Impaired Cerebral Autoregulation Research Articles

Post-Carotid Artery Stenting Hyperperfusion Syndrome in a Hypotensive Patient: Case Report and Systematic Review of Literature

Cerebral hyperperfusion syndrome (CHS) is a serious post-procedural complication of carotid artery stenting (CAS). The pathophysiological mechanisms of CHS in the absence of arterial hypertension (AH) remain only partially understood. We performed a systematic literature search of the PubMed database using the terms »cerebral hyperperfusion syndrome«, »hypotension«, »hyperperfusion«, »stroke«, »intracranial hemorrhages«, »risk factors«, »carotid revascularization«, »carotid stenting«, »carotid endarterectomy«, »blood-brain barrier«, »endothelium«, »contrast encephalopathy«, and combinations. We present a case of a normotensive female patient who developed CHS post-CAS for symptomatic carotid stenosis while being hypotensive with complete recovery. We identified 393 papers, among which 65 were deemed relevant to the topic. The weighted average prevalence of CHS after CAS is 1.2% [0.0–37.7%] with that of intracranial hemorrhage (ICH) being 0.51% [0–9.3%]. Recently symptomatic carotid stenosis or contralateral carotid revascularization, urgent intervention, acute carotid occlusion, contralateral ≥70% stenosis, and the presence of leptomeningeal collaterals were associated with CHS. A prolonged hemodynamic instability after CAS conveys a higher risk for CHS. However, none of the articles mentioned isolated hypotension as a risk factor for CHS. Whereas mortality after ICH post-CAS ranges from 40 to 75%, in the absence of ICH, CHS generally carries a good prognosis. AH is not obligatory in CHS development. Even though impaired cerebral autoregulation and post-revascularization changes in cerebral hemodynamics seem to play a pivotal role in CHS pathophysiology, our case highlights the complexity of CHS, involving factors like endothelial dysfunction and sudden reperfusion. Further research is needed to refine diagnostic and management approaches for this condition.

Correlation between antihypertensive drugs and cerebral hemodynamic parameters: insights from observational findings using transcranial Doppler.

Antihypertensives (AHD) can influence cerebral autoregulation (CA) and attenuate hypertrophic concentric remodelling of arterioles. The aim of this study was to examine the associations between AHD, CA and structural and functional properties of cerebral arteries. In this observational, cross-sectional study 115 volunteers were divided in group 1 (non-hypertensive) [n = 30]; group 2 (hypertensive with systolic blood pressure [SBP] < 140 and diastolic blood pressure [DBP] < 90 mmHg) [n = 54]; group 3 (hypertensive with SBP ≥ 140 or DBP ≥ 90 mmHg) [n = 31] and simultaneous measurements of systemic blood pressure (BP) and middle cerebral artery blood flow velocity (CBFV) were obtained from digital plethysmography and transcranial Doppler. Beat-to-beat, critical closing pressure (CrCP), resistance-area product (RAP) and autoregulation index (ARI) values were extracted by linear regression analysis of instantaneous BP and CBFV waveforms using computerised analysis. Pulsatility index (PI) was calculated and CO2 reactivity was assessed by the breath-holding test. Despite their higher RAP (1.7 [±0.7], p < 0.001) compared to groups 1 and 2, uncontrolled hypertensive using diuretics (p = 0.047) and α2-agonists (p = 0.009) had significantly lower PI. Impaired CO2 reactivity was common between the two hypertensive groups (p = 0.008), however ARI, CrCP and CBFV did not differ between them and non-hypertensive individuals and also did not correlate with any AHD used. Unlike the RAP, PI does not seem to reflect the real cerebrovascular resistence resulting from chronic arterial remodelling. Despite impaired CO2 reactivity, hypertensivehavearterial tonus and CA comparable to non-hypertensive. Experimental studies involving an untreated hypertensive control group are required to robustly make definitive conclusions about these questions.

Cerebral Overperfusion Despite Reduced Cortical Metabolism Is Associated with Postoperative Delirium in Cardiac Surgery Patients: A Prospective Observational Study.

