@article{MTMT:33218349, title = {Impact of Chronological Age and Biological Sex on Cerebrovascular Reactivity in Moderate/Severe Traumatic Brain Injury: A CAnadian High-Resolution Traumatic Brain Injury (CAHR-TBI) Study}, url = {https://m2.mtmt.hu/api/publication/33218349}, author = {Batson, Carleen and Froese, Logan and Sekhon, Mypinder and Griesdale, Donald and Gomez, Alwyn and Thelin, Eric P. and Raj, Rahul and Aries, Marcel and Gallagher, Clare and Bernard, Francis and Kramer, Andreas H. and Zeiler, Frederick A.}, doi = {10.1089/neu.2022.0293}, journal-iso = {J NEUROTRAUM}, journal = {JOURNAL OF NEUROTRAUMA}, volume = {40}, unique-id = {33218349}, issn = {0897-7151}, abstract = {Impaired cerebrovascular reactivity has emerged as an important associate with poor long-term outcome after moderate/severe traumatic brain injury (TBI). However, our understanding of what drives or modulates the degree of impaired cerebrovascular function remains poor. Age and biological sex remain important modifiers of cerebrovascular function in health and disease, yet their impact on cerebrovascular reactivity after TBI remains unclear. The aim of this study was to explore subgroup responses based on age and biological sex on cerebral physiology. Data from 283 TBI patients from the CAnadian High Resolution TBI (CAHR-TBI) Research Collaborative were evaluated. Cerebrovascular reactivity was determined using high-frequency cerebral physiology for the derivation of three intracranial pressure (ICP)-based indices: 1) pressure reactivity index (PRx)-correlation between ICP and mean arterial pressure (MAP); 2) pulse amplitude index (PAx)-correlation between pulse amplitude of ICP (AMP) and MAP; and 3) RAC-correlation between AMP and cerebral perfusion pressure (CPP). Insult burden (% time above clinically defined thresholds) were calculated for these indices. These cerebral physiology indices were studied for their relationship with age via linear regression, age trichotomization (< 40, 40 - 60, > 60), and decades of age (< 30, 30-39, 40-49, 50-59, 60-69, > 69) schemes. Similarly, differences based on biological sex were assessed. A statistically significant positive linear correlation was found between PAx, RAC, and age. In corollary, a statistically significant relationship was found between increasing age on trichotomized and decades of age analysis with PAx and RAC measures. PRx failed to demonstrate such relationships to advancing age. There was no clear difference in cerebrovascular reactivity profiles between biological sex categories. These findings suggest that AMP-based cerebrovascular reactivity indices may be better positioned to detect impairment in TBI patients with advancing age. Further investigation into the utility of PAx and RAC is required, as they may prove useful for certain subgroups of patients.}, keywords = {AGE; Cerebrovascular reactivity; Rac; biological sex; PRx; Pax}, year = {2023}, eissn = {1557-9042}, pages = {1098-1111}, orcid-numbers = {Raj, Rahul/0000-0003-4243-9591} } @article{MTMT:33937372, title = {Neurological and respiratory effects of lung protective ventilation in acute brain injury patients without lung injury: brain vent, a single centre randomized interventional study}, url = {https://m2.mtmt.hu/api/publication/33937372}, author = {Beqiri, Erta and Smielewski, Peter and Guerin, Claude and Czosnyka, Marek and Robba, Chiara and Bjertnaes, Lars and Frisvold, Shirin K.}, doi = {10.1186/s13054-023-04383-z}, journal-iso = {CRIT CARE}, journal = {CRITICAL CARE}, volume = {27}, unique-id = {33937372}, issn = {1364-8535}, abstract = {Introduction Lung protective ventilation (LPV) comprising low tidal volume ( VT) and high positive end-expiratory pressure (PEEP) may compromise cerebral perfusion in acute brain injury (ABI). In patients with ABI, we investigated whether LPV is associated with increased intracranial pressure (ICP) and/or deranged cerebral autoregulation (CA), brain compensatory reserve and oxygenation. Methods In a prospective, crossover study, 30 intubated ABI patients with normal ICP and no lung injury were randomly assigned to receive low VT [6 ml/kg/predicted (pbw)]/at either low (5 -cmH(2)O) or high PEEP (12 -cmH(2)O). Between each intervention, baseline ventilation ( VT 9 ml/kg/pbw and PEEP 5 -cmH(2)O) were resumed. The safety limit for interruption of the intervention was ICP above 22 mmHg for more than 5 min. Airway and transpulmonary pressures were continuously monitored to assess respiratory mechanics. We recorded ICP by using external ventricular drainage or a parenchymal probe. CA and brain compensatory reserve were derived from ICP waveform analysis. Results We included 27 patients (intracerebral haemorrhage, traumatic brain injury, subarachnoid haemorrhage), of whom 6 reached the safety limit, which required interruption of at least one intervention. For those without intervention interruption, the ICP change from baseline to "low VT/low PEEP" and "low VT/high PEEP" were 2.2 mmHg and 2.3 mmHg, respectively, and considered clinically non-relevant. None of the interventions affected CA or oxygenation significantly. Interrupted events were associated with high baseline ICP (p < 0.001), low brain compensatory reserve (p < 0.01) and mechanical power (p < 0.05). The transpulmonary driving pressure was 5 +/- 2 -cmH(2)O in both interventions. Partial arterial pressure of carbon dioxide was kept in the range 34-36 mmHg by adjusting the respiratory rate, hence, changes in carbon dioxide were not associated with the increase in ICP. Conclusions The present study found that most patients did not experience any adverse effects of LPV, neither on ICP nor CA. However, in almost a quarter of patients, the ICP rose above the safety limit for interrupting the interventions. Baseline ICP, brain compensatory reserve, and mechanical power can predict a potentially deleterious effect of LPV and can be used to personalize ventilator settings.}, keywords = {traumatic brain injury; Intracranial Pressure; Positive end-expiratory pressure; Cerebral autoregulation; Acute brain injury; Subarachnoid haemorrhage; Lung protective ventilation; transpulmonary pressure}, year = {2023}, eissn = {1466-609X} } @article{MTMT:34021464, title = {The lower limit of reactivity as a potential individualised cerebral perfusion pressure target in traumatic brain injury : a CENTER-TBI high-resolution sub-study analysis}, url = {https://m2.mtmt.hu/api/publication/34021464}, author = {Beqiri, Erta and Zeiler, Frederick A and Ercole, Ari and Placek, Michal M and Tas, Jeanette and Donnelly, Joseph and Aries, Marcel J H and Hutchinson, Peter J and Menon, David and Stocchetti, Nino and Czosnyka, Marek and Smielewski, Peter}, doi = {10.1186/s13054-023-04485-8}, journal-iso = {CRIT CARE}, journal = {CRITICAL CARE}, volume = {27}, unique-id = {34021464}, issn = {1364-8535}, abstract = {A previous retrospective single-centre study suggested that the percentage of time spent with cerebral perfusion pressure (CPP) below the individual lower limit of reactivity (LLR) is associated with mortality in traumatic brain injury (TBI) patients. We aim to validate this in a large multicentre cohort.Recordings from 171 TBI patients from the high-resolution cohort of the CENTER-TBI study were processed with ICM+ software. We derived LLR as a time trend of CPP at a level for which the pressure reactivity index (PRx) indicates impaired cerebrovascular reactivity with low CPP. The relationship with mortality was assessed with Mann-U test (first 7-day period), Kruskal-Wallis (daily analysis for 7 days), univariate and multivariate logistic regression models. AUCs (CI 95%) were calculated and compared using DeLong's test.Average LLR over the first 7 days was above 60 mmHg in 48% of patients. %time with CPP < LLR could predict mortality (AUC 0.73, p = < 0.001). This association becomes significant starting from the third day post injury. The relationship was maintained when correcting for IMPACT covariates or for high ICP.Using a multicentre cohort, we confirmed that CPP below LLR was associated with mortality during the first seven days post injury.}, keywords = {traumatic brain injury; Cerebral autoregulation; Lower limit of reactivity; Individualised cerebral perfusion pressure}, year = {2023}, eissn = {1466-609X}, orcid-numbers = {Czeiter, Endre/0000-0002-9578-6944} } @article{MTMT:33936272, title = {Cerebrovascular Reactivity Is Not Associated With Therapeutic Intensity in Adult Traumatic Brain Injury: A Validation Study}, url = {https://m2.mtmt.hu/api/publication/33936272}, author = {Froese, Logan and Gomez, Alwyn and Sainbhi, Amanjyot Singh and Vakitbilir, Nuray and Marquez, Izzy and Amenta, Fiorella and Park, Kangyun and Stein, Kevin Y. and Thelin, Eric P. and Zeiler, Frederick A.}, doi = {10.1089/neur.2023.0011}, journal-iso = {NEUROTRAUMA REP}, journal = {NEUROTRAUMA REPORTS}, volume = {4}, unique-id = {33936272}, abstract = {Within traumatic brain injury (TBI) care, there is growing interest in pathophysiological markers as surrogates of disease severity, which may be used to improve and individualize care. Of these, assessment of cerebrovascular reactivity (CVR) has been extensively studied given that it is a consistent, independent factor associated with mortality and functional outcome. However, to date, the literature supports little-to-no impact of current guideline-supported therapeutic interventions on continuously measured CVR. Previous work in this area has suffered from a lack of validation studies, given the rarity of time-matched high-frequency cerebral physiology with serially recorded therapeutic interventions; thus, we undertook a validation study. Utilizing the Winnipeg Acute TBI database, we evaluated the association between daily treatment intensity levels, as measured through the therapeutic intensity level (TIL) scoring system, and continuous multi-modal-derived CVR measures. CVR measures included the intracranial pressure (ICP)-derived pressure reactivity index, pulse amplitude index, and RAC index (a correlation between the pulse amplitude of ICP and cerebral perfusion pressure), as well as the cerebral autoregulation measure of near-infrared spectroscopy-based cerebral oximetry index. These measures were also derived over a key threshold for each day and were compared to the daily total TIL measure. In summary, we could not observe any overall relationship between TIL and these CVR measures. This validates previous findings and represents only the second such analysis to date. This helps to confirm that CVR appears to remain independent of current therapeutic interventions and is a potential unique physiological target for critical care. Further work into the high-frequency relationship between critical care and CVR is required.}, keywords = {Critical care; Cerebral autoregulation; Pressure reactivity; high-frequency data assessment; therapeutic intensity level}, year = {2023}, eissn = {2689-288X}, pages = {307-317} } @article{MTMT:34288225, title = {The impact of sedative and vasopressor agents on cerebrovascular reactivity in severe traumatic brain injury}, url = {https://m2.mtmt.hu/api/publication/34288225}, author = {Froese, Logan and Hammarlund, Emma and Akerlund, Cecilia A. I. and Tjerkaski, Jonathan and Hong, Erik and Lindblad, Caroline and Nelson, David W. and Thelin, Eric P. and Zeiler, Frederick A.}, doi = {10.1186/s40635-023-00524-4}, journal-iso = {INTENSIVE CARE MED EXP}, journal = {INTENSIVE CARE MEDICINE EXPERIMENTAL}, volume = {11}, unique-id = {34288225}, abstract = {BackgroundThe aim of this study is to evaluate the impact of commonly administered sedatives (Propofol, Alfentanil, Fentanyl, and Midazolam) and vasopressor (Dobutamine, Ephedrine, Noradrenaline and Vasopressin) agents on cerebrovascular reactivity in moderate/severe TBI patients. Cerebrovascular reactivity, as a surrogate for cerebral autoregulation was assessed using the long pressure reactivity index (LPRx). We evaluated the data in two phases, first we assessed the minute-by-minute data relationships between different dosing amounts of continuous infusion agents and physiological variables using boxplots, multiple linear regression and ANOVA. Next, we assessed the relationship between continuous/bolus infusion agents and physiological variables, assessing pre-/post- dose of medication change in physiology using a Wilcoxon signed-ranked test. Finally, we evaluated sub-groups of data for each individual dose change per medication, focusing on key physiological thresholds and demographics.ResultsOf the 475 patients with an average stay of 10 days resulting in over 3000 days of recorded information 367 (77.3%) were male with a median Glasgow coma score of 7 (4-9). The results of this retrospective observational study confirmed that the infusion of most administered agents do not impact cerebrovascular reactivity, which is confirmed by the multiple linear regression components having p value > 0.05. Incremental dose changes or bolus doses in these medications in general do not lead to significant changes in cerebrovascular reactivity (confirm by Wilcoxon signed-ranked p value > 0.05 for nearly all assessed relationships). Within the sub-group analysis that separated the data based on LPRx pre-dose, a significance between pre-/post-drug change in LPRx was seen, however this may be more of a result from patient state than drug impact.ConclusionsOverall, this study indicates that commonly administered agents with incremental dosing changes have no clinically significant influence on cerebrovascular reactivity in TBI (nor do they impair cerebrovascular reactivity). Though further investigation in a larger and more diverse TBI patient population is required.