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Introduction: Experimental studies in animals have yielded conflicting results on the role of Tumor Necrosis Factor (TNF) in sepsis and endotoxemia, with some reporting adaptive and others inappropriate effects. A meta-analysis of the available literature was performed to determine the factors explaining this discrepancy., Methods: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The protocol was registered with PROSPERO (CRD42020167384) prior to data collection. PubMed and Embase were the databases queried. Risk of bias was evaluated using the SYRCLE Risk of Bias Tool. All animal studies investigating sepsis-related mortality and modified TNF signaling were considered eligible. The exclusion criteria were: lack of mortality data, 7-day mortality rates below 10% in both wild type and TNF-altered pathway animals, and absence of an English abstract. To determine the role of TNF according to the experimental protocol, three approaches were used: first an approach based on the statistical significance of each experiment, then the pooled mortality was calculated, and finally the weighted risk ratio for mortality was assessed., Results: A total of 175 studies were included in the analysis, comprising a total of 760 experiments and involving 19,899 animals. The main species used were mice (77%) and rats (21%). The most common method of TNF pathway modulation was TNF pathway inactivation that was primarily associated with an inappropriate secretion of TNF. At the opposite, TNF injection was associated with an adaptive role of TNF. Lipopolysaccharide (LPS) injection was the most used stimulus to establish an infectious model (42%) and was strongly associated with an inappropriate role of TNF. Conversely, live bacterial models, especially the cecal ligation and puncture (CLP) model, pneumonia, meningitis, and gastrointestinal infection, were associated with an adaptive role. This was particularly evident for Listeria monocytogenes, Streptococcus pneumoniae., Conclusion: The role of TNF during infection varies depending on the experimental model used. Models that mimic clinical conditions, based on virulent bacteria that cause high mortality even at low inocula, demonstrated an adaptive role of TNF. Conversely, models based on LPS or low-pathogenic live bacteria, administered at doses well above physiological thresholds and combined with early antibiotic therapy, were associated with an inappropriate role., (© 2024. The Author(s).)

Background: Preoperative identification of patients with hemostasis abnormalities leading to an increased bleeding risk is based on routine hemostasis tests: prothrombin time (PT), activated partial thromboplastin time (APTT), and platelet count. Because of their low predictive performance, guidelines recommend replacing them with structured bleeding risk questionnaires, but none is validated in this population., Objectives: To assess the diagnostic accuracy of 3 strategies, performed at the preanesthesia visit before scheduled interventions, and to identify patients with hemostasis abnormalities leading to an increased bleeding risk METHODS: A multicenter study was performed in 7 French academic hospitals, involving patients scheduled for surgical intervention, without antiplatelet/anticoagulant treatment. The 3 strategies consisted of 1-a structured screening questionnaire; 2-PT, APTT, and platelet count ordered in selected patients; and 3-systematic PT, APTT, and platelet count. The reference standard comprised von Willebrand factor activity/antigen, factor (F)VIII, FIX, FXI, platelet function analyzer, and, when required, FII, FV, FX, and FVII and hemostasis consultation., Results: Eighteen (1.2%) of 1484 patients had a hemostasis abnormality leading to an increased bleeding risk according to reference standard. In the overall cohort, sensitivity of the questionnaire-based strategy was 50% (95% CI, 26%-74%; specificity, 87% [95% CI, 85%-88%]); sensitivity was 0% (95% CI, 0%-41%) in men vs 82% (95% CI, 48%-98%) in women. For selective routine tests, sensitivity was 33% (95% CI, 13%-59%) and specificity 97% (95% CI, 96%-98%). Corresponding values for systematic routine tests were 44% (95% CI, 22%-69%) and 93% (95% CI, 91%-94%)., Conclusion: Sensitivity was low for all 3 strategies investigated. The structured screening questionnaire had clinically acceptable diagnostic accuracy only in women., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Rationale: For veno-arterial extracorporeal membrane oxygenation (ECMO), the femoral artery is the preferred cannulation site (femoro-femoral: Vf-Af). This results in retrograde aortic flow, which increases the left ventricular afterload and can lead to severe pulmonary edema and thrombosis of the cardiac chambers. Right axillary artery cannulation (femoral-axillary: Vf-Aa) provides partial anterograde aortic flow, which may prevent some complications. This study aimed to compare the 90-day mortality and complication rates between VF-AA and VF-AF., Methods: Consecutive adult patients with cardiogenic shock who received peripheral VA-ECMO between 2013 and 2019 at our institution were retrospectively included. The exclusion criteria were refractory cardiac arrest, multiple VA-ECMO implantations due to vascular access changes, weaning failure, or ICU readmission. A statistical approach using inverse probability of treatment weighting was used to estimate the effect of the cannulation site on the outcomes. The primary endpoint was the 90-day mortality. The secondary endpoints