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Ronney B. Panerai - One of the best experts on this subject based on the ideXlab platform.

  • Feasibility of improving Cerebral Autoregulation in acute intraCerebral hemorrhage (BREATHE-ICH) study: Results from an experimental interventional study.
    2019
    Co-Authors: Jatinder S. Minhas, Ronney B. Panerai, David Swienton, Thompson G Robinson
    Abstract:

    BACKGROUND: Cerebral Autoregulation is impaired in a multitude of neurological conditions. Increasingly, clinical studies are correlating the nature of this impairment with prognostic markers. In acute intraCerebral hemorrhage, impairment of Cerebral Autoregulation has been associated with worsening clinical outcomes including poorer Glasgow Coma Score and larger hematoma volume. Hypocapnia has been shown to improve Cerebral Autoregulation despite concerns over hypoperfusion and consequent ischemic risks, and it is therefore hypothesized that hypocapnia (via hyperventilation) in acute intraCerebral hemorrhage may improve Cerebral Autoregulation and consequently clinical outcome. AIMS: To assess the feasibility and acceptability of the first Cerebral Autoregulation-targeted intervention in acute intraCerebral hemorrhage utilizing a simple bed-side hyperventilatory maneuver. METHODS: Twelve patients with acute intraCerebral hemorrhage within 48 h of onset were enrolled. The experimental setup measured Cerebral blood flow velocity (transcranial Doppler), blood pressure (Finometer), and end-tidal CO2 (EtCO2, capnography) at baseline, and in response to hypocapnia (-5 mmHg below baseline) achieved via a 90-s hyperventilatory maneuver. Cerebral Autoregulation was evaluated with transfer function analysis and autoregulatory index calculations. RESULTS: We observed tolerance to the protocol in a cohort of mild (National Institutes of Health Scale 4) supratentorial intraCerebral hemorrhage patients with small volume hematomas without intraventricular extension. Importantly, a significant difference was noted between ipsilateral autoregulatory index at baseline 4.8 (1.7) and autoregulatory index during hypocapnic intervention 7.0 (0.8) (p = 0.0004), reflecting improved Cerebral Autoregulation, though a dose-dependent effect of EtCO2 on autoregulatory index was not observed. CONCLUSIONS: In this small study, there was no observed effect on 14-day death and disability in recruited participants. This is the first report of improvement in Cerebral Autoregulation in acute intraCerebral hemorrhage using a non-invasive interventional maneuver, through induction of hypocapnia via hyperventilation. ClinicalTrials.gov Identifier: NCT03324321 URL: https://clinicaltrials.gov/ct2/show/NCT03324321

  • increased blood pressure variability upon standing up improves reproducibility of Cerebral Autoregulation indices
    Medical Engineering & Physics, 2017
    Co-Authors: Adam Mahdi, Ronney B. Panerai, Dragana Nikolic, Anthony A Birch, Mette S Olufsen, David M Simpson, Stephen J Payne
    Abstract:

    Abstract Dynamic Cerebral Autoregulation, that is the transient response of Cerebral blood flow to changes in arterial blood pressure, is currently assessed using a variety of different time series methods and data collection protocols. In the continuing absence of a gold standard for the study of Cerebral Autoregulation it is unclear to what extent does the assessment depend on the choice of a computational method and protocol. We use continuous measurements of blood pressure and Cerebral blood flow velocity in the middle Cerebral artery from the cohorts of 18 normotensive subjects performing sit-to-stand manoeuvre. We estimate Cerebral Autoregulation using a wide variety of black-box approaches (including the following six Autoregulation indices ARI, Mx, Sx, Dx, FIR and ARX) and compare them in the context of reproducibility and variability. For all Autoregulation indices, considered here, the intra-class correlation was greater during the standing protocol, however, it was significantly greater (Fisher’s Z -test) for Mx ( p p p

  • increased blood pressure variability upon standing up improves reproducibility of Cerebral Autoregulation indices
    Medical Engineering & Physics, 2017
    Co-Authors: Adam Mahdi, Ronney B. Panerai, D. M. Simpson, Dragana Nikolic, Anthony A Birch, Mette S Olufsen, Stephen J Payne
    Abstract:

    Dynamic Cerebral Autoregulation, that is the transient response of Cerebral blood flow to changes in arterial blood pressure, is currently assessed using a variety of different time series methods and data collection protocols. In the continuing absence of a gold standard for the study of Cerebral Autoregulation it is unclear to what extent does the assessment depend on the choice of a computational method and protocol. We use continuous measurements of blood pressure and Cerebral blood flow velocity in the middle Cerebral artery from the cohorts of 18 normotensive subjects performing sit-to-stand manoeuvre. We estimate Cerebral Autoregulation using a wide variety of black-box approaches (including the following six Autoregulation indices ARI, Mx, Sx, Dx, FIR and ARX) and compare them in the context of reproducibility and variability. For all Autoregulation indices, considered here, the intra-class correlation was greater during the standing protocol, however, it was significantly greater (Fisher's Z-test) for Mx (p < 0.03), Sx (p < 0.003) and Dx (p < 0.03). In the specific case of the sit-to-stand manoeuvre, measurements taken immediately after standing up greatly improve the reproducibility of the Autoregulation coefficients. This is generally coupled with an increase of the within-group spread of the estimates.

