Bench-to-bedside review: Glucose and stress conditions in the intensive care unit

The physiological response to blood glucose elevation is the pancreatic release of insulin, which blocks hepatic glucose production and release, and stimulates glucose uptake and storage in insulin-dependent tissues. When this first regulatory level is overwhelmed (that is, by exogenous glucose supplementation), persistent hyperglycaemia occurs with intricate consequences related to the glucose acting as a metabolic substrate and as an intracellular mediator. It is thus very important to unravel the glucose metabolic pathways that come into play during stress as well as the consequences of these on cellular functions. During acute injuries, activation of serial hormonal and humoral responses inducing hyperglycaemia is called the 'stress response'. Central activation of the nervous system and of the neuroendocrine axes is involved, releasing hormones that in most cases act to worsen the hyperglycaemia. These hormones in turn induce profound modifications of the inflammatory response, such as cytokine and mediator profiles. The hallmarks of stress-induced hyperglycaemia include 'insulin resistance' associated with an increase in hepatic glucose output and insufficient release of insulin with regard to glycaemia. Although both acute and chronic hyperglycaemia may induce deleterious effects on cells and organs, the initial acute endogenous hyperglycaemia appears to be adaptive. This acute hyperglycaemia participates in the maintenance of an adequate inflammatory response and consequently should not be treated aggressively. Hyperglycaemia induced by an exogenous glucose supply may, in turn, amplify the inflammatory response such that it becomes a disproportionate response. Since chronic exposure to glucose metabolites, as encountered in diabetes, induces adverse effects, the proper roles of these metabolites during acute conditions need further elucidation

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/)

Rôle du glucose sur le métabolisme mitochondrial et l hyperproduction d espèces radicalaires de l oxygène par les cellules mononuclées du sang périphérique au cours du sepsis chez l homme

Lors d un sepsis, le contrôle strict de la glycémie est recommandé sans que le mécanisme d action soit bien défini. L objectif de l étude est de déterminer l effet de l hyperglycémie et du plasma septique sur la consommation d oxygène des cellules mononuclées du sang périphérique humain (CMSP), actrices principales de la réponse immunitaire innée. Le CMSP de volontaires sains sont incubées dans le plasma de donneur (contrôle) ou dans un pool de plasmas septiques (plS), avec ajout de glucose (hyperglycémie : HG) ou sans (normoglycémie : NG). Leur consommation d oxygène est étudiée après stimulation par PMA-ionomycine (radicalaire et mitochondriale) ou ADP (mitochondriale pure) et en bloquant la glycolyse (2-désoxyglucose) ou le shunt des pentoses (épiandrostérone et 6-animo nicotinamide). Nous vérifions l importance de la NADPH oxydase sur la production radicalaire par un inhibiteur spécifique : le DPI. Les résultats montraient une augmentation de l incorporation cellulaire du glucose en HG et en plS. En condition contrôle, il n y avait pas d effet de l HG sur la réponse de l ADP, mais une amplification de celle à PMA-ionomycine (p<.05). L étude de la glycolyse et du shunt des pentoses mettait en évidence le rôle de ce dernier dans l effet du glucose et du plasma septique sur le métabolisme radicalaire. Le DPI permettait de confirmer l activation de la production radicalaire. En situation septique, les CMSP en HG présentent une réponse radicalaire plus explosive, utile pour lutter contre les bactéries, mais potentiellement nuisible pour les cellules tissulaires.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Tracheostomy and long-term mortality in ICU patients undergoing prolonged mechanical ventilation

International audienceIntroductionIn critically ill patients undergoing prolonged mechanical ventilation (MV), the difference in long-term outcomes between patients with or without tracheostomy remains unexplored.MethodsAncillary study of a prospective international multicentre observational cohort in 21 centres in France and Belgium, including 2087 patients, with a one-year follow-up after admission. We included patients with a MV duration ≥10 days, with or without tracheostomy. We explored the one-year mortality with a classical Cox regression model (adjustment on age, SAPS II, baseline diagnosis and withdrawal of life-sustaining therapies) and a Cox regression model using tracheostomy as a time-dependant variable.Results29.5% patients underwent prolonged MV, out of which 25.6% received tracheostomy and 74.4% did not. At one-year, 45.2% patients had died in the tracheostomy group and 51.5% patients had died in the group without tracheostomy (p = 0.001). In the Cox-adjusted regression model, tracheostomy was not associated with improved one-year outcome (HR CI95 0.7 [0.5–1.001], p = 0.051), as well as in the model using tracheostomy as a time-dependent variable (OR CI 95 1 [0.7–1.4], p = 0.9).ConclusionsIn our study, there was no statistically significant difference in the one-year mortality of patients undergoing prolonged MV when receiving tracheostomy or not

Multicenter Testing of the Rapid Quantification of Radical Oxygen Species in Cerebrospinal Fluid to Diagnose Bacterial Meningitis

<div><p>Purpose</p><p>Meningitis is a serious concern after traumatic brain injury (TBI) or neurosurgery. This study tested the level of reactive oxygen species (ROS) in cerebrospinal fluid (CSF) to diagnose meningitis in febrile patients several days after trauma or surgery.</p><p>Methods</p><p>Febrile patients (temperature > 38°C) after TBI or neurosurgery were included prospectively. ROS were measured in CSF within 4 hours after sampling using luminescence in the basal state and after cell stimulation with phorbol 12-myristate 13-acetate (PMA). The study was conducted in a single-center cohort 1 (n = 54, training cohort) and then in a multicenter cohort 2 (n = 136, testing cohort) in the Intensive Care and Neurosurgery departments of two teaching hospitals. The performance of the ROS test was compared with classical CSF criteria, and a diagnostic decision for meningitis was made by two blinded experts.</p><p>Results</p><p>The production of ROS was higher in the CSF of meningitis patients than in non-infected CSF, both in the basal state and after PMA stimulation. In cohort 1, ROS production was associated with a diagnosis of meningitis with an AUC of 0.814 (95% confidence interval (CI) [0.684–0.820]) for steady-state and 0.818 (95% CI [0.655–0.821]) for PMA-activated conditions. The best threshold value obtained in cohort 1 was tested in cohort 2 and showed high negative predictive values and low negative likelihood ratios of 0.94 and 0.36 in the basal state, respectively, and 0.96 and 0.24 after PMA stimulation, respectively.</p><p>Conclusion</p><p>The ROS test in CSF appeared suitable for eliminating a diagnosis of bacterial meningitis.</p></div