were vascular access complications, stroke, and other complications related to retrograde blood flow. Outcomes were estimated using logistic regression analysis., Results: VA-ECMO was performed on 534 patients. Patients with refractory cardiac arrest ( n = 77 (14%)) and those supported by multiple VA-ECMO ( n = 92, (17%)) were excluded. Out of the 333 patients studied ( n = 209 Vf-Aa; n = 124 VF-AF), the main indications for VA-ECMO implantation were post-cardiotomy (33%, n = 109), dilated cardiomyopathy (20%, n = 66), post-cardiac transplantation (15%, n = 50), acute myocardial infarction (14%, n = 46) and other etiologies (18%, n = 62). The median SOFA score was 9 [7-11], and the crude 90-day mortality rate was 53% ( n = 175). After IPTW, the 90-day mortality was similar in the Vf-Aa and VF-AF groups (54% vs 58%, IPTW-OR = 0.84 [0.54-1.29]). Axillary artery cannulation was associated with significantly fewer local infections (OR = 0.21, 95% CI:0.09-0.51), limb ischemia (OR = 0.37, 95% CI:0.17-0.84), bowel ischemia (OR = 0.16, 95% CI:0.05-0.51) and pulmonary edema (OR = 0.52, 95% CI:0.29-0.92) episodes, but with a higher rate of stroke (OR = 2.87, 95% CI:1.08-7.62) than femoral artery cannulation., Conclusion: Compared to VF-AF, axillary cannulation was associated with similar 90-day mortality rates. The high rate of stroke associated with axillary artery cannulation requires further investigation., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: In the intensive care unit (ICU) patients, fluid overload and congestion are associated with worse outcomes. Because of the heterogeneity of ICU patients, we hypothesized that there may exist different endotypes of congestion. The aim of this study was to identify endotypes of congestion and their association with outcomes., Methods: We conducted an unsupervised hierarchical clustering analysis on 145 patients admitted to ICU to identify endotypes. We measured several parameters related to clinical context, volume status, filling pressure, and venous congestion. These parameters included NT-proBNP, central venous pressure (CVP), the mitral E/e' ratio, the systolic/diastolic ratio of hepatic veins' flow velocity, the mean diameter of the inferior vena cava (IVC) and its variations, stroke volume changes following passive leg raising, the portal vein pulsatility index, and the venous renal impedance index., Results: Three distinct endotypes were identified: (1) "hemodynamic congestion" endotype (n = 75) with moderate alterations of ventricular function, increased CVP and left filling pressure values, and moderate fluid overload; (2) "volume overload congestion" endotype (n = 50); with normal cardiac function and filling pressure despite high positive fluid balance (fluid overload); (3) "systemic congestion" endotype (n = 20) with severe alterations of left and right ventricular functions, increased CVP and left ventricular filling pressure values. These endotypes vary significantly in ICU admission reasons, acute kidney injury rates, mortality, and length of ICU/hospital stay., Conclusions: Our analysis revealed three unique congestion endotypes in ICU patients, each with distinct pathophysiological features and outcomes. These endotypes are identifiable through key ultrasonographic characteristics at the bedside., Clinical Trial Gov: NCT04680728., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background: Perioperative anaphylaxis is a rare and acute systemic manifestation of drug-induced hypersensitivity reactions that occurs following anesthesia induction; the two main classes of drugs responsible for these reactions being neuromuscular blocking agents (NMBA) and antibiotics. The sensitization mechanisms to the drugs are not precisely known, and few risk factors have been described. A growing body of evidence underlines a link between occurrence of allergy and microbiota composition. However, no data exist on microbiota in perioperative anaphylaxis. The aim of this study was to compare circulating microbiota richness and composition between perioperative anaphylaxis patients and matched controls., Methods: Circulating 16s rDNA was quantified and sequenced in serum samples from 20 individuals with fully characterized IgE-mediated NMBA-related anaphylaxis and 20 controls matched on sex, age, NMBA received, type of surgery and infectious status. Microbiota composition was analyzed with a published bioinformatic pipeline and links with patients clinical and biological data investigated., Results: Analysis of microbiota diversity showed that anaphylaxis patients seem to have a richer circulating microbiota than controls, but no major differences of composition could be detected with global diversity indexes. Pairwise comparison showed a difference in relative abundance between patients and controls for Saprospiraceae, Enterobacteriaceae, Veillonellaceae, Escherichia-Shigella, Pseudarcicella, Rhodoferax , and Lewinella . Some taxa were associated with concentrations of mast cell tryptase and specific IgE., Conclusion: We did not find a global difference in terms of microbiota composition between anaphylaxis patient and controls. However, several taxa were associated with anaphylaxis patients and with their biological data. These findings must be further confirmed in different settings to broaden our understanding of drug anaphylaxis pathophysiology and identify predisposition markers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 de Chaisemartin, Ciocan, Gouel-Chéron, Granger, Longrois, Montravers, Cassard and Chollet-Martin.)

