Convalescent Plasma for Covid-19-Induced ARDS in Mechanically Ventilated Patients.

BACKGROUND: Passive immunization with plasma collected from convalescent patients has been regularly used to treat coronavirus disease 2019 (Covid-19). Minimal data are available regarding the use of convalescent plasma in patients with Covid-19-induced acute respiratory distress syndrome (ARDS). METHODS: In this open-label trial, we randomly assigned adult patients with Covid-19-induced ARDS who had been receiving invasive mechanical ventilation for less than 5 days in a 1:1 ratio to receive either convalescent plasma with a neutralizing antibody titer of at least 1:320 or standard care alone. Randomization was stratified according to the time from tracheal intubation to inclusion. The primary outcome was death by day 28. RESULTS: A total of 475 patients underwent randomization from September 2020 through March 2022. Overall, 237 patients were assigned to receive convalescent plasma and 238 to receive standard care. Owing to a shortage of convalescent plasma, a neutralizing antibody titer of 1:160 was administered to 17.7% of the patients in the convalescent-plasma group. Glucocorticoids were administered to 466 patients (98.1%). At day 28, mortality was 35.4% in the convalescent-plasma group and 45.0% in the standard-care group (P = 0.03). In a prespecified analysis, this effect was observed mainly in patients who underwent randomization 48 hours or less after the initiation of invasive mechanical ventilation. Serious adverse events did not differ substantially between the two groups. CONCLUSIONS: The administration of plasma collected from convalescent donors with a neutralizing antibody titer of at least 1:160 to patients with Covid-19-induced ARDS within 5 days after the initiation of invasive mechanical ventilation significantly reduced mortality at day 28. This effect was mainly observed in patients who underwent randomization 48 hours or less after ventilation initiation. (Funded by the Belgian Health Care Knowledge Center; ClinicalTrials.gov number, NCT04558476.).

Epidemiology and outcome predictors in 450 patients with hanging-induced cardiac arrest: a retrospective study.

Background: Cardiac arrest is the most life-threatening complication of attempted suicide by hanging. However, data are scarce on its characteristics and outcome predictors. Methods: This retrospective observational multicentre study in 31 hospitals included consecutive adults admitted after cardiac arrest induced by suicidal hanging. Factors associated with in-hospital mortality were identified by multivariate logistic regression with multiple imputations for missing data and adjusted to the temporal trends over the study period. Results: Of 450 patients (350 men, median age, 43 [34-52] years), 305 (68%) had a psychiatric history, and 31 (6.9%) attempted hanging while hospitalized. The median time from unhanging to cardiopulmonary resuscitation was 0 [0-5] min, and the median time to return of spontaneous circulation (ROSC) was 20 [10-30] min. Seventy-nine (18%) patients survived to hospital discharge. Three variables were independently associated with higher in-hospital mortality: time from collapse or unhanging to ROSC>20 min (odds ratio [OR], 4.71; 95% confidence intervals [95%CIs], 2.02-10.96; p = 0.0004); glycaemia >1.4 g/L at admission (OR, 6.38; 95%CI, 2.60-15.66; p < 0.0001); and lactate >3.5 mmol/L at admission (OR, 6.08; 95%CI, 1.71-21.06; p = 0.005). A Glasgow Coma Scale (GCS) score of >5 at admission was associated with lower in-hospital mortality (OR, 0.009; 95%CI, 0.02-0.37; p = 0.0009). Conclusion: In patients with hanging-induced cardiac arrest, time from collapse or unhanging to return of spontaneous circulation, glycaemia, arterial lactate, and coma depth at admission were independently associated with survival to hospital discharge. Knowledge of these risk factors may help guide treatment decisions in these patients at high risk of hospital mortality.

Red Blood Cell Transfusion in the Intensive Care Unit.

Importance: Red blood cell (RBC) transfusion is common among patients admitted to the intensive care unit (ICU). Despite multiple randomized clinical trials of hemoglobin (Hb) thresholds for transfusion, little is known about how these thresholds are incorporated into current practice. Objective: To evaluate and describe ICU RBC transfusion practices worldwide. Design, Setting, and Participants: International, prospective, cohort study that involved 3643 adult patients from 233 ICUs in 30 countries on 6 continents from March 2019 to October 2022 with data collection in prespecified weeks. Exposure: ICU stay. Main Outcomes and Measures: The primary outcome was the occurrence of RBC transfusion during ICU stay. Additional outcomes included the indication(s) for RBC transfusion (consisting of clinical reasons and physiological triggers), the stated Hb threshold and actual measured Hb values before and after an RBC transfusion, and the number of units transfused. Results: Among 3908 potentially eligible patients, 3643 were included across 233 ICUs (median of 11 patients per ICU [IQR, 5-20]) in 30 countries on 6 continents. Among the participants, the mean (SD) age was 61 (16) years, 62% were male (2267/3643), and the median Sequential Organ Failure Assessment score was 3.2 (IQR, 1.5-6.0). A total of 894 patients (25%) received 1 or more RBC transfusions during their ICU stay, with a median total of 2 units per patient (IQR, 1-4). The proportion of patients who received a transfusion ranged from 0% to 100% across centers, from 0% to 80% across countries, and from 19% to 45% across continents. Among the patients who received a transfusion, a total of 1727 RBC transfusions were administered, wherein the most common clinical indications were low Hb value (n = 1412 [81.8%]; mean [SD] lowest Hb before transfusion, 7.4 [1.2] g/dL), active bleeding (n = 479; 27.7%), and hemodynamic instability (n = 406 [23.5%]). Among the events with a stated physiological trigger, the most frequently stated triggers were hypotension (n = 728 [42.2%]), tachycardia (n = 474 [27.4%]), and increased lactate levels (n = 308 [17.8%]). The median lowest Hb level on days with an RBC transfusion ranged from 5.2 g/dL to 13.1 g/dL across centers, from 5.3 g/dL to 9.1 g/dL across countries, and from 7.2 g/dL to 8.7 g/dL across continents. Approximately 84% of ICUs administered transfusions to patients at a median Hb level greater than 7 g/dL. Conclusions and Relevance: RBC transfusion was common in patients admitted to ICUs worldwide between 2019 and 2022, with high variability across centers in transfusion practices.

High Mobility Group Box 1 (HMGB1): Potential Target in Sepsis-Associated Encephalopathy.

Sepsis-associated encephalopathy (SAE) remains a challenge for intensivists that is exacerbated by lack of an effective diagnostic tool and an unambiguous definition to properly identify SAE patients. Risk factors for SAE development include age, genetic factors as well as pre-existing neuropsychiatric conditions. Sepsis due to certain infection sites/origins might be more prone to encephalopathy development than other cases. Currently, ICU management of SAE is mainly based on non-pharmacological support. Pre-clinical studies have described the role of the alarmin high mobility group box 1 (HMGB1) in the complex pathogenesis of SAE. Although there are limited data available about the role of HMGB1 in neuroinflammation following sepsis, it has been implicated in other neurologic disorders, where its translocation from the nucleus to the extracellular space has been found to trigger neuroinflammatory reactions and disrupt the blood-brain barrier. Negating the inflammatory cascade, by targeting HMGB1, may be a strategy to complement non-pharmacologic interventions directed against encephalopathy. This review describes inflammatory cascades implicating HMGB1 and strategies for its use to mitigate sepsis-induced encephalopathy.

Serum Metabolomic Profiles in Critically Ill Patients with Shock on Admission to the Intensive Care Unit.

Inflammatory processes are common in intensive care (ICU) patients and can induce multiple changes in metabolism, leading to increased risks of morbidity and mortality. Metabolomics enables these modifications to be studied and identifies a patient's metabolic profile. The objective is to precise if the use of metabolomics at ICU admission can help in prognostication. This is a prospective ex-vivo study, realized in a university laboratory and a medico-surgical ICU. Metabolic profiles were analyzed by proton nuclear magnetic resonance. Using multivariable analysis, we compared metabolic profiles of volunteers and ICU patients divided into predefined subgroups: sepsis, septic shock, other shock and ICU controls. We also assessed possible correlations between metabolites and mortality. One hundred and eleven patients were included within 24 h of ICU admission, and 19 healthy volunteers. The ICU mortality rate was 15%. Metabolic profiles were different in ICU patients compared to healthy volunteers (p < 0.001). Among the ICU patients, only the subgroup of patients with septic shock had significant differences compared to the ICU control patients in several metabolites: pyruvate, lactate, carnitine, phenylalanine, urea, creatine, creatinine and myo-inositol. However, there was no correlation between these metabolite profiles and mortality. On the first day of ICU admission, we observed changes in some metabolic products in patients with septic shock, suggesting increased anaerobic glycolysis, proteolysis, lipolysis and gluconeogenesis. These changes were not correlated with prognosis.

