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Patients treated with direct oral anticoagulants (DOACs) may require urgent procedures. Managing these patients is challenging due to different bleeding risks and may include laboratory testing, procedural delays, or haemostatic/reversal agent administration.We evaluated management strategies and outcomes of urgent, non-haemostatic invasive procedures in patients treated with DOACs.In a descriptive cohort study, we prospectively evaluated 478 patients in the GIHP-NACO registry, from June 2013 to November 2015. Hospitalised patients receiving dabigatran (n = 160), rivaroxaban (n = 274), or apixaban (n = 44) requiring urgent, procedural interventions were evaluated, of which 384/478 (80 %) were surgical procedures. Orthopaedic surgery included 216/384 patients (56 %), while gastrointestinal surgery included 75/384 (20 %) patients. On admission, the median age was 79 (70-85), and creatinine clearance was60 mL·minIn the GIHP-NACO registry, before specific antidotes were available, DOAC treated patients undergoing urgent invasive procedures were delayed in nearly half of the cases, and showed a low rate of excessive bleeding, suggesting that most urgent procedures can be performed safely without DOAC reversal.www.gov. Identifier: NCT02185027.

BackgroundLittle is known on the burden of ICU care for stroke patients. The aim of this study was to provide a description of management strategies, resource use, complications and their association with prognosis of stroke patients admitted to ICU.MethodsUsing a population-based stroke registry, we analyzed consecutive stroke patients admitted to 3 ICU with at least one organ failure between 2008 and 2017. The study period was divided into two periods corresponding to the arrival of mechanical reperfusion technique.Predictors of ICU mortality were separately assessed in two multivariable logistic regression models, a “clinical model” and an “intervention model”. The same analysis was performed for predictors of functional status at hospital discharge.Results215 patients were included. Stroke etiology was ischemia in 109 patients (50.7%) and hemorrhage in 106 patients (49.3%). Median NIHSS score was 20.0 (9.0; 40.0). The most common reason for ICU admission was coma (41.2%) followed by acute circulatory failure (41%) and respiratory failure (27.4%). 112 patients (52%) died in the ICU and 20 patients (11.2%) had a good functional outcome (mRS≤3) at hospital discharge.In the “clinical model,” factors independently associated with ICU mortality were: age (OR = 1.03 [95%CI, 1.0 to 1.06];p=0.04) and intracranial hypertension (OR = 6.89 [95%CI, 3.55 to 13.38];p). In the “intervention model,” the need for invasive mechanical ventilation (OR = 7.39 [95%CI, 1.93 to 28.23];p=0.004), the need for vasopressor therapy (OR = 3.36 [95%CI, 1.5 to 7.53];p=0.003) and decision of withholding life support treatments (OR = 19.24 [95%CI, 7.6 to 48.65];p) were associated with bad outcome.ConclusionOur study showed the very poor prognosis of acute stroke patients admitted to ICU. These results also suggest that the clinical evolution of these patients during ICU hospitalization may provide important information for prognostication.

Background: There is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes. Methods: In this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale ≤ 12 before intubation) who required mechanical ventilation (MV) ≥ 24h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS). Results: We included 1217 patients (mean age 51.2years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9J/min [IQR 9.2-15.1], 13J/min [IQR 10-17], and 14J/min [IQR 11-20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9J/min, aRR at 17J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22). Conclusions: Exposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation.

Background: The lack of a clear definition and strong methodology has led to differing results in terms of unplanned extubation (UE) epidemiology and outcomes. We aimed to determine the UE incidence and clinical significance of both accidental extubation and self-extubation. Methods: A multicentric prospective cohort study was conducted in 47 French ICUs. The number of mechanical ventilation (MV) days, planned and unplanned extubation were recorded in each centre over a minimum period of three consecutive months to evaluate UE incidence. Patient characteristics, UE environmental factors, and outcomes (follow-up until ICU discharge or day 28) were compared based on the UE mechanism (accidental or self-extubation). Finally, we determined ‘failed’ self-extubation (re-intubation at day 7) prognosis and risk factors. Results: During the 12-month inclusion period, we found a pooled UE incidence of 1.0 per 100 MV days. UE accounted for 9% of all endotracheal removals. Of the 635 UE, 88% were self-extubations and 12% were accidental extubations. The latter had a worse prognosis than self-extubations (34% vs 14% mortality, p 2/FiO2, weaning process not ongoing, and immediate post-extubation respiratory failure were independent predictors of failed self-extubation. Discomfort was the leading cause of self-extubation reported by both patients and physicians, ahead of agitation. Conclusion: Unplanned extubation is common in ICU and accounts for 9% of all endotracheal removals. Accidental extubation has a poorer prognosis than self-extubation.

The production and emission of fugitive dust is a topic ofconcern that Concrush brought to the MISG, 2020. Concrushis recycled concrete manufacturing company in the Hunterregion of New South Wales. Concrush's operations producefugitive dust, fine particles that can escape the site. Fugitive dust can travel long distances from the site ofemission, and can have negative health impacts includingrespiratory illnesses. Presently, concrete recyclingfacilities are managed by the Environmental ProtectionAgency using guidelines initially developed for the coalindustry. Concrush seeks to understand the appropriatenessof these guidelines, and how they can reduce and managefugitive dust on their Teralba site. Mathematical modellingof dust emission and transport, together with a review ofsimilar processes in the literature, identified a number ofpractical options for Concrush to reduce their dustemissions. In addition, opportunities for improved datacollection are identified.

Background To evaluate if the increase of chloride intake during a continuous infusion of 20% hypertonic saline solution (HSS) is associated with an increase in the incidence of acute kidney injury (AKI) compared to standard of care in traumatic brain injury patients. Methods In this post-hoc analysis of COBI trial, 370 patients admitted for a moderate-to-severe TBI in the 9 participating ICUs were enrolled. The intervention consisted in a continuous infusion of HSS to maintain a blood sodium level ranging from 150 to 155 mmol/l for at least 48 hours. Patients enrolled in the control arm were treated as recommended by the last Brain Trauma foundation guidelines. The primary outcome was the occurrence of AKI defined by stages 2 or 3 according to KDIGO criteria from inclusion to Day 30. Results After exclusion of missing data, 322 patients were included in this post-hoc analysis. The patients randomized in the intervention arm received a significantly higher amount of chloride during the first 4 days. (intervention group: 97.3 ± 31.6 g vs. control group: 61.3 ± 38.1 g; p

There are currently no data regarding characteristics of critically ill patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant of concern (VOC) 20H/501Y.V2. We therefore aimed to describe changes of characteristics in critically ill patients with Covid-19 between the first and the second wave when viral genome sequencing indicated that VOC was largely dominant in Mayotte Island (Indian Ocean). Consecutive patients with Covid-19 and over 18 years admitted in the unique intensive care unit (ICU) of Mayotte during wave 2 were compared with an historical cohort of patients admitted during wave 1. We performed a LR comparing wave 1 and wave 2 as outcomes. To complete analysis, we built a Random Forest model (RF), that is, a machine learning classification tool- using the same variable set as that of the LR. We included 156 patients, 41 (26.3%) and 115 (73.7%) belonging to the first and second waves respectively. Univariate analysis did not find difference in demographic data or in mortality. Our multivariate LR found that patients in wave 2 had less fever (absence of fever aOR 5.23, 95% confidence interval (CI) 1.89-14.48, p = .001) and a lower simplified acute physiology score (SAPS II) (aOR 0.95, 95% CI 0.91-0.99, p = .007) at admission; at 24 hours, the need of invasive mechanical ventilation was higher (aOR 3.49, 95% CI 0.98-12.51, p = .055) and pO2/FiO2 ratio was lower (aOR 0.99, 95 % CI 0.98-0.99, p = .03). Patients in wave 2 had also an increased risk of ventilator-associated pneumonia (VAP) (aOR 4.64, 95% CI 1.54-13.93, p = .006). Occurrence of VAP was also a key variable to classify patients between wave 1 and wave 2 in the variable importance plot of the RF model. Our data suggested that VOC 20H/501Y.V2 could be associated with a higher severity of respiratory failure at admission and a higher risk for developing VAP. We hypothesized that the expected gain in survival brought by recent improvements in critical care management could have been mitigated by increased transmissibility of the new lineage leading to admission of more severe patients. The immunological role of VOC 20H/501Y.V2 in the propensity for VAP requires further investigations.

Background Rapid-onset paralytic agents are recommended to achieve muscle relaxation and facilitate tracheal intubation during rapid sequence induction in patients at risk of pulmonary aspiration of gastric contents. However, opioids are frequently used in this setting. The study’s objective is to demonstrate the non-inferiority of remifentanil compared to rapid-onset paralytic agents, in association with an hypnotic drug, for tracheal intubation in patients undergoing procedure under general anesthesia and at risk of pulmonary aspiration of gastric contents. Methods The REMICRUSH (Remifentanil for Rapid Sequence Induction of Anaesthesia) study is a multicenter, single-blinded, non-inferiority randomized controlled trial comparing remifentanil (3 to 4 μg/kg) with rapid-onset paralytic agents (succinylcholine or rocuronium 1 mg/kg) for rapid sequence induction in 1150 adult surgical patients requiring tracheal intubation during general anesthesia. Enrolment started in October 2019 in 15 French anesthesia units. The expected date of the final follow-up is October 2021. The primary outcome is the proportion of successful tracheal intubation without major complications. A non-inferiority margin of 7% was chosen. Analyses of the intent-to-treat and per-protocol populations are planned. Discussion The REMICRUSH trial protocol has been approved by the ethics committee of The Comité de Protection des Personnes Sud-Ouest et Outre-Mer II and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentations at scientific conferences and publications in peer-reviewed journals. The REMICRUSH trial is the first randomized controlled trial powered to investigate whether remifentanil with hypnotics is non-inferior to rapid-onset paralytic agents with hypnotic in rapid sequence induction of anesthesia for full stomach patients considering successful tracheal intubation without major complication. Trial registration ClinicalTrials.gov NCT03960801. Registered on May 23, 2019.

Background Hypophosphataemia affects up to one-third of patients in the intensive care unit (ICU) and is particularly common during sepsis. Experimental data suggest that hypophosphataemia leads to an acquired dysfunction of leukocytes, thus promoting infections and increasing the risk of death during sepsis. Objectives The aim of our study was to investigate the association between hypophosphataemia and mortality in critically ill patients with a bloodstream infection (BSI). Methods We performed a retrospective study in three ICUs during an 18-month period. All adults with a BSI diagnosed in the ICU were eligible. Patients with and without hypophosphataemia, defined as phosphataemia below 0.8 mmol/L, were compared. A multivariate survival analysis using a Cox proportional hazard regression model was conducted to study the association between hypophosphataemia and 90-d mortality. Results/Findings Among the 3783 patients admitted to the three participating ICUs within the 18-month study period, 203 met the inclusion criteria and 193 were analysed. Fifty-four patients had hypophosphataemia. After adjusting for confounders, hypophosphataemia was significantly associated with a twofold increased risk of 90-d mortality (hazard ratio = 2.10 [1.177−3.80], p = 0.013). This association is particularly strong in patients without shock. Conclusions Hypophosphataemia was independently associated with a twofold increase in 90-d mortality in ICU patients with a BSI. These results suggest that investigators and physicians should include phosphataemia as a predictor of the severity of BSIs. Further research is warranted to better understand this association and to determine the potential benefits of systematic monitoring of phosphataemia and phosphorus supplementation. Clinical trial registration: NCT03529058.

International audience; Background: It is speculated that the anesthetic strategy during endovascular therapy for stroke may have an impact on the outcome of the patients. The authors hypothesized that conscious sedation is associated with a better functional outcome 3 months after endovascular therapy for the treatment of stroke compared with general anesthesia. Methods: In this single-blind, randomized trial, patients received either a standardized general anesthesia or a standardized conscious sedation. Blood pressure control was also standardized in both groups. The primary outcome measure was a modified Rankin score less than or equal to 2 (0 = no symptoms; 5 = severe disability) assessed 3 months after treatment. The main secondary outcomes were complications, mortality, reperfusion results, and National Institutes of Health Stroke Scores at days 1 and 7. Results: Of 351 randomized patients, 345 were included in the analysis. The primary outcome occurred in 129 of 341 (38%) of the patients: 63 (36%) in the conscious sedation group and 66 (40%) in the general anesthesia group (relative risk, 0.91 [95% CI, 0.69 to 1.19]; P = 0.474). Patients in the general anesthesia group experienced more intraoperative hypo- or hypertensive episodes, while the cumulative duration was not different (mean +/- SD, 36 +/- 31 vs. 39 +/- 25 min; P = 0.079). The time from onset and from arrival to puncture were longer in the general anesthesia group (mean difference, 19 min [i.e., -00:19] [95% CI, -0:38 to 0] and mean difference, 9 min [95% CI, -0:18 to -0:01], respectively), while the time from onset to recanalization was similar in both groups. Recanalization was more often successful in the general anesthesia group (144 of 169 [85%] vs. 131 of 174 [75%]; P = 0.021). The incidence of symptomatic intracranial hemorrhage was similar in both groups. Conclusions: The functional outcomes 3 months after endovascular treatment for stroke were similar with general anesthesia and sedation. Our results, therefore, suggest that clinicians can use either approach.

BackgroundThere are currently no data regarding characteristics of critically ill patients with SARS-CoV-2 Variant of Concern (VOC) 20H/501Y.V2. We therefore aimed to describe changes of characteristics in critically ill patients with Covid-19 between the first and the second wave when viral genome sequencing indicated that VOC was largely dominant in Mayotte Island (Indian Ocean).MethodsConsecutive patients with Covid-19 and over 18 years admitted in the unique Intensive Care Unit (ICU) of Mayotte during wave 2 were compared with an historical cohort of patients admitted during wave 1. We performed a Logistic Regression (LR) comparing wave 1 and wave 2 as outcomes. To complete analysis of changes in characteristics and outcomes, we built a Random Forest model (RF) -i.e., a machine learning classification tool- using the same variable set as that of the LR.ResultsWe included 156 patients, 41 (26.3%) and 115 (73.7%) belonging to the first and second waves respectively. Univariate analysis did not find difference in demographic data or in mortality. Our multivariate LR found that patients in wave 2 had less fever (absence of fever aOR 5.23, 95% CI 1.89 – 14.48, p=0.001) and a lower SAPS II (aOR 0.95, 95% CI 0.91 – 0.99, p=0.007) at admission; at 24 hours, the need of invasive mechanical ventilation was higher (aOR 3.49, 95% CI 0.98 – 12.51, p=0.055) and pO2/FiO2 ratio was lower (aOR 0.99, 95 % CI 0.98-0.99, p=0.03). Patients in wave 2 had also an increased risk of VAP (aOR 4.64, 95% CI 1.54-13.93, p=0.006). Occurrence of VAP was also a key variable to classify patients between wave 1 and wave 2 in the variable importance plot of the RF model.ConclusionOur data suggested that VOC 20H/501Y.V2 could be associated with a higher severity of respiratory failure at admission and a higher risk for developing VAP. We hypothesized that the expected gain in survival brought by recent improvements in critical care management could have been mitigated by increased transmissibility of the new lineage leading to admission of more severe patients. The immunological role of VOC 20H/501Y.V2 in the propensity for VAP requires further investigations.

Laboratory Method to Detect VITT The rare vaccine-induced immune thrombotic thrombocytopenia that may follow adenovirus-based Covid-19 vaccination resembles heparin-induced thrombocytopenia, but ra...

The EPO-TBI multi-national randomized controlled trial found that erythropoietin (EPO), when compared to placebo, did not affect 6-month neurological outcome, but reduced illness severity-adjusted mortality in patients with traumatic brain injury (TBI), making the cost-effectiveness of EPO in TBI uncertain. The current study uses patient-level data from the EPO-TBI trial to evaluate the cost-effectiveness of EPO in patients with moderate or severe TBI from the healthcare payers' perspective. We addressed the issue of transferability in multi-national trials by estimating costs and effects for specific geographical regions of the study (Australia/New Zealand, Europe, and Saudi Arabia). Unadjusted mean quality-adjusted life-years (QALYs; 95% confidence interval [CI]) at 6 months were 0.027 (0.020-0.034; p

Despite a large body of evidence, the implementation of guidelines on hemodynamic optimization and goal-directed therapy remains limited in daily routine practice. To facilitate/accelerate this implementation, a panel of experts in the field proposes an approach based on six relevant questions/answers that are frequently mentioned by clinicians, using a critical appraisal of the literature and a modified Delphi process. The mean arterial pressure is a major determinant of organ perfusion, so that the authors unanimously recommend not to tolerate absolute values below 65 mmHg during surgery to reduce the risk of postoperative organ dysfunction. Despite well-identified limitations, the authors unanimously propose the use of dynamic indices to rationalize fluid therapy in a large number of patients undergoing non-cardiac surgery, pending the implementation of a “validity criteria checklist” before applying volume expansion. The authors recommend with a good agreement mini- or non-invasive stroke volume/cardiac output monitoring in moderate to high-risk surgical patients to optimize fluid therapy on an individual basis and avoid volume overload. The authors propose to use fluids and vasoconstrictors in combination to achieve optimal blood flow and maintain perfusion pressure above the thresholds considered at risk. Although purchase of disposable sensors and stand-alone monitors will result in additional costs, the authors unanimously acknowledge that there are data strongly suggesting this may be counterbalanced by a sustained reduction in postoperative morbidity and hospital lengths of stay. Beside existing guidelines, knowledge and explicit clinical reasoning tools followed by decision algorithms are mandatory to implement individualized hemodynamic optimization strategies and reduce postoperative morbidity and duration of hospital stay in high-risk surgical patients.

Fluid administration is one of the first lines of treatment for hemodynamic management of sepsis and septic shock. Studies investigating the effects of chloride-rich fluids including normal saline on renal function report controversial findings.This is a prospective, observational, multicenter study. Patients with septic shock, defined according to Sepsis-2 definition, were eligible. A "high-dose" of chloride was defined as a chloride intake greater than 18 g administrated within the first 48 h of septic shock management. The purpose of this study was to investigate the impact of cumulative chloride infusion within the first 48 h of septic shock resuscitation on acute kidney injury (AKI).Two hundred thirty-nine patients with septic shock were included. Patients who received a "high-dose" of chloride had significantly higher Sequential Organ Failure Assessment score at the time of enrolment (P 0.001). Cumulative chloride load was higher in patients requiring renal replacement therapy (RRT) (31.1 vs. 25.2 g/48 h; P 0.005). Propensity score-weighted regression did not find any association between "high-dose" of chloride and AKI requiring RRT (OR: 0.97 [0.88-1.1]; P = 0.69). There was no association between "high-dose" of chloride and worsening kidney function at H48 (OR: 0.94 [0.83-1.1]; P = 0.42). There was also no association between "high-dose" of chloride and ICU length of stay (P = 0.61), 28-day mortality (P = 0.83), or hospital mortality (P = 0.89).At the early stage of resuscitation of critically ill patients with septic shock, administration of "high-dose" of chloride (18 g/48 h) was not associated with renal prognosis.

The aetiology and progression of hypertension involves various endogenous systems, such as the renin angiotensin system, the sympathetic nervous system, and endothelial dysfunction. Recent data suggest that vascular inflammation may also play a key role in the pathogenesis of hypertension. This study sought to determine whether high intraluminal pressure results in vascular inflammation. Leukocyte adhesion was assessed in rat carotid arteries exposed to 1 h of high intraluminal pressure. The effect of intraluminal pressure on signaling mechanisms including reactive oxygen species production (ROS), arginase expression, and NFĸB translocation was monitored. 1 h exposure to high intraluminal pressure (120 mmHg) resulted in increased leukocyte adhesion and inflammatory gene expression in rat carotid arteries. High intraluminal pressure also resulted in a downstream signaling cascade of ROS production, arginase expression, and NFĸB translocation. This process was found to be angiotensin II-independent and mediated by the mechanosensor caveolae, as caveolin-1 (Cav1)-deficient endothelial cells and mice were protected from pressure-induced vascular inflammatory signaling and leukocyte adhesion. Cav1 deficiency also resulted in a reduction in pressure-induced glomerular macrophage infiltration in vivo. These findings demonstrate Cav1 is an important mechanosensor in pressure-induced vascular and renal inflammation.

International audience; BACKGROUND: The present study aims at identifying the risk factors for ventilator-associated pneumonia (VAP) Staphylococcus aureus (S. aureus) in patients with severe brain injury (SBI). METHODS: In this multicentre, retrospective, observational study, patients ≥ 18 year old who had SBI (Glasgow coma scale GCS score < 9) who received mechanical ventilation for at least 48 h were analysed. The main objective was to identify risk factors for S. aureus VAP vs VAP due to other pathogens and to identify risk factors for S. aureus VAP vs patients who did not experience VAP. RESULTS: 847 patients with SBI were admitted in ICU after severe traumatic brain injury (n = 489, 58%), aneurysmal SAH (n = 156, 18%), stroke (n = 27, 3%), spontaneous intracranial haemorrhage (n = 80, 9%), arteriovenous malformation rupture (n = 25, 3%), and other causes (n = 70, 8%). Three hundred fifty of 847 patients (41%) had VAP with S. aureus (n = 161) or other pathogens (n = 189). In patients with VAP, the multivariate analysis shows that age per 10 years of ageing (OR 0.80, 95%CI [0.70; 0.90]; p < 0.001) and no tobacco use (OR 0.54, 95%CI [0.33;0.88]; p = 0.014) were protective factors against S. aureus. Age per 10 years of ageing remained a protective factor against S. aureus VAP vs no VAP (OR 0.80, 95%CI [0.73; 0.89], p < 0.001). CONCLUSIONS: In this retrospective study involving patients with SBI and who experienced VAP, increased age and no tobacco use were protective factors against VAP due to S. aureus. Increased age remained protective against S. aureus in VAP vs no VAP analysis.

Contains fulltext : 245661.pdf (Publisher’s version ) (Closed access) IMPORTANCE: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson). OBJECTIVE: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination. EXPOSURES: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria. MAIN OUTCOMES AND MEASURES: Clinical characteristics and mortality rate. RESULTS: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later. CONCLUSIONS AND RELEVANCE: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination.

IntroductionThe use of sedation in intensive care units (ICUs) is necessary and ubiquitous. The impact of sedation strategy on outcome, particularly when delivered early after initiation of mechanical ventilation, is unknown. Evidence is increasing that volatile anaesthetic agents could be associated with better outcome. Their use in delirium prevention is unknown.Methods and analysisThis study is an investigator-initiated, prospective, multicentre, two-arm, randomised, control, open-trial comparing inhaled sedation strategy versus intravenous sedation strategy in mechanically ventilated patients in ICU. Two hundred and fifty patients will be randomly assigned to the intravenous sedation group or inhaled sedation group, with a 1:1 ratio in two groups according to the sedation strategy. The primary outcome is the occurrence of delirium assessed using two times a day confusion assessment method for the ICU (CAM-ICU). Secondary outcomes include cognitive and functional outcomes at 3 and 12 months.Ethics and disseminationThe study has been approved by the Regional Ethics Committee (CPP Ouest) and national authorities (ANSM). The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT04341350

Despite numerous studies, controversies about the best intraoperative FiO2 remain. In 2016, the World Health Organization (WHO) recommended that adult patients undergoing general anaesthesia should be ventilated intraoperatively with an 80% FiO2 to reduce surgical site infection (SSI). However, several data suggest that hyperoxia could have adverse effects. In order to determine the potential effect of FiO2 on SSI, we included in this systematic review 23 studies (among which 21 randomised controlled trials [RCT]) published between 1999 and 2020, comparing intraoperative high versus low FiO2. Results were heterogeneous but most recent studies on one hand, and the largest RCTs on the other hand, reported no difference on the incidence of SSI regarding intraoperative FiO2 during general anaesthesia. There was also no difference in the incidence of SSI depending of intraoperative FiO2 in patients receiving regional anaesthesia. The review on secondary endpoints (respiratory and cardiovascular adverse events, postoperative nausea and vomiting, postoperative length-of-stay and mortality) also failed to support the use of high FiO2. On the opposite, some data from follow-up analyses and registry studies suggested a possible negative effect of high intraoperative FiO2 on long-term outcomes. In conclusion, the systematic administration of a high intraoperative FiO2 in order to decrease SSI or improve other perioperative outcomes seems unjustified in the light of the evidence currently available in the literature.

BACKGROUND AND OBJECTIVES Equipoise remains on the optimal transfusion strategy in surgical oncologic patients. The primary objective of our study was to determine the impact of anaemia and red blood cells (RBCs) transfusion on severe postoperative complications in surgical oncologic critically ill patients. MATERIALS AND METHODS Retrospective single-centre study. Adults admitted to intensive care unit after major oncologic surgery were eligible. Analyses to determine the independent risk factors, including anaemia or RBC transfusion, for postoperative complications and/or hospital mortality were performed. RESULTS Of the 283 patients included, 246 patients (86.9%) had anaemia. Fifty-five patients (19·4%) were transfused. Patients exposed to moderate-to-severe anaemia or RBC transfusion had more often severe complications, especially acute kidney injury and infectious complications. Multivariate analysis found an independent association between moderate and severe anaemia and severe postoperative complications (moderate anaemia: OR 14·02 [2·52-264]; severe anaemia: OR 16·25 [2·62-318·5]; P

IntroductionIncidence of delirium after cardiac surgery remains high and delirium has a significant burden on short-term and long-term outcomes. Multiple causes can trigger delirium occurence, and it has been hypothesised that sleep disturbances can be one of them. Preserving the circadian rhythm with overnight infusion of low-dose dexmedetomidine has been shown to lower the occurrence of delirium in older patients after non-cardiac surgery. However, these results remain controversial. The aim of this study was to demonstrate the usefulness of sleep induction by overnight infusion of dexmedetomidine to prevent delirium after cardiac surgery.Methods and analysisDexmedetomidine after Cardiac Surgery for Prevention of Delirium is an investigator-initiated, randomised, placebo-controlled, parallel, multicentre, double-blinded trial. Nine centres in France will participate in the study. Patients aged 65 years or older and undergoing cardiac surgery will be enrolled in the study. The intervention starts on day 0 (the day of surgery) until intensive care unit (ICU) discharge; the treatment is administered from 20:00 to 08:00 on the next day. Infusion rate is modified by the treating nurse or the clinician with an objective of Richmond Agitation and Sedation Scale score from −1 to +1. The primary outcome is delirium occurrence evaluated with confusion assessment method for the ICU two times per day during 7 days following surgery. Secondary outcomes include incidence of agitation related events, self-evaluated quality of sleep, cognitive evaluation 3 months after surgery and quality of life 3 months after surgery. The sample size is 348.Ethics and disseminationThe study was approved for all participating centers by the French Central Ethics Committee (Comité de Protection des Personnes Ile de France VI, registration number 2018-000850-22). The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT03477344.

IntroductionExpanded-criteria donors (ECDs) are used to reduce the shortage of kidneys for transplantation. However, kidneys from ECDs are associated with an increased risk of delayed graft function (DGF), a risk factor for allograft loss and mortality. HYPOREME will be a multicentre randomised controlled trial (RCT) comparing targeted hypothermia to normothermia in ECDs, in a country where the use of machine perfusion for organ storage is the standard of care. We hypothesise that hypothermia will decrease the incidence of DGF.Methods and analysisHYPOREME is a multicentre RCT comparing the effect on kidney function in recipients of targeted hypothermia (34°C–35°C) and normothermia (36.5°C–37.5°C) in the ECDs. The temperature intervention starts from randomisation and is maintained until aortic clamping in the operating room. We aim to enrol 289 ECDs in order to analyse the kidney function of 516 recipients in the 53 participating centres. The primary outcome is the occurrence of DGF in kidney recipients, defined as a requirement for renal replacement therapy within 7 days after transplantation (not counting a single session for hyperkalemia during the first 24 hours). Secondary outcomes include the proportion of patients with individual organs transplanted in each group; the number of organs transplanted from each ECD and the vital status and kidney function of the recipients 7 days, 28 days, 3 months and 1 year after transplantation. An interim analysis is planned after the enrolment of 258 kidney recipients.Ethics and disseminationThe trial was approved by the ethics committee of the French Intensive Care Society (CE-SRLF-16-07) on 26 April 2016 and by the competent French authorities on 20 April 2016 (Comité de Protection des Personnes-TOURS-Région Centre-Ouest 1, registration #2016-S3). Findings will be published in peer-reviewed journals and presented during national and international scientific meetings.Trial registration numberNCT03098706.

Bowel dysfunction, especially ileus, has been increasingly recognized in critically ill patients. Ileus is commonly associated to constipation, however abnormal motility can also concern the upper digestive tract, therefore impaired gastrointestinal transit (IGT) seems to be a more appropriate term. IGT, especially constipation, is common among patients under mechanical ventilation, occurring in up to 80% of the patients during the first week, and has been associated with worse outcome in intensive care unit (ICU). It is acknowledged that the most relevant definition for constipation in ICU is the absence of stool for the first six days after admission. Concerning the upper digestive intolerance (UDI), the diagnosis should rely only on vomiting and the systematic gastric residual volume (GRV) monitoring should be avoided. IGT results from a complex pathophysiology in which both the critical illness and its specific treatments may have a deleterious role. Both observational and experimental studies have shown the deleterious effect of sepsis, multiorgan failure, sedation (especially opioids) and mechanical ventilation on gut function. To date few studies have reported effect of treatment on IGT and the level of evidence is low. However, cholinesterase inhibitors seem safe and could probably be used in case of constipation but remains poorly prescribed. Prevention with bowel management protocol using osmotic laxatives appears to be safe but did not demonstrate its effectiveness. For patients treated with high posology of opioids during sedation, enteral opioid antagonists may be a promising strategy.