Background: In recent years, there has been increasing focus on the use of cardiac biomarkers in patients undergoing noncardiac surgery., Aims: The aim of this focused guideline was to provide updated guidance regarding the pre-, post- and combined pre-and postoperative use of cardiac troponin and B-type natriuretic peptides in adult patients undergoing noncardiac surgery., Methods: The guidelines were prepared using Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. This included the definition of critical outcomes, a systematic literature search, appraisal of certainty of evidence, evaluation of biomarker measurement in terms of the balance of desirable and undesirable effects including clinical outcomes, resource use, health inequality, stakeholder acceptance, and implementation. The panel differentiated between three different scopes of applications: cardiac biomarkers as prognostic factors, as tools for risk prediction, and for biomarker-enhanced management strategies., Results: In a modified Delphi process, the task force defined 12 critical outcomes. The systematic literature search resulted in over 25,000 hits, of which 115 full-text articles formed the body of evidence for recommendations. The evidence appraisal indicated heterogeneity in the certainty of evidence across critical outcomes. Further, there was relevant gradient in the certainty of evidence across the three scopes of application. Recommendations were issued and if this was not possible due to limited evidence, clinical practice statements were produced., Conclusion: The ESAIC focused guidelines provide guidance on the perioperative use of cardiac troponin and B-type natriuretic peptides in patients undergoing noncardiac surgery, for three different scopes of application., (Copyright © 2023 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Plasma viscosity (PV) is a key factor in microcirculatory flow resistance and capillary perfusion during hemodilution, we hypothesized a possible relationship between cardiac surgery-associated acute kidney injury (CSA-AKI) and PV. We conducted a prospective, observational, single-center study on 50 adult cardiac surgery patients with cardiopulmonary bypass (age 64 years, male sex 80%, baseline serum creatinine 1.04 mg/dL). We assessed perioperative characteristics, management, short-term outcomes, blood analysis, PV, serum creatinine, and diuresis. CSA-AKI was identified using KDIGO criteria. Data were collected at 10 time points during the first perioperative week. CSA-AKI occurred in 17 patients (34%): 12 (24%) stage 1, 1 (2%) stage 2, and 4 (8%) stage 3. Most patients (88%) developed CSA-AKI within 48 h post-surgery. Patients with CSA-AKI had higher body mass index (BMI), more frequent chronic kidney disease (CKD), and lower hemoglobin and hematocrit levels. The median baseline PV for the entire cohort was 1.50 cP on EDTA and 1.37 cP on citrate. No significant differences in PV levels were found between patients with CSA-AKI and normal kidney function, both at baseline and at the 48-h. Logistic and Cox regression analyses showed no significant relationship between PV and CSA-AKI. However, CSA-AKI was related to increased BMI, lower hemoglobin and hematocrit levels, and pre-existing CKD. The present study found no significant association between PV and CSA-AKI. Nevertheless, more research is needed to validate this finding and to investigate the role of PV in other clinical settings., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background and Aims: Inflammatory bowel disease (IBD) is associated with increased risk of thromboembolic events. The rotational thromboelastometry (ROTEM®) is a validated integrative assessment of coagulation, but it has never been studied in IBD patients., Methods: We performed a monocentric prospective observational study in a national tertiary center. Adult IBD patients underwent ROTEM® analysis on admission to our IBD Department. Parameters evaluated with ROTEM® tests (INTEM, EXTEM and FIBTEM) were clotting time (CT), the time of clot formation (CFT), clot firmness amplitude after 5 and 10 minutes (A5 and A10) and maximum clot firmness (MCF). ROC curves were performed in order to evaluate the ability of ROTEM® to predict active IBD., Results: Several ROTEM® parameters were significantly associated with active IBD compared to patients in remission, towards a hypercoagulable status for patients with active disease: CT, CFT, A5, A10, MCF. ROC analysis demonstrated that parameters related to clot robustness showed a very good prediction ability of active IBD (AUC >0.8): A5, A10, MCF in INTEM (p<0.001), in EXTEM (p<0.001) and MCF in FIBTEM (p<0.001). ROTEM® parameters showed high correlations with inflammation markers as C-reactive protein (CRP) and faecal calprotectin (FC)., Conclusions: Our study showed that ROTEM® parameters are modified in patients with active IBD, being correlating with inflammation markers and demonstrating a high prediction ability of active IBD. Future research is needed to validate ROTEM® as a method to discriminate patterns of active IBD and to guide anticoagulant therapy in patients with active IBD.

