Publications by authors named "Bruno Lévy"

162 Publications

Outcomes in patients treated with chimeric antigen receptor T-cell therapy who were admitted to intensive care (CARTTAS): an international, multicentre, observational cohort study.

Lancet Haematol 2021 May;8(5):e355-e364

Critical Care Department, APHP, Hôpital Saint-Louis, University of Paris, Paris, France.

Background: Chimeric antigen receptor (CAR) T-cell therapy can induce side-effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS), which often require intensive care unit admission. The aim of this study was to describe management of critically ill CAR T-cell recipients in intensive care.

Methods: This international, multicentre, observational cohort study was done in 21 intensive care units in France, Spain, the USA, the UK, Russia, Canada, Germany, and Austria. Eligible patients were aged 18 years or older; had received CAR T-cell therapy in the past 30 days; and had been admitted to intensive care for any reason. Investigators retrospectively included patients admitted between Feb 1, 2018, and Feb 1, 2019, and prospectively included patients admitted between March 1, 2019, and Feb 1, 2020. Demographic, clinical, laboratory, treatment, and outcome data were extracted from medical records. The primary endpoint was 90-day mortality. Factors associated with mortality were identified using a Cox proportional hazard model.

Findings: 942 patients received CAR T-cell therapy, of whom 258 (27%) required admission to intensive care and 241 (26%) were included in the analysis. Admission to intensive care was needed within median 4·5 days (IQR 2·0-7·0) of CAR T-cell infusion. 90-day mortality was 22·4% (95% CI 17·1-27·7; 54 deaths). At initial evaluation on admission, isolated cytokine release syndrome was identified in 101 patients (42%), cytokine release syndrome and ICANS in 93 (39%), and isolated ICANS in seven (3%) patients. Grade 3-4 cytokine release syndrome within 1 day of admission to intensive care was found in 50 (25%) of 200 patients and grade 3-4 ICANS in 38 (35%) of 108 patients. Bacterial infection developed in 30 (12%) patients. Life-saving treatments were used in 75 (31%) patients within 24 h of admission to intensive care, primarily vasoactive drugs in 65 (27%) patients. Factors independently associated with 90-day mortality by multivariable analysis were frailty (hazard ratio 2·51 [95% CI 1·37-4·57]), bacterial infection (2·12 [1·11-4·08]), and lifesaving therapy within 24 h of admission (1·80 [1·05-3·10]).

Interpretation: Critical care management is an integral part of CAR T-cell therapy and should be standardised. Studies to improve infection prevention and treatment in these high-risk patients are warranted.

Funding: Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique.
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http://dx.doi.org/10.1016/S2352-3026(21)00060-0DOI Listing
May 2021

The medical treatment of cardiogenic shock: cardiovascular drugs.

Curr Opin Crit Care 2021 Mar 31. Epub 2021 Mar 31.

Department of Intensive Care, CHIREC Hospitals, Université Libre de Bruxelles, Brussels, Belgium Department of Intensive Care, National ECMO Center, Calderon Guardia Hospital, Universidad de Costa Rica, San José, Costa Rica CHRU Nancy, Service de Réanimation Médicale Brabois, Pôle Cardiovasculaire et Réanimation Médicale, Hôpital Brabois, Vandoeuvre les Nancy, France INSERM U 1116, Groupe Choc, Equipe 2, Faculté de Médecine, Vandoeuvre les Nancy, France Université de Lorraine, Faculté de Médecine, Nancy, France.

Purpose Of Review: To discuss the use of vasopressors and inotropes in cardiogenic shock.

Recent Findings: The classic form or cardiogenic shock requires administration of inotropic and/or vasopressor agents to try to improve the impaired tissue perfusion. Among vasopressors various alpha-adrenergic agents, vasopressin derivatives and angiotensin can be used. The first-line therapy remains norepinephrine as it is associated with minimal adverse effects and appears to be associated by the best outcome in network meta-analyses. On the contrary, epinephrine is associated with an increased incidence of refractory shock and observational studies suggest an increased risk of death. Vasopressin may be an excellent alternative in tachycardiac patients or in the presence of pulmonary hypertension. Concerning inotropic agents, dobutamine is the first-line agent but levosimendan is an excellent alternative or additional agent in cases not responding to dobutamine. The impact on outcome of inotropic agents remains controversial.

Summary: Recent studies have refined the position of the various vasopressor and inotropic agents. Norepinephrine is recommended as first-line vasopressor agent by various guidelines. Among inotropic agents, selection between the agents should be individualized and based on the hemodynamic response.
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http://dx.doi.org/10.1097/MCC.0000000000000822DOI Listing
March 2021

The Fundamentals of Respiratory Physiology to Manage the COVID-19 Pandemic: An Overview.

Front Physiol 2020 18;11:615690. Epub 2021 Feb 18.

EA 3450 DevAH-Développement, Adaptation et Handicap, Régulations cardio-respiratoires et de la motricité, Université de Lorraine, Nancy, France.

The growing coronavirus disease (COVID-19) crisis has stressed worldwide healthcare systems probably as never before, requiring a tremendous increase of the capacity of intensive care units to handle the sharp rise of patients in critical situation. Since the dominant respiratory feature of COVID-19 is worsening arterial hypoxemia, eventually leading to acute respiratory distress syndrome (ARDS) promptly needing mechanical ventilation, a systematic recourse to intubation of every hypoxemic patient may be difficult to sustain in such peculiar context and may not be deemed appropriate for all patients. Then, it is essential that caregivers have a solid knowledge of physiological principles to properly interpret arterial oxygenation, to intubate at the satisfactory moment, to adequately manage mechanical ventilation, and, finally, to initiate ventilator weaning, as safely and as expeditiously as possible, in order to make it available for the next patient. Through the expected mechanisms of COVID-19-induced hypoxemia, as well as the notion of silent hypoxemia often evoked in COVID-19 lung injury and its potential parallelism with high altitude pulmonary edema, from the description of hemoglobin oxygen affinity in patients with severe COVID-19 to the interest of the prone positioning in order to treat severe ARDS patients, this review aims to help caregivers from any specialty to handle respiratory support following recent knowledge in the pathophysiology of respiratory SARS-CoV-2 infection.
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http://dx.doi.org/10.3389/fphys.2020.615690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930571PMC
February 2021

Soluble triggering receptor expressed on myeloid cells-1 is a marker of organ injuries in cardiogenic shock: results from the CardShock Study.

Clin Res Cardiol 2021 Mar 7. Epub 2021 Mar 7.

Université de Lorraine, CHRU de Nancy, Médecine Intensive et Réanimation Central, INSERM U1116, Nancy, France.

