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/)

Le muscle diaphragme dans les pathologies cardiovasculaires : évaluation, évolution clinique et mécanisme des atteintes

The relationship between the dependence of respiration on the diaphragm muscle and circulatory characteristics is intricately connected within the cardiothoracic anatomical entity. Consequently, it serves as the locus of specific assaults that give rise to dysfunction, which in turn frequently leads to dyspnea and challenges in liberating critically ill patients from mechanical ventilation. We conducted a study to examine the characteristics of the interplay between breathing and circulation by analyzing the properties of the diaphragm muscle in the following contexts: 1) the perioperative setting of elective cardiac surgery, 2) following stabilization of an assisted cardiogenic shock during veno-arterial extracorporeal membrane oxygenation (VA-ECMO) weaning, and 3) throughout the progression of a cardiogenic shock also assisted by VA-ECMO.We assessed diaphragm thickness and its performance by employing an ultrasound technique to measure the contractility index of the thickening fraction. In the setting of cardiac surgery, we observed that contractility was frequently compromised due to the duration of procedures and assistances, although its impact on patient outcomes remained unclear. The evolution of thickness was a common occurrence and exhibited an association with the contractility pattern. Moreover, it was linked to prolonged stays in the intensive care unit (ICU). In the VA-ECMO weaning process following a cardiogenic shock, we established that contractility correlated with the recovery of left ventricle ejection fraction and the settings of VA-ECMO, with the sweep gas flow being the primary influencing factor. Diaphragm thickness varied in accordance with the severity of the patient's condition, sweep gas flow for CO2 removal, and metabolic disorders, particularly disturbances in acid-base balance. The evolution of thickness, primarily driven by the development of muscle atrophy rather than the contractility pattern, was associated with impaired respiratory function, prolonged mechanical ventilation, and unfavorable outcomes in the ICU.In summary, alterations in diaphragm structure and performance were frequently observed. The patterns of their evolution were influenced by extracorporeal assistance, and careful titration of such assistance could serve as a therapeutic target for preserving respiratory function.La respiration est étroitement liée aux propriétés du muscle diaphragme et aux conditions de circulation au sein de l'unité cardiothoracique. Les altérations de ces éléments sont responsables de symptômes tels que la dyspnée et les difficultés de sevrage de la ventilation mécanique chez les patients en état critique. Notre étude s'est donc intéressée aux caractéristiques de cette relation à travers l'analyse du muscle diaphragme dans trois contextes : 1) en période périopératoire lors de chirurgies cardiaques programmées, 2) après stabilisation d'un choc cardiogénique sous assistance circulatoire, et 3) lors de l'évolution d'un choc cardiogénique sous assistance par oxygénation par membrane extracorporelle veino-artérielle (ECMO-VA).Nous avons principalement étudié deux paramètres du muscle diaphragme : son épaisseur mesurée par ultrasons et sa performance évaluée à l'aide d'un indice de contractilité échographique, la fraction d'épaississement. Dans le contexte des chirurgies cardiaques, nous avons observé une diminution rapide de la contractilité du diaphragme en lien avec la durée des procédures et de l'assistance circulatoire, sans qu'un impact évident sur le pronostic des patients ne soit observé. L'épaisseur du muscle diaphragme varie fréquemment en association avec sa contractilité en période périopératoire, et elle semble associée à des séjours plus longs en réanimation. Lors du sevrage de l'ECMO-VA, la contractilité du diaphragme est liée à la récupération de la fonction systolique du ventricule gauche, ainsi qu'aux conditions d'assistance circulatoire, notamment l'élimination du dioxyde de carbone (CO2) par le débit de gaz frais. L'évolution de l'épaisseur du diaphragme est influencée par la gravité des patients, les réglages de l'ECMO-VA en termes d'élimination du CO2, et les variations métaboliques liées à l'équilibre acido-basique. Les modifications de l'épaisseur, notamment l'atrophie du diaphragme, semblent être associées à une altération de la fonction respiratoire, caractérisée par des durées de ventilation invasive prolongées et une évolution défavorable en réanimation.En résumé, la structure et la performance du muscle diaphragme sont fréquemment altérées dans les contextes étudiés. Leur évolution est conditionnée notamment par les conditions d'assistance circulatoire, ce qui ouvre des perspectives thérapeutiques potentielles pour préserver la fonction respiratoire

