Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

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/)

Evaluation of therapeutics strategies in murin models of pneumonia

L'émergence de bactéries résistantes à plusieurs classes d'antibiotiques rend difficile le traitement des pneumonies nosocomiales. Notre objectif était d'évaluer de nouvelles stratégies thérapeutiques et hypothèses physiopathologiques dans des modèles murins de pneumonie.Dans un premier modèle de pneumonie aigue létale à A. baumannii chez le rat, nous avons comparé la virulence de 2 souches nosocomiales, l'une sensible (ABCS) et l'autre résistante (ABCR) à la colistine. Nous avons montré une diminution de la mortalité, du compte bactérien pulmonaire, de l'incidence des bactériémies et des lésions histologiques pulmonaires chez les animaux infectés avec ABCR, ceci confirmant la baisse de virulence associée à l'acquisition de la résistance à la colistine. Dans un second travail, nous avons développé un modèle de pneumonie chronique à P. aeruginosa chez le rat et montré que des aérosols de squalamine permettaient une diminution de la charge bactérienne pulmonaire et du nombre de lésions histologiques de pneumonie. Au cours d'un troisième travail, nous avons évalué l'effet inhibiteur du quorum sensing d'une lactonase in vitro et dans un modèle de pneumonie aigue létale à P. aeruginosa chez le rat. Nous avons constaté une diminution de l'activation de gènes de virulence et de la synthèse de biofilm bactérien in vitro. Ceci était associé à une diminution de la mortalité de 75 à 20 % chez les animaux traités.ConclusionsCe travail de thèse nous a permis de montrer le potentiel thérapeutique de 2 molécules dans des pneumonies à P. aeruginosa et d'illustrer la perte de virulence associée à la résistance à la colistine dans une souche clinique d'A. baumannii.The emergence multi-drug resistant bacteria hardens the treatment of nosocomial pneumonia. Our objective was to evaluate new therapeutic strategies and pathophysiological hypotheses in murine models of pneumonia.In a first model of acute lethal pneumonia with A. baumannii in rats, we compared the virulence of two hospital strains, one susceptible (ABCS) and the other resistant (ABCR) to colistin. We showed a reduction in mortality, pulmonary bacterial count, incidence of bacteremia and pulmonary histological lesions in animals infected with ABCR. This confirms the impaired virulence associated with the acquisition of resistance to colistin. In a second study, we developed a model of chronic pneumonia with P. aeruginosa in rats and showed thataerosols of squalamine permitted a reduction in pulmonary bacterial load and the number of histological lesions of pneumonia. In a third study, we evaluated the quorum quenching effects of a lactonase in vitro and in a model of acute lethal P. aeruginosa pneumonia in rats. We found a decrease in virulence gene activation and bacterial biofilm synthesis in vitro. This was associated with a decreased mortality from 75 to 20% in the treated animals.ConclusionsIn this work, we described the therapeutic potential of 2 molecules in P. aeruginosa pneumonia and illustratesd the loss of virulence associated with resistance to colistin in a clinical strain of A. baumannii

Pharmacological interventions in acute respiratory distress syndrome

International audiencePharmacological interventions are commonly considered in acute respiratory distress syndrome (ARDS) patients. Inhaled nitric oxide (iNO) and neuromuscular blockers (NMBs) are used in patients with severe hypoxemia. No outcome benefit has been observed with the systematic use of iNO. However, a sometimes important improvement in oxygenation can occur shortly after starting administration. Therefore, its ease of use and its good tolerance justify iNO optionally combined with almitirne as a rescue therapy on a trial basis. Recent data from the literature support the use of a 48-h infusion of NMBs in patients with a PaO2 to FiO2 ratio < 120 mmHg. No strong evidence exists on the increase of ICU-acquired paresis after a short course of NMBs. Fluid management with the goal to obtain zero fluid balance in ARDS patients without shock or renal failure significantly increases the number of days without mechanical ventilation. On the other hand, patients with hemodynamic failure must receive early and adapted fluid resuscitation. Liberal and conservative fluid strategies therefore are complementary and should ideally follow each other in time in the same patient whose hemodynamic state progressively stabilizes. At present, albumin treatment does not appear to be justified for limitation of pulmonary edema and respiratory morbidity. Aerosolized β2-agonists do not improve outcome in patients with ARDS and one study strongly suggests that intravenous salbutamol may worsen outcome in those patients. The early use of high doses of corticosteroids for the prevention of ARDS in septic shock patients or in patients with confirmed ARDS significantly reduced the duration of mechanical ventilation but had no effect or even increased mortality. In patients with persistent ARDS after 7 to 28 days, a randomized trial showed no reduction in mortality with moderate doses of corticosteroids but an increased PaO2 to FiO2 ratio and thoracopulmonary compliance were found, as well as shorter durations of mechanical ventilation and of ICU stay. Conflicting data exist on the interest of low doses of corticosteroids (200 mg/day of hydrocortisone) in ARDS patients. In the context of a persistent ARDS with histological proof of fibroproliferation, a corticosteroid treatment with a progressive decrease of doses can be proposed

Determinants of long-term outcomes in patients with COVID-19 supported with ECMO

International audienc

A Rare Cause of Heart Failure Treated by Heart Transplantation: Noncompaction of the Ventricular Myocardium

Noncompaction of the ventricular myocardium is a rare cardiomyopathy due to an arrest of myocardial morphogenesis. The characteristic echocardiographic findings are prominent myocardial trabeculations and deep intertrabecular spaces communicating with the left ventricular cavity. The clinical manifestations include heart failure (HF) signs, ventricular arrhythmias, and cardioembolic events. We describe an illustrative case of noncompaction of the ventricular myocardium associated with bicuspid aortic valve, a 42-year-old male presenting a refractory acute heart failure successfully treated by emergency heart transplantation

Effect of high-frequency oscillatory ventilation on esophageal and transpulmonary pressures in moderate-to-severe acute respiratory distress syndrome

International audienceBackground: High-frequency oscillatory ventilation (HFOV) has not been shown to be beneficial in the management of moderate-to-severe acute respiratory distress syndrome (ARDS). There is uncertainty about the actual pressure applied into the lung during HFOV. We therefore performed a study to compare the transpulmonary pressure (PL) during conventional mechanical ventilation (CMV) and different levels of mean airway pressure (mPaw) during HFOV. Methods: This is a prospective randomized crossover study in a university teaching hospital. An esophageal balloon catheter was used to measure esophageal pressures (Pes) at end inspiration and end expiration and to calculate P-L. Measurements were taken during ventilation with CMV (CMVpre) after which patients were switched to HFOV with three 1-h different levels of mPaw set at +5, +10 and +15 cm H2O above the mean airway pressure measured during CMV. Patients were thereafter switched back to CMV (CMVpost). Results: Ten patients with moderate-to-severe ARDS were included. We demonstrated a linear increase in Pes and P-L with the increase in mPaw during HFOV. Contrary to CMV, P-L was always positive during HFOV whatever the level of mPaw applied but not associated with improvement in oxygenation. We found significant correlations between mPaw and Pes. Conclusion: HFOV with high level of mPaw increases transpulmonary pressures without improvement in oxygenation