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/)

Étude observationnelle rétrospective sur les caractéristiques épidémiologiques des sujets atteints par la grippe ayant consulté au sein des services d'accueil des urgences adultes des Hôpitaux universitaires de Strasbourg de septembre 2018 à mars 2019

MédecineIntroduction : les épidémies de grippe sont responsables chaque année d’un nombre considérable de décès, notamment de sujets âgés et/ou présentant des comorbidités. Elles participent à la saturation des services d’urgence en période hivernale alors que ceux-ci voient leur activité quotidienne croitre d’années en années. La saison 2018-2019 a semblé être marquée par un nombre de malades ne se majorant pas par rapport aux années précédentes mais avec des présentations cliniques essentiellement sous la forme de décompensations de maladies cardiaques ou respiratoires sous-jacentes. L’objectif principal de cette étude est de décrire les caractéristiques épidémiologiques des patients atteints par la grippe ayant consulté aux urgences (SAU) adultes des sites du Nouvel Hôpital Civil et de Hautepierre du CHU de Strasbourg entre septembre 2018 et mars 2019. Les objectifs secondaires sont de réaliser un travail sur les différents modes de présentation clinique de ces malades, leur évolution ainsi que l’impact de cette pathologie sur les services d’accueil des urgences mais également sur les services de réanimation et de médecine du CHU de Strasbourg en période d’infection grippale saisonnière. Méthode : il s’agit d’une étude non interventionnelle, rétrospective, monocentrique sur des données issues des dossiers médicaux informatisés des patients ayant consultés au sein des services d’accueil des urgences adultes des sites du Nouvel Hôpital Civil et de Hautepierre du CHU de Strasbourg. Résultats : au total, 383 individus ont été inclus. La moyenne d’âge de la cohorte était de 66,89 ans ; 136 (35,60 %) malades avaient plus de 80 ans. La majorité des malades (88,35 %) venaient du domicile, orientés par le SAMU (48,57 %). Une comorbidité est retrouvée chez 324 (84,60 %) d’entre eux, essentiellement cardio-vasculaires et respiratoires. Les malades présentaient essentiellement de la fièvre (71,55 %), une dyspnée (3-,29 %) mais également, des symptômes plus atypiques tels qu’une chute (16,97 %), une douleur thoracique (13,32 %). Le temps moyen de séjour au SAU pour les malades inclus est estimé à 16,95 heures Le délai moyen pour la réception du résultat positif du frottis grippal était de 27,33 heures, avec une différence significative de 2,40 heures significative (p-value à 2,54.10⁻²) en faveur du NHC. Sur la totalité des prélèvements grippaux demandés par les urgentistes, 31% étaient positifs au cours de la dernière saison hivernale. La majorité des malades inclus (60,83 %) ont été hospitalisés, dont 38,38 % à l’UHCD. Concernant le taux de grippe grave, il s’est élevé à 10,96 %, le nombre de décès représentait 1,83 % et les transferts en réanimation 8,09 %. Les paramètres responsables d’une majoration significative du risque de grippe grave sont : l’existence d’une décompensation cardiaque qui l’augmente de 7 (IC 95 % [1,55 ;32,55] ; p-value = 0,01), d’une déshydratation qui l’augmente de 103 (IC 95 % [14 ;945,46] ; p-value inférieure à 10⁻³), d’une oxygénorequérance qui l’augmente de 3,6 (IC 95 % [1,10 ;13,20] ; p=0,04), de la réalisation de séances de VNI qui l’augmente de 33,6 (IC 95 % [8,00 ;167,00] ; p-value inférieure à 10⁻³). Différents paramètres ont été déterminés comme majorant significativement le risque de mortalité, il s’agit de l’existence d’une déshydratation (élévation du risque de 36,30) (IC 95 % [3,60 ;0,90] ; p-value inférieure à 10⁻³), d’une immunodépression (majoration de 17,55) (IC 95 % [1,40 ;219,65] ; p-value = 3.10⁻²), d’une oxygénorequérance (majoration de 4,60) (IC 95 % [1,40 ;15,00] ; p-value = 1.10⁻²), la nécessité de séances de VNI (majoration de 38) (IC 95 % [9,80 ; 148,00] ; p-value inférieure à 10⁻³). L’augmentation du temps de présence au SAU augmente le risque de 0,99 de décéder, significativement (IC 95 % [0,997 ; 0,999] ; p=0,03). Discussion : l’épidémie grippale de l’hiver 2018-2019 a principalement affecté des malades âgés de plus de 80 ans, vivant à leur domicile et porteurs de lourdes comorbidités cardio-vasculaires et respiratoires. Les individus appartenant à cette catégorie d’âge ont eu plus fréquemment recours aux urgences en raison de tableaux atypiques ou de formes d’emblée grave en lien avec la décompensation d’une pathologie chronique cardiaque ou respiratoire. Ces services ont constitué la principale porte d’entrée pour les malades grippés au cours de cette dernière saison. En raison de l’âge avancé de nos malades, de leur terrain et de la présentation de l’infection grippale, le taux d’hospitalisation était très élevé, 3 fois supérieur au taux national. Ce phénomène a nécessité une adaptation des secteurs d’hospitalisation et notamment une activation de la cellule hôpital en tension pour y faire face. Le taux de décès a été particulièrement bas. Dans l’optique d’améliorer la