}, keywords = {Cerebrovascular reactivity; AUTOREGULATION; vasopressors; Sedative drugs}, year = {2023}, eissn = {2197-425X}, orcid-numbers = {Froese, Logan/0000-0002-6076-0189} } @article{MTMT:34330738, title = {Evaluation and Application of Ultra-Low-Resolution Pressure Reactivity Index in Moderate or Severe Traumatic Brain Injury}, url = {https://m2.mtmt.hu/api/publication/34330738}, author = {Gritti, Paolo and Bonfanti, Marco and Zangari, Rosalia and Farina, Alessia and Longhi, Luca and Rasulo, Frank A. and Bertuetti, Rita and Biroli, Antonio and Biroli, Francesco and Lorini, Ferdinando Luca}, doi = {10.1097/ANA.0000000000000847}, journal-iso = {J NEUROSURG ANESTH}, journal = {JOURNAL OF NEUROSURGICAL ANESTHESIOLOGY}, volume = {35}, unique-id = {34330738}, issn = {0898-4921}, abstract = {Background:The pressure reactivity index (PRx) has emerged as a surrogate method for the continuous bedside estimation of cerebral autoregulation and a predictor of unfavorable outcome after traumatic brain injury (TBI). However, calculation of PRx require continuous high-resolution monitoring currently limited to specialized intensive care units. The aim of this study was to evaluate a new index, the ultra-low-frequency PRx (UL-PRx) sampled at similar to 0.0033 Hz at similar to 5 minutes periods, and to investigate its association with outcome. Methods:Demographic data, admission Glasgow coma scale, in-hospital mortality and Glasgow outcome scale extended at 12 months were extracted from electronic records. The filtering and preparation of time series of intracranial pressure (ICP), mean arterial pressure and cerebral perfusion pressure (CPP), and calculation of the indices (UL-PRx, Delta-optimal CPP), were performed in MATLAB using an in-house algorithm. Results:A total of 164 TBI patients were included in the study; in-hospital and 12-month mortality was 29.3% and 38.4%, respectively, and 64% of patients had poor neurological outcome at 12 months. On univariate analysis, ICP, CPP, UL-PRx, and Delta CPPopt were associated with 12-month mortality. After adjusting for age, Glasgow coma scale, ICP and CPP, mean UL-PRx and UL-PRx thresholds of 0 and +0.25 remained associated with 12-month mortality. Similar findings were obtained for in-hospital mortality. For mean UL-PRx, the area under the receiver operating characteristic curves for in-hospital and 12-month mortality were 0.78 (95% confidence interval [CI]: 0.69-0.87; P<0.001) and 0.70 (95% CI: 0.61-0.79; P<0.001), respectively, and 0.65 (95% CI: 0.57-0.74; P=0.001) for 12-month neurological outcome. Conclusions:Our findings indicate that ultra-low-frequency sampling might provide sufficient resolution to derive information about the state of cerebrovascular autoregulation and prediction of 12-month outcome in TBI patients.}, keywords = {Cerebrovascular reactivity; traumatic brain injury; Intracranial Pressure; neuromonitoring; Cerebral autoregulation; Sampling rate; Pressure reactivity index; STATIC AUTOREGULATION; ultra-low-frequency pressure reactivity index; optimal cerebral perfusion}, year = {2023}, eissn = {1537-1921}, pages = {313-321} } @article{MTMT:34333769, title = {Critical Care Experience With Clinical Cerebral Autoregulation Testing in Adults With Traumatic Brain Injury}, url = {https://m2.mtmt.hu/api/publication/34333769}, author = {Kunapaisal, Thitikan and Vavilala, Monica S. and Moore, Anne and Theard, Marie A. and Lele, Abhijit V}, doi = {10.7759/cureus.43451}, journal-iso = {CUREUS}, journal = {CUREUS}, volume = {15}, unique-id = {34333769}, abstract = {Background: To describe the setting, feasibility, and safety of static cerebral autoregulation testing in critically injured adults with traumatic brain injury (TBI).Methods: We reviewed static autoregulation testing using transcranial Doppler (TCD) ultrasound in patients > 18 years with TBI ICD codes between January 1, 2014, and December 31, 2021. Adverse events during testing were defined as systemic hypertension (systolic blood pressure (SBP>180 mmHg), bradycardia (HR<40 bpm), and high ICP (>30 mmHg). Impaired and absent cerebral autoregulation was defined as an autoregulatory index (ARI) <0.4 and ARI 0, respectively. We characterized prescribed changes in intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targets by autoregulation testing results.Results: A total of 135 patients, median age 31 (interquartile range (IQR) 24, 43) years, 71.9% male, admission Glasgow coma scale (GCS) score 3 (IQR 3, 5.5), and 70.9% with subdural hematoma from severe (GCS 3-8; 133 (98.5%)) and moderate (GCS 9-12; 2 (1.5%)) TBI, underwent 309 attempted testing. All patients were mechanically ventilated and had ICP monitoring; 246 (80%) had brain tissue oxygen monitoring, and 68 (22%) had an external ventricular drain. The median number of autoregulation tests was two (range 1-3) tests/patient, and the median admission to the first test time was two days (IQR 1, 3). Of 55 (17.8%) tests not completed, systemic hypertension (32, 10.4%), intracranial hypertension (10, 3.2%), and bradycardia (3, 0.9%) were transient. Fifty-three (51%) of the first (n=104) autoregulation tests showed impaired/absent cerebral autoregulation. Impaired/absent autoregulation results at the first test were associated with repeat cerebral autoregulation testing (RR 2.25, 95% CI [1.40-3.60], p=0.0007) than intact cerebral autoregulation results. Pre-testing cerebral hemodynamic targets were maintained (n=131; 86.8%) when cerebral autoregulation was impaired (n=151; RR 1.49, 95% CI [1.25-1.77], p<0.0001). However, 15 (9.9%) test results led to higher ICP targets (from 20 mmHg to 25 mmHg), 5 (3.3%) results led to an increase in CPP target (from 60 mmHg to 70 mmHg), and five out of 131 (3.8%) patients underwent decompressive craniectomy and placement of an external ventricular drain. Intact cerebral autoregulation results (n=43/103, 41.7%) were associated with a change in ICP targets from 20 mmHg to 25 mmHg (RR 3.15, 95% CI [1.97-5.03], p<0.0001).Conclusions: Static cerebral autoregulation testing was feasible, safe, and useful in individualizing the care of patients with moderate-severe TBI receiving multimodal neuromonitoring. Testing results guided future testing, cerebral hemodynamic targets, and procedural decisions. Impaired cerebral autoregulation was very common.}, keywords = {SAFETY; COMPLICATIONS; clinical practice; traumatic brain injury; TRANSCRANIAL DOPPLER; Adults; MODERATE; TBI; Cerebral autoregulation; Severe}, year = {2023}, eissn = {2168-8184}, orcid-numbers = {Kunapaisal, Thitikan/0000-0002-6988-9632} } @article{MTMT:33944061, title = {High spatial and temporal resolution cerebrovascular reactivity for humans and large mammals: A technological description of integrated fNIRS and niABP mapping system}, url = {https://m2.mtmt.hu/api/publication/33944061}, author = {Sainbhi, Amanjyot Singh and Froese, Logan and Gomez, Alwyn and Marquez, Izzy and Amenta, Fiorella and Batson, Carleen and Stein, Kevin Y. and Zeiler, Frederick A.}, doi = {10.3389/fphys.2023.1124268}, journal-iso = {FRONT PHYSIOL}, journal = {FRONTIERS IN PHYSIOLOGY}, volume = {14}, unique-id = {33944061}, abstract = {Introduction: The process of cerebral vessels maintaining cerebral blood flow (CBF) fairly constant over a wide range of arterial blood pressure is referred to as cerebral autoregulation (CA). Cerebrovascular reactivity is the mechanism behind this process, which maintains CBF through constriction and dilation of cerebral vessels. Traditionally CA has been assessed statistically, limited by large, immobile, and costly neuroimaging platforms. However, with recent technology advancement, dynamic autoregulation assessment is able to provide more detailed information on the evolution of CA over long periods of time with continuous assessment. Yet, to date, such continuous assessments have been hampered by low temporal and spatial resolution systems, that are typically reliant on invasive point estimations of pulsatile CBF or cerebral blood volume using commercially available technology.Methods: Using a combination of multi-channel functional near-infrared spectroscopy and non-invasive arterial blood pressure devices, we were able to create a system that visualizes CA metrics by converting them to heat maps drawn on a template of human brain.Results: The custom Python heat map module works in "offline " mode to visually portray the CA index per channel with the use of colourmap. The module was tested on two different mapping grids, 8 channel and 24 channel, using data from two separate recordings and the Python heat map module was able read the CA indices file and represent the data visually at a preselected rate of 10 s.Conclusion: The generation of the heat maps are entirely non-invasive, with high temporal and spatial resolution by leveraging the recent advances in NIRS technology along with niABP. The CA mapping system is in its initial stage and development plans are ready to transform it from "offline " to real-time heat map generation.}, keywords = {near-infrared spectroscopy; High spatial resolution; Cerebral autoregulation; HIGH TEMPORAL RESOLUTION; cerebrovascular reactivity mapping system; neuroimaging system; cerebral heat maps; NIRS-based indices}, year = {2023}, eissn = {1664-042X}, orcid-numbers = {Sainbhi, Amanjyot Singh/0000-0003-3231-5683} } @article{MTMT:34333770, title = {Non-Invasive Mapping of Cerebral Autoregulation Using Near-Infrared Spectroscopy: A Study Protocol}, url = {https://m2.mtmt.hu/api/publication/34333770}, author = {Sainbhi, Amanjyot Singh and Vakitbilir, Nuray and Gomez, Alwyn and Stein, Kevin Y. and Froese, Logan and Zeiler, Frederick A.}, doi = {10.3390/mps6030058}, journal-iso = {METHODS PROTOC}, journal = {METHODS AND PROTOCOLS}, volume = {6}, unique-id = {34333770}, abstract = {The ability of cerebral vessels to maintain a fairly constant cerebral blood flow is referred to as cerebral autoregulation (CA). Using near-infrared spectroscopy (NIRS) paired with arterial blood pressure (ABP) monitoring, continuous CA can be assessed non-invasively. Recent advances in NIRS technology can help improve the understanding of continuously assessed CA in humans with high spatial and temporal resolutions. We describe a study protocol for creating a new wearable and portable imaging system that derives CA maps of the entire brain with high sampling rates at each point. The first objective is to evaluate the CA mapping system's performance during various perturbations using a block-trial design in 50 healthy volunteers. The second objective is to explore the impact of age and sex on regional disparities in CA using static recording and perturbation testing in 200 healthy volunteers. Using entirely non-invasive NIRS and ABP systems, we hope to prove the feasibility of deriving CA maps of the entire brain with high spatial and temporal resolutions. The development of this imaging system could potentially revolutionize the way we monitor brain physiology in humans since it would allow for an entirely non-invasive continuous assessment of regional differences in CA and improve our understanding of the impact of the aging process on cerebral vessel function.}, keywords = {near infrared spectroscopy; Healthy Volunteers; High spatial resolution; Cerebral autoregulation; HIGH TEMPORAL RESOLUTION; non-invasive system; neuroimaging system; cerebral heat maps; NIRS-based indices; cerebrovascular reactivity system}, year = {2023}, eissn = {2409-9279}, orcid-numbers = {Sainbhi, Amanjyot Singh/0000-0003-3231-5683; Vakitbilir, Nuray/0000-0003-2764-145X; Froese, Logan/0000-0002-6076-0189} } @article{MTMT:34330734, title = {Regional disparity in continuously measured time-domain cerebrovascular reactivity indices: a scoping review of human literature}, url = {https://m2.mtmt.hu/api/publication/34330734}, author = {Sainbhi, Amanjyot Singh and Marquez, Izabella and Gomez, Alwyn and Stein, Kevin Y. and Amenta, Fiorella and Vakitbilir, Nuray and Froese, Logan and Zeiler, Frederick A.}, doi = {10.1088/1361-6579/acdfb6}, journal-iso = {PHYSIOL MEAS}, journal = {PHYSIOLOGICAL MEASUREMENT}, volume = {44}, unique-id = {34330734}, issn = {0967-3334}, abstract = {Objective: Cerebral blood vessels maintaining relatively constant cerebral blood flow (CBF) over wide range of systemic arterial blood pressure (ABP) is referred to as cerebral autoregulation (CA). Impairments in CA expose the brain to pressure-passive flow states leading to hypoperfusion and hyperperfusion. Cerebrovascular reactivity (CVR) metrics refer to surrogate metrics of pressure-based CA that evaluate the relationship between slow vasogenic fluctuations in cerebral perfusion pressure/ABP and a surrogate for pulsatile CBF/cerebral blood volume. Approach: We performed a systematically conducted scoping review of all available human literature examining the association between continuous CVR between more than one brain region/channel using the same CVR index. Main Results: In all the included 22 articles, only handful of transcranial doppler (TCD) and near-infrared spectroscopy (NIRS) based metrics were calculated for only two brain regions/channels. These metrics found no difference between left and right sides in healthy volunteer, cardiac surgery, and intracranial hemorrhage patient studies. In contrast, significant differences were reported in endarterectomy, and subarachnoid hemorrhage studies, while varying results were found regarding regional disparity in stroke, traumatic brain injury, and multiple population studies. Significance: Further research is required to evaluate regional disparity using NIRS-based indices and to understand if NIRS-based indices provide better regional disparity information than TCD-based indices.}, keywords = {Cerebral autoregulation; regional disparity; cerebrovascular reactivity metrics; time-domain metrics; NIRS-based indices; TCD-based indices}, year = {2023}, eissn = {1361-6579}, orcid-numbers = {Sainbhi, Amanjyot Singh/0000-0003-3231-5683; Gomez, Alwyn/0000-0002-3737-2065; Vakitbilir, Nuray/0000-0003-2764-145X} } @article{MTMT:33908189, title = {Associations between intracranial pressure thresholds and multimodal monitoring in acute traumatic neural injury: a scoping review}, url = {https://m2.mtmt.hu/api/publication/33908189}, author = {Stein, Kevin Y. and Amenta, Fiorella and Gomez, Alwyn and Froese, Logan and Sainbhi, Amanjyot Singh and Vakitbilir, Nuray and Marquez, Izabella and Zeiler, Frederick A.}, doi = {10.1007/s00701-023-05587-6}, journal-iso = {ACTA NEUROCHIR}, journal = {ACTA NEUROCHIRURGICA}, volume = {165}, unique-id = {33908189}, issn = {0001-6268}, abstract = {BackgroundCurrent moderate/severe traumatic brain injury (TBI) guidelines suggest the use of an intracranial pressure (ICP) treatment threshold of 20 mmHg or 22 mmHg. Over the past decade, the use of various cerebral physiology monitoring devices has been incorporated into neurocritical care practice and termed "multimodal monitoring." Such modalities include those that monitor systemic hemodynamics, systemic and brain oxygenation, cerebral blood flow (CBF), cerebral autoregulation, electrophysiology, and cerebral metabolism. Given that the relationship between ICP and outcomes is not yet entirely understood, a comprehensive review of the literature on the associations between ICP thresholds and multimodal monitoring is still needed.MethodsWe conducted a scoping review of the literature for studies that present an objective statistical association between ICP above/below threshold and any multimodal monitoring variable. MEDLINE, BIOSIS, Cochrane library, EMBASE, Global Health, and SCOPUS were searched from inception to July 2022 for relevant articles. Full-length, peer-reviewed, original works with a sample size of >= 50 moderate-severe TBI patients were included in this study.ResultsA total of 13 articles were deemed eligible for final inclusion. The included articles were significantly heterogenous in terms of their designs, demographics, and results, making it difficult to draw any definitive conclusions. No literature describing the association between guideline-based ICP thresholds and measures of brain electrophysiology, cerebral metabolism, or direct metrics of CBF was found.ConclusionThere is currently little literature that presents objective statistical associations between ICP thresholds and multimodal monitoring physiology. However, overall, the literature indicates that having ICP above guideline based thresholds is associated with increased blood pressure, increased cardiac decoupling, reduced parenchymal brain oxygen tension, and impaired cerebral autoregulation, with no association with CBF velocity within the therapeutic range of ICP. There was insufficient literature to comment on other multimodal monitoring measures.