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/)

Introducing physical relaxation terms in Bloch equations

International audienceThe Bloch equation models the evolution of the state of electrons in matter described by a Hamiltonian. To model more physical phenomena we have to introduce phenomenological relaxation terms. The introduction of these terms has to conserve some positiveness properties. The aim of this paper is to review possible relaxation models and to provide insight into how to discretize them properly in view of numerical computations

Multi-level Maxwell-Bloch simulations

International audienceWe present the Maxwell-Bloch equations that are a model for the semi-classical description of laser-matter interactions. After having discussed both models and their numerical coupling in a general context regarding relaxation terms and the number of energy levels, we give examples of simulations that show the capacities of our approach

Multi-level Maxwell-Bloch simulations

International audienceWe present the Maxwell-Bloch equations that are a model for the semi-classical description of laser-matter interactions. After having discussed both models and their numerical coupling in a general context regarding relaxation terms and the number of energy levels, we give examples of simulations that show the capacities of our approach

Impact of the duration of oestradiol treatment on live birth rate in Hormonal Replacement Therapy cycle before frozen blastocyst transfer

International audienceAlthough the duration of progesterone administration in Hormonal Replacement Therapy (HRT) cycles before frozen embryo transfer is standardized, the optimal duration of oestrogen treatment remains controversial. In this monocentric retrospective study conducted in all single frozen blastocyst transfer (FBT) performed with HRT between January 2016 and July 2019, we evaluated the association between the duration of oestradiol treatment before FBT and live birth rate (LBR) in HRT cycles. Cycles were gathered in 3 groups according to quartiles of duration of oestrogen treatment. LBR was compared across the 3 groups and multivariate analysis was performed. We included 2235 single FBT cycles; 507, 1257 and 471 with E2 treatment below 23 days, 23-30 days (reference) and more than 30 days respectively. After multivariate analysis and adjustment, no significant difference in LBR was found between below 23 or more than 30 days and reference groups (OR = 0.93 [0.68-1.27] and OR = 1.29 [0.88-1.89] respectively). Complementary sensitivity analysis led to a non-significant adjusted OR = 1.66 [IC 0.9-3.1]. In conclusion, our study showed that the duration of E2 treatment in HRT cycles before FBT is not associated with LBR

High-flow nasal cannula oxygen during endotracheal intubation in hypoxemic patients: a randomized controlled clinical trial

International audienceIntubation of hypoxemic patients is associated with life-threatening adverse events. High-flow therapy by nasal cannula (HFNC) for preoxygenation before intubation has never been assessed by randomized study. Our objective was to evaluate the efficiency of HFNC for preoxygenation, compared to high fraction-inspired oxygen facial mask (HFFM)

Effect of High-Dose Baclofen on Agitation-Related Events Among Patients With Unhealthy Alcohol Use Receiving Mechanical Ventilation

International audienceImportance: Unhealthy alcohol use can lead to agitation in the intensive care unit (ICU).Objective: To assess whether high-dose baclofen reduces agitation-related events compared with placebo in patients with unhealthy alcohol use receiving mechanical ventilation.Design, settings, and participants: This phase 3, double-blind, placebo-controlled, randomized clinical trial conducted in 18 ICUs in France recruited adults receiving mechanical ventilation who met criteria for unhealthy alcohol use. Patients were enrolled from June 2016 to February 2018; the last follow-up was in May 2019.Interventions: Baclofen (n = 159), adjusted from 50 to 150 mg per day based on estimated glomerular filtration rate, or placebo (n = 155) during mechanical ventilation up to a maximum of 15 days before gradual dose reduction over 3 to 6 days.Main outcomes and measures: The primary end point was the percentage of patients with at least 1 agitation-related event over the treatment period. Secondary outcomes included duration of mechanical ventilation, length of ICU stay, and 28-day mortality.Results: Among 314 patients who were randomized (mean age, 57 years; 60 [17.2%] women), 313 (99.7%) completed the trial. There was a statistically significant decrease in the percentage of patients who experienced at least 1 agitation-related event in the baclofen group vs the placebo group (31 [19.7%] vs 46 [29.7%]; difference, -9.93% [95% CI, -19.45% to -0.42%]; adjusted odds ratio, 0.59 [95% CI, 0.35-0.99]). Of 18 prespecified secondary end points, 14 were not significantly different. Compared with the placebo group, the baclofen group had a significantly longer median length of mechanical ventilation (9 vs 8 days; difference, 2.00 [95% CI, 0.00-3.00]; hazard ratio [HR] for extubation, 0.76 [95% CI, 0.60-0.97]) and stay in the ICU (14 vs 11 days; difference, 2.00 [95% CI, 0.00-4.00]; HR for discharge, 0.70 [95% CI, 0.54-0.90]). At 28 days, there was no significant difference in mortality in the baclofen vs placebo group (25.3% vs 21.6%; adjusted odds ratio, 1.24 [95% CI, 0.72-2.13]). Delayed awakening (no eye opening at 72 hours after cessation of sedatives and analgesics) occurred in 14 patients (8.9%) in the baclofen group vs 3 (1.9%) in the placebo group.Conclusions and relevance: Among patients with unhealthy alcohol use receiving mechanical ventilation, treatment with high-dose baclofen, compared with placebo, resulted in a statistically significant reduction in agitation-related events. However, considering the modest effect and the totality of findings for the secondary end points and adverse events, further research is needed to determine the possible role of baclofen in this setting and to potentially optimize dosing.Trial registration: ClinicalTrials.gov Identifier: NCT02723383

