Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO) is an efficient ventilatory support in patients with refractory Covid-19-related Acute Respiratory Distress Syndrome (ARDS), however the ...duration of invasive mechanical ventilation (IMV) before ECMO initiation as a contraindication is still controversial. The aim of this study was to investigate the impact of prolonged IMV prior to VV-ECMO in patients suffering from refractory Covid-19-related ARDS.
This single-center retrospective study included all patients treated with VV-ECMO for refractory Covid-19-related ARDS between January 1, 2020 and May 31, 2022. The impact of IMV duration was investigated by comparing patients on VV-ECMO during the 7 days (and 10 days) following IMV with those assisted after 7 days (and 10 days). The primary endpoint was in-hospital mortality.
Sixty-four patients were hospitalized in the ICU for Covid-19-related refractory ARDS requiring VV-ECMO. Global in-hospital mortality was 55 %. Median duration of IMV was 4 2; 8 days before VV-ECMO initiation. There was no significant difference in in-hospital mortality between patients assisted with IMV pre-VV-ECMO for a duration of ≤7 days (≤10 days) and those assisted after 7 days (and 10 days) ((p = 0.59 and p = 0.45).
This study suggests that patients assisted with VV-ECMO after prolonged IMV had the same prognosis than those assisted earlier in refractory Covid-19-related ARDS. Therefore, prolonged mechanical ventilation of more than 7–10 days should not contraindicate VV-ECMO support. An individual approach is necessary to balance the risks and benefits of ECMO in this population.
•VV-ECMO is an efficient ventilatory support in patient with refractory ARDS.•Duration of invasive mechanical ventilation (IMV) before ECMO as contraindication is controversial in Covid-19-related ARDS.•Patients assisted after 7 or 10 days of (IMV) had the same prognosis as those assisted earlier.
The Artificial Kidney Initiation in Kidney Injury (AKIKI) trial showed that a delayed renal replacement therapy (RRT) strategy for severe acute kidney injury (AKI) in critically ill patients was safe ...and associated with major reduction in RRT initiation compared with an early strategy. The five criteria which mandated RRT initiation in the delayed arm were: severe hyperkalemia, severe acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia, serum urea concentration > 40 mmol/l and oliguria/anuria > 72 h. However, duration of anuria/oliguria and level of blood urea are still criteria open to debate. The objective of the study is to compare the delayed strategy used in AKIKI (now termed "standard") with another in which RRT is further delayed for a longer period (termed "delayed strategy").
This is a prospective, multicenter, open-label, two-arm randomized trial. The study is composed of two stages (observational and randomization stages). At any time, the occurrence of a potentially severe condition (severe hyperkalemia, severe metabolic or mixed acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia) suggests immediate RRT initiation. Patients receiving (or who have received) intravenously administered catecholamines and/or invasive mechanical ventilation and presenting with AKI stage 3 of the KDIGO classification and with no potentially severe condition are included in the observational stage. Patients presenting a serum urea concentration > 40 mmol/l and/or an oliguria/anuria for more than 72 h are randomly allocated to a standard (RRT is initiated within 12 h) or a delayed RRT strategy (RRT is initiated only if an above-mentioned potentially severe condition occurs or if the serum urea concentration reaches 50 mmol/l). The primary outcome will be the number of RRT-free days at day 28. One interim analysis is planned. It is expected to include 810 patients in the observational stage and to randomize 270 subjects.
The AKIKI2 study should improve the knowledge of RRT initiation criteria in critically ill patients. The potential reduction in RRT use allowed by a delayed RRT strategy might be associated with less invasive care and decreased costs. Enrollment is ongoing. Inclusions are expected to be completed by November 2019.
ClinicalTrials.gov, ID: NCT03396757. Registered on 11 January 2018.
Delaying renal replacement therapy (RRT) for some time in critically ill patients with severe acute kidney injury and no severe complication is safe and allows optimisation of the use of medical ...devices. Major uncertainty remains concerning the duration for which RRT can be postponed without risk. Our aim was to test the hypothesis that a more-delayed initiation strategy would result in more RRT-free days, compared with a delayed strategy.
This was an unmasked, multicentre, prospective, open-label, randomised, controlled trial done in 39 intensive care units in France. We monitored critically ill patients with severe acute kidney injury (defined as Kidney Disease: Improving Global Outcomes stage 3) until they had oliguria for more than 72 h or a blood urea nitrogen concentration higher than 112 mg/dL. Patients were then randomly assigned (1:1) to either a strategy (delayed strategy) in which RRT was started just after randomisation or to a more-delayed strategy. With the more-delayed strategy, RRT initiation was postponed until mandatory indication (noticeable hyperkalaemia or metabolic acidosis or pulmonary oedema) or until blood urea nitrogen concentration reached 140 mg/dL. The primary outcome was the number of days alive and free of RRT between randomisation and day 28 and was done in the intention-to-treat population. The study is registered with ClinicalTrial.gov, NCT03396757 and is completed.
Between May 7, 2018, and Oct 11, 2019, of 5336 patients assessed, 278 patients underwent randomisation; 137 were assigned to the delayed strategy and 141 to the more-delayed strategy. The number of complications potentially related to acute kidney injury or to RRT were similar between groups. The median number of RRT-free days was 12 days (IQR 0–25) in the delayed strategy and 10 days (IQR 0–24) in the more-delayed strategy (p=0·93). In a multivariable analysis, the hazard ratio for death at 60 days was 1·65 (95% CI 1·09–2·50, p=0·018) with the more-delayed versus the delayed strategy. The number of complications potentially related to acute kidney injury or renal replacement therapy did not differ between groups.
In severe acute kidney injury patients with oliguria for more than 72 h or blood urea nitrogen concentration higher than 112 mg/dL and no severe complication that would mandate immediate RRT, longer postponing of RRT initiation did not confer additional benefit and was associated with potential harm.
Programme Hospitalier de Recherche Clinique.
Targeted temperature management (TTM) between 32 and 36°C is recommended after out-of-hospital cardiac arrest (OHCA). We aimed to assess the feasibility and safety of the “Esophageal Cooling Device” ...(ECD) in performing TTM.
This single-centre, prospective, interventional study included 17 comatose OHCA patients. Main exclusion criteria were: delay between OHCA and return of spontaneous circulation (ROSC)>60min, delay between sustained ROSC and inclusion >360min, known oesophageal disease. A TTM between 32 and 34°C was performed using the ECD (Advanced Cooling Therapy, USA) connected to a heat exchanger console (Meditherm III®, Gaymar, France), without cold fluids’ use. Primary endpoint was feasibility of inducing, maintaining TTM, and rewarming using the ECD alone. Secondary endpoints were adverse events, focusing on potential digestive damages. Results were expressed as median (interquartiles 25–75).
Cooling rate to reach the Target Temperature (33°C-TT) was 0.26°C/h 0.19-0.36. All patients reached the 32–34°C range with a time spent within the range of 26h 21–28 (3 patients did not reach 33°C). Temperature deviation outside the TT during TTM-maintenance was 0.10°C 0.03–0.20. Time with deviation >1°C was 0h. Rewarming rate was 0.20°C/h 0.18–0.22. Among the 16 gastrointestinal endoscopy procedures performed, 10 (62.5%) were normal. Minor oeso-gastric injuries (37.5% and 19%, respectively) were similar to usual orogastric tube injuries. One patient experienced severe oesophagitis mimicking peptic lesions, not cooling-related. No patient among the 9 alive at 3-month follow-up had gastrointestinal complains.
ECD seems an interesting, safe, accurate, semi-invasive cooling method in OHCA patients treated with 33°C-TTM, particularly during the maintenance phase.
Purpose
Cardiac arrest may occur unexpectedly in intensive care units (ICU). We hypothesize that certain patient characteristics and treatments are associated with survival and long-term functional ...outcome following in-ICU cardiac arrest.
Methods
Over a 12-month period, cardiac arrests with resuscitation attempts were prospectively investigated in 45 French ICUs. Survivors were followed for 6 months.
Results
In total, 677 (2.16%) of 31,399 admitted patients had at least one in-ICU cardiac arrest with resuscitation attempt, 42% of which occurred on the day of admission. In 79% cases, one or more condition(s) likely to promote the occurrence of cardiac arrest was/were identified, including hypoxia (179 patients), metabolic disorders (122), hypovolemia (94), and adverse events linked to the life-sustaining devices in place (98). Return of spontaneous circulation was achieved in 478 patients, of whom 163 were discharged alive from ICU and 146 from hospital. Six-month survival with no or moderate functional sequel (118 of 125 patients alive) correlated with a number of organ failures ≤ 2 when cardiac arrest occurred (OR 4.17 1.92–9.09), resuscitation time ≤ 5 min (3.32 2.01–5.47), shockable rhythm cardiac arrests (2.13 1.26–3.45) or related to the life-sustaining devices in place (2.11 1.22–3.65), absence of preexisting disability (1.98 1.09–3.60) or disease deemed fatal within 5 years (1.70 1.05–2.77), and sedation (1.71 1.06–2.75).
Conclusion
Only one in six patients with in-ICU cardiac arrest and resuscitation attempt was alive at 6 months with good functional status. Certain characteristics specific to cardiac arrests, resuscitation maneuvers, and the pathological context in which they happen may help clarify prognosis and inform relatives.
Purpose
The effect of renal replacement therapy (RRT) in comatose patients with acute kidney injury (AKI) remains unclear. We compared two RRT initiation strategies on the probability of awakening in ...comatose patients with severe AKI.
Methods
We conducted a post hoc analysis of a trial comparing two delayed RRT initiation strategies in patients with severe AKI. Patients were monitored until they had oliguria for more than 72 h and/or blood urea nitrogen higher than 112 mg/dL and then randomized to a delayed strategy (RRT initiated after randomization) or a more-delayed one (RRT initiated if complication occurred or when blood urea nitrogen exceeded 140 mg/dL). We included only comatose patients (Richmond Agitation-Sedation scale RASS < − 3), irrespective of sedation, at randomization. A multi-state model was built, defining five mutually exclusive states: death, coma (RASS < − 3), incomplete awakening (RASS − 3; − 2), awakening (RASS − 1; + 1 two consecutive days), and agitation (RASS > + 1). Primary outcome was the transition from coma to awakening during 28 days after randomization.
Results
A total of 168 comatose patients (90 delayed and 78 more-delayed) underwent randomization. The transition intensity from coma to awakening was lower in the more-delayed group (hazard ratio HR = 0.36 0.17–0.78;
p
= 0.010). Time spent awake was 10.11 days 8.11–12.15 and 7.63 days 5.57–9.64 in the delayed and the more-delayed groups, respectively. Two sensitivity analyses were performed based on sedation status and sedation practices across centers, yielding comparable results.
Conclusion
In comatose patients with severe AKI, a more-delayed RRT initiation strategy resulted in a lower chance of transitioning from coma to awakening.