Background: Decreased cerebral oximetry (rSO2) in cardiac surgery is associated with postoperative delirium (POD). However, interventions optimizing intraoperative rSO2 are inconclusive. Methods: In this prospective observational cohort study, the relationship between rSO2, middle cerebral artery blood flow velocity (MCAV), and processed EEG was assessed in cardiac surgery patients with and without POD. MCAV was continuously recorded by transcranial Doppler sonography (TCD), together with continuous rSO2 and bispectral index (BIS) monitoring. Cardiopulmonary bypass (CPB) flow rate was adjusted according to body surface area. The cohort was divided into the POD and control groups, according to the postoperative results of the confusion assessment method (CAM/CAM-ICU), the 4A's test (4AT), and the Delirium Observation Scale (DOS). A mixed model analysis was performed for intraoperative raw data. The cerebral autoregulation index was calculated from TCD, rSO2, and arterial pressure values. Differences in impaired autoregulation were compared using the Mann-Whitney U test. Results: A total of 41 patients were included in this study. A total of 13 patients (36.11%) developed postoperative delirium. There were no significant differences in the baseline characteristics of patients with or without POD. Patients with POD had lower BIS values during CPB (adjusted mean difference -4.449 (95% CI [-7.978, -0.925])). RSO2 was not significantly reduced in POD, (adjusted mean difference: -5.320, 95% CI [-11.508, 0.874]). In contrast, MCAV was significantly increased in POD (10.655, 95% CI [0.491, 20.819]). The duration of cerebral autoregulation impairment did not differ significantly for TCD and cerebral oximetry-derived indices (p = 0.4528, p = 0.2715, respectively). Conclusions: Our results suggest that disturbed cerebral metabolism reflects a vulnerable brain which may be more susceptible to overperfusion during CPB, which can be seen in increased MCAV values. These phenomena occur irrespectively of cerebral autoregulation.

Heart Rate Variability and Cerebral Autoregulation in Patients with Traumatic Brain Injury with Paroxysmal Sympathetic Hyperactivity Syndrome.

Severe traumatic brain injury (TBI) can lead to transient changes in autonomic nervous system (ANS) functioning and development of paroxysmal sympathetic hyperactivity (PSH) syndrome. Clinical manifestation of ANS disorders may be obscured by therapeutic interventions in TBI. This study aims to analyze ANS metrics and cerebral autoregulation in patients with PSH syndrome to determine their significance in early prognostication. This single-center retrospective study investigated the relationship between changes in ANS metrics, cerebral autoregulation, and PSH syndrome. Arterial blood pressure and intracranial pressure signals were monitored for 5 days post TBI. ANS metrics included time and frequency domain heart rate variability (HRV) metrics. Cerebral autoregulation was assessed using the pressure reactivity index. Sixty-six patients with severe TBI (median age 33 [interquartile range 26-50] years) were analyzed, and PSH was confirmed in nine cases. Impairment of cerebral autoregulation was observed in 67% of patients with PSH and 72% without the syndrome. Patients with PSH had higher HRV in the low-frequency range (LF; 253 ± 178 vs. 176 ± 227 ms2; p = 0.035) and lower heart rates (HRs; 70 ± 7 vs. 78 ± 19 bpm; p = 0.027) compared to those without PSH. A receiver operating characteristic curve analysis indicated that HR (area under the curve(AUC) = 0.73, p = 0.006) and HRV in the LF (AUC = 0.70, p = 0.009) are moderate predictors of PSH. In the multiple logistic regression model for PSH, diffuse axonal trauma (odds ratio(OR) = 10.82, 95% confidence interval(CI) = 1.70-68.98, p = 0.012) and HR (OR =0.91, 95% CI 0.84-0.98, p = 0.021) were significant factors. Elevated HRV in the LF and decreased HR may serve as early predictors of PSH syndrome development, particularly in patients with diffuse axonal trauma. Further research is needed to investigate the utility of the cerebral autoregulation-ANS relationship in PSH prognostication.

Cerebral haemodynamics and intracranial pressure during haemorrhagic shock and resuscitation with total endovascular balloon occlusion of the aorta in an animal model.

