Refractory cor pulmonale under extracorporeal membrane oxygenation for acute respiratory distress syndrome: the role of conversion to veno-pulmonary arterial assist-a case series.

Introduction: Pulmonary vascular dysfunction during severe acute respiratory distress syndrome (ARDS) may lead to right ventricle (RV) dysfunction and acute cor pulmonale (ACP). The occurrence/persistence of ACP despite conventional extracorporeal membrane oxygenation (ECMO) is a challenging situation. We explored the usefulness of a specific dual-lumen cannula that bypasses the RV, and on which a veno-pulmonary arterial assist (V-P ECMO) was mounted, in ARDS patients. Methods: We report a case-series of ARDS patients put on conventional veno-arterial or veno-venous ECMO and presented refractory ACP as an indication for a reconfiguration to V-P ECMO using the ProtekDuo cannula. The primary endpoint was the mitigation of RV and pulmonary vascular dysfunction as assessed by the change in end-diastolic RV/left ventricle (LV) surface ratio. Results: Six patients had their conventional ECMO reconfigured to V-P ECMO to treat refractory ACP. There was a decrease in end-diastolic RV/LV surface ratio, as well as end-systolic LV eccentricity index, and lactatemia immediately after V-P ECMO initiation. The resolution of refractory ACP was immediately achieved in four of our six (66%) patients. The V-P ECMO was weaned after a median of 26 [8-93] days after implantation. All but one patient were discharged home. We detected one case of severe hemolysis with V-P ECMO and two suspected cases of right-sided infective endocarditis. Conclusion: V-P ECMO is useful to mitigate RV overload and to improve hemodynamics in case of refractory ACP despite conventional ECMO.

Effect of volume infusion on left atrial strain in acute circulatory failure.

BACKGROUND: Left atrial strain (LAS) is a measure of atrial wall deformation during cardiac cycle and reflects atrial contribution to cardiovascular performance. Pathophysiological significance of LAS in critically ill patients with hemodynamic instability has never been explored. This study aimed at describing LAS and its variation during volume expansion and to assess the relationship between LAS components and fluid responsiveness. METHODS: This prospective observational study was performed in a French ICU and included patients with acute circulatory failure, for whom the treating physician decided to proceed to volume expansion (rapid infusion of 500 mL of crystalloid solution). Trans-thoracic echocardiography was performed before and after the fluid infusion. LAS analysis was performed offline. Fluid responsiveness was defined as an increase in velocity-time integral (VTI) of left ventricular outflow tract ≥ 10%. RESULTS: Thirty-eight patients were included in the final analysis. Seventeen (45%) patients were fluid responders. LAS analysis had a good feasibility and reproducibility. Overall, LAS was markedly reduced in all its components, with values of 19 [15 - 32], -9 [-19 - -7] and - 9 [-13 - -5] % for LAS reservoir (LASr), conduit (LAScd) and contraction (LASct), respectively. LASr, LAScd and LASct significantly increased during volume expansion in the entire population. Baseline value of LAS did not predict fluid responsiveness and the changes in LAS and VTI during volume expansion were not significantly correlated. CONCLUSIONS: LAS is severely altered during acute circulatory failure. LAS components significantly increase during fluid administration, but cannot be used to predict or assess fluid responsiveness.

Bleeding complications, coagulation disorders, and their management in acute myocardial infarction-related cardiogenic shock rescued by veno-arterial ECMO: A retrospective cohort study.

PURPOSE: Management of dual antiplatelet therapy (DAPT) in patients on venoarterial-extracorporeal membrane (VA-ECMO) after acute myocardial infarction (AMI) is challenging. Our objective was to describe the frequency, management and outcomes of severe bleeding complications and determine their occurrence risk factors. MATERIAL AND METHODS: We conducted a retrospective observational cohort study including post-AMI cardiogenic shock patients requiring VA-ECMO. Severe bleeding was defined based on the Bleeding Academic Research Consortium classification. We calculated multivariable Fine-Gray models to assess factors associated with risk of severe bleeding. RESULTS: From January 2015 to July 2019, 176 patients received VA-ECMO after AMI and 132 patients were included. Sixty-five (49%) patients died. Severe bleeding occurred in 39% of cases. Severe thrombocytopenia (< 50 G/L) and hypofibrinogenemia (<1,5 g/L) occurred in respectively 31% and 19% of patients. DAPT was stopped in 32% of patients with a 6% rate of stent thrombosis. Anticoagulation was stopped in 39% of patients. Using a multivariate competing risk model, female sex, time on ECMO, troponin at admission and Impella® implantation were independently associated with severe bleeding. CONCLUSIONS: Bleeding complications and coagulation disorders were frequent and severe in patients on VA-ECMO after AMI, leading of antiplatelet therapy withdrawal in one third of patients.

