Impact of early enteral versus parenteral nutrition on mortality in patients requiring mechanical ventilation and catecholamines: study protocol for a randomized controlled trial (NUTRIREA-2)

BACKGROUND: Nutritional support is crucial to the management of patients receiving invasive mechanical ventilation (IMV) and the most commonly prescribed treatment in intensive care units (ICUs). International guidelines consistently indicate that enteral nutrition (EN) should be preferred over parenteral nutrition (PN) whenever possible and started as early as possible. However, no adequately designed study has evaluated whether a specific nutritional modality is associated with decreased mortality. The primary goal of this trial is to assess the hypothesis that early first-line EN, as compared to early first-line PN, decreases day 28 all-cause mortality in patients receiving IMV and vasoactive drugs for shock. METHODS/DESIGN: The NUTRIREA-2 study is a multicenter, open-label, parallel-group, randomized controlled trial comparing early PN versus early EN in critically ill patients requiring IMV for an expected duration of at least 48 hours, combined with vasoactive drugs, for shock. Patients will be allocated at random to first-line PN for at least 72 hours or to first-line EN. In both groups, nutritional support will be started within 24 hours after IMV initiation. Calorie targets will be 20 to 25 kcal/kg/day during the first week, then 25 to 30 kcal/kg/day thereafter. Patients receiving PN may be switched to EN after at least 72 hours in the event of shock resolution (no vasoactive drugs for 24 consecutive hours and arterial lactic acid level below 2 mmol/L). On day 7, all patients receiving PN and having no contraindications to EN will be switched to EN. In both groups, supplemental PN may be added to EN after day 7 in patients with persistent intolerance to EN and inadequate calorie intake. We plan to recruit 2,854 patients at 44 participating ICUs. DISCUSSION: The NUTRIREA-2 study is the first large randomized controlled trial designed to assess the hypothesis that early EN improves survival compared to early PN in ICU patients. Enrollment started on 22 March 2013 and is expected to end in November 2015. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01802099 (registered 27 February 2013)

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old

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/)

Diagnostic de l'insuffisance cardiaque aiguë aux urgences (intérêt d'un dosage combiné de biomarqueurs)