Background: Neuromuscular blocking agents (NMBAs) are among the leading cause of perioperative anaphylaxis, and most of these reactions are IgE mediated. Allergic sensitisation induced by environmental exposure to other quaternary ammonium-containing compounds, such as pholcodine, has been suggested. The aim of this study was to assess the relationship between pholcodine exposure and NMBA-related anaphylaxis., Methods: ALPHO was a multicentre case-control study, comparing pholcodine exposure within a year before anaesthesia between patients with NMBA-related perioperative anaphylaxis (cases) and control patients with uneventful anaesthesia in France. Each case was matched to two controls by age, sex, type of NMBA, geographic area, and season. Pholcodine exposure was assessed by a self-administered questionnaire and pharmaceutical history retrieved from pharmacy records. The diagnostic values of anti-pholcodine and anti-quaternary ammonium specific IgE (sIgE) were also evaluated., Results: Overall, 167 cases were matched with 334 controls. NMBA-related anaphylaxis was significantly associated with pholcodine consumption (odds ratio 4.2; 95% confidence interval 2.3-7.0) and occupational exposure to quaternary ammonium compounds (odds ratio 6.1; 95% confidence interval 2.7-13.6), suggesting that apart from pholcodine, other environmental factors can also lead to sensitisation to NMBAs. Pholcodine and quaternary ammonium sIgEs had a high negative predictive value (99.9%) but a very low positive predictive value (<3%) for identifying NMBA-related reactions., Conclusions: Patients exposed to pholcodine 12 months before NMBA exposure have a significantly higher risk of an NMBA-related anaphylaxis. The low positive predictive values of pholcodine and quaternary ammonium sIgEs precludes their use to identify a population with a high risk of NMBA-related anaphylaxis., Clinical Trial Registration: NCT02250729., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pulmonary hypertension (PH) is associated with pulmonary vasoconstriction and endothelial dysfunction leading to impaired nitric oxide (NO) and prostacyclin (PGI 2 ) pathways. Metformin, the first line treatment for type 2 diabetes and AMP-activated protein kinase (AMPK) activator, has been recently highlighted as a potential PH treatment. AMPK activation has been reported to improve endothelial function by enhancing endothelial NO synthase (eNOS) activity and to have relaxant effects in blood vessels. In this study, we examined the effect of metformin treatment on PH as well as on NO and PGI 2 pathways in monocrotaline (MCT)-injected rats with established PH. Moreover, we investigated the anti-contractile effects of AMPK activators on endothelium-denuded human pulmonary arteries (HPA) from Non-PH and Group 3 PH patients (due to lung diseases and/or hypoxia). Furthermore, we explored the interaction between treprostinil and the AMPK/eNOS pathway. Our results showed that metformin protected against PH progression in MCT rats where it reduced the mean pulmonary artery pressure, pulmonary vascular remodeling and right ventricular hypertrophy and fibrosis compared to vehicle-treated MCT rats. The protective effects on rat lungs were mediated in part by increasing eNOS activity and protein kinase G-1 expression but not through the PGI 2 pathway. In addition, incubation with AMPK activators reduced the phenylephrine-induced contraction of endothelium-denuded HPA from Non-PH and PH patients. Finally, treprostinil also augmented eNOS activity in HPA smooth muscle cells. In conclusion, we found that AMPK activation can enhance the NO pathway, attenuate vasoconstriction by direct effects on smooth muscles, and reverse established MCT-induced PH in rats., Competing Interests: Declaration of competing interest Over the last three years, Christophe Guignabert reports grants from Acceleron and Janssen and grants and personal fees from Merck and ShouTi, outside of this submitted work. Xavier Norel has received educational research grants from United Therapeutics. Adam M. Silverstein is employee of United Therapeutics. The other authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In patients with coronary artery disease (CAD), plasma levels of pro-inflammatory lipid mediators such as PGE 2 and TxA 2 are increased. They could increase vascular contraction while EPA and DHA could reduce it. Studies have been mostly conducted on animal vessels. Therefore, the aim of the study was to investigate if EPA, DHA, and DHA-derived metabolites: RvD1, RvD5 and MaR1 can modulate contraction of human coronary arteries (HCA) induced by PGE 2 or TxA 2 stable analogue (U46619). DHA and EPA relaxed HCA pre-contracted with PGE 2 . 18 h-incubation with DHA but not EPA reduced the PGE 2 -induced contractions. Pre-incubation with RvD1, RvD5 and MaR1 reduced the PGE 2 -induced contractions. Indomethacin did not significantly modify the PGE 2 responses. L-NOARG (inhibitor of nitric oxide synthase), reduced only the PGE 2 -induced contractions in RvD1-treated rings. Finally, FPR2/ALX, GPR32 and LGR6 receptors are detected in HCA by immunofluorescence. Our results indicate that DHA and its metabolites could be beneficial for HCA blood flow and could be a therapeutic perspective for patients with CAD., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Electroencephalography (EEG) signals contain transient oscillation patterns commonly used to classify brain states in responses to action, sleep, coma or anesthesia., Methods: Using a time-frequency analysis of the EEG, we search for possible causal correlations between the successive phases of general anesthesia. We hypothesize that it could be possible to anticipate recovery patterns from the induction or maintenance phases. For that goal, we track the maximum power of the α-band and follow its time course., Results and Discussion: We quantify the frequency shift of the α-band during the recovery phase and the associated duration. Using Pearson coefficient and Bayes factor, we report non-significant linear correlation between the α-band frequency and duration shifts during recovery and the presence of the δ or the α rhythms during the maintenance phase. We also found no correlations between the α-band emergence trajectory and the total duration of the flat EEG epochs (iso-electric suppressions) induced by a propofol bolus injected during induction. Finally, we quantify the instability of the α-band using the mathematical total variation that measures possible deviations from a flat line. To conclude, the present correlative analysis shows that EEG dynamics extracted from the initial and maintenance phases of general anesthesia cannot anticipate both the emergence trajectory and the extubation time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sun, Longrois and Holcman.)