Antibiotic definitive treatment in ventilator associated pneumonia caused by AmpC-producing Enterobacterales in critically ill patients: a prospective multicenter observational study.

BACKGROUND: Ventilator associated pneumonia (VAP) due to wild-type AmpC-producing Enterobacterales (wtAE) is frequent in intensive care unit (ICU) patients. Despite a low level of evidence, definitive antimicrobial therapy (AMT) with third generation cephalosporins (3GCs) or piperacillin is discouraged. METHODS: Observational prospective study including consecutive wtAE VAP patients in 20 French ICUs. The primary objective was to assess the association of the choice of definitive AMT, i.e. piperacillin ± tazobactam (PTZ), 3GCs or other molecule (4GCs, carbapenems, quinolones, cotrimoxazole; control group), with treatment success at day-7. Recurrence of infection was collected as a secondary outcome, and analyzed accounting for the competing risk of death. RESULTS: From February 2021 to June 2022, 274 patients were included. Enterobacter cloacae was the most prevalent specie (31%). Seventy-eight patients (28%) had PTZ as definitive AMT while 44 (16%) had 3GCs and 152 (56%) were classified in the control group. Day-7 success rate was similar between the 3 groups (74% vs. 73% vs. 68% respectively, p = 0.814). Recurrence probability at day-28 was 31% (95% CI 21-42), 40% (95% CI 26-55) and 21% (95% CI 15-28) for PTZ, 3GCs and control groups (p = 0.020). In multivariable analysis, choice of definitive AMT was not associated with clinical success, but definitive AMT with 3GCs was associated with recurrence at day-28 [csHR(95%CI) 10.9 (1.92-61.91)]. CONCLUSION: Choice of definitive antimicrobial therapy was not associated with treatment success at day 7. However, recurrence of pneumonia at day-28 was higher in patients treated with third generation cephalosporins with no differences in mortality or mechanical ventilation duration.

Dual titration of minute ventilation and sweep gas flow to control carbon dioxide variations in patients on venovenous extracorporeal membrane oxygenation.

BACKGROUND: The implantation of venovenous extracorporeal membrane oxygenation (VV-ECMO) support to manage severe acute respiratory distress syndrome generates large variations in carbon dioxide partial pressure (PaCO2) that are associated with intracranial bleeding. We assessed the feasibility and efficacy of a pragmatic protocol for progressive dual titration of sweep gas flow and minute ventilation after VV-ECMO implantation in order to limit significant PaCO2 variations. PATIENTS AND METHODS: A protocol for dual titration of sweep gas flow and minute ventilation following VV-ECMO implantation was implemented in our unit in September 2020. In this single-centre retrospective before-after study, we included patients who required VV-ECMO from March, 2020 to May, 2021, which corresponds to two time periods: from March to August, 2020 (control group) and from September, 2020 to May, 2021 (protocol group). The primary endpoint was the mean absolute change in PaCO2 in consecutive arterial blood gases samples drawn over the first 12 h following VV-ECMO implantation. Secondary endpoints included large (> 25 mmHg) initial variations in PaCO2, intracranial bleedings and mortality in both groups. RESULTS: Fifty-one patients required VV-ECMO in our unit during the study period, including 24 in the control group and 27 in the protocol group. The protocol was proved feasible. The 12-h mean absolute change in PaCO2 was significantly lower in patients of the protocol group as compared with their counterparts (7 mmHg [6-12] vs. 12 mmHg [6-24], p = 0.007). Patients of the protocol group experienced less large initial variations in PaCO2 immediately after ECMO implantation (7% vs. 29%, p = 0.04) and less intracranial bleeding (4% vs. 25%, p = 0.04). Mortality was similar in both groups (35% vs. 46%, p = 0.42). CONCLUSION: Implementation of our protocol for dual titration of minute ventilation and sweep gas flow was feasible and associated with less initial PaCO2 variation than usual care. It was also associated with less intracranial bleeding.

Cardiac and vascular effects of low-dose steroids during the early phase of septic shock: An echocardiographic study.

