Ventriculo-arterial (un)coupling in septic shock: Impact of current and upcoming hemodynamic drugs

Sepsis is an archetype of distributive shock and combines different levels of alterations in preload, afterload, and often cardiac contractility. The use of hemodynamic drugs has evolved over the past few years, along with the invasive and non-invasive tools used to measure these components in real time. However, none of them is impeccable, which is why the mortality of septic shock remains too high. The concept of ventriculo-arterial coupling (VAC) allows for the integration of these three fundamental macroscopic hemodynamic components. In this mini review, we discuss the knowledge, tools, and limitations of VAC measurement, along with the evidence supporting ventriculo-arterial uncoupling in septic shock. Finally, the impact of recommended hemodynamic drugs and molecules on VAC is detailed

Impact of respiratory viruses in intensive care unit patient with community-acquired pneumonia : a one-year retrospective single-centre study.

International audienc

High-flow oxygen therapy versus noninvasive ventilation: a randomised physiological crossover study of alveolar recruitment in acute respiratory failure.

High-flow nasal cannula (HFNC) oxygen therapy has recently shown clinical benefits in hypoxaemic acute respiratory failure (ARF) patients, while the value of noninvasive ventilation (NIV) remains debated. The primary end-point was to compare alveolar recruitment using global end-expiratory electrical lung impedance (EELI) between HFNC and NIV. Secondary end-points compared regional EELI, lung volumes (global and regional tidal volume variation (V (T))), respiratory parameters, haemodynamic tolerance, dyspnoea and patient comfort between HFNC and NIV, relative to face mask (FM). A prospective randomised crossover physiological study was conducted in patients with hypoxaemic ARF due to pneumonia. They received alternately HFNC, NIV and FM. 16 patients were included. Global EELI was 4083 with NIV and 2921 with HFNC (p=0.4). Compared to FM, NIV and HFNC significantly increased global EELI by 1810.5 (95% CI 857-2646) and 826 (95% CI 399.5-2361), respectively. Global and regional V (T) increased significantly with NIV compared to HFNC or FM, but not between HFNC and FM. NIV yielded a significantly higher pulse oxygen saturation/inspired oxygen fraction ratio compared to HFNC (p=0.03). No significant difference was observed between HFNC, NIV and FM for dyspnoea. Patient comfort score with FM was not significantly different than with HFNC (p=0.1), but was lower with NIV (p=0.001). This study suggests a potential benefit of HFNC and NIV on alveolar recruitment in patients with hypoxaemic ARF. In contrast with HFNC, NIV increased lung volumes, which may contribute to overdistension and its potentially deleterious effect in these patients

Case report: CAR-T cell therapy-induced cardiac tamponade

CD19-specific chimeric antigen receptor T (CAR-T) cell therapy has recently been shown to improve the prognosis of refractory diffuse large B-cell lymphoma (DLBCL). However, CAR-T cells may induce numerous adverse events, in particular cytokine release syndrome (CRS) which is frequently associated with cardiovascular manifestations. Among the latter, acute pericardial effusion represents less than 1% of cases and cardiac tamponade has only been reported once. The management and outcome of these severe complications are not well established. We report here, a case of cardiac tamponade associated with CRS in a context of CAR-T cell therapy, which required urgent pericardiocentesis.Case summaryA 65-year-old man with refractory DLBCL was treated with CAR-T cell therapy. He had a history of dilated cardiomyopathy with preserved ejection fraction and transient atrial fibrillation. A pericardial localization of the lymphoma was observed on the second relapse. One day after CAR-T cell infusion the patient was diagnosed with grade 1 CRS. Due to hypotension, he was treated with tocilizumab and dexamethasone, and then transferred to intensive care unit (ICU). Echocardiography performed at ICU admission showed acute pericardial effusion with signs of right ventricular heart failure due to cardiac tamponade. It was decided to perform pericardiocentesis despite grade IV thrombocytopenia in a context of aplasia. Analysis of pericardial fluid showed a large number of lymphoma cells and 73% of CAR-T cells amongst lymphocytes, a level that was similar in blood. Hemodynamic status improved after pericardiocentesis, and no recurrence of pericardial effusion was observed. The presence of a high count of activated CAR-T cells in the pericardial fluid as well as the short interval between CAR-T cells injection and the symptoms appear as potential arguments for a direct action of CAR-T cells in the mechanism of this adverse event. The patient was discharged from ICU after two days and initially exhibited a good response to DLBCL treatment. Unfortunately, he died fifty days after starting CAR-T cell therapy due to a new DLBCL relapse.ConclusionPatients with a pericardial localization of DLBCL should be assessed for a risk of cardiac tamponade if receiving CAR-T cell therapy and presenting CRS. In this case, cardiac tamponade seems directly related to CAR-T cell expansion. Pericardiocentesis should be considered as a feasible and effective treatment if the risk of bleeding is well controlled, in association with anti-IL6 and corticosteroids

PathFinder 2015

担当教員:姉川雄大平成27年度(2015)教養展開科目(国際コア関連),授業コード:Ｇ15N1060

Relationship between ventilator-associated pneumonia and mortality in COVID-19 patients: a planned ancillary analysis of the coVAPid cohort