Background: Romania is one of the European countries with low COVID-19 vaccination coverage. The main goal of this study was to describe the COVID-19 vaccination status in patients admitted to Romanian ICUs with a severe COVID-19 infection. The study describes the patients' characteristics according to their vaccination status and evaluates the association between vaccination status and ICU mortality., Methods: This retrospective, observational, multicenter study included patients with confirmed vaccination status admitted to Romanian ICUs from January 2021 to March 2022., Results: Two thousand, two hundred and twenty-two patients with confirmed vaccination status were included. Five point one three percent of patients were vaccinated with two vaccine doses and one point seventeen percent of patients were vaccinated with one vaccine dose. The vaccinated patients showed a higher rate of comorbidities but had similar clinical characteristics at ICU admission and lower mortality rates compared to non-vaccinated patients. Vaccinated status and higher Glasgow Coma Scale at ICU admission were independently associated with ICU survival. Ischemic heart disease, chronic kidney disease, higher SOFA score at ICU admission and the need for mechanical ventilation in ICU were independently associated with ICU mortality., Conclusion: Lower rates of ICU admission were observed in fully vaccinated patients even in a country with low vaccination coverage. The ICU mortality was lower for fully vaccinated patients compared to non-vaccinated patients. The benefit of vaccination on ICU survival could be more important in patients with associated comorbidities.

Acute hypersensitivity reactions (AHRs) occurring in present-day anaesthesia can have severe, sometimes fatal, consequences and their incidence is increasing. The most frequent allergens responsible for AHR during anaesthesia are neuromuscular blocking agents (NMBAs) (70% of the cases) followed by antibiotics (18%), patent blue dye and methylene blue dye (5%), and latex (5%). Following an AHR, strategies for subsequent anaesthetic procedures (especially the choice of an NMBA) may be difficult to formulate due to inconclusive diagnostic analysis in up to 30% of AHRs. Current diagnosis of AHR relies on the detection of mast cell degranulation products and drug-specific type E immunoglobulins (IgE) in order to document an IgE-mediated anaphylaxis (IgE endotype). Nonetheless, other IgE-independent pathways can be involved in AHR, but their detection is not currently available in standard situations. The different mechanisms (endotypes) involved in peri-operative AHR may contribute to the inconclusive diagnostic work-up and this generates uncertainty concerning the culpable drug and strategy for subsequent anaesthetic procedures. This review provides details on the IgE endotype; an update on non-IgE related endotypes and the novel diagnostic tools that could characterise them. This detailed update is intended to provide explicit clinical reasoning tools to the anaesthesiologist faced with an incomplete AHR diagnostic work-up and to facilitate the decision-making process regarding anaesthetic procedures following an AHR to NMBAs., (Copyright © 2022 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Recent data indicated a high incidence of inappropriate management of neuromuscular block, with a high rate of residual paralysis and relaxant-associated postoperative complications. These data are alarming in that the available neuromuscular monitoring, as well as myorelaxants and their antagonists basically allow well tolerated management of neuromuscular blockade. In this first European Society of Anaesthesiology and Intensive Care (ESAIC) guideline on peri-operative management of neuromuscular block, we aim to present aggregated and evidence-based recommendations to assist clinicians provide best medical care and ensure patient safety. We identified three main clinical questions: Are myorelaxants necessary to facilitate tracheal intubation in adults? Does the intensity of neuromuscular blockade influence a patient's outcome in abdominal surgery? What are the strategies for the diagnosis and treatment of residual paralysis? On the basis of this, PICO (patient, intervention, comparator, outcome) questions were derived that guided a structured literature search. A stepwise approach was used to reduce the number of trials of the initial research ( n  = 24 000) to the finally relevant clinical studies ( n  = 88). GRADE methodology (Grading of Recommendations, Assessment, Development and Evaluation) was used for formulating the recommendations based on the findings of the included studies in conjunction with their methodological quality. A two-step Delphi process was used to determine the agreement of the panel members with the recommendations: R1 We recommend using a muscle relaxant to facilitate tracheal intubation (1A). R2 We recommend the use of muscle relaxants to reduce pharyngeal and/or laryngeal injury following endotracheal intubation (1C). R3 We recommend the use of a fast-acting muscle relaxant for rapid sequence induction intubation (RSII) such as succinylcholine 1 mg kg -1 or rocuronium 0.9 to 1.2 mg kg -1 (1B). R4 We recommend deepening neuromuscular blockade if surgical conditions need to be improved (1B). R5 There is insufficient evidence to recommend deep neuromuscular blockade in general to reduce postoperative pain or decrease the incidence of peri-operative complications. (2C). R6 We recommend the use of ulnar nerve stimulation and quantitative neuromuscular monitoring at the adductor pollicis muscle to exclude residual paralysis (1B). R7 We recommend using sugammadex to antagonise deep, moderate and shallow neuromuscular blockade induced by aminosteroidal agents (rocuronium, vecuronium) (1A). R8 We recommend advanced spontaneous recovery (i.e. TOF ratio >0.2) before starting neostigmine-based reversal and to continue quantitative monitoring of neuromuscular blockade until a TOF ratio of more than 0.9 has been attained. (1C)., (Copyright © 2022 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Current trends in anesthetic depth (i.e., hypnosis) and antinociception monitoring are unclear. We thus aimed to determine contemporary perspectives on monitoring these components of anesthesia during general anesthesia. Participants received and responded anonymously to an internet-based international survey supported by the European Society of Anaesthesiology and Intensive Care. Comparisons, when applicable, were carried out using Chi 2 analysis or Fischer's exact test. A total of 564 respondents, predominantly from Europe (80.1%), participated. There was a strong participation from Belgium (11.5%). A majority (70.9%) of