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Transcranial Doppler Based Cerebrovascular Reactivity Indices in Adult Traumatic Brain Injury: A Scoping Review of Associations With Patient Oriented Outcomes.

ABSTRACT: Background: Disruption in cerebrovascular reactivity following traumatic brain injury (TBI) is a known phenomenon that may hold prognostic value and clinical relevance. Ultimately, improved knowledge of this process and more robust means of continuous assessment may lead to advances in precision medicine following TBI. One such method is transcranial Doppler (TCD), which has been employed to evaluate cerebrovascular reactivity following injury utilizing a continuous time-series approach. Objective: The present study undertakes a scoping review of the literature on the association of continuous time-domain TCD based indices of cerebrovascular reactivity, with global functional outcomes, cerebral physiologic correlates, and imaging evidence of lesion change. Design: Multiple databases were searched from inception to November 2020 for articles relevant to the association of continuous time-domain TCD based indices of cerebrovascular reactivity with global functional outcomes, cerebral physiologic correlates, and imaging evidence of lesion change. Results: Thirty-six relevant articles were identified. There was significant evidence supporting an association with continuous time-domain TCD based indices and functional outcomes following TBI. Indices based on mean flow velocity, as measured by TCD, were most numerous while more recent studies point to systolic flow velocity-based indices encoding more prognostic utility. Physiologic parameters such as intracranial pressure, cerebral perfusion pressure, Carbon Dioxide (CO2) reactivity as well as more established indices of cerebrovascular reactivity have all been associated with these TCD based indices. The literature has been concentrated in a few centres and is further limited by the lack of multivariate analysis. Conclusions: This systematic scoping review of the literature identifies that there is a substantial body of evidence that cerebrovascular reactivity as measured by time-domain TCD based indices have prognostic utility following TBI. Indices based on mean flow velocities have the largest body of literature for their support. However, recent studies indicate that indices based on systolic flow velocities may contain the most prognostic utility and more closely follow more established measures of cerebrovascular reactivity. To a lesser extent, the literature supports some associations between these indices and cerebral physiologic parameters. These indices provide a more complete picture of the patient's physiome following TBI and may ultimately lead to personalized and precise clinical care. Further validation in multi-institution studies is required before these indices can be widely adopted clinically.

SUBMITTER: Gomez A

PROVIDER: S-EPMC8290494 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundTo explore the relationship between various autoregulatory indices in order to determine which approximate small vessel/microvascular (MV) autoregulatory capacity most accurately.MethodsUtilizing a retrospective cohort of traumatic brain injury patients (N = 41) with: transcranial Doppler (TCD), intracranial pressure (ICP) and cortical laser Doppler flowmetry (LDF), we calculated various continuous indices of autoregulation and cerebrovascular responsiveness: A. ICP derived [pressure reactivity index (PRx)-correlation between ICP and mean arterial pressure (MAP), PAx-correlation between pulse amplitude of ICP (AMP) and MAP, RAC-correlation between AMP and cerebral perfusion pressure (CPP)], B. TCD derived (Mx-correlation between mean flow velocity (FVm) and CPP, Mx_a-correlation between FVm and MAP, Sx-correlation between systolic flow velocity (FVs) and CPP, Sx_a-correlation between FVs and MAP, Dx-correlation between diastolic flow index (FVd) and CPP, Dx_a-correlation between FVd and MAP], and LDF derived (Lx-correlation between LDF cerebral blood flow [CBF] and CPP, Lx_a-correlation between LDF-CBF and MAP). We assessed the relationship between these indices via Pearson correlation, Friedman test, principal component analysis (PCA), agglomerative hierarchal clustering (AHC), and k-means cluster analysis (KMCA).ResultsLDF-based autoregulatory index (Lx) was most associated with TCD-based Mx/Mx_a and Dx/Dx_a across Pearson correlation, PCA, AHC, and KMCA. Lx was only remotely associated with ICP-based indices (PRx, PAx, RAC). TCD-based Sx/Sx_a was more closely associated with ICP-derived PRx, PAx and RAC. This indicates that vascular-derived indices of autoregulatory capacity (i.e., TCD and LDF based) covary, with Sx/Sx_a being the exception, whereas indices of cerebrovascular reactivity derived from pulsatile CBV (i.e., ICP indices) appear to not be closely related to those of vascular origin.ConclusionsTranscranial Doppler Mx is the most closely associated with LDF-based Lx/Lx_a. Both Sx/Sx-a and the ICP-derived indices appear to be dissociated with LDF-based cerebrovascular reactivity, leaving Mx/Mx-a as a better surrogate for the assessment of cortical small vessel/MV cerebrovascular reactivity. Sx/Sx_a cocluster/covary with ICP-derived indices, as seen in our previous work.