To assess changes of cerebral haemodynamic and intracranial pressure (ICP) in animals, with or without elevated ICP, during controlled haemorrhagic shock and resuscitation with Total REBOA (tREBOA). In 22 anaesthetized and normoventilated pigs, after placement of catheters for monitoring invasive proximal blood pressure (pMAP), ICP, and vital parameters, and 60min stabilisation phase, a controlled haemorrhagic shock (HS), was conducted. In 11 pigs (EICPG), an elevated ICP of 25-30 mmHg at the end HS was achieved by simulating an epidural mass. In 11 pigs (NICPG), the ICP was normal. tREBOA was then applied for 120min. The changes of pMAP and ICP were followed, and cerebral perfusion pressure (CPP) calculated. The integrity of the autoregulation was estimated using a calculated Modified-Long Pressure Reactivity Index (mL-PRx). After stabilisation, hemodynamics and physiological parameters were similar and normal in both groups. At the end of the HS, ICP was 16 mmHg in NICPG vs. 32 in EICPG (p = 0.0010). CPP was 30 mmHg in NICPG vs. 6 mmHg in EICPG (p = 0.0254). After aorta occlusion CPP increased immediately in both groups reaching after 15min up to104 mmHg in NICPG vs. 126 mmHg in EICPG. Cerebrovascular reactivity seems to be altered during bleeding and occlusion phases in both groups with positive mL-PRx. The alteration was more pronounced in EICPG, but reversible in both groups. tREBOA is lifesaving by restoration the cerebral circulation defined as CPP in animals with HS with normal or elevated ICP. Despite the observation of short episodes of cerebral autoregulation impairment during the occlusion, mainly in EICPG, tREBOA seems to be an effective tool for improving cerebral perfusion in HS that extends the crucial early window sometimes known as the "golden hour" for resuscitation even after a traumatic brain injury.

Impact of different blood pressure targets on cerebral hemodynamics in septic shock: A prospective pilot study protocol-SEPSIS-BRAIN.

Septic shock, a life-threatening condition, can result in cerebral dysfunction and heightened mortality rates. In these patients, disturbances in cerebral hemodynamics, as reflected by impairment of myogenic cerebral autoregulation (CA), metabolic regulation, expressed by critical closing pressure (CrCP) and reductions in intracranial compliance (ICC), can adversely impact septic shock outcomes. The general recommendation is to maintain a target mean arterial pressure (MAP) of 65 mmHg but the effect of different MAP targets on cerebral hemodynamics in these patients is not clear and optimal targets might be dependent on the status of CA. This protocol aims to assess the cerebral hemodynamics profile at different pressure targets in septic shock patients. Prospective, non-randomized, single-center trial, which will study cerebral hemodynamics in patients with septic shock within 48 hours of its onset. Patients will be studied at their baseline MAP and at three MAP targets (T1: 65, T2: 75, T3: 85 mmHg). Cerebral hemodynamics will be assessed by transcranial Doppler (TCD) and a skull micro-deformation sensor (B4C). Dynamic CA will be expressed by the autoregulation index (ARI), calculated by transfer function analysis, using fluctuations of MAP as input and corresponding oscillations in cerebral blood velocity (CBv). The instantaneous relationship between arterial blood pressure and CBv will be used to estimate CrCP and resistance-area product (RAP) for each cardiac cycle using the first harmonic method. The B4C will access ICC by intracranial pressure waveforms (P2/P1). The primary aim is to assess cerebral hemodynamics (ARI, CrCP, RAP, and P2/P1) at different targets of MAP in septic shock patients. Our secondary objective is to assess cerebral hemodynamics at 65mmHg (target recommended by guidelines). In addition, we will assess the correlation between markers of organ dysfunction (such as lactate levels, vasoactive drugs usage, SOFA score, and delirium) and CA. The results of this study may help to understand the effect of the recommended MAP and variations in blood pressure in patients with septic shock and impaired CA and ICC. Furthermore, the results can assist large trials in establishing new hypotheses about neurological management in this group of patients. Approval was obtained from the local Ethics Committee (28134720.1.0000.0048). It is anticipated that the results of this study will be presented at national and international conferences and will be published in peer-reviewed journals in 2024 and 2025. Trial registration number: NCT05833607. https://clinicaltrials.gov/study/NCT05833607.