anesthetists considered hypnotic monitoring important on most occasions to always. In contrast, a majority (62.6%) never or only occasionally considered antinociception monitoring important. This difference in the perceived importance of anesthetic depth versus antinociception monitoring was significant (p < 0.0001). A majority of respondents (70.1%) believed that guiding hypnosis and antinociception using these monitors would improve patient care on most occasions to always. Nonetheless, a substantial number of participants were unsure if hypnotic (23%) or antinociception (32%) monitoring were recommended and there was a lack of knowledge (58%) of any published algorithms to titrate hypnotic and/or antinociceptive drugs based on the information provided by the monitors. In conclusion, current trends in European academic centers prioritize anesthesia depth over antinociception monitoring. Despite an agreement among respondents that applying strategies that optimize anesthetic depth and antinociception could improve outcome, there remains a lack of knowledge of appropriate algorithms. Future studies and recommendations should focus on clarifying goal-directed anesthetic strategies and determine their impact on perioperative patient outcome., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: Postoperative cardiac troponin I concentration is predictive of worsened outcomes in cardiac surgery. Lung transplantation (LT) surgery shares common features with cardiac surgery, but postoperative troponin has yet to be investigated. The authors aimed to evaluate the association between early postoperative troponin concentration and the 1-year mortality after transplantation., Design: A retrospective, observational, single-center study., Setting: At a tertiary care, university hospital., Participants: Patients who underwent lung transplantation from January 2011 to December 2017 INTERVENTIONS: For each patient, preoperative, intraoperative, and postoperative data were collected, as well as the troponin I measurement at the moment of postoperative intensive care unit admission., Measurements and Main Results: Two hundred twenty LT procedures were analyzed. Troponin I was elevated in all LT patients, with a median of 3.82 ng/mL -1 (2-6.42) ng/mL -1 significantly higher in non-survivors than in survivors with 5.39 (2.88-7.44) v 3.50 ng/mL (1.74-5.76), p = 0.005. In the multivariate analysis, the authors found that only the Simplified Acute Physiology Score II score (hazard ratio [HR] 1.03; 95% confidence interval [CI] [1.001; 1.05]; p = 0.007) and the need to maintain extracorporeal life support at the end of surgery (HR 2.54; 95% CI [1.36; 4.73]; p = 0.003) were independently associated with the 1-year mortality. The multiple linear regression model found that troponin levels were associated with the need for extracorporeal life support (ECLS) (p = 0.014), the amount of transfused packed red blood cells (p = 0.008), and bilateral LT (p < 0.001)., Conclusion: Early postoperative troponin serum levels were not independently associated with 1-year mortality. Early postoperative troponin I levels were correlated to bilateral LT, the need for ECLS, and intraoperative blood transfusion., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Cardiac surgery increasingly is being performed in patients with a history of or with active cancer. The aim of this study was to analyze the association between a history of cancer and 1-year mortality after cardiac surgery with cardiopulmonary bypass (CPB)., Design: An observational monocentric study, with data collected from a prospective institutional database was conducted., Setting: A single academic center., Participants: All consecutive patients undergoing cardiac surgery with CPB between 2005 and 2017., Intervention: None., Methods: A history of cancer was preoperatively identified. Mortality rates were estimated by the Kaplan-Meier method. The 1-year mortality risk of patients with and without cancer was compared using a multivariate Cox model., Measurements and Main Results: During the study period, 12,143 patients underwent cardiac surgery with CPB, including 4,681 (39%) isolated coronary artery bypass surgeries. Their median EuroSCORE II was 3.1, interquartile range 1.5-to-6.4. Nine hundred thirty patients (8%) had a diagnosis of cancer, out of whom 469 (50%) were diagnosed ≤5 years before the index surgery; 103 (11%) patients had hemopathy, and 825 (89%) had solid cancers. The estimated unadjusted 1-year mortality was significantly higher among patients with cancer, 11% (95% confidence interval [CI] 10-14) versus 8% (95%CI 7-9) p < 0.01. After adjustment, a diagnosis of cancer was not associated with the risk of 1-year mortality (adjusted hazard ratio = 1.17 [95%CI 0.96-1.43]; p = 0.13)., Conclusions: In a large cohort of patients undergoing cardiac surgery with CPB, cancer was not independently associated with 1-year mortality. An isolated cancer history should not lead to denial of cardiac surgery. The impact of cancer on complications and long-term survival after cardiac surgery requires further research., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Plasma viscosity is one of the critical factors that regulate microcirculatory flow but has received scant research attention. The main objective of this study was to evaluate plasma viscosity in cardiac surgery with respect to perioperative trajectory, main determinants, and impact on outcome., Methods: Prospective, single center, observational study, including 50 adult patients undergoing cardiac surgery with cardiopulmonary bypass between February 1, 2020 and May 31, 2021. Clinical perioperative characteristics, short term outcome, standard blood analysis, plasma viscosity, total proteins, and fibrinogen concentrations were recorded at 10 distinct time points during the first perioperative week., Results: The longitudinal analysis showed that plasma viscosity is strongly influenced by proteins and measurement time points. Plasma viscosity showed a coefficient of variation of 11.3 ± 1.08 for EDTA and 12.1 ± 2.1 for citrate, similarly to total proteins and hemoglobin, but significantly lower than fibrinogen (p < .001). Plasma viscosity had lower percentage changes compared to hemoglobin (RANOVA, p < .001), fibrinogen (RANOVA, p < .001), and total proteins (RANOVA, p < .001). The main determinant of plasma viscosity was protein concentrations. No association with outcome was found, but the study may have been underpowered to detect it., Conclusion: Plasma viscosity had a low coefficient of variation and low perioperative changes, suggesting tight regulation. Studies linking plasma viscosity with outcome would require large patient cohorts., (© 2022 John Wiley & Sons Ltd.)

