < 0.001) of the RVsD group. Cardiogenic shock (n = 7/37 vs. 2/49, p = 0.03) and acute cor pulmonale (n = 18/37 vs. 10/49, p = 0.009) were more frequent in the RVsD group. The 30-day mortality was higher in the RVsD group (15/37 vs. 4/49, p = 0.001). In a multivariable Cox model, RV-LSF was an independent mortality factor (HR 4.45, 95%CI (1.43−13.8), p = 0.01). Conclusion: in a cohort of moderate-to-severe CARDS patients under mechanical ventilation, RVsD defined by the RV-LSF was associated with higher 30-day mortalities.

Portal Vein Pulsatility Index as a Potential Risk of Venous Congestion Assessed by Magnetic Resonance Imaging: A Prospective Study on Healthy Volunteers.

High values of the portal vein pulsatility index (PI) have been associated with adverse outcomes in perioperative or critically ill patients. However, data on dynamic changes of PI related to fluid infusion are scarce. We aimed to determine if dynamic changes in PI are associated with the fluid challenge (FC). To address this challenge, we conducted a prospective single-center study. The population study included healthy subjects. FC consisted in the administration of 500 ml of Ringer lactate infusion over 5 min. The portal blood flow and PI were assessed by magnetic resonance imaging. The responsiveness to FC was defined as an increase in the cardiac stroke volume of at least 10% as assessed by echocardiography. We included 24 healthy volunteers. A total of fourteen (58%) subjects were responders, and 10 (42%) were non-responders. In the responder group, FC induced a significant increase in portal blood flow from 881 (762-1,001) at the baseline to 1,010 (778-1,106) ml min-1 (p = 0.005), whilst PI remained stable (from 31 [25-41] to 35 (25-42) %; p = 0.12). In the non-responder group, portal blood flow remained stable after FC (from 1,042 to 1,034 ml min-1; p = 0.084), whereas PI significantly increased from 32 (22-40) to 48% *(25-85) after FC (p = 0.027). PI was negatively correlated to portal blood flow (Rho coefficient = -0.611; p = 0.002). To conclude, PI might be a sensitive marker of early congestion in healthy subjects that did not respond to FC. This finding requires further validation in clinical settings with a larger sample size.

Individualised or liberal red blood cell transfusion after cardiac surgery: a randomised controlled trial.

BACKGROUND: Current practice guidelines for red blood cell (RBC) transfusion in ICUs are based on haemoglobin threshold, without consideration of oxygen delivery or consumption. We aimed to evaluate an individual physiological threshold-guided by central venous oxygen saturation ScvO2. METHODS: In a randomised study in two French academic hospitals, 164 patients who were admitted to ICU after cardiac surgery with postoperative haemoglobin <9 g dl-1 were randomised to receive a transfusion with one unit of RBCs (haemoglobin group) or transfusion only if the ScvO2 was <70% (individualised group). The primary outcome was the number of subjects receiving at least one unit of RBCs. The secondary composite outcome was acute kidney injury, stroke, myocardial infarction, acute heart failure, mesenteric ischaemia, or in-hospital mortality. One- and 6-month mortality were evaluated during follow-up. RESULTS: The primary outcome was observed for 80 of 80 subjects (100%) in the haemoglobin group and in 61 of 77 patients (79%) in the individualised group (absolute risk -21% [-32.0; -14.0]; P<0.001). There was no significant difference in the secondary outcome between the two groups. Follow-up showed a non-significant difference in mortality at 1 and 6 months. CONCLUSIONS: An individualised strategy based on an central venous oxygen saturation threshold of 70% allows for a more restrictive red blood cell transfusion strategy with no incidence on postoperative morbidity or 6-month mortality. CLINICAL TRIAL REGISTRATION: NCT02963883.

Interchangeability of right ventricular longitudinal shortening fraction assessed by transthoracic and transoesophageal echocardiography in the perioperative setting: A prospective study.

Background: Conventional transthoracic (TTE) and transoesophageal echocardiography (TEE) parameters assessing right ventricle (RV) systolic function are daily used assuming their clinical interchangeability. RV longitudinal shortening fraction (RV-LSF) is a two-dimensional speckle tracking parameter used to assess RV systolic function. RV-LSF is based on tricuspid annular displacement analysis and could be measured with TTE or TEE. Objective: The aim of the study was to determine if RV-LSFTTE and RV-LSFTEE measurements were interchangeable in the perioperative setting. Methods: Prospective perioperative TTE and TEE echocardiography were performed under general anesthesia during scheduled cardiac surgery in 90 patients. RV-LSF was measured by semi-automatic software. Comparisons were performed using Pearson correlation and Bland-Altman plots. RV-LSF clinical agreement was determined as a range of -5 to 5%. Results: Of the 114 patients who met the inclusion criteria, 90 were included. The mean preoperative RV-LSFTTE was 20.4 ± 4.3 and 21.1 ± 4.1% for RV-LSFTEE. The agreement between RV-LSF measurements was excellent, with a bias at -0.61 and limits of agreement of -4.18 to 2.97 %. All measurements fell within the determined clinical agreement interval in the Bland-Altman plot. Linear regression analysis showed a high correlation between RV-LSFTTE and RV-LSFTEE measurement (r = 0.9; confidence interval [CI] 95%: [0.87-0.94], p < 0.001). Conclusion: RV-LSFTTE and RV-LSFTEE measurements are interchangeable, allowing RV-LSF to be a helpful parameter for assessing perioperative changes in RV systolic function. NCT: NCT05404737. https://www.clinicaltrials.gov/ct2/show/NCT05404737.

