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Background: Frailty is a predictor of morbidity and mortality in older patients. This study aimed to investigate the influence of frailty status on likelihood, rate, duration, and severity of intraoperative hypotension (IOH), which can lead to severe organ dysfunction., Methods: Surgical patients (≥70 yr old) with preoperative frailty assessment were analysed retrospectively. Frailty status was defined as robust, prefrail, or frail based on modified Fried criteria. IOH was defined as mean arterial pressure <65 mm Hg. For likelihood, rate, duration, and severity of IOH, logistic and Poisson regression were used., Results: We included 2495 patients. There was no significant difference in likelihood of IOH. An increase of 9% in rate of IOH during surgery for prefrail (incidence rate ratio [IRR] 1.09 [95% CI 1.03-1.16], P=0.002), and 16% increase for frail patients (IRR 1.16 [1.04-1.29], P=0.007) was observed. During anaesthesia induction, prefrail patients exhibited a 28% increase in IOH (IRR 1.28 [1.12-1.47], P<0.001). Although there were no differences in the severity of IOH if surgery or anaesthesia induction duration was taken into account, frailty status was associated with a 15% longer time-weighted duration of IOH during anaesthesia induction (IRR 1.15 [1.06-1.24], P=0.001). Mediator analysis revealed that frailty status accounted for >90% after considering number of measured blood pressures and surgical duration and >70% after accounting for total propofol dose., Conclusions: Prefrail and frail patients aged ≥70 yr experienced up to 16% more IOH during surgery and 28% more during anaesthesia induction compared with robust patients. Preoperative optimisation (prehabilitation) and modification of intraoperative management (e.g. invasive blood pressure management) have the potential to reduce IOH in prefrail and frail patients., Competing Interests: Declaration of interest The authors declare that they have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The role of antithrombotic therapy in the prevention of ischemic stroke after non-cardiac surgery is unclear. In this study, we tested the hypothesis that the association of new-onset postoperative atrial fibrillation (POAF) on ischemic stroke can be mitigated by postoperative oral anticoagulation therapy. Of 251,837 adult patients (155,111 female (61.6%) and 96,726 male (38.4%)) who underwent non-cardiac surgical procedures at two sites, POAF was detected in 4,538 (1.8%) patients. The occurrence of POAF was associated with increased 1-year ischemic stroke risk (3.6% versus 2.3%; adjusted risk ratio (RRadj) = 1.60 (95% confidence interval (CI): 1.37-1.87), P < 0.001). In patients with POAF, the risk of developing stroke attributable to POAF was 1.81 (95% CI: 1.44-2.28; P < 0.001) without oral anticoagulation, whereas, in patients treated with anticoagulation, no significant association was observed between POAF and stroke (RRadj = 1.04 (95% CI: 0.71-1.51), P = 0.847, P for interaction = 0.013). Furthermore, we derived and validated a computational model for the prediction of POAF after non-cardiac surgery based on demographics, comorbidities and procedural risk. These findings suggest that POAF is predictable and associated with an increased risk of postoperative ischemic stroke in patients who do not receive postoperative anticoagulation., Competing Interests: Competing interests M.E. receives funding from the National Institutes of Health (NIH) (R01AG065554 and R01HL132887) that does not pertain to this manuscript. He holds two patents for acyclic curcubiturils for reversal of drugs of abuse and neuromuscular blocking agents (patent numbers 9956229 and 9469648). He is a member of the associated editorial board for the British Journal of Anaesthesia. D.L.B. discloses the following relationships. Advisory Board: Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma and Stasys; Board of Directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options) and High Enroll (stock); Consultant: Broadview Ventures, Hims, SFJ and Youngene; Data Monitoring Committee: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (chair, PEITHO trial), Cleveland Clinic, Contego Medical (chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute and Rutgers University (for the NIH-funded MINT Trial); Honoraria: American College of Cardiology (ACC) (senior associate editor, Clinical Trials and News; chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee, funded by Boehringer Ingelheim; AEGIS-II executive committee, funded by CSL Behring), Belvoir Publications (editor in chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (American Heart Association lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor in chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor and associate editor), K2P (co-chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (course director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee and steering committee and USA national co-leader, funded by Bayer), WebMD (CME steering committees) and Wiley (steering committee); Other: Clinical Cardiology (deputy editor); Patent: sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital, assigned to Lexicon; neither D.L.B. nor Brigham and Women's Hospital receive any income from this patent); Research Funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Eli Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene and 89Bio; Royalties: Elsevier (editor, Braunwald’s Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte and Vascular Solutions; Trustee: ACC; Unfunded Research: FlowCo. M.S.S. received funding for investigator-initiated studies from Merck & Co., which does not pertain to this manuscript. He is an associate editor for BMC Anesthesiology. He received honoraria for lectures from Fisher & Paykel Healthcare and Mindray Medical International Limited. He received an unrestricted philanthropic grant from Jeff and Judy Buzen. All other authors have no support from any organization for the submitted work, no financial relationships with any organizations that might have an interest in the submitted work and no other relationships or activities that could appear to have influenced the submitted work., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Study Objective: A low dynamic driving pressure during mechanical ventilation for general anesthesia has been associated with a lower risk of postoperative respiratory complications (PRC), a key driver of healthcare costs. It is, however, unclear whether maintaining low driving pressure is clinically relevant to measure and contain costs. We hypothesized that a lower dynamic driving pressure is associated with lower costs., Design: Multicenter retrospective cohort study., Setting: Two academic healthcare networks in New York and Massachusetts, USA., Patients: 46,715 adult surgical patients undergoing general anesthesia for non-ambulatory (inpatient and same-day admission) surgery between 2016 and 2021., Interventions: The primary exposure was the median intraoperative dynamic driving pressure., Measurements: The primary outcome was direct perioperative healthcare-associated costs, which were matched with data from the Healthcare Cost and Utilization Project-National Inpatient Sample (HCUP-NIS) to report absolute differences in total costs in United States Dollars (US$). We assessed effect modification by patients' baseline risk of PRC (score for prediction of postoperative respiratory complications [SPORC] ≥ 7) and effect mediation by rates of PRC (including post-extubation saturation < 90%, re-intubation or non-invasive ventilation within 7 days) and other major complications., Main Results: The median intraoperative dynamic driving pressure was 17.2cmH 2 O (IQR 14.0-21.3cmH 2 O). In adjusted analyses, every 5cmH 2 O reduction in dynamic driving pressure was associated with a decrease of -0.7% in direct perioperative healthcare-associated costs (95%CI -1.3 to -0.1%; p = 0.020). When a dynamic driving pressure below 15cmH 2 O was maintained, -US$340 lower total perioperative healthcare-associated costs were observed (95%CI -US$546 to -US$132; p = 0.001). This association was limited to patients at high baseline risk of PRC (n = 4059; -US$1755;97.5%CI -US$2495 to -US$986; p < 0.001), where lower risks of PRC and other major complications mediated 10.7% and 7.2% of this association (p < 0.001 and p = 0.015, respectively)., Conclusions: Intraoperative mechanical ventilation targeting low dynamic driving pressures could be a relevant measure to reduce perioperative healthcare-associated costs in high-risk patients., Competing Interests: Declaration of competing interest Daniel Talmor received speaking fees and grant funds from Hamilton Medical, Inc. and Mindray Medical, outside the submitted work. Matthias Eikermann received grants from Merck & Co and serves as an Associate Editor for the British Journal of Anaesthesia. Maximilian S. Schaefer received funding for investigator-initiated studies from Merck & Co., which do not pertain to this manuscript. He is an associate editor for BMC Anesthesiology. He received honoraria for lectures from Fisher & Paykel Healthcare and Mindray Medical International Limited. He received an unrestricted philanthropic grant from Dr. Jeffrey and Judith Buzen. All other authors have no support from any organization for the submitted work, no financial relationships with any organizations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work. This work was supported by an unrestricted grant from Dr. Jeffrey and Judith Buzen to Maximilian S. Schaefer. Dr. Jeffrey and Judith Buzen had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication., (Copyright © 2024. Published by Elsevier Inc.)