}, keywords = {TBI; Multimodal monitoring; ICP thresholds; Acute traumatic neural injury}, year = {2023}, eissn = {0942-0940}, pages = {1987-2000}, orcid-numbers = {Gomez, Alwyn/0000-0002-3737-2065; Froese, Logan/0000-0002-6076-0189; Sainbhi, Amanjyot Singh/0000-0003-3231-5683; Vakitbilir, Nuray/0000-0003-2764-145X} } @article{MTMT:34555602, title = {Intracranial Pressure-Derived Cerebrovascular Reactivity Indices and Their Critical Thresholds: A Canadian High Resolution-Traumatic Brain Injury Validation Study}, url = {https://m2.mtmt.hu/api/publication/34555602}, author = {Stein, Kevin Y. and Froese, Logan and Sekhon, Mypinder and Griesdale, Donald and Thelin, Eric P. and Raj, Rahul and Tas, Jeanette and Aries, Marcel and Gallagher, Clare and Bernard, Francis and Gomez, Alwyn and Kramer, Andreas H. and Zeiler, Frederick A.}, doi = {10.1089/neu.2023.0374}, journal-iso = {J NEUROTRAUM}, journal = {JOURNAL OF NEUROTRAUMA}, unique-id = {34555602}, issn = {0897-7151}, abstract = {Current neurointensive care guidelines recommend intracranial pressure (ICP) and cerebral perfusion pressure (CPP) centered management for moderate-severe traumatic brain injury (TBI) because of their demonstrated associations with patient outcome. Cerebrovascular reactivity metrics, such as the pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC index, have also demonstrated significant prognostic capabilities with regard to outcome. However, critical thresholds for cerebrovascular reactivity indices have only been identified in two studies conducted at the same center. In this study, we aim to determine the critical thresholds of these metrics by leveraging a unique multi-center database. The study included a total of 354 patients from the CAnadian High-Resolution TBI (CAHR-TBI) Research Collaborative. Based on 6-month Glasgow Outcome Scores, patients were dichotomized into alive versus dead and favorable versus unfavorable. Chi-square values were then computed for incrementally increasing values of each physiological parameter of interest against outcome. The values that generated the greatest chi-squares for each parameter were considered to be the thresholds with the greatest outcome discriminatory capacity. To confirm that the identified thresholds provide prognostic utility, univariate and multivariable logistical regression analyses were performed adjusting for the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) variables. Through the chi-square analysis, a lower limit CPP threshold of 60 mm Hg and ICP thresholds of 18 mm Hg and 22 mm Hg were identified for both survival and favorable outcome predictions. For the cerebrovascular reactivity metrics, different thresholds were identified for the two outcome dichotomizations. For survival prediction, thresholds of 0.35, 0.25, and 0 were identified for PRx, PAx, and RAC, respectively. For favorable outcome prediction, thresholds of 0.325, 0.20, and 0.05 were found. Univariate logistical regression analysis demonstrated that the time spent above/below thresholds were associated with outcome. Further, multivariable logistical regression analysis found that percent time above/below the identified thresholds added additional variance to the IMPACT core model for predicting both survival and favorable outcome. In this study, we were able to validate the results of the previous two works as well as to reaffirm the ICP and CPP guidelines from the Brain Trauma Foundation (BTF) and the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC).}, keywords = {FALSE DISCOVERY RATE; MANAGEMENT; Cerebrovascular reactivity; Intracranial Pressure; pulse amplitude; PART II; cerebral perfusion pressure; Clinical Neurology; Critical Care Medicine; CENTER-TBI; CEREBRAL PERFUSION-PRESSURE; Critical thresholds; BLOOD-FLOW AUTOREGULATION; LOWER LIMIT; NEUROTRAUMA EFFECTIVENESS RESEARCH}, year = {2023}, eissn = {1557-9042}, orcid-numbers = {Thelin, Eric P./0000-0002-2338-4364; Raj, Rahul/0000-0003-4243-9591; Zeiler, Frederick A./0000-0003-1737-0510} } @article{MTMT:34555681, title = {Time spent above optimal cerebral perfusion pressure is not associated with failure to improve in outcome in traumatic brain injury}, url = {https://m2.mtmt.hu/api/publication/34555681}, author = {Stein, Kevin Y. and Froese, Logan and Gomez, Alwyn and Sainbhi, Amanjyot Singh and Vakitbilir, Nuray and Ibrahim, Younis and Islam, Abrar and Marquez, Izabella and Amenta, Fiorella and Bergmann, Tobias and Zeiler, Frederick A.}, doi = {10.1186/s40635-023-00579-3}, journal-iso = {INTENSIVE CARE MED EXP}, journal = {INTENSIVE CARE MEDICINE EXPERIMENTAL}, volume = {11}, unique-id = {34555681}, abstract = {BackgroundOptimal cerebral perfusion pressure (CPPopt) has emerged as a promising personalized medicine approach to the management of moderate-to-severe traumatic brain injury (TBI). Though literature demonstrating its association with poor outcomes exists, there is yet to be work done on its association with outcome transition due to a lack of serial outcome data analysis. In this study we investigate the association between various metrics of CPPopt and failure to improve in outcome over time.MethodsCPPopt was derived using three different cerebrovascular reactivity indices; the pressure reactivity index (PRx), the pulse amplitude index (PAx), and the RAC index. For each index, % times spent with cerebral perfusion pressure (CPP) above and below its CPPopt and upper and lower limits of reactivity were calculated. Patients were dichotomized based on improvement in Glasgow Outcome Scale-Extended (GOSE) scores into Improved vs. Not Improved between 1 and 3 months, 3 and 6 months, and 1- and 6-month post-TBI. Logistic regression analyses were then conducted, adjusting for the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) variables.ResultsThis study included a total of 103 patients from the Winnipeg Acute TBI Database. Through Mann-Whitney U testing and logistic regression analysis, it was found that % time spent with CPP below CPPopt was associated with failure to improve in outcome, while % time spent with CPP above CPPopt was generally associated with improvement in outcome.ConclusionsOur study supports the existing narrative that time spent with CPP below CPPopt results in poorer outcomes. However, it also suggests that time spent above CPPopt may not be associated with worse outcomes and is possibly even associated with improvement in outcome.}, keywords = {VALIDATION; INDEX; MANAGEMENT; Cerebrovascular reactivity; traumatic brain injury; THRESHOLDS; pulse amplitude; INTRACRANIAL-PRESSURE; CPPopt; optimal cerebral perfusion pressure; Outcome transition}, year = {2023}, eissn = {2197-425X}, orcid-numbers = {Froese, Logan/0000-0002-6076-0189; Gomez, Alwyn/0000-0002-3737-2065; Sainbhi, Amanjyot Singh/0000-0003-3231-5683; Vakitbilir, Nuray/0000-0003-2764-145X; Zeiler, Frederick A./0000-0003-1737-0510} } @article{MTMT:34555993, title = {The pressure reactivity index as a measure of cerebral autoregulation and its application in traumatic brain injury management}, url = {https://m2.mtmt.hu/api/publication/34555993}, author = {Tsigaras, Zac A. and Weeden, Mark and Mcnamara, Robert and Jeffcote, Toby and Udy, Andrew A.}, doi = {10.1016/j.ccrj.2023.10.009}, journal-iso = {CRIT CARE RESUSC}, journal = {Critical Care and Resuscitation}, volume = {25}, unique-id = {34555993}, issn = {1441-2772}, abstract = {Severe traumatic brain injury (TBI) is a major cause of morbidity and mortality globally. The Brain Trauma Foundation guidelines advocate for the maintenance of a cerebral perfusion pressure (CPP) between 60 and 70 mmHg following severe TBI. However, such a uniform goal does not account for changes in cerebral autoregulation (CA). CA refers to the complex homeostatic mechanisms by which cerebral blood flow is maintained, despite variations in mean arterial pressure and intracranial pressure. Disruption to CA has become increasingly recognised as a key mediator of secondary brain injury following severe TBI. The pressure reactivity index is calculated as the degree of statistical correlation between the slow wave components of mean arterial pressure and intracranial pressure signals and is a validated dynamic marker of CA status following brain injury. The widespread acceptance of pressure reactivity index has precipitated the consideration of individualised CPP targets or an optimal cerebral perfusion pressure (CPPopt). CPPopt represents an alternative target for cerebral haemodynamic optimisation following severe TBI, and early observational data suggest improved neurological outcomes in patients whose CPP is more proximate to CPPopt. The recent publication of a prospective randomised feasibility study of CPPopt guided therapy in TBI, suggests clinicians caring for such patients should be increasingly familiar with these concepts. In this paper, we present a narrative review of the key landmarks in the development of CPPopt and offer a summary of the evidence for CPPopt-based therapy in comparison to current standards of care.(c) 2023 The Authors. Published by Elsevier B.V. on behalf of College of Intensive Care Medicine of Australia and New Zealand. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).}, keywords = {Adult; ASSOCIATION; VISUALIZATION; TIME; traumatic brain injury; TRAUMA; PERFUSION-PRESSURE; THRESHOLDS; Intracranial Hypertension; Decompressive craniectomy; Anaesthesia and intensive care; Monitoring data; Trauma care delivery}, year = {2023}, pages = {229-236} } @article{MTMT:32689003, title = {Intracranial Pressure-Derived Cerebrovascular Reactivity Indices, Chronological Age, and Biological Sex in Traumatic Brain Injury: A Scoping Review}, url = {https://m2.mtmt.hu/api/publication/32689003}, author = {Batson, Carleen and Stein, Kevin Y. and Gomez, Alwyn and Sainbhi, Amanjyot Singh and Froese, Logan and Alizadeh, Arsalan and Mathieu, Francois and Zeiler, Frederick A.}, doi = {10.1089/neur.2021.0054}, journal-iso = {NEUROTRAUMA REP}, journal = {NEUROTRAUMA REPORTS}, volume = {3}, unique-id = {32689003}, abstract = {To date, there has been limited literature exploring the association between age and sex with cerebrovascular reactivity (CVR) in moderate/severe traumatic brain injury (TBI). Given the known link between age, sex, and cerebrovascular function, knowledge of the impacts on continuously assessed CVR is critical for the development of future therapeutics. We conducted a scoping review of the literature for studies that had a direct statistical interrogation of the relationship between age, sex, and continuous intracranial pressure (ICP)-based indices of CVR in moderate/severe TBI. The ICP-based indices researched included: pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC. MEDLINE, BIOSIS, EMBASE, SCOPUS, Global Health, and the Cochrane library were searched from inception to June 2021 for relevant articles. A total of 10 original studies fulfilled our inclusion criteria. Nine of the articles documented a correlation between advanced age and worse CVR, with eight using PRx (2192 total patients), three using PAx (978 total patients), and one using RAC (358 total patients), p < 0.05; R ranging from 0.17 to 0.495 for all indices across all studies. Three articles (1256 total patients) displayed a correlation between biological sex and PRx, with females trending towards higher PRx values (p < 0.05) in the limited available literature. However, no literature exists comparing PAx or RAC with biological sex. Findings showed that aging was associated with impaired CVR. We observed a trend between female sex and worse PRx values, but the literature was limited and statistical significance was borderline. The identified studies were few in number, carried significant population heterogeneity, and utilized grand averaging of large epochs of physiology during statistical comparisons with age and biological sex. Because of the heterogeneous nature of TBI populations and limited focus on the effects of age and sex on outcomes in TBI, it is challenging to highlight the differences between the indices and patient age groups and sex. The largest study showing an association between PRx and age was done by Zeiler and colleagues, where 165 patients were studied noting that patients with a mean PRx value above zero had a mean age above 51.4 years versus a mean age of 41.4 years for those with a mean PRx value below zero (p = 0.0007). The largest study showing an association between PRx and sex was done by Czosnyka and colleagues, where 469 patients were studied noting that for patients <50 years of age, PRx was worse in females (0.11 +/- 0.047) compared to males (0.044 +/- 0.031), p < 0.05. The findings from these 10 studies provide preliminary data, but are insufficient to definitively characterize the impact of age and sex on CVR in moderate/severe TBI. Future work in the field should focus on the impact of age and sex on multi-modal cerebral physiological monitoring.}, keywords = {VALIDATION; AGE; HYPERTENSION; AUTOREGULATION; AUTOREGULATION; CARE; pulse amplitude; PART II; Clinical Neurology; biological sex; Compensatory reserve; CEREBRAL PERFUSION-PRESSURE; LOWER LIMIT}, year = {2022}, eissn = {2689-288X}, pages = {44-56} } @article{MTMT:34560050, title = {Continuous Determination of the Optimal Bispectral Index Value Based on Cerebrovascular Reactivity in Moderate/Severe Traumatic Brain Injury: A Retrospective Observational Cohort Study of a Novel Individualized Sedation Target}, url = {https://m2.mtmt.hu/api/publication/34560050}, author = {Froese, L. and Gomez, A. and Sainbhi, A.S. and Batson, C. and Stein, K. and Alizadeh, A. and Mendelson, A.A. and Zeiler, F.A.