Project description: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.

Project description:OBJECTIVES:To assess whether microemboli burden, assessed noninvasively by bedside transcranial Doppler ultrasonography, correlates with risk of subsequent stroke greater than 24 hours after hospital arrival among patients with blunt cerebrovascular injury. The greater than 24-hour time frame provides a window for transcranial Doppler examinations and therapeutic interventions to prevent stroke. DESIGN:Retrospective cohort study. SETTING:Level I trauma center. PATIENTS:One thousand one hundred forty-six blunt cerebrovascular injury patients over 10 years. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:We identified 1,146 blunt cerebrovascular injury patients; 54 (4.7%) experienced stroke detected greater than 24 hours after arrival. Among those with isolated internal carotid artery injuries, five of nine with delayed stroke had positive transcranial Dopplers (at least one microembolus detected with transcranial Dopplers) before stroke, compared with 46 of 248 without (risk ratio, 5.05; 95% CI, 1.41-18.13). Stroke risk increased with the number of microemboli (adjusted risk ratio, 1.03/microembolus/hr; 95% CI, 1.01-1.05) and with persistently positive transcranial Dopplers over multiple days (risk ratio, 16.0; 95% CI, 2.00-127.93). Among patients who sustained an internal carotid artery injury with or without additional vessel injuries, positive transcranial Dopplers predicted stroke after adjusting for ipsilateral and contralateral internal carotid artery injury grade (adjusted risk ratio, 2.91; 95% CI, 1.42-5.97). No patients with isolated vertebral artery injuries had positive transcranial Dopplers before stroke, and positive transcranial Dopplers were not associated with delayed stroke among patients who sustained a vertebral artery injury with or without additional vessel injuries (risk ratio, 0.90; 95% CI, 0.21-3.83). CONCLUSIONS:Microemboli burden is associated with higher risk of stroke due to internal carotid artery injuries, but monitoring was not useful for vertebral artery injuries.

Project description:BackgroundImpaired cerebrovascular reactivity in adult traumatic brain injury (TBI) is known to be associated with poor outcome. However, there has yet to be an analysis of the association between the comprehensively assessed intracranial hypertension therapeutic intensity level (TIL) and cerebrovascular reactivity.MethodsUsing the Collaborative European Neuro Trauma Effectiveness Research in TBI (CENTER-TBI) high-resolution intensive care unit (ICU) cohort, we derived pressure reactivity index (PRx) as the moving correlation coefficient between slow-wave in ICP and mean arterial pressure, updated every minute. Mean daily PRx, and daily % time above PRx of 0 were calculated for the first 7 days of injury and ICU stay. This data was linked with the daily TIL-Intermediate scores, including total and individual treatment sub-scores. Daily mean PRx variable values were compared for each TIL treatment score via mean, standard deviation, and the Mann U test (Bonferroni correction for multiple comparisons). General fixed effects and mixed effects models for total TIL versus PRx were created to display the relation between TIL and cerebrovascular reactivity.ResultsA total of 249 patients with 1230 ICU days of high frequency physiology matched with daily TIL, were assessed. Total TIL was unrelated to daily PRx. Most TIL sub-scores failed to display a significant relationship with the PRx variables. Mild hyperventilation (p < 0.0001), mild hypothermia (p = 0.0001), high levels of sedation for ICP control (p = 0.0001), and use vasopressors for CPP management (p < 0.0001) were found to be associated with only a modest decrease in mean daily PRx or % time with PRx above 0.ConclusionsCerebrovascular reactivity remains relatively independent of intracranial hypertension therapeutic intensity, suggesting inadequacy of current TBI therapies in modulating impaired autoregulation. These findings support the need for investigation into the molecular mechanisms involved, or individualized physiologic targets (ICP, CPP, or Co2) in order to treat dysautoregulation actively.