Optimal target mean arterial pressure for patients with sepsis-associated encephalopathy: a retrospective cohort study

BackgroundSepsis-associated encephalopathy (SAE) patients often experience changes in intracranial pressure and impaired cerebral autoregulation. Mean arterial pressure (MAP) plays a crucial role in cerebral perfusion pressure, but its relationship with mortality in SAE patients remains unclear. This study aims to investigate the relationship between MAP and the risk of 28-day and in-hospital mortality in SAE patients, providing clinicians with the optimal MAP target.MethodsWe retrospectively collected clinical data of patients diagnosed with SAE on the first day of ICU admission from the MIMIC-IV (v2.2) database. Patients were divided into four groups based on MAP quartiles. Kruskal-Wallis H test and Chi-square test were used to compare clinical characteristics among the groups. Restricted cubic spline and segmented Cox regression models, both unadjusted and adjusted for multiple variables, were employed to elucidate the relationship between MAP and the risk of 28-day and in-hospital mortality in SAE patients and to identify the optimal MAP. Subgroup analyses were conducted to assess the stability of the results.ResultsA total of 3,816 SAE patients were included. The Q1 group had higher rates of acute kidney injury and vasoactive drug use on the first day of ICU admission compared to other groups (P < 0.01). The Q1 and Q4 groups had longer ICU and hospital stays (P < 0.01). The 28-day and in-hospital mortality rates were highest in the Q1 group and lowest in the Q3 group. Multivariable adjustment restricted cubic spline curves indicated a nonlinear relationship between MAP and mortality risk (P for nonlinearity < 0.05). The MAP ranges associated with HRs below 1 for 28-day and in-hospital mortality were 74.6–90.2 mmHg and 74.6–89.3 mmHg, respectively.The inflection point for mortality risk, determined by the minimum hazard ratio (HR), was identified at a MAP of 81.5 mmHg. The multivariable adjusted segmented Cox regression models showed that for MAP < 81.5 mmHg, an increase in MAP was associated with a decreased risk of 28-day and in-hospital mortality (P < 0.05). In Model 4, each 5 mmHg increase in MAP was associated with a 15% decrease in 28-day mortality risk (HR: 0.85, 95% CI: 0.79–0.91, p < 0.05) and a 14% decrease in in-hospital mortality risk (HR: 0.86, 95% CI: 0.80–0.93, p < 0.05). However, for MAP ≥ 81.5 mmHg, there was no significant association between MAP and mortality risk (P > 0.05). Subgroup analyses based on age, congestive heart failure, use of vasoactive drugs, and acute kidney injury showed consistent results across different subgroups.Subsequent analysis of SAE patients with septic shock also showed results similar to those of the original cohort.However, for comatose SAE patients (GCS ≤ 8), there was a negative correlation between MAP and the risk of 28-day and in-hospital mortality when MAP was < 81.5 mmHg, but a positive correlation when MAP was ≥ 81.5 mmHg in adjusted models 2 and 4.ConclusionThere is a nonlinear relationship between MAP and the risk of 28-day and in-hospital mortality in SAE patients. The optimal MAP target for SAE patients in clinical practice appears to be 81.5 mmHg.

Neuraxial anesthesia for non-neurological emergency surgery in a patient with acute ischemic stroke: a case report

BackgroundThe recent guidelines recommend delaying elective non-neurological surgery after an index stroke, but there is a lack of consensus regarding emergency surgery in patients with a recent stroke. Impaired cerebral autoregulation and altered baroreceptor function elevate the risk of recurrent stroke in this group. Moreover, the impact of anesthesia type (general vs. regional) for non-cardiovascular, non-neurological surgery in patients with an index stroke remains inconclusive.Case presentationA 67-year-old male with an acute mild ischemic stroke underwent emergency surgery for an obstructed right-sided direct inguinal hernia under combined spinal-epidural anesthesia. Pre-operative assessment showed stable hemodynamics, and perioperative measures were taken to ensure stable blood pressure. Neuraxial anesthesia was employed successfully, and the patient remained hemodynamically stable throughout the surgery and postoperative period. No neurological deficits were observed post-surgery, and follow-up up to 3 months revealed no cognitive impairment or neurological decline.ConclusionsNeuraxial anesthesia can be considered for patients with acute mild strokes requiring urgent non-neurological surgery, provided they are hemodynamically stable and without coagulopathy. However, the choice of anesthesia should be individualized based on factors such as neurological status, stroke severity, coagulation, and existing disabilities. This case highlights the importance of a personalized approach to anesthesia in emergency surgery for stroke patients.