Automated left atrial strain analysis for predicting atrial fibrillation in severe COVID-19 pneumonia: a prospective study.

BACKGROUND: Atrial fibrillation (AF) is the most documented arrhythmia in COVID-19 pneumonia. Left atrial (LA) strain (LAS) analysis, a marker of LA contractility, have been associated with the development of AF in several clinical situations. We aimed to assess the diagnostic ability of LA strain parameters to predict AF in patients with severe hypoxemic COVID-19 pneumonia. We conducted a prospective single center study in Amiens University Hospital intensive care unit (ICU) (France). Adult patients with severe or critical COVID-19 pneumonia according to the World Health Organization definition and in sinus rhythm were included. Transthoracic echocardiography was performed within 48 h of ICU admission. LA strain analysis was performed by an automated software. The following LA strain parameters were recorded: LA strain during reservoir phase (LASr), LA strain during conduit phase (LAScd) and LA strain during contraction phase (LASct). The primary endpoint was the occurrence of AF during ICU stay. RESULTS: From March 2020 to February of 2021, 79 patients were included. Sixteen patients (20%) developed AF in ICU. Patients of the AF group were significantly older with a higher SAPS II score than those without AF. LAScd and LASr were significantly more impaired in the AF group compared to the other group (- 8.1 [- 6.3; - 10.9] vs. - 17.2 [- 5.0; - 10.2] %; P < 0.001 and 20.2 [12.3;27.3] % vs. 30.5 [23.8;36.2] %; P = 0.002, respectively), while LASct did not significantly differ between groups (p = 0.31). In a multivariate model, LAScd and SOFA cv were significantly associated with the occurrence of AF. A LAScd cutoff value of - 11% had a sensitivity of 76% and a specificity of 75% to identify patients with AF. The 30-day cumulative risk of AF was 42 ± 9% with LAScd > - 11% and 8 ± 4% with LAScd ≤ - 11% (log rank test P value < 0.0001). CONCLUSION: For patients with severe COVID-19 pneumonia, development of AF during ICU stay is common (20%). LAS parameters seem useful in predicting AF within the first 48 h of ICU admission. TRIAL REGISTRATION: NCT04354558.

Portal Vein Pulsatility as a Dynamic Marker of Venous Congestion Following Cardiac Surgery: An Interventional Study Using Positive End-Expiratory Pressure.

We aimed to assess variations in the portal vein pulsatility index (PI) during mechanical ventilation following cardiac surgery. METHOD: After ethical approval, we conducted a prospective monocentric study at Amiens University Hospital. Patients under mechanical ventilation following cardiac surgery were enrolled. Doppler evaluation of the portal vein (PV) was performed by transthoracic echography. The maximum velocity (VMAX) and minimum velocity (VMIN) of the PV were measured in pulsed Doppler mode. The PI was calculated using the following formula (VMAX - VMIN)/(VMax). A positive end-expiratory pressure (PEEP) incremental trial was performed from 0 to 15 cmH2O, with increments of 5 cmH2O. The PI (%) was assessed at baseline and PEEP 5, 10, and 15 cmH2O. Echocardiographic and hemodynamic parameters were recorded. RESULTS: In total, 144 patients were screened from February 2018 to March 2019 and 29 were enrolled. Central venous pressure significantly increased for each PEEP increment. Stroke volumes were significantly lower after PEEP incrementation, with 52 mL (50-55) at PEEP 0 cmH2O and 30 mL (25-45) at PEEP 15 cmH2O, (p < 0.0001). The PI significantly increased with PEEP incrementation, from 9% (5-15) at PEEP 0 cmH2O to 15% (5-22) at PEEP 5 cmH2O, 34% (23-44) at PEEP 10 cmH2O, and 45% (25-49) at PEEP 15 cmH2O (p < 0.001). CONCLUSION: In the present study, PI appears to be a dynamic marker of the interaction between mechanical ventilation and right heart pressure after cardiac surgery. The PI could be a useful noninvasive tool to monitor venous congestion associated with mechanical ventilation.

Effect of the oXiris membrane on microcirculation after cardiac surgery under cardiopulmonary bypass: study protocol for a randomised controlled trial (OXICARD Study).

INTRODUCTION: Cytokine storm and endotoxin release during cardiac surgery with cardiopulmonary bypass (CPB) have been related to vasoplegic shock and organ dysfunction. We hypothesised that early (during CPB) cytokine adsorption with oXiris membrane for patients at high risk of inflammatory syndrome following cardiac surgery may improve microcirculation, endothelial function and outcomes. METHODS AND ANALYSIS: The Oxicard trial is a prospective, monocentric trial, randomising 70 patients scheduled for cardiac surgery. The inclusion criterion is patients aged more than 18 years old undergoing elective cardiac surgery under CPB with an expected CPB time >90 min (double valve replacement or valve replacement plus coronary arterial bypass graft). Patients will be allocated to the intervention group (n=35) or the control group (n=35). In the intervention group, oXiris membrane will be used on the Prismaflex device (Baxter) at blood pump flow of 450 mL/min during cardiac surgery under CPB. In the control group, cardiac surgery under CPB will be conducted as usual without oXiris membrane. An intention-to-treat analysis will be performed. The primary endpoint will be the microcirculatory flow index measured by sublingual microcirculation device at day 1 following cardiac surgery. The secondary endpoints will be other microcirculation variables at CPB end, 6 hours after CPB, at day 1 and at day 2. We also aim to evaluate the occurrence of major cardiovascular and cerebral events (eg, myocardial infarction, stroke, ischaemic mesenteric, resuscitated cardiac arrest, acute kidney injury) within the first 30 days. Cumulative catecholamine use, intensive care unit length of stay, endothelium glycocalyx shedding parameters (syndecan-1, heparan-sulfate and hyaluronic acid), inflammatory cytokines (tumour necrosis factor (TNF) alpha, interleukin 1 (IL1) beta, IL 10, IL 6, lipopolysaccharide, endothelin) and endothelial permeability biomarkers (angiopoietin 1, angiopoietin 2, Tie2 soluble receptor and Vascular Endothelial Growth Factor (VEGF) will also be evaluated. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Institutional Review Board of the University Hospital of Amiens (registration number ID RDB: 2019-A02437-50 in February 2020). Results of the study will be disseminated via peer-reviewed publications and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT04201119.

Almitrine for COVID-19 critically ill patients - a vascular therapy for a pulmonary vascular disease: Three case reports.

BACKGROUND: Several reports with clinical, histological and imaging data have observed the involvement of lung vascular function to explain the severe hypoxemia in coronavirus disease 2019 (COVID-19) patients. It has been hypothesized that an increased pulmonary blood flow associated with an impairment of hypoxic pulmonary vasoconstriction is responsible for an intrapulmonary shunt. COVID-19 may lead to refractory hypoxemia (PaO2/FiO2 ratio below 100 mmHg) despite mechanical ventilation and prone positioning. We hypothesized that the use of a pulmonary vasoconstrictor may help decrease the shunt and thus enhance oxygenation. CASE SUMMARY: We report our experience with three patients with refractory hypoxemia treated with almitrine to enhance oxygenation. Low dose almitrine (Vectarion®; Servier, Suresnes, France) was started at an infusion rate of 4 µg × kg/min on a central line. The PaO2/FiO2 ratio and total respiratory system compliance during almitrine infusion were measured. For the three patients, the PaO2/FiO2 ratio time-course showed a dramatic increase whereas total respiratory system compliance was unchanged. The three patients were discharged from the intensive care unit. The intensive care unit length of stay for patient 1, patient 2 and patient 3 was 30 d, 32 d and 31 d, respectively. Weaning from mechanical ventilation was performed 13 d, 18 d and 15 d after almitrine infusion for patient 1, 2 and 3, respectively. We found no deleterious effects on the right ventricular function, which was similar to previous studies on almitrine safety. CONCLUSION: Almitrine may be effective and safe to enhance oxygenation in coronavirus disease 2019 patients. Further controlled studies are required.

Hemodynamic impact of molecular adsorbent recirculating system in refractory vasoplegic shock due to calcium channel blocker poisoning.

