Tranexamic acid: a narrative review of its current role in perioperative medicine and acute medical bleeding.

Purpose: Tranexamic acid (TXA) is the most widely prescribed antifibrinolytic for active bleeding or to prevent surgical bleeding. Despite numerous large multi-center randomized trials involving thousands of patients being conducted, TXA remains underutilized in indications where it has demonstrated efficacy and a lack of harmful effects. This narrative review aims to provide basic concepts about fibrinolysis and TXA's mode of action and is focused on the most recent and important trials evaluating this drug in different hemorrhagic situations. Methods: We selected every low bias RCT, and we highlighted their strengths and limitations throughout this review. Principal findings: While TXA appears to have a favorable benefit-risk ratio in most situations (trauma, obstetrics, at-risk for bleeding surgeries) evidence of benefit is lacking in certain medical settings (SAH, digestive bleeding). Conclusion: Although in some situations the drug's effect on significant outcomes is modest, its favorable safety profile allows it to be recommended for trauma patients, in obstetrics, and in scheduled surgeries at risk of bleeding. However, it cannot be recommended in cases of spontaneous intracranial bleeding, subarachnoid hemorrhage (SAH), or gastrointestinal bleeding.

Continuation vs Discontinuation of Renin-Angiotensin System Inhibitors Before Major Noncardiac Surgery: The Stop-or-Not Randomized Clinical Trial.

Importance: Before surgery, the best strategy for managing patients who are taking renin-angiotensin system inhibitors (RASIs) (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) is unknown. The lack of evidence leads to conflicting guidelines. Objective: To evaluate whether a continuation strategy vs a discontinuation strategy of RASIs before major noncardiac surgery results in decreased complications at 28 days after surgery. Design, Setting, and Participants: Randomized clinical trial that included patients who were being treated with a RASI for at least 3 months and were scheduled to undergo a major noncardiac surgery between January 2018 and April 2023 at 40 hospitals in France. Intervention: Patients were randomized to continue use of RASIs (n = 1107) until the day of surgery or to discontinue use of RASIs 48 hours prior to surgery (ie, they would take the last dose 3 days before surgery) (n = 1115). Main Outcomes and Measures: The primary outcome was a composite of all-cause mortality and major postoperative complications within 28 days after surgery. The key secondary outcomes were episodes of hypotension during surgery, acute kidney injury, postoperative organ failure, and length of stay in the hospital and intensive care unit during the 28 days after surgery. Results: Of the 2222 patients (mean age, 67 years [SD, 10 years]; 65% were male), 46% were being treated with angiotensin-converting enzyme inhibitors at baseline and 54% were being treated with angiotensin receptor blockers. The rate of all-cause mortality and major postoperative complications was 22% (245 of 1115 patients) in the RASI discontinuation group and 22% (247 of 1107 patients) in the RASI continuation group (risk ratio, 1.02 [95% CI, 0.87-1.19]; P = .85). Episodes of hypotension during surgery occurred in 41% of the patients in the RASI discontinuation group and in 54% of the patients in the RASI continuation group (risk ratio, 1.31 [95% CI, 1.19-1.44]). There were no other differences in the trial outcomes. Conclusions and Relevance: Among patients who underwent major noncardiac surgery, a continuation strategy of RASIs before surgery was not associated with a higher rate of postoperative complications than a discontinuation strategy. Trial Registration: ClinicalTrials.gov Identifier: NCT03374449.

Continuous non-invasive vs. invasive arterial blood pressure monitoring during neuroradiological procedure: a comparative, prospective, monocentric, observational study.