Oxygen-Based Autoregulation Indices Associated with Clinical Outcomes and Spreading Depolarization in Aneurysmal Subarachnoid Hemorrhage.

Impairment in cerebral autoregulation has been proposed as a potentially targetable factor in patients with aneurysmal subarachnoid hemorrhage (aSAH); however, there are different continuous measures that can be used to calculate the state of autoregulation. In addition, it has previously been proposed that there may be an association of impaired autoregulation with the occurrence of spreading depolarization (SD) events. Study participants with invasive multimodal monitoring and aSAH were enrolled in an observational study. Autoregulation indices were prospectively calculated from this database as a 10s moving correlation coefficient between various cerebral blood flow (CBF) surrogates and mean arterial pressure (MAP). In study participants with subdural electrocorticography (ECoG) monitoring, SD was also scored. Associations between clinical outcomes using the modified Rankin scale and occurrence of either isolated or clustered SD were assessed. A total of 320 study participants were included, 47 of whom also had ECoG SD monitoring. As expected, baseline severity factors, such as modified Fisher scale score and World Federation of Neurosurgical Societies scale grade, were strongly associated with the clinical outcome. SD probability was related to blood pressure in a triphasic pattern, with a linear increase in probability below MAP of ~ 100 mm Hg. Multiple autoregulation indices were available for review based on moving correlations between mean arterial pressure (MAP) and various surrogates of cerebral blood flow (CBF). We calculated the pressure reactivity (PRx) using two different sources for intracranial pressure (ICP). We calculated the oxygen reactivity (ORx) using the partial pressure of brain tissue oxygen (PbtO2) from the Licox probe. We calculated the cerebral blood flow reactivity (CBFRx) using perfusion measurements from the Bowman perfusion probe. Finally, we calculated the cerebral oxygen saturation reactivity (OSRx) using regional cerebral oxygen saturation measured by near-infrared spectroscopy from the INVOS sensors. Only worse ORx and OSRx were associated with worse clinical outcomes. Both ORx and OSRx also were found to increase in the hour prior to SD for both sporadic and clustered SD. Impairment in autoregulation in aSAH is associated with worse clinical outcomes and occurrence of SD when using ORx and OSRx. Impaired autoregulation precedes SD occurrence. Targeting the optimal MAP or cerebral perfusion pressure in patients with aSAH should use ORx and/or OSRx as the input function rather than intracranial pressure.

Vascular Function and Ion Channels in Alzheimer's Disease.

This review paper explores the critical role of vascular ion channels in the regulation of cerebral artery function and examines the impact of Alzheimer's disease (AD) on these processes. Vascular ion channels are fundamental in controlling vascular tone, blood flow, and endothelial function in cerebral arteries. Dysfunction of these channels can lead to impaired cerebral autoregulation, contributing to cerebrovascular pathologies. AD, characterized by the accumulation of amyloid beta (Aβ) plaques and neurofibrillary tangles, has been increasingly linked to vascular abnormalities, including altered vascular ion channel activity. Here, we briefly review the role of vascular ion channels in cerebral blood flow control and neurovascular coupling. We then examine the vascular defects in AD, the current understanding of how AD pathology affects vascular ion channel function, and how these changes may lead to compromised cerebral blood flow and neurodegenerative processes. Finally, we provide future perspectives and conclusions. Understanding this topic is important as ion channels may be potential therapeutic targets for improving cerebrovascular health and mitigating AD progression.

Monitoring of Cerebral Blood Flow Autoregulation after Cardiac Arrest.

