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Background: The Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II randomized controlled trial used a tier-based management protocol based on brain tissue oxygen (PbtO 2 ) and intracranial pressure (ICP) monitoring to reduce brain tissue hypoxia after severe traumatic brain injury. We performed a secondary analysis to explore the relationship between brain tissue hypoxia, blood pressure (BP), and interventions to improve cerebral perfusion pressure (CPP). We hypothesized that BP management below the lower limit of autoregulation would lead to cerebral hypoperfusion and brain tissue hypoxia that could be improved with hemodynamic augmentation., Methods: Of the 119 patients enrolled in the Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II trial, 55 patients had simultaneous recordings of arterial BP, ICP, and PbtO 2 . Autoregulatory function was measured by interrogating changes in ICP and PbtO 2 in response to fluctuations in CPP using time-correlation analysis. The resulting autoregulatory indices (pressure reactivity index and oxygen reactivity index) were used to identify the "optimal" CPP and limits of autoregulation for each patient. Autoregulatory function and percent time with CPP outside personalized limits of autoregulation were calculated before, during, and after all interventions directed to optimize CPP., Results: Individualized limits of autoregulation were computed in 55 patients (mean age 38 years, mean monitoring time 92 h). We identified 35 episodes of brain tissue hypoxia (PbtO 2  < 20 mm Hg) treated with CPP augmentation. Following each intervention, mean CPP increased from 73 ± 14 mm Hg to 79 ± 17 mm Hg (p = 0.15), and mean PbtO 2 improved from 18.4 ± 5.6 mm Hg to 21.9 ± 5.6 mm Hg (p = 0.01), whereas autoregulatory function trended toward improvement (oxygen reactivity index 0.42 vs. 0.37, p = 0.14; pressure reactivity index 0.25 vs. 0.21, p = 0.2). Although optimal CPP and limits remained relatively unchanged, there was a significant decrease in the percent time with CPP below the lower limit of autoregulation in the 60 min after compared with before an intervention (11% vs. 23%, p = 0.05)., Conclusions: Our analysis suggests that brain tissue hypoxia is associated with cerebral hypoperfusion characterized by increased time with CPP below the lower limit of autoregulation. Interventions to increase CPP appear to improve autoregulation. Further studies are needed to validate the importance of autoregulation as a modifiable variable with the potential to improve outcomes., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Infarct growth rate (IGR) differs among patients with acute ischemic stroke due to large vessel occlusion (LVO-AIS), and this variability has critical clinical repercussions. We explored IGR patterns and their association with blood pressure during endovascular therapy (EVT)., Methods: This is a two-center cohort observational study that included consecutive anterior circulation LVO-AIS patients who underwent EVT and achieved modified Thrombolysis in Cerebral Infarction (mTICI) 2 c-3. Initial and final infarct volumes (FIV) were defined using admission computed tomography perfusion (CTP) defined as relative cerebral blood flow (rCBF) <30%, and diffusion-weighted imaging-magnetic resonance imaging (DWI-MRI) at 24 hours post-EVT. We categorized IGR patterns as exponential (ExpIGR) and Non-exponential (NonExp) based on their growth curves. We then dichotomized ExpIGR clinical significance based on the association of infarct growth with 90-day Modified Rankin Score (mRS) as ExpIGR-A ( > 13 mL) and ExpIGR-B (<13 mL). Intraprocedural blood pressure (BP) drops were calculated as the difference between median arterial pressure (MAP) at admission and the lowest intraprocedural MAP reading before recanalization, and the area between admission MAP threshold and all lower measurements of intraprocedural MAP. Logistic and linear regression were used to investigate associations between variables of interest., Results: Of 159 modified Thrombolysis in Cerebral Infarction (mTICI) 2 c-3 patients, we found that 36% demonstrated ExpIGR-A, 31% ExpIGR-B, and 32.7% NonExp patterns. The Exp-A and Exp-B groups differed significantly in National Institutes of Health Stroke Scale (NIHSS) score, Alberta Stroke Program Early CT Score (ASPECTS), glucose, and FIV. The Exp-A and NonExp groups differed in rCBF <30% vol, and time of stroke onset (SO) to admission CTP; and the Exp-B and NonExp groups in NIHSS, rCBF <30%, Tmax <6 s volume, collateral flow measured by hypoperfusion intensity ratio (HIR), and FIV. Hypotensive MAP area (HMA) was independently associated with an ExpIGR-A pattern. Infarct volume increased by 1 mL per 100 units of hypotensive area and 4.2 mL per 0.1 units of HIR, with a significant interaction between both variables., Conclusion: After an LVO-AIS, the IGR can be differentiated into two distinct exponential and non-exponential patterns. A subgroup of patients with the exponential pattern experienced clinically meaningful infarct growth rates between CTP acquisition and reperfusion and seem to be highly vulnerable to episodes of sustained intraprocedural BP drops during EVT., Competing Interests: Competing interests: NP reports research support from the NIH/NINDS (K23NS110980) and Liminal Sciences. SOG reports research support from the NIH-NINDS (R01NS127114-01), Stryker, Medtronic, Microvention, Methinks, IschemiaView, Viz.ai, and Siemens; and consulting fees from Medtronic and Stryker Neurovascular. The other authors do not report conflict of interests., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We aimed to describe the safety and efficacy of mechanical thrombectomy (MT) with or without intravenous thrombolysis (IVT) for patients with tandem lesions and whether using intraprocedural antiplatelet therapy influences MT's safety with IVT treatment., Methods: This is a subanalysis of a pooled, multicenter cohort of patients with acute anterior circulation tandem lesions treated with MT from 16 stroke centers between January 2015 and December 2020. Primary outcomes included symptomatic intracranial hemorrhage (sICH) and parenchymal hematoma type 2. Additional outcomes included hemorrhagic transformation, successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b-3), complete reperfusion (modified Thrombolysis in Cerebral Infarction score 3), favorable functional outcome (90-day modified Rankin Scale score 0-2), excellent functional outcome (90-day modified Rankin Scale score 0-1), in-hospital mortality, and 90-day mortality., Results: Of 691 patients, 512 were included (218 underwent IVT+MT and 294 MT alone). There was no difference in the risk of sICH (adjusted odds ratio [aOR], 1.22 [95% CI, 0.60-2.51]; P =0.583), parenchymal hematoma type 2 (aOR, 0.99 [95% CI, 0.47-2.08]; P =0.985), and hemorrhagic transformation (aOR, 0.95 [95% CI, 0.62-1.46]; P =0.817) between the IVT+MT and MT alone groups after adjusting for confounders. Administration of IVT was associated with an increased risk of sICH in patients who received intravenous antiplatelet therapy (aOR, 3.04 [95% CI, 0.99-9.37]; P =0.05). The IVT+MT group had higher odds of a 90-day modified Rankin Scale score 0 to 2 (aOR, 1.72 [95% CI, 1.01-2.91]; P =0.04). The odds of successful reperfusion, complete reperfusion, 90-day modified Rankin Scale score 0 to 1, in-hospital mortality, or 90-day mortality did not differ between the IVT+MT versus MT alone groups., Conclusions: Our study showed that the combination of IVT with MT for tandem lesions did not increase the overall risk of sICH, parenchymal hematoma type 2, or overall hemorrhagic transformation independently of the cervical revascularization technique used. However, intraprocedural intravenous antiplatelet therapy during acute stent implantation might be associated with an increased risk of sICH in patients who received IVT before MT. Importantly, IVT+MT treatment was associated with a higher rate of favorable functional outcomes at 90 days., Competing Interests: Disclosures A.E. Hassan is a consultant/speaker at Medtronic, Microvention, Stryker, Penumbra, Cerenovus, Genentech, GE Healthcare, Scientia, Balt, vizai, Insera therapeutics, Proximie, NeuroVasc, NovaSignal, Vesalio, Rapid Medical, Imperative Care and Galaxy Therapeutics; principal investigator for COMPLETE study—Penumbra, LVO SYNCHRONISE—vizai, Millipede Stroke Trial—Perfuze, RESCUE—ICAD, Medtronic; steering committee/publication committee member for SELECT, DAWN, SELECT 2, EXPEDITE II, EMBOLISE, CLEAR, ENVI, DELPHI, DISTALS. Dr Divani performed fundings at the University of New Mexico Center for Brain Recovery and Repair Center of Biomedical Research Excellence through Grant Number (NIH P20GM109089, Pilot PI), W81XWH-17-2-0053 (PI), 1R21NS130423-01 (PI). Dr Ribo is consultant at aptaTargets, Anaconda Biomed, Philips, Medtronic, Cerenovus, Vesalio, and Rapid Pulse outside the submitted work. Dr Abraham is a consultant at Penumbra Inc, Qapel, Stryker Corporation. Dr Fifi is a consultant at Cerenovus, Stryker Corporation, Microvention Inc; received stock from Cerebrotech, Imperative Care, Sime&Cure; and received grants from viz AI. Data and Safety Monitoring: MIVI. Dr Yoo is a consultant for Johnson & Johnson Medical Devices & Diagnostics Group—Latin America, LLC, Nicolab, Penumbra Inc, Philips, Vesalio, ZOLL Circulation Inc; received grants from Genetech, USA Inc, Johnson & Johnson Medical Devices & Diagnostics Group—Latin America, LLC, Medtronic, Penumbra Inc, Stryker; Employment at HCA Healthcare; received stock from Insera, Nicolab; performed data and safety monitoring at National Institutes of Health. Dr Mokin is a consultant at Johnson & Johnson Medical Devices & Diagnostics Group—Latin America, LLC, Medtronic, MicroVention Inc, received stock from Bendit Technology, BrainQ, Serenity medical, Synchrone. Dr Yavagal is a consultant at Athersys, Gravity Medical Technology, Johnson & Johnson Health Care Systems Inc, Medtronic USA Inc, Poseydon, Stryker Corporation, Vascular Dynamics; received stock from Athersys, Poseydon, Rapid Medical. Dr Jovin is a consultant at Contego Medical Inc received stock from Anaconda, Freeox Biotech, Galaxy, Kandu, Methinks, Route92, vizai. Grant: Medtronicm, USA, Inc, Stryker Corporation; performed data and safety monitoring at Johnson & Johnson, Cerenovus. Dr Sheth is a consultant at vizAI, Penumbra, Imperative Care; received grants from NIH, vizAI; and took ownership for Motif Neuroscience (not related to this article). Dr Ortega-Gutierrez received grants from NIH-NINDS (R01NS127114-01, R03NS126804), Stryker, Medtronics, Microvention, Penumbra, IschemiaView, vizai, and Siemens; he is a consultant at Medtronic and Stryker Neurovascular. The other authors report no conflicts.

Introduction: Observational studies have found an increased risk of hemorrhagic transformation and worse functional outcomes in patients with higher systolic blood pressure variability (BPV). However, the time-varying behavior of BPV after endovascular thrombectomy (EVT) and its effects on functional outcome have not been well characterized., Patients and Methods: We analyzed data from an international cohort of patients with large-vessel occlusion stroke who underwent EVT at 11 centers across North America, Europe, and Asia. Repeated time-stamped blood pressure data were recorded for the first 72 h after thrombectomy. Parameters of BPV were calculated in 12-h epochs using five established methodologies. Systolic BPV trajectories were generated using group-based trajectory modeling, which separates heterogeneous longitudinal data into groups with similar patterns., Results: Of the 2041 patients (age 69 ± 14, 51.4% male, NIHSS 15 ± 7, mean number of BP measurements 50 ± 28) included in our analysis, 1293 (63.4%) had a poor 90-day outcome (mRS ⩾ 3) or a poor discharge outcome (mRS ⩾ 3). We identified three distinct SBP trajectories: low (25%), moderate (64%), and high (11%). Compared to patients with low BPV, those in the highest trajectory group had a significantly greater risk of a poor functional outcome after adjusting for relevant confounders (OR 2.2; 95% CI 1.2-3.9; p  = 0.008). In addition, patients with poor outcomes had significantly higher systolic BPV during the epochs that define the first 24 h after EVT ( p  < 0.001)., Discussion and Conclusions: Acute ischemic stroke patients demonstrate three unique systolic BPV trajectories that differ in their association with functional outcome. Further research is needed to rapidly identify individuals with high-risk BPV trajectories and to develop treatment strategies for targeting high BPV., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Spiotta reports grants and personal fees from Penumbra, grants and personal fees from Stryker, grants from Medtronic, non-financial support from RAPID, personal fees from Terumo, and personal fees from Cerenovus outside the submitted work. Dr. Liman reports personal fees from Stryker outside the submitted work. Dr. de Havenon reports grants from AMAG and grants from Regeneron outside the submitted work. Dr. Ortega-Gutierrez reports grants from Stryker, IschemiaView, Viz.ai, and Siemens; personal fees from Medtronic and personal fees from Stryker outside the submitted work. Dr. Sheth reports grants from NIH, grants from AHA, grants from Hyperfine, grants from Biogen, grants from Zoll, and other support from Alva outside the submitted work., (© European Stroke Organisation 2022.)

Background: Evidence suggests that there are substantial inconsistencies in the practice of anesthesia. There has not yet been a comprehensive summary of the anesthesia literature that can guide future knowledge translation interventions to move evidence into practice. As the first step toward identifying the most promising interventions for systematic implementation in anesthesia practice, this scoping review of multicentre RCTs aimed to explore and map the existing literature investigating perioperative anesthesia-related interventions and clinical patient outcomes., Methods: Multicenter randomized controlled trials were eligible for inclusion if they involved a tested anesthesia-related intervention administered to adult surgical patients (≥ 16 years old), with a control group receiving either another anesthesia intervention or no intervention at all. The electronic databases Embase (via OVID), MEDLINE, and MEDLINE in Process (via OVID), and Cochrane Central Register of Control Trials (CENTRAL) were searched from inception to February 26, 2021. Studies were screened and data were extracted by pairs of independent reviewers in duplicate with disagreements resolved through consensus or a third reviewer. Data were summarized narratively., Results: We included 638 multicentre randomized controlled trials (n patients = 615,907) that met the eligibility criteria. The most commonly identified anesthesia-related intervention theme across all studies was pharmacotherapy (n studies = 361 [56.6%]; n patients = 244,610 [39.7%]), followed by anesthetic technique (n studies = 80 [12.5%], n patients = 48,455 [7.9%]). Interventions were most often implemented intraoperatively (n studies = 233 [36.5%]; n patients = 175,974 [28.6%]). Studies typically involved multiple types of surgeries (n studies = 187 [29.2%]; n patients = 206 667 [33.5%]), followed by general surgery only (n studies = 115 [18.1%]; n patients = 201,028 [32.6%]) and orthopedic surgery only (n studies = 94 [14.7%]; n patients = 34,575 [5.6%]). Functional status was the most commonly investigated outcome (n studies = 272), followed by patient experience (n studies = 168), and mortality (n studies = 153)., Conclusions: This scoping review provides a map of multicenter RCTs in anesthesia which can be used to optimize future research endeavors in the field. Specifically, we have identified key knowledge gaps in anesthesia that require further systematic assessment, as well as areas where additional research would likely not add value. These findings provide the foundation for streamlining knowledge translation in anesthesia in order to reduce practice variation and enhance patient outcomes., (© 2021. The Author(s).)