BACKGROUND: In the perioperative setting, the most accurate way to continuously measure arterial blood pressure (ABP) is using an arterial catheter. Surrogate methods such as finger cuff have been developed to allow non-invasive measurements and are increasingly used, but need further evaluation. The aim of this study is to evaluate the accuracy and clinical concordance between two devices for the measurement of ABP during neuroradiological procedure. METHODS: This is a prospective, monocentric, observational study. All consecutive patients undergoing a neuroradiological procedure were eligible. Patients who needed arterial catheter for blood pressure measurement were included. During neuroradiological procedure, ABP (systolic, mean and diatolic blood pressure) was measured with two different technologies: radial artery catheter and Nexfin. Bland-Altman and error grid analyses were performed to evaluate the accuracy and clinical concordance between devices. RESULTS: From March 2022 to November 2022, we included 50 patients, mostly ASA 3 (60%) and required a cerebral embolization (94%) under general anaesthesia (96%). Error grid analysis showed that 99% of non-invasive ABP measures obtained with the Nexfin were located in the risk zone A or B. However, 65.7% of hypertension events and 41% of hypotensive events were respectively not detected by Nexfin. Compared to the artery catheter, a significant relationship was found for SAP (r2 = 0.78) and MAP (r2 = 0.80) with the Nexfin (p < 0.001). Bias and limits of agreement (LOA) were respectively 9.6 mmHg (- 15.6 to 34.8 mmHg) and - 0.8 mmHg (- 17.2 to 15.6 mmHg), for SAP and MAP. CONCLUSIONS: Nexfin is not strictly interchangeable with artery catheter for ABP measuring. Further studies are needed to define its clinical use during neuroradiological procedure. TRIAL REGISTRATION: Clinicaltrials.gov, registration number: NCT05283824.

Nationwide Audit of Postoperative Mortality and Complications After Digestive Cancer Surgery: Will New Legal Thresholds be Sufficient?

BACKGROUND: French policymakers recently chose to regulate high-risk digestive cancer surgery (DCS). A minimum of five cases per year should be performed for each of the following types of curative cancer surgery: esophagus/esogastric junction (ECS), stomach (GCS), liver (LCS, metastasis included), pancreas (PCS), and rectum (RCS). This study aimed to evaluate the hypothetical beneficial effects of the new legal minimal volume thresholds on the rates of 90-day postoperative mortality (90POM) for each high-risk DCS. METHODS: This nationwide observational population-based cohort study used data extracted from the French National Health Insurance Database from 1 January 2015-31 December 2017. Mixed-effects logistic regression models were performed to estimate the independent effect of hospital volume. RESULTS: During the study period, 61,169 patients (57.1 % male, age 69.7 ±12.2 years) underwent high-risk DCS including ECS (n = 4060), GCS (n = 5572), PCS (n = 8598), LCS (n = 10,988), and RCS (n = 31,951), with 90POM of 6.6 %, 6.9 %, 6.0 %, 5.2 %, and 2.9 %, respectively. For hospitals fulfilling the new criteria, 90POM was lower after adjustment only for LCS (odds ratio [OR],15.2; 95 % confidence interval [CI], 9.5-23.2) vs OR, 7.6; 95 % CI, 5.2-11.0; p < 0.0001) and PCS (OR, 3.6; 95 % CI, 1.7-7.6 vs OR, 2.1; 95 % CI, 1.0-4.4; p<0.0001). With higher thresholds, all DCSs showed a lower adjusted risk of 90POM (e.g., OR, 0.38; 95 % CI, 0.28-0.51) for PCS of 40 or higher. CONCLUSION: Based on retrospective data, thresholds higher than those promulgated would better improve the safety of high-risk DCS. New policies aiming to further centralize high-risk DCS should be considered, associated with a clear clinical pathway of care for patients to improve accessibility to complex health care in France.

Moderate Exercise Modulates Inflammatory Responses and Improves Survival in a Murine Model of Acute Pneumonia.

