Charles Hugh Brown IV

All Publications

• Early Relative Hypotension Below Noninvasive Cerebral Oximetry-Derived Optimal Blood Pressure Thresholds in Aneurysmal Subarachnoid Hemorrhage: A Pilot Study. Critical care medicine Shah, V. A., Humayun, M., Radzik, B., Healy, R., Palmisano, C., Anderson-White, M., Calvillo, E., Geocadin, R., Brown, C., Hogue, C., Ziai, W., Cho, S. M., Suarez, J. I., Rivera-Lara, L. 2025

  Abstract

  Impairment in cerebral autoregulation (CA) after aneurysmal subarachnoid hemorrhage (aSAH) is associated with delayed cerebral ischemia (DCI) and poor outcomes. We assessed: 1) feasibility of defining CA-based optimal mean arterial pressure (MAPOpt) thresholds using noninvasive cerebral oximetry and 2) associations of relative hypotension below MAPOpt in the early brain injury (EBI) and pre-DCI phase with DCI and long-term outcomes after aSAH.Pilot observational study on a prospective cohort.Single-center Neuro-ICU.aSAH patients with altered consciousness.Continuous noninvasive cerebral oximetry neuromonitoring.Daily MAPOpt was defined as observed MAP (MAPObs) corresponding to lowest cerebral oximetry-derived autoregulation index. Outcomes included DCI and 1-year modified Rankin Scale (mRS). Mixed-effects linear regression assessed MAPOpt trajectories. Multivariable generalized estimating equation models assessed associations between daily %time below MAPOpt ± 5 mm Hg (MAPOpt range) and DCI and poor 1-year mRS (mRS 4-6). We included 118 daily MAPOpt measurements (118/128 epochs = 92.2% feasibility) estimated from 35 aSAH patients receiving cerebral oximetry monitoring for median duration of 4 days (interquartile range [IQR], 3-4 d), beginning on median of hospital day 2 (1-3). Median (IQR) age was 64 years (52-69 yr), World Federation of Neurological Surgeons grade 4 (2-5), and modified Fisher Scale 4 (3-4). DCI and poor 1-year outcome occurred in 15 (42.9%) and 20 (57.1%) patients, respectively. Patients that developed DCI had higher median MAPOpt (102.5 vs. 85 mm Hg; p = 0.03), upward trajectory of MAPOpt (β-coefficient = +19 mm Hg; p = 0.04 vs. +4 mm Hg; p = 0.56), and greater %time with MAPObs below MAPOpt range (39.7% vs. 12.7%; p = 0.01) in the early phase. In covariate-adjusted models, %time below MAPOpt range was independently associated with DCI and poor 1-year mRS (adjusted odds ratio, 1.02; 95% CI, 1.002-1.03; p = 0.03).Defining individualized MAPOpt thresholds using noninvasive cerebral oximetry was feasible. Relative hypotension below oximetry-based MAPOpt in the EBI and pre-DCI phase (days~2-6) was associated with DCI and poor long-term functional outcome, supporting further exploration of individualized hemodynamic optimization in the early phase of aSAH.

  View details for DOI 10.1097/CCM.0000000000006826

  View details for PubMedID 40826499

• The Impact of Cognitive Impairment on Cardiovascular Disease. Journal of the American College of Cardiology Jamil, Y., Krishnaswami, A., Orkaby, A. R., Stimmel, M., Brown Iv, C. H., Mecca, A. P., Forman, D. E., Rich, M. W., Nanna, M. G., Damluji, A. A. 2025; 85 (25): 2472-2491

  Abstract

  The older adult population is the fastest-growing segment of the U.S. population. Cardiovascular disease is common among older patients, which leads to excess morbidity, mortality, and health care utilization. Cognitive impairment is also common in older adults with cardiovascular disease and is expected to increase in parallel with cardiovascular disease because both conditions share the same underlying risk factors. Cardiovascular disease also exacerbates cognitive impairment through hypertension, cerebral hypoperfusion, inflammation, arrhythmia, emboli, and medication adverse events. Moreover, cognitive impairment can undermine the treatment of patients with cardiovascular disease because of changes in health literacy, adherence, and even the likelihood that guideline-directed medical and/or interventional management are under-prescribed. Patients with cognitive impairment are also more likely to endure delays in care and reduced participation in formative cardiovascular trials. In this State-of-the-Art review, we aim to: 1) examine the distinct types of cognitive impairment prevalent among cardiac patients; 2) explore the fundamental pathophysiology and mechanisms of cognitive impairment in adults with cardiovascular disease; 3) delineate the bidirectional impact of cognitive impairment and cardiovascular disease; and 4) discuss evidence-based management strategies to mitigate cognitive impairment in patients with cardiovascular diseases.

  View details for DOI 10.1016/j.jacc.2025.04.057

  View details for PubMedID 40562512

• Mind the messenger: role of extracellular vesicle signalling in postoperative neurocognitive dysfunction. British journal of anaesthesia Das, S., Devinney, M. J., Berger, M., Brown, C. H. 2025

  Abstract

  Extracellular vesicles are secreted by virtually every cell and allow the transfer of bioactive molecules including proteins, nucleic acids, and lipids to other cell types across the body. This study of the role of extracellular vesicles and their cargo in postoperative cognitive dysfunction after hip or knee replacement surgery reports differential protein and microRNA expression in patients with postoperative cognitive decline versus improvement. This small study in a select surgical population highlights the potential for extracellular vesicles and their contents to play a signalling role in postoperative neurocognitive disorders.

