Cardiogenic shock in adults with congenital heart disease: Insights from the FRENSHOCK registry.

BACKGROUND: Data on cardiogenic shock in adults with congenital heart disease (ACHD) are scarce. AIM: We sought to describe cardiogenic shock in ACHD patients in a nationwide cardiogenic shock registry. METHODS: From the multicentric FRENSHOCK registry (772 patients with cardiogenic shock from 49 French centres between April and October 2016), ACHD patients were compared with adults without congenital heart disease (non-ACHD). The primary outcome was defined by all-cause mortality, chronic ventricular assist device or heart transplantation at 1year. RESULTS: Out of the 772 patients, seven (0.9%) were ACHD, who were younger (median age: 56 vs. 67years), had fewer cardiovascular risk factors, such as hypertension (14.3% vs. 47.5%) and diabetes (14.3% vs. 28.3%), and no previous ischaemic cardiopathy (0 vs. 61.5%). Right heart catheterization (57.1% vs. 15.4%), pacemakers (28.6% vs. 4.6%) and implantable cardioverter-defibrillators (28.6% vs. 4.8%) were indicated more frequently in the management of ACHD patients compared with non-ACHD patients, whereas temporary mechanical circulatory support (0 vs. 18.7%) and invasive mechanical ventilation (14.3% vs. 38.1%) were less likely to be used in ACHD patients. At 1year, the primary outcome occurred in 85.7% (95% confidence interval: 42.1-99.6) ACHD patients and 52.3% (95% confidence interval: 48.7-55.9) non-ACHD patients. Although 1-year mortality was not significantly different between ACHD patients (42.9%) and non-ACHD patients (45.4%), ventricular assist devices and heart transplantation tended to be more frequent in the ACHD group. CONCLUSIONS: Cardiogenic shock in ACHD patients is rare, accounting for only 0.9% of an unselected cardiogenic shock population. Despite being younger and having fewer co-morbidities, the prognosis of ACHD patients with cardiogenic shock remains severe, and is similar to that of other patients.

Laboratory diagnosis of heparin-induced thrombocytopenia: A retrospective experience.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a severe complication of heparin therapy associated with thrombosis that requires a quick diagnosis. Therefore, laboratory assays must provide an accurate and swift answer. This work aims to evaluate the performances of an ELISA assay, especially when combined with 4T risk score, and a functional assay. METHODS: Data were collected for 894 patients treated by heparin who underwent anticoagulant switch because of HIT suspicion and were examined by a multidisciplinary expert team who confirmed or ruled out HIT diagnosis. All patients were tested for anti-PF4 IgG with Asserachrom HPIA IgG (ELISA), and 307 were tested with a platelet aggregation test done on platelet-rich plasma (PRP-PAT). The 4T risk score was available for 607 of them. RESULTS: HIT was diagnosed in 232 patients. 4T risk score had a 94.2% negative predictive value (NPV) for risk scores ≤3 and 77.3% for risk scores ≤5. The sensitivity of ELISA was 90.9%, its specificity 79.0%, and its NPV 96.1%. When combined with 4T risk score, its NPV reached 100% and 97% for risk scores ≤3 and ≤5, respectively. PRP-PAT sensitivity was 70.4%, and its specificity was 92.3%. Combination of ELISA and PRP-PAT had a 0.7% false-negative rate. CONCLUSION: This study shows that ELISA can rule out HIT with an excellent NPV, especially when combined with the 4T risk score. Nonetheless, it has low specificity; hence, it needs to be associated with a functional assay.

Study of Modifications Induced by Continued Direct Oral Anticoagulant Therapy during Atrial Fibrillation Ablation Procedures on Standard Hemostasis Parameters.

BACKGROUND: Unfractionated heparin (UFH) is used as an anticoagulant during the atrial fibrillation (AF) ablation procedure to prevent the occurrence of thromboembolic events. Guidelines recommend an activated clotting time (ACT) greater than 300 s (s) based on studies of patients treated with vitamin K antagonist (VKA) for their AF. However, direct oral anticoagulants (DOACs) have supplanted VKAs in AF and are now used as first-line therapy. It is recommended not to interrupt them during the procedure, which could interfere with the ACT measures. OBJECTIVE: To assess the real-life relationship between ACT, DOAC concentrations, and UFH anti-Xa activity in patients treated by uninterrupted DOAC therapy. METHODS: We conducted a single-center retrospective study. We analyzed consecutive patients with AF who underwent catheter ablation under DOAC therapy. RESULTS: In total, 40 patients were included, including 15 (37.5%), 20 (50.0%), and 5 (12.5%) on rivaroxaban, apixaban, and dabigatran, respectively. Baseline ACT was significantly lower in the apixaban group. ACT was linearly correlated with the residual concentration of apixaban and dabigatran but not with rivaroxaban. After UFH injection, ACT was linearly correlated with the anti-Xa activity, regardless of DOAC. Patients in the apixaban group received a higher total dose of UFH during the procedure to achieve a target ACT > 300 s, which resulted in significantly higher anti-Xa activity during the procedure. CONCLUSION: Our results raise the question of optimal management of intra-procedural heparin therapy and highlight the limitations of the ACT test, particularly in patients on apixaban.

One-year outcomes in cardiogenic shock triggered by ventricular arrhythmia: An analysis of the FRENSHOCK multicenter prospective registry.

Background: Cardiogenic shock (CS) is a life-threatening condition carrying poor prognosis, potentially triggered by ventricular arrhythmia (VA). Whether the occurrence of VA as trigger of CS worsens the prognosis compared to non-VA triggers  remains  unclear.  The  aim  of  this  study  was  to  evaluate  1-year  outcomes [mortality, heart transplantation, ventricular assist devices (VAD)] between VA-triggered and non-VA-triggered CS. Methods: FRENSHOCK is a prospective multicenter registry including 772 CS patients from 49 centers. One to three triggers can be identified in the registry (ischemic, mechanical complications, ventricular/supraventricular arrhythmia, bradycardia, iatrogenesis, infection, non-compliance). Baseline characteristics, management and 1-year outcomes were analyzed according to the VA-trigger in the CS population. Results: Within 769 CS patients included, 94 were VA-triggered (12.2%) and were compared to others. At 1 year, although there was no mortality difference [42.6 vs. 45.3%, HR 0.94 (0.67-1.30), p = 0.7], VA-triggered CS resulted in more heart transplantations and VAD (17 vs. 9%, p = 0.02). Into VA-triggered CS group, though there was no 1-year mortality difference between ischemic and non-ischemic cardiomyopathies [42.5 vs. 42.6%, HR 0.97 (0.52-1.81), p = 0.92], non-ischemic cardiomyopathy led to more heart transplantations and VAD (25.9 vs. 5%, p = 0.02). Conclusion: VA-triggered CS did not show higher mortality compared to other triggers but resulted in more heart transplantation and VAD at 1 year, especially in non-ischemic cardiomyopathy, suggesting the need for earlier evaluation by advanced heart failure specialized team for a possible indication of mechanical circulatory support or heart transplantation. Clinical trial registration: https://clinicaltrials.gov, identifier NCT02703038.

Platelet dysfunction and thrombus instability in flow conditions in patients with severe COVID-19.

Severe COVID-19 has been associated with a high rate of thrombotic events but also of bleeding events, particularly when the level of prophylactic anticoagulation was increased. Data on the contribution of platelets to these thrombotic events are discordant between reports, while the involvement of platelets in bleeding events has never been investigated. The objective of the present study was to assess platelet function during the first week of ICU hospitalization in patients with severe COVID-19 pneumonia. A total of 35 patients were prospectively included and blood samples were drawn on day (D) 0, D2 and D7. COVID-19 pneumonia was severe with a median PaO2/FiO2 ratio of 91 [68-119] on D0. Platelets from these patients showed evidence of pre-activation and exhaustion with a significant reduction in the surface expression of GPVI, GPIb and GPIIbIIIa, together with a decrease in serotonin content. Platelets from patients with severe COVID-19 were hyporesponsive with a reduced maximal aggregation response to several platelet agonists and decreased adhesion to immobilized fibrinogen. Aggregation of washed platelets and plasma substitution experiments indicated that a plasma factor was at least partially responsible for this hyporeactivity of platelets. Blood flow experiments showed that severe COVID-19 platelets formed smaller, less stable aggregates on a collagen-coated surface, which could explain why some patients develop bleeding events. These findings should prompt us to carefully evaluate the risks and benefits of high-dose prophylactic anticoagulation, and to decrease the level of anticoagulation once the initial phase of the disease has resolved. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04359992.

Baseline characteristics, management, and predictors of early mortality in cardiogenic shock: insights from the FRENSHOCK registry.

AIMS: Published data on cardiogenic shock (CS) are scarce and are mostly focused on small registries of selected populations. The aim of this study was to examine the current CS picture and define the independent correlates of 30 day mortality in a large non-selected cohort. METHODS AND RESULTS: FRENSHOCK is a prospective multicentre observational survey conducted in metropolitan French intensive care units and intensive cardiac care units between April and October 2016. There were 772 patients enrolled (mean age 65.7 ± 14.9 years; 71.5% male). Of these patients, 280 (36.3%) had ischaemic CS. Organ replacement therapies (respiratory support, circulatory support or renal replacement therapy) were used in 58.3% of patients. Mortality at 30 days was 26.0% in the overall population (16.7% to 48.0% depending on the main cause and first place of admission). Multivariate analysis showed that six independent factors were associated with a higher 30 day mortality: age [per year, odds ratio (OR) 1.06, 95% confidence interval (CI): 1.04-1.08], diuretics (OR 1.74, 95% CI: 1.05-2.88), circulatory support (OR 1.92, 95% CI: 1.12-3.29), left ventricular ejection fraction <30% (OR 2.15, 95% CI: 1.40-3.29), norepinephrine (OR 2.55, 95% CI: 1.69-3.84), and renal replacement therapy (OR 2.72, 95% CI: 1.65-4-49). CONCLUSIONS: Non-ischaemic CS accounted for more than 60% of all cases of CS. CS is still associated with significant but variable short-term mortality according to the cause and first place of admission, despite frequent use of haemodynamic support, and organ replacement therapies.

Transfusion of fresh washed platelets does not prevent experimental polymicrobial-induced septic shock in mice.

INTRODUCTION: The specific role of platelets during sepsis is not yet fully understood, probably related to the paradox of platelets being potentially beneficial but also deleterious via their thrombotic functions. OBJECTIVE: To evaluate the impact of thrombocytopenia on septic shock in mice and to investigate whether transfusion of fresh washed platelets, either fully functional or with impaired hemostatic properties, might have beneficial effects. METHODS: Septic shock was induced by cecal ligation and puncture (CLP). Experimental depletion of circulating platelets was induced with a rat anti-mouse GPIbα monoclonal antibody. Transfusion of either wild-type washed platelets, platelets treated with the antiplatelet drugs acetylsalicylic acid (ASA) and clopidogrel, or GPIIbIIIa-deficient washed platelets treated with ASA and clopidogrel was performed 4 h after CLP surgery. RESULTS: Depletion of circulating platelets negatively affected septic shock, worsening systemic inflammation, coagulopathy, organ damage, and mortality, raising the question of whether a higher platelet count could be protective. Transfusion of fully functional platelets or platelets with combined treatment with ASA and clopidogrel, with or without additional GPIIbIIIa deficiency, afforded an immediate return of circulating platelet counts to their initial values before surgery. However, transfusion of each of the three types of platelets did not prevent arterial hypotension, inflammatory response, coagulopathy, and organ damage during septic shock. CONCLUSION: Depletion of circulating platelets negatively affects septic shock, while transfusion of washed platelets has no significant beneficial effect in mice.

Platelet P2Y 12 Receptor Deletion or Pharmacological Inhibition does not Protect Mice from Sepsis or Septic Shock.