Background: Low-dose steroids are known to increase arterial pressure during septic shock through restoration of vasopressor response to norepinephrine. However, their effects on cardiac performance and ventriculo-arterial coupling (VAC) have never been scrutinized during human septic shock. The aim of this study was to perform a comprehensive description of the cardiovascular effects of low-dose steroids using modern echocardiographic tools (including speckle tracking imaging). Methods: This prospective study was conducted in the intensive care unit (ICU) of a university hospital in France. Consecutive adult patients admitted for septic shock and requiring low-dose steroid therapy were prospectively enrolled within 24 h of septic shock onset. We recorded hemodynamic and echocardiographic data to explore left ventricle (LV) contractility, loading conditions and VAC just before the initiation of low-dose steroids (50 mg intravenous hydrocortisone plus 50 µg enteral fludrocortisone) and 2-4 h after. Results: Fifty patients [65 (55-73) years; 33 men] were enrolled. Arterial pressure, heart rate, almost all LV afterload parameters, and most cardiac contractility parameters significantly improved after steroids. VAC improved with steroid therapy and less patients had uncoupled VAC (> 1.36) after (24%) than before (44%) treatment. Conclusion: In this comprehensive echocardiographic study, we confirmed an improvement of LV afterload after initiation of low-dose steroids. We also observed an increase in LV contractility with improved cardiovascular efficiency (less uncoupling with decreased VAC).

Echocardiography findings in COVID-19 patients admitted to intensive care units: a multi-national observational study (the ECHO-COVID study).

PURPOSE: Severely ill patients affected by coronavirus disease 2019 (COVID-19) develop circulatory failure. We aimed to report patterns of left and right ventricular dysfunction in the first echocardiography following admission to intensive care unit (ICU). METHODS: Retrospective, descriptive study that collected echocardiographic and clinical information from severely ill COVID-19 patients admitted to 14 ICUs in 8 countries. Patients admitted to ICU who received at least one echocardiography between 1st February 2020 and 30th June 2021 were included. Clinical and echocardiographic data were uploaded using a secured web-based electronic database (REDCap). RESULTS: Six hundred and seventy-seven patients were included and the first echo was performed 2 [1, 4] days after ICU admission. The median age was 65 [56, 73] years, and 71% were male. Left ventricle (LV) and/or right ventricle (RV) systolic dysfunction were found in 234 (34.5%) patients. 149 (22%) patients had LV systolic dysfunction (with or without RV dysfunction) without LV dilatation and no elevation in filling pressure. 152 (22.5%) had RV systolic dysfunction. In 517 patients with information on both paradoxical septal motion and quantitative RV size, 90 (17.4%) had acute cor pulmonale (ACP). ACP was associated with mechanical ventilation (OR > 4), pulmonary embolism (OR > 5) and increased PaCO2. Exploratory analyses showed that patients with ACP and older age were more likely to die in hospital (including ICU). CONCLUSION: Almost one-third of this cohort of critically ill COVID-19 patients exhibited abnormal LV and/or RV systolic function in their first echocardiography assessment. While LV systolic dysfunction appears similar to septic cardiomyopathy, RV systolic dysfunction was related to pressure overload due to positive pressure ventilation, hypercapnia and pulmonary embolism. ACP and age seemed to be associated with mortality in this cohort.

Acute Kidney Injury in Critically-Ill COVID-19 Patients.

Purpose: Acute kidney injury (AKI) is common in patients with COVID-19, however, its mechanism is still controversial, particularly in ICU settings. Urinary proteinuria profile could be a non-invasive tool of interest to scrutinize the pathophysiological process underlying AKI in COVID-19 patients. Material and Methods: We conducted a retrospective study between March 2020 and April 2020. All patients with laboratory-confirmed COVID-19 and without end-stage kidney disease requiring renal replacement therapy before ICU admission were included. Our objectives were to assess the incidence and risk factors for AKI and to describe its clinical and biological characteristics, particularly its urinary protein profile. Results: Seventy patients were included; 87% needed mechanical ventilation and 61% needed vasopressor during their ICU stay; 64.3% of patients developed AKI and half of them needed dialysis. Total and tubular proteinuria on day 1 were higher in patients with AKI, whereas glomerular proteinuria was similar in both groups. The main risk factor for AKI was shock at admission (OR = 5.47 (1.74−17.2), p < 0.01). Mortality on day 28 was higher in AKI (23/45, 51.1%) than in no-AKI patients (1/25, 4%), p < 0.001. Risk factors for 28-days mortality were AKI with need for renal replacement therapy, non-renal SOFA score and history of congestive heart failure. Conclusions: AKI is common in COVID-19 patients hospitalized in ICU; it seems to be related to tubular lesions rather than glomerular injury and is related to shock at ICU admission.