Glycosaminoglycans (GAGs) pooling has long been considered as one of the histopathological characteristics defining thoracic aortic aneurysm (TAA) together with smooth muscle cells (SMCs) apoptosis and elastin fibers degradation. However, little information is known about GAGs composition or their potential implication in TAA pathology. Syndecan-1 (SDC-1) is a heparan sulfate proteoglycan that is implicated in extracellular matrix (ECM) interaction and assembly, regulation of SMCs phenotype, and various aspects of inflammation in the vascular wall. Therefore, the aim of this study was to determine whether SDC-1 expression was regulated in human TAA and to analyze its role in a mouse model of this disease. In the current work, the regulation of SDC-1 was examined in human biopsies by RT-qPCR, ELISA, and immunohistochemistry. In addition, the role of SDC-1 was evaluated in descending TAA in vivo using a mouse model combining both aortic wall weakening and hypertension. Our results showed that both SDC-1 mRNA and protein are overexpressed in the media layer of human TAA specimens. RT-qPCR experiments revealed a 3.6-fold overexpression of SDC-1 mRNA ( p = 0.0024) and ELISA assays showed that SDC-1 protein was increased 2.3 times in TAA samples compared with healthy counterparts (221 ± 24 vs. 96 ± 33 pg/mg of tissue, respectively, p = 0.0012). Immunofluorescence imaging provided evidence that SMCs are the major cell type expressing SDC-1 in TAA media. Similarly, in the mouse model used, SDC-1 expression was increased in TAA specimens compared to healthy samples. Although its protective role against abdominal aneurysm has been reported, we observed that SDC-1 was dispensable for TAA prevalence or rupture. In addition, SDC-1 deficiency did not alter the extent of aortic wall dilatation, elastin degradation, collagen deposition, or leukocyte recruitment in our TAA model. These findings suggest that SDC-1 could be a biomarker revealing TAA pathology. Future investigations could uncover the underlying mechanisms leading to regulation of SDC-1 expression in TAA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zalghout, Vo, Arocas, Jadoui, Hamade, Badran, Oudar, Charnaux, Longrois, Boulaftali, Bouton and Richard.)

Background: During the COVID-19 pandemic, resource allocation became a major problem in globally overwhelmed ICUs. The main goal of this study was to describe the clinical characteristics of the very elderly patients (aged ≥ 80 years) with COVID-19 admitted in Romanian ICUs. The study objectives were to evaluate and determine the factors associated with ICU mortality., Methods: We designed a national, multicentric, observational platform with prospective enrolment. This study included patients aged ≥ 80 years admitted in Romanian ICUs with SARS-CoV-2 infection from March 2020 to December 2021., Results: We included 1666 patients with a median age of 83 years and 78% ICU mortality. Male sex, dyspnoea, lower Glasgow Coma Scale and lower SpO2 at ICU admission, the need for mechanical ventilation (MV), and corticosteroid use were independently associated with mortality. A total of 886/1666 (53%) elderly patients underwent invasive mechanical ventilation, with a mortality of 97%. The age impact on mortality was confirmed by a 1:1 propensity matching with less elderly ICU patients., Conclusion: In extremely elderly patients with COVID-19 admitted in the ICU, mortality is high, particularly when requiring MV. Therapy should be directed towards the optimization of less invasive ventilatory methods and the use of MV and corticosteroids only in highly selected patients.

Introduction: The determination of ventriculo-arterial coupling is gaining an increasing role in cardiovascular and sport medicine. However, its relevance in critically ill patients is still under investigation. In this study we measured the association between ventriculo-arterial coupling and oxygen consumption (VO 2 ) response after hemodynamic interventions in cardiac surgery patients with acute circulatory instability., Material and Methods: Sixty-one cardio-thoracic ICU patients (67 ± 12 years, 80% men) who received hemodynamic therapeutic interventions (fluid challenge or norepinephrine infusion) were included. Arterial pressure, cardiac output, heart rate, arterial (E A ), and ventricular elastances (E V ), total indexed peripheral resistances were assessed before and after hemodynamic interventions. VO 2 responsiveness was defined as VO 2 increase >15% following the hemodynamic intervention. Ventriculo-arterial coupling was assessed measuring the E A /E V ratio by echocardiography. The left ventricle stroke work to pressure volume area ratio (SW/PVA) was also calculated., Results: In the overall cohort, 24 patients (39%) were VO 2 responders, and 48 patients had high ventriculo-arterial (E A /E V ) coupling ratio with a median value of 1.9 (1.6-2.4). Most of those patients were classified as VO 2 responders (28 of 31 patients, p = 0.031). Changes in VO 2 were correlated with those of indexed total peripheral resistances, E A , E A /E V and cardiac output. E A /E V ratio predicted VO 2 increase with an AUC of 0.76 [95% CI: 0.62-0.87]; p = 0.001. In principal component analyses, E A /E V and SW/PVA ratios were independently associated ( p < 0.05) with VO 2 response following interventions., Conclusions: VO 2 responders were characterized by baseline high ventriculo-arterial coupling ratio due to high E A and low E V . Baseline E A /E V and SW/PVA ratios were associated with VO 2 changes independently of the hemodynamic intervention used. These results underline the pathophysiological significance of measuring ventriculo-arterial coupling in patients with hemodynamic instability, as a potential therapeutic target., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Andrei, Nguyen, Longrois, Popescu, Bouhemad and Guinot.)

Acute hypersensitivity reactions to drugs occur infrequently during anaesthesia and the peri-operative period. When clinical presentation includes the classical triad, erythema, cardiovascular abnormalities and increased airway pressure, the diagnosis is evident and the challenge is to prescribe a therapeutic regimen according to guidelines and to manage refractory signs in a timely manner. In many situations, however, the initial clinical signs are isolated, such as increased airway pressure or arterial hypotension. Rendering a differential diagnosis with causes and mechanisms other than acute hypersensitivity reactions (AHRs) is difficult, delaying treatment with possible worsening of the clinical signs, and even death, in previously healthy individuals. In these difficult diagnostic situations, clinical reasoning is mandatory, and guidelines do not explicitly explain the elements on which clinical reasoning can be built. In this article, based on clinical evidence whenever available, experimental data and pathophysiology, we propose algorithms that have been evaluated by experts. The goal of these algorithms is to provide explicit elements on which the differential diagnosis of AHRs can be made, accelerating the implementation of adequate therapy., (Copyright © 2021 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Cardiac, ventilatory and kidney management in the critical care setting has been optimized over the past decades. Cognition and sedation represent one of the last remaning challenges. As conventional sedation is suboptimal and as the sedation evoked by alpha-2 adrenergic agonists ("cooperative" sedation with dexmedetomidine, clonidine or guanfacine) represents a valuable alternative, this manuscript covers three practical topics for which evidence-based medicine is lacking: a) Switching from conventional to cooperative sedation ("switching"): the short answer is the abrupt withdrawal of conventional sedation, immediate implementation of alpha-2 agonist infusion and the use of "rescue sedation" (midazolam bolus[es]) or "breakthrough sedation" (haloperidol bolus[es]) to stabilize cooperative sedation. b) Switching from conventional to cooperative sedation in unstable patients (e.g., refractory delirium tremens, septic shock, acute respiratory distress syndrome, etc.): to avoid hypotension and bradycardia evoked by sympathetic deactivation, the short answer is to maintain the stroke volume through volume loading, vasopressors and inotropes. c) To avoid these switches and associated difficulties, alpha-2 agonists may be considered first-line sedatives. The short answer is to administer alpha-2 agonists slowly from admission or endotracheal intubation up to stabilized cooperative sedation. The "take home" message is as follows: a) alpha-2 agonists are jointly sympathetic deactivators and sedative agents; b) sympathetic deactivation implies maintaining the stroke volume and iterative assessment of volemia. Evidence-based medicine should document our propositions.

Introduction: Prostacyclin (PGI 2 ) is synthetized by PGI 2 synthase (PGIS) and induces vasorelaxation via activation of cyclic AMP (cAMP) generating IP-receptor. Several components of the PGI 2 signaling pathway are reduced in patients with pulmonary hypertension (PH)., Aim: To study the effect of 17β-estradiol (E2) on the PGI 2 signaling pathway in human pulmonary arteries (HPA) and in their smooth muscle cells (hPASMC) derived from Group-3 PH and non-PH patients., Methods: Following E2-treatments of isolated HPA and cultured hPASMC, we measured: 6-keto-Prostaglandin F 1α (PGI 2 stable metabolite) by ELISA, PGIS and IP protein levels by Western blot and HPA vasorelaxations with an organ bath system., Results: Incubation with E2 (24/48 h, doses ≥ 10 nM) significantly increased the expression of PGIS in hPASMC derived from both PH (65-98%) and non-PH (21-33%) patients, whereas incubation with E2 (2 h, 0.1 and 1 µM) increased 6-keto-PGF 1α production in HPA from Group-3 PH patients only, and did not affect 6-keto-PGF 1α production in hPASMC from either non-PH or Group-3 PH patients. Increases in IP receptor expression were observed following 10 mM E2-treatment of hPASMC from non-PH (33% after 48 h) and Group-3 PH (23% after 24 h) patient lungs. Finally, preincubation with 100 nM E2 significantly increased arachidonic acid-induced vasorelaxation of HPA from non-PH patient lungs but not of HPA from Group-3 PH patient lungs., Conclusion: E2-treatment may help to restore the PGI 2 -pathway in Group-3 PH., (Copyright © 2021. Published by Elsevier Ltd.)