Changes in brain tissue oxygenation after treatment of diffuse traumatic brain injury by erythropoietin.

International audienceOBJECTIVES: To investigate the effects of recombinant human erythropoietin on brain oxygenation in a model of diffuse traumatic brain injury. DESIGN: Adult male Wistar rats. SETTING: Neurosciences and physiology laboratories. INTERVENTIONS: Thirty minutes after diffuse traumatic brain injury (impact-acceleration model), rats were intravenously administered with either a saline solution or a recombinant human erythropoietin (5000 IU/kg). A third group received no traumatic brain injury insult (sham-operated). MEASUREMENTS AND MAIN RESULTS: Three series of experiments were conducted 2 hours after traumatic brain injury to investigate: 1) the effect of recombinant human erythropoietin on brain edema using diffusion-weighted magnetic resonance imaging and measurements of apparent diffusion coefficient (n = 11 rats per group); local brain oxygen saturation, mean transit time, and blood volume fraction were subsequently measured using a multiparametric magnetic resonance-based approach to estimate brain oxygenation and brain perfusion in the neocortex and caudoputamen; 2) the effect of recombinant human erythropoietin on brain tissue PO₂ in similar experiments (n = 5 rats per group); and 3) the cortical ultrastructural changes after treatment (n = 1 rat per group). Compared with the sham-operated group, traumatic brain injury saline rats showed a significant decrease in local brain oxygen saturation and in brain tissue PO₂ alongside brain edema formation and microvascular lumen collapse at H2. Treatment with recombinant human erythropoietin reversed all of these traumatic brain injury-induced changes. Brain perfusion (mean transit time and blood volume fraction) was comparable between the three groups of animals. CONCLUSION: Our findings indicate that brain hypoxia can be related to microcirculatory derangements and cell edema without evidence of brain ischemia. These changes were reversed with post-traumatic administration of recombinant human erythropoietin, thus offering new perspectives in the use of this drug in brain injury

Erythropoietin and Its Derivates Modulate Mitochondrial Dysfunction after Diffuse Traumatic Brain Injury

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Prognostic factors for extracorporeal cardiopulmonary resuscitation recipients following out-of-hospital refractory cardiac arrest. A systematic review and meta-analysis

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Outcomes after extracorporeal membrane oxygenation for the treatment of high-risk pulmonary embolism: a multicentre series of 52 cases

International audienceAims The role of extracorporeal membrane oxygenation (ECMO) remains ill defined in pulmonary embolism (PE). We investigated outcomes in patients with high-risk PE undergoing ECMO according to initial therapeutic strategy. Methods and results From 01 January 2014 to 31 December 2015, 180 patients from 13 Departments in nine centres with high-risk PE were retrospectively included. Among those undergoing ECMO, we compared characteristics and outcomes according to adjunctive treatment strategy (systemic thrombolysis, surgical embolectomy, or no reperfusion therapy). Primary outcome was all-cause 30-day mortality. Secondary outcome was 90-day major bleeding. One hundred and twenty-eight patients were treated without ECMO; 52 (mean age 47.6 years) underwent ECMO. Overall 30-day mortality was 48.3% [95% confidence interval (CI) 41-56] (87/180); 43% (95% CI 34-52) (55/128) in those treated without ECMO vs. 61.5% (95% CI 52-78) (32/52) in those with ECMO (P = 0.008). In patients undergoing ECMO, 30-day mortality was 76.5% (95% CI 57-97) (13/17) for ECMO+fibrinolysis, 29.4% (95% CI 51-89) (5/17) for ECMO+surgical embolectomy, and 77.7% (95% CI 59-97) (14/18) for ECMO alone (P = 0.004). Among patients with ECMO, 20 (38.5%, 95% CI 25-52) had a major bleeding event in-hospital; without significant difference across groups. Conclusion In patients with high-risk PE, those with ECMO have a more severe presentation and worse prognosis. Extracorporeal membrane oxygenation in patients with failed fibrinolysis and in those with no reperfusion seems to be associated with particularly unfavourable prognosis compared with ECMO performed in addition to surgical embolectomy. Our findings suggest that ECMO does not appear justified as a stand-alone treatment strategy in PE patients, but shows promise as a complement to surgical embolectomy

Effect of Moderate Hypothermia vs Normothermia on 30-Day Mortality in Patients With Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation: A Randomized Clinical Trial

IMPORTANCE: The optimal approach to the use of venoarterial extracorporeal membrane oxygenation (ECMO) during cardiogenic shock is uncertain. OBJECTIVE: To determine whether early use of moderate hypothermia (33-34 °C) compared with strict normothermia (36-37 °C) improves mortality in patients with cardiogenic shock receiving venoarterial ECMO. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of patients (who were eligible if they had been endotracheally intubated and were receiving venoarterial ECMO for cardiogenic shock for <6 hours) conducted in the intensive care units at 20 French cardiac shock care centers between October 2016 and July 2019. Of 786 eligible patients, 374 were randomized. Final follow-up occurred in November 2019. INTERVENTIONS: Early moderate hypothermia (33-34 °C; n = 168) for 24 hours or strict normothermia (36-37 °C; n = 166). MAIN OUTCOMES AND MEASURES: The primary outcome was mortality at 30 days. There were 31 secondary outcomes including mortality at days 7, 60, and 180; a composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at days 30, 60, and 180; and days without requiring a ventilator or kidney replacement therapy at days 30, 60, and 180. Adverse events included rates of severe bleeding, sepsis, and number of units of packed red blood cells transfused during venoarterial ECMO. RESULTS: Among the 374 patients who were randomized, 334 completed the trial (mean age, 58 [SD, 12] years; 24% women) and were included in the primary analysis. At 30 days, 71 patients (42%) in the moderate hypothermia group had died vs 84 patients (51%) in the normothermia group (adjusted odds ratio, 0.71 [95% CI, 0.45 to 1.13], P = .15; risk difference, -8.3% [95% CI, -16.3% to -0.3%]). For the composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at day 30, the adjusted odds ratio was 0.61 (95% CI, 0.39 to 0.96; P = .03) for the moderate hypothermia group compared with the normothermia group and the risk difference was -11.5% (95% CI, -23.2% to 0.2%). Of the 31 secondary outcomes, 30 were inconclusive. The incidence of moderate or severe bleeding was 41% in the moderate hypothermia group vs 42% in the normothermia group. The incidence of infections was 52% in both groups. The incidence of bacteremia was 20% in the moderate hypothermia group vs 30% in the normothermia group. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial involving patients with refractory cardiogenic shock treated with venoarterial ECMO, early application of moderate hypothermia for 24 hours did not significantly increase survival compared with normothermia. However, because the 95% CI was wide and included a potentially important effect size, these findings should be considered inconclusive. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02754193

Additional file 1 of Healthcare-associated infections in patients with severe COVID-19 supported with extracorporeal membrane oxygenation: a nationwide cohort study

Additional file 1 of Healthcare-associated infections in patients with severe COVID-19 supported with extracorporeal membrane oxygenation: a nationwide cohort study

Healthcare-associated infections in patients with severe COVID-19 supported with extracorporeal membrane oxygenation: a nationwide cohort study

International audienceBackground Both critically ill patients with coronavirus disease 2019 (COVID-19) and patients receiving extracorporeal membrane oxygenation (ECMO) support exhibit a high incidence of healthcare-associated infections (HAI). However, data on incidence, microbiology, resistance patterns, and the impact of HAI on outcomes in patients receiving ECMO for severe COVID-19 remain limited. We aimed to report HAI incidence and microbiology in patients receiving ECMO for severe COVID-19 and to evaluate the impact of ECMO-associated infections (ECMO-AI) on in-hospital mortality. Methods For this study, we analyzed data from 701 patients included in the ECMOSARS registry which included COVID-19 patients supported by ECMO in France. Results Among 602 analyzed patients for whom HAI and hospital mortality data were available, 214 (36%) had ECMO-AI, resulting in an incidence rate of 27 ECMO-AI per 1000 ECMO days at risk. Of these, 154 patients had bloodstream infection (BSI) and 117 patients had ventilator-associated pneumonia (VAP). The responsible microorganisms were Enterobacteriaceae (34% for BSI and 48% for VAP), Enterococcus species (25% and 6%, respectively) and non-fermenting Gram-negative bacilli (13% and 20%, respectively). Fungal infections were also observed (10% for BSI and 3% for VAP), as were multidrug-resistant organisms (21% and 15%, respectively). Using a Cox multistate model, ECMO-AI were not found associated with hospital death (HR = 1.00 95% CI [0.79–1.26], p = 0.986). Conclusions In a nationwide cohort of COVID-19 patients receiving ECMO support, we observed a high incidence of ECMO-AI. ECMO-AI were not found associated with hospital death. Trial registration number NCT04397588 (May 21, 2020)

Veno-Arterial Extracorporeal Membrane Oxygenation for Circulatory Failure in COVID-19 Patients: Insights from the ECMOSARS Registry

International audienceObjectives: The clinical profile and outcomes of patients with Covid-19 who require veno-arterial or veno-venous-arterial extracorporeal membrane oxygenation (VA-ECMO - VAV-ECMO) are poorly understood. We aimed to describe the characteristics and outcomes of these patients and to identify predictors of both favorable and unfavorable outcomes.Methods: ECMOSARS is a multicenter, prospective, nationwide French registry enrolling patients who require VV/VA-ECMO in the context of Covid-19 infection (652 patients at 41 centers). We focused on 47 patients supported with VA- or VAV-ECMO for refractory cardiogenic shock.Results: Median age was 49. 14% of patients had a prior diagnosis of heart failure. The most common etiologies of cardiogenic shock were acute pulmonary embolism (30%), myocarditis (28%), and acute coronary syndrome (4%). E-CPR (Extracorporeal Cardiopulmonary Resuscitation) occurred in 38%. In-hospital survival was 28% in the whole cohort, and 43% when E-CPR patients were excluded. ECMO cannulation was associated with significant improvements in pH and FiO2 on day one, but non-survivors showed significantly more severe acidosis and higher FiO2 than survivors at this point (p = 0.030 and p = 0.006). Other factors associated with death were greater age (p = 0.02), higher BMI (p = 0.03), E-CPR (p = 0.001), non-myocarditis etiology (p = 0.02), higher serum lactates (p = 0.004), epinephrine (but not noradrenaline) use before initiation of ECMO (p = 0.003), hemorrhagic complications (p = 0.001), greater transfusion requirements (p = 0.001), and more severe SAVE and SAFE scores (p = 0.01 and p = 0.03).Conclusions: We report the largest focused analysis of VA- and VAV-ECMO recipients in Covid-19. Although relatively rare, the need for temporary mechanical circulatory support in these patients is associated with poor prognosis. However, VA-ECMO remains a viable solution to rescue carefully selected patients. We identified factors associated with poor prognosis and suggest that E-CPR is not a reasonable indication for VA-ECMO in this population

Bleeding and thrombotic events in patients with severe COVID-19 supported with extracorporeal membrane oxygenation: a nationwide cohort study

International audiencePurpose: To describe bleeding and thrombotic events and their risk factors in patients receiving extracorporeal membrane oxygenation (ECMO) for severe coronavirus disease 2019 (COVID-19) and to evaluate their impact on in-hospital mortality.Methods: The ECMOSARS registry included COVID-19 patients supported by ECMO in France. We analyzed all patients included up to March 31, 2022 without missing data regarding bleeding and thrombotic events. The association of bleeding and thrombotic events with in-hospital mortality and pre-ECMO variables was assessed using multivariable logistic regression models.Results: Among 620 patients supported by ECMO, 29% had only bleeding events, 16% only thrombotic events and 20% both bleeding and thrombosis. Cannulation site (18% of patients), ear nose and throat (12%), pulmonary bleeding (9%) and intracranial hemorrhage (8%) were the most frequent bleeding types. Device-related thrombosis and pulmonary embolism/thrombosis accounted for most of thrombotic events. In-hospital mortality was 55.7%. Bleeding events were associated with in-hospital mortality (adjusted odds ratio (adjOR) = 2.91[1.94-4.4]) but not thrombotic events (adjOR = 1.02[0.68-1.53]). Intracranial hemorrhage was strongly associated with in-hospital mortality (adjOR = 13.5[4.4-41.5]). Ventilation duration before ECMO ≥ 7 days and length of ECMO support were associated with bleeding. Thrombosis-associated factors were fibrinogen ≥ 6 g/L and length of ECMO support.Conclusions: In a nationwide cohort of COVID-19 patients supported by ECMO, bleeding incidence was high and associated with mortality. Intracranial hemorrhage incidence was higher than reported for non-COVID patients and carried the highest risk of death. Thrombotic events were less frequent and not associated with mortality. Length of ECMO support was associated with a higher risk of both bleeding and thrombosis, supporting the development of strategies to minimize ECMO duration