}, doi = {10.1097/CCE.0000000000000656}, journal-iso = {CRITICAL CARE EXPLORATIONS}, journal = {CRITICAL CARE EXPLORATIONS}, volume = {4}, unique-id = {34560050}, year = {2022}, eissn = {2639-8028}, pages = {E0656} } @article{MTMT:34560548, title = {Dynamic Temporal Relationship Between Autonomic Function and Cerebrovascular Reactivity in Moderate/Severe Traumatic Brain Injury}, url = {https://m2.mtmt.hu/api/publication/34560548}, author = {Froese, L. and Gomez, A. and Sainbhi, A.S. and Batson, C. and Stein, K. and Alizadeh, A. and Zeiler, F.A.}, doi = {10.3389/fnetp.2022.837860}, journal-iso = {FRONT NETW PHYSIOL}, journal = {FRONTIERS IN NETWORK PHYSIOLOGY}, volume = {2}, unique-id = {34560548}, year = {2022}, eissn = {2674-0109} } @article{MTMT:33430527, title = {Optimal bispectral index level of sedation and cerebral oximetry in traumatic brain injury: a non-invasive individualized approach in critical care?}, url = {https://m2.mtmt.hu/api/publication/33430527}, author = {Froese, Logan and Gomez, Alwyn and Sainbhi, Amanjyot Singh and Batson, Carleen and Slack, Trevor and Stein, Kevin Y. and Mathieu, Francois and Zeiler, Frederick A.}, doi = {10.1186/s40635-022-00460-9}, journal-iso = {INTENSIVE CARE MED EXP}, journal = {INTENSIVE CARE MEDICINE EXPERIMENTAL}, volume = {10}, unique-id = {33430527}, abstract = {Background: Impaired cerebral autoregulation has been linked with worse outcomes, with literature suggesting that current therapy guidelines fail to significantly impact cerebrovascular reactivity. The cerebral oximetry index (COx_a) is a surrogate measure of cerebrovascular reactivity which can in theory be obtained non-invasively using regional brain tissue oxygen saturation and arterial blood pressure. The goal of this study was to assess the relationship between objectively measured depth of sedation through BIS and autoregulatory capacity measured through COx_a.Methods: In a prospectively maintained observational study, we collected continuous regional brain tissue oxygen saturation, intracranial pressure, arterial blood pressure and BIS in traumatic brain injury patients. COx_a was obtained using the Pearson's correlation between regional brain tissue oxygen saturation and arterial blood pressure and ranges from - 1 to 1 with higher values indicating impairment of cerebrovascular reactivity. Using BIS values and COx_a, a curve-fitting method was applied to determine the minimum value for the COx_a. The associated BIS value with the minimum COx_a is called BISopt. This BISopt was both visually and algorithmically determined, which were compared and assessed over the whole dataset.Results: Of the 42 patients, we observed that most had a parabolic relationship between BIS and COx_a. This suggests a potential "optimal" depth of sedation where COx_a is the most intact. Furthermore, when comparing the BISopt algorithm with visual inspection of BISopt, we obtained similar results. Finally, BISopt % yield (determined algorithmically) appeared to be independent from any individual sedative or vasopressor agent, and there was agreement between BISopt found with COx_a and the pressure reactivity index (another surrogate for cerebrovascular reactivity).Conclusions: This study suggests that COx_a is capable of detecting disruption in cerebrovascular reactivity which occurs with over-/under-sedation, utilizing a non-invasive measure of determination and assessment. This technique may carry implications for tailoring sedation in patients, focusing on individualized neuroprotection.}, keywords = {Cerebrovascular reactivity; traumatic brain injury; Depth of sedation; Cerebral oximetry index; Optimal bispectral index}, year = {2022}, eissn = {2197-425X}, orcid-numbers = {Froese, Logan/0000-0002-6076-0189; Gomez, Alwyn/0000-0002-3737-2065; Sainbhi, Amanjyot Singh/0000-0003-3231-5683; Mathieu, Francois/0000-0002-7894-2466} } @article{MTMT:33449980, title = {Differential Hemodynamic Response of Pial Arterioles Contributes to a Quadriphasic Cerebral Autoregulation Physiology}, url = {https://m2.mtmt.hu/api/publication/33449980}, author = {Klein, Samuel P. and De Sloovere, Veerle and Meyfroidt, Geert and Depreitere, Bart}, doi = {10.1161/JAHA.121.022943}, journal-iso = {J AM HEART ASSOC}, journal = {JOURNAL OF THE AMERICAN HEART ASSOCIATION}, volume = {11}, unique-id = {33449980}, issn = {2047-9980}, abstract = {Background Cerebrovascular autoregulation (CA) regulates cerebral vascular tone to maintain near-constant cerebral blood flow during fluctuations in cerebral perfusion pressure (CPP). Preclinical and clinical research has challenged the classic triphasic pressure-flow relationship, leaving the normal pressure-flow relationship unclear. Methods and Results We used in vivo imaging of the hemodynamic response in pial arterioles to study CA in a porcine closed cranial window model during nonpharmacological blood pressure manipulation. Red blood cell flux was determined in 52 pial arterioles during 10 hypotension and 10 hypertension experiments to describe the pressure-flow relationship. We found a quadriphasic pressure-flow relationship with 4 distinct physiological phases. Smaller arterioles demonstrated greater vasodilation during low CPP when compared with large arterioles (P<0.01), whereas vasoconstrictive capacity during high CPP was not significantly different between arterioles (P>0.9). The upper limit of CA was defined by 2 breakpoints. Increases in CPP lead to a point of maximal vasoconstriction of the smallest pial arterioles (upper limit of autoregulation [ULA] 1). Beyond ULA1, only larger arterioles maintain a limited additional vasoconstrictive capacity, extending the buffer for high CPP. Beyond ULA2, vasoconstrictive capacity is exhausted, and all pial arterioles passively dilate. There was substantial intersubject variability, with ranges of 29.2, 47.3, and 50.9 mm Hg for the lower limit, ULA1, and ULA2, respectively. Conclusions We provide new insights into the quadriphasic physiology of CA, differentiating between truly active CA and an extended capacity to buffer increased CPP with progressive failure of CA. In this experimental model, the limits of CA widely varied between subjects.}, keywords = {cerebral blood flow; cerebral perfusion pressure; CEREBROVASCULAR AUTOREGULATION}, year = {2022}, eissn = {2047-9980}, orcid-numbers = {Meyfroidt, Geert/0000-0003-4259-3935; Depreitere, Bart/0000-0002-7458-0648} } @article{MTMT:33176428, title = {Traumatic brain injury: progress and challenges in prevention, clinical care, and research}, url = {https://m2.mtmt.hu/api/publication/33176428}, author = {Maas, Andrew I R and Menon, David K and Manley, Geoffrey T and Abrams, Mathew and Åkerlund, Cecilia and Andelic, Nada and Aries, Marcel and Bashford, Tom and Bell, Michael J and Bodien, Yelena G and Brett, Benjamin L and Büki, András and Chesnut, Randall M and Citerio, Giuseppe and Clark, David and Clasby, Betony and Cooper, D Jamie and Czeiter, Endre and Czosnyka, Marek and Dams-O'Connor, Kristen and De Keyser, Véronique and Diaz-Arrastia, Ramon and Ercole, Ari and van Essen, Thomas A and Falvey, Éanna and Ferguson, Adam R and Figaji, Anthony and Fitzgerald, Melinda and Foreman, Brandon and Gantner, Dashiell and Gao, Guoyi and Giacino, Joseph and Gravesteijn, Benjamin and Guiza, Fabian and Gupta, Deepak and Gurnell, Mark and Haagsma, Juanita A and Hammond, Flora M and Hawryluk, Gregory and Hutchinson, Peter and van der Jagt, Mathieu and Jain, Sonia and Jain, Swati and Jiang, Ji-yao and Kent, Hope and Kolias, Angelos and Kompanje, Erwin J O and Lecky, Fiona and Lingsma, Hester F and Maegele, Marc and Majdan, Marek and Markowitz, Amy and McCrea, Michael and Meyfroidt, Geert and Mikolić, Ana and Mondello, Stefania and Mukherjee, Pratik and Nelson, David and Nelson, Lindsay D and Newcombe, Virginia and Okonkwo, David and Orešič, Matej and Peul, Wilco and Pisică, Dana and Polinder, Suzanne and Ponsford, Jennie and Puybasset, Louis and Raj, Rahul and Robba, Chiara and Røe, Cecilie and Rosand, Jonathan and Schueler, Peter and Sharp, David J and Smielewski, Peter and Stein, Murray B and von Steinbüchel, Nicole and Stewart, William and Steyerberg, Ewout W and Stocchetti, Nino and Temkin, Nancy and Tenovuo, Olli and Theadom, Alice and Thomas, Ilias and Espin, Abel Torres and Turgeon, Alexis F and Unterberg, Andreas and Van Praag, Dominique and van Veen, Ernest and Verheyden, Jan and Vyvere, Thijs Vande and Wang, Kevin K W and Wiegers, Eveline J A and Williams, W Huw and Wilson, Lindsay and Wisniewski, Stephen R and Younsi, Alexander and Yue, John K and Yuh, Esther L and Zeiler, Frederick A and Zeldovich, Marina and Zemek, Roger}, doi = {10.1016/S1474-4422(22)00309-X}, journal-iso = {LANCET NEUROL}, journal = {LANCET NEUROLOGY}, volume = {21}, unique-id = {33176428}, issn = {1474-4422}, year = {2022}, eissn = {1474-4465}, pages = {1004-1060}, orcid-numbers = {Czeiter, Endre/0000-0002-9578-6944} } @article{MTMT:33449985, title = {Precision Medicine in Acute Brain Injury: A Narrative Review}, url = {https://m2.mtmt.hu/api/publication/33449985}, author = {Mahajan, Charu and Kapoor, Indu and Prabhakar, Hemanshu}, doi = {10.1097/ANA.0000000000000710}, journal-iso = {J NEUROSURG ANESTH}, journal = {JOURNAL OF NEUROSURGICAL ANESTHESIOLOGY}, volume = {34}, unique-id = {33449985}, issn = {0898-4921}, abstract = {Over the past few years, the concept of personalized medicine has percolated into the management of different neurological conditions. Improving outcomes after acute brain injury (ABI) continues to be a major challenge. Unrecognized individual multiomic variations in addition to multiple interacting processes may explain why we fail to observe comprehensive improvements in ABI outcomes even when applied treatments appear to be beneficial logically. The provision of clinical care based on a multiomic approach may revolutionize the management of traumatic brain injury, delayed cerebral ischemia after subarachnoid hemorrhage, acute ischemic stroke, and several other neurological diseases. The challenge is to incorporate all the information obtained from genomic studies, other omic data, and individual variability into a practical tool that can be used to assist clinical decision-making. The effective execution of such strategies, which is still far away, requires the development of protocols on the basis of these complex interactions and strict adherence to management protocols. In this review, we will discuss various omics and physiological targets to guide individualized patient management after ABI.}, keywords = {GENOMICS; traumatic brain injury; Acute ischemic stroke; Pharmacogenomics; epigenetics; Precision Medicine; ANEURYSMAL SUBARACHNOID HEMORRHAGE; individualized targeted treatment}, year = {2022}, eissn = {1537-1921}, pages = {E14-E23} } @article{MTMT:33048099, title = {Technical considerations on the use of Granger causality in neuromonitoring}, url = {https://m2.mtmt.hu/api/publication/33048099}, author = {Placek, M.M. and Beqiri, E. and Czosnyka, M. and Smielewski, P.}, doi = {10.1016/j.brain.2022.100044}, journal-iso = {Brain Multiphysics}, journal = {Brain Multiphysics}, volume = {3}, unique-id = {33048099}, issn = {2666-5220}, year = {2022} } @{MTMT:34560103, title = {Traumatic brain injury}, url = {https://m2.mtmt.hu/api/publication/34560103}, author = {Smith, C.}, booktitle = {Neurobiology of Brain Disorders}, doi = {10.1016/B978-0-323-85654-6.00010-1}, unique-id = {34560103}, year = {2022}, pages = {443-455} } @article{MTMT:33303150, title = {Association between cerebrovascular reactivity in adult traumatic brain injury and improvement in patient outcome over time: an exploratory analysis}, url = {https://m2.mtmt.hu/api/publication/33303150}, author = {Stein, K.Y. and Froese, L. and Gomez, A. and Sainbhi, A.S. and Batson, C. and Mathieu, F. and Zeiler, F.A.}, doi = {10.1007/s00701-022-05366-9}, journal-iso = {ACTA NEUROCHIR}, journal = {ACTA NEUROCHIRURGICA}, volume = {164}, unique-id = {33303150}, issn = {0001-6268}, abstract = {Background: Impaired cerebrovascular reactivity following moderate/severe traumatic brain injury (TBI) has emerged as a key potential driver of morbidity and mortality. However, the major contributions to the literature so far have been solely focused on single point measures of long-term outcome. Therefore, it remains unknown whether cerebrovascular reactivity impairment, during the acute phase of TBI, is associated with failure to improve in outcome across time. Methods: Cerebrovascular reactivity was measured using three intracranial pressure-based surrogate metrics. For each patient, % time spent above various literature-defined thresholds was calculated. Patients were dichotomized based on outcome transition into Improved vs Not Improved between 1 and 3 months, 3 and 6 months, and 1 and 6 months, based on the Glasgow Outcome Scale-Extended (GOSE). Univariate and multivariable logistic regression analyses were performed, adjusting for the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) variables. Results: Seventy-eight patients from the Winnipeg Acute TBI Database were included in this study. On univariate logistic regression analysis, higher % time with cerebrovascular reactivity metrics above clinically defined thresholds was associated with a lack of clinical improvement between 1 and 3 months and 1 and 6 months post injury (p < 0.05). These relationships held true on multivariable logistic regression analysis. Conclusion: Our study demonstrates that impaired cerebrovascular reactivity, during the acute phase of TBI, is associated with failure to improve clinically over time. These preliminary findings highlight the significance that cerebrovascular reactivity monitoring carries in outcome recovery association in moderate/severe TBI. © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.