Barotrauma in COVID-19 acute respiratory distress syndrome: retrospective analysis of the COVADIS prospective multicenter observational database.

BACKGROUND: Despite evidence suggesting a higher risk of barotrauma during COVID-19-related acute respiratory distress syndrome (ARDS) compared to ARDS due to other causes, data are limited about possible associations with patient characteristics, ventilation strategy, and survival. METHODS: This prospective observational multicenter study included consecutive patients with moderate-to-severe COVID-19 ARDS requiring invasive mechanical ventilation and managed at any of 12 centers in France and Belgium between March and December 2020. The primary objective was to determine whether barotrauma was associated with ICU mortality (censored on day 90), and the secondary objective was to identify factors associated with barotrauma. RESULTS: Of 586 patients, 48 (8.2%) experienced barotrauma, including 35 with pneumothorax, 23 with pneumomediastinum, 1 with pneumoperitoneum, and 6 with subcutaneous emphysema. Median time from mechanical ventilation initiation to barotrauma detection was 3 [0-17] days. All patients received protective ventilation and nearly half (23/48) were in volume-controlled mode. Barotrauma was associated with higher hospital mortality (P < 0.001) even after adjustment on age, sex, comorbidities, PaO2/FiO2 at intubation, plateau pressure at intubation, and center (P < 0.05). The group with barotrauma had a lower mean body mass index (28.6 ± 5.8 vs. 30.3 ± 5.9, P = 0.03) and a higher proportion of patients given corticosteroids (87.5% vs. 63.4%, P = 0.001). CONCLUSION: Barotrauma during mechanical ventilation for COVID-19 ARDS was associated with higher hospital mortality.

Hyperbaric oxygenation improve red blood cell deformability in patients with acute or chronic inflammation.

INTRODUCTION: Red blood cells (RBC) are one of the key elements of the microcirculation. Their ability to pass through capillaries and to deliver oxygen to cells is due to their large degree of deformability linked to the characteristics of the RBC membrane. Alterations in RBC deformability as a result of membrane damage, linked in part to increased synthesis of reactive oxygen species (ROS), can be observed in several diseases, such as sepsis, and may contribute to the altered microcirculation observed in these pathologies. Hyperbaric oxygen therapy (HBOT), with inhalation of 100 % oxygen, has been proposed in several acute or chronic pathologies, including carbon monoxide poisoning. OBJECTIVE: We investigated the effects of HBOT on oxidative stress from ROS produced by myeloperoxidase (MPO) and on RBC deformability in patients with acute or chronic inflammation (n = 10), in patients with acute carbon monoxide poisoning (n = 10), and in healthy volunteers (n = 10). METHODS: RBC deformability was evaluated before and after HBOT in the various populations using the ektacytometry technique (Laser-assisted Optical Rotational Red Cell Analyzer - LORRCA). Deformability was determined by the elongation index (EI) in relation to the shear stress (SS) over a range of 0.3 to 50 Pa. Oxidative stress was estimated through changes in proteins (chlorotyrosine and homocitrulline) induced by MPO activity measured by liquid chromatography-tandem mass spectrometry analysis. RESULTS: Before HBOT, EI was significantly lower in patients with acute or chronic inflammation than in healthy volunteers and patients with acute carbon monoxide poisoning for the majority of SS values studied. After one session of HBOT, the EI was significantly higher than before HBOT for SS values of 1.93 Pa or higher in patients with acute or chronic inflammation. This effect remains constant after 10 sessions. There were no differences before and after HBOT in protein or amino acid oxidation due to ROS generation mediated by MPO in the three populations. CONCLUSIONS: Our results confirm altered RBC deformability in patients with acute and chronic conditions associated with an underlying inflammatory process. HBOT improves deformability only after one session and therefore may improve microcirculation in this population. According to our results, this improvement does not seem mediated by the ROS pathway via MPO. These results need to be confirmed in a larger population.