CONTEXTE : Le diagnostic étiologique d une dyspnée aiguë grave est difficile. L objectif de notre travail a été d évaluer l intérêt d un dosage combiné de biomarqueurs pour le diagnostic d une insuffisance cardiaque (IC) aiguë responsable d une dyspnée aiguë grave. METHODE Etude prospective monocentrique observationnelle de cohorte de patients admis pour dyspnée aiguë grave (SpO2 = 25/min) au CHU de Grenoble sur une période de 9 mois. Approche clinico-biologique (examen physique, électrocardiogramme, radiographie thoracique, biologie standard, dosages plasmatiques de 5 biomarqueurs : partie N-terminale du peptide natriurétique de type B (NT-proBNP), troponine T, protéine C-réactive (CRP), procalcitonine (ProCT) et D-Dimères). Intervention : aucune. Recueil de mortalité à J28. Concordance du diagnostic des médecins urgentistes avec un comité d experts (test Kappa) ; analyse univariée des facteurs cliniques d IC ; construction d un modèle clinico-biologique prédictif d IC par analyse multivariée. Identification de valeurs seuils de biomarqueurs basées sur les terciles de distribution de la population. RESULTATS : 150 patients ont été inclus (âge 74 ans ; écart interquartiles [62-81], sex ratio 1.2/1, SpO2 90% ; écart interquartiles [87-93], FR 30/min ; écart interquartiles [27-40]). Diagnostic d IC retenu par le comité d experts pour 34 patients contre 21 par l urgentiste (kappa 0.45). Création d un score clinico-biologique prédictif d IC (ASC ROC=0.901). Avec des valeurs terciles, une CRP basse, une ProCT basse et un NT-proBNP élevé utilisés en combinaison avec le score clinico-biologique augmentent la discrimination pour le diagnostic d IC (AUC ROC=0,947). Le taux de mortalité globale à J28 est de 18%. Les patients décédés à J28 présentaient un profil de biomarqueurs élevé. CONCLUSIONS : Dans une population de patients présentant une dyspnée aiguë grave, la performance diagnostique en urgence de l IC apparaît améliorée par une approche combinée de biomarqueurs sous réserve de l utilisation de seuils spécifiques. Un impact direct sur la prise en charge et la filière patient est attendu. L application, la validation de cette démarche et son incidence médico-économique restent à évaluer.BACKGROUND : The diagnosis approach of severe acute dyspnea is difficult. Our objective was to examine the incremental usefulness of adding multiple biomarkers for diagnosing acute heart failure (AHF) in patients presenting with severe acute dyspnea. METHODS : During 9 months, we conducted a single-center prospective observational study in patients presenting with severe acute dyspnea (SpO2 25/minute) in the emergency department or intensive medical care. Approach was clinico-biological (physical examination, ECG, chest X-ray, usual blood tests, plasmatic measurements of 5 biomarkers: NT-proBNP, CRP, Troponin T, procalcitonin (ProCT) and D-Dimers) Vital status at 28 days was recorded. We evaluated concordance between expert diagnosis of acute heart failure and emergency physician diagnosis (kappa s test). Univariate analysis assessed predictive features of AHF, allowing a clinico-biological model performed using multivariate analysis. Biomarkers cut offs were identified from the population of the present study to achieve optimal discrimination for AHF diagnosis. Intervention: none. RESULTS : 150 patients were included (median [IQR]: 74 [62-81] years, SpO2 90% [87-93], RR 30/min [27-40]). 34 patients had a AHF diagnosis by the experts, only 21 were correctly diagnosed by emergency physician. Clinico-biological model predicted AHF with AUC = 0.901. Using special defined cut offs points, incorporating low levels of CRP, ProCT, and high levels of NT-proBNP to the established model significantly increased the diagnosis accuracy (AUC = 0.947). One month mortality rate was 18%. All biomarkers were significantly elevated in patients who died. CONCLUSION : In patients presenting with severe acute dyspnea, our findings suggest that using special defined cut offs points, a simultaneous assessment of NT-proBNP, CRP and ProCT demonstrates potential to assist clinicians in diagnosing AHF with accuracy.GRENOBLE1-BU Médecine pharm. (385162101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Pronostic des patients âgés admis en unité de soins intensifs d'urgence (USIU)

Objectifs : évaluer la survie et le devenir des patients de 80 ans et plus admis en unité de soins intensifs d'urgence (USIU). Méthode : Etude rétrospective descriptive dans l'USIU du Centre Hospitalier Universitaire de Grenoble, du 01/01 au 31/12/2000. Intervention : aucune. Résultats : nous recueillons les paramètres suivants : âge, sexe, diagnostics, antécédents, hospitalisation récente, critères de fragilité, traitements, durées de séjour dans l'USIU et hospitaliére, scores IGS II et Oméga, mortalité à six mois. 22% des admissions totales ont plus de 80 ans (85.9, 80-99), de sexe ratio 1/1, en détresse cardio-circulatoire (38%), respiratoire (33%), neurologique (11%), syndrome hémorragique (7%), période post-opératoire (3%), provenant du domicile (70)% et adressées par le service des urgences (52%) et le SAMU (32%), sans différence jour/nuit ou semaine/week-end.22% sont sous assistance respiratoire. IGS II et Oméga moyens sont à 44 et 19.4 points respectivement. Le séjour moyen dans l'USIU et hospitalier est 1.8 jours et 13.5 respectivement. La mortalité dans l'USIU et hospitalière est 21.7% et 39% respectivement.Etat de choc, détresse neurologique, IGS II>51, Oméga>23, intubation ou séjour dans l'unité>3 jours sont des facteurs pronostiques de mortalité hospitalière. L'âge>90 ans, les antécédents pulmonaires ou le diagnostic de décompensation cardiaque sont associés à un meilleur pronostic. 42.9% sont vivants à 6 mois et 30% vivent à domicile. Ni l'âge, ni les hospitalisations récentes n'influencent le devenir.La mortalité dépend plus de la sévérité de la maladie aiguë et de l'assistance respiratoire.Conclusion : Le grand âge ne doit pas limiter l'admission en USIU. Des études ultérieures sont nécessaires pour confirmer ces données et développer des stratégies pour identifier les patients agés qui bénéficieraient le plus de ce type de structures.Objective: to evaluate the survival and outcome of patients over 80 admitted to an ICU .Design and setting: Retrospective descriptive evaluation in a multidisciplinary ICU, university referral hospital, over a 1 year-period (01/01- 31/12/2000 (...) Mortality depends mainly on the severity of illness or intubation. Conclusion: Age is not a limitating factor for admission in ICU. Further clinical studies are needed to confirm these data in order to develop stategies to identify older patients who should benefit most of ICU care.GRENOBLE1-BU Médecine pharm. (385162101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Argatroban for an alternative anticoagulant in HIT during ECMO