}, keywords = {Adult; Adult; Female; Middle Aged; Male; Humans; ARTICLE; human; data base; disease association; major clinical study; controlled study; outcome assessment; Cerebrovascular reactivity; Brain Injuries; traumatic brain injury; traumatic brain injury; traumatic brain injury; AUTOREGULATION; Glasgow Outcome Scale; Glasgow Outcome Scale; blood vessel reactivity; Intracranial Pressure; Intracranial Pressure; brain injury; brain blood vessel; exploratory research; Benchmarking; Benchmarking; TBI; Brain Injuries, Traumatic; Outcome transition}, year = {2022}, eissn = {0942-0940}, pages = {3107-3118} } @article{MTMT:33430531, title = {Cerebral Pressure Autoregulation in Brain Injury and Disorders - A Review on Monitoring, Management, and Future Directions}, url = {https://m2.mtmt.hu/api/publication/33430531}, author = {Wettervik, Teodor Svedung and Fahlstrom, Markus and Enblad, Per and Lewen, Anders}, doi = {10.1016/j.wneu.2021.11.027}, journal-iso = {WORLD NEUROSURG}, journal = {WORLD NEUROSURGERY}, volume = {158}, unique-id = {33430531}, issn = {1878-8750}, abstract = {The role of cerebral pressure autoregulation (CPA) in brain injury and disorders has gained increased interest. The CPA is often disturbed as a consequence of acute brain injury, which contributes to further brain damage and worse outcome. Specifically, in severe traumatic brain injury, CPA disturbances predict worse clinical outcome and targeting an autoregulatory-oriented optimal cerebral perfusion pressure threshold may improve brain energy metabolism and clinical outcome. In aneurysmal subarachnoid hemorrhage, cerebral vasospasm in combination with distal autoregulatory disturbances precipitate delayed cerebral ischemia. The role of optimal cerebral perfusion pressure targets is less clear in aneurysmal subarachnoid hemorrhage, but high cerebral perfusion pressure targets are generally favorable in the vasospasm phase. In acute ischemia, autoregulatory disturbances may occur and autoregulatory-oriented blood pressure (optimal mean arterial pressure) management reduces the risk of hemorrhagic transformation, brain edema, and unfavorable outcome. In chronic occlusive disease such as moyamoya, the gradual reduction of the cerebral circulation leads to compensatory distal vasodilation and the residual CPA capacity predicts the risk for cerebral ischemia. In spontaneous intracerebral hemorrhage, the role of autoregulatory disturbances is less clear, but CPA disturbances correlate with worse clinical outcome. Also, in communityacquired bacterial meningitis, CPA dysfunction is frequent and correlates with worse clinical outcome, but autoregulatory management is yet to be evaluated. In this review, we discuss the role of CPA in different types of brain injury and disease, the strengths and limitations of the monitoring methods, the potentials of autoregulatory management, and future directions in the field.}, keywords = {HEMORRHAGE; traumatic brain injury; SUBARACHNOID HEMORRHAGE; stroke; Intracerebral hemorrhage; cerebral pressure autoregulation}, year = {2022}, eissn = {1878-8769}, pages = {118-131} } @article{MTMT:33183789, title = {Cerebral Autoregulation Monitoring in Traumatic Brain Injury: An Overview of Recent Advances in Personalized Medicine}, url = {https://m2.mtmt.hu/api/publication/33183789}, author = {Zeiler, Frederick A. A. and Aries, Marcel and Czosnyka, Marek and Smielewski, Peter}, doi = {10.1089/neu.2022.0217}, journal-iso = {J NEUROTRAUM}, journal = {JOURNAL OF NEUROTRAUMA}, volume = {39}, unique-id = {33183789}, issn = {0897-7151}, abstract = {Impaired cerebral autoregulation (CA) in moderate/severe traumatic brain injury (TBI) has been identified as a strong associate with poor long-term outcomes, with recent data highlighting its dominance over cerebral physiological dysfunction seen in the acute phase post-injury. With advances in bedside continuous cerebral physiological signal processing, continuously derived metrics of CA capacity have been described over the past two decades, leading to improvements in cerebral physiological insult detection and development of novel personalized approaches to TBI care in the intensive care unit (ICU). This narrative review focuses on highlighting the concept of continuous CA monitoring and consequences of impairment in moderate/severe TBI. Further, we provide a comprehensive description and overview of the main personalized cerebral physiological targets, based on CA monitoring, that are emerging as strong associates with patient outcomes. The CA-based personalized targets, such as optimal cerebral perfusion pressure (CPPopt), lower/upper limit of regulation (LLR/ULR), and individualized intracranial pressure (iICP) are positioned to change the way we care for patients with TBI in the ICU, moving away from the "one treatment fits all" paradigm of current guideline-based therapeutic approaches toward a true personalized medicine approach tailored to the individual patient. Future perspectives regarding research needs in this field are also discussed.}, keywords = {traumatic brain injury; personalized medicine; AUTOREGULATION; Individualized care; digital medicine}, year = {2022}, eissn = {1557-9042}, pages = {1477-1494} } @article{MTMT:32439144, title = {Cerebrovascular pressure reactivity and intracranial pressure are associated with neurologic outcome after hypoxic-ischemic brain injury}, url = {https://m2.mtmt.hu/api/publication/32439144}, author = {Balu, Ramani and Rajagopalan, Swarna and Baghshomali, Sanam and Kirschen, Matthew and Amurthur, Ashwin and Kofke, W. Andrew and Abella, Benjamin S.}, doi = {10.1016/j.resuscitation.2021.04.023}, journal-iso = {RESUSCITATION}, journal = {RESUSCITATION}, volume = {164}, unique-id = {32439144}, issn = {0300-9572}, abstract = {Aim: We evaluated the association of physiological parameters measured by intracranial multimodality neuromonitoring with neurologic outcome in a consecutive series of patients with hypoxic-ischemic brain injury (HIBI).Methods: We retrospectively identified all patients with HIBI who underwent combined invasive intracranial pressure (ICP) and brain tissue oxygen (PbtO2) monitoring over a 3 year period. Cerebrovascular pressure reactivity index (PRx) was calculated continuously as a surrogate of cerebral autoregulation. Favorable outcome was defined as recovery of consciousness (Glasgow Coma Scale motor score = 6). Differences in mean ICP, PRx and PbtO2 for the entire monitoring period across outcomes were measured. Logistic regression and area under receiver operating characteristic (AUROC) curve were used to assess the association of each monitoring parameter with neurologic outcome.Results: We analyzed data from 36 patients. Most (89%) had an antecedent sudden cardiac arrest. Favorable outcome occurred in 8 (22%) patients. ICP and PRx were higher in patients with unfavorable outcome (ICP: 26 +/- 4.1 mmHg vs 7.5 +/- 2 mmHg, p = 0.0002; PRx: 0.51 +/- 0.05 vs 0.11 +/- 0.05, p < 0.0001). There was no significant difference in PbtO2 between groups (unfavorable: 20 +/- 2.4 mmHg vs favorable: 25 +/- 1.5 mmHg, p = 0.12). Both ICP (AUROC 0.84, 95%CI 0.72-0.98, p = 0.003) and PRx (AUROC 0.94, 95%CI 0.85-1, p = 0.0002) discriminated between favorable and unfavorable outcome, in contrast to PbtO2, (AUROC 0.59, 95%CI 0.39-0.78, p = 0.52). ICP > 15 mmHg, PRx > 0.2, and PbtO2 < 18 mmHg had sensitivity/specificity of 68%/100%, 89%/88%, and 40%/100% respectively for discriminating outcomes.Conclusion: Cerebrovascular pressure reactivity and intracranial pressure appear to be associated with neurologic outcome in patients with HIBI.}, keywords = {Intracranial Pressure; Cerebral autoregulation; Cardiac arrest; prognostication}, year = {2021}, eissn = {1873-1570}, pages = {114-121}, orcid-numbers = {Rajagopalan, Swarna/0000-0002-0490-503X; Kirschen, Matthew/0000-0003-3585-2687} } @article{MTMT:33341051, title = {Association of Age and Sex With Multi-Modal Cerebral Physiology in Adult Moderate/Severe Traumatic Brain Injury: A Narrative Overview and Future Avenues for Personalized Approaches}, url = {https://m2.mtmt.hu/api/publication/33341051}, author = {Batson, C. and Gomez, A. and Sainbhi, A. S. and Froese, L. and Zeiler, F. A.}, doi = {10.3389/fphar.2021.676154}, journal-iso = {FRONT PHARMACOL}, journal = {FRONTIERS IN PHARMACOLOGY}, volume = {12}, unique-id = {33341051}, abstract = {The impact of age and biological sex on outcome in moderate/severe traumatic brain injury (TBI) has been documented in large cohort studies, with advanced age and male sex linked to worse long-term outcomes. However, the association between age/biological sex and high-frequency continuous multi-modal monitoring (MMM) cerebral physiology is unclear, with only sparing reference made in guidelines and major literature in moderate/severe TBI. In this narrative review, we summarize some of the largest studies associating various high-frequency MMM parameters with age and biological sex in moderate/severe TBI. To start, we present this by highlighting the representative available literature on high-frequency data from Intracranial Pressure (ICP), Cerebral Perfusion Pressure (CPP), Extracellular Brain Tissue Oxygenation (PbtO(2)), Regional Cerebral Oxygen Saturations (rSO(2)), Cerebral Blood Flow (CBF), Cerebral Blood Flow Velocity (CBFV), Cerebrovascular Reactivity (CVR), Cerebral Compensatory Reserve, common Cerebral Microdialysis (CMD) Analytes and their correlation to age and sex in moderate/severe TBI cohorts. Then we present current knowledge gaps in the literature, discuss biological implications of age and sex on cerebrovascular monitoring in TBI and some future avenues for bedside research into the cerebrovascular physiome after TBI.}, keywords = {SEX; Aging; traumatic brain injury; TBI; cerebral physiology; traumatic brain injury (craniocerebral trauma)}, year = {2021}, eissn = {1663-9812} } @article{MTMT:32689036, title = {Impact of Age and Biological Sex on Cerebrovascular Reactivity in Adult Moderate/Severe Traumatic Brain Injury: An Exploratory Analysis}, url = {https://m2.mtmt.hu/api/publication/32689036}, author = {Batson, Carleen and Froese, Logan and Gomez, Alwyn and Sainbhi, Amanjyot Singh and Stein, Kevin Y. and Alizadeh, Arsalan and Zeiler, Frederick A.}, doi = {10.1089/neur.2021.0039}, journal-iso = {NEUROTRAUMA REP}, journal = {NEUROTRAUMA REPORTS}, volume = {2}, unique-id = {32689036}, abstract = {Age and biological sex are two potential important modifiers of cerebrovascular reactivity post-traumatic brain injury (TBI) requiring close evaluation for potential subgroup responses. The goal of this study was to provide a preliminary exploratory analysis of the impact of age and biological sex on measures of cerebrovascular function in moderate/severe TBI. Forty-nine patients from the prospectively maintained TBI database at the University of Manitoba with archived high-frequency digital cerebral physiology were evaluated. Cerebrovascular reactivity indices were derived as follows: PRx (correlation between intracranial pressure [ICP] and mean arterial pressure [MAP]), PAx (correlation between pulse amplitude of ICP [AMP] and MAP), and RAC (correlation between AMP and cerebral perfusion pressure [CPP]). Time above clinically significant thresholds for each index was calculated over different periods of the acute intensive care unit stay. The association between PRx, PAx, and RAC measures with age was assessed using linear regression, and an age trichotomization scheme (<40, 40-60, >60) using Kruskal-Wallis testing. Similarly, association with biological sex was tested using Mann-Whitney U testing. Biological sex did not demonstrate an impact on any measures of cerebrovascular reactivity. Linear regression between age and PAx and RAC demonstrated a statistically significant positive linear relationship. Median PAx and RAC measures between trichotomized age categories demonstrated statistically significant increases with advancing age. The PRx failed to demonstrate any statistically significant relationship with age in this cohort, suggesting that in elderly patients with controlled ICP, PAx and RAC may be better metrics for detecting impaired cerebrovascular reactivity. Biological sex appears to not be associated with differences in cerebrovascular reactivity in this cohort. The PRx performed the worst in detecting impaired cerebrovascular reactivity in those with advanced age, where PAx and RAC appear to have excelled. Future work is required to validate these findings and explore the utility of different cerebrovascular reactivity indices.}, keywords = {Aging; MANAGEMENT; Cerebrovascular reactivity; Signal processing; CARE; Clinical Neurology; INTRACRANIAL-PRESSURE; biological sex; CENTER-TBI; NEUROTRAUMA EFFECTIVENESS RESEARCH}, year = {2021}, eissn = {2689-288X}, pages = {488-501}, orcid-numbers = {Sainbhi, Amanjyot Singh/0000-0003-3231-5683; Zeiler, Frederick A./0000-0003-1737-0510} } @article{MTMT:32439149, title = {Sedation and cerebrovascular reactivity in traumatic brain injury: another potential avenue for personalized approaches in neurocritical care?}, url = {https://m2.mtmt.hu/api/publication/32439149}, author = {Froese, L. and Dian, J. and Gomez, A. and Zeiler, F. A.}, doi = {10.1007/s00701-020-04662-6}, journal-iso = {ACTA NEUROCHIR}, journal = {ACTA NEUROCHIRURGICA}, volume = {163}, unique-id = {32439149}, issn = {0001-6268}, abstract = {Background Impaired cerebrovascular reactivity appears to be linked to worse global outcome in adult traumatic brain injury (TBI). Literature suggests that current treatments administered in TBI care, in the intensive care unit (ICU), fail to greatly impact recorded cerebrovascular reactivity measures. In particular, the impact of sedation on cerebrovascular reactivity in traumatic brain injury (TBI) remains unclear in vivo. The goal of this study was to preliminarily assess the relationship between objectively measured depth of sedation and cerebrovascular reactivity in TBI.Methods Within, we describe a case series of 5 adult TBI patients with TBI, during which objective high-frequency physiology for sedation depth, using bispectral index (BIS), and both intracranial pressure (ICP) and arterial blood pressure (ABP) were recorded. Pressure reactivity index (PRx) and RAP (a metric of cerebral compensatory reserve) were derived. Relationships between cerebrovascular reactivity and compensatory reserve monitoring with BIS metrics were explored using descriptive plots.Results A total of 5 cases in our prospectively maintained database with high-frequency physiology for ICP, ABP, and BIS. Through error bar plotting, it can be seen that each patient displays a parabolic relationship between BIS and PRx. This suggests a potential "optimal" depth of sedation where cerebrovascular reactivity is the most intact.Conclusions This small series highlights the potential impact of depth of sedation on cerebrovascular reactivity in TBI. It suggests that there may be an individual optimal depth of sedation, so as to optimize cerebrovascular reactivity. Further study of objective depth of sedation and its impact on cerebrovascular physiology in TBI is required.}, keywords = {Cerebrovascular reactivity; TBI; Depth of sedation; Optimal sedation}, year = {2021}, eissn = {0942-0940}, pages = {1383-1389} } @article{MTMT:34556000, title = {Non-Invasive Continuous Cerebrovascular Monitoring for Subacute Bedside and Outpatient Settings: An Important Advancement}, url = {https://m2.mtmt.hu/api/publication/34556000}, author = {Gomez, Alwyn and Zeiler, Frederick A.