Percutaneous angio-guided versus surgical veno-arterial ECLS implantation in patients with cardiogenic shock or cardiac arrest.

BACKGROUND: Veno-arterial Extracorporeal Life Support (V-A ECLS) has gained increasing place into the management of patients with refractory cardiogenic shock or cardiac arrest. Both surgical and percutaneous approach can be used for cannulation, but percutaneous approach has been associated with fewer complications. Angio-guided percutaneous cannulation and decannulation may further decrease the rate of complication. We aimed to compare outcome and complication rates in patients supported with V-A ECLS through percutaneous angio-guided versus surgical approach. METHODS: We included all patients with emergent peripheral femoro-femoral V-A ECLS implantation for refractory cardiogenic shock or cardiac arrest in our center from March 2018 to March 2021. Survival and major complications (major bleeding, limb ischemia and groin infection) rates were compared between the percutaneous angio-guided and the surgical groups. RESULTS: One hundred twenty patients received V-A ECLS, 59 through surgical approach and 61 through angio-guided percutaneous approach. Patients' baseline characteristics and severity scores were equally balanced between the 2 groups. Thirty-day mortality was not significantly different between the 2 approaches. However, angio-guided percutaneous cannulation was associated with fewer major vascular complications (42% vs. 11%, p > 0.0001) and a higher rate of V-A ECLS decannulation. In multivariate analysis, percutaneous angio-guided implantation of V-A ECLS was independently associated with a lower probability of major complications. CONCLUSION: Compared to surgical approach, angio-guided percutaneous V-A ECLS implantation is associated with fewer major vascular complications. Larger studies are needed to confirm those results and address their impact on mortality.

Aortic Root Anatomy Is Related to the Bicuspid Aortic Valve Phenotype.

BACKGROUND: Bicuspid aortic valve (BAV) is associated with an asymmetric (not circular) aortic root, resulting in variability in the aortic root diameter measurements obtained using different techniques. The objective of this study was to describe aortic root asymmetry, including its orientation in the thorax, in relation to the various phenotypes of BAV and its impact on aortic root diameter measurements obtained using transthoracic echocardiography. METHODS: Aortic root asymmetry, orientation of the largest root diameter, and orientation of the valve opening were studied using computed tomographic scans of patients with BAV without significant aortic valve dysfunction referred for evaluation of a thoracic aortic aneurysm. Eighty-five patients with BAV were evaluated; BAV with fusion of the left and the right coronary cusps (L-R BAV), with or without raphe (n = 63), was compared with BAV with fusion of the right coronary and noncoronary cusps (N-R BAV), with or without raphe (n = 22). RESULTS: Asymmetry of the aortic root and its orientation in the thorax can be predicted from BAV phenotype: orientation of the valve opening differed from orientation of the largest root diameter by nearly 75° in both groups. The angle of the largest root diameter with the reference sagittal plane was 64.3° in the L-R BAV group versus 143.1° in the N-R BAV group (P < .0001). Therefore, using the parasternal long-axis view on transthoracic echocardiography, in N-R BAV, the ultrasound beam is roughly parallel to the valve opening orientation and almost orthogonal to the maximum diameter of the root. On the contrary, in L-R BAV, the ultrasound beam is roughly perpendicular to the valve opening orientation and almost parallel to the maximum diameter of the root. Consequently, the parasternal long-axis view on transthoracic echocardiography significantly underestimates maximal aortic root diameter in N-R BAV and modestly underestimates root diameter in L-R BAV (-6.1 ± 0.96 vs -2.3 ± 0.47 mm, P = .0008). CONCLUSIONS: Aortic root morphology in patients with BAV can be predicted by BAV phenotype: the largest root diameter is roughly perpendicular to the orientation of the valve opening. Therefore, echocardiographic measurements according to present recommendations (parasternal long-axis view) underestimate maximal diameter in patients with N-R BAV.

ECT-induced cognitive side effects are associated with hippocampal enlargement.