  View details for DOI 10.1016/j.bja.2025.03.003

  View details for PubMedID 40251056

• Continuous Monitoring of Cerebral Autoregulation in Adults Supported by Extracorporeal Membrane Oxygenation. Neurocritical care Zhang, L. Q., Chang, H., Kalra, A., Humayun, M., Rosenblatt, K. R., Shah, V. A., Geocadin, R. G., Brown, C. H., Kim, B. S., Whitman, G. J., Rivera-Lara, L., Cho, S. M. 2024

  Abstract

  Impaired cerebral autoregulation (CA) is one of several proposed mechanisms of acute brain injury in patients supported by extracorporeal membrane oxygenation (ECMO). The primary aim of this study was to determine the feasibility of continuous CA monitoring in adult ECMO patients. Our secondary aims were to describe changes in cerebral oximetry index (COx) and other metrics of CA over time and in relation to functional neurologic outcomes.This is a single-center prospective observational study. We measured COx, a surrogate measurement of cerebral blood flow measured by near-infrared spectroscopy, which is an index of CA derived from the moving correlation between mean arterial pressure (MAP) and slow waves of regional cerebral oxygen saturation. A COx value that approaches 1 indicates impaired CA. Using COx, we determined the optimal MAP (MAPOPT) and lower and upper limits of autoregulation for individual patients. These measurements were examined in relation to modified Rankin Scale (mRS) scores.Fifteen patients (median age 57 years [interquartile range 47-69]) with 150 autoregulation measurements were included for analysis. Eleven were on veno-arterial ECMO (VA-ECMO), and four were on veno-venous ECMO (VV-ECMO). Mean COx was higher on postcannulation day 1 than on day 2 (0.2 vs. 0.09, p < 0.01), indicating improved CA over time. COx was higher in VA-ECMO patients than in VV-ECMO patients (0.12 vs. 0.06, p = 0.04). Median MAPOPT for the entire cohort was highly variable, ranging from 55 to 110 mm Hg. Patients with mRS scores 0-3 (good outcome) at 3 and 6 months spent less time outside MAPOPT compared with patients with mRS scores 4-6 (poor outcome) (74% vs. 82%, p = 0.01). The percentage of time when observed MAP was outside the limits of autoregulation was higher on postcannulation day 1 than on day 2 (18.2% vs. 3.3%, p < 0.01).In ECMO patients, it is feasible to monitor CA continuously at the bedside. CA improved over time, most significantly between postcannulation days 1 and 2. CA was more impaired in VA-ECMO patients than in VV-ECMO patients. Spending less time outside MAPOPT may be associated with achieving a good neurologic outcome.

  View details for DOI 10.1007/s12028-023-01932-w

  View details for PubMedID 38326536

  View details for PubMedCentralID 8170265

• Continuous Monitoring of Cerebral Autoregulation in Adults Supported by Extracorporeal Membrane Oxygenation. Research square Zhang, L. Q., Chang, H., Kalra, A., Humayun, M., Rosenblatt, K. R., Shah, V. A., Geocadin, R. G., Brown, C. H., Kim, B. S., Whitman, G. J., Rivera-Lara, L., Cho, S. M. 2023

  Abstract

  Impaired cerebral autoregulation (CA) is one of several proposed mechanisms of acute brain injury in patients supported by extracorporeal membrane oxygenation (ECMO). The primary aim of this study was to determine the feasibility of continuous CA monitoring in adult ECMO patients. Our secondary aims were to describe changes in cerebral oximetry index (COx) and other metrics of CA over time and in relation to functional neurologic outcomes.This is a single-center prospective observational study. We measured Cox, a surrogate measurement of cerebral blood flow, measured by near-infrared spectroscopy, which is an index of CA derived from the moving correlation between mean arterial pressure and slow waves of regional cerebral oxygen saturation. A COx value that approaches 1 indicates impaired CA. Using COx, we determined the optimal MAP (MAPOPT), lower and upper limits of autoregulation for individual patients. These measurements were examined in relation to modified Rankin Scale (mRS) scores.Fifteen patients (median age=57 years [IQR=47-69]) with 150 autoregulation measurements were included for analysis. Eleven were on veno-arterial ECMO and 4 on veno-venous. Mean COx was higher on post-cannulation day 1 than on day 2 (0.2 vs 0.09, p<0.01), indicating improved CA over time. COx was higher in VA-ECMO patients than in VV-ECMO (0.12 vs 0.06, p=0.04). Median MAPOPT for entire cohort was highly variable, ranging 55-110 mmHg. Patients with mRS 0-3 (good outcome) at 3 and 6 months spent less time outside of MAPOPT compared to patients with mRS 4-6 (poor outcome) (74% vs 82%, p=0.01). The percentage of time when observed MAP was outside the limits of autoregulation was higher on post-cannulation day 1 than on day 2 (18.2% vs 3.3%, p<0.01).In ECMO patients, it is feasible to monitor CA continuously at the bedside. CA improved over time, most significantly between post-cannulation days 1 and 2. CA was more impaired in VA-ECMO than VV-ECMO. Spending less time outside of MAPOPT may be associated with achieving a good neurologic outcome.

  View details for DOI 10.21203/rs.3.rs-3300834/v1

  View details for PubMedID 37790309

  View details for PubMedCentralID PMC10543291

• CEREBRAL OXIMETRY-DERIVED OPTIMAL BLOOD PRESSURE TARGETS IN ANEURYSMAL SUBARACHNOID HEMORRHAGE Shah, V., Humayun, M., Radzik, B., Palmisano, C., Anderson-White, M., Calvillo, E., Chang, H., Zhang, L., Hogue, C., Brown, C., Suarez, J., Geocadin, R., Cho, S., Ziai, W., Rivera-Lara, L. LIPPINCOTT WILLIAMS & WILKINS. 2023: 253

  View details for Web of Science ID 000921450900495