}, doi = {10.1089/neur.2020.0064}, journal-iso = {NEUROTRAUMA REP}, journal = {NEUROTRAUMA REPORTS}, volume = {2}, unique-id = {34556000}, keywords = {Clinical Neurology}, year = {2021}, eissn = {2689-288X}, pages = {25-26} } @article{MTMT:33047617, title = {Prediction of Life-Threatening Intracranial Hypertension During the Acute Phase of Traumatic Brain Injury Using Machine Learning}, url = {https://m2.mtmt.hu/api/publication/33047617}, author = {Lee, Hack-Jin and Kim, Hakseung and Kim, Young-Tak and Won, Kanghee and Czosnyka, Marek and Kim, Dong-Joo}, doi = {10.1109/JBHI.2021.3085881}, journal-iso = {IEEE J BIOMED HEALTH}, journal = {IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS}, volume = {25}, unique-id = {33047617}, issn = {2168-2194}, abstract = {Intracranial hypertension (IH) following acute phase traumatic brain injury (TBI) is associated with high mortality. Objective: This study proposes a novel parameter that may identify a potentially life-threatening IH (LTH) event and designs a machine learning model to predict LTH. Continuous recordings of intracranial pressure (ICP) and arterial blood pressure (ABP) from 273 TBI patients were used as the development dataset. The pressure-time dose (PTD) and pressure reactivity index (PRx) were calculated for each IH event, and an IH event with PRx > 0 and PTD > 5 was considered an LTH event. The association between the LTH parameters accumulated over five days and mortality was analyzed. A categorical boosting (CatBoost) model was employed to predict the occurrence of a future LTH event from the onset of IH using the ABP- and ICP-related parameters. Training and validation were performed on a total of 5,938 IH events. External performance evaluation was performed in 307 IH events included in the Cerebral Haemodynamic Autoregulatory Information System (CHARIS) database. The performance of the proposed model was evaluated through the area under the receiver operating characteristic curve (AUROC). The LTH parameters were able to distinguish between the deceased and surviving patients (AUROC > 0.7, p < 0.001). The CatBoost model predicted LTH with an AUROC = 0.7 on the external test dataset. This study demonstrated that the proposed LTH prediction model has a reasonable predictive capacity for mortality. The CatBoost model anticipates whether an IH event will develop into an LTH event. The findings of this study support the usefulness of ICP monitoring.}, keywords = {PRESSURE; HYPERTENSION; REACTIVITY; MONITORING; machine learning; MANAGEMENT; traumatic brain injury; Standards; THRESHOLDS; Clinical outcome; Intracranial Hypertension; Windows; Predictive models; Computer Science, Interdisciplinary Applications; neuromonitoring; Computer Science, Information Systems; Mathematical & Computational Biology; WAVE-FORM; brain modeling; AUTOREGULATORY INDEXES}, year = {2021}, eissn = {2168-2208}, pages = {3967-3976}, orcid-numbers = {Kim, Hakseung/0000-0001-5407-293X} } @article{MTMT:33449982, title = {Continuous Time-Domain Cerebrovascular Reactivity Metrics and Discriminate Capacity for the Upper and Lower Limits of Autoregulation: A Scoping Review of the Animal Literature}, url = {https://m2.mtmt.hu/api/publication/33449982}, author = {Sainbhi, Amanjyot Singh and Froese, Logan and Gomez, Alwyn and Batson, Carleen and Stein, Kevin Y. and Alizadeh, Arsalan and Zeiler, Frederick A.}, doi = {10.1089/neur.2021.0043}, journal-iso = {NEUROTRAUMA REP}, journal = {NEUROTRAUMA REPORTS}, volume = {2}, unique-id = {33449982}, abstract = {Over a wide range of systemic arterial pressures, cerebral blood flow (CBF) is regulated fairly constantly by the cerebral vessels in a process termed cerebral autoregulation (CA), which is depicted by the Lassen autoregulatory curve. After traumatic brain injury (TBI), CA can get impaired and these impairments manifest in changes of the Lassen autoregulatory curve. Continuous surrogate metrics of pressure-based CA, termed cerebrovascular reactivity (CVR) metrics, evaluate the relationship between slow vasogenic fluctuations in a driving pressure for cerebral blood flow, and the most commonly studied and utilized measures are based in the time domain and have been increasingly applied in bedside TBI care and have sparked the investigation of individualized cerebral perfusion pressure targets. However, not all CVR metrics have been validated as true measures of autoregulation in the pre-clinical setting. We reviewed all available pre-clinical animal literature that assessed the association between continuous time-domain metrics of CVR and some aspect of the Lassen autoregulatory curve. All 15 articles found associated the evaluated continuous metrics to the lower limit of autoregulation curve whereas none looked at the upper limit. Most of the evaluated metrics showed the ability to discriminate the lower limit of autoregulation with various methods of perturbation. Further work is required to evaluate the utility of such surrogate measures against the upper limit of autoregulation, while also providing validation to the existing literature supporting specific indices and their ability to discriminate the lower limit.}, keywords = {CEREBROVASCULAR AUTOREGULATION; cerebrovascular reactivity metrics; Lassen autoregulatory curve; lower limit of autoregulation; time-domain metrics}, year = {2021}, eissn = {2689-288X}, pages = {639-659}, orcid-numbers = {Sainbhi, Amanjyot Singh/0000-0003-3231-5683} } @article{MTMT:32438129, title = {Advanced Bio-signal Analytics for Continuous Bedside Monitoring of Aneurysmal Subarachnoid Hemorrhage: The Future}, url = {https://m2.mtmt.hu/api/publication/32438129}, author = {Zeiler, Frederick A.}, doi = {10.1007/s12028-020-01170-4}, journal-iso = {NEUROCRIT CARE}, journal = {NEUROCRITICAL CARE}, volume = {34}, unique-id = {32438129}, issn = {1541-6933}, year = {2021}, eissn = {1556-0961}, pages = {375-378} } @article{MTMT:31722244, title = {Association between Physiological Signal Complexity and Outcomes in Moderate and Severe Traumatic Brain Injury: A CENTER-TBI Exploratory Analysis of Multi-Scale Entropy}, url = {https://m2.mtmt.hu/api/publication/31722244}, author = {Zeiler, Frederick A. and Ercole, Ari and Placek, Michal M. and Hutchinson, Peter J. and Stocchetti, Nino and Czosnyka, Marek and Smielewski, Peter}, doi = {10.1089/neu.2020.7249}, journal-iso = {J NEUROTRAUM}, journal = {JOURNAL OF NEUROTRAUMA}, volume = {38}, unique-id = {31722244}, issn = {0897-7151}, abstract = {In traumatic brain injury (TBI), preliminary retrospective work on signal entropy suggests an association with global outcome. The goal of this study was to provide multi-center validation of the association between multi-scale entropy (MSE) of cardiovascular and cerebral physiological signals, with six-month outcome. Using the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) high-resolution intensive care unit (ICU) cohort, we selected patients with a minimum of 72 h of physiological recordings and a documented six-month Glasgow Outcome Scale Extended (GOSE) score. The 10-sec summary data for heart rate (HR), mean arterial pressure (MAP), intracranial pressure (ICP), and pulse amplitude of ICP (AMP) were derived across the first 72 h of data. The MSE complexity index (MSE-Ci) was determined for HR, MAP, ICP, and AMP, with the association between MSE and dichotomized six-month outcomes assessed using Mann-WhitneyUtesting and logistic regression analysis. A total of 160 patients had a minimum of 72 h of recording and a documented outcome. Decreased HR MSE-Ci (7.3 [interquartile range (IQR) 5.4 to 10.2] vs. 5.1 [IQR 3.1 to 7.0];p = 0.002), lower ICP MSE-Ci (11.2 [IQR 7.5 to 14.2] vs. 7.3 [IQR 6.1 to 11.0];p = 0.009), and lower AMP MSE-Ci (10.9 [IQR 8.0 to 13.7] vs. 8.7 [IQR 6.6 to 11.0];p = 0.022), were associated with death. Similarly, lower HR MSE-Ci (8.0 [IQR 6.2 to 10.9] vs. 6.2 [IQR 3.9 to 8.7];p = 0.003) and lower ICP MSE-Ci (11.4 [IQR 8.6 to 14.4)] vs. 9.2 [IQR 6.0 to 13.5]), were associated with unfavorable outcome. Logistic regression analysis confirmed that lower HR MSE-Ci and ICP MSE-Ci were associated with death and unfavorable outcome at six months. These findings suggest that a reduction in cardiovascular and cerebrovascular system entropy is associated with worse outcomes. Further work in the field of signal complexity in TBI multi-modal monitoring is required.}, keywords = {AUTOREGULATION; outcome; complexity; cerebral physiology; multi-scale entropy}, year = {2021}, eissn = {1557-9042}, pages = {272-282} } @article{MTMT:32383412, title = {Integrative Neuroinformatics for Precision Prognostication and Personalized Therapeutics in Moderate and Severe Traumatic Brain Injury}, url = {https://m2.mtmt.hu/api/publication/32383412}, author = {Zeiler, Frederick A. and Iturria-Medina, Yasser and Thelin, Eric P. and Gomez, Alwyn and Shankar, Jai J. and Ko, Ji Hyun and Figley, Chase R. and Wright, Galen E. B. and Anderson, Chris M.}, doi = {10.3389/fneur.2021.729184}, journal-iso = {FRONT NEUR}, journal = {FRONTIERS IN NEUROLOGY}, volume = {12}, unique-id = {32383412}, issn = {1664-2295}, abstract = {Despite changes in guideline-based management of moderate/severe traumatic brain injury (TBI) over the preceding decades, little impact on mortality and morbidity have been seen. This argues against the "one-treatment fits all" approach to such management strategies. With this, some preliminary advances in the area of personalized medicine in TBI care have displayed promising results. However, to continue transitioning toward individually-tailored care, we require integration of complex "-omics" data sets. The past few decades have seen dramatic increases in the volume of complex multi-modal data in moderate and severe TBI care. Such data includes serial high-fidelity multi-modal characterization of the cerebral physiome, serum/cerebrospinal fluid proteomics, admission genetic profiles, and serial advanced neuroimaging modalities. Integrating these complex and serially obtained data sets, with patient baseline demographics, treatment information and clinical outcomes over time, can be a daunting task for the treating clinician. Within this review, we highlight the current status of such multi-modal omics data sets in moderate/severe TBI, current limitations to the utilization of such data, and a potential path forward through employing integrative neuroinformatic approaches, which are applied in other neuropathologies. Such advances are positioned to facilitate the transition to precision prognostication and inform a top-down approach to the development of personalized therapeutics in moderate/severe TBI.}, keywords = {traumatic brain injury; big data; Multi-modal data; Precision Medicine; neuroinformatics}, year = {2021}, eissn = {1664-2295} } @article{MTMT:32439146, title = {Point-of-Care Noninvasive Assessments of Cerebrovascular Reactivity in Traumatic Brain Injury: Integrating the Physiome with Clinical Phenotype}, url = {https://m2.mtmt.hu/api/publication/32439146}, author = {Zeiler, Frederick A.}, doi = {10.1002/ana.26092}, journal-iso = {ANN NEUROL}, journal = {ANNALS OF NEUROLOGY}, volume = {90}, unique-id = {32439146}, issn = {0364-5134}, year = {2021}, eissn = {1531-8249}, pages = {19-21} } @article{MTMT:31813170, title = {Systemic Markers of Injury and Injury Response Are Not Associated with Impaired Cerebrovascular Reactivity in Adult Traumatic Brain Injury: A Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study}, url = {https://m2.mtmt.hu/api/publication/31813170}, author = {Zeiler, Frederick A. and Mathieu, Francois and Monteiro, Miguel and Glocker, Ben and Ercole, Ari and Cabeleira, Manuel and Stocchetti, Nino and Smielewski, Peter and Czosnyka, Marek and Newcombe, Virginia and Menon, David K.}, doi = {10.1089/neu.2020.7304}, journal-iso = {J NEUROTRAUM}, journal = {JOURNAL OF NEUROTRAUMA}, volume = {38}, unique-id = {31813170}, issn = {0897-7151}, abstract = {The role of extra-cranial injury burden and systemic injury response on cerebrovascular response in traumatic brain injury (TBI) is poorly documented. This study preliminarily assesses the association between admission features of extra-cranial injury burden on cerebrovascular reactivity. Using the Collaborative European Neurotrauma Effectiveness Research in TBI High-Resolution ICU (HR ICU) sub-study cohort, we evaluated those patients with both archived high-frequency digital intra-parenchymal intra-cranial pressure monitoring data of a minimum of 6 h in duration, and the presence of a digital copy of their admission computed tomography (CT) scan. Digital physiologic signals were processed for pressure reactivity index (PRx) and both the percent time above defined PRx thresholds and mean hourly dose above threshold. This was conducted for both the first 72 h and entire duration of recording. Admission extra-cranial injury characteristics and CT injury scores were obtained from the database, with quantitative contusion, edema, intraventricular hemorrhage, and extra-axial lesion volumes were obtained via semi-automated segmentation. Comparison between admission extra-cranial markers of injury and PRx metrics was conducted using Mann-Whitney U testing, and logistic regression techniques, adjusting for known CT injury metrics associated with impaired PRx. A total of 165 patients were included. Evaluating the entire ICU recording period, there was limited association between metrics of extra-cranial injury burden and impaired cerebrovascular reactivity. Using the first 72 h of recording, admission temperature (p = 0.042) and white blood cell % (WBC %; p = 0.013) were statistically associated with impaired cerebrovascular reactivity on Mann-Whitney U and univariate logistic regression. After adjustment for admission age, pupillary status, GCS motor score, pre-hospital hypoxia/hypotension, and intra-cranial CT characteristics associated with impaired reactivity, temperature (p = 0.021) and WBC % (p = 0.013) remained significantly associated with mean PRx values above +0.25 and +0.35, respectively. Markers of extra-cranial injury burden and systemic injury response do not appear to be strongly associated with impaired cerebrovascular reactivity in TBI during both the initial and entire ICU stay.