prise en charge de ces malades au sein de nos SAU nous avons souhaité déterminer des facteurs de gravité et de mortalité. Leur connaissance permettre d’optimiser la prise en charge, la surveillance des malades les présentant. L’augmentation de la durée a donc un effet protecteur (probablement parce que c’est la gravité qui entraîne une prise en charge plus précoce et donc une diminution de la durée au SAU) tant sur le risque de grippe grave que sur la mortalité.Influenza epidemics are responsible for a considerable number of deaths each year, including elderly and/or co-morbidity patients. They contribute to the saturation of emergency services during the winter, as they see their daily activity increasing from year to year. The 2018-2019 season seemed to be marked by a number of patients not increasing compared to previous years, but with clinical presentations mainly in the form of the awards of underlying heart or respiratory diseases. The main objective of this study is to describe the epidemiological characteristics of influenza patients who visited adult emergency rooms (SAUs) at the sites of the New Civil Hospital and Hautepierre of the CHU of Strasbourg between September 2018 and March 2019. The secondary objectives are to carry out work on the different modes of clinical presentation of these patients, their evolution and the impact of this pathology on the emergency reception services, but also on the resuscitation and medical services of the CHU of Strasbourg during periods of seasonal influenza infection. Method: This is a non-interventional, retrospective, monocentric study of data from computerized medical records of patients who have consulted in the adult emergency reception services of the sites of the New Civil Hospital and Hautepierre of the CHU of Strasbourg. Results: A total of 383 individuals were included. The average age of the cohort was 66.89 years; 136 (35.60%) were over 80 years old. The majority of patients (88.35 per cent) came from the home, headed by SAMU (48.57 per cent). Comorbidity is found in 324 (84.60%) of them, mainly cardiovascular and respiratory. Patients were mainly affected by fever (71.55%), dyspnea (3-29%), but also more atypical symptoms such as falling (16.97%), chest pain (13.32%). Average time to stay in the UAS for the patients included is estimated at 16.95 hours The average time to receive the positive result of influenza smear was 27.33 hours, with a significant difference of 2.40 hours (p-value at 2.54.10 ²) in favor of the NHC. Of the total influenza samples requested by emergency workers, 31% were positive during the last winter season. The majority of patients included (60.83%) were hospitalized, of whom 38.38% were hospitalized at UHCD. In the case of severe influenza, it was 10.96%, the number of deaths was 1.83% and transfers to resuscitation 8.09%. The parameters responsible for a significant increase in the risk of severe influenza are: The existence of cardiac compensation which increases it by 7 (95% CI [1,55 ;32,55]; p-value = 0,01), dehydration which increases it by 103 (IC 95 % [14 ;945,46]; p-value less than 10 ³), an oxygenorequence which increases it by 3,6 (95 % CI [1,10 ;13,20]; p=0.04), the completion of NIV sessions which increases it by 33.6 (IC 95% [8.00 ;167.00]; p-value less than 10 ³). Different parameters were determined as significantly increasing the risk of mortality, namely dehydration (36.30 risk increase) (CI 95% [3.60; 0.90]; p-value less than 10 ³, immunodepression (17,55) (IC 95 % [1,40 ;219,65]; p-value = 3.10 ²), of an oxygenorequence (increase of 4.60) (IC 95 % [1,40 ;15,00]; p-value = 1.10 ²), the need for VNI sessions (increase of 38) (IC 95 % [9,80 ; 148,00]; p-value less than 10 ³). Increasing UAS attendance increases the risk of death by 0.99, significantly (IC 95% [0.997; 0.999]; p=0.03). Discussion: The influenza epidemic in the winter of 2018-2019 mainly affected patients over 80 years of age, living in their homes and carrying heavy cardiovascular and respiratory co-morbidities. Individuals in this age group were more likely to use emergencies because of atypical tables or severe early forms related to the offsetting of chronic cardiac or respiratory disease. These services have been the main gateway for influenza patients in the last season. Due to the advanced age of our patients, their terrain and the presentation of influenza infection, the hospitalization rate was very high, 3 times higher than the national rate. This has necessitated the adaptation of hospital areas and in particular the activation of the hospital cell in tension in order to cope with it. The death rate was particularly low. With a view to improving the care of these patients within our UAS, we wanted to identify factors of severity and mortality. Their knowledge allows us to optimize the care, the monitoring of patients presenting them. The increase in duration therefore has a protective effect (probably because it is severity that causes earlier care and therefore a decrease in duration in the UAS) on both the risk of severe influenza and mortality

Clinical phenotypes and outcomes associated with SARS-CoV-2 variant Omicron in critically ill French patients with COVID-19

Infection with SARS-CoV-2 variant Omicron is considered to be less severe than infection with variant Delta, with rarer occurrence of severe disease requiring intensive care. Little information is available on comorbid factors, clinical conditions and specific viral mutational patterns associated with the severity of variant Omicron infection. In this multicenter prospective cohort study, patients consecutively admitted for severe COVID-19 in 20 intensive care units in France between December 7th 2021 and May 1st 2022 were included. Among 259 patients, we show that the clinical phenotype of patients infected with variant Omicron (n = 148) is different from that in those infected with variant Delta (n = 111). We observe no significant relationship between Delta and Omicron variant lineages/sublineages and 28-day mortality (adjusted odds ratio [95% confidence interval] = 0.68 [0.35-1.32]; p = 0.253). Among Omicroninfected patients, 43.2% are immunocompromised, most of whom have received two doses of vaccine or more (85.9%) but display a poor humoral response to vaccination. The mortality rate of immunocompromised patients infected with variant Omicron is significantly higher than that of nonimmunocompromised patients (46.9% vs 26.2%; p = 0.009). In patients infected with variant Omicron, there is no association between specific sublineages (BA.1/BA.1.1 (n = 109) and BA.2 (n = 21)) or any viral genome polymorphisms/ mutational profile and 28-day mortality

Clinical phenotypes and outcomes associated with SARS-CoV-2 variant Omicron in critically ill French patients with COVID-19

Infection with SARS-CoV-2 variant Omicron is considered to be less severe than infection with variant Delta, with rarer occurrence of severe disease requiring intensive care. Little information is available on comorbid factors, clinical conditions and specific viral mutational patterns associated with the severity of variant Omicron infection. In this multicenter prospective cohort study, patients consecutively admitted for severe COVID-19 in 20 intensive care units in France between December 7th 2021 and May 1st 2022 were included. Among 259 patients, we show that the clinical phenotype of patients infected with variant Omicron (n = 148) is different from that in those infected with variant Delta (n = 111). We observe no significant relationship between Delta and Omicron variant lineages/sublineages and 28-day mortality (adjusted odds ratio [95% confidence interval] = 0.68 [0.35-1.32]; p = 0.253). Among Omicroninfected patients, 43.2% are immunocompromised, most of whom have received two doses of vaccine or more (85.9%) but display a poor humoral response to vaccination. The mortality rate of immunocompromised patients infected with variant Omicron is significantly higher than that of nonimmunocompromised patients (46.9% vs 26.2%; p = 0.009). In patients infected with variant Omicron, there is no association between specific sublineages (BA.1/BA.1.1 (n = 109) and BA.2 (n = 21)) or any viral genome polymorphisms/ mutational profile and 28-day mortality