Background: Recruitment maneuvers are used in patients with ARDS to enhance oxygenation and lung mechanics. Heterogeneous lung and chest-wall mechanics lead to unpredictable transpulmonary pressures and could impact recruitment maneuver success. Tailoring care based on individualized transpulmonary pressure might optimize recruitment, preventing overdistention. This study aimed to identify the optimal transpulmonary pressure for effective recruitment and to explore its association with baseline characteristics., Methods: We performed post hoc analysis on the Esophageal Pressure Guided Ventilation (EpVent2) trial. We estimated the dose-response relationship between end-recruitment end-inspiratory transpulmonary pressure and the change in lung elastance after a recruitment maneuver by using logistic regression weighted by a generalized propensity score. A positive change in lung elastance was indicative of overdistention. We examined how patient characteristics, disease severity markers, and respiratory parameters predict transpulmonary pressure by using multivariate linear regression models and dominance analyses., Results: Of 121 subjects, 43.8% had a positive change in lung elastance. Subjects with a positive change in lung elastance had a mean ± SD transpulmonary pressure of 15.1 ± 4.9 cm H 2 O, compared with 13.9 ± 3.9 cm H 2 O in those with a negative change in lung elastance. Higher transpulmonary pressure was associated with increased probability of a positive change in lung elastance (adjusted odds ratio 1.35 per 1 cm H 2 O of transpulmonary pressure, 95% CI 1.13-1.61; P = .001), which indicated an S-shaped dose-response curve, with overdistention probability > 50% at transpulmonary pressure values > 18.3 cm H 2 O. The volume of recruitment was transpulmonary pressure-dependent ( P < .001; R 2 = 0.49) and inversely related to a change in lung elastance after adjusting for baseline lung elastance ( P < .001; R 2 = 0.43). Negative correlations were observed between transpulmonary pressure and body mass index, PEEP, Sequential Organ Failure Assessment score, and P aO 2 /F IO 2 , whereas baseline lung elastance showed a positive correlation. The body mass index emerged as the dominant negative predictor of transpulmonary pressure (ranking 1; contribution to R 2 = 0.08), whereas pre-recruitment elastance was the sole positive predictor (contribution to R 2 = 0.06)., Conclusions: Higher end-recruitment transpulmonary pressure increases the volume of recruitment but raises the risk of overdistention, providing the rationale for transpulmonary pressure to be used as a clinical target. Predictors, for example, body mass index, could guide recruitment maneuver individualization to balance adequate volume gain with overdistention., (Copyright © 2024 by Daedalus Enterprises.)