}, keywords = {MANAGEMENT; Cerebrovascular reactivity; AUTOREGULATION; AUTOREGULATION; MODERATE; Clinical Neurology; Critical Care Medicine; INTRACRANIAL-PRESSURE; CEREBRAL PERFUSION-PRESSURE; extra-cranial injury; injury burden}, year = {2021}, eissn = {1557-9042}, pages = {870-878}, orcid-numbers = {Zeiler, Frederick A./0000-0003-1737-0510; Ercole, Ari/0000-0001-8350-8093} } @article{MTMT:32519800, title = {Novel approaches to prediction in severe brain injury}, url = {https://m2.mtmt.hu/api/publication/32519800}, author = {Fidali, Brian C. and Stevens, Robert D. and Claassen, Jan}, doi = {10.1097/WCO.0000000000000875}, journal-iso = {CURR OPIN NEUROL}, journal = {CURRENT OPINION IN NEUROLOGY}, volume = {33}, unique-id = {32519800}, issn = {1350-7540}, abstract = {Purpose of review Recovery after severe brain injury is variable and challenging to accurately predict at the individual patient level. This review highlights new developments in clinical prognostication with a special focus on the prediction of consciousness and increasing reliance on methods from data science. Recent findings Recent research has leveraged serum biomarkers, quantitative electroencephalography, MRI, and physiological time-series to build models for recovery prediction. The analysis of high-resolution data and the integration of features from different modalities can be approached with efficient computational techniques. Advances in neurophysiology and neuroimaging, in combination with computational methods, represent a novel paradigm for prediction of consciousness and functional recovery after severe brain injury. Research is needed to produce reliable, patient-level predictions that could meaningfully impact clinical decision making.}, keywords = {Electroencephalography; traumatic brain injury; Consciousness; Coma; Anoxic brain injury}, year = {2020}, eissn = {1473-6551}, pages = {669-675} } @article{MTMT:32689230, title = {Cerebrovascular Response to Phenylephrine in Traumatic Brain Injury: A Scoping Systematic Review of the Human and Animal Literature}, url = {https://m2.mtmt.hu/api/publication/32689230}, author = {Froese, Logan and Dian, Joshua and Gomez, Alwyn and Unger, Bertram and Zeiler, Frederick A.}, doi = {10.1089/neur.2020.0008}, journal-iso = {NEUROTRAUMA REP}, journal = {NEUROTRAUMA REPORTS}, volume = {1}, unique-id = {32689230}, abstract = {Intravenous phenylephrine (PE) is utilized commonly in critical care for cardiovascular support. Its impact on the cerebrovasculature is unclear and its use may have important implications during states of critical neurological illness. The aim of this study was to perform a scoping review of the literature on the cerebrovascular/cerebral blood flow (CBF) effects of PE in traumatic brain injury (TBI), evaluating both animal models and human studies. We searched MEDLINE, BIOSIS, EMBASE, Global Health, SCOPUS, and the Cochrane Library from inception to January 2020. We identified 12 studies with various animal models and 4 studies in humans with varying TBI pathology. There was a trend toward a consistent increase in mean arterial pressure (MAP) by the injection of PE systemically, and by proxy, an increase of the cerebral perfusion pressure (CPP). There was a consistent constriction of cerebral vessels by PE reported in the small number of studies documenting such a response. However, the heterogeneity of the literature on the CBF/cerebral blood volume (CBV) response makes the strength of the conclusions on PE limited. Studies were heterogeneous in design and had significant limitations, with most failing to adjust for confounding factors in cerebrovascular/CBF response. This review highlights the significant knowledge gap on the cerebrovascular/CBF effects of PE administration in TBI, calling for further study on the impact of PE on the cerebrovasculature both in vivo and in experimental settings.}, keywords = {Therapy; REACTIVITY; MANAGEMENT; hypotension; Cerebrovascular reactivity; cerebral blood flow; Clinical Neurology; INTRACRANIAL-PRESSURE; Cerebral blood volume; CEREBRAL PERFUSION-PRESSURE; cerebrovascular response; BLOOD-FLOW AUTOREGULATION; LOWER LIMIT; NEUROTRAUMA EFFECTIVENESS RESEARCH}, year = {2020}, eissn = {2689-288X}, pages = {46-62} } @article{MTMT:34555652, title = {Cerebrovascular Response to Propofol, Fentanyl, and Midazolam in Moderate/Severe Traumatic Brain Injury: A Scoping Systematic Review of the Human and Animal Literature}, url = {https://m2.mtmt.hu/api/publication/34555652}, author = {Froese, Logan and Dian, Joshua and Batson, Carleen and Gomez, Alwyn and Unger, Bertram and Zeiler, Frederick A.}, doi = {10.1089/neur.2020.0040}, journal-iso = {NEUROTRAUMA REP}, journal = {NEUROTRAUMA REPORTS}, volume = {1}, unique-id = {34555652}, abstract = {Intravenous propofol, fentanyl, and midazolam are utilized commonly in critical care for metabolic suppression and anesthesia. The impact of propofol, fentanyl, andmidazolamon cerebrovasculature and cerebral blood flow (CBF) is unclear in traumatic brain injury (TBI) and may carry important implications, as care is shifting to focus on cerebrovascular reactivity monitoring/directed therapies. The aim of this study was to perform a scoping review of the literature on the cerebrovascular/CBF effects of propofol, fentanyl, and midazolam in human patients with moderate/severe TBI and animal models with TBI. A search of MEDLINE, BIOSIS, EMBASE, Global Health, SCOPUS, and the Cochrane Library from inception to May 2020 was performed. All articles were included pertaining to the administration of propofol, fentanyl, and midazolam, in which the impact on CBF/cerebral vasculature was recorded. We identified 14 studies: 8 that evaluated propofol, 5 that evaluated fentanyl, and 2 that evaluated midazolam. All studies suffered fromsignificant limitations, including: small sample size, and heterogeneous design and measurement techniques. In general, there was no significant change seen in CBF/cerebrovascular response to administration of propofol, fentanyl, or midazolam during experiments where PCO2 and mean arterial pressure (MAP) were controlled. This review highlights the current knowledge gap surrounding the impact of commonly utilized sedative drugs in TBI care. This work supports the need for dedicated studies, both experimental and human-based, evaluating the impact of these drugs on CBF and cerebrovascular reactivity/response in TBI.}, keywords = {BLOOD-FLOW; metabolism; OXYGEN; REACTIVITY; midazolam; fentanyl; AUTOREGULATION; HEAD-INJURY; brain injury; cerebral blood flow; Clinical Neurology; INTRACRANIAL-PRESSURE; CEREBRAL PERFUSION-PRESSURE; cerebrovascular response; NEUROTRAUMA EFFECTIVENESS RESEARCH}, year = {2020}, eissn = {2689-288X}, pages = {100-112}, orcid-numbers = {Zeiler, Frederick A./0000-0003-1737-0510} } @article{MTMT:31684897, title = {The cerebrovascular response to norepinephrine: A scoping systematic review of the animal and human literature}, url = {https://m2.mtmt.hu/api/publication/31684897}, author = {Froese, Logan and Dian, Joshua and Gomez, Alwyn and Unger, Bertram and Zeiler, Frederick A.}, doi = {10.1002/prp2.655}, journal-iso = {PHARMACOL RES PERSPECT}, journal = {PHARMACOLOGY RESEARCH AND PERSPECTIVES}, volume = {8}, unique-id = {31684897}, issn = {2052-1707}, abstract = {Intravenous norepinephrine (NE) is utilized commonly in critical care for cardiovascular support. NE's impact on cerebrovasculature is unclear and may carry important implications during states of critical neurological illness. The aim of the study was to perform a scoping review of the literature on the cerebrovascular/cerebral blood flow (CBF) effects of NE. A search of MEDLINE, BIOSIS, EMBASE, Global Health, SCOPUS, and Cochrane Library from inception to December 2019 was performed. All manuscripts pertaining to the administration of NE, in which the impact on CBF/cerebral vasculature was recorded, were included. We identified 62 animal studies and 26 human studies. Overall, there was a trend to a direct vasoconstriction effect of NE on the cerebral vasculature, with conflicting studies having demonstrated both increases and decreases in regional CBF (rCBF) or global CBF. Healthy animals and those undergoing cardiopulmonary resuscitation demonstrated a dose-dependent increase in CBF with NE administration. However, animal models and human patients with acquired brain injury had varied responses in CBF to NE administration. The animal models indicate an increase in cerebral vasoconstriction with NE administration through the alpha receptors in vessels. Global and rCBF during the injection of NE displays a wide variation depending on treatment and model/patient.}, keywords = {NOREPINEPHRINE; cerebral blood flow; cerebrovascular response}, year = {2020}, eissn = {2052-1707}, orcid-numbers = {Froese, Logan/0000-0002-6076-0189} } @article{MTMT:31722247, title = {The impact of hypertonic saline on cerebrovascular reactivity and compensatory reserve in traumatic brain injury: an exploratory analysis}, url = {https://m2.mtmt.hu/api/publication/31722247}, author = {Froese, Logan and Dian, Joshua and Batson, Carleen and Gomez, Alwyn and Unger, Bertram and Zeiler, Frederick A.}, doi = {10.1007/s00701-020-04579-0}, journal-iso = {ACTA NEUROCHIR}, journal = {ACTA NEUROCHIRURGICA}, volume = {162}, unique-id = {31722247}, issn = {0001-6268}, abstract = {Background Intravenous hypertonic saline is utilized commonly in critical care for treatment of acute or refractory elevations of intracranial pressure (ICP) in traumatic brain injury (TBI) patients. Though there is a clear understanding of the general physiological effects of a hypertonic saline solution over long periods of time, smaller epoch effects of hypertonic saline (HTS) have not been thoroughly analyzed. The aim of this study was to perform a direct evaluation of the high-frequency response of HTS on the cerebrovascular physiological responses in TBI. Methods We retrospectively reviewed our prospectively maintained adult TBI database for those with archived high-frequency cerebral physiology and available HTS treatment information. We evaluated different epochs of physiology around HTS bolus dosing, comparing pre- with post-HTS. We assessed for changes in slow fluctuations in ICP, pulse amplitude of ICP (AMP), cerebral perfusion pressure (CPP), mean arterial pressure (MAP), cerebrovascular reactivity (as measured through pressure reactivity index (PRx)), and cerebral compensatory reserve (correlation (R) between AMP (A) and ICP (P)). Comparisons of mean measures and percentage time above clinically relevant thresholds for the physiological parameters were compared pre- and post-HTS using descriptive statistics and Mann-WhitneyUtesting. We assessed for subgroups of physiological responses using latent profile analysis (LPA). Results Fifteen patients underwent 69 distinct bolus infusions of hypertonic saline. Apart from the well-documented decrease in ICP, there was also a reduction in AMP. The analysis of cerebrovascular reactivity response to HTS solution had two main effects. For patients with grossly impaired cerebrovascular reactivity pre-HTS (PRx > + 0.30), HTS bolus led to improved reactivity. However, for those with intact cerebrovascular reactivity pre-HTS (PRx < 0), HTS bolus demonstrated a trend towards more impaired reactivity. This indicates that HTS has different impacts, dependent on pre-bolus cerebrovascular status. There was no significant change in metrics of cerebral compensatory reserve. LPA failed to demonstrate any subgroups of physiological responses to HTS administration. Conclusions The direct decrease in ICP and AMP confirms that a bolus dose of a HTS solution is an effective therapeutic agent for intracranial hypertension. However, in patients with intact autoregulation, hypertonic saline may impair cerebral hemodynamics. These findings regarding cerebrovascular reactivity remain preliminary and require further investigation.}, keywords = {Cerebrovascular Circulation; sodium chloride; Intracranial Pressure; HYPERTONIC SALINE; cerebrovascular response; Pressure reactivity index}, year = {2020}, eissn = {0942-0940}, pages = {2683-2693} } @article{MTMT:32689227, title = {The Impact of Vasopressor and Sedative Agents on Cerebrovascular Reactivity and Compensatory Reserve in Traumatic Brain Injury: An Exploratory Analysis}, url = {https://m2.mtmt.hu/api/publication/32689227}, author = {Froese, Logan and Dian, Joshua and Batson, Carleen and Gomez, Alwyn and Alarifi, Norah and Unger, Bertram and Zeiler, Frederick A.}, doi = {10.1089/neur.2020.0028}, journal-iso = {NEUROTRAUMA REP}, journal = {NEUROTRAUMA REPORTS}, volume = {1}, unique-id = {32689227}, abstract = {The impact of vasopressor and sedative drugs on cerebrovascular reactivity in traumatic brain injury (TBI) remains unclear. The aim of this study was to evaluate the impact of changes of doses of commonly administered sedation (i.e., propofol, fentanyl, and ketamine) and vasopressor agents (i.e., norepinephrine [NE], phenylephrine [PE], and vasopressin[VSP]) on cerebrovascular reactivity and compensatory reserve in patients with moderate/severe TBI. Using the Winnipeg Acute TBI Database, we identified 38 patients with more than 1000 distinct changes of infusion rates and more than 500 h of paired drug infusion/physiology data. Cerebrovascular reactivity was assessed using pressure reactivity index (PRx) and cerebral compensatory reserve was assessed using RAP (the correlation [R] between pulse amplitude of intracranial pressure [ICP; A] and ICP [P]). We evaluated the data in two phases. First, we assessed the relationship between mean hourly dose of medication and its relation to both mean hourly index values, and time spent above a given index threshold. Second, we evaluated time-series data for each individual dose change per medication, assessing for a statistically significant change in PRx and RAP metrics. The results of the analysis confirmed that, overall, the mean hourly dose of sedative (propofol, fentanyl, and ketamine) and vasopressor (NE, PE, and VSP) agents does not impact hourly cerebrovascular reactivity or compensatory reserve measures. Similarly, incremental dose changes in these medications in general do not lead to significant changes in cerebrovascular reactivity or compensatory reserve. For propofol with incremental dose increases, in situations where PRx is intact (i.e., PRx < 0 prior), a statistically significant increase in PRx was seen. However, this may not indicate deteriorating cerebrovascular reactivity as the final PRx (similar to 0.05) may still be considered to be intact cerebrovascular reactivity. As such, this finding with regards to propofol remains "weak." This study indicates that commonly administered sedative and vasopressor agents with incremental dosing changes have no clinically significant influence on cerebrovascular reactivity or compensatory reserve in TBI. These results should be considered preliminary, requiring further investigation.}, keywords = {VALIDATION; MANAGEMENT; Cerebrovascular reactivity; AUTOREGULATION; AUTOREGULATION; THRESHOLDS; Clinical Neurology; Compensatory reserve; CEREBRAL PERFUSION-PRESSURE; Sedative drugs; LOWER LIMIT; NEUROTRAUMA EFFECTIVENESS RESEARCH}, year = {2020}, eissn = {2689-288X}, pages = {157-168}, orcid-numbers = {Zeiler, Frederick A./0000-0003-1737-0510} } @article{MTMT:34423687, title = {Continuous and entirely non-invasive method for cerebrovascular reactivity assessment: technique and implications}, url = {https://m2.mtmt.hu/api/publication/34423687}, author = {Gomez, A. and Dian, J. and Zeiler, F. A.