Cerebro-spinal fluid glucose and lactate concentrations changes in response to therapies in patIents with primary brain injury: the START-TRIP study.

INTRODUCTION: Altered levels of cerebrospinal fluid (CSF) glucose and lactate concentrations are associated with poor outcomes in acute brain injury patients. However, no data on changes in such metabolites consequently to therapeutic interventions are available. The aim of the study was to assess CSF glucose-to-lactate ratio (CGLR) changes related to therapies aimed at reducing intracranial pressure (ICP). METHODS: A multicentric prospective cohort study was conducted in 12 intensive care units (ICUs) from September 2017 to March 2022. Adult (> 18 years) patients admitted after an acute brain injury were included if an external ventricular drain (EVD) for intracranial pressure (ICP) monitoring was inserted within 24 h of admission. During the first 48-72 h from admission, CGLR was measured before and 2 h after any intervention aiming to reduce ICP ("intervention"). Patients with normal ICP were also sampled at the same time points and served as the "control" group. RESULTS: A total of 219 patients were included. In the intervention group (n = 115, 53%), ICP significantly decreased and CPP increased. After 2 h from the intervention, CGLR rose in both the intervention and control groups, although the magnitude was higher in the intervention than in the control group (20.2% vs 1.6%; p = 0.001). In a linear regression model adjusted for several confounders, therapies to manage ICP were independently associated with changes in CGLR. There was a weak inverse correlation between changes in ICP and CGRL in the intervention group. CONCLUSIONS: In this study, CGLR significantly changed over time, regardless of the study group. However, these effects were more significant in those patients receiving interventions to reduce ICP.

Effects of Preconditioning on RBC Deformability in Critically Ill Patients.

RBCs from critically ill patients have depressed deformability, especially in sepsis. Prolonged exposure of RBCs from healthy volunteers to physiologic shear stress (the preconditioning technique) has been associated with improved deformability, but the effect of preconditioning on RBCs from critically ill patients with or without sepsis has never been studied. DESIGN: Prospective study. SETTING: A 32-bed medico-surgical ICU and a university-affiliated cell biology laboratory. SUBJECTS: RBCs from 26 healthy volunteers and 40 critically ill patients (20 with and 20 without sepsis). INTERVENTIONS: RBC deformability was measured using the elongation index (EI) with an ektacytometer, at shear stress levels ranging from 0.3 to 50 Pa. To assess the effects of preconditioning in the three groups, we measured EI after first applying a shear stress of 5 Pa for 300 seconds. To study the potential mechanisms involved in preconditioning, we looked at deformability after incubation of an RBC solution from the healthy volunteers with glutaraldehyde, a membrane-stabilizing protein, and neuraminidase, an enzyme that releases membrane sialic acid. MEASUREMENTS AND MAIN RESULTS: Baseline RBC deformability was significantly depressed in the septic patients compared with the volunteers at all shear stress levels greater than or equal to 4.89 Pa. Preconditioning improved deformability only in the volunteers (at shear stress levels of 0.48 and 0.76 Pa). Among the critically ill patients, preconditioning worsened RBC deformability at higher shear stress levels. After incubation (with glutaraldehyde or neuraminidase) of RBCs from five volunteers in whom preconditioning had significantly improved deformability, the positive effect of preconditioning was lost with glutaraldehyde. CONCLUSIONS: RBC deformability is depressed in septic patients. There was a deleterious effect of preconditioning on RBC deformability in septic patients, unlike the positive effect on RBCs from healthy volunteers. The effect of preconditioning may be associated with elasticity of the cell membrane.

Evolution of red blood cell membrane complement regulatory proteins and rheology in septic patients: An exploratory study.