Aims: Optimal outcome after cardiogenic shock (CS) depends on a coordinated healing response in which both debris removal and extracellular matrix tissue repair play a crucial role. Excessive inflammation can perpetuate a vicious circle, positioning leucocytes as central protagonists and potential therapeutic targets. High levels of circulating Triggering Receptor Expressed on Myeloid cells-1 (TREM-1), were associated with death in acute myocardial infarction confirming excessive inflammation as determinant of bad outcome. The present study aims to describe the association of soluble TREM-1 with 90-day mortality and with various organ injuries in patients with CS.

Methods And Results: This is a post-hoc study of CardShock, a prospective, multicenter study assessing the clinical presentation and management in patients with CS. At the time of this study, 87 patients had available plasma samples at either baseline, and/or 48 h and/or 96-120 h for soluble TREM-1 (sTREM-1) measurements. Plasma concentration of sTREM-1 was higher in 90-day non-survivors than survivors at baseline [median: 1392 IQR: (724-2128) vs. 621 (525-1233) pg/mL, p = 0.008), 48 h (p = 0.019) and 96-120 h (p = 0.029). The highest tertile of sTREM-1 at baseline (threshold: 1347 pg/mL) was associated with 90-day mortality with an unadjusted HR 3.08 CI 95% (1.48-6.42). sTREM-1 at baseline was not associated to hemodynamic parameters (heart rate, blood pressure, use of vasopressors or inotropes) but rather with organ injury markers: renal (estimated glomerular filtration rate, p = 0.0002), endothelial (bio-adrenomedullin, p = 0.018), myocardial (Suppression of Tumourigenicity 2, p = 0.002) or hepatic (bilirubin, p = 0.008).

Conclusion: In CS patients TREM-1 pathway is highly activated and gives an early prediction of vital organ injuries and outcome.
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http://dx.doi.org/10.1007/s00392-021-01823-0DOI Listing
March 2021

Six-Month Survival After Extracorporeal Membrane Oxygenation for Severe COVID-19.

J Cardiothorac Vasc Anesth 2021 Jan 19. Epub 2021 Jan 19.

Service de Chirurgie Thoracique et Cardio-vasculaire, Hôpital Henri-Mondor, Assistance Publique - Hôpitaux de Paris, Créteil, France.

Objectives: The authors evaluated the outcome of adult patients with coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) requiring the use of extracorporeal membrane oxygenation (ECMO).

Design: Multicenter retrospective, observational study.

Setting: Ten tertiary referral university and community hospitals.

Participants: Patients with confirmed severe COVID-19-related ARDS.

Interventions: Venovenous or venoarterial ECMO.

Measurements And Main Results: One hundred thirty-two patients (mean age 51.1 ± 9.7 years, female 17.4%) were treated with ECMO for confirmed severe COVID-19-related ARDS. Before ECMO, the mean Sequential Organ Failure Assessment score was 10.1 ± 4.4, mean pH was 7.23 ± 0.09, and mean PaO/fraction of inspired oxygen ratio was 77 ± 50 mmHg. Venovenous ECMO was adopted in 122 patients (92.4%) and venoarterial ECMO in ten patients (7.6%) (mean duration, 14.6 ± 11.0 days). Sixty-three (47.7%) patients died on ECMO and 70 (53.0%) during the index hospitalization. Six-month all-cause mortality was 53.0%. Advanced age (per year, hazard ratio [HR] 1.026, 95% CI 1.000-1-052) and low arterial pH (per unit, HR 0.006, 95% CI 0.000-0.083) before ECMO were the only baseline variables associated with increased risk of six-month mortality.

Conclusions: The present findings suggested that about half of adult patients with severe COVID-19-related ARDS can be managed successfully with ECMO with sustained results at six months. Decreased arterial pH before ECMO was associated significantly with early mortality. Therefore, the authors hypothesized that initiation of ECMO therapy before severe metabolic derangements subset may improve survival rates significantly in these patients. These results should be viewed in the light of a strict patient selection policy and may not be replicated in patients with advanced age or multiple comorbidities.

Clinical Trial Registration: identifier, NCT04383678.
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http://dx.doi.org/10.1053/j.jvca.2021.01.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816613PMC
January 2021

Comparison of Vasopressin versus Norepinephrine in a Pig Model of Refractory Cardiogenic Shock Complicated by Cardiac Arrest and Resuscitated with Veno-Arterial ECMO.

Shock 2021 Feb 3. Epub 2021 Feb 3.

CHRU Nancy, Service de Réanimation Médicale Brabois, Pôle Cardiovasculaire et Réanimation Médicale, Hôpital Brabois, Vandoeuvre les Nancy, France INSERM U 1116, Groupe Choc, Equipe 2, Faculté de Médecine, Vandoeuvre les Nancy, France Université de Lorraine, Faculté de Médecine, Nancy, France CHRU Nancy, Service de Chirurgie Cardiaque, Pôle Cardiovasculaire et Réanimation Médicale, Hôpital Brabois, Vandoeuvre les Nancy, France Ecole de Chirurgie, Faculté de médecine, Université de Lorraine, Nancy, France CHRU de Nancy, Service de Biochimie, Pôle Laboratoires Hôpital Central, Nancy, France CHRU de Nancy, Plateforme d'aide à la recherche clinique (PARC), ESPRI-Biobase, Hôpital de Brabois, Vandoeuvre les Nancy, France.

Background: The choice of the best vasopressor after ECMO implantation after cardiac arrest is not well defined. Circulatory flow recovery with ECMO is associated with vasoplegia and vasopressor need. The present study aimed to compare the effects of norepinephrine and vasopressin in the first six hours after ECMO initiation.

Methods: Cardiac arrest was induced in 20 pigs by coronary surgical ligature and VA-ECMO was started after a 30-min period of cardio-pulmonary resuscitation. Pigs were randomised into two groups, AVP or NE, with the drugs titrated to maintain a MAP at 65 mmHg. Macrocirculatory and metabolic parameters were assessed by lactate clearance. Microcirculatory parameters were assessed by sublingual microcirculation with Sidestream Dark Field (SDF) imaging and peripheral Near InfraRed Spectroscopy (NIRS). Pulmonary oedema was evaluated by measuring lung wet/dry weight ratio.

Results: No difference was found between groups regarding ECMO flow and Mean Arterial Pressure. Fluid resuscitation volume was higher in the NE group (14000 [11250-15250] mL versus 3500 [1750 - 4000] mL in the AVP group, p < 0.05). Lung wet/dry weight ratio was higher in the Norepinephrine group. Lactate clearance between H0 and H6 was higher in the AVP group (47.84 [13.42 - 82.73] % versus the NE group 25.66 [-7.31 - 35.34) % vs., p < 0.05). No significant difference was observed for sublingual microcirculation values. Baseline tissue oxygen saturation was comparable and higher at both H3 and H6 in the Vasopressin group comparatively to the Norepinephrine group (p < 0.05) (Table 5). Renal and liver function evolution also remained similar in the two groups throughout the study.