  • increased blood pressure variability upon standing up improves reproducibility of Cerebral Autoregulation indices
    arXiv: Quantitative Methods, 2017
    Co-Authors: Adam Mahdi, Ronney B. Panerai, Dragana Nikolic, Anthony A Birch, Mette S Olufsen, David M Simpson, Stephen J Payne
    Abstract:

    Dynamic Cerebral Autoregulation, that is the transient response of Cerebral blood flow to changes in arterial blood pressure, is currently assessed using a variety of different time series methods and data collection protocols. In the continuing absence of a gold standard for the study of Cerebral Autoregulation it is unclear to what extent does the assessment depend on the choice of a computational method and protocol. We use continuous measurements of blood pressure and Cerebral blood flow velocity in the middle Cerebral artery from the cohorts of 18 normotensive subjects performing sit-to-stand manoeuvre. We estimate Cerebral Autoregulation using a wide variety of black-box approaches (ARI, Mx, Sx, Dx, FIR and ARX) and compare them in the context of reproducibility and variability. For all Autoregulation indices, considered here, the ICC was greater during the standing protocol, however, it was significantly greater (Fisher's Z-test) for Mx (p < 0.03), Sx (p<0.003)$ and Dx (p<0.03). In the specific case of the sit-to-stand manoeuvre, measurements taken immediately after standing up greatly improve the reproducibility of the Autoregulation coefficients. This is generally coupled with an increase of the within-group spread of the estimates.

  • transfer function analysis of dynamic Cerebral Autoregulation a white paper from the international Cerebral Autoregulation research network
    Journal of Cerebral Blood Flow and Metabolism, 2016
    Co-Authors: Jurgen A.h.r. Claassen, Aisha Meelvan Den S S Abeelen, D. M. Simpson, Ronney B. Panerai
    Abstract:

    Cerebral Autoregulation is the intrinsic ability of the brain to maintain adequate Cerebral perfusion in the presence of blood pressure changes. A large number of methods to assess the quality of Cerebral Autoregulation have been proposed over the last 30 years. However, no single method has been universally accepted as a gold standard. Therefore, the choice of which method to employ to quantify Cerebral Autoregulation remains a matter of personal choice. Nevertheless, given the concept that Cerebral Autoregulation represents the dynamic relationship between blood pressure (stimulus or input) and Cerebral blood flow (response or output), transfer function analysis became the most popular approach adopted in studies based on spontaneous fluctuations of blood pressure. Despite its sound theoretical background, the literature shows considerable variation in implementation of transfer function analysis in practice, which has limited comparisons between studies and hindered progress towards clinical application. Therefore, the purpose of the present white paper is to improve standardisation of parameters and settings adopted for application of transfer function analysis in studies of dynamic Cerebral Autoregulation. The development of these recommendations was initiated by (but not confined to) the Cerebral Autoregulation Research Network

Marek Czosnyka - One of the best experts on this subject based on the ideXlab platform.

  • predictors of outcome with Cerebral Autoregulation monitoring a systematic review and meta analysis
    Critical Care Medicine, 2017
    Co-Authors: Lucia Riveralara, Peter Smielewski, Marek Czosnyka, Romergryko G. Geocadin, Ryan Healy, Wendy C. Ziai, Andres Zorrillavaca, Richard E Thompson, Charles W. Hogue
    Abstract:

    Objective:To compare Cerebral Autoregulation indices as predictors of patient outcome and their dependence on duration of monitoring.Data Sources:Systematic literature search and meta-analysis using PubMed, EMBASE, and the Cochrane Library from January 1990 to October 2015.Study Selection:We chose a

  • prediction of delayed Cerebral ischemia after subarachnoid hemorrhage using Cerebral blood flow velocities and Cerebral Autoregulation assessment
    Neurocritical Care, 2015
    Co-Authors: Lionel Calviere, Marek Czosnyka, Nathalie Nasr, Catherine Arnaud, Alain Viguier, Bernard Tissot, Jeanchristophe Sol, Vincent Larrue
    Abstract:

    The risk of delayed Cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) is associated with large Cerebral artery vasospasm, but vasospasm is not a strong predictor for DCI. Assessment of Cerebral Autoregulation with transcranial Doppler (TCD) may improve the prediction of DCI. The aim of this prospective study was to assess the value of TCD-derived variables to be used alone or in combination for prediction of DCI. We included consecutive patients with low-grade aneurysmal SAH within 4 days of aneurysm rupture. Cerebral Autoregulation was evaluated using the moving correlation coefficient Mx calculated from spontaneous fluctuations of Cerebral blood flow velocities and arterial blood pressure. Transcranial color-coded sonography was performed to assess large artery vasospasm. Thirty patients (19 women and 11 men; mean age ± SD 44.7 ± 12.1 years) were included. Twenty (66.7 %) patients had vasospasm. DCI occurred in six (20 %) patients after a median delay of 10 days (range 8–13 days). Cerebral Autoregulation was impaired at baseline and at day 7 and then returned to normal at day 14. Neither Cerebral Autoregulation impairment nor large artery vasospasm alone was associated with DCI. In contrast, the combination of large artery vasospasm with worsening impairment of Cerebral Autoregulation from baseline to day 7 was significantly correlated to subsequent DCI (p = 0.007). Early deterioration of Cerebral Autoregulation was strongly predictive of DCI in patients with large artery vasospasm after low-grade SAH. Our results suggest that consideration to both Cerebral blood flow velocities and Cerebral Autoregulation may improve the prediction of DCI.