OBJECTIVE: To report the hemodynamic effect of to the molecular adsorbent recirculating system (MARS™) therapy for patients in refractory vasoplegic shock due to calcium channel blocker (CCB) poisoning. METHODS: We report a retrospective cohort of patients who were hospitalized for CCB poisoning with refractory vasoplegic shock and treated by MARS therapy, at Amiens Hospital University, from January 2010 to December 2019. Improvement in hemodynamic was assessed by dynamic changes in mean arterial pressure (MAP) and norepinephrine levels over a 24-h period after MARS therapy. Cardiac function was assessed by transthoracic echocardiography. RESULTS: MARS therapy was performed on seven patients for CCB poisoning. CCB poisoning included nicardipine (n = 3, 43%) amlodipine (n = 3, 43%), and verapamil (n = 1, 14%). The median time to start MARS therapy was 24 [14-27] h after drug ingestion and 6 [2-9] h after ICU admission. Cardiac output was preserved for all patients. MAP values improved from 56 [43-58] to 65 [61-78] 16 mmHg (p = 0.005). Norepinephrine dose significantly decreased from 3.2 [0.8-10] µg/kg/min to 1.2 [0.1-1.9] µg/kg/min (p = 0.008) and lactate level decreased from 3.2 [2.4-3.4] mmol/l-1 to 1.6 [0.9-2.2] mmol/l-1 (p = 0.008). The median length of ICU stay was 4 (2-7) days and hospital stay was 4 (4-16) days. No complication related to the MARS therapy were reported. No patient died and all were discharged from the hospital. CONCLUSION: We reported the largest case-series of MARS therapy for refractory vasoplegic shock due to CCB poisoning. We observed that MARS therapy was associated with an improvement of hemodynamic parameters.

Changes in Plasma Angiopoietin Levels After Transcatheter Aortic Valve Replacement and Surgical Aortic Valve Replacement: A Prospective Cohort Study.

OBJECTIVE: Angiopoietins (Angs) regulate endothelial permeability. Ang-1 and 2 (Ang-1 and Ang-2) are implied in endothelial stability through an antagonism effect. The objectives of the present study were to describe and compare changes in Ang levels after transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). DESIGN: A prospective, single-center study. PARTICIPANTS: Adult patients with aortic stenosis scheduled for SAVR or TAVR. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ang-1 and Ang-2 were measured using an enzyme-linked immunosorbent assay right before surgery (T0), at the end of surgery (T1), and at day one (T2). Sixty consecutive patients (SAVR group [n = 30] and TAVR group [n = 30]) were included between January and June 2017. Ang-1 decreased significantly after both TAVR (T0: 3,663 [2,602-4,262]; T1: 1,611 [981-2,409]; T2: 1,082 [652-1,589] ng/mL; p < 0.0001) and SAVR (T0: 1,603 [975-2,849]; T1: 783 [547-1,024]; T2: 828 [460-1,227] ng/mL; p = 0.0001). Ang-2 increased significantly after SAVR (T0: 2,472 [1,502-3,622]; T1: 2,997 [1,759-3,839]; T2: 5,421 [3,557-7,087] ng/mL; p < 0.0001) but did not change markedly after TAVR (T0: 3,343 [2,661-6,272]; T1: 3,788 [2,574-5,016]; T2: 3,446 [3,029-6,313] ng/mL; p = 0.066). Among patients with paravalvular leakage, the changes in the plasma Ang-2 level and the Ang-2/Ang-1 ratio were greater. CONCLUSION: SAVR induces greater alterations of Ang homeostasis than TAVR, confirming a role for the use of cardiopulmonary bypass. Paravalvular leakage after TAVR is associated with Ang changes similar to those observed with SAVR.

Microvascular flow alterations in critically ill COVID-19 patients: A prospective study.

BACKGROUND: Data on microcirculatory pattern of COVID-19 critically ill patients are scarce. The objective was to compare sublingual microcirculation parameters of critically ill patients according to the severity of the disease. METHODS: The study is a single-center prospective study with critically ill COVID-19 patients admitted in ICU. Sublingual microcirculation was assessed by IDF microscopy within 48 hours of ICU admission. Microcirculatory flow index (MFI), proportion of perfused vessel (PPV), total vessel density (TVD), De Backer score (DBS), perfused vessel density (PVD) and heterogeneity index (HI) were assessed. Patients were divided in 2 groups (severe and critical) according to the World health organization definition. FINDINGS: From 19th of March to 7th of April 2020, 43 patients were included. Fourteen patients (33%) were in the severe group and twenty-nine patients (67%) in the critical group. Patients in the critical group were all mechanically ventilated. The critical group had significantly higher values of MFI, DBS and PVD in comparison to severe group (respectively, PaCO2: 49 [44-45] vs 36 [33-37] mmHg; p<0,0001, MFI: 2.8 ± 0.2 vs 2.5 ± 0.3; p = 0.001, DBS: 12.7 ± 2.6 vs 10.8 ± 2.0 vessels mm-2; p = 0.033, PVD: 12.5 ± 3.0 vs 10.1 ± 2.4 mm.mm-2; p = 0.020). PPV, HI and TVD were similar between groups Correlation was found between microcirculatory parameters and PaCO2 levels. CONCLUSION: Critical COVID-19 patients under mechanical ventilation seem to have higher red blood cell velocity than severe non-ventilated patients.