}, doi = {10.1007/s10877-020-00472-4}, journal-iso = {J CLIN MONITOR COMP}, journal = {JOURNAL OF CLINICAL MONITORING AND COMPUTING}, volume = {35}, unique-id = {34423687}, issn = {1387-1307}, abstract = {Continuous cerebrovascular reactivity assessment in traumatic brain injury (TBI) has been limited by the need for invasive monitoring of either cerebral physiology or arterial blood pressure (ABP). This restricts the application of continuous measures to the acute phase of care, typically in the intensive care unit. It remains unknown if ongoing impairment of cerebrovascular reactivity occurs in the subacute and long-term phase, and if it drives ongoing morbidity in TBI. We describe an entirely non-invasive method for continuous assessment of cerebrovascular reactivity. We describe the technique for entirely non-invasive continuous assessment of cerebrovascular reactivity utilizing near-infrared spectroscopy (NIRS) and robotic transcranial Doppler (rTCD) technology, with details provided for NIRS. Recent advances in continuous high-frequency non-invasive ABP measurement, combined with NIRS or rTCD, can be employed to derive continuous and entirely non-invasive cerebrovascular reactivity metrics. Such non-invasive measures can be obtained during any aspect of patient care post-TBI, and even during outpatient follow-up, avoiding classical intermittent techniques and costly neuroimaging based metrics obtained only at specialized centers. This combination of technology and signal analytic techniques creates avenues for future investigation of the long-term consequences of cerebrovascular reactivity, integrating high-frequency non-invasive cerebral physiology, neuroimaging, proteomics and clinical phenotype at various stages post-injury.}, keywords = {Cerebrovascular reactivity; SUBARACHNOID HEMORRHAGE; TRANSCRANIAL DOPPLER; AUTOREGULATION; INDEXES; TRAUMATIC BRAIN-INJURY; STATEMENT; PART I; Non-invasive; NIRS; CEREBRAL PERFUSION-PRESSURE; AUTOREGULATION MEASUREMENT TECHNIQUES; MULTIDISCIPLINARY CONSENSUS CONFERENCE}, year = {2020}, eissn = {1573-2614}, pages = {307-315} } @article{MTMT:34771642, title = {Alternative continuous intracranial pressure-derived cerebrovascular reactivity metrics in traumatic brain injury: a scoping overview}, url = {https://m2.mtmt.hu/api/publication/34771642}, author = {Hasen, M. and Gomez, A. and Froese, L. and Dian, J. and Raj, R. and Thelin, E.P. and Zeiler, F.A.}, doi = {10.1007/s00701-020-04378-7}, journal-iso = {ACTA NEUROCHIR}, journal = {ACTA NEUROCHIRURGICA}, volume = {162}, unique-id = {34771642}, issn = {0001-6268}, year = {2020}, eissn = {0942-0940}, pages = {1647-1662} } @article{MTMT:34556001, title = {Effects of Norepinephrine, Propofol, and Hemoglobin Concentration on Dynamic Measurements of Cerebrovascular Reactivity in Acute Brain Injury}, url = {https://m2.mtmt.hu/api/publication/34556001}, author = {Klein, Samuel P. and Fieuws, Steffen and Meyfroidt, Geert and Depreitere, Bart}, doi = {10.1089/neu.2020.7160}, journal-iso = {J NEUROTRAUM}, journal = {JOURNAL OF NEUROTRAUMA}, volume = {38}, unique-id = {34556001}, issn = {0897-7151}, abstract = {Effects of treatment-associated variables on cerebrovascular autoregulation (CA) in acute brain injury patients remain unclear. As deficient CA is associated with worse outcomes and ideas about CA-steered management are emerging, this question is relevant. We investigated effects of norepinephrine and propofol infusion rates and hemoglobin concentration on dynamic measurements of cerebrovascular reactivity as surrogate for CA. A retrospective analysis of 91 traumatic brain injury (TBI) and 13 stroke patients admitted to the intensive care unit (ICU) of the Leuven University Hospitals was performed. Low-resolution autoregulation index (LAx) and high-frequency pressure reactivity index (PRx) were calculated as measurements of cerebrovascular reactivity. Data was binned into 5-, 15-, and 60-min intervals. Bivariate time-series analysis using lagged cross-correlations were calculated after pre-whitening and differencing. Linear mixed models evaluated effects of age, gender, cardiovascular risk, brain comorbidity, Glasgow Coma Scale (GCS), pupil reactivity, and type of injury. Median dose of norepinephrine, propofol and hemoglobin concentration was 7.8 mu g/kg/h (Q1 3.6-Q3 13.8), 3 mg/kg/h (Q1 1.9-Q3 4.3), and 9.2 g center dot dL(-1)(Q1 8.2-Q3 10.5), respectively. Mean cross-correlations for 24 lags were close to zero and not significant for all variables. No significant differences as function of age, gender, cardiovascular risk, brain comorbidity, GCS, pupil reactivity, and type of injury were found. Dynamic intracranial pressure-based measurements of cerebrovascular reactivity in acute brain injured patients are not affected by gradually adjusted norepinephrine or propofol infusion rates or slow changes in hemoglobin concentration within the typical ranges during ICU admission. Future trials on cerebrovascular reactivity-steered management and treatment of CA impairment may not have to take these variables into account.}, keywords = {BLOOD-FLOW; NOREPINEPHRINE; brain injury; TRANSFUSION; Clinical Neurology; Critical Care Medicine; Cerebral autoregulation; Cerebral autoregulation; HEMOGLOBIN CONCENTRATION; Pressure reactivity}, year = {2020}, eissn = {1557-9042}, pages = {506-512}, orcid-numbers = {Klein, Samuel P./0000-0001-5595-4440; Meyfroidt, Geert/0000-0003-4259-3935} } @article{MTMT:34423328, title = {The State of Autoregulation}, url = {https://m2.mtmt.hu/api/publication/34423328}, author = {Wolf, Stefan}, doi = {10.1007/s12028-020-01021-2}, journal-iso = {NEUROCRIT CARE}, journal = {NEUROCRITICAL CARE}, volume = {34}, unique-id = {34423328}, issn = {1541-6933}, keywords = {TRAUMATIC BRAIN-INJURY; Critical Care Medicine; INTRACRANIAL-PRESSURE; CEREBRAL PERFUSION-PRESSURE}, year = {2020}, eissn = {1556-0961}, pages = {5-7} } @article{MTMT:31591540, title = {Descriptive analysis of low versus elevated intracranial pressure on cerebral physiology in adult traumatic brain injury : a CENTER-TBI exploratory study}, url = {https://m2.mtmt.hu/api/publication/31591540}, author = {Zeiler, Frederick A and Ercole, Ari and Cabeleira, Manuel and Czosnyka, Marek and Stocchetti, Nino and Hutchinson, Peter J and Smielewski, Peter}, doi = {10.1007/s00701-020-04485-5}, journal-iso = {ACTA NEUROCHIR}, journal = {ACTA NEUROCHIRURGICA}, volume = {162}, unique-id = {31591540}, issn = {0001-6268}, abstract = {To date, the cerebral physiologic consequences of persistently elevated intracranial pressure (ICP) have been based on either low-resolution physiologic data or retrospective high-frequency data from single centers. The goal of this study was to provide a descriptive multi-center analysis of the cerebral physiologic consequences of ICP, comparing those with normal ICP to those with elevated ICP.The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) High-Resolution Intensive Care Unit (HR-ICU) sub-study cohort was utilized. The first 3 days of physiologic recording were analyzed, evaluating and comparing those patients with mean ICP < 15 mmHg versus those with mean ICP > 20 mmHg. Various cerebral physiologic parameters were derived and evaluated, including ICP, brain tissue oxygen (PbtO2), cerebral perfusion pressure (CPP), pulse amplitude of ICP (AMP), cerebrovascular reactivity, and cerebral compensatory reserve. The percentage time and dose above/below thresholds were also assessed. Basic descriptive statistics were employed in comparing the two cohorts.185 patients were included, with 157 displaying a mean ICP below 15 mmHg and 28 having a mean ICP above 20 mmHg. For admission demographics, only admission Marshall and Rotterdam CT scores were statistically different between groups (p = 0.017 and p = 0.030, respectively). The high ICP group displayed statistically worse CPP, PbtO2, cerebrovascular reactivity, and compensatory reserve. The high ICP group displayed worse 6-month mortality (p < 0.0001) and poor outcome (p = 0.014), based on the Extended Glasgow Outcome Score.Low versus high ICP during the first 72 h after moderate/severe TBI is associated with significant disparities in CPP, AMP, cerebrovascular reactivity, cerebral compensatory reserve, and brain tissue oxygenation metrics. Such ICP extremes appear to be strongly related to 6-month patient outcomes, in keeping with previous literature. This work provides multi-center validation for previously described single-center retrospective results.}, keywords = {Cerebrovascular reactivity; OUTCOMES; cerebral physiology; ICP extremes}, year = {2020}, eissn = {0942-0940}, pages = {2695-2706}, orcid-numbers = {Czeiter, Endre/0000-0002-9578-6944} } @article{MTMT:31467449, title = {Brain Tissue Oxygen and Cerebrovascular Reactivity in Traumatic Brain Injury: A Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Exploratory Analysis of Insult Burden}, url = {https://m2.mtmt.hu/api/publication/31467449}, author = {Zeiler, Frederick A. and Beqiri, Erta and Cabeleira, Manuel and Hutchinson, Peter J. and Stocchetti, Nino and Menon, David K. and Czosnyka, Marek and Smielewski, Peter and Ercole, Ari}, doi = {10.1089/neu.2020.7024}, journal-iso = {J NEUROTRAUM}, journal = {JOURNAL OF NEUROTRAUMA}, volume = {37}, unique-id = {31467449}, issn = {0897-7151}, abstract = {Pressure reactivity index (PRx) and brain tissue oxygen (PbtO(2)) are associated with outcome in traumatic brain injury (TBI). This study explores the relationship between PRx and PbtO(2) in adult moderate/severe TBI. Using the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) high resolution intensive care unit (ICU) sub-study cohort, we evaluated those patients with archived high-frequency digital intraparenchymal intracranial pressure (ICP) and PbtO(2) monitoring data of, a minimum of 6 h in duration, and the presence of a 6 month Glasgow Outcome Scale -Extended (GOSE) score. Digital physiological signals were processed for ICP, PbtO(2), and PRx, with the % time above/below defined thresholds determined. The duration of ICP, PbtO(2), and PRx derangements was characterized. Associations with dichotomized 6-month GOSE (alive/dead, and favorable/unfavorable outcome; <= 4 = unfavorable), were assessed. A total of 43 patients were included. Severely impaired cerebrovascular reactivity was seen during elevated ICP and low PbtO(2) episodes. However, most of the acute ICU physiological derangements were impaired cerebrovascular reactivity, not ICP elevations or low PbtO(2) episodes. Low PbtO(2) without PRx impairment was rarely seen. % time spent above PRx threshold was associated with mortality at 6 months for thresholds of 0 (area under the curve [AUC] 0.734, p = 0.003), > +0.25 (AUC 0.747, p = 0.002) and > +0.35 (AUC 0.745, p = 0.002). Similar relationships were not seen for % time with ICP >20 mm Hg, and PbtO(2) < 20 mm Hg in this cohort. Extreme impairment in cerebrovascular reactivity is seen during concurrent episodes of elevated ICP and low PbtO(2). However, the majority of the deranged cerebral physiology seen during the acute ICU phase is impairment in cerebrovascular reactivity, with most impairment occurring in the presence of normal PbtO(2) levels. Measures of cerebrovascular reactivity appear to display the most consistent associations with global outcome in TBI, compared with ICP and PbtO(2).}, keywords = {AUTOREGULATION; ICP; Brain tissue oxygen; physiological burden}, year = {2020}, eissn = {1557-9042}, pages = {1854-1863}, orcid-numbers = {Ercole, Ari/0000-0001-8350-8093} } @article{MTMT:31492224, title = {Diffuse Intracranial Injury Patterns Are Associated with Impaired Cerebrovascular Reactivity in Adult Traumatic Brain Injury: A CENTER-TBI Validation Study}, url = {https://m2.mtmt.hu/api/publication/31492224}, author = {Zeiler, Frederick A. and Mathieu, Francois and Monteiro, Miguel and Glocker, Ben and Ercole, Ari and Beqiri, Erta and Cabeleira, Manuel and Stocchetti, Nino and Smielewski, Peter and Czosnyka, Marek and Newcombe, Virginia and Menon, David K.}, doi = {10.1089/neu.2019.6959}, journal-iso = {J NEUROTRAUM}, journal = {JOURNAL OF NEUROTRAUMA}, volume = {37}, unique-id = {31492224}, issn = {0897-7151}, abstract = {Recent single-center retrospective analysis displayed the association between admission computed tomography (CT) markers of diffuse intracranial injury and worse cerebrovascular reactivity. The goal of this study was to further explore these associations using the prospective multi-center Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) high-resolution intensive care unit (HR ICU) data set. Using the CENTER-TBI HR ICU sub-study cohort, we evaluated those patients with both archived high-frequency digital physiology (100 Hz or higher) and the presence of a digital admission CT scan. Physiological signals were processed for pressure reactivity index (PRx) and both the percent (%) time above defined PRx thresholds and mean hourly dose above threshold. Admission CT injury scores were obtained from the database. Quantitative contusion, edema, intraventricular hemorrhage (IVH), and extra-axial lesion volumes were obtained via semi-automated segmentation. Comparison between admission CT characteristics and PRx metrics was conducted using Mann-U, Jonckheere-Terpstra testing, with a combination of univariate linear and logistic regression techniques. A total of 165 patients were included. Cisternal compression and high admission Rotterdam and Helsinki CT scores, and Marshall CT diffuse injury sub-scores were associated with increased percent (%) time and hourly dose above PRx threshold of 0, +0.25, and +0.35 (p < 0.02 for all). Logistic regression analysis displayed an association between deep peri-contusional edema and mean PRx above a threshold of +0.25. These results suggest that diffuse injury patterns, consistent with acceleration/deceleration forces, are associated with impaired cerebrovascular reactivity. Diffuse admission intracranial injury patterns appear to be consistently associated with impaired cerebrovascular reactivity, as measured through PRx. This is in keeping with the previous single-center retrospective literature on the topic. This study provides multi-center validation for those results, and provides preliminary data to support potential risk stratification for impaired cerebrovascular reactivity based on injury pattern.}, keywords = {CT; computed tomography; Image segmentation; AUTOREGULATION; PRx; injury patterns}, year = {2020}, eissn = {1557-9042}, pages = {1597-1608}, orcid-numbers = {Ercole, Ari/0000-0001-8350-8093; Newcombe, Virginia/0000-0001-6044-9035} }