Conclusions: AVP administration in refractory cardiac arrest resuscitated by VA-ECMO is associated with a faster lactate clearance, less fluid resuscitation and less pulmonary oedema when compared to NE for similar global and regional hemodynamic effects.
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http://dx.doi.org/10.1097/SHK.0000000000001747DOI Listing
February 2021

Current use of inotropes in circulatory shock.

Ann Intensive Care 2021 Jan 29;11(1):21. Epub 2021 Jan 29.

Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, USA.

Background: Treatment decisions on critically ill patients with circulatory shock lack consensus. In an international survey, we aimed to evaluate the indications, current practice, and therapeutic goals of inotrope therapy in the treatment of patients with circulatory shock.

Methods: From November 2016 to April 2017, an anonymous web-based survey on the use of cardiovascular drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 14 questions focused on the profile of respondents, the triggering factors, first-line choice, dosing, timing, targets, additional treatment strategy, and suggested effect of inotropes. In addition, a group of 42 international ESICM experts was asked to formulate recommendations for the use of inotropes based on 11 questions.

Results: A total of 839 physicians from 82 countries responded. Dobutamine was the first-line inotrope in critically ill patients with acute heart failure for 84% of respondents. Two-thirds of respondents (66%) stated to use inotropes when there were persistent clinical signs of hypoperfusion or persistent hyperlactatemia despite a supposed adequate use of fluids and vasopressors, with (44%) or without (22%) the context of low left ventricular ejection fraction. Nearly half (44%) of respondents stated an adequate cardiac output as target for inotropic treatment. The experts agreed on 11 strong recommendations, all of which were based on excellent (> 90%) or good (81-90%) agreement. Recommendations include the indications for inotropes (septic and cardiogenic shock), the choice of drugs (dobutamine, not dopamine), the triggers (low cardiac output and clinical signs of hypoperfusion) and targets (adequate cardiac output) and stopping criteria (adverse effects and clinical improvement).

Conclusion: Inotrope use in critically ill patients is quite heterogeneous as self-reported by individual caregivers. Eleven strong recommendations on the indications, choice, triggers and targets for the use of inotropes are given by international experts. Future studies should focus on consistent indications for inotrope use and implementation into a guideline for circulatory shock that encompasses individualized targets and outcomes.
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http://dx.doi.org/10.1186/s13613-021-00806-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846624PMC
January 2021

Hemodynamic and anti-inflammatory effects of early esmolol use in hyperkinetic septic shock: a pilot study.

Crit Care 2021 01 7;25(1):21. Epub 2021 Jan 7.

INSERM CIC1433, Nancy University Hospital, 54000, Nancy, France.

Background: Several studies have shown that heart rate control with selective beta-1 blockers in septic shock is safe. In these trials, esmolol was administered 24 h after onset of septic shock in patients who remained tachycardic. While an earlier use of beta-blockers might be beneficial, such use remains challenging due to the difficulty in distinguishing between compensatory and non-compensatory tachycardia. Therefore, the Esmosepsis study was designed to study the effects of esmolol aimed at reducing the heart rate by 20% after the initial resuscitation process in hyperkinetic septic shock patients on (1) cardiac index and (2) systemic and regional hemodynamics as well as inflammatory patterns.

Methods: Nine consecutive stabilized tachycardic hyperkinetic septic shock patients treated with norepinephrine for a minimum of 6 h were included. Esmolol was infused during 6 h in order to decrease the heart rate by 20%. The following data were recorded at hours H0 (before esmolol administration), H1-H6 (esmolol administration) and 1 h after esmolol cessation (H7): systolic arterial pressure, diastolic arterial pressure, mean arterial pressure, central venous pressure, heart rate, PICCO transpulmonary thermodilution, sublingual and musculo-cutaneous microcirculation, indocyanine green clearance and echocardiographic parameters, diuresis, lactate, and arterial and venous blood gases.

Results: Esmolol was infused 9 (6.4-11.6) hours after norepinephrine introduction. Esmolol was ceased early in 3 out of 9 patients due to a marked increase in norepinephrine requirement associated with a picture of persistent cardiac failure at the lowest esmolol dose. For the global group, during esmolol infusion, norepinephrine infusion increased from 0.49 (0.34-0.83) to 0.78 (0.3-1.11) µg/min/kg. The use of esmolol was associated with a significant decrease in heart rate from 115 (110-125) to 100 (92-103) beats/min and a decrease in cardiac index from 4.2 (3.1-4.4) to 2.9 (2.5-3.7) l/min/m. Indexed stroke volume remained unchanged. Cardiac function index and global ejection fraction also markedly decreased. Using echocardiography, systolic, diastolic as well as left and right ventricular function parameters worsened. After esmolol cessation, all parameters returned to baseline values. Lactate and microcirculatory parameters did not change while the majority of pro-inflammatory proteins decreased in all patients.

Conclusion: In the very early phase of septic shock, heart rate reduction using fast esmolol titration is associated with an increased risk of hypotension and decreased cardiac index despite maintained adequate tissue perfusion (NCT02068287).
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http://dx.doi.org/10.1186/s13054-020-03445-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791811PMC
January 2021

Hemodynamic Profiles of Cardiogenic Shock Depending on Their Etiology.

J Clin Med 2020 Oct 22;9(11). Epub 2020 Oct 22.

Cardiology Department, APHM, Mediterranean Association for Research and Studies in Cardiology (MARS Cardio), Centre for CardioVascular and Nutrition Research (C2VN), Aix-Marseille Univ, INSERM 1263, INRA 1260, Hopital Nord, 13015 Marseille, France.

The pathophysiology of cardiogenic shock (CS) varies depending on its etiology, which may lead to different hemodynamic profiles (HP) and may help tailor therapy. We aimed to assess the HP of CS patients according to their etiologies of acute myocardial infarction (AMI) and acute decompensated chronic heart failure (ADCHF). We included patients admitted for CS secondary to ADCHF and AMI. HP were measured before the administration of any inotrope or vasopressor. Systemic Vascular Resistances index (SVRi), Cardiac Index (CI), and Cardiac Power Index (CPI) were measured by trans-thoracic Doppler echocardiography on admission. Among 37 CS patients, 28 had CS secondary to ADCHF or AMI and were prospectively included. The two groups were similar in terms of demographic data and shock severity criteria. AMI CS was associated with lower SVRi compared to CS related to ADCHF: 2010 (interquartile range (IQR): 1895-2277) vs. 2622 (2264-2993) dynes-s·cm·m ( = 0.002). A trend toward a higher CI was observed: respectively 2.13 (1.88-2.18) vs. 1.78 (1.65-1.96) L·min·m ( = 0.067) in AMICS compared to ADCHF. CS patients had different HP according to their etiologies. AMICS had lower SVR and tended to have a higher CI compared to ADHF CS. These differences should be taken into account for patient selection in future research.
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http://dx.doi.org/10.3390/jcm9113384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690259PMC
October 2020

The spectrum of biochemical alterations associated with organ dysfunction and inflammatory status and their association with disease outcomes in severe COVID-19: A longitudinal cohort and time-series design study.