Objective: Anemia is very common in critical care patients, on admission (affecting about two-thirds of patients), but also during and after their stay, due to repeated blood loss, the effects of inflammation on erythropoiesis, a decreased red blood cell life span, and haemodilution. Anemia is associated with severity of illness and length of stay. Methods: A committee composed of 16 experts from four scientific societies, SFAR, SRLF, SFTS and SFVTT, evaluated three fields: (1) anemia prevention, (2) transfusion strategies and (3) non-transfusion treatment of anemia. Population, Intervention, Comparison, and Outcome (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Analysis of the literature and formulation of recommendations were then conducted according to the GRADE® methodology. Results: The SFAR–SRLF guideline panel provided ten statements concerning the management of anemia in adult critical care patients. Acute haemorrhage and chronic anemia were excluded from the scope of these recommendations. After two rounds of discussion and various amendments, a strong consensus was reached for ten recommendations. Three of these recommendations had a high level of evidence (GRADE 1±) and four had a low level of evidence (GRADE 2±). No GRADE recommendation could be provided for two questions in the absence of strong consensus. Conclusions: The experts reached a substantial consensus for several strong recommendations for optimal patient management. The experts recommended phlebotomy reduction strategies, restrictive red blood cell transfusion and a single-unit transfusion policy, the use of red blood cells regardless of storage time, treatment of anaemic patients with erythropoietin, especially after trauma, in the absence of contraindications and avoidance of iron therapy (except in the context of erythropoietin therapy)., SCOPUS: re.j, info:eu-repo/semantics/published

Despite numerous studies, controversies about the best intraoperative FiO

Importance Fluid therapy is an important component of care for patients with traumatic brain injury, but whether it modulates clinical outcomes remains unclear. Objective To determine whether continuous infusion of hypertonic saline solution improves neurological outcome at 6 months in patients with traumatic brain injury. Design, Setting, and Participants Multicenter randomized clinical trial conducted in 9 intensive care units in France, including 370 patients with moderate to severe traumatic brain injury who were recruited from October 2017 to August 2019. Follow-up was completed in February 2020. Interventions Adult patients with moderate to severe traumatic brain injury were randomly assigned to receive continuous infusion of 20% hypertonic saline solution plus standard care (n = 185) or standard care alone (controls; n = 185). The 20% hypertonic saline solution was administered for 48 hours or longer if patients remained at risk of intracranial hypertension. Main Outcomes and Measures The primary outcome was Extended Glasgow Outcome Scale (GOS-E) score (range, 1-8, with lower scores indicating worse functional outcome) at 6 months, obtained centrally by blinded assessors and analyzed with ordinal logistic regression adjusted for prespecified prognostic factors (with a common odds ratio [OR] >1.0 favoring intervention). There were 12 secondary outcomes measured at multiple time points, including development of intracranial hypertension and 6-month mortality. Results Among 370 patients who were randomized (median age, 44 [interquartile range, 27-59] years; 77 [20.2%] women), 359 (97%) completed the trial. The adjusted common OR for the GOS-E score at 6 months was 1.02 (95% CI, 0.71-1.47;P = .92). Of the 12 secondary outcomes, 10 were not significantly different. Intracranial hypertension developed in 62 (33.7%) patients in the intervention group and 66 (36.3%) patients in the control group (absolute difference, −2.6% [95% CI, −12.3% to 7.2%]; OR, 0.80 [95% CI, 0.51-1.26]). There was no significant difference in 6-month mortality (29 [15.9%] in the intervention group vs 37 [20.8%] in the control group; absolute difference, −4.9% [95% CI, −12.8% to 3.1%]; hazard ratio, 0.79 [95% CI, 0.48-1.28]). Conclusions and Relevance Among patients with moderate to severe traumatic brain injury, treatment with continuous infusion of 20% hypertonic saline compared with standard care did not result in a significantly better neurological status at 6 months. However, confidence intervals for the findings were wide, and the study may have had limited power to detect a clinically important difference. Trial Registration ClinicalTrials.gov Identifier:NCT03143751