Author Correction: Clinical phenotypes and outcomes associated with SARS-CoV-2 variant Omicron in critically ill French patients with COVID-19

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Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron variants BA.2, BA.5 and BQ.1.1 in critically ill patients with COVID-19: a prospective, multicenter cohort study

International audienceBackground: Despite current broad natural and vaccine-induced protection, a substantial number of patients infected with emerging SARS-CoV-2 variants (e.g., BF.7 and BQ.1.1) still experience severe COVID-19. Real-life studies investigating the impact of these variants on clinical outcomes of severe cases are currently not available. We performed a prospective multicenter observational cohort study. Adult patients with acute respiratory failure admitted between December 7, 2021 and December 15, 2022, in one of the 20 participating intensive care units (17 from the Greater Paris area and 3 from the North of France) were eligible for inclusion if they had SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR). Full-length SARS-CoV-2 genomes from all included patients were sequenced by means of next-generation sequencing. The primary endpoint of the study was day-28 mortality. Results: The study included 158 patients infected with three groups of Omicron sublineages, including (i) BA.2 variants and their early sublineages referred as “BA.2” (n = 50), (ii) early BA.4 and BA.5 sublineages (including BA.5.1 and BA.5.2, n = 61) referred as “BA.4/BA.5”, and (iii) recent emerging BA.5 sublineages (including BQ.1, BQ.1.1, BF.7, BE.1 and CE.1, n = 47) referred as “BQ.1.1”. The clinical phenotype of BQ1.1-infected patients compared to earlier BA.2 and BA.4/BA.5 sublineages, showed more frequent obesity and less frequent immunosuppression. There was no significant difference between Omicron sublineage groups regarding the severity of the disease at ICU admission, need for organ failure support during ICU stay, nor day 28 mortality (21.7%, n = 10/47 in BQ.1.1 group vs 26.7%, n = 16/61 in BA.4/BA.5 vs 22.0%, n = 11/50 in BA.2, p = 0.791). No significant relationship was found between any SARS-CoV-2 substitution and/or deletion on the one hand and survival on the other hand over hospital follow-up. Conclusions: Critically-ill patients with Omicron BQ.1.1 infection showed a different clinical phenotype than other patients infected with earlier Omicron sublineage but no day-28 mortality difference

Randomized Clinical Study of Temporary Transvenous Phrenic Nerve Stimulation in Difficult-to-Wean Patients

Rationale: Diaphragm dysfunction is frequently observed in critically ill patients with difficult weaning from mechanical ventilation. Objectives: To evaluate the effects of temporary transvenous diaphragm neurostimulation on weaning outcome and maximal inspiratory pressure. Methods: Multicenter, open-label, randomized, controlled study. Patients aged >= 18 years on invasive mechanical ventilation for >= 4 days and having failed at least two weaning attempts received temporary transvenous diaphragm neurostimulation using a multielectrode stimulating central venous catheter (bilateral phrenic stimulation) and standard of care (treatment) (n = 57) or standard of care (control) (n= 55). In seven patients, the catheter could not be inserted, and in seven others, pacing therapy could not be delivered; consequently, data were available for 43 patients. The primary outcome was the proportion of patients successfully weaned. Other endpoints were mechanical ventilation duration, 30-day survival, maximal inspiratory pressure, diaphragm-thickening fraction, adverse events, and stimulation-related pain. Measurements and Main Results: The incidences of successful weaning were 82% (treatment) and 74% (control) (absolute difference [95% confidence interval (CI)], 7% [-10 to 25]), P = 0.59. Mechanical ventilation duration (mean +/- SD) was 12.7 +/- 9.9 days and 14.1 +/- 10.8 days, respectively, P = 0.50; maximal inspiratory pressure increased by 16.6 cm H2O and 4.8 cm H2O, respectively (difference [95% CI], 11.8 [5 to 19]), P = 0.001; and right hemidiaphragm thickening fraction during unassisted spontaneous breathing was +17% and -14%, respectively, P = 0.006, without correlation with changes in maximal inspiratory pressure. Serious adverse event frequency was similar in both groups. Median stimulation-related pain in the treatment group was 0 (no pain). Conclusions: Temporary transvenous diaphragm neurostimulation did not increase the proportion of successful weaning from mechanical ventilation. It was associated with a significant increase in maximal inspiratory pressure, suggesting reversal of the course of diaphragm dysfunction