EClinicalMedicine 2020 Oct 20;27:100554. Epub 2020 Sep 20.

Department of Molecular Medicine, Division of Biochemistry, Molecular Biology, and Nutrition, University Hospital of Nancy, F-54000 Nancy, France.

Background: In patients with severe COVID-19, no data are available on the longitudinal evolution of biochemical abnormalities and their ability to predict disease outcomes.

Methods: Using a retrospective, longitudinal cohort study design on consecutive patients with severe COVID-19, we used an extensive biochemical dataset of serial data and time-series design to estimate the occurrence of organ dysfunction and the severity of the inflammatory reaction and their association with acute respiratory failure (ARF) and death.

Findings: On the 162 studied patients, 1151 biochemical explorations were carried out for up to 59 biochemical markers, totaling 15,260 biochemical values. The spectrum of biochemical abnormalities and their kinetics were consistent with a multi-organ involvement, including lung, kidney, heart, liver, muscle, and pancreas, along with a severe inflammatory syndrome. The proportion of patients who developed an acute kidney injury (AKI) stage 3, increased significantly during follow-up (0·9%, day 0; 21·4%, day 14; <0·001). On the 20 more representative biochemical markers (>250 iterations), only CRP >90 mg/L (odds ratio [OR] 6·87, 95% CI, 2·36-20·01) and urea nitrogen >0·36 g/L (OR 3·91, 95% CI, 1·15-13·29) were independently associated with the risk of ARF. Urea nitrogen >0·42 g/L was the only marker associated with the risk of COVID-19 related death.

Interpretation: Our results point out the lack of the association between the inflammatory markers and the risk of death but rather highlight a significant association between renal dysfunction and the risk of COVID-19 related acute respiratory failure and death.
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http://dx.doi.org/10.1016/j.eclinm.2020.100554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502281PMC
October 2020

Venoarterial extracorporeal membrane oxygenation to rescue sepsis-induced cardiogenic shock: a retrospective, multicentre, international cohort study.

Lancet 2020 08;396(10250):545-552

Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France; Sorbonne Université INSERM-UMRS 1166, Institute of Cardiometabolism and Nutrition, Paris, France.

Background: Patients with sepsis-induced cardiomyopathy with cardiogenic shock have a high mortality. This study assessed venoarterial extracorporeal membrane oxygenation (VA-ECMO) support for sepsis-induced cardiogenic shock refractory to conventional treatments.

Methods: In this retrospective, multicentre, international cohort study, we compared outcomes of 82 patients (aged ≥18 years) with septic shock who received VA-ECMO at five academic ECMO centres, with 130 controls (not receiving ECMO) obtained from three large databases of septic shock. All patients had severe myocardial dysfunction (cardiac index 3 L/min per m or less or left ventricular ejection fraction [LVEF] 35% or less) and severe haemodynamic compromise (inotrope score at least 75 μg/kg per min or lactic acidaemia at least 4 mmol/L) at time of inclusion. The primary endpoint was survival at 90 days. A propensity score-weighted analysis was done to control for confounders.

Findings: At baseline, patients treated with VA-ECMO had more severe myocardial dysfunction (mean cardiac index 1·5 L/min per mvs 2·2 L/min per m, LVEF 17% vs 27%), more severe haemodynamic impairment (inotrope score 279 μg/kg per min vs 145 μg/kg per min, lactataemia 8·9 mmol/L vs 6·5 mmol/L), and more severe organ failure (Sequential Organ Failure Assessment score 17 vs 13) than did controls, with p<0·0001 for each comparison. Survival at 90 days for patients treated with VA-ECMO was significantly higher than for controls (60% vs 25%, risk ratio [RR] for mortality 0·54, 95% CI [0·40-0·70]; p<0·0001). After propensity score weighting, ECMO remained associated with improved survival (51% vs 14%, adjusted RR for mortality 0·57, 95% CI [0·35-0·93]; p=0·0029). Lactate and catecholamine clearance were also significantly enhanced in patients treated with ECMO. Among the 49 survivors treated with ECMO, 32 who had been treated at the largest centre reported satisfactory Short Form-36 evaluated health-related quality of life at 1-year follow-up.

Interpretation: Patients with severe sepsis-induced cardiogenic shock treated with VA-ECMO had a large and significant improvement in survival compared with controls not receiving ECMO. However, despite the careful propensity-weighted analysis, we cannot rule out unmeasured confounders.

Funding: None.
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http://dx.doi.org/10.1016/S0140-6736(20)30733-9DOI Listing
August 2020

Usefulness and safety of a dedicated team to prone patients with severe ARDS due to COVID-19.

Crit Care 2020 08 18;24(1):509. Epub 2020 Aug 18.

CHRU-Nancy, Centre Universitaire de Médecine du Sport et Activité Physique Adaptée, Explorations Fonctionnelles Respiratoires, EA DevAH, Département de Physiologie, Université de Lorraine, F-54000, Nancy, France.

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http://dx.doi.org/10.1186/s13054-020-03128-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431895PMC
August 2020

Coronavirus disease 2019: acute Fanconi syndrome precedes acute kidney injury.

Clin Kidney J 2020 Jun 8;13(3):362-370. Epub 2020 Jun 8.

Department of Molecular Medicine, Division of Biochemistry, Molecular Biology, Nutrition, and Metabolism, University of Lorraine, CHRU-Nancy, Vandoeuvre, France.

Background: Recent data have shown that severe acute respiratory syndrome coronavirus 2 can infect renal proximal tubular cells via Angiotensin Converting Enzyme 2 (ACE2) . Our objective was to determine whether Fanconi syndrome is a frequent clinical feature in coronavirus disease 2019 (COVID-19) patients.

Methods: A retrospective cohort of 42 laboratory-confirmed COVID-19 patients without history of kidney disease hospitalized in University Hospital of Nancy was investigated. Patients were admitted to the intensive care unit (ICU) ( = 28) or the Medical department ( = 14) and were screened at least once for four markers of proximal tubulopathy.