  • further understanding of Cerebral Autoregulation at the bedside possible implications for future therapy
    Expert Review of Neurotherapeutics, 2015
    Co-Authors: Joseph Donnelly, Marcel J.h. Aries, Marek Czosnyka
    Abstract:

    Cerebral Autoregulation reflects the ability of the brain to keep the Cerebral blood flow (CBF) relatively constant despite changes in Cerebral perfusion pressure. It is an intrinsic neuroprotective physiological phenomenon often suggested as part of pathophysiological pathways in brain research. However, despite increasing knowledge of this phenomenon for over 50 years, harnessing Cerebral Autoregulation as a basis for therapy remains an elegant concept rather than a practical reality. This raises the question is it useful to measure at the bedside or is it merely a scientific curiosity that is too complex and has little pragmatic relevance. In this article, we attempt to answer this question by demonstrating how Cerebral Autoregulation assessment can have prognostic value, indicate pathological states, and potentially even influence therapy with the use of the 'optimal Cerebral perfusion pressure' paradigm. Evidence from the literature is combined with bedside clinical examples to address the following fundamental questions about Cerebral Autoregulation: What is it? How do we measure it? Why is it important? Can we use it as a basis for therapy?

  • Further understanding of Cerebral Autoregulation at the bedside: possible implications for future therapy
    Expert Review of Neurotherapeutics, 2015
    Co-Authors: Joseph Donnelly, Marcel J.h. Aries, Marek Czosnyka
    Abstract:

    Cerebral Autoregulation reflects the ability of the brain to keep the Cerebral blood flow (CBF) relatively constant despite changes in Cerebral perfusion pressure. It is an intrinsic neuroprotective physiological phenomenon often suggested as part of pathophysiological pathways in brain research. However, despite increasing knowledge of this phenomenon for over 50 years, harnessing Cerebral Autoregulation as a basis for therapy remains an elegant concept rather than a practical reality. This raises the question is it useful to measure at the bedside or is it merely a scientific curiosity that is too complex and has little pragmatic relevance. In this article, we attempt to answer this question by demonstrating how Cerebral Autoregulation assessment can have prognostic value, indicate pathological states, and potentially even influence therapy with the use of the ‘optimal Cerebral perfusion pressure’ paradigm. Evidence from the literature is combined with bedside clinical examples to address the following ...

  • continuous time domain monitoring of Cerebral Autoregulation in neurocritical care
    Medical Engineering & Physics, 2014
    Co-Authors: Peter Smielewski, Christian Zweifel, Celeste Dias, Marek Czosnyka
    Abstract:

    Integration of various brain signals can be used to determine Cerebral Autoregulation in neurocritical care patients to guide clinical management and to predict outcome. In this review, we will discuss current methodology of multimodal brain monitoring focusing on secondary 'reactivity indices' derived from various brain signals which are based on a 'moving correlation coefficient'. This algorithm was developed in order to analyze in a time dependent manner the degree of correlation between two factors within a time series where the number of paired observations is large. Of the various primary neuromonitoring sources which can be used to calculate reactivity indices, we will focus in this review on indices based on transcranial Doppler (TCD), intracranial pressure (ICP), brain tissue oxygenation (PbtO2) and near infrared spectroscopy (NIRS). Furthermore, we will demonstrate how reactivity indices can show transient changes of Cerebral Autoregulation and can be used to optimize management of arterial blood pressure (ABP) and Cerebral perfusion pressure (CPP).

Monica S. Vavilala - One of the best experts on this subject based on the ideXlab platform.

  • translational approach towards determining the role of Cerebral Autoregulation in outcome after traumatic brain injury
    Experimental Neurology, 2019
    Co-Authors: William M Armstead, Monica S. Vavilala
    Abstract:

    Abstract Cerebral Autoregulation is impaired after traumatic brain injury (TBI), contributing to poor outcome. In the context of the neurovascular unit, Cerebral Autoregulation contributes to neuronal cell integrity and clinically Glasgow Coma Scale is correlated to intactness of Autoregulation after TBI. Cerebral Perfusion Pressure (CPP) is often normalized by use of vasoactive agents to increase mean arterial pressure (MAP) and thereby limit impairment of Cerebral Autoregulation and neurological deficits. However, current vasoactive agent choice used to elevate MAP to increase CPP after TBI is variable. Vasoactive agents, such as phenylephrine, dopamine, norepinephrine, and epinephrine, clinically have not sufficiently been compared regarding effect on CPP, Autoregulation, and survival after TBI. The Cerebral effects of these clinically commonly used vasoactive agents are incompletely understood. This review will describe translational studies using a more human like animal model (the pig) of TBI to identify better therapeutic strategies to improve outcome post injury. These studies also investigated the role of age and sex in outcome and mechanism(s) involved in improvement of outcome in the setting of TBI. Additionally, this review considers use of inhaled nitric oxide as a novel neuroprotective strategy in treatment of TBI.