Background: Previous studies suggested that surgeon sex is associated with differential patient outcomes. Whether this also applies to anaesthesia providers is unclear. We hypothesised that female sex of the primary anaesthesia provider is associated with lower risk of perioperative complications., Methods: The first case for all adult patients undergoing anaesthesia care between 2008 and 2022 at two academic healthcare networks in the USA was included in this retrospective cohort study. The primary exposure was the sex of the anaesthesia provider who spent the most time in the operating theatre during the case. The primary outcome was intraoperative complications, defined as hypotension (mean arterial blood pressure <55 mm Hg for ≥5 cumulative minutes) or hypoxaemia (oxygen saturation <90% for >2 consecutive minutes). The co-primary outcome was 30-day adverse postoperative events (including complications, readmission, and mortality). Analyses were adjusted for a priori defined confounders., Results: Among 364,429 included patients, 57,550 (15.8%) experienced intraoperative complications and 55,168 (15.1%) experienced adverse postoperative events. Care by female compared with male anaesthesia providers was associated with lower risk of intraoperative complications (adjusted odds ratio [aOR] 0.95, 95% confidence interval [CI] 0.94-0.97, P<0.001), which was magnified among non-trainees (aOR 0.84, 95% CI 0.82-0.87, P-for-interaction<0.001). Anaesthesia provider sex was not associated with the composite of adverse postoperative events (aOR 1.00, 95% CI 0.98-1.02, P=0.88)., Conclusions: Care by a female anaesthesia provider was associated with a lower risk of intraoperative complications, which was magnified among non-trainees. Future studies should investigate underlying mechanisms., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: ChatGPT is an AI platform whose relevance in the peer review of scientific articles is steadily growing. Nonetheless, it has sparked debates over its potential biases and inaccuracies. This study aims to assess ChatGPT's ability to qualitatively emulate human reviewers in scientific research., Methods: We included the first submitted version of the latest twenty original research articles published by the 3rd of July 2023, in a high-profile medical journal. Each article underwent evaluation by a minimum of three human reviewers during the initial review stage. Subsequently, three researchers with medical backgrounds and expertise in manuscript revision, independently and qualitatively assessed the agreement between the peer reviews generated by ChatGPT version GPT-4 and the comments provided by human reviewers for these articles. The level of agreement was categorized into complete, partial, none, or contradictory., Results: 720 human reviewers' comments were assessed. There was a good agreement between the three assessors (Overall kappa >0.6). ChatGPT's comments demonstrated complete agreement in terms of quality and substance with 48 (6.7 %) human reviewers' comments, partially agreed with 92 (12.8 %), identifying issues necessitating further elaboration or recommending supplementary steps to address concerns, had no agreement with a significant 565 (78.5 %), and contradicted 15 (2.1 %). ChatGPT comments on methods had the lowest proportion of complete agreement (13 comments, 3.6 %), while general comments on the manuscript displayed the highest proportion of complete agreement (17 comments, 22.1 %)., Conclusion: ChatGPT version GPT-4 has a limited ability to emulate human reviewers within the peer review process of scientific research., Competing Interests: Declaration of competing interest Maximilian S. Schaefer received funding for investigator-initiated studies from Merck & Co., which do not pertain to this manuscript. He is an associate editor for BMC Anesthesiology. He received honoraria for presentations from Fisher & Paykel Healthcare and Mindray Medical International Limited and an unrestricted philantropic grant from Jeffrey and Judith Buzen. All other authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Acetaminophen and 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists are administered as standard prophylaxes for postoperative pain, nausea, and vomiting. Preclinical studies, however, suggest that 5-HT3 antagonists may compromise acetaminophen's analgesic effect. This hospital registry study investigates whether 5-HT3 antagonists mitigate the analgesic effect of prophylactic acetaminophen in a perioperative setting., Methods: This study included 55,016 adult patients undergoing general anesthesia for ambulatory procedures at a tertiary healthcare center in Massachusetts from 2015 to 2022. Using binary exposure variables and a comprehensive selection of preplanned patient- and procedure-related covariates for confounder control, the authors investigated whether intraoperative 5-HT3 antagonists affected the association between pre- or intraoperative acetaminophen and postoperative opioid consumption, gauged by opioid dose in milligram oral morphine equivalents (OME) administered in the postanesthesia care unit. A multivariable, zero-inflated