Background: During sepsis, red blood cell (RBC) deformability is altered. Persistence of these alterations is associated with poor outcome. Activation of the complement system is enhanced during sepsis and RBCs are protected by membrane surface proteins like CD35, CD55 and CD59. In malaria characterized by severe anemia, a study reported links between the modifications of the expression of these RBCs membrane proteins and erythrophagocytosis. We studied the evolution of RBCs deformability and the expression of RBC membrane surface IgG and regulatory proteins in septic patients. Methods: By flow cytometry technics, we measured at ICU admission and at day 3-5, the RBC membrane expression of IgG and complement proteins (CD35, 55, 59) in septic patients compared to RBCs from healthy volunteers. Results were expressed in percentage of RBCs positive for the protein. RBC shape was assessed using Pearson's second coefficient of dissymmetry (PCD) on the histogram obtained with a flow cytometer technique. A null value represents a perfect spherical shape. RBC deformability was determined using ektacytometry by the elongation index in relation to the shear stress (0.3-50 Pa) applied to the RBC membrane. A higher elongation index indicates greater RBC deformability. Results: RBCs from 11 septic patients were compared to RBCs from 21 volunteers. At ICU admission, RBCs from septic patients were significantly more spherical and RBC deformability was significantly lower in septic patients for all shear stress ≥1.93 Pa. These alterations of shape and deformability persists at day 3-5. We observed a significant decrease at ICU admission only in CD35 expression on RBCs from septic patients. This low expression remained at day 3-5. Conclusions: We observed in RBCs from septic patients a rapid decrease expression of CD35 membrane protein protecting against complement activation. These modifications associated with altered RBC deformability and shape could facilitate erythrophagocytosis, contributing to anemia observed in sepsis. Other studies with a large number of patients and assessment of erythrophagocytosis were needed to confirm these preliminary data.

Management and outcomes of pregnant women admitted to intensive care unit for severe pneumonia related to SARS-CoV-2 infection: the multicenter and international COVIDPREG study.

PURPOSE: Management and outcomes of pregnant women with coronavirus disease 2019 (COVID-19) admitted to intensive care unit (ICU) remain to be investigated. METHODS: A retrospective multicenter study conducted in 32 ICUs in France, Belgium and Switzerland. Maternal management as well as maternal and neonatal outcomes were reported. RESULTS: Among the 187 pregnant women with COVID-19 (33 ± 6 years old and 28 ± 7 weeks' gestation), 76 (41%) were obese, 12 (6%) had diabetes mellitus and 66 (35%) had pregnancy-related complications. Standard oxygenation, high-flow nasal oxygen therapy (HFNO) and non-invasive ventilation (NIV) were used as the only oxygenation technique in 41 (22%), 55 (29%) and 18 (10%) patients, respectively, and 73 (39%) were intubated. Overall, 72 (39%) patients required several oxygenation techniques and 15 (8%) required venovenous extracorporeal membrane oxygenation. Corticosteroids and tocilizumab were administered in 157 (84%) and 25 (13%) patients, respectively. Awake prone positioning or prone positioning was performed in 49 (26%) patients. In multivariate analysis, risk factors for intubation were obesity (cause-specific hazard ratio (CSH) 2.00, 95% CI (1.05-3.80), p = 0.03), term of pregnancy (CSH 1.07, 95% CI (1.02-1.10), per + 1 week gestation, p = 0.01), extent of computed tomography (CT) scan abnormalities > 50% (CSH 2.69, 95% CI (1.30-5.60), p < 0.01) and NIV use (CSH 2.06, 95% CI (1.09-3.90), p = 0.03). Delivery was required during ICU stay in 70 (37%) patients, mainly due to maternal respiratory worsening, and improved the driving pressure and oxygenation. Maternal and fetal/neonatal mortality rates were 1% and 4%, respectively. The rate of maternal and/or neonatal complications increased with the invasiveness of maternal respiratory support. CONCLUSION: In ICU, corticosteroids, tocilizumab and prone positioning were used in few pregnant women with COVID-19. Over a third of patients were intubated and delivery improved the driving pressure.

Extubation in neurocritical care patients: the ENIO international prospective study.