Background Patients with SARS-CoV-2 infection are at higher risk for ventilator-associated pneumonia (VAP). No study has evaluated the relationship between VAP and mortality in this population, or compared this relationship between SARS-CoV-2 patients and other populations. The main objective of our study was to determine the relationship between VAP and mortality in SARS-CoV-2 patients. Methods Planned ancillary analysis of a multicenter retrospective European cohort. VAP was diagnosed using clinical, radiological and quantitative microbiological criteria. Univariable and multivariable marginal Cox's regression models, with cause-specific hazard for duration of mechanical ventilation and ICU stay, were used to compare outcomes between study groups. Extubation, and ICU discharge alive were considered as events of interest, and mortality as competing event. Findings Of 1576 included patients, 568 were SARS-CoV-2 pneumonia, 482 influenza pneumonia, and 526 no evidence of viral infection at ICU admission. VAP was associated with significantly higher risk for 28-day mortality in SARS-CoV-2 group (adjusted HR 1.65 (95% CI 1.11-2.46), p = 0.013), but not in influenza (1.74 (0.99-3.06), p = 0.052), or no viral infection groups (1.13 (0.68-1.86), p = 0.63). VAP was associated with significantly longer duration of mechanical ventilation in the SARS-CoV-2 group, but not in the influenza or no viral infection groups. VAP was associated with significantly longer duration of ICU stay in the 3 study groups. No significant difference was found in heterogeneity of outcomes related to VAP between the 3 groups, suggesting that the impact of VAP on mortality was not different between study groups. Interpretation VAP was associated with significantly increased 28-day mortality rate in SARS-CoV-2 patients. However, SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, did not significantly modify the relationship between VAP and 28-day mortality

a retrospective multicenter study

Funding This study was supported in part by a grant from the French government through the « Programme Investissement d’Avenir» (I-SITE ULNE) managed by the Agence Nationale de la Recherche (coVAPid project). Prof. Ignacio Martin-Loeches has been supported by SFI (Science Foundation Ireland), Grant number 20/COV/0038. The funders of the study had no role in the study design, data collection, analysis or interpretation, writing of the report or deci sion to submit for publication.BACKGROUND: Ventilator-associated pneumonia (VAP) is common in patients with severe SARS-CoV-2 pneumonia. The aim of this ancillary analysis of the coVAPid multicenter observational retrospective study is to assess the relationship between adjuvant corticosteroid use and the incidence of VAP. METHODS: Planned ancillary analysis of a multicenter retrospective European cohort in 36 ICUs. Adult patients receiving invasive mechanical ventilation for more than 48 h for SARS-CoV-2 pneumonia were consecutively included between February and May 2020. VAP diagnosis required strict definition with clinical, radiological and quantitative microbiological confirmation. We assessed the association of VAP with corticosteroid treatment using univariate and multivariate cause-specific Cox's proportional hazard models with adjustment on pre-specified confounders. RESULTS: Among the 545 included patients, 191 (35%) received corticosteroids. The proportional hazard assumption for the effect of corticosteroids on the incidence of VAP could not be accepted, indicating that this effect varied during ICU stay. We found a non-significant lower risk of VAP for corticosteroid-treated patients during the first days in the ICU and an increased risk for longer ICU stay. By modeling the effect of corticosteroids with time-dependent coefficients, the association between corticosteroids and the incidence of VAP was not significant (overall effect p = 0.082), with time-dependent hazard ratios (95% confidence interval) of 0.47 (0.17-1.31) at day 2, 0.95 (0.63-1.42) at day 7, 1.48 (1.01-2.16) at day 14 and 1.94 (1.09-3.46) at day 21. CONCLUSIONS: No significant association was found between adjuvant corticosteroid treatment and the incidence of VAP, although a time-varying effect of corticosteroids was identified along the 28-day follow-up.publishersversionpublishe

a planned ancillary analysis of the coVAPid cohort

Funding: This study was supported in part by a grant from the French government through the «Programme Investissement d’Avenir» (I-SITE ULNE) managed by the Agence Nationale de la Recherche (coVAPid project). The funders of the study had no role in the study design, data collection, analysis, or interpreta tion, writing of the report, or decision to submit for publication.BACKGROUND: Patients with SARS-CoV-2 infection are at higher risk for ventilator-associated pneumonia (VAP). No study has evaluated the relationship between VAP and mortality in this population, or compared this relationship between SARS-CoV-2 patients and other populations. The main objective of our study was to determine the relationship between VAP and mortality in SARS-CoV-2 patients. METHODS: Planned ancillary analysis of a multicenter retrospective European cohort. VAP was diagnosed using clinical, radiological and quantitative microbiological criteria. Univariable and multivariable marginal Cox's regression models, with cause-specific hazard for duration of mechanical ventilation and ICU stay, were used to compare outcomes between study groups. Extubation, and ICU discharge alive were considered as events of interest, and mortality as competing event. FINDINGS: Of 1576 included patients, 568 were SARS-CoV-2 pneumonia, 482 influenza pneumonia, and 526 no evidence of viral infection at ICU admission. VAP was associated with significantly higher risk for 28-day mortality in SARS-CoV-2 (adjusted HR 1.70 (95% CI 1.16-2.47), p = 0.006), and influenza groups (1.75 (1.03-3.02), p = 0.045), but not in the no viral infection group (1.07 (0.64-1.78), p = 0.79). VAP was associated with significantly longer duration of mechanical ventilation in the SARS-CoV-2 group, but not in the influenza or no viral infection groups. VAP was associated with significantly longer duration of ICU stay in the 3 study groups. No significant difference was found in heterogeneity of outcomes related to VAP between the 3 groups, suggesting that the impact of VAP on mortality was not different between study groups. INTERPRETATION: VAP was associated with significantly increased 28-day mortality rate in SARS-CoV-2 patients. However, SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, did not significantly modify the relationship between VAP and 28-day mortality. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov, number NCT04359693.publishersversionpublishe

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Therapeutic (dis)illusion during sepsis: the initial concept of the dark side of inflammation may be wrong.

peer reviewe