The diaphragm muscle in cardiothoracic disease : evaluation, clinical follow-up and mechanisms of impairment

La respiration est étroitement liée aux propriétés du muscle diaphragme et aux conditions de circulation au sein de l'unité cardiothoracique. Les altérations de ces éléments sont responsables de symptômes tels que la dyspnée et les difficultés de sevrage de la ventilation mécanique chez les patients en état critique. Notre étude s'est donc intéressée aux caractéristiques de cette relation à travers l'analyse du muscle diaphragme dans trois contextes : 1) en période périopératoire lors de chirurgies cardiaques programmées, 2) après stabilisation d'un choc cardiogénique sous assistance circulatoire, et 3) lors de l'évolution d'un choc cardiogénique sous assistance par oxygénation par membrane extracorporelle veino-artérielle (ECMO-VA).Nous avons principalement étudié deux paramètres du muscle diaphragme : son épaisseur mesurée par ultrasons et sa performance évaluée à l'aide d'un indice de contractilité échographique, la fraction d'épaississement. Dans le contexte des chirurgies cardiaques, nous avons observé une diminution rapide de la contractilité du diaphragme en lien avec la durée des procédures et de l'assistance circulatoire, sans qu'un impact évident sur le pronostic des patients ne soit observé. L'épaisseur du muscle diaphragme varie fréquemment en association avec sa contractilité en période périopératoire, et elle semble associée à des séjours plus longs en réanimation. Lors du sevrage de l'ECMO-VA, la contractilité du diaphragme est liée à la récupération de la fonction systolique du ventricule gauche, ainsi qu'aux conditions d'assistance circulatoire, notamment l'élimination du dioxyde de carbone (CO2) par le débit de gaz frais. L'évolution de l'épaisseur du diaphragme est influencée par la gravité des patients, les réglages de l'ECMO-VA en termes d'élimination du CO2, et les variations métaboliques liées à l'équilibre acido-basique. Les modifications de l'épaisseur, notamment l'atrophie du diaphragme, semblent être associées à une altération de la fonction respiratoire, caractérisée par des durées de ventilation invasive prolongées et une évolution défavorable en réanimation.En résumé, la structure et la performance du muscle diaphragme sont fréquemment altérées dans les contextes étudiés. Leur évolution est conditionnée notamment par les conditions d'assistance circulatoire, ce qui ouvre des perspectives thérapeutiques potentielles pour préserver la fonction respiratoire.The relationship between the dependence of respiration on the diaphragm muscle and circulatory characteristics is intricately connected within the cardiothoracic anatomical entity. Consequently, it serves as the locus of specific assaults that give rise to dysfunction, which in turn frequently leads to dyspnea and challenges in liberating critically ill patients from mechanical ventilation. We conducted a study to examine the characteristics of the interplay between breathing and circulation by analyzing the properties of the diaphragm muscle in the following contexts: 1) the perioperative setting of elective cardiac surgery, 2) following stabilization of an assisted cardiogenic shock during veno-arterial extracorporeal membrane oxygenation (VA-ECMO) weaning, and 3) throughout the progression of a cardiogenic shock also assisted by VA-ECMO.We assessed diaphragm thickness and its performance by employing an ultrasound technique to measure the contractility index of the thickening fraction. In the setting of cardiac surgery, we observed that contractility was frequently compromised due to the duration of procedures and assistances, although its impact on patient outcomes remained unclear. The evolution of thickness was a common occurrence and exhibited an association with the contractility pattern. Moreover, it was linked to prolonged stays in the intensive care unit (ICU). In the VA-ECMO weaning process following a cardiogenic shock, we established that contractility correlated with the recovery of left ventricle ejection fraction and the settings of VA-ECMO, with the sweep gas flow being the primary influencing factor. Diaphragm thickness varied in accordance with the severity of the patient's condition, sweep gas flow for CO2 removal, and metabolic disorders, particularly disturbances in acid-base balance. The evolution of thickness, primarily driven by the development of muscle atrophy rather than the contractility pattern, was associated with impaired respiratory function, prolonged mechanical ventilation, and unfavorable outcomes in the ICU.In summary, alterations in diaphragm structure and performance were frequently observed. The patterns of their evolution were influenced by extracorporeal assistance, and careful titration of such assistance could serve as a therapeutic target for preserving respiratory function