Introduction Platelets are increasingly appreciated as key effectors during sepsis, raising the question of the usefulness of antiplatelet drugs to treat patients with sepsis. Objective Evaluate the potential contribution of the platelet P2Y 12 receptor in the pathogenesis of polymicrobial-induced sepsis and septic shock in mice. Methods The effects of P2Y 12 inhibition using clopidogrel treatment and of platelet-specific deletion of the P2Y 12 receptor in mice were examined in two severity grades of cecal ligation and puncture (CLP) leading to mild sepsis or septic shock. Results Twenty hours after induction of the high grade CLP, clopidogrel- and vehicle-treated mice displayed a similar 30% decrease in mean arterial blood pressure (MAP) characteristic of shock. Septic shock-induced thrombocytopenia was not modified by clopidogrel treatment. Plasma concentrations of inflammatory cytokines and myeloperoxidase (MPO) were similarly increased in clopidogrel- and vehicle-treated mice, indicating comparable increase in systemic inflammation. Thrombin-antithrombin (TAT) complexes and the extent of organ damage were also similar. In mild-grade CLP, clopidogrel- and vehicle-treated mice did not display a significant decrease in MAP, while thrombocytopenia and plasma concentrations of TNFα, IL6, IL10, MPO, TAT and organ damage reached similar levels in both groups, although lower than those reached in the high grade CLP. Similarly, mice with platelet-specific deletion of the P2Y 12 receptor were not protected from CLP-induced sepsis or septic shock. Conclusion The platelet P2Y 12 receptor does not contribute to the pathogenesis of sepsis or septic shock in mice, suggesting that P2Y 12 receptor antagonists may not be beneficial in patients with sepsis or septic shock.

Impact of COVID-19 and lockdown regarding blood transfusion.

BACKGROUND: The outbreak of a SARS-CoV-2 resulted in a massive afflux of patients in hospital and intensive care units with many challenges. Blood transfusion was one of them regarding both blood banks (safety, collection, and stocks) and consumption (usual care and unknown specific demand of COVID-19 patients). The risk of mismatch was sufficient to plan blood transfusion restrictions if stocks became limited. STUDY DESIGN AND METHODS: Analyses of blood transfusion in a tertiary hospital and blood collection in the referring blood bank between February 24 and May 31, 2020. RESULTS: Withdrawal of elective surgery and non-urgent care and admission of 2291 COVID-19 patients reduced global activity by 33% but transfusion by 17% only. Only 237 (10.3) % of COVID-19 patients required blood transfusion, including 45 (2.0%) with acute bleeding. Lockdown and cancellation of mobile collection resulted in an 11% reduction in blood donation compared to 2019. The ratio of reduction in blood transfusion to blood donation remained positive and stocks were slightly enhanced. DISCUSSION: Reduction of admissions due to SARS-CoV-2 pandemic results only in a moderate decrease of blood transfusion. Incompressible blood transfusions concern urgent surgery, acute bleeding (including some patients with COVID-19, especially under high anticoagulation), or are supportive for chemotherapy-induced aplasia or chronic anemia. Lockdown results in a decrease of blood donation by cancellation of mobile donation but with little impact on a short period by mobilization of usual donors. No mismatch between demand and donation was evidenced and no planned restriction to blood transfusion was necessary.

Liposomal encapsulation of trans-crocetin enhances oxygenation in patients with COVID-19-related ARDS receiving mechanical ventilation.

Current therapeutic treatments improving the impaired transportation of oxygen in acute respiratory distress syndrome (ARDS) have been found to be relevant and beneficial for the therapeutic treatment of COVID-19 patients suffering from severe respiratory complications. Hence, we report the preclinical and the preliminary results of the Phase I/II clinical trial of LEAF-4L6715, a liposomal nanocarrier encapsulating the kosmotropic agent trans-crocetin (TC), which, once injected, enhance the oxygenation of vascular tissue and therefore has the potential to improve the clinical outcomes of ARDS and COVID-19 in severely impacted patients. We demonstrated that the liposomal formulation enabled to increase from 30 min to 48 h the reoxygenation properties of free TCs in vitro in endothelial cells, but also to improve the half-life of TC by 6-fold in healthy mice. Furthermore, we identified 25 mg/kg as the maximum tolerated dose in mice. This determined concentration led to the validation of the therapeutic efficacy of LEAF-4 L6715 in a sepsis mouse model. Finally, we report the preliminary outcomes of an open-label multicenter Phase I/II clinical trial (EudraCT 2020-001393-30; NCT04378920), which was aimed to define the appropriate schedule and dosage of LEAF-4L6715 and to confirm its tolerability profile and preliminary clinical activity in COVID-19 patients treated in intensive care unit.