Effects of Fluid Resuscitation With Colloids vs Crystalloids on Mortality in Critically Ill Patients Presenting With Hypovolemic Shock

International audienceIMPORTANCE:Evidence supporting the choice of intravenous colloid vs crystalloid solutions for management of hypovolemic shock remains unclear.OBJECTIVE:To test whether use of colloids compared with crystalloids for fluid resuscitation alters mortality in patients admitted to the intensive care unit (ICU) with hypovolemic shock.DESIGN, SETTING, AND PARTICIPANTS:A multicenter, randomized clinical trial stratified by case mix (sepsis, trauma, or hypovolemic shock without sepsis or trauma). Therapy in the Colloids Versus Crystalloids for the Resuscitation of the Critically Ill (CRISTAL) trial was open label but outcome assessment was blinded to treatment assignment. Recruitment began in February 2003 and ended in August 2012 of 2857 sequential ICU patients treated at 57 ICUs in France, Belgium, North Africa, and Canada; follow-up ended in November 2012.INTERVENTIONS:Colloids (n = 1414; gelatins, dextrans, hydroxyethyl starches, or 4% or 20% of albumin) or crystalloids (n = 1443; isotonic or hypertonic saline or Ringer lactate solution) for all fluid interventions other than fluid maintenance throughout the ICU stay.MAIN OUTCOMES AND MEASURES:The primary outcome was death within 28 days. Secondary outcomes included 90-day mortality; and days alive and not receiving renal replacement therapy, mechanical ventilation, or vasopressor therapy.RESULTS:Within 28 days, there were 359 deaths (25.4%) in colloids group vs 390 deaths (27.0%) in crystalloids group (relative risk [RR], 0.96 [95% CI, 0.88 to 1.04]; P = .26). Within 90 days, there were 434 deaths (30.7%) in colloids group vs 493 deaths (34.2%) in crystalloids group (RR, 0.92 [95% CI, 0.86 to 0.99]; P = .03). Renal replacement therapy was used in 156 (11.0%) in colloids group vs 181 (12.5%) in crystalloids group (RR, 0.93 [95% CI, 0.83 to 1.03]; P = .19). There were more days alive without mechanical ventilation in the colloids group vs the crystalloids group by 7 days (mean: 2.1 vs 1.8 days, respectively; mean difference, 0.30 [95% CI, 0.09 to 0.48] days; P = .01) and by 28 days (mean: 14.6 vs 13.5 days; mean difference, 1.10 [95% CI, 0.14 to 2.06] days; P = .01) and alive without vasopressor therapy by 7 days (mean: 5.0 vs 4.7 days; mean difference, 0.30 [95% CI, -0.03 to 0.50] days; P = .04) and by 28 days (mean: 16.2 vs 15.2 days; mean difference, 1.04 [95% CI, -0.04 to 2.10] days; P = .03).CONCLUSIONS AND RELEVANCE:Among ICU patients with hypovolemia, the use of colloids vs crystalloids did not result in a significant difference in 28-day mortality. Although 90-day mortality was lower among patients receiving colloids, this finding should be considered exploratory and requires further study before reaching conclusions about efficacy