Diaphragm Thickening During Venoarterial Extracorporeal Membrane Oxygenation Weaning: An Observational Prospective Study

International audienceObjectives: The respiratory workload, according to the diaphragm thickening fraction (TF) during sweep gas flow (SGF), decrease during weaning from venoarterial extracorporeal membrane oxygenation (VA ECMO) was evaluated for the present study.Design: Prospective observational study.Setting: Monocentric.Participants: Patients were included if they were suitable for a first VA ECMO weaning trial and were breathing spontaneously.Interventions: SGF was set for 15 minutes when the TF was measured at 4 L/min, 2 L/min, and 1 L/min, with a 10-minute return to baseline between each step. Mechanical ventilation, when required, was set to pressure-support ventilation mode with 7 cmH2O (pressure support) and a positive end-expiratory pressure of 0 cmH2O. Diaphragm ultrasound was used to assess the TF at the end of each step. Demographics, left ventricular ejection fraction (LVEF), and outcome were collected.Measurements and main results: Fifteen patients were included. Ten patients were extubated, and five were ventilated. TF values were 6.3% [0-10] at 4 L/min, 13.3% [10-26] at 2 L/min, and 26.7% [22-44] at 1 L/min (analysis of variance: p < 0.001 between 4 L/min and 2 L/min and p = 0.03 between 2 L/min and 1 L/min). TF did not differ whether patients were or were not ventilated or whether they were or were not weaned successfully from ECMO. TF was correlated with LVEF at 1 L/min SGF (Pearson R 0.67 [0.21-0.88]; p = 0.009) and at 2 L/min (R 0.7 [0.27-0.89]; p = 0.005) but not at 4 L/min. SGF mitigated the relationship between LVEF and TF (analysis of covariance: p < 0.005).Conclusions: Diaphragm TF was related to the SGF of the venoarterial ECMO settings and LVEF at the time of weaning

Successful COVID-19 elimination after an alpha variant outbreak in a “safe travel zone”

International audienc

Evaluating the strategies to control SARS-CoV-2 Delta variant spread in New Caledonia, a Zero COVID country until September 2021

Objectives New Caledonia, a former Zero-COVID country, was confronted with a SARS-CoV-2 Delta variant outbreak in September 2021. We evaluate the relative contribution of vaccination, lockdown and timing of interventions on healthcare burden. Methods We developed an age-stratified mathematical model of SARS-CoV-2 transmission and vaccination calibrated for New Caledonia and evaluated three alternative scenarios. Results High virus transmission early on was estimated, R0 equal to 6.6 (95% CI [6.4 – 6.7]). Lockdown reduced R0 by 73% (95% CI [70 - 76%]). Easing the lockdown increased transmission (39% reduction of the initial R0); but we did not observe an epidemic rebound. This contrasts with the rebound in hospital admissions (+116% total hospital admissions) that would have been expected in the absence of an intensified vaccination campaign (76,220 people or 34.12% of the eligible population were first-dose vaccinated during one month of lockdown). A 15-day earlier lockdown would have led to a significant reduction in the magnitude of the epidemic (-53% total hospital admissions). Conclusions The success of the response against the Delta variant epidemic in New Caledonia was due to an effective lockdown that provided additional time for people to vaccinate. Earlier lockdown would have greatly mitigated the magnitude of the epidemic

