Daily Anesthesiology Research Analysis

BACKGROUND: Two biological subphenotypes in acute respiratory distress syndrome (ARDS) have been identified in retrospective analyses, with differential clinical outcomes and post-hoc responses to investigational treatments. The ability to identify biological subphenotypes in real-time is unknown. We aimed to evaluate the feasibility of using the multisite ISPY COVID Network to prospectively evaluate biological subphenotypes in real-time. METHODS: This prospective, observational, cohort study enrolled patients with ARDS and severe acute hypoxaemic respiratory failure (AHRF) and assessed the feasibility of real-time stratification into biological subphenotypes using plasma concentrations of IL-6, soluble tumour necrosis factor-1 (TNFR1), and clinical variables. Participants were eligible if they were receiving mechanical ventilation, non-invasive positive pressure ventilation, or heated high flow nasal oxygen (at flow rates ≥30 L/min); had severe AHRF (defined by an SpO FINDINGS: From June 15, 2023, to Oct 31, 2024, 844 patients at 17 hospitals in the ISPY COVID Network across the USA were screened for the study. After 504 exclusions and two withdrawals of consent, 338 patients were enrolled. 124 (37%) of the enrolled cohort were classified as AHRF, and 214 (63%) were classified as ARDS. 199 (59%) of patients were male and 138 (41%) were female, and the median age at enrolment was 64 years (IQR 54-74). The majority of patients were white (239 [71%]). 250 (74%) of the enrolled cohort completed subphenotype assignment using fresh plasma and were defined as successfully subphenotyped. Successful real-time subphenotyping increased from 59 for the first 100 enrolled participants (59% [95% CI 49-69]) to 82 for the last 100 enrolled participants (82% [73-89]), meeting the predefined feasibility threshold. Median time to subphenotype assignment from blood collection in the overall cohort and the successfully subphenotyped subgroup was 2·2 h (IQR 1·5-19·8) and 1·9 h (1·3-2·3) from the time of blood collection, respectively. The hyperinflammatory subphenotype was identified in 61 (29%) of 214 participants with ARDS and 29 (23%) of the 124 participants with severe AHRF. Clinical outcomes including mortality, organ support-free days and ventilator-free days were worse in patients with hyperinflammatory ARDS compared with those with hypoinflammatory ARDS. INTERPRETATION: Rapid real-time biological subphenotyping for ARDS and severe AHRF in a multisite US hospital network is feasible; and successful real-time subphenotyping both improved over the study time-course and was completed within 2·2 h from study blood collection. These results support the feasibility of real-time precision trials of therapies targeting biological subphenotypes in ARDS. FUNDING: COVID R&D Consortium, Allergan, Amgen, Takeda Pharmaceutical Company, Ingenus Pharmaceuticals, Implicit Bioscience, Johnson & Johnson, Pfizer, Roche-Genentech, Apotex, FAST Grant from Emergent Venture George Mason University, and The Grove Foundation. This work was supported by the US Defense Threat Reduction Agency (MCDC-2013-001). This project has been funded in whole or in part with Federal funds from the US Department of Health and Human Services; Administration for Strategic Preparedness and Response; and Biomedical Advanced Research and Development Authority (MCDC-2014-001).

INTRODUCTION: Patients with malignant brain tumors exhibit a hypercoagulable state. The risk of postoperative deep venous thrombosis (DVT) is elevated. The association between intraoperative blood pressure and postoperative DVT in this population remains poorly defined. METHODS: This secondary analysis included adults undergoing elective craniotomy for presumed high-grade glioma from a randomized, double-blind, placebo-controlled trial. Intraoperative mean arterial pressure (MAP) was recorded invasively at 10-second intervals. Hypotension exposure was quantified as cumulative duration, area under the curve, and time-weighted average below absolute thresholds (65, 70, 75 mmHg) and relative thresholds (20%, 30%, 40% decrease from baseline). Baseline imbalances were assessed using absolute standardized differences (ASD), with a pre-specified threshold of 0.32 derived from pre-analysis adaptation to this neurosurgical cohort. Variables exceeding this threshold guided multivariable model construction. A 1:4 propensity score-matched sensitivity analysis was performed with conditional logistic regression. RESULTS: Among 480 patients, 41 (8.5%) developed postoperative lower-extremity DVT. One patient had confirmed pulmonary embolism. Fifteen baseline variables exceeded the pre-specified ASD threshold of 0.32. After adjustment for nine covariates in the expanded multivariable model, midline shift (adjusted OR 4.01, 95% CI 1.59-10.13, P=0.003) and surgery duration ≥5 hours (adjusted OR 2.96, 95% CI 1.40-6.27, P=0.004) remained independent risk factors. Cumulative duration below MAP 75 mmHg remained associated with DVT after comprehensive adjustment (adjusted OR per 10-minute increase 1.029, 95% CI 1.001-1.057, P=0.041). In the 1:4 propensity-matched cohort (n=205), this association persisted with an OR of 1.22 per 30-minute increase (95% CI 1.07-1.39, P=0.003). CONCLUSIONS: In patients undergoing craniotomy for presumed high-grade glioma, cumulative intraoperative hypotension below a MAP threshold of 75 mmHg is associated with postoperative DVT after rigorous confounder adjustment and propensity matching. These observational findings support consideration of MAP maintenance ≥75 mmHg in this high-risk population. Prospective validation is required.

OBJECTIVES: To evaluate the predictive performance of the Eleveld target-controlled infusion model for propofol during deep hypothermia, characterise temperature-dependent changes in propofol pharmacokinetics, and explore the relationship between depth of anaesthesia monitoring and the perioperative stress response during deep hypothermic circulatory arrest. DESIGN: Prospective, single-centre, low-intervention study. SETTING: Tertiary cardiac surgery centre. PATIENTS: Thirty adult patients undergoing elective pulmonary endarterectomy with cardiopulmonary bypass and deep hypothermic circulatory arrest. METHODS: Serial blood samples (T0-T13) were obtained to determine propofol serum concentrations and endogenous norepinephrine levels. Model performance of the Eleveld target-controlled infusion system was assessed using linear regression across temperature phases, and population pharmacokinetic analysis was performed using nonlinear mixed-effects modelling. RESULTS: Predictive performance deteriorated during cooling and improved during rewarming. A two-compartment model identified temperature as a significant covariate on propofol clearance, with marked reduction during hypothermia and relative increase during rewarming. Processed EEG monitoring demonstrated profound cortical suppression (mean suppression ratio 98.4%, PSI 0.4). Despite this, norepinephrine levels decreased during cooling and increased significantly during reperfusion, indicating activation of the stress response in the absence of cortical activity. No intraoperative awareness was detected. CONCLUSIONS: Deep hypothermia alters propofol pharmacokinetics, reducing clearance and impairing model performance, while rewarming increases clearance. Autonomic stress responses may occur despite profound cortical suppression, highlighting limitations of EEG-based depth of anaesthesia monitoring during deep hypothermic circulatory arrest. These findings support temperature-adaptive dosing and warrant confirmation in prospective randomised studies.