Abstract Background Extracorporeal membrane oxygenation (ECMO) have become more frequently used in daily ICU practice, heparin-induced thrombocytopenia (HIT) is a rare but life-threatening complication while on extracorporeal membrane oxygenation (ECMO). HIT confirmation directly impacts on anticoagulant strategy requiring no delay unfractionated heparin discontinuation to be replaced by alternative systemic anticoagulant treatment. Case presentation We report two clinical cases of HIT occurring during ECMO in various settings with subsequent recovery with argatroban and provide literature review to help physicians treat HIT during ECMO in clinical daily practice. Conclusions HIT during ECMO is uncommon, and despite the absence of recommendation, argatroban seems to be an appropriate and safe therapeutic option. Finally, there are not enough arguments favouring routine circuit change in the event of HIT during ECM

Does endo-tracheal tube clamping prevent air leaks and maintain positive end-expiratory pressure during the switching of a ventilator in a patient in an intensive care unit? A bench study

International audienceOBJECTIVES:When patients with acute respiratory distress syndrome are moved out of an intensive care unit, the ventilator often requires changing. This procedure suppresses positive end expiratory pressure and promotes lung derecruitment. Clamping the endotracheal tube may prevent this from occurring. Whether or not such clamping maintains positive end-expiratory pressure has never been investigated. We designed a bench study to explore this further.HOW THE STUDY WAS DONE:We used the Elysee 350 ventilator in 'volume controlled' mode with a positive end-expiratory pressure of 15 cmH2O, connected to an endotracheal tube with an 8 mm internal diameter inserted into a lung model with 40 ml/cmH2O compliance and 10 cmH2O/L/s resistance. We measured airway pressure and flow between the distal end of the endotracheal tube and the lung model. We tested a plastic, a metal, and an Extra Corporeal Membrane Oxygenation clamp, each with an oral/nasal, a nasal, and a reinforced endotracheal tube. We performed an end-expiratory hold then clamped the endotracheal tube and disconnected the ventilator. We measured the change in airway pressure and volume for 30 s following the disconnection of the ventilator.RESULTS:Airway pressure decreased thirty seconds after disconnection with all combinations of clamp and endotracheal tube. The largest fall in airway pressure (-17.486 cmH2O/s at 5 s and -18.834 cmH2O/s at 30 s) was observed with the plastic clamp combined with the reinforced endotracheal tube. The smallest decrease in airway pressure (0 cmH2O/s at 5 s and -0.163 cmH2O/s at 30 s) was observed using the Extra Corporeal Membrane Oxygenation clamp with the nasal endotracheal tube.CONCLUSIONS:Only the Extra Corporeal Membrane Oxygenation clamp was efficient. Even with an Extra Corporeal Membrane Oxygenation clamp, it is important to limit the duration the ventilator is disconnected to a few seconds (ideally 5 s)

Consequences of Switching to Blended Learning: The Grenoble Medical School Key Elements.

International audienceIn 2006, the Grenoble-Alpes University Medical School decided to switch the learning paradigm of the first year to a blended learning model based on a flipped classroom with a continuous dual assessment system providing personal follow-up. We report a descriptive analysis of two pedagogical models