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/)

Co-Digestion of Extended Aeration Sewage Sludge with Whey, Grease and Septage: Experimental and Modeling Determination

International audienceThe potential of co-digestion mixing thickened secondary sludge (TS) from extended aeration wastewater treatment plant and locally available substrates (whey, grease and septage) has been studied in this work, using three steps. The first step was a batch test to determine the biological methane potential (BMP) of different mixtures of the three co-substrates with TS. The second step was carried out with lab-scale reactors (20 L), simulating anaerobic continuous stirred tank reactors, fed by three mixtures of co-substrates that were determined according to the previous step results. Modeling was applied in the third step, using ADM1 as a mechanistic model to help understand the co-digestion process. According to the BMP step, septage used as a co-substrate has a negative effect on performance, and the addition of 10–30% grease or whey would lead to a gain of around 60–70% in the production of methane. The results from the reactor tests did not validate the positive effects observed with the BMP assay but confirmed good biodegradation efficiency (> 85%). The main purpose of co-digestion in this scenario is to recover energy from waste and effluents that would require even more energy for their treatment. The protein and lipid percentages of particulate biodegradable COD are important variables for digester stability and methane production, as predicted by modeling. The results of simulations with the ADM1 model, adapted to co-digestion, confirmed that this model is a powerful tool to optimize the process of biogas production

Immune thrombocytopenia in a patient with COVID-19

International audienceThis case report describes immune thrombocytopenic purpura in a 41-year-old man hospitalized in the intensive-care unit for COVID-19, 13 days after the onset of COVID-19 symptoms with respiratory failure at admission. Acute respiratory distress syndrome was treated with, among other drugs, low-molecular-weight heparin. On day 8, his platelet count began descending rapidly. On day 10, heparin treatment was replaced by danaparoid sodium, but by day 13, the continued low platelet count made a diagnosis of heparin-induced thrombocytopenia unlikely. Normocytic nonregenerative anemia gradually developed. On day 13, a bone marrow aspiration showed numerous megakaryocytes and a few signs of hemophagocytosis. Corticosteroids were introduced on day 14, and platelets began rising after 3 days and then fell again on day 19. Intravenous immunoglobulin (IV Ig) was then administered. Two days later, the platelet count returned to normal. The immune cause was confirmed by ruling out the differential diagnoses and the excellent and rapid response to intravenous immunoglobulins. Finally, the patient's respiratory state improved. He was discharged to a respiratory rehabilitation unit on day 38. Our case suggests that an immunological cause should be considered in patients with thrombocytopenia during COVID-19

Not all patients with convulsive status epilepticus intubated in pre-hospital settings meet the criteria for refractory status epilepticus

International audienceIntroduction: Mechanically ventilated patients admitted to the intensive care unit (ICU) for generalized convulsive status epilepticus (GCSE) are a heterogeneous population. Our objective was to evaluate the number of patients who fulfilled the diagnostic criteria for refractory GCSE and describe their initial management and prognosis.Methods: This multicenter retrospective study was conducted in four French ICUs in Pitié-Salpêtrière University Hospital in Paris and in the Hospital of Jossigny. Mechanically ventilated patients admitted to the ICU for GCSE between, January 1, 2014, and, December 31, 2016, were included. Patients with anoxia and traumatic brain injury were excluded. Their pre-hospital and ICU medical records were reviewed. The collected data included pre-hospital clinical status, pre-hospital antiepileptic treatment, reason for mechanical ventilation, duration of general anesthesia, and prognosis in the ICU. A retrospective initial diagnosis based on the findings of the analysis of the clinical records was attributed to each patient.Results: Among the 98 patients included, 88.8% (n = 87/98) fulfilled the diagnostic criteria for GCSE; of these cases, 16.1% (n = 14/87) were refractory. Eleven percent of the patients did not fulfill the criteria for GCSE at the time of initial management (retrospective diagnosis of single convulsive seizure, repetitive convulsive seizures, or psychogenic non-epileptic seizures). Most patients were intubated for coma (58.9%, n = 56/95, missing data: n = 3). In the ICU, the median [Q1-Q3] duration of general anesthesia before weaning was 12.3 h (5.0-18.0 h); 7% of the patients had a relapse of status epilepticus, and 2% died in the ICU.Conclusion: Among the cases of confirmed GCSE in the mechanically ventilated patients admitted to the ICU, 16.1% were refractory, with an overall good prognosis. A significant proportion of patients did not fulfill the diagnostic criteria for refractory GCSE