Coronavirus Disease 2019: Associated Multiple Organ Damage.

A 56-year-old man presented a particularly severe and multisystemic case of coronavirus disease 2019 (COVID-19). In addition to the common lung and quite common pulmonary embolism and kidney injuries, he presented ocular and intestinal injuries that, to our knowledge, have not been described in COVID-19 patients. Although it is difficult to make pathophysiological hypotheses about a single case, the multiplicity of injured organs argues for a systemic response to pulmonary infection. A better understanding of physiopathology should feed the discussion about therapeutic options in this type of multifocal damage related to severe acute respiratory syndrome coronavirus 2.

High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study.

PURPOSE: Little evidence of increased thrombotic risk is available in COVID-19 patients. Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection. METHODS: All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included. Medical history, symptoms, biological data and imaging were prospectively collected. Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients. RESULTS: 150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points). Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting. Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO. Most patients (> 95%) had elevated D-dimer and fibrinogen. No patient developed disseminated intravascular coagulation. Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant. Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs. 2.1%, p < 0.008). Coagulation parameters significantly differed between the two groups. CONCLUSION: Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications. Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.

Acute Pulmonary Embolism in Patients with COVID-19 at CT Angiography and Relationship to d-Dimer Levels.

Online supplemental material is available for this article.

Septic Shock Alters Mitochondrial Respiration of Lymphoid Cell-Lines and Human Peripheral Blood Mononuclear Cells: The Role of Plasma.

INTRODUCTION: In septic shock patients, postseptic immunosuppression state after the systemic inflammatory response syndrome is responsible for nosocomial infections, with subsequent increased mortality. The aim of the present study was to assess the underlying cellular mechanisms of the postseptic immunosuppression state, by investigating mitochondrial functions of peripheral blood mononuclear cells (PBMCs) from septic shock patients over 7 days. MATERIALS AND METHODS: Eighteen patients admitted to a French intensive care unit for septic shock were included. At days 1 and 7, PBMCs were isolated by Ficoll density gradient centrifugation. Mitochondrial respiration of intact septic PBMCs was assessed versus control group PBMCs, by measuring O2 consumption in plasma, using high-resolution respirometry. Mitochondrial respiration was then compared between septic plasmas and control plasmas for control PBMCs, septic PBMCs, and lymphoid cell-line (CEM). To investigate the role of plasma, we measured several plasma cytokines, among them High-Mobility Group Box 1 (HMGB1), by enzyme-linked immunosorbent assays. RESULTS: Basal O2 consumption of septic shock PBMCs was of 8.27 ±â€Š3.39 and 10.48 ±â€Š3.99 pmol/s/10 cells at days 1 and 7, respectively, significantly higher than in control PBMCs (5.37 ±â€Š1.46 pmol/s/10 cells, P < 0.05). Septic patient PBMCs showed a lower response to oligomycin, suggesting a reduced ATP-synthase activity, as well as an increased response to carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) suggesting an increased mitochondrial respiratory capacity. At 6 h, septic plasmas showed a decreased O2 consumption of CEM (4.73 ±â€Š1.46 vs. 6.58 ±â€Š1.53, P < 0.05) as well as in control group PBMCs (1.76 ±â€Š0.36 vs. 2.70 ±â€Š0.42, P < 0.05), and triggered a decreased ATP-synthase activity but an increased response to FCCP. These differences are not explained by different cell survival. High HMGB1 levels were significantly associated with reduced PBMCs mitochondrial respiration. CONCLUSIONS: Septic plasma impairs mitochondrial respiration in immune cells, with a possible role of the proinflammatory protein HMGB1, leading to a subsequent compensation, probably by enzymatic activation. This compensation result is an improvement of global mitochondrial respiratory capacity, but without restoring ATP-synthase activity.

Immunohaemostasis: a new view on haemostasis during sepsis.

Host infection by a micro-organism triggers systemic inflammation, innate immunity and complement pathways, but also haemostasis activation. The role of thrombin and fibrin generation in host defence is now recognised, and thrombin has become a partner for survival, while it was seen only as one of the "principal suspects" of multiple organ failure and death during septic shock. This review is first focused on pathophysiology. The role of contact activation system, polyphosphates and neutrophil extracellular traps has emerged, offering new potential therapeutic targets. Interestingly, newly recognised host defence peptides (HDPs), derived from thrombin and other "coagulation" factors, are potent inhibitors of bacterial growth. Inhibition of thrombin generation could promote bacterial growth, while HDPs could become novel therapeutic agents against pathogens when resistance to conventional therapies grows. In a second part, we focused on sepsis-induced coagulopathy diagnostic challenge and stratification from "adaptive" haemostasis to "noxious" disseminated intravascular coagulation (DIC) either thrombotic or haemorrhagic. Besides usual coagulation tests, we discussed cellular haemostasis assessment including neutrophil, platelet and endothelial cell activation. Then, we examined therapeutic opportunities to prevent or to reduce "excess" thrombin generation, while preserving "adaptive" haemostasis. The fail of international randomised trials involving anticoagulants during septic shock may modify the hypothesis considering the end of haemostasis as a target to improve survival. On the one hand, patients at low risk of mortality may not be treated to preserve "immunothrombosis" as a defence when, on the other hand, patients at high risk with patent excess thrombin and fibrin generation could benefit from available (antithrombin, soluble thrombomodulin) or ongoing (FXI and FXII inhibitors) therapies. We propose to better assess coagulation response during infection by an improved knowledge of pathophysiology and systematic testing including determination of DIC scores. This is one of the clues to allocate the right treatment for the right patient at the right moment.

Clinical pathologists and physician in France: which partnership and which future?

Medical biology is a major area of medical specialization in French health care system. It is going through massive changes in public as in private sector since the 2010 Ballereau edict with the merging of laboratories and new quality standards based on accreditation. We have suggested that physicians had a negative feeling about the restructuring of medical biology in recent years. An electronic questionnaire has been sent to physicians so as to find out what they thought about the evolution of medical biology and to get suggestions to improve the taking care of the patient. Have answered 1364 residents and physicians from all specializations, all regions, practicing in public or private hospitals or in general practices. Doctors have on the whole a negative feeling about how medical biology has evolved in recent years thinking that it is moving towards industrialization with delay increasing. They are convinced that tests must be made on site. They remain satisfied with the quality of the tests and have a positive feeling about scientific evolutions and are in favor of a better clinical-biological cooperation. The study points out a lack of clarity concerning how private laboratories are organized and how they operate. A computer link between clinical pathologists and physicians to access results and a list of urgent medical examinations could be set up so as to have a more rapid access to results. Rapid diagnostic tests or delocalized biology could be used but doctors do not want these tests to replace the clinical pathologist.

Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome After Pneumonectomy.