OBJECTIVES: An association between physical inactivity and worse outcome during infectious disease has been reported. The effect of moderate exercise preconditioning on the immune response during an acute pneumonia in a murine model was evaluated. SETTING: Laboratory experiments. SUBJECTS: C57BL6/j male mice. INTERVENTIONS: Six-week-old C57BL/6J mice were divided in two groups: an exercise group and a control group. In the exercise group, a moderate, progressive, and standardized physical exercise was applied for 8 weeks. It consisted in a daily treadmill training lasting 60 minutes and with an intensity of 65% of the maximal theoretical oxygen uptake. Usual housing recommendation were applied in the control group during the same period. After 8 weeks, pneumonia was induced in both groups by intratracheal instillation of a fixed concentration of a Klebsiella pneumoniae (5 × 103 colony-forming unit) solution. MEASUREMENTS AND MAIN RESULTS: Mice preconditioned by physical exercise had a less sever onset of pneumonia as shown by a significant decrease of the Mouse Clinical Assessment Severity Score and had a significantly lower mortality compared with the control group (27% vs. 83%; p = 0.019). In the exercise group, we observed a significantly earlier but transient recruitment of inflammatory immune cells with a significant increase of neutrophils, CD4+ cells and interstitial macrophages counts compared with control group. Lung tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and IL-10 were significantly decreased at 48 hours after pneumonia induction in the exercise group compared with the control group. CONCLUSIONS: In our model, preconditioning by moderate physical exercise improves outcome by reducing the severity of acute pneumonia with an increased but transient activation of the innate immune response.

From early risk to 1-year mortality: a comprehensive assessment of postoperative venous thromboembolism in upper gastrointestinal cancer patients - a nationwide cohort study.

BACKGROUND: Venous thromboembolism (VTE) is a well-recognized complication following gastrointestinal cancer surgery, particularly early postoperatively. The incidence and risk factors of VTE within 1-year after esophageal (including esophago-gastric junction) (ECS) and gastric (GCS) cancer surgeries, and especially its impact on 1-year global mortality, are yet under-explored. METHODS: This nationwide observational population-based cohort study used data extracted from all patients undergoing ECS and GCS in France between 1 January 2015 and 31 December 2017. Multivariate logistic regression was used to identify risk factors for 90 postoperative days (POD) VTE (OR 95% CI). Cox proportional hazards models investigated the impact of 1-year postoperative VTE on 1-year global mortality [HR (95% CI)]. RESULTS: During the study period, 8005 patients underwent ECS ( N =3429) or GCS ( N =4576) (31.8% female; 66.7±12.1 years old). Majority ( N =4951) of patients had preoperative treatment (chemotherapy or radiochemotherapy). Ninety POD incidence of VTE were 4.7% (ECS=6.2%) (GCS=3.6%) (44.7% during first hospitalization, 19.0% needing readmission, and 36.3% ambulatory management). Main risk factors were three and two field esophagectomy [3.6 (2.20-5.83) and 2.2 (1.68-3.0)], obesity [1.9 (1.40-2.58)] and history of VTE [5.1 (2.72-9.45)]. Late-onset VTE rates (occurring between the 6th and 12th month) represented 1.80 and 1.46% of the overall ECS and GCS groups. Patients with VTE within 1-year had higher risks of 1-year global mortality: (2.04 1.52; 2.73) and 2.71 (2.09; 3.51), respectively. CONCLUSION: Our extensive analysis of a nationwide database highlights the significant risk of postoperative VTE after ECS and GCS, persisting within 90 POD and up to 1-year. Crucially, a higher risk of global mortality within 1-year for patients experiencing early or late VTE was found. These findings could advocate for further research into extended prophylactic regimens, particularly for those most at risk.

Guidelines for reducing the environmental impact of general anaesthesia.

OBJECTIVE: To provide guidelines for reducing the environmental impact of general anaesthesia. DESIGN: A committee of ten experts from SFAR and SF2H and SFPC learned societies was set up. A policy of declaration of competing interests was applied and observed throughout the guideline-writing process. Likewise, it did not benefit from any funding from a company marketing a health product (drug or medical device). The committee followed the GRADE® method (Grading of Recommendations Assessment, Development and Evaluation) to assess the quality of the evidence on which the recommendations were based. METHODS: We aimed to formulate recommendations according to the GRADE® methodology for three different fields: anaesthesia vapours and gases; intravenous drugs; medical devices and the working environment. Each question was formulated according to the PICO format (Population, Intervention, Comparator, Outcome). The literature review and recommendations were formulated according to the GRADE® methodology. RESULTS: The experts' work on the synthesis and application of the GRADE® method led to the formulation of 17 recommendations. Since the GRADE® method could not be entirely applied to all of the questions, some of the recommendations were formulated as expert opinions. CONCLUSION: Based on strong agreement between experts, we produced 17 recommendations designed to guide reducing the environmental impact of general anaesthesia.

Guidelines on perioperative optimization protocol for the adult patient 2023.

OBJECTIVE: The French Society of Anesthesiology and Intensive Care Medicine [Société Française d'Anesthésie et de Réanimation (SFAR)] aimed at providing guidelines for the implementation of perioperative optimization programs. DESIGN: A consensus committee of 29 experts from the SFAR was convened. A formal conflict-of-interest policy was developed at the outset of the process and enforced throughout. The entire guidelines process was conducted independently of any industry funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence. METHODS: Four fields were defined: 1) Generalities on perioperative optimization programs; 2) Preoperative measures; 3) Intraoperative measures and; 4) Postoperative measures. For each field, the objective of the recommendations was to answer a number of questions formulated according to the PICO model (population, intervention, comparison, and outcomes). Based on these questions, an extensive bibliographic search was carried out using predefined keywords according to PRISMA guidelines and analyzed using the GRADE® methodology. The recommendations were formulated according to the GRADE® methodology and then voted on by all the experts according to the GRADE grid method. As the GRADE® methodology could have been fully applied for the vast majority of questions, the recommendations were formulated using a "formalized expert recommendations" format. RESULTS: The experts' work on synthesis and application of the GRADE® method resulted in 30 recommendations. Among the formalized recommendations, 19 were found to have a high level of evidence (GRADE 1±) and ten a low level of evidence (GRADE 2±). For one recommendation, the GRADE methodology could not be fully applied, resulting in an expert opinion. Two questions did not find any response in the literature. After two rounds of rating and several amendments, strong agreement was reached for all the recommendations. CONCLUSIONS: Strong agreement among the experts was obtained to provide 30 recommendations for the elaboration and/or implementation of perioperative optimization programs in the highest number of surgical fields.

SARS-CoV-2 vaccination efficacy on hospitalisation and variants.

We report data regarding three countries with similar healthcare systems which had three different vaccinal strategies between 1st of January and 10th of April 2021: rapid full vaccination (Israel), rapid first-dose vaccination (United Kingdom) and a delayed vaccination strategy (France).

Tracheostomy and long-term mortality in ICU patients undergoing prolonged mechanical ventilation.

INTRODUCTION: In critically ill patients undergoing prolonged mechanical ventilation (MV), the difference in long-term outcomes between patients with or without tracheostomy remains unexplored. METHODS: Ancillary study of a prospective international multicentre observational cohort in 21 centres in France and Belgium, including 2087 patients, with a one-year follow-up after admission. We included patients with a MV duration ≥10 days, with or without tracheostomy. We explored the one-year mortality with a classical Cox regression model (adjustment on age, SAPS II, baseline diagnosis and withdrawal of life-sustaining therapies) and a Cox regression model using tracheostomy as a time-dependant variable. RESULTS: 29.5% patients underwent prolonged MV, out of which 25.6% received tracheostomy and 74.4% did not. At one-year, 45.2% patients had died in the tracheostomy group and 51.5% patients had died in the group without tracheostomy (p = 0.001). In the Cox-adjusted regression model, tracheostomy was not associated with improved one-year outcome (HR CI95 0.7 [0.5-1.001], p = 0.051), as well as in the model using tracheostomy as a time-dependent variable (OR CI 95 1 [0.7-1.4], p = 0.9). CONCLUSIONS: In our study, there was no statistically significant difference in the one-year mortality of patients undergoing prolonged MV when receiving tracheostomy or not. TRIAL REGISTRATION: NCT01367093.