Results: The mean (standard deviation) follow-up was 19.7 (±12.2) days. Of the patients, 75% (30/40) showed at least two proximal tubule abnormalities (incomplete Fanconi syndrome). The main disorders were proteinuria (88%, = 35), renal phosphate leak defined by renal phosphate threshold/glomerular filtration rate (TmPi/GFR) <0.77 (55%,  = 22), hyperuricosuria (43%,  = 17) and normoglycaemic glycosuria (30%,  = 12). At the time of the first renal evaluation, ICU patients presented more frequent (96 versus 62%, P = 0.0095) and more severe (844 ± 343 versus 350 ± 221 mg/g, P = 0.0001) proteinuria, and a trend for an increased number of proximal tubule abnormalities (P = 0.038). During follow-up, they presented a lower nadir of serum phosphate [median (interquartile range) 0.68 (0.43-0.76) versus 0.77 (0.66-1.07) mmol/L, P = 0.044] and Acute kidney Injury (AKI) during the hospitalization (P = 0.045). Fanconi syndrome preceded severe AKI KDIGO Stages 2 and 3 in 88% (7/8) of patients. Proximal tubular abnormalities (such as proteinuria, TmPi/GFR and glycosuria in five, two and two patients, respectively) were not detected anymore in recovering patients before hospital discharge.

Conclusion: Incomplete Fanconi syndrome is highly frequent in COVID-19 patients and precedes AKI or disappears during the recovery phase.
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http://dx.doi.org/10.1093/ckj/sfaa109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314200PMC
June 2020

Long-term ACE Inhibitor/ARB Use Is Associated With Severe Renal Dysfunction and Acute Kidney Injury in Patients With Severe COVID-19: Results From a Referral Center Cohort in the Northeast of France.

Clin Infect Dis 2020 12;71(9):2447-2456

Department of Molecular Medicine, Division of Biochemistry, Molecular Biology, Nutrition, and Metabolism, University Hospital of Nancy, Nancy, France.

Background: In patients with severe coronavirus disease 2019 (COVID-19), data are scarce and conflicting regarding whether chronic use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) influences disease outcomes. In patients with severe COVID-19, we assessed the association between chronic ACEI/ARB use and the occurrence of kidney, lung, heart, and liver dysfunctions and the severity of the inflammatory reaction as evaluated by biomarkers kinetics, and their association with disease outcomes.

Methods: We performed a retrospective longitudinal cohort study on consecutive patients with newly diagnosed severe COVID-19. Independent predictors were assessed through receiver operating characteristic analysis, time-series analysis, logistic regression analysis, and multilevel modeling for repeated measures.

Results: On the 149 patients included in the study 30% (44/149) were treated with ACEI/ARB. ACEI/ARB use was independently associated with the following biochemical variations: phosphorus >40 mg/L (odds ratio [OR], 3.35, 95% confidence interval [CI], 1.83-6.14), creatinine >10.1 mg/L (OR, 3.22, 2.28-4.54), and urea nitrogen (UN) >0.52 g/L (OR, 2.65, 95% CI, 1.89-3.73). ACEI/ARB use was independently associated with acute kidney injury stage ≥1 (OR, 3.28, 95% CI, 2.17-4.94). The daily dose of ACEI/ARB was independently associated with altered kidney markers with an increased risk of +25 to +31% per each 10 mg increment of lisinopril-dose equivalent. In multivariable multilevel modeling, UN >0.52 g/L was independently associated with the risk of acute respiratory failure (OR, 3.54, 95% CI, 1.05-11.96).

Conclusions: Patients chronically treated with ACEI/ARB who have severe COVID-19 are at increased risk of acute kidney injury. In these patients, the increase in UN associated with ACEI/ARB use could predict the development of acute respiratory failure.
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http://dx.doi.org/10.1093/cid/ciaa677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454376PMC
December 2020

Clinical recurrences of COVID-19 symptoms after recovery: Viral relapse, reinfection or inflammatory rebound?

J Infect 2020 Nov 30;81(5):816-846. Epub 2020 Jun 30.

Infectious Diseases Department, University Hospital of Saint-Etienne, 42055 cedex 02 Saint-Etienne, GIMAP (EA 3064), France; University of Saint-Etienne, University of Lyon, Faculty of Medicine of Saint-Etienne, 42023 cedex 02 Saint-Etienne, France. Electronic address:

For the first 3 months of COVID-19 pandemic, COVID-19 was expected to be an immunizing non-relapsing disease. We report a national case series of 11 virologically-confirmed COVID-19 patients having experienced a second clinically- and virologically-confirmed acute COVID-19 episode. According to the clinical history, we discuss either re-infection or reactivation hypothesis. Larger studies including further virological, immunological and epidemiologic data are needed to understand the mechanisms of these recurrences.
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http://dx.doi.org/10.1016/j.jinf.2020.06.073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326402PMC
November 2020

The I-MICRO trial, Ilomedin for treatment of septic shock with persistent microperfusion defects: a double-blind, randomized controlled trial-study protocol for a randomized controlled trial.

Trials 2020 Jul 1;21(1):601. Epub 2020 Jul 1.

Department of Anaesthesiology, Critical Care Medicine and Burn Unit, AP-HP, Saint Louis and Lariboisière University Hospitals, 2 rue A. Paré, 75010, Paris, France.

Background: Septic shock remains a significant cause of death in critically ill patients. During septic shock, some patients will retain microcirculatory disorders despite optimal hemodynamic support (i.e., fluid resuscitation, vasopressors, inotropes). Alterations in the microcirculation are a key pathophysiological factor of organ dysfunction and death in septic shock patients. Ilomedin is a prostacyclin analog with vasodilatory effect and anti-thrombotic properties (i.e., inhibition of platelet aggregation) preferentially at the microcirculatory level. We hypothesize that early utilization of intravenous Ilomedin in septic shock patients with clinical persistence of microperfusion disorders would improve the recovery of organ dysfunction.

Methods: The I-MICRO trial is a multicenter, prospective, randomized, double-blinded, placebo-controlled study. We plan to recruit 236 adult patients with septic shock and persistent microcirculatory disorders (i.e., skin mottling or increased capillary refill time) despite hemodynamic support. Participants will be randomized to receive a 48-h intravenous infusion of either Ilomedin or placebo starting at the earliest 6 h and later 24 h after septic shock. The primary outcome will be the change (delta) of sequential organ failure assessment (SOFA) score between randomization and day 7. Secondary outcomes will include mean SOFA score during the first 7 days after randomization, mortality at day 28 post-randomization, number of ventilation-free survival days in the 28 days post-randomization, number of renal replacement therapy-free survival days in the 28 days post-randomization, number of vasopressor-free survival days in the 28 days post-randomization, and mottling score at day 1 after randomization.

Discussion: The trial aims to provide evidence on the efficacy and safety of Ilomedin in patients with septic shock and persistent microcirculatory disorders.