  • Cerebral perfusion pressure directed therapy modulates cardiac dysfunction after traumatic brain injury to influence Cerebral Autoregulation in pigs
    Neurocritical Care, 2019
    Co-Authors: William M Armstead, Monica S. Vavilala
    Abstract:

    BACKGROUND: Traumatic brain injury (TBI) is an important contributor to morbidity and mortality. Low Cerebral perfusion pressure (CPP, mean arterial pressure [MAP] minus intracranial pressure) after TBI is associated with Cerebral ischemia, impaired Cerebral Autoregulation, and poor outcomes. Normalization of CPP and limitation of Cerebral Autoregulation impairment is a key therapeutic goal. However, some vasoactive agents used to elevate MAP such as phenylephrine (Phe) improve outcome in females but not male piglets after TBI while dopamine (DA) does so in both sexes. Clinical evidence has implicated neurological injuries as a cause of cardiac dysfunction, and we recently described cardiac dysfunction after TBI. Cardiac dysfunction may, in turn, influence brain health. One mechanism of myocyte injury may involve catecholamine excess. We therefore tested the hypothesis that TBI caused cardiac dysfunction and catecholamine excess which may reciprocally be modulated by vasoactive agent choice to normalize CPP and prevent impairment of Cerebral Autoregulation after injury. METHODS: TBI was produced in anesthetized pigs equipped with a closed cranial window, and Phe or DA administered to normalize CPP. RESULTS: Plasma cardiac enzymes troponin and creatine kinase and catecholamines epinephrine and norepinephrine were elevated by TBI, such release potentiated by Phe in males but blocked in female piglets and blocked in both sexes after DA. Cerebral Autoregulation was impaired after TBI, worsened by Phe in males but protected in females and males treated with DA. Papaverine-induced dilation was unchanged by fluid percussion brain injury, DA, and Phe. CONCLUSIONS: These data indicate that pressor choice in elevation of CPP is important in limiting cardiac dysfunction and suggest that DA protects Cerebral Autoregulation in both sexes via reduction of cardiac biomarkers of injury and catecholamines released after TBI.

  • Cerebral perfusion pressure directed therapy modulates cardiac dysfunction after traumatic brain injury to influence Cerebral Autoregulation in pigs
    Neurocritical Care, 2019
    Co-Authors: William M Armstead, Monica S. Vavilala
    Abstract:

    Traumatic brain injury (TBI) is an important contributor to morbidity and mortality. Low Cerebral perfusion pressure (CPP, mean arterial pressure [MAP] minus intracranial pressure) after TBI is associated with Cerebral ischemia, impaired Cerebral Autoregulation, and poor outcomes. Normalization of CPP and limitation of Cerebral Autoregulation impairment is a key therapeutic goal. However, some vasoactive agents used to elevate MAP such as phenylephrine (Phe) improve outcome in females but not male piglets after TBI while dopamine (DA) does so in both sexes. Clinical evidence has implicated neurological injuries as a cause of cardiac dysfunction, and we recently described cardiac dysfunction after TBI. Cardiac dysfunction may, in turn, influence brain health. One mechanism of myocyte injury may involve catecholamine excess. We therefore tested the hypothesis that TBI caused cardiac dysfunction and catecholamine excess which may reciprocally be modulated by vasoactive agent choice to normalize CPP and prevent impairment of Cerebral Autoregulation after injury. TBI was produced in anesthetized pigs equipped with a closed cranial window, and Phe or DA administered to normalize CPP. Plasma cardiac enzymes troponin and creatine kinase and catecholamines epinephrine and norepinephrine were elevated by TBI, such release potentiated by Phe in males but blocked in female piglets and blocked in both sexes after DA. Cerebral Autoregulation was impaired after TBI, worsened by Phe in males but protected in females and males treated with DA. Papaverine-induced dilation was unchanged by fluid percussion brain injury, DA, and Phe. These data indicate that pressor choice in elevation of CPP is important in limiting cardiac dysfunction and suggest that DA protects Cerebral Autoregulation in both sexes via reduction of cardiac biomarkers of injury and catecholamines released after TBI.

  • prevalence evolution and extent of impaired Cerebral Autoregulation in children hospitalized with complex mild traumatic brain injury
    Pediatric Critical Care Medicine, 2019
    Co-Authors: Jerry J. Zimmerman, William M Armstead, Abhijit V Lele, Arraya Watanitanon, Viharika Lakireddy, Crystalyn Clarkbell, Anne Moore, Randall M Chesnut, Monica S. Vavilala
    Abstract:

    OBJECTIVES To examine Cerebral Autoregulation in children with complex mild traumatic brain injury. DESIGN Prospective observational convenience sample. SETTING PICU at a level I trauma center. PATIENTS Children with complex mild traumatic brain injury (trauma, admission Glasgow Coma Scale score 13-15 with either abnormal head CT, or history of loss of consciousness). INTERVENTIONS Cerebral Autoregulation was tested using transcranial Doppler ultrasound between admission day 1 and 8. MEASUREMENTS AND MAIN RESULTS The primary outcome was prevalence of impaired Cerebral Autoregulation (Autoregulation index < 0.4),determined using transcranial Doppler ultrasonography and tilt testing. Secondary outcomes examined factors associated with and evolution and extent of impairment. Cerebral Autoregulation testing occurred in 31 children 10 years (SD, 5.2 yr), mostly male (59%) with isolated traumatic brain injury (91%), median admission Glasgow Coma Scale 15, Injury Severity Scores 14.2 (SD, 7.7), traumatic brain injury due to fall (50%), preadmission loss of consciousness (48%), and abnormal head CT scan (97%). Thirty-one children underwent 56 Autoregulation tests. Impaired Cerebral Autoregulation occurred in 15 children (48.4%) who underwent 19 tests; 68% and 32% of tests demonstrated unilateral and bilateral impairment, respectively. Compared with children on median day 6 of admission after traumatic brain injury, impaired Autoregulation was most common in the first 5 days after traumatic brain injury (day 1: relative risk, 3.7; 95% CI, 1.9-7.3 vs day 2: relative risk, 2.7; 95% CI, 1.1-6.5 vs day 5: relative risk, 1.33; 95% CI, 0.7-2.3). Children with impaired Autoregulation were older (12.3 yr [SD, 1.3 yr] vs 8.7 yr [SD, 1.1 yr]; p = 0.04) and tended to have subdural hematoma (64% vs 44%), epidural hematoma (29% vs 17%), and subarachnoid hemorrhage (36% vs 28%). Eight children (53%) were discharged home with ongoing impaired Cerebral Autoregulation. CONCLUSIONS Impaired Cerebral Autoregulation is common in children with complex mild traumatic brain injury, despite reassuring admission Glasgow Coma Scale 13-15. Children with complex mild traumatic brain injury have abnormal cerebrovascular hemodynamics, mostly during the first 5 days. Impairment commonly extends to the contralateral hemisphere and discharge of children with ongoing impaired Cerebral Autoregulation is common.

  • early changes in Cerebral Autoregulation among youth hospitalized after sports related traumatic brain injury
    Brain Injury, 2018
    Co-Authors: Monica S. Vavilala, Arraya Watanitanon, Anne Moore, Carly K Farr, Bs Crystalyn Clarkbell, Theerada Chandee, William M Armstead
    Abstract:

    ABSTRACTObjective: To examine early Cerebral haemodynamic changes among youth hospitalized with sports-related traumatic brain injury (TBI).Study design: Youth 0–18 years admitted to a level one trauma centre with sports-related TBI were enrolled. Daily measures included clinical symptoms and Glasgow Coma Scale (GCS) score. Using Transcranial Doppler (TCD) ultrasonography and tilt testing, we measured middle Cerebral artery flow velocity (Vmca) and Cerebral Autoregulation index (ARI).Results: Six previously healthy males age 14 (IQR 12–16) years with headache and abnormal head CT were admitted with median admission GCS 15. Six patients underwent 12 TCD examinations between hospital days 0–9. Low Vmca occurred in 3/6 patients and on the side of TBI, whereas high Vmca occurred in 2/6 patients. Five patients had at least one measurement of impaired and five patients had absent Cerebral Autoregulation of at least one hemisphere; all these five patients had GCS 15 and headache during TCD examinations. Three pa...

William M Armstead - One of the best experts on this subject based on the ideXlab platform.

  • translational approach towards determining the role of Cerebral Autoregulation in outcome after traumatic brain injury
    Experimental Neurology, 2019
    Co-Authors: William M Armstead, Monica S. Vavilala
    Abstract:

    Abstract Cerebral Autoregulation is impaired after traumatic brain injury (TBI), contributing to poor outcome. In the context of the neurovascular unit, Cerebral Autoregulation contributes to neuronal cell integrity and clinically Glasgow Coma Scale is correlated to intactness of Autoregulation after TBI. Cerebral Perfusion Pressure (CPP) is often normalized by use of vasoactive agents to increase mean arterial pressure (MAP) and thereby limit impairment of Cerebral Autoregulation and neurological deficits. However, current vasoactive agent choice used to elevate MAP to increase CPP after TBI is variable. Vasoactive agents, such as phenylephrine, dopamine, norepinephrine, and epinephrine, clinically have not sufficiently been compared regarding effect on CPP, Autoregulation, and survival after TBI. The Cerebral effects of these clinically commonly used vasoactive agents are incompletely understood. This review will describe translational studies using a more human like animal model (the pig) of TBI to identify better therapeutic strategies to improve outcome post injury. These studies also investigated the role of age and sex in outcome and mechanism(s) involved in improvement of outcome in the setting of TBI. Additionally, this review considers use of inhaled nitric oxide as a novel neuroprotective strategy in treatment of TBI.

  • Cerebral perfusion pressure directed therapy modulates cardiac dysfunction after traumatic brain injury to influence Cerebral Autoregulation in pigs
    Neurocritical Care, 2019
    Co-Authors: William M Armstead, Monica S. Vavilala
    Abstract:

    BACKGROUND: Traumatic brain injury (TBI) is an important contributor to morbidity and mortality. Low Cerebral perfusion pressure (CPP, mean arterial pressure [MAP] minus intracranial pressure) after TBI is associated with Cerebral ischemia, impaired Cerebral Autoregulation, and poor outcomes. Normalization of CPP and limitation of Cerebral Autoregulation impairment is a key therapeutic goal. However, some vasoactive agents used to elevate MAP such as phenylephrine (Phe) improve outcome in females but not male piglets after TBI while dopamine (DA) does so in both sexes. Clinical evidence has implicated neurological injuries as a cause of cardiac dysfunction, and we recently described cardiac dysfunction after TBI. Cardiac dysfunction may, in turn, influence brain health. One mechanism of myocyte injury may involve catecholamine excess. We therefore tested the hypothesis that TBI caused cardiac dysfunction and catecholamine excess which may reciprocally be modulated by vasoactive agent choice to normalize CPP and prevent impairment of Cerebral Autoregulation after injury. METHODS: TBI was produced in anesthetized pigs equipped with a closed cranial window, and Phe or DA administered to normalize CPP. RESULTS: Plasma cardiac enzymes troponin and creatine kinase and catecholamines epinephrine and norepinephrine were elevated by TBI, such release potentiated by Phe in males but blocked in female piglets and blocked in both sexes after DA. Cerebral Autoregulation was impaired after TBI, worsened by Phe in males but protected in females and males treated with DA. Papaverine-induced dilation was unchanged by fluid percussion brain injury, DA, and Phe. CONCLUSIONS: These data indicate that pressor choice in elevation of CPP is important in limiting cardiac dysfunction and suggest that DA protects Cerebral Autoregulation in both sexes via reduction of cardiac biomarkers of injury and catecholamines released after TBI.