BACKGROUND: Postpneumonectomy acute respiratory distress syndrome (ppARDS) is a life-threatening condition with a disastrous prognosis. This study assessed the efficacy of venovenous extracorporeal membrane oxygenation (VV-ECMO) in adult patients with unresponsive severe ppARDS. METHODS: We retrospectively reviewed data of all patients treated with VV-ECMO for ppARDS from January 2009 to December 2015. We calculated the Sequential Organ Failure Assessment score before ECMO insertion and monitored the subsequent mechanical ventilation settings. The primary end point was hospital survival. The secondary end point was the ability to achieve a protective ventilatory strategy allowing lung recovery on ECMO. RESULTS: VV-ECMO was indicated in 8 ppARDS patients for refractory hypoxemia (median partial pressure of arterial oxygen/fraction of inspired oxygen: 68 [range, 60 to 75] mm Hg). Median Sequential Organ Failure Assessment before ECMO was 15 (range, 12 to 17), predicting a mortality rate greater than 80%. Median duration of ECMO was 9.5 (range, 5 to 16) days. Tidal volumes and plateau pressures both decreased on ECMO (pre-ECMO tidal volume: 412 [range, 250 to 450 mL] vs ECMO tidal volume: 277 [range, 105 to 367 mL], p = 0.0156; pre-ECMO plateau pressure: 34 [range, 32 to 40] cm H2O vs ECMO plateau pressure: 24.5 [range, 23.3 to 27.3] cm H2O, p = 0.0195). ECMO could be weaned in 7 patients (87.5%). Hospital survival was 50%. CONCLUSIONS: Hospital survival was better than predicted before ECMO insertion. In severe and refractory ppARDS, VV-ECMO allows lung recovery and therefore increased survival.

Evidence of Netosis in Septic Shock-Induced Disseminated Intravascular Coagulation.

INTRODUCTION: Neutrophils extracellular traps (NETs) have recently emerged as a new potential link between inflammation, immunity, and thrombosis and could play a key role in septic shock-induced disseminated intravascular coagulation (DIC) pathogenesis. The objective of our study was to investigate a potential link between NETosis and septic shock-induced DIC. METHODS: Twenty patients with septic shock (10 without and 10 with DIC according to JAAM 2006 score) were prospectively included in our study. Vascular cell activation was assessed by microparticle (MP) measurement. NETosis was investigated at days 1, 3, and 7 using two different approaches: probing and measurement of neutrophil DNA decompaction by neutrophil-side fluorescence light (NEUT-SFL) as recorded by an automated blood cell cytometer and the assessment of nucleosomes and NETs (DNA-bound myeloperoxidase, DNA-MPO). RESULTS: Endothelial-derived CD105-MPs, leucocyte-derived CD11a-MPs/leucocyte, and neutrophil-derived CD66b-MPs/neutrophil count ratios significantly increased in DIC compared with non-DIC patients, indicating on-going cell activation (P <0.05). NEUT-SFL, indicating DNA decompaction, was significantly higher in DIC patients. Circulating nucleosomes and DNA-MPO were increased in DIC patients (P <0.05). There were significant correlations between: nucleosomes and NETs (r = 0.397, P = 0.004), NEUT-SFL and nucleosomes (r = 0.243, P = 0.032), NEUT-SFL and DNA-MPO (r = 0.266, P = 0.024). CONCLUSION: NEUT-SFL, NETs, and elevated nucleosome concentrations were all correlated to DIC (P <0.05). We have shown that NETosis is significantly correlated to septic shock-induced DIC.

Neutrophil Fluorescence: A New Indicator of Cell Activation During Septic Shock-Induced Disseminated Intravascular Coagulation.

OBJECTIVE: To investigate the contribution of neutrophil activation as innate immune cells during septic shock-induced disseminated intravascular coagulation. DESIGN: Prospective study. SETTING: One University Hospital ICU. PARTICIPANTS: Hundred patients with septic shock. Thirty-five patients had disseminated intravascular coagulation according to Japanese Association for Acute Medicine 2006 score. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Neutrophil chromatin decondensation was assessed by measuring neutrophil fluorescence (NEUT-side-fluorescence light) labeled by a fluorochrome-based polymethine reagent using a routine automated flow cytometer Sysmex XN20 (Sysmex, Kobe, Japan) and neutrophil-derived CD66b microparticles by prothrombinase assay. Measurements in disseminated intravascular coagulation and no disseminated intravascular coagulation patients showed that a mean value of NEUT-side-fluorescence light above 57.3 arbitrary units had a sensitivity of 90.91% and a specificity of 80.60% for disseminated intravascular coagulation diagnosis. NEUT-side-fluorescence light was correlated to the CD66b microparticles/neutrophil count, a surrogate of neutrophil activation associated with septic shock-induced disseminated intravascular coagulation. CONCLUSION: NEUT-side-fluorescence light, routinely available, could prove an accurate biomarker of neutrophil activation.