Benefits and risks of noninvasive oxygenation strategy in COVID-19: a multicenter, prospective cohort study (COVID-ICU) in 137 hospitals

International audienceAbstract Rational To evaluate the respective impact of standard oxygen, high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) on oxygenation failure rate and mortality in COVID-19 patients admitted to intensive care units (ICUs). Methods Multicenter, prospective cohort study (COVID-ICU) in 137 hospitals in France, Belgium, and Switzerland. Demographic, clinical, respiratory support, oxygenation failure, and survival data were collected. Oxygenation failure was defined as either intubation or death in the ICU without intubation. Variables independently associated with oxygenation failure and Day-90 mortality were assessed using multivariate logistic regression. Results From February 25 to May 4, 2020, 4754 patients were admitted in ICU. Of these, 1491 patients were not intubated on the day of ICU admission and received standard oxygen therapy (51%), HFNC (38%), or NIV (11%) ( P < 0.001). Oxygenation failure occurred in 739 (50%) patients (678 intubation and 61 death). For standard oxygen, HFNC, and NIV, oxygenation failure rate was 49%, 48%, and 60% ( P < 0.001). By multivariate analysis, HFNC (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.36–0.99, P = 0.013) but not NIV (OR 1.57, 95% CI 0.78–3.21) was associated with a reduction in oxygenation failure). Overall 90-day mortality was 21%. By multivariable analysis, HFNC was not associated with a change in mortality (OR 0.90, 95% CI 0.61–1.33), while NIV was associated with increased mortality (OR 2.75, 95% CI 1.79–4.21, P < 0.001). Conclusion In patients with COVID-19, HFNC was associated with a reduction in oxygenation failure without improvement in 90-day mortality, whereas NIV was associated with a higher mortality in these patients. Randomized controlled trials are needed

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

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Characteristics, management, and prognosis of elderly patients with COVID-19 admitted in the ICU during the first wave: insights from the COVID-ICU study

International audienceBackground: The COVID-19 pandemic is a heavy burden in terms of health care resources. Future decision-making policies require consistent data on the management and prognosis of the older patients (&gt; 70 years old) with COVID-19 admitted in the intensive care unit (ICU). Methods: Characteristics, management, and prognosis of critically ill old patients (&gt; 70 years) were extracted from the international prospective COVID-ICU database. A propensity score weighted-comparison evaluated the impact of intubation upon admission on Day-90 mortality. Results: The analysis included 1199 (28% of the COVID-ICU cohort) patients (median [interquartile] age 74 [72–78] years). Fifty-three percent, 31%, and 16% were 70–74, 75–79, and over 80 years old, respectively. The most frequent comorbidities were chronic hypertension (62%), diabetes (30%), and chronic respiratory disease (25%). Median Clinical Frailty Scale was 3 (2–3). Upon admission, the PaO2/FiO2 ratio was 154 (105–222). 740 (62%) patients were intubated on Day-1 and eventually 938 (78%) during their ICU stay. Overall Day-90 mortality was 46% and reached 67% among the 193 patients over 80 years old. Mortality was higher in older patients, diabetics, and those with a lower PaO2/FiO2 ratio upon admission, cardiovascular dysfunction, and a shorter time between first symptoms and ICU admission. In propensity analysis, early intubation at ICU admission was associated with a significantly higher Day-90 mortality (42% vs 28%; hazard ratio 1.68; 95% CI 1.24–2.27; p &lt; 0·001). Conclusion: Patients over 70 years old represented more than a quarter of the COVID-19 population admitted in the participating ICUs during the first wave. Day-90 mortality was 46%, with dismal outcomes reported for patients older than 80 years or those intubated upon ICU admission