Daily Anesthesiology Research Analysis

BACKGROUND: The IMOTEC study aims to determine whether a point-of-care viscoelastic hemostatic assay (VHA)-guided algorithm is cost-effective for the management of ongoing bleeding. METHODS: Stepped wedge cluster randomized trial, patient blinded, conducted at 16 French academic cardiac surgery centers from 01/2017 to 02/2020. Adults undergoing elective or urgent cardiac surgery with ongoing bleeding were enrolled during 2 successive inclusion periods: 1) transfusion guided on standard hemostasis tests (control period), and 2) transfusion using a VHA-guided algorithm. The primary objective was to estimate the efficiency of VHA based on the 1-year incremental cost-utility ratio (ICUR, primary outcome). Secondary outcomes included transfusion, postoperative complications, duration of stay in-hospital, reintervention, and mortality. RESULTS: 1095 patients were randomized, and 1044 (95.3%) were analyzed. The mean utility was 0.60 (±0.30) in the VHA vs. 0.61 (±0.30) in the control period, adjusted difference, -0.01 [95% CI, -0.09 to 0.07]. The ICUR did not suggest that the VHA-guided algorithm was cost-effective. One-year mortality was 12.0% for VHA and 10.9% for control, Hazard Ratio, 1.69 [95% CI, 0.98 to 2.89], P =  .06. The frequency of plasma and platelet transfusions was significantly lower in the VHA compared to the control period (respectively, 48.8% vs. 72.4%, P <  0.0001 and 52.3% vs. 74.1%, P =  .0002), whereas fibrinogen administration was more frequent in the VHA period (58.4% vs. 47.0 %, P =  .002). The median in-hospital length of stay was significantly shorter in the VHA vs. control period: 11.0 days (8.0 to 18.0) vs. 14.0 (9.0 to 22.0), P =  .02. CONCLUSIONS: The ICUR did not suggest that VHA was cost-effective in cardiac surgery patients with ongoing bleeding, compared with standard tests. TRIAL REGISTRATION: Clinical trial submission: November 2, 2016 Registry name: Cost-Utility Analysis of Management of Peri Operative Hemorrhage Following Cardiac Surgery With Cardiopulmonary Bypass (IMOTEC) ClinicalTrials.gov Identifier: NCT02972684 URL registry: https://clinicaltrials.gov/study/NCT02972684.

BACKGROUND: Blood-brain barrier (BBB) dysfunction and neuroimmune inflammatory response are persistent in patients with perioperative neurocognitive disorders (PND). Despite the clinical evidence, the mechanisms linking leaky BBB to neuropathology remain poorly understood. Fibrinogen, a BBB leakage-derived blood protein, is implicated in neurodegenerative diseases, but its role in PND and the underlying mechanisms are unknown. METHODS: Here, we established PND model in aged mice with exploratory laparotomy. Behavioral testing, BBB permeability detection, transcriptional changes, immunofluorescence staining and western blot were employed to discern the neuropathology in PND. BV2 cells were used for in vitro studies. Interventions included uPA administration, intracerebroventricular injection antibody, PI3K inhibitor administration. RESULTS: Here, we show that fibrinogen binds to CD11b, which activates the PI3K/Akt/RhoA pathway in microglia, triggering neuroinflammation and cognitive deficits in aged PND model. In aged mice, fibrinogen is required for neurotoxic microglia polarization and proinflammatory factors increase after anesthesia and surgery. Antibody targeting fibrinogen-CD11b signaling provides protection from microglia activation and cognitive deficits in PND model. CONCLUSION: Our study identifies fibrinogen-CD11b signaling as a critical mediator driving age-dependent neuroinflammation and neuropathology in PND. Targeting of this signaling may represent a therapeutic intervention for PND. Our findings link vascular leakage and neuroimmune activation, providing mechanistic insights for PND intervention strategies.

BACKGROUND: Paediatric perioperative blood transfusion trends remain poorly described. The purpose of this study was to determine the incidence and associated outcomes of red blood cell (RBC) transfusion in paediatric surgical patients over a recent decade in North America. METHODS: This retrospective cohort study utilised data from the American College of Surgeons National Surgical Quality Improvement Program paediatric databases spanning a decade. Patients aged 0-18 yr who underwent noncardiac surgery were included. Patient characteristics and outcome variables were compared between patients exposed to a transfusion and those who were not using the Wilcoxon rank sum test for continuous variables and χ RESULTS: Among the 1 303 500 paediatric patients included during 2012-23, 82 742 (6.3%) received RBC transfusion in the perioperative period (defined as intraoperatively up to 72 h after surgery). There was an upward trajectory in paediatric transfusions over the 11-yr period, ranging from 4.7% (2016) to 7% (2021). The 30-day mortality rate in those transfused was 2.4% compared with 0.2% in those not transfused (adjusted P-value <0.001). Those transfused experienced more complications (adjusted P-value <0.001 for all comparisons) which was distinct for higher volumes given. Neonates and older children (≥12 yr old) had higher transfusion exposure at 13.3% and 9.6%, respectively. Neonates and children had higher associated rates of 30-day mortality (14.9% for neonates, 1.4% for children aged 1-6 yr) and adverse outcomes. Comparing death at 30 days with and without blood transfusion, there was an independent association between transfusion and 30-day mortality (adjusted odds ratio 2.11, 95% confidence interval 1.95-2.27). CONCLUSIONS: We describe the incidence of RBC transfusion and associated mortality over a decade for paediatric patients undergoing noncardiac surgery. Ongoing vigilance in perioperative transfusion management and tailored interventions to mitigate associated risks and optimise perioperative outcomes are needed in bleeding and anaemic paediatric surgical patients.