Catastrophic COVID-19 Delta Variant Surge in French West Indies: Report of an ICU Triage Policy.

OBJECTIVES: Here, we report the management of a catastrophic COVID-19 Delta variant surge, which overloaded ICU capacity, using crisis standards of care (CSC) based on a multiapproach protocol. DESIGN: Retrospective observational study. SETTING: University Hospital of Guadeloupe. PATIENTS: This study retrospectively included all patients who were hospitalized for COVID-19 pneumonia between August 11, 2021, and September 10, 2021, and were eligible for ICU admission. INTERVENTION: Based on age, comorbidities, and disease severity, patients were assigned to three groups: Green (ICU admission as soon as possible), Orange (ICU admission after the admission of all patients in the Green group), and Red (no ICU admission). MEASUREMENTS AND MAIN RESULTS: Among the 328 patients eligible for ICU admission, 100 (30%) were assigned to the Green group, 116 (35%) to the Orange group, and 112 (34%) to the Red group. No patient in the Green group died while waiting for an ICU bed, whereas 14 patients (12%) in the Orange group died while waiting for an ICU bed. The 90-day mortality rates were 24%, 37%, and 78% in the Green, Orange, and Red groups, respectively. A total of 130 patients were transferred to the ICU, including 79 from the Green group, 51 from the Orange group, and none from the Red group. Multivariate analysis revealed that among patients admitted to the ICU, death was independently associated with a longer time between ICU referral and ICU admission, the Sequential Organ Failure Assessment score, and the number of comorbidities, but not with triage group. CONCLUSIONS: CSC based on a multiapproach protocol allowed admission of all patients with a good prognosis. Higher mortality was associated with late admission, rather than triage group.

Platelet caspase-1 and Bruton tyrosine kinase activation in patients with COVID-19 is associated with disease severity and reversed in vitro by ibrutinib.

Background: Severity of coronavirus disease 2019 (COVID-19) is often associated with thrombotic complications and cytokine storm leading to intensive are unit (ICU) admission. Platelets are known to be responsible for abnormal hemostasis parameters (thrombocytopenia, raised D-dimers, and prolonged prothrombin time) in other viral infections through the activation of the nucleotide-binding domain leucine repeat rich containing protein 3 inflammasome induced by signaling pathways driven by Bruton tyrosine kinase (BTK) and leading to caspase-1 activation. Objectives: We hypothesized that caspase-1 activation and the phosphorylation of BTK could be associated with the severity of the disease and that ibrutinib, a BTK inhibitor, could inhibit platelet activation. Methods and Results: We studied caspase-1 activation by flow cytometry and the phosphorylation of BTK by Western blot in a cohort of 51 Afro-Carribean patients with COVID-19 disease (19 not treated in ICU and 32 treated in ICU). Patients with a platelet count of 286.7 × 109/L (69-642 × 109/L) were treated by steroids and heparin preventive anticoagulation. Caspase-1 and BTK activation were associated with the severity of the disease and with the procoagulant state of the patients. Furthermore, we showed in vitro that the plasma of ICU patients with COVID-19 was able to increase CD62P expression and caspase-1 activity of healthy platelets and that ibrutinib could prevent it. Conclusions: Our results show that caspase-1 and BTK activation are related to disease severity and suggest the therapeutic hope raised by ibrutinib in the treatment of COVID-19 by reducing the procoagulant state of the patients.

Very late intubation in COVID-19 patients: a forgotten prognosis factor?

Description of all consecutive critically ill COVID 19 patients hospitalized in ICU in University Hospital of Guadeloupe and outcome according to delay between steroid therapy initiation and mechanical ventilation onset. Very late mechanical ventilation defined as intubation after day 7 of dexamethasone therapy was associated with grim prognosis and a high mortality rate of 87%.

Plasma microparticles of intubated COVID-19 patients cause endothelial cell death, neutrophil adhesion and netosis, in a phosphatidylserine-dependent manner.

COVID-19 has compelled scientists to better describe its pathophysiology to find new therapeutic approaches. While risk factors, such as older age, obesity, and diabetes mellitus, suggest a central role of endothelial cells (ECs), autopsies have revealed clots in the pulmonary microvasculature that are rich in neutrophils and DNA traps produced by these cells, called neutrophil extracellular traps (NETs.) Submicron extracellular vesicles, called microparticles (MPs), are described in several diseases as being involved in pro-inflammatory pathways. Therefore, in this study, we analyzed three patient groups: one for which intubation was not necessary, an intubated group, and one group after extubation. In the most severe group, the intubated group, platelet-derived MPs and endothelial cell (EC)-derived MPs exhibited increased concentration and size, when compared to uninfected controls. MPs of intubated COVID-19 patients triggered EC death and overexpression of two adhesion molecules: P-selectin and vascular cell adhesion molecule-1 (VCAM-1). Strikingly, neutrophil adhesion and NET production were increased following incubation with these ECs. Importantly, we also found that preincubation of these COVID-19 MPs with the phosphatidylserine capping endogenous protein, annexin A5, abolished cytotoxicity, P-selectin and VCAM-1 induction, all like increases in neutrophil adhesion and NET release. Taken together, our results reveal that MPs play a key role in COVID-19 pathophysiology and point to a potential therapeutic: annexin A5.

Impact of early low-calorie low-protein versus standard-calorie standard-protein feeding on outcomes of ventilated adults with shock: design and conduct of a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3).

INTRODUCTION: International guidelines include early nutritional support (≤48 hour after admission), 20-25 kcal/kg/day, and 1.2-2 g/kg/day protein at the acute phase of critical illness. Recent data challenge the appropriateness of providing standard amounts of calories and protein during acute critical illness. Restricting calorie and protein intakes seemed beneficial, suggesting a role for metabolic pathways such as autophagy, a potential key mechanism in safeguarding cellular integrity, notably in the muscle, during critical illness. However, the optimal calorie and protein supply at the acute phase of severe critical illness remains unknown. NUTRIREA-3 will be the first trial to compare standard calorie and protein feeding complying with guidelines to low-calorie low-protein feeding. We hypothesised that nutritional support with calorie and protein restriction during acute critical illness decreased day 90 mortality and/or dependency on intensive care unit (ICU) management in mechanically ventilated patients receiving vasoactive amine therapy for shock, compared with standard calorie and protein targets. METHODS AND ANALYSIS: NUTRIREA-3 is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients receiving invasive mechanical ventilation and vasoactive amine therapy for shock and given early nutritional support according to one of two strategies: early calorie-protein restriction (6 kcal/kg/day-0.2-0.4 g/kg/day) or standard calorie-protein targets (25 kcal/kg/day, 1.0-1.3 g/kg/day) at the acute phase defined as the first 7 days in the ICU. We will include 3044 patients in 61 French ICUs. Two primary end-points will be evaluated: day 90 mortality and time to ICU discharge readiness. The trial will be considered positive if significant between-group differences are found for one or both alternative primary endpoints. Secondary outcomes include hospital-acquired infections and nutritional, clinical and functional outcomes. ETHICS AND DISSEMINATION: The NUTRIREA-3 study has been approved by the appropriate ethics committee. Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03573739.

Critical care medicine in the French Territories in the Americas: Current situation and prospects.

Hospitals in the French Territories in the Americas (FTA) work according to international and French standards. This paper aims to describe different aspects of critical care in the FTA. For this, we reviewed official information about population size and intensive care unit (ICU) bed capacity in the FTA and literature on FTA ICU specificities. Persons living in or visiting the FTA are exposed to specific risks, mainly severe road traffic injuries, envenoming, stab or ballistic wounds, and emergent tropical infectious diseases. These diseases may require specific knowledge and critical care management. However, there are not enough ICU beds in the FTA. Indeed, there are 7.2 ICU beds/100 000 population in Guadeloupe, 7.2 in Martinique, and 4.5 in French Guiana. In addition, seriously ill patients in remote areas regularly have to be transferred, most often by helicopter, resulting in a delay in admission to intensive care. The COVID-19 crisis has shown that the health care system in the FTA is unready to face such an epidemic and that intensive care bed capacity must be increased. In conclusion, the critical care sector in the FTA requires upgrading of infrastructure, human resources, and equipment as well as enhancement of multidisciplinary care. Also needed are promotion of training, research, and regional and international medical and scientific cooperation.

Los hospitales en los territorios franceses de la Región de las Américas funcionan según las normas francesas e internacionales. El objetivo de este artículo es describir distintos aspectos de los cuidados intensivos en los territorios franceses. Para ello, hemos revisado los datos oficiales sobre el tamaño de la población y el número de camas de las unidades de cuidados intensivos (UCI), así como la bibliografía sobre algunos aspectos específicos de las UCI, en los territorios franceses. Las personas que viven en los territorios franceses, o que están de visita en ellos, están expuestas a riesgos específicos: principalmente traumatismos graves causados por el tránsito, envenenamiento por mordeduras, heridas de bala o por apuñalamiento, y enfermedades infecciosas tropicales emergentes. La atención de estos traumatismos y enfermedades puede requerir conocimientos específicos y cuidados intensivos. Sin embargo, no hay suficientes camas de UCI en los territorios franceses. De hecho, hay 7,2 camas de UCI por 100 000 habitantes en Guadalupe, 7,2 en Martinica y 4,5 en Guayana Francesa. Además, los pacientes gravemente enfermos que viven en zonas remotas a menudo tienen que ser trasladados, normalmente por helicóptero, lo que retrasa su ingreso en la unidad de cuidados intensivos. La crisis de la COVID-19 ha puesto de manifiesto que el sistema de atención de salud en los territorios franceses no está preparado para enfrentarse a una epidemia de estas dimensiones y que debe aumentarse la capacidad hospitalaria de las unidades de cuidados intensivos. En conclusión, el sector de los cuidados intensivos en los territorios franceses tiene que mejorar su infraestructura, recursos humanos y equipamiento, así como perfeccionar la atención multidisciplinaria. También es necesario promover la capacitación, la investigación y la cooperación médica y científica, tanto regional como internacional.

Os hospitais nos territórios ultramarinos franceses nas Américas funcionam segundo os padrões franceses e internacionais. O objetivo deste artigo é descrever os diversos aspectos da atenção intensiva nesta região. Analisamos os dados oficiais relativos ao tamanho da população e ao número de leitos de unidade de terapia intensiva (UTI) nestes territórios junto com uma revisão da literatura científica sobre as características particulares destes centros de terapia intensiva. Os residentes locais ou visitantes dos territórios ultramarinos franceses nas Américas são expostos a riscos específicos, sobretudo acidentes de trânsito graves, envenenamentos por animais peçonhentos, ferimentos por armas brancas ou armas de fogo e doenças infecciosas tropicais emergentes que requerem conhecimento especializado e atenção intensiva. Porém, não há leitos suficientes de UTI nos territórios ultramarinos franceses nas Américas: são 7,2 leitos de UTI por 100.000 habitantes em Guadalupe, 7,2 na Martinica e 4,5 na Guiana Francesa. Ademais, em áreas remotas, os pacientes em estado crítico frequentemente precisam ser transferidos por helicóptero, o que causa demora na internação em UTI. A crise da COVID-19 demonstra o despreparo do sistema de saúde para enfrentar a pandemia e a necessidade de aumentar o número de leitos de UTI nestes territórios. Em conclusão, é imprescindível modernizar a infraestrutura e os equipamentos, capacitar melhor os recursos humanos e melhorar a atenção multidisciplinar. Incentivar a formação profissional, pesquisa e cooperação médico-científica regional e mundial é também fundamental.