negative binomial regression model was applied., Results: A total of 3,166 patients (5.8%) received only acetaminophen, 15,438 (28.1%) only 5-HT3 antagonists, 31,850 (57.9%) both drugs, and 4,562 (8.3%) neither drug. The median postanesthesia care unit opioid dose was 7.5 mg OME (interquartile range, 7.5 to 14.3 mg OME) among 16,640 of 55,016 (30.2%) patients who received opioids, and the mean opioid dose was 3.2 mg OME across all patients (maximum cumulative dose, 20.4 mg OME). Acetaminophen administration was associated with a -5.5% (95% CI, -9.6 to -1.4%; P = 0.009; adjusted absolute difference, -0.19 mg OME; 95% CI, -0.33 to -0.05; P = 0.009) reduction in opioid consumption among patients who did not receive a 5-HT3 antagonist, while there was no effect in patients who received a 5-HT3 antagonist (adjusted absolute difference, 0.00 mg OME; 95% CI, -0.06 to 0.05; P = 0.93; P for interaction = 0.013)., Conclusions: A dose-dependent association of pre- or intraoperative acetaminophen with decreased postoperative opioid consumption was not observed when 5-HT3 antagonists were coadministered, suggesting that physicians might consider reserving 5-HT3 antagonists as rescue medication for postoperative nausea or vomiting when acetaminophen is administered for pain prophylaxis., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

Introduction: Perioperative opioid use has been associated with adverse clinical outcomes. Additionally, opioid disposal carries significant costs, due to the waste of pharmaceutical products and the time needed by skilled labor to report the waste. In this study, we aimed to estimate costs and predict factors of opioid-associated intraoperative product waste, as well as to evaluate whether higher intraoperative opioid doses are associated with increased risk of adverse postoperative outcomes., Methods: We included 170,607 patients undergoing general anesthesia and receiving intraoperative fentanyl, hydromorphone, or morphine at Beth Israel Deaconess Medical Center, Boston, MA, USA, between January 2010 and June 2020. We estimated product waste-associated costs based on various opioid syringe sizes and determined predictors of opioid waste. Further, we evaluated whether higher opioid doses were associated with postoperative adverse events according to the severity-indexed, incident report-based medication error-reporting program classification. The primary outcome included post-extubation desaturation, postoperative nausea or vomiting, or postoperative somnolence or sedation., Results: The use of the smallest syringe sizes (50 mcg for fentanyl, 0.2 mg for hydromorphone, and 2 mg for morphine) resulted in the lowest product waste-associated costs. The main predictor of opioid waste was the administration of more than one intraoperative opioid (adjusted odds ratio [aOR] = 7.64, 95% CI 7.40-7.89, P < 0.001). Intraoperative doses of fentanyl > 50-100 mcg (aOR = 1.17 [1.10-1.25], P < 0.001, adjusted risk difference [ARD] 2%) and > 100 mcg (aOR = 1.24 [1.16-1.33], P < 0.001, ARD 3%), hydromorphone > 1 mg (aOR = 1.13 [1.06-1.20], P < 0.001, ARD 2%), and morphine > 2-4 mg (aOR = 1.26 [1.02-1.56], P = 0.04, ARD 3%) and > 4 mg (aOR = 1.45 [1.18-1.77], P < 0.001, ARD 5%) were associated with higher risk of the primary outcome., Conclusion: Smaller syringe sizes of intraoperative opioids may help to reduce product waste and associated costs, as well postoperative adverse events through utilization of lower intraoperative opioid doses., (© 2024. The Author(s).)

Rationale: Lung-protective mechanical ventilation strategies have been proven beneficial in the operating room (OR) and the ICU. However, differential practices in ventilator management persist, often resulting in adjustments of ventilator parameters when transitioning patients from the OR to the ICU. Objectives: To characterize patterns of ventilator adjustments during the transition of mechanically ventilated surgical patients from the OR to the ICU and assess their impact on 28-day mortality. Methods: Hospital registry study including patients undergoing general anesthesia with continued, controlled mechanical ventilation in the ICU between 2008 and 2022. Ventilator parameters were assessed 1 hour before and 6 hours after the transition. Measurements and Main Results: Of 2,103 patients, 212 (10.1%) died within 28 days. Upon OR-to-ICU transition, V T and driving pressure decreased (-1.1 ml/kg predicted body weight [IQR, -2.0 to -0.2]; P  < 0.001; and -4.3 cm H 2 O [-8.2 to -1.2]; P  < 0.001). Concomitantly, respiratory rates increased (+5.0 breaths/min [2.0 to 7.5]; P  < 0.001), resulting overall in slightly higher mechanical power (MP) in the ICU (+0.7 J/min [-1.9 to 3.0]; P  < 0.001). In adjusted analysis, increases in MP were associated with a higher 28-day mortality rate (adjusted odds ratio, 1.10; 95% confidence interval, 1.06-1.14; P  < 0.001; adjusted risk difference, 0.7%; 95% confidence interval, 0.4-1.0, both per 1 J/min). Conclusion: During transition of mechanically ventilated patients from the OR to the ICU, ventilator adjustments resulting in higher MP were associated with a greater risk of 28-day mortality.

Purpose: Latent class analysis (LCA) has identified hyper- and non-hyper-inflammatory subphenotypes in patients with acute respiratory distress syndrome (ARDS). It is unknown how early inflammatory subphenotypes can be identified in patients at risk of ARDS. We aimed to test for inflammatory subphenotypes upon presentation to the emergency department., Methods: LIPS-A was a trial of aspirin to prevent ARDS in at-risk patients presenting to the emergency department. In this secondary analysis, we performed LCA using clinical, blood test, and biomarker variables., Results: Among 376 (96.4%) patients from the LIPS-A trial, two classes were identified upon presentation to the emergency department (day 0): 72 (19.1%) patients demonstrated characteristics of a hyper-inflammatory and 304 (80.9%) of a non-hyper-inflammatory subphenotype. 15.3% of patients in the hyper- and 8.2% in the non-hyper-inflammatory class developed ARDS (p = 0.07). Patients in the hyper-inflammatory class had fewer ventilator-free days (median [interquartile range, IQR] 28[23-28] versus 28[27-28]; p = 0.010), longer intensive care unit (3[2-6] versus 0[0-3] days; p < 0.001) and hospital (9[6-18] versus 5[3-9] days; p < 0.001) length of stay, and higher 1-year mortality (34.7% versus 20%; p = 0.008). Subphenotypes were identified on day 1 and 4 in a subgroup with available data (n = 244). 77.9% of patients remained in their baseline class throughout day 4. Patients with a hyper-inflammatory subphenotype throughout the study period (n = 22) were at higher risk of ARDS (36.4% versus 10.4%; p = 0.003)., Conclusion: Hyper- and non-hyper-inflammatory subphenotypes may precede ARDS development, remain identifiable over time, and can be identified upon presentation to the emergency department. A hyper-inflammatory subphenotype predicts worse outcomes., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

The endovascular filament perforation model to mimic subarachnoid hemorrhage (SAH) is a commonly used model - however, the technique can cause a high mortality rate as well as an uncontrollable volume of SAH and other intracranial complications such as stroke or intracranial hemorrhage. In this protocol, a standardized SAH mouse model is presented, induced by endovascular filament perforation, combined with magnetic resonance imaging (MRI) 24 h after operation to ensure the correct bleeding site and exclude other relevant intracranial pathologies. Briefly, C57BL/6J mice are anesthetized with an intraperitoneal ketamine/xylazine (70 mg/16 mg/kg body weight) injection and placed in a supine position. After midline neck incision, the common carotid artery (CCA) and carotid bifurcation are exposed, and a 5-0 non-absorbable monofilament polypropylene suture is inserted in a retrograde fashion into the external carotid artery (ECA) and advanced into the common carotid artery. Then, the filament is invaginated into the internal carotid artery (ICA) and pushed forward to perforate the anterior cerebral artery (ACA). After recovery from surgery, mice undergo a 7.0 T MRI 24 h later. The volume of bleeding can be quantified and graded via postoperative MRI, enabling a robust experimental SAH group with the option to perform further subgroup analyses based on blood quantity.