BACKGROUND: Delaying renal replacement therapy (RRT) for some time in critically ill patients with severe acute kidney injury and no severe complication is safe and allows optimisation of the use of ...medical devices. Major uncertainty remains concerning the duration for which RRT can be postponed without risk. Our aim was to test the hypothesis that a more-delayed initiation strategy would result in more RRT-free days, compared with a delayed strategy. METHODS: This was an unmasked, multicentre, prospective, open-label, randomised, controlled trial done in 39 intensive care units in France. We monitored critically ill patients with severe acute kidney injury (defined as Kidney Disease: Improving Global Outcomes stage 3) until they had oliguria for more than 72 h or a blood urea nitrogen concentration higher than 112 mg/dL. Patients were then randomly assigned (1:1) to either a strategy (delayed strategy) in which RRT was started just after randomisation or to a more-delayed strategy. With the more-delayed strategy, RRT initiation was postponed until mandatory indication (noticeable hyperkalaemia or metabolic acidosis or pulmonary oedema) or until blood urea nitrogen concentration reached 140 mg/dL. The primary outcome was the number of days alive and free of RRT between randomisation and day 28 and was done in the intention-to-treat population. The study is registered with ClinicalTrial.gov, NCT03396757 and is completed. FINDINGS: Between May 7, 2018, and Oct 11, 2019, of 5336 patients assessed, 278 patients underwent randomisation; 137 were assigned to the delayed strategy and 141 to the more-delayed strategy. The number of complications potentially related to acute kidney injury or to RRT were similar between groups. The median number of RRT-free days was 12 days (IQR 0-25) in the delayed strategy and 10 days (IQR 0-24) in the more-delayed strategy (p=0·93). In a multivariable analysis, the hazard ratio for death at 60 days was 1·65 (95% CI 1·09-2·50, p=0·018) with the more-delayed versus the delayed strategy. The number of complications potentially related to acute kidney injury or renal replacement therapy did not differ between groups. INTERPRETATION: In severe acute kidney injury patients with oliguria for more than 72 h or blood urea nitrogen concentration higher than 112 mg/dL and no severe complication that would mandate immediate RRT, longer postponing of RRT initiation did not confer additional benefit and was associated with potential harm. FUNDING: Programme Hospitalier de Recherche Clinique.
Understanding the mechanisms of coronavirus disease 2019 (COVID-19) disease severity to efficiently design therapies for emerging virus variants remains an urgent challenge of the ongoing pandemic. ...Infection and immune reactions are mediated by direct contacts between viral molecules and the host proteome, and the vast majority of these virus-host contacts (the 'contactome') have not been identified. Here, we present a systematic contactome map of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with the human host encompassing more than 200 binary virus-host and intraviral protein-protein interactions. We find that host proteins genetically associated with comorbidities of severe illness and long COVID are enriched in SARS-CoV-2 targeted network communities. Evaluating contactome-derived hypotheses, we demonstrate that viral NSP14 activates nuclear factor κB (NF-κB)-dependent transcription, even in the presence of cytokine signaling. Moreover, for several tested host proteins, genetic knock-down substantially reduces viral replication. Additionally, we show for USP25 that this effect is phenocopied by the small-molecule inhibitor AZ1. Our results connect viral proteins to human genetic architecture for COVID-19 severity and offer potential therapeutic targets.
Vehicles makers are now extremely concerned by the perceived quality of their products. For the design of many parts of vehicles, sensory profiling techniques are used, which are traditionally ...carried out by experts. These tests incur a significant financial effort and are time consuming. We propose in this paper an evaluation method with naive subjects, based on paired comparisons. Two studies have been carried out on diesel motor sounds: firstly, the panel of experts of a car maker made a conventional sensory profile and an evaluation by paired comparison. Secondly, 30 naive subjects also completed two tests (ratings and paired comparisons). For the experts, we noticed a very good agreement between the sensory profile and the paired comparisons. For the naives, the paired comparisons gave a better agreement between the subjects and were more discriminating than the ratings. The results of these two tests with the naives were then compared with the conventional sensory profile of the experts using Generalized Procrustes Analysis. Results show that the consensus is better with the paired comparison test. As a result, the evaluation method proposed with naives could be an interesting method for the perceptual evaluation of products.
To stay competitive, a company must take into account customer’s perception and react quickly to other competitors. Industry needs efficient techniques for evaluating the perceived quality of industrial products, and to integrate this data into the design process. Using naive subjects in perceptual tests can save the industry significant costs and time reaching customer need.
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