Impact of lockdown on cardiovascular disease hospitalizations in a Zero-COVID-19 country

International audienceObjectives: There are concerns about the potential effect of social distancing used to control COVID-19 on the incidence of cardiovascular diseases (CVD). Study design: Retrospective cohort study. Methods: We examined the association between lockdown and CVD incidence in a Zero-COVID country, New Caledonia. Inclusion criteria were defined by a positive troponin sample during hospitalization. The study period lasted for 2 months, starting March 20, 2020 (strict lockdown: first month; loose lockdown: second month) compared with the same period of the three previous years to calculate incidence ratio (IR). Demographic characteristics and main CVD diagnoses were collected. The primary endpoint was the change in incidence of hospital admission with CVD during lockdown compared with the historical counterpart. The secondary endpoint included influence of strict lockdown, change in incidence of the primary endpoint by disease, and outcome incidences (intubation or death) analyzed with inverse probability weighting method. Results: A total of 1215 patients were included: 264 in 2020 vs 317 (average of the historical period). CVD hospitalizations were reduced during strict lockdown (IR 0.71 [0.58e0.88]), but not during loose lockdown (IR 0.94 [0.78e1.12]). The incidence of acute coronary syndromes was similar in both periods. The incidence of acute decompensated heart failure was reduced during strict lockdown (IR 0.42 [0.24 e0.73]), followed by a rebound (IR 1.42 [1e1.98]). There was no association between lockdown and short-term outcomes. Conclusions: Our study showed that lockdown was associated with a striking reduction in CVD hospitalizations, independently from viral spread, and a rebound of acute decompensated heart failure hospitalizations during looser lockdown

Implementation of a combo videolaryngoscope for intubation in critically ill patients: a before-after comparative study

International audienc

Ann Biol Clin (Paris)

La Société française de biologie clinique (SFBC) a mis en place un groupe de travail « Marqueurs biochimiques de Covid-19 » dont l’objectif principal est de revoir, d’analyser et de suivre les prescriptions biologiques en fonction du parcours de soins du patient. Cette étude couvre tous les secteurs publics et privés de la biologie médicale en métropole et en Outre-mer et s’étend à la Francophonie. Nous présentons une synthèse des retours d’expériences après 2 ans de pandémie. Au stade précoce de la Covid-19, pour les régions interrogées, une symptomatologie commune avec des zoonoses locales (dengue, zika, paludisme, leptospirose…) complique le diagnostic de la Covid-19. À un stade plus avancé, il s’agit de gérer un afflux de patients atteints de syndrome de détresse respiratoire aiguë. La biologie est alors plus simple, et les dispositifs de biologie médicale délocalisée ont prouvé leur efficacité. De ce fait, les réanimateurs peuvent mieux gérer les comorbidités fréquentes rencontrées dans ces régions : obésité, diabète, insuffisance rénale chronique ou maladies cardiovasculaires.The French Society of Clinical Biology (SFBC) set up a working group “Biochemical markers of Covid-19” whose main objective is to review, analyse and monitor biological prescriptions according to the patient’s care path. This study covers all public and private sectors of medical biology in metropolitan France and overseas and extends to the French-speaking world. We present a summary of feedbacks after 2 years of the pandemic. At the early stage of Covid-19, with regard to the regions surveyed, a common symptomatology with local zoonosis (dengue fever, zika, malaria, leptospirosis, etc.) complicates the diagnosis of Covid-19. At a more advanced stage, it is a question of managing an influx of patients suffering from acute respiratory distress syndrome. In this case, the biology is then simpler and delocalized medical biology devices have proven their effectiveness. As a result, ICU clinicians can better manage the frequent comorbidities encountered in these regions: obesity, diabetes, chronic renal failure, cardiovascular diseases