  • Cerebral perfusion pressure directed therapy modulates cardiac dysfunction after traumatic brain injury to influence Cerebral Autoregulation in pigs
    Neurocritical Care, 2019
    Co-Authors: William M Armstead, Monica S. Vavilala
    Abstract:

    Traumatic brain injury (TBI) is an important contributor to morbidity and mortality. Low Cerebral perfusion pressure (CPP, mean arterial pressure [MAP] minus intracranial pressure) after TBI is associated with Cerebral ischemia, impaired Cerebral Autoregulation, and poor outcomes. Normalization of CPP and limitation of Cerebral Autoregulation impairment is a key therapeutic goal. However, some vasoactive agents used to elevate MAP such as phenylephrine (Phe) improve outcome in females but not male piglets after TBI while dopamine (DA) does so in both sexes. Clinical evidence has implicated neurological injuries as a cause of cardiac dysfunction, and we recently described cardiac dysfunction after TBI. Cardiac dysfunction may, in turn, influence brain health. One mechanism of myocyte injury may involve catecholamine excess. We therefore tested the hypothesis that TBI caused cardiac dysfunction and catecholamine excess which may reciprocally be modulated by vasoactive agent choice to normalize CPP and prevent impairment of Cerebral Autoregulation after injury. TBI was produced in anesthetized pigs equipped with a closed cranial window, and Phe or DA administered to normalize CPP. Plasma cardiac enzymes troponin and creatine kinase and catecholamines epinephrine and norepinephrine were elevated by TBI, such release potentiated by Phe in males but blocked in female piglets and blocked in both sexes after DA. Cerebral Autoregulation was impaired after TBI, worsened by Phe in males but protected in females and males treated with DA. Papaverine-induced dilation was unchanged by fluid percussion brain injury, DA, and Phe. These data indicate that pressor choice in elevation of CPP is important in limiting cardiac dysfunction and suggest that DA protects Cerebral Autoregulation in both sexes via reduction of cardiac biomarkers of injury and catecholamines released after TBI.

  • prevalence evolution and extent of impaired Cerebral Autoregulation in children hospitalized with complex mild traumatic brain injury
    Pediatric Critical Care Medicine, 2019
    Co-Authors: Jerry J. Zimmerman, William M Armstead, Abhijit V Lele, Arraya Watanitanon, Viharika Lakireddy, Crystalyn Clarkbell, Anne Moore, Randall M Chesnut, Monica S. Vavilala
    Abstract:

    OBJECTIVES To examine Cerebral Autoregulation in children with complex mild traumatic brain injury. DESIGN Prospective observational convenience sample. SETTING PICU at a level I trauma center. PATIENTS Children with complex mild traumatic brain injury (trauma, admission Glasgow Coma Scale score 13-15 with either abnormal head CT, or history of loss of consciousness). INTERVENTIONS Cerebral Autoregulation was tested using transcranial Doppler ultrasound between admission day 1 and 8. MEASUREMENTS AND MAIN RESULTS The primary outcome was prevalence of impaired Cerebral Autoregulation (Autoregulation index < 0.4),determined using transcranial Doppler ultrasonography and tilt testing. Secondary outcomes examined factors associated with and evolution and extent of impairment. Cerebral Autoregulation testing occurred in 31 children 10 years (SD, 5.2 yr), mostly male (59%) with isolated traumatic brain injury (91%), median admission Glasgow Coma Scale 15, Injury Severity Scores 14.2 (SD, 7.7), traumatic brain injury due to fall (50%), preadmission loss of consciousness (48%), and abnormal head CT scan (97%). Thirty-one children underwent 56 Autoregulation tests. Impaired Cerebral Autoregulation occurred in 15 children (48.4%) who underwent 19 tests; 68% and 32% of tests demonstrated unilateral and bilateral impairment, respectively. Compared with children on median day 6 of admission after traumatic brain injury, impaired Autoregulation was most common in the first 5 days after traumatic brain injury (day 1: relative risk, 3.7; 95% CI, 1.9-7.3 vs day 2: relative risk, 2.7; 95% CI, 1.1-6.5 vs day 5: relative risk, 1.33; 95% CI, 0.7-2.3). Children with impaired Autoregulation were older (12.3 yr [SD, 1.3 yr] vs 8.7 yr [SD, 1.1 yr]; p = 0.04) and tended to have subdural hematoma (64% vs 44%), epidural hematoma (29% vs 17%), and subarachnoid hemorrhage (36% vs 28%). Eight children (53%) were discharged home with ongoing impaired Cerebral Autoregulation. CONCLUSIONS Impaired Cerebral Autoregulation is common in children with complex mild traumatic brain injury, despite reassuring admission Glasgow Coma Scale 13-15. Children with complex mild traumatic brain injury have abnormal cerebrovascular hemodynamics, mostly during the first 5 days. Impairment commonly extends to the contralateral hemisphere and discharge of children with ongoing impaired Cerebral Autoregulation is common.