Trial Registration: NCT NCT03788837 . Registered on 28 December 2018.
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http://dx.doi.org/10.1186/s13063-020-04549-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329442PMC
July 2020

Vasopressor use in cardiogenic shock.

Curr Opin Crit Care 2020 08;26(4):411-416

Service de Réanimation Médicale Brabois, CHRU Nancy, Pôle Cardio-Médico-Chirurgical.

Purpose Of Review: Data and interventional trials on vasopressor use during cardiogenic shock are scarce. Their use is limited by their side-effects and the lack of solid evidence regarding their effectiveness in improving outcomes. In the present article, we review the current use of vasopressor therapy during cardiogenic shock.

Recent Findings: Two recent Cochrane analyses concluded that there was insufficient evidence to prove that any one vasopressor was superior to others in terms of mortality. A recent RCT and a meta-analysis on individual data suggested that norepinephrine may be preferred over epinephrine in patients with cardiogenic shock, in particular, after myocardial infarction. In patients with right ventricular failure and pulmonary hypertension, the use of vasopressin may be advocated under advanced monitoring.

Summary: When blood pressure needs to be restored, norepinephrine is a reasonable first-line agent. Information regarding comparative effective outcomes is sparse and their use should be limited to a temporary measure as a bridge to recovery, mechanical circulatory support or heart transplantation.
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http://dx.doi.org/10.1097/MCC.0000000000000743DOI Listing
August 2020

Spinal cord infarction during venoarterial-extracorporeal membrane oxygenation support.

J Artif Organs 2020 Dec 30;23(4):388-393. Epub 2020 May 30.

Hopital Universitaire Pitie Salpetriere, Paris, France.

Spinal cord infarction (SCI) is a rare disease among central nervous system vascular diseases. Only a little is known about venoarterial extracorporeal membrane oxygenation (VA-ECMO)-related SCI. Retrospective observational study conducted, from 2006 to 2019, in a tertiary referral center on patients who developed VA-ECMO-related neurovascular complications, focusing on SCI. During this period, among the 1893 patients requiring VA-ECMO support, 112 (5.9%) developed an ECMO-related neurovascular injury: 65 (3.4%) ischemic strokes, 40 (2.1%) intracranial bleeding, one cerebral thrombophlebitis (0.05%) and 6 (0.3%) spinal cord infarction. Herein, we report a series of six patients with refractory cardiogenic shock or cardiac arrest receiving circulatory support with VA-ECMO who developed subsequent SCI during ECMO course, confirmed by spine MRI after ECMO withdrawal. All six patients had long-term neurological disabilities. VA-ECMO-related SCI is a rare but catastrophic complication. Its diagnosis is usually delayed due to sedation requirement and/or ICU acquired weakness after sedation withdrawal, leading to difficulties in monitoring their neurological status. Even if no specific treatment exist for SCI, its prompt diagnosis is mandatory, to prevent secondary spine insults of systemic origin. Based on these results, we suggest that daily sedation interruption and neurological exam of the lower limbs should be performed in all VA-ECMO patients. Large registries are mandatory to determine VA-ECMO-related SCI risk factor and potential therapy.
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http://dx.doi.org/10.1007/s10047-020-01179-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260457PMC
December 2020

Liberal or Conservative Oxygen Therapy for Acute Respiratory Distress Syndrome.

N Engl J Med 2020 03;382(11):999-1008

From the Medical Intensive Care Unit (L.B., H.W., L.V., G.C.), the Anesthesia and Intensive Care Unit (L.B., S.P.-F.), Unité de Méthodologie, INSERM Clinical Investigation Center 1431, University Hospital (F. Mauny, M.P.), and Research Unit EA3920, Université de Franche Comté (L.B., H.W. S.P.-F., G.C.), Besançon, the Medical Intensive Care Unit, University Hospital of Angers, Angers (P.A.), the Intensive Care Unit, General Hospital of Avignon, Avignon (F. Montini), the Intensive Care Unit, General Hospital of Nord Franche-Comté, Trévenans (J.B.), the Medical Intensive Care Unit (J.-P.Q.) and the Anesthesia and Intensive Care Unit (B.B.), University Hospital of Dijon, Dijon, the Intensive Care Unit, General Hospital of Metz-Thionville, Metz (G.L.), the Medical Intensive Care Unit (B.S.) and the Anesthesia and Intensive Care Unit (J.-M.C.), University Hospital of Clermont-Ferrand, Clermont-Ferrand, the Anesthesia and Intensive Care Unit, University Hospital of Strasbourg, Strasbourg (O.C., J.P.), and the Medical Intensive Care Unit, University Hospital of Nancy, Nancy (B.L.) - all in France; and the Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia (G.C.).

Background: In patients with acute respiratory distress syndrome (ARDS), the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network recommends a target partial pressure of arterial oxygen (Pao) between 55 and 80 mm Hg. Prospective validation of this range in patients with ARDS is lacking. We hypothesized that targeting the lower limit of this range would improve outcomes in patients with ARDS.

Methods: In this multicenter, randomized trial, we assigned patients with ARDS to receive either conservative oxygen therapy (target Pao, 55 to 70 mm Hg; oxygen saturation as measured by pulse oximetry [Spo], 88 to 92%) or liberal oxygen therapy (target Pao, 90 to 105 mm Hg; Spo, ≥96%) for 7 days. The same mechanical-ventilation strategies were used in both groups. The primary outcome was death from any cause at 28 days.

Results: After the enrollment of 205 patients, the trial was prematurely stopped by the data and safety monitoring board because of safety concerns and a low likelihood of a significant difference between the two groups in the primary outcome. Four patients who did not meet the eligibility criteria were excluded. At day 28, a total of 34 of 99 patients (34.3%) in the conservative-oxygen group and 27 of 102 patients (26.5%) in the liberal-oxygen group had died (difference, 7.8 percentage points; 95% confidence interval [CI], -4.8 to 20.6). At day 90, 44.4% of the patients in the conservative-oxygen group and 30.4% of the patients in the liberal-oxygen group had died (difference, 14.0 percentage points; 95% CI, 0.7 to 27.2). Five mesenteric ischemic events occurred in the conservative-oxygen group.

Conclusions: Among patients with ARDS, early exposure to a conservative-oxygenation strategy with a Pao between 55 and 70 mm Hg did not increase survival at 28 days. (Funded by the French Ministry of Health; LOCO ClinicalTrials.gov number, NCT02713451.).
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http://dx.doi.org/10.1056/NEJMoa1916431DOI Listing
March 2020

Levosimendan in the light of the results of the recent randomized controlled trials: an expert opinion paper.

Crit Care 2019 Nov 29;23(1):385. Epub 2019 Nov 29.

Université Paris Diderot, Sorbonne Paris Cité, Paris, France.

Despite interesting and unique pharmacological properties, levosimendan has not proven a clear superiority to placebo in the patient populations that have been enrolled in the various recent multicenter randomized controlled trials. However, the pharmacodynamic effects of levosimendan are still considered potentially very useful in a number of specific situations.Patients with decompensated heart failure requiring inotropic support and receiving beta-blockers represent the most widely accepted indication. Repeated infusions of levosimendan are increasingly used to facilitate weaning from dobutamine and avoid prolonged hospitalizations in patients with end-stage heart failure, awaiting heart transplantation or left ventricular assist device implantation. New trials are under way to confirm or refute the potential usefulness of levosimendan to facilitate weaning from veno-arterial ECMO, to treat cardiogenic shock due to left or right ventricular failure because the current evidence is mostly retrospective and requires confirmation with better-designed studies. Takotsubo syndrome may represent an ideal target for this non-adrenergic inotrope, but this statement also relies on expert opinion. There is no benefit from levosimendan in patients with septic shock. The two large trials evaluating the prophylactic administration of levosimendan (pharmacological preconditioning) in cardiac surgical patients with poor left ventricular ejection fraction could not show a significant reduction in their composite endpoints reflecting low cardiac output syndrome with respect to placebo. However, the subgroup of those who underwent isolated CABG appeared to have a reduction in mortality. A new study will be required to confirm this exploratory finding.Levosimendan remains a potentially useful inodilator agent in a number of specific situations due to its unique pharmacological properties. More studies are needed to provide a higher level of proof regarding these indications.
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http://dx.doi.org/10.1186/s13054-019-2674-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883606PMC
November 2019

Protocol for a multicentre randomised controlled trial evaluating the effects of moderate hypothermia versus normothermia on mortality in patients with refractory cardiogenic shock rescued by venoarterial extracorporeal membrane oxygenation (VA-ECMO) (HYPO-ECMO study).

BMJ Open 2019 10 14;9(10):e031697. Epub 2019 Oct 14.

Groupe Choc, équipe 2, Inserm U1116, Vandoeuvre les Nancy, France

Introduction: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is widely used to support the most severe forms of cardiogenic shock (CS). Nevertheless, despite extracorporeal membrane oxygenation (ECMO) use, mortality still remains high (50%). Moderate hypothermia (MH) (33°C-34°C) may improve cardiac performance and decrease ischaemia-reperfusion injuries. The use of MH during VA-ECMO is strongly supported by experimental and preliminary clinical data.

Methods And Analysis: The Hypothermia-Extracorporeal Membrane Oxygenation (HYPO-ECMO) study is a multicentre, prospective, controlled randomised trial between an MH group (33°C≤T°C≤34°C) and normothermia group (36°C≤T°C≤37°C). The primary endpoint is all-cause mortality at day 30 following randomisation. The study will also assess as secondary endpoints the effects of targeted temperature management strategies on (1) mortality rate at different time points, (2) organ failure and supportive treatment use and (3) safety. All intubated adults with refractory CS supported with VA-ECMO will be screened. Exclusion criteria are patients having undergone cardiac surgery for heart transplantation or left or biventricular assist device implantation, acute poisoning with cardiotoxic drugs, pregnancy, uncontrolled bleeding and refractory cardiac arrest.Three-hundred and thirty-four patients will be randomised and followed up to 6 months to detect a 15% difference in mortality. Data analysis will be intention to treat. The differences between the two study groups in the risk of all-cause mortality at day 30 following randomisation will be studied using logistic regression analysis adjusted for postcardiotomy setting, prior cardiac arrest, prior myocardial infarction, age, vasopressor dose, Sepsis-related Organ Failure Assessment (SOFA) score and lactate at randomisation.

Ethics And Dissemination: Ethics approval has been granted by the Comité de Protection des Personnes Est III Ethics Committee. The trial has been approved by the French Health Authorities (Agence Nationale de la Sécurité du Médicament et des Produits de Santé). Dissemination of results will be performed via journal articles and presentations at national and international conferences. Since this study is also the first step in the constitution of an 'ECMO Trials Group', its results will also be disseminated by the aforementioned group.

Trial Registration Number: NCT02754193.
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http://dx.doi.org/10.1136/bmjopen-2019-031697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797322PMC
October 2019

Spontaneous breathing during extracorporeal membrane oxygenation treatment of sickle cell disease acute chest syndrome.

Respir Med Case Rep 2019 14;28:100924. Epub 2019 Aug 14.

Service de réanimation médicale, Centre Hospitalo-Universitaire de Nancy, Vandœuvre-Lès-Nancy, F-54511, France.

Sickle cell disease (SCD) is a hereditary hemoglobinopathy resulting in sickling hemoglobin. Acute chest syndrome (ACS) is a serious complication of SCD and an important cause of morbidity and mortality. Management of ACS is complex and may necessitate mechanical ventilation and veno-venous extracorporeal membrane oxygenation (VV-ECMO) therapy in the more severe cases. We present herein the case of a young female adult (19 y.o.) with SCD who developed severe respiratory failure due to ACS occurring twice within 15 months and treated by VV-ECMO. We describe the management of ACS with VV-ECMO using two different approaches, namely with and without mechanical ventilation.
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http://dx.doi.org/10.1016/j.rmcr.2019.100924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733779PMC
August 2019

Circulating dipeptidyl peptidase 3 and alteration in haemodynamics in cardiogenic shock: results from the OptimaCC trial.

Eur J Heart Fail 2020 02 31;22(2):279-286. Epub 2019 Aug 31.

Inserm UMR-S 942, Cardiovascular Markers in Stress Conditions (MASCOT), University of Paris, Paris, France.

Aims: Dipeptidyl peptidase 3 (DPP3) is a protease involved in the degradation of cardiovascular mediators. Its administration has been shown to be associated with impaired cardiac contraction and kidney haemodynamics while its inhibition restored cardiac contraction in a pre-clinical model of severe heart failure in mice. Circulating DPP3 (cDPP3) was found to be elevated in shock. The present study aims to assess the association between cDPP3 and worsening haemodynamics, namely refractory shock, in a cohort of cardiogenic shock (CS).