Electroconvulsive therapy (ECT) is of the most effective treatments available for treatment-resistant depression, yet it is underutilized in part due to its reputation of causing cognitive side effects in a significant number of patients. Despite intensive neuroimaging research on ECT in the past two decades, the underlying neurobiological correlates of cognitive side effects remain elusive. Because the primary ECT-related cognitive deficit is memory impairment, it has been suggested that the hippocampus may play a crucial role. In the current study, we investigated 29 subjects with longitudinal MRI and detailed neuropsychological testing in two independent cohorts (N = 15/14) to test if volume changes were associated with cognitive side effects. The two cohorts underwent somewhat different ECT study protocols reflected in electrode placements and the number of treatments. We used longitudinal freesurfer algorithms (6.0) to obtain a bias-free estimate of volume changes in the hippocampus and tested its relationship with neurocognitive score changes. As an exploratory analysis and to evaluate how specific the effects were to the hippocampus, we also calculated this relationship in 41 other areas. In addition, we also analyzed cognitive data from a group of healthy volunteers (N = 29) to assess practice effects. Our results supported the hypothesis that hippocampus enlargement was associated with worse cognitive outcomes, and this result was generalizable across two independent cohorts with different diagnoses, different electrode placements, and a different number of ECT sessions. We found, in both cohorts, that treatment robustly increased the volume size of the hippocampus (Cohort 1: t = 5.07, Cohort 2: t = 4.82; p < 0.001), and the volume increase correlated with the neurocognitive T-score change. (Cohort 1: r = -0.68, p = 0.005; Cohort 2: r = -0.58; p = 0.04). Overall, our research indicates that novel treatment methods serving to avoid hippocampal volume increase may result in a better side effect profile.

Extracorporeal Membrane Oxygenation Induces Early Alterations in Coagulation and Fibrinolysis Profiles in COVID-19 Patients with Acute Respiratory Distress Syndrome.

Hemostatic changes induced by extracorporeal membrane oxygenation (ECMO) support have been yet poorly documented in coronavirus-19 (COVID-19) patients who have a baseline complex hypercoagulable state. In this prospective monocentric study of patients with severe acute respiratory distress syndrome (ARDS) rescued by ECMO, we performed longitudinal measurements of coagulation and fibrinolysis markers throughout the course of ECMO support in 20 COVID-19 and 10 non-COVID-19 patients. Blood was sampled before and then 24 hours, 7, and 14 days after ECMO implantation. Clinical outcomes were prospectively assessed until discharge from the intensive care unit or death. The median age of participants was 47 (35-56) years, with a median body mass index of 30 (27-35) kg/m2, and a Sepsis-related Organ Failure Assessment score of 12 (8-16). Baseline levels of von Willebrand factor, fibrinogen, factor VIII, prothrombin F1 + 2, thrombin-antithrombin, D-dimer, and plasminogen activator inhibitor-1 (PAI-1) were elevated in both COVID-19 and non-COVID-19 ARDS patients, indicating that endothelial activation, endogenous thrombin generation, and fibrinolysis shutdown occur in all ARDS patients before ECMO implantation. From baseline to day 7, thrombin generation (prothrombin F1 + 2, p < 0.01) and fibrin formation markers (fibrin monomers, p < 0.001) significantly increased, further resulting in significant decreases in platelet count (p < 0.0001) and fibrinogen level (p < 0.001). PAI-1 levels significantly decreased from baseline to day 7 (p < 0.0001) in all ARDS patients. These changes were more marked in COVID-19 patients, resulting in 14 nonfatal and 3 fatal bleeding. Additional studies are warranted to determine whether monitoring of thrombin generation and fibrinolysis markers might help to early predict bleeding complications in COVID-19 patients supported by ECMO.

Arrhythmia-induced cardiomyopathy: A potentially reversible cause of refractory cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation.

BACKGROUND: The most severe form of arrhythmia-induced cardiomyopathy in adults- refractory cardiogenic shock requiring mechanical circulatory support-has rarely been reported. OBJECTIVE: The purpose of this study was to describe the management of critically ill patients admitted for acute, nonischemic, or worsening of previously known cardiac dysfunction and recent-onset supraventricular arrhythmia who developed refractory cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation (VA-ECMO). METHODS: This study is a retrospective analysis of prospectively collected data. RESULTS: Between 2004 and 2018, 35 patients received VA-ECMO for acute, nonischemic cardiogenic shock and recent supraventricular arrhythmia (77% atrial fibrillation [AF]). Cardiogenic shock was the first disease manifestation in 21 patients (60%). Characteristics at ECMO implantation [median (interquartile range)] were Sequential Organ Failure Assessment score 10 (7-13); inotrope score 29 (11-80); left ventricular ejection (LVEF) fraction 10% (10%-15%); and lactate level 8 (4-11) mmol/L. For 12 patients, amiodarone and/or electric cardioversion successfully reduced arrhythmia, improved LVEF, and enabled weaning off VA-ECMO; 11 had long-term survival without transplantation or long-term assist device. Eight patients experiencing arrhythmia-reduction failure underwent ablation procedures (7 atrioventricular node [AVN] with pacing, 1 atrial tachycardia) and were weaned off VA-ECMO; 7 survived. Of the remaining 15 patients without arrhythmia reduction or ablation, only the 6 bridged to heart transplantation or left ventricular (LV) assist device survived. CONCLUSION: Arrhythmia-induced cardiomyopathy, mainly AF-related, is an underrecognized cause of refractory cardiogenic shock and should be considered in patients with nonischemic cardiogenic shock and recent-onset supraventricular arrhythmia. VA-ECMO support allowed safe arrhythmia reduction or rate control by AVN ablation while awaiting recovery, even among those with severe LV dilation.

Advanced echocardiographic phenotyping of critically ill patients with coronavirus-19 sepsis: a prospective cohort study.

BACKGROUND: Sepsis is characterized by various hemodynamic alterations which could happen concomitantly in the heart, pulmonary and systemic circulations. A comprehensive demonstration of their interactions in the clinical setting of COVID-19 sepsis is lacking. This study aimed at evaluating the feasibility, clinical implications, and physiological coherence of the various indices of hemodynamic function and acute myocardial injury (AMI) in COVID-19 sepsis. METHODS: Hemodynamic and echocardiographic data of septic critically ill COVID-19 patients were prospectively recorded. A dozen hemodynamic indices exploring contractility and loading conditions were assessed. Several cardiac biomarkers were measured, and AMI was considered if serum concentration of high-sensitive troponin T (hs-TNT) was above the 99th percentile, upper reference. RESULTS: Sixty-seven patients were assessed (55 males), with a median age of 61 [50-70] years. Overall, the feasibility of echocardiographic parameters was very good, ranging from 93 to 100%. Hierarchical clustering method identified four coherent clusters involving cardiac preload, left ventricle (LV) contractility, LV afterload, and right ventricle (RV) function. LV contractility indices were not associated with preload indices, but some of them were positively correlated with RV function parameters and negatively correlated with a single LV afterload parameter. In most cases (n = 36, 54%), echocardiography results prompted therapeutic changes. Mortality was not influenced by the echocardiographic variables in multivariable analysis. Cardiac biomarkers' concentrations were most often increased with high incidence of AMI reaching 72%. hs-TNT was associated with mortality and inversely correlated with most of LV and RV contractility indices. CONCLUSIONS: In this comprehensive hemodynamic evaluation in critically ill COVID-19 septic patients, we identified four homogeneous and coherent clusters with a good feasibility. AMI was common and associated with alteration of LV and RV functions. Echocardiographic assessment had a clinical impact on patient management in most cases.

Rescue therapy with inhaled nitric oxide and almitrine in COVID-19 patients with severe acute respiratory distress syndrome.

BACKGROUND: In COVID-19 patients with severe acute respiratory distress syndrome (ARDS), the relatively preserved respiratory system compliance despite severe hypoxemia, with specific pulmonary vascular dysfunction, suggests a possible hemodynamic mechanism for VA/Q mismatch, as hypoxic vasoconstriction alteration. This study aimed to evaluate the capacity of inhaled nitric oxide (iNO)-almitrine combination to restore oxygenation in severe COVID-19 ARDS (C-ARDS) patients. METHODS: We conducted a monocentric preliminary pilot study in intubated patients with severe C-ARDS. Respiratory mechanics was assessed after a prone session. Then, patients received iNO (10 ppm) alone and in association with almitrine (10 µg/kg/min) during 30 min in each step. Echocardiographic and blood gases measurements were performed at baseline, during iNO alone, and iNO-almitrine combination. The primary endpoint was the variation of oxygenation (PaO2/FiO2 ratio). RESULTS: Ten severe C-ARDS patients were assessed (7 males and 3 females), with a median age of 60 [52-72] years. Combination of iNO and almitrine outperformed iNO alone for oxygenation improvement. The median of PaO2/FiO2 ratio varied from 102 [89-134] mmHg at baseline, to 124 [108-146] mmHg after iNO (p = 0.13) and 180 [132-206] mmHg after iNO and almitrine (p < 0.01). We found no correlation between the increase in oxygenation caused by iNO-almitrine combination and that caused by proning. CONCLUSION: In this pilot study of severe C-ARDS patients, iNO-almitrine combination was associated with rapid and significant improvement of oxygenation. These findings highlight the role of pulmonary vascular function in COVID-19 pathophysiology.