Project description:ObjectiveThis study aimed to investigate the feasibility of Transcranial Doppler Ultrasonography (TCD) in evaluating neonatal hypoxic-ischemic encephalopathy (NHIE) modeling through monitoring the alteration of cerebrovascular flow in neonatal hypoxic-ischemic (HI) rats.MethodsPostnatal 7-day-old Sprague Dawley (SD) rats were divided into the control group, HI group, and hypoxia (H) group. TCD was applied to assess the changes of cerebral blood vessels, cerebrovascular flow velocity, and heart rate (HR) in sagittal and coronal sections at 1, 2, 3, and 7 days after the operation. For accuracy, cerebral infarct of rats was examined by 2,3,5-Triphenyl tetrazolium chloride (TTC) staining and Nissl staining to simultaneously verify the establishment of NHIE modeling.ResultsCoronal and sagittal TCD scans revealed obvious alteration of cerebrovascular flow in main cerebral vessels. Obvious cerebrovascular back-flow was observed in anterior cerebral artery (ACA), basilar artery (BA), middle cerebral artery (MCA) of HI rats, along with accelerated cerebrovascular flows in the left internal carotid artery (ICA-L) and BA, decreased flows in right internal carotid artery (ICA-R) relative to those in the H and control groups. The alterations of cerebral blood flows in neonatal HI rats indicated successful ligation of right common carotid artery. Besides, TTC staining further validated the cerebral infarct was indeed caused due to ligation-induced insufficient blood supply. Damage to nervous tissues was also revealed by Nissl staining.ConclusionCerebral blood flow assessment by TCD in neonatal HI rats contributed to cerebrovascular abnormalities observed in a real-time and non-invasive way. The present study elicits the potentials to utilize TCD as an effective means for monitoring the progression of injury as well as NHIE modeling. The abnormal appearance of cerebral blood flow is also beneficial to the early warning and effective detection in clinical practice.

Project description:BACKGROUND:Monitoring cerebrovascular reactivity in adult traumatic brain injury (TBI) has been linked to global patient outcome. Three intra-cranial pressure (ICP)-derived indices have been described. It is unknown which index is superior for outcome association in TBI outside previous single-center evaluations. The goal of this study is to evaluate indices for 6- to 12-month outcome association using uniform data harvested in multiple centers. METHODS:Using the prospectively collected data from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study, the following indices of cerebrovascular reactivity were derived: PRx (correlation between 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)). Univariate logistic regression models were created to assess the association between vascular reactivity indices with global dichotomized outcome at 6 to 12 months, as assessed by Glasgow Outcome Score-Extended (GOSE). Models were compared via area under the receiver operating curve (AUC) and Delong's test. RESULTS:Two separate patient groups from this cohort were assessed: the total population with available data (n = 204) and only those without decompressive craniectomy (n = 159), with identical results. PRx, PAx, and RAC perform similar in outcome association for both dichotomized outcomes, alive/dead and favorable/unfavorable, with RAC trending towards higher AUC values. There were statistically higher mean values for the index, % time above threshold, and hourly dose above threshold for each of PRx, PAx, and RAC in those patients with poor outcomes. CONCLUSIONS:PRx, PAx, and RAC appear similar in their associations with 6- to 12-month outcome in moderate/severe adult TBI, with RAC showing tendency to achieve stronger associations. Further work is required to determine the role for each of these cerebrovascular indices in monitoring of TBI patients.

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Transcranial Doppler Based Cerebrovascular Reactivity Indices in Adult Traumatic Brain Injury: A Scoping Review of Associations With Patient Oriented Outcomes.

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