Methods And Results: This is an ancillary study of OptimaCC, a prospective, double-blind, multicentre, randomized study assessing efficacy and safety of catecholamines in 57 patients with CS after acute myocardial infarction. cDPP3 was measured in plasma at inclusion, 24 h, 48 h, and 72 h, and haemodynamic and biological parameters were recorded at inclusion. cDPP3 values were higher in refractory CS than non-refractory CS at inclusion (median [interquartile range]; 76.1 [37.9-238.7] ng/mL vs. 32.8 [23.9-47.6] ng/mL, P = 0.014), at 24 h (P < 0.001) and up to 48 h (P = 0.027). Furthermore, cDPP3 at inclusion discriminated CS patients who did develop refractory shock vs. non-refractory with an area under the curve of 0.73 (95% confidence interval [CI] 0.55-0.92). The high cDPP3 group (cDPP3 ≥59.1 ng/mL) at inclusion had a higher Simplified Acute Physiology Score II (SAPS II), lower cardiac index and lower estimated glomerular filtration rate. More importantly, in CS patients with high cDPP3 at inclusion, those who rapidly decreased cDPP3 at 24 h exhibited a striking reduction in the occurrence of refractory shock and death.

Conclusion: In CS patients, cDPP3 gives an early prediction of outcome, including development of refractory status and/or survival.

Clinical Trial Registration: clinicaltrials.gov Identifier NCT01367743.
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http://dx.doi.org/10.1002/ejhf.1600DOI Listing
February 2020

Ischemic limb necrosis in septic shock: What is the role of high-dose vasopressor therapy?

J Thromb Haemost 2019 11 23;17(11):1973-1978. Epub 2019 Jul 23.

Departments of Pathology, Molecular Medicine, and Medicine, McMaster University, Hamilton, ON, Canada.

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http://dx.doi.org/10.1111/jth.14566DOI Listing
November 2019

Levels of Growth Differentiation Factor 15 and Early Mortality Risk Stratification in Cardiogenic Shock.

J Card Fail 2019 Nov 13;25(11):894-901. Epub 2019 Jul 13.

Cardiology, Helsinki University and Heart and Lung Center, Helsinki University Hospital, Helsinki, Finland. Electronic address:

Background: The aim of this study was to assess the levels, kinetics, and prognostic value of growth differentiation factor 15 (GDF-15) in cardiogenic shock (CS).

Methods And Results: Levels of GDF-15 were determined in serial plasma samples (0-120 h) from 177 CS patients in the CardShock study. Kinetics of GDF-15, its association with 90-day mortality, and incremental value for risk stratification were assessed. The median GDF-15 level was 9647 ng/L (IQR 4500-19,270 ng/L) and levels above median were significantly associated with acidosis, hyperlactatemia, renal dysfunction, and higher 90-day mortality (56% vs 28%, P < .001). Serial sampling showed that non-survivors had significantly higher GDF-15 levels at all time points (P < .001 for all). Furthermore, non-survivors displayed increasing and survivors declining GDF-15 levels during the first days in CS. Higher levels of GDF-15 were independently associated with mortality. A GDF-15 cutoff >7000 ng/L was identified as a strong predictor of death (OR 5.0; 95% CI 1.9-3.8, P = .002). Adding GDF-15 >7000 ng/L to the CardShock risk score improved discrimination and risk stratification for 90-day mortality.

Conclusions: GDF-15 levels are highly elevated in CS and associated with markers of systemic hypoperfusion and end-organ dysfunction. GDF-15 helps to discriminate survivors from non-survivors very early in CS.
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http://dx.doi.org/10.1016/j.cardfail.2019.07.003DOI Listing
November 2019

Inotropes and vasopressors use in cardiogenic shock: when, which and how much?

Curr Opin Crit Care 2019 08;25(4):384-390

Service de Réanimation Médicale Brabois, CHRU Nancy, Pôle Cardio-Médico-Chirurgical.

Purpose Of Review: Data and interventional trials regarding vasopressor and inotrope use during cardiogenic shock are scarce. Their use is limited by their side-effects and the lack of solid evidence regarding their effectiveness in improving outcomes. In this article, we review the current use of vasopressor and inotrope agents during cardiogenic shock.

Recent Findings: Two recent Cochrane analyses concluded that there was not sufficient evidence to prove that any one vasopressor or inotrope was superior to another in terms of mortality. A recent RCT and a meta-analysis on individual data suggested that norepinephrine may be preferred over epinephrine in patients with cardiogenic shock . For inotrope agents, when norepinephrine fails to restore perfusion, dobutamine represents the first-line agent. Levosimendan is a calcium sensitizer agent, which improves acute hemodynamics, albeit with uncertain effects on mortality.

Summary: When blood pressure needs to be restored, norepinephrine is a reasonable first-line agent. Dobutamine is the first-line inotrope agent wheraes levosimendan can be used as a second-line agent or preferentially in patients previously treated with beta-blockers. Current information regarding comparative effective outcomes is nonetheless sparse and their use should be limited as a temporary bridge to recovery, mechanical circulatory support or heart transplantation.
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http://dx.doi.org/10.1097/MCC.0000000000000632DOI Listing
August 2019

Design and preliminary results of FRENSHOCK 2016: A prospective nationwide multicentre registry on cardiogenic shock.

Arch Cardiovasc Dis 2019 May 11;112(5):343-353. Epub 2019 Apr 11.

Inserm, CNRS, PhyMedExp, cardiology department, université de Montpellier, CHU de Montpellier, 34295 Montpellier, France.

Background: Most data on the epidemiology of cardiogenic shock (CS) have come from patients with acute myocardial infarction admitted to intensive cardiac care units (ICCUs). However, CS can have other aetiologies, and could be managed in intensive care units (ICUs), especially the most severe forms of CS.

Aim: To gather data on the characteristics, management and outcomes of patients hospitalized in ICCUs and ICUs for CS, whatever the aetiology, in France in 2016.

Methods: We included all adult patients with CS between April and October 2016 in metropolitan France. CS was defined (at admission or during hospitalization) by: low cardiac output, defined by systolic blood pressure<90mmHg and/or the need for amines to maintain systolic blood pressure>90mmHg and/or cardiac index<2.2L/min/m; elevation of the left and/or right heart pressures, defined by clinical, radiological, biological, echocardiographic or invasive haemodynamic overload signs; and clinical and/or biological signs of malperfusion (lactate>2mmol/L, hepatic insufficiency, renal failure).

Results: Over a 6-month period, 772 patients were included in the survey (mean age 65.7±14.9 years; 71.5% men) from 49 participating centres (91.8% were public, and 77.8% of these were university hospitals). Ischaemic trigger was the most common cause (36.3%).

Conclusions: To date, FRENSHOCK is the largest CS survey; it will provide a detailed and comprehensive global description of the spectrum and management of patients with CS in a high-income country.
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http://dx.doi.org/10.1016/j.acvd.2019.02.001DOI Listing
May 2019

Fifty Years of Management of Vasodilatory Shock.

Int Anesthesiol Clin 2019 ;57(2):31-47

Department of Intensive Care, CHIREC Hospitals, Université Libre de Bruxelles, Brussels, Belgium.

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http://dx.doi.org/10.1097/AIA.0000000000000226DOI Listing
January 2020