  • inhaled nitric oxide protects Cerebral Autoregulation and reduces hippocampal necrosis after traumatic brain injury through inhibition of et 1 erk mapk and il 6 upregulation in pigs
    Neurocritical Care, 2019
    Co-Authors: Victor Curvello, Hugh Hekierski, Philip Pastor, William M Armstead
    Abstract:

    OBJECTIVE Traumatic brain injury (TBI) is an important contributor to morbidity and mortality. Cerebral Autoregulation is impaired after TBI, contributing to poor outcome. Extracellular signal-related kinase (ERK) mitogen activated protein kinase (MAPK) and ET-1 are upregulated and contribute to impairment of Cerebral Autoregulation and histopathology after porcine fluid percussion brain injury (FPI). Recent studies show that inhaled nitric oxide (iNO) prevents impairment of Cerebral Autoregulation and histopathology after FPI in pigs. Unrelated studies indicated an association between ERK and increased IL-6 after FPI. However, the role of IL-6 in central nervous system (CNS) pathology is not well understood. We investigated whether iNO protects Autoregulation and limits histopathology after FPI in pigs due to modulation of brain injury associated upregulation of ET-1, ERK MAPK, and IL-6. METHODS Lateral FPI was produced in anesthetized pigs equipped with a closed cranial window and iNO administered at 30 min or 2 h post injury. RESULTS CSF ET-1, ERK MAPK, and IL-6 were increased by FPI, but release was blocked by iNO administered at 30 min or 2 h after TBI. The IL-6 antagonist LMT-28 prevented impairment of Cerebral Autoregulation and hippocampal CA1 and CA3 neuronal necrosis after FPI. Papaverine induced dilation was unchanged by FPI and LMT-28. Protection lasted for at least 2 h after iNO administration was stopped. CONCLUSIONS These data indicate that iNO protects Cerebral Autoregulation and reduces hippocampal necrosis after traumatic brain injury through inhibition of ET-1, ERK MAPK, and IL-6 upregulation in pigs.

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  • personalized blood pressure management during cardiac surgery with Cerebral Autoregulation monitoring a randomized trial
    Seminars in Thoracic and Cardiovascular Surgery, 2020
    Co-Authors: Charles W. Hogue, Daijiro Hori, Yohei Nomura, Charles H. Brown, Masa Ono, Lauren C Balmert, Nina Srdanovic, Jordan Grafman, Ken M Brady, Duke E Cameron
    Abstract:

    The purpose of this study was to determine if setting mean arterial pressure (MAP) targets during cardiopulmonary bypass (CPB) based on individualized Cerebral Autoregulation data reduces the frequency of neurological complications compared with usual care. Patients (n=460) ≥ 55 years old at risk for neurological complications were randomized to have MAP targets during CPB to be above the lower limit of transcranial Doppler determined Cerebral Autoregulation versus usual institutional practices. The primary outcome was the frequency of the composite endpoint of clinical stroke, or new brain MRI detected ischemic injury, or cognitive decline 4 to 6 weeks after surgery from baseline. Secondary outcomes were components of the primary composite outcome and clinically detected delirium. Complete outcome data were available from 194 patients (stroke assessments, n=460; MRI data, n=164; cognitive data n=336). There was no difference between groups in the frequency of the composite neurological end-point or its components (p=0.752). Compared with the usual care there was a 45% reduction in the frequency of clinically detected delirium in the Autoregulation group (8.2% versus 14.9%, risk ratio=0.55, 95% CI=0.32, 0.93, p=0.035) and improved performance on test of memory 4 to 6 weeks after surgery from baseline (p=0.019). Basing MAP during CPB on Cerebral Autoregulation monitoring did not reduce the frequency of the primary neurological outcome in high-risk patients compared with usual care but it was associated with a reduction in the frequency of delirium and better performance on tests of memory 4 to 6 weeks after surgery.

  • optimal blood pressure during cardiopulmonary bypass defined by Cerebral Autoregulation monitoring
    The Journal of Thoracic and Cardiovascular Surgery, 2017
    Co-Authors: Daijiro Hori, Masahiro Ono, Brijen Joshi, Yohei Nomura, Kaushik Mandal, Duke E Cameron, Masha Kocherginsky, Charles W. Hogue
    Abstract:

    Abstract Objectives We sought to define the lower and upper limits of Cerebral blood flow Autoregulation and the optimal blood pressure during cardiopulmonary bypass. We further sought to identify variables predictive of these Autoregulation end points. Methods Cerebral Autoregulation was monitored continuously with transcranial Doppler in 614 patients during cardiopulmonary bypass enrolled in 3 investigations. A moving Pearson's correlation coefficient was calculated between Cerebral blood flow velocity and mean arterial pressure to generate the variable mean velocity index. Optimal mean arterial pressure was defined as the mean arterial pressure with the lowest mean velocity index indicating the best Autoregulation. The lower and upper limits of Cerebral blood flow Autoregulation were defined as the mean arterial pressure at which mean velocity index was increasingly pressure passive (ie, mean velocity index ≥0.4) with declining or increasing blood pressure, respectively. Results The mean (± standard deviation) lower and upper limits of Cerebral blood flow Autoregulation, and optimal mean arterial pressure were 65 ± 12 mm Hg, 84 ± 11 mm Hg, and 78 ± 11 mm Hg, respectively, after adjusting for study enrollment. In 17% of patients, though, the lower limit of Cerebral Autoregulation was above this optimal mean arterial pressure, whereas in 29% of patients the upper limit of Autoregulation was below the population optimal mean arterial pressure. Variables associated with optimal mean arterial pressure based on multivariate regression analysis were nonwhite race (increased 2.7 mm Hg; P  = .034), diuretics use (decreased 1.9 mm Hg; P  = .049), prior carotid endarterectomy (decreased 5.5 mm Hg; P  = .019), and duration of cardiopulmonary bypass (decreased 1.28 per 60 minutes of cardiopulmonary bypass). The product of the duration and magnitude that mean arterial pressure during cardiopulmonary bypass was below the lower limit of Cerebral Autoregulation was associated with the risk for stroke ( P  = .02). Conclusions Real-time monitoring of Autoregulation may improve individualizing mean arterial pressure during cardiopulmonary bypass and improving patient outcomes.

  • predictors of outcome with Cerebral Autoregulation monitoring a systematic review and meta analysis
    Critical Care Medicine, 2017
    Co-Authors: Lucia Riveralara, Peter Smielewski, Marek Czosnyka, Romergryko G. Geocadin, Ryan Healy, Wendy C. Ziai, Andres Zorrillavaca, Richard E Thompson, Charles W. Hogue
    Abstract:

    Objective:To compare Cerebral Autoregulation indices as predictors of patient outcome and their dependence on duration of monitoring.Data Sources:Systematic literature search and meta-analysis using PubMed, EMBASE, and the Cochrane Library from January 1990 to October 2015.Study Selection:We chose a

  • effect of carotid revascularization on Cerebral Autoregulation in combined cardiac surgery
    European Journal of Cardio-Thoracic Surgery, 2016
    Co-Authors: Daijiro Hori, Hideo Adachi, Charles W. Hogue
    Abstract:

    OBJECTIVES: Combined carotid artery endarterectomy (CEA) and coronary artery bypass grafting surgery is considered to reduce long-term stroke risk for patients with severe carotid artery stenosis. The benefits of CEA for improving Cerebral perfusion during subsequent cardiopulmonary bypass (CPB) are unclear. The purpose of this pilot study was to assess Cerebral Autoregulation and Cerebral oximetry in patients undergoing combined CEA and cardiac surgery with those undergoing cardiac surgery without significant carotid artery stenosis or with uncorrected stenosis. METHODS: Cerebral Autoregulation was monitored continuously in 257 patients with the Cerebral oximetry index (COx). COx represents a moving Pearson's correlation coefficient between low-frequency changes in regional Cerebral oxygen saturation (rScO2) and mean arterial pressure that has been validated in previous investigations. Impaired Autoregulation was defined as a value of COx ≥0.3. RESULTS: Nineteen patients had prior CEA, 8 underwent combined CEA and cardiac surgery, 8 had uncorrected stenosis >70% and 197 had stenosis 70% had a higher COx before CPB compared with those with stenosis <50% (median, 0.26, 25th percentile and 75th percentile [p25-p75], 0.18-0.33 vs 0.18, p25-p75, 0.07-0.27, respectively, P = 0.054). Patients who underwent combined CEA and cardiac surgery had a higher COx before surgery compared with those with prior CEA (P = 0.027) and stenosis <50% (P = 0.026). There were no differences in average COx or rScO2 during CPB in patients undergoing combined CEA and cardiac surgery compared with those with prior CEA (P = 0.53, 0.27) and those with stenosis <50% (P = 0.71, 0.19), respectively. During CPB, patients with uncorrected stenosis had an average COx of 0.36 (p25-p75, 0.28-0.56) indicating Cerebral Autoregulation impairment, and lower rScO2 compared with patients with prior CEA (P = 0.006) and stenosis <50% (P = 0.005). CONCLUSIONS: While higher at baseline, patients undergoing CEA immediately before cardiac surgery had COx and rScO2 measurements during CPB similar to those with non-significant stenosis in contrast to those patients with uncorrected stenosis who had evidence of impaired Autoregulation and lower rScO2. These preliminary results suggest the potential utility of COx, possibly for complimenting patient selection for CEA as well as for individual patient management during surgery.

  • Cerebral Autoregulation monitoring with ultrasound tagged near infrared spectroscopy in cardiac surgery patients
    Anesthesia & Analgesia, 2015
    Co-Authors: Daijiro Hori, Charles W. Hogue, Charles H. Brown, Ashish S Shah, Karin J Neufeld, John V Conte, Joel Price, Christopher M Sciortino, Laura Max, Andrew Laflam
    Abstract:

    BACKGROUND:Individualizing mean arterial blood pressure (MAP) based on Cerebral blood flow (CBF) Autoregulation monitoring during cardiopulmonary bypass (CPB) holds promise as a strategy to optimize organ perfusion. The purpose of this study was to evaluate the accuracy of Cerebral Autoregulation mo