Background: Cardiac arrest remains one of the leading causes of death. After successful resuscitation of patients in cardiac arrest, post-cardiac arrest syndrome develops, part of it being an impaired cerebral blood flow autoregulation. Monitoring cerebral blood flow autoregulation after cardiac arrest is important for optimizing patient care and prognosticating patients' survival, yet remains a challenge. There are still gaps in clinical implications and everyday use. In this article, we present a systematic review of studies with different methods of monitoring cerebral blood flow autoregulation after non-traumatic cardiac arrest. Methods: A comprehensive literature search was performed from 1 June 2024 to 27 June 2024 by using multiple databases: PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials. Inclusion criteria were studies with an included description of the measurement of cerebral blood flow autoregulation in adult patients after non-traumatic cardiac arrest. Results: A total of 16 studies met inclusion criteria. Our data show that the most used methods in the reviewed studies were near-infrared spectroscopy and transcranial Doppler. The most used mathematical methods for calculating cerebral autoregulation were cerebral oximetry index, tissue oxygenation reactivity index, and mean flow index. Conclusions: The use of various monitoring and mathematical methods for calculating cerebral blood flow autoregulation poses a challenge for standardization, validation, and daily use in clinical practice. In the future studies, focus should be considered on clinical validation and transitioning autoregulation monitoring techniques to everyday clinical practice, which could improve the survival outcomes of patients after cardiac arrest.

The Association of Cerebral Autoregulation Dysfunction and Postoperative Memory Impairment in Cardiac Surgery Patients.

Background and Objectives: Cardiac surgery is associated with various durations of cerebral autoregulation (CA) impairment and can significantly impact cognitive function. Cognitive functions such as memory, psychomotor speed, and attention are significantly impacted after cardiac surgery, necessitating prioritization of these areas in cognitive function tests. There is a lack of research connecting cerebral autoregulation impairment to specific cognitive function domains after cardiac surgery. This study aimed to determine if impaired cerebral autoregulation is associated with postoperative memory impairment and to test the hypothesis that the duration of this impairment affects the development of postoperative memory issues. Materials and Methods: A prospective study was conducted in 2021-2023. After approval of the Ethics Committee and with patient's written consent, 83 adult patients undergoing elective on-pump coronary artery bypass graft (CABG) surgery were enrolled. All patients were assessed for cognitive function 1 day before surgery using the Mini-Mental state examination (MMSE-2) test as a screening tool and the Hopkins Verbal Learning Test-Revised (HVLT-R) to assess memory specifically. To diagnose possible memory impairment (IM), all patients underwent a repeat assessment of cognitive function on the 7th-10th postoperative day. Cerebral autoregulation monitoring using transcranial Doppler was performed. Cerebral autoregulation status index (Mx) was recorded using Intensive Care Brain Monitoring System software, 9.1.5.23 (Cambridge, UK). Results: According to our research, the incidence of postoperative memory impairment is 30.1%. Temporary cerebral autoregulation impairment occurs in all patients undergoing elective in-pump CABG surgery. The duration of the single longest CA impairment event in seconds (LCAI) and the LCAI dose were higher in patients with postoperative memory impairment, p = 0.006 and p < 0.007, respectively. Conclusions: Cerebral autoregulation impairment is important in developing memory loss after cardiac surgery. The duration and dose of the LCAI event are predictive of postoperative memory impairment.

Dynamics of Critical Closing Pressure Explain Cerebral Autoregulation Impairment in Acute Cerebrovascular Disease.

Cerebral autoregulation (CA) is impaired in acute ischemic stroke (AIS) and is associated with worse patient outcomes, but the underlying physiological cause is unclear. This study tests whether depressed CA in AIS can be linked to the dynamic responses of critical closing pressure (CrCP) and resistance area product (RAP). Continuous recordings of middle cerebral blood velocity (MCAv, transcranial Doppler), arterial blood pressure (BP), end-tidal CO2 and electrocardiography allowed dynamic analysis of the instantaneous MCAv-BP relationship to obtain estimates of CrCP and RAP. The dynamic response of CrCP and RAP to a sudden change in mean BP was obtained by transfer function analysis. Comparisons were made between younger controls (≤50 years), older controls (&gt;50 years), and AIS patients. Data from 24 younger controls (36.4 ± 10.9 years, 9 male), 38 older controls (64.7 ± 8.2 years, 20 male), and 20 AIS patients (63.4 ± 13.8 years, 9 male) were included. Dynamic CA was impaired in AIS, with lower autoregulation index (affected hemisphere: 4.0 ± 2.3, unaffected: 4.5 ± 1.8) compared to younger (right: 5.8 ± 1.4, left: 5.8 ± 1.4) and older (right: 4.9 ± 1.6, left: 5.1 ± 1.5) controls. AIS patients also demonstrated an early (0-3 s) peak in CrCP dynamic response that was not influenced by age. These early transient differences in the CrCP dynamic response are a novel finding in stroke and occur too early to reflect underlying regulatory mechanisms. Instead, these may be caused by structural changes to cerebral vasculature.

Intracranial Pressure Thresholds for Cerebral Autoregulation Impairment: Age-Stratified Analysis of Ultra-Low-Frequency Pressure Reactivity Index (UL-PRx) in Traumatic Brain Injury.

The study investigated the effectiveness of low-frequency sampling in detecting alterations in cerebrovascular reactivity (CVR) associated with changes in intracranial pressure (ICP) in patients with traumatic brain injury (TBI) across different age groups. The primary objective was to investigate an ICP threshold that indicates a decrease in CVR as evidenced by a significant increase in the ultra-low-frequency pressure reactivity index (UL-PRx). Additionally, the study aimed to develop an age-based categorization method for patients with TBI to investigate the differences between these ICP thresholds in different age groups. In this retrospective analysis, data from 263 patients with TBI were prospectively collected. ICP and mean arterial pressure were extracted from the hospital database at 5-min intervals. Demographic details, clinical presentation, computed tomography scans, neurosurgical interventions, and 12-months outcome were recorded. ICP versus UL-PRx values were categorized into ICP bins and graphically represented with boxplots for each age group, illustrating how as ICP values rise, there is a bin (age-tailored ICP [AT-ICP]) beyond which UL-PRx shows a sudden increase, indicating CVR loss. Homogeneous age groups were established to obtain a consistent AT-ICP threshold. The discriminatory ability of the AT-ICP thresholds was compared with the guideline-recommended thresholds by calculating the area under the Receiver Operating Characteristic curve of the ICP-derived indices (dose above threshold, and the hourly dosage above threshold). Age groups 0-5, 6-20, 21-60, 61-70, and 71-85years were the best age subdivisions, corresponding to AT-ICP thresholds of 20, 30, 35, 25, and 30mmHg, respectively. The AT-ICP thresholds exhibited better discriminative ability compared with the guideline-recommended thresholds. The AT-ICP thresholds offer a novel approach for estimating CVR impairment and the developed method represents an alternative solution to address the age stratification issue in patients with TBI.

Increased impairment of cerebral autoregulation in COVID-19 associated pulmonary failure requiring extracorporeal membrane oxygenation.

Cerebrovascular complications are feared but also commonly reported in patients with COVID-19 requiring extracorporeal membrane oxygenation (ECMO) support therapy. Besides other reasons, a connection between impaired cerebral autoregulation and SARS-CoV-2 infection as a mechanism for an increase in cerebrovascular complications has been hypothesized. In an observational single-center study, we investigated a cohort of 48 patients requiring veno-venous ECMO support therapy with (n = 31) and without SARS-CoV-2 infection (n = 17). Cerebral autoregulation was assessed with the cerebral oximetry-derived autoregulation index (ORx) based on a moving correlation between arterial pressure and cerebral oximetry. Patients with ECMO support therapy and SARS-CoV-2 experienced more time with impaired cerebral autoregulation than without SARS-CoV-2 [17 ± 9 vs. 13 ± 9% (p = 0.027)]. Patients with SARS-CoV-2 suffering from cerebrovascular complications had more time with impaired autoregulation than non SARS-CoV-2 patients with these complications (19 ± 9 vs. 10 ± 4%, p = 0.032). Our results suggest a connection between SARS-CoV-2 and impaired cerebral autoregulation as well as cerebrovascular complications in SARS-CoV-2 patients.

Reversible Cerebral Vasoconstriction Syndrome during Cesarean Section Complicated by Seizure Activity, Intraparenchymal and Subarachnoid Hemorrhage

Body of the Abstract: (1) To report a rare case of Reversible Cerebral Vasoconstriction Syndrome (RCVS) and associated intraparenchymal and subarachnoid hemorrhage following induction of spinal anesthesia in an uncomplicated, elective C-section (2) To discuss its potentially life threatening or well-being altering effects (3) To review the pathophysiology, diagnosis and potential treatments of the syndrome. Introduction: Reversible cerebral vasoconstriction syndrome (RCVS) is a rare condition defined clinically by symptoms of a severe recurrent headache described as a thunderclap headache, cerebral vasoconstriction of at least two different arteries on imaging, and resolution of vasoconstriction within three months. Complications include non-aneurysmal subarachnoid hemorrhage, seizure, stroke, and intracerebral hemorrhage. More than half of cases of RCVS occur postpartum or after use of vasoactive substances such as adrenergic or serotonergic drugs. Triggers include illicit drugs, eclampsia, or strenuous physical or sexual activity. As RCVS most commonly occurs during the postpartum period, it is extremely rare to encounter RCVS during the antepartum or peripartum periods. There has been only one other reported case of RCVS while undergoing spinal anesthesia for a C-section. Presented is a patient diagnosed with RCVS after spinal anesthesia during an elective C-section subsequently complicated by seizure, intracerebral and subarachnoid hemorrhage. Case Presentation: A 32-yearold G2 now P2002 patient presented at 39 6/7 weeks gestational age for elective primary C-section for a history of delivery complications with the first pregnancy. Medical history was unremarkable. First pregnancy labor epidural analgesia was uncomplicated. Spinal anesthesia induction was uneventful. Shortly thereafter, dizziness was reported and hypotension and bradycardia (P 42, BP 76/41) developed. Treatment included IV Ephedrine and Glycopyrrolate. Frontal headache developed. The patient then developed a tonic-clonic seizure with gaze deviation and upper limb rigidity lasting 45 seconds. An oral airway was placed for respiratory assistance with 100% oxygen. The patient became alert five minutes later. Vital signs: BP 168/98 P 122.C-section was performed. After incision, the patient had a second tonic-clonic seizure lasting 30 seconds. Midazolam was given. A healthy baby was delivered with Apgars of 7 and 9. The C-section was otherwise uncomplicated. Postoperatively, the patient was alert with stable vital signs. The neurologic exam was intact. The CT showed a 1.9 x 3.8 x 1.2 cm intraparenchymal hemorrhage-right frontal lobe with a subarachnoid hemorrhage in both the right frontal lobe and right sylvian fissure. Exam was normal. Headache continued. Tertiary care facility transfer was arranged. Tertiary care evaluation with 24-hour EEG monitoring, CT angiography (CTA) and CT venogram showed no evidence of venous sinus or cortical vein thrombosis. Magnetic resonance imaging (MRI) and transcranial doppler showed vasospasm diagnostic of RCVS. Subsequent CTA showed vasospasm of three branches of the carotid artery. Hospital discharge occurred on day 6. Six-month neurological follow-up showed resolution of hemorrhage and minimal residual symptoms. Discussion: Literature review discovered only one other case of RCVS with induction of regional anesthesia. To our knowledge the associated seizure activity coupled with intraparenchymal/subarachnoid hemorrhages has not been previously reported. RCVS, an extremely rare phenomenon is estimated to occur in 0.26% of headache patients; is more frequent in middle aged women and may have variable triggering factors. It may be associated with antidepressants, illicit drugs or sympathomimetic meds. Pregnancy and vasoconstrictive meds are risk factors with an occurrence rate of 5%. The pathophysiology is unknown but felt to be due to impaired cerebral vessel autoregulation. It is hypothesized that other factors and substances including endothelial dysfunction, pro and antiangiogenic factors, serotonin, cytokines and vascular endothelial growth factor may play some role. While MRI and doppler imaging may be of assistