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.

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.

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.

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.

Central venous-to-arterial CO2 difference is a poor tool to predict adverse outcomes after cardiac surgery: a retrospective study.

PURPOSE: The venous-to-arterial carbon dioxide partial pressure difference (CO2 gap) has been reported to be a sensitive indicator of cardiac output adequacy. We aimed to assess whether the CO2 gap can predict postoperative adverse outcomes after cardiac surgery. METHODS: A retrospective study was conducted of 5,151 patients from our departmental database who underwent cardiac surgery from 1 January 2008 to 31 December 2018. Lactate level (mmol·L-1), central venous oxygen saturation (ScVO2) (%), and the venous-to-arterial carbon dioxide difference (CO2 gap) were measured at intensive care unit (ICU) admission and on days 1 and 2 after cardiac surgery. The following postoperative adverse outcomes were collected: ICU mortality, hemopericardium or tamponade, resuscitated cardiac arrest, acute kidney injury, major bleeding, acute hepatic failure, mesenteric ischemia, and pneumonia. The primary outcome was the presence of at least one postoperative adverse outcome. Logistic regression was used to assess the association between ScVO2, lactate, and the CO2 gap with adverse outcomes. Their diagnostic performance was compared using a receiver operating characteristic (ROC) curve. RESULTS: There were 1,933 patients (38%) with an adverse outcome. Cardiopulmonary bypass (CPB) parameters were similar between groups. The CO2 gap was slightly higher for the "adverse outcomes" group than for the "no adverse outcomes" group. Arterial lactate at admission, day 1, and day 2 was also slightly higher in patients with adverse outcomes. Central venous oxygen saturation was not significantly different between patients with and without adverse outcomes. The area under the ROC curve to predict outcomes after CPB for the CO2 gap at admission, day 1, and day 2 were 0.52, 0.55, and 0.53, respectively. CONCLUSION: After cardiac surgery with CPB, the CO2 gap at ICU admission, day 1, and day 2 was associated with postoperative adverse outcomes but showed poor diagnostic performance.

RéSUMé: OBJECTIF: La différence de pression partielle de dioxyde de carbone veineux versus artériel (gradient de CO2) a été rapportée comme étant un indicateur sensible d'un débit cardiaque adéquat. Nous avons tenté d'évaluer si le gradient de CO2 pouvait prédire les devenirs postopératoires défavorables après une chirurgie cardiaque. MéTHODE: Une étude rétrospective a été réalisée en se basant sur les dossiers de 5151 patients issus de notre base de données départementale ayant subi une chirurgie cardiaque entre le 1er janvier 2008 et le 31 décembre 2018. Les taux de lactate (mmol·L−1), la saturation en oxygène veineux central (ScVO2) (%), et la différence de dioxyde de carbone veineux versus artériel (gradient de CO2) ont été mesurés lors de l'admission en réanimation (ICU) et aux jours 1 et 2 après la chirurgie cardiaque. Les complications postopératoires suivantes ont été colligées : mortalité en réanimation, hémopéricarde ou tamponnade, arrêt cardiaque récupéré, insuffisance rénale aiguë, saignements majeurs, insuffisance hépatique aiguë, ischémie mésentérique et pneumonie. Le critère d'évaluation principal était la présence d'au moins une complication postopératoire. La régression logistique a été utilisée pour évaluer l'association entre ScVO2, taux de lactate et gradient de CO2 et les complications. Leur performance diagnostique a été comparée à l'aide d'une courbe ROC (receiver operating characteristic). RéSULTATS: Des complications sont survenues chez 1933 patients (38 %). Les paramètres de circulation extracorporelle (CEC) étaient semblables entre les groupes. Le gradient de CO2 était légèrement plus élevé dans le groupe « complications ¼ que dans le groupe « pas de complication ¼. Les taux de lactate artériels à l'admission, au jour 1 et au jour 2 étaient également légèrement plus élevés chez les patients ayant subi des complications. La différence de saturation en oxygène veineux central n'était pas significative entre les patients avec ou sans complications. L'aire sous la courbe ROC pour prédire les devenirs après la CEC pour le gradient de CO2 à l'admission, au jour 1 et au jour 2 était de 0,52, 0,55 et 0,53, respectivement. CONCLUSION: Après une chirurgie cardiaque avec CEC, le gradient de CO2 à l'admission en réanimation, au jour 1 et au jour 2 était associé aux complications postopératoires, mais sa performance diagnostique était médiocre.

Preload Dependency of 2D Right Ventricle Speckle Tracking Echocardiography Parameters in Healthy Volunteers: A Prospective Pilot Study.

(1) Background: Right ventricular (RV) strain parameters derived from the analysis of the tricuspid annular displacement (TAD) are emergent two-dimensional speckle tracking echocardiography (2D-STE) parameter used for the quantitative assessment of RV systolic function. Few data are available regarding 2D-STE parameters and their dependency on RV preload. Our aim was to evaluate the effect of an acute change in RV preload on 2D-STE parameters in healthy volunteers. (2) Methods: Acute modification of RV preload was performed by a fluid challenge (FC): an infusion of 500 mL of 0.9% sodium chloride was given over 5 min in supine position. Preload dependency (responder group) was confirmed by a stroke volume increase of at least 10% measured by echocardiography. (3) Results: Among 32 healthy volunteers, 19 (59%) subjects were classified as non-responders and 13 (41%) as responders. In the responder group, the tricuspid annular plane systolic excursion (TAPSE) significantly increased (20 (20-23.5) mm to 24 (20.5-26.5) mm; p = 0.018), while RV strain parameters significantly decreased after FC: -23.5 ((-22.3)-(-27.3))% to -25 ((-24)-(29.6))%; p = 0.03) for RV free wall longitudinal strain and -22.8 ((-20.4)-(-30.7))% to -23.7 ((-21.2)-(-27))%; p = 0.02) for RV four-chamber longitudinal strain. 2D-STE parameters derived from the TAD analysis were not influenced by the FC (all p > 0.05). (4) Conclusions: In young, healthy volunteers, RV strain parameters and TAPSE are preload dependent, while TAD parameters were not. The loading conditions must be accounted for when evaluating RV systolic function by 2D-STE parameters.

Abnormal laboratory findings and plasma concentration monitoring of lopinavir and ritonavir in COVID-19.

It is not known whether the adverse events (AEs) associated with the administration of lopinavir and ritonavir (LPV/r) in the treatment of COVID-19 are concentration-dependent. In a retrospective study of 65 patients treated with LPV/r and therapeutic drug monitoring (TDM) for severe forms of COVID-19 (median age: 67; males: 41 [63.1%]), 33 (50.8%) displayed a grade ≥2 increase in plasma levels of hepatobiliary markers, lipase and/or triglycerides. A causal relationship between LPV/r and the AE was suspected in 9 of the 65 patients (13.8%). At 400 mg b.i.d., the plasma trough concentrations of LPV/r were high and showed marked interindividual variability (median [interquartile range]: 16,600 [11,430-20,842] ng/ml for lopinavir and 501 [247-891] ng/ml for ritonavir). The trough lopinavir concentration was negatively correlated with body mass index, while the trough ritonavir concentration was positively correlated with age and negatively correlated with prothrombin activity. However, the occurrence of abnormal laboratory values was not associated with higher trough plasma concentrations of LPV/r. Further studies will be needed to determine the value of TDM in LPV/r-treated patients with COVID-19.

Iatrogenic Acute Type A Aortic Dissection following Elective Cardiopulmonary Bypass.

We report a 62-year-old woman who was scheduled for an elective Tirone David valve sparing aortic root replacement under cardiopulmonary bypass. Within the next few hours, the patient developed bilateral acute ischemia of both lower limbs. A thoracic and abdominopelvic computed tomography scan showed acute Type A aortic dissection with a perforation at the brachiocephalic arterial trunk and a complete malperfusion of the inferior mesenteric and iliac arteries.

Acute Cor Pulmonale in COVID-19-Related ARDS: Improvement With Almitrine Infusion.

Coronavirus disease-19 (COVID-19)-related severe acute respiratory distress syndrome can lead to acute cor pulmonale. We report a case of acute cor pulmonale secondary to severe COVID-19 acute respiratory distress syndrome diagnosed with transesophageal echocardiography. Almitrine infusion allowed rapid enhancement of right ventricular function as well as improvement in oxygenation. (Level of Difficulty: Intermediate.).