Valproic Acid as an Adjuvant Treatment for Generalized Convulsive Status Epilepticus in Adults Admitted to Intensive Care Units: Protocol for a Double-Blind, Multicenter Randomized Controlled Trial

International audienceBackground: Generalized convulsive status epilepticus (GCSE) is a frequent medical emergency. GCSE treatment focuses on the administration of benzodiazepines followed by a second-line antiepileptic drug (AED). Despite this stepwise strategy, GCSE is not controlled in one-quarter of patients and is associated with protracted hospitalization, high mortality, and long-term disability. Valproic acid (VPA) is an AED with good tolerability and neuroprotective properties.Objective: This study aims to demonstrate that administration of VPA as an adjuvant for first- and second-line treatment in GCSE can improve outcomes.Methods: A multicenter, double-blind, randomized controlled trial was conducted, comparing VPA with a placebo in adults admitted to intensive care units (ICUs) for GCSE in France. GCSE was diagnosed by specifically trained ICU physicians according to standard criteria. All patients received standard of care, including a benzodiazepine and a second-line AED (not VPA), at the discretion of the treating medical team. In the intervention arm, VPA was administered intravenously at a loading dose of 30 mg/kg over 15 minutes, followed by a continuous infusion of 1 mg/kg/hour over the next 12 hours. In the placebo group, an identical intravenous administration of 0.9% saline was used. The primary outcome was the proportion of patients discharged alive from the hospital by day 15. Secondary outcomes were frequency of refractory and super refractory GCSE, ICU-related morbidity, adverse events related to VPA, and cognitive dysfunction at 3 months. Statistical analyses will be performed according to the intent-to-treat principle.Results: The first patient was randomized on February 18, 2013, and the last patient was randomized on July 7, 2018. Of 248 planned patients, 98.7% (245/248) were enrolled across 20 ICUs. At present, data management is still ongoing, and all parties involved in the trial remain blinded.Conclusions: The Valproic Acid as an Adjuvant Treatment for Generalized Convulsive Status Epilepticus (VALSE) trial will evaluate whether the use of VPA as an adjuvant for first- and second-line treatment in GCSE improves outcomes.Trial Registration: ClinicalTrials.gov NCT01791868; https://clinicaltrials.gov/ct2/show/NCT01791868.International Registered Report Identifier (IRRID): DERR1-10.2196/2251

Functional outcome of patients with prolonged hypoglycemic encephalopathy

Abstract Background Little is known about the causes, clinical course and long-term outcome of comatose patients with prolonged hypoglycemic encephalopathy. Methods In a multicenter retrospective study conducted in patients hospitalized from July 1, 2004, to July 1, 2014, we investigated functional long-term prognosis and identified prognosis factors of patients admitted in an intensive care unit (ICU) with prolonged neurological manifestations related to hypoglycemia. Eligible patients were adults admitted to the ICU with a Glasgow Coma Score  3 improved enough to be in the good outcome group 1 year later. Twenty-two (45%) patients underwent therapeutic limitation, mainly related to no expected hope for improvement. On multivariate analysis, only low mRS prior to ICU admission (OR 2.6; 95% CI 1.1–6.3; P = 0.03) and normal brain imaging (OR 7.1; 95% CI 1.1–44; P = 0.03) were significantly predictive of a good outcome. All patients (n = 15) who remained hypoglycemic >480 min had a poor outcome. Conclusion Poor outcome was observed in about 60% of this population of hypoglycemic encephalopathy. However, some patients can recover satisfactorily over time