PURPOSE: Neurocritical care patients receive prolonged invasive mechanical ventilation (IMV), but there is poor specific information in this high-risk population about the liberation strategies of invasive mechanical ventilation. METHODS: ENIO (NCT03400904) is an international, prospective observational study, in 73 intensive care units (ICUs) in 18 countries from 2018 to 2020. Neurocritical care patients with a Glasgow Coma Score (GCS) ≤ 12, receiving IMV ≥ 24 h, undergoing extubation attempt or tracheostomy were included. The primary endpoint was extubation failure by day 5. An extubation success prediction score was created, with 2/3 of patients randomly allocated to the training cohort and 1/3 to the validation cohort. Secondary endpoints were the duration of IMV and in-ICU mortality. RESULTS: 1512 patients were included. Among the 1193 (78.9%) patients who underwent an extubation attempt, 231 (19.4%) failures were recorded. The score for successful extubation prediction retained 20 variables as independent predictors. The area under the curve (AUC) in the training cohort was 0.79 95% confidence interval (CI95) [0.71-0.87] and 0.71 CI95 [0.61-0.81] in the validation cohort. Patients with extubation failure displayed a longer IMV duration (14 [7-21] vs 6 [3-11] days) and a higher in-ICU mortality rate (8.7% vs 2.4%). Three hundred and nineteen (21.1%) patients underwent tracheostomy without extubation attempt. Patients with direct tracheostomy displayed a longer duration of IMV and higher in-ICU mortality than patients with an extubation attempt (success and failure). CONCLUSIONS: In neurocritical care patients, extubation failure is high and is associated with unfavourable outcomes. A score could predict extubation success in multiple settings. However, it will be mandatory to validate our findings in another prospective independent cohort.

Early Corticosteroid Therapy May Increase Ventilator-Associated Lower Respiratory Tract Infection in Critically Ill Patients with COVID-19: A Multicenter Retrospective Cohort Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has put significant pressure on hospitals and in particular on intensive care units (ICU). Some patients develop acute hypoxemic respiratory failure with profound hypoxia, which likely requires invasive mechanical ventilation during prolonged periods. Corticosteroids have become a cornerstone therapy for patients with severe COVID-19, though only little data are available regarding their potential harms and benefits, especially concerning the risk of a ventilator-associated lower respiratory tract infection (VA-LRTI). METHODS: This retrospective multicenter study included patients admitted in four ICUs from Belgium and France for severe COVID-19, who required invasive mechanical ventilation (MV). We compared clinical and demographic variables between patients that received corticosteroids or not, using univariate, multivariate, and Fine and Gray analyses to identify factors influencing VA-LRTI occurrence. RESULTS: From March 2020 to January 2021, 341 patients required MV for acute respiratory failure related to COVID-19, 322 of whom were included in the analysis, with 60.6% of them receiving corticosteroids. The proportion of VA-LRTI was significantly higher in the early corticosteroid group (63.1% vs. 48.8%, p = 0.011). Multivariable Fine and Gray modeling considering death and extubation as competing events revealed that the factors independently associated with VA-LRTI occurrence were male gender (adjusted sHR:1.7, p = 0.0022) and corticosteroids (adjusted sHR: 1.44, p = 0.022). CONCLUSIONS: in our multicenter retrospective cohort of COVID-19 patients undergoing MV, early corticosteroid therapy was independently associated with VA-LRTI.

Red Blood Cell Shape and Deformability in Patients With COVID-19 Acute Respiratory Distress Syndrome.

Background: Acute respiratory distress syndrome due to coronavirus disease 2019 (COVID-19) is associated with high mortality. Several studies have reported that the microcirculation responds adequately to hypoxia in COVID-19 patients by increasing oxygen availability, in contrast to the inadequate response observed in patients with bacterial sepsis. Red blood cells (RBCs), the key cells for oxygen transport, and notably their rheology, are altered during bacterial sepsis, but few data are available in patients with COVID-19. Methods: In this prospective, non-interventional study, shape was assessed on admission (or inclusion for the volunteers) using Pearson's second coefficient of dissymmetry (PCD) on the histogram obtained with a flow cytometer technique. A null value represents a perfect spherical shape. RBC deformability was determined using ektacytometry by the elongation index in relation to the shear stress (0.3 to 50 Pa) applied to the RBC membrane. A higher elongation index indicates greater RBC deformability. Results were compared across groups. Scanning electronic microscopy was performed on RBCs from COVID-19 patients. RBC shape and deformability were also assessed on days 3 and 7 in COVID-19 patients. Results: Forty-nine ICU patients were included (30 with COVID-19 ARDS and 19 with bacterial sepsis). ARDS was more severe in patients with COVID-19 than in those with sepsis (PaO2/FiO2 99 [73-154] vs. 270 [239-295] mmHg p < 0.001) and mechanical ventilation was more frequently required (87 vs. 21%; p < 0.001). Mortality was significantly higher in COVID-19 patients (15/30 [50%] vs. 4/19 [21%], p = 0.046). RBCs were significantly more spherical in septic patients (PCD -0.40 [-0.56; -0.18]) than in healthy volunteers (PCD -0.54 [-0.66; -0.49]) but not than in COVID-19 patients (-0.48 [-0.55; -0.43]). In COVID-19 non-survivors (n = 11), sphericity was more marked on day 7 (PCD -0.40 [-0.47; -0.28]) than on day 1 (PCD vs. -0.49 [-0.59; -0.44]); p = 0.045. At ICU admission, RBC deformability was altered for all shear stress values studied in septic patients compared to COVID-19 patients and healthy volunteers (maximum elongation index for septic patients: 0.600 [0.594-0.630] vs. 0.646 [0.637-0.653] for COVID-19 patients and 0.640 [0.635-0.650] for healthy volunteers; both p < 0.001). In the 18 COVID-19 patients studied for 7 days, RBC deformability did not change over time and was not related to outcome. At day 1, RBCs from COVID-19 patients showed a normal structure on scanning electronic microscopy. Conclusion: In contrast to the significantly altered shape and decreased deformability in patients with bacterial sepsis, RBCs from severely hypoxemic COVID-19 patients had normal deformability on admission, and this pattern did not change over the first week despite a more spherical shape in non-survivors. As RBCs are the key cell for oxygen transport, this maintenance of normal deformability may contribute to the adequate microcirculatory response to severe hypoxia of the microcirculation that has been observed in these patients.

Critically ill cancer patient's resuscitation: a Belgian/French societies' consensus conference.

To respond to the legitimate questions raised by the application of invasive methods of monitoring and life-support techniques in cancer patients admitted in the ICU, the European Lung Cancer Working Party and the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique, set up a consensus conference. The methodology involved a systematic literature review, experts' opinion and a final consensus conference about nine predefined questions1. Which triage criteria, in terms of complications and considering the underlying neoplastic disease and possible therapeutic limitations, should be used to guide admission of cancer patient to intensive care units?2. Which ventilatory support [High Flow Oxygenation, Non-invasive Ventilation (NIV), Invasive Mechanical Ventilation (IMV), Extra-Corporeal Membrane Oxygenation (ECMO)] should be used, for which complications and in which environment?3. Which support should be used for extra-renal purification, in which conditions and environment?4. Which haemodynamic support should be used, for which complications, and in which environment?5. Which benefit of cardiopulmonary resuscitation in cancer patients and for which complications?6. Which intensive monitoring in the context of oncologic treatment (surgery, anti-cancer treatment …)?7. What specific considerations should be taken into account in the intensive care unit?8. Based on which criteria, in terms of benefit and complications and taking into account the neoplastic disease, patients hospitalized in an intensive care unit (or equivalent) should receive cellular elements derived from the blood (red blood cells, white blood cells and platelets)?9. Which training is required for critical care doctors in charge of cancer patients?

What Do We Know about Thromboprophylaxis and Its Monitoring in Critically Ill Patients?

Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, is an important complication in patients hospitalized in intensive care units (ICU). Thromboprophylaxis is mainly performed with Low Molecular Weight Heparin (LMWH) and, in some specific patients, with Unfractionated Heparin (UFH). These intensive units are an environment where individual patient variability is extreme and where traditional antithrombotic protocols are frequently ineffective. This was known for a long time, but the hospitalization of many patients with COVID-19 inflammatory storms suddenly highlighted this knowledge. It is therefore reasonable to propose variable antithrombotic prevention protocols based initially on a series of individual criteria (weight, BMI, and thrombotic risks). Secondly, they should be adjusted by the monitoring of anticoagulant activity, preferably by measuring the anti-Xa activity. However, we still face unresolved questions, such as once- or twice-daily LMWH injections, monitoring at the peak and/or trough, and poorly defined therapeutic targets. Equally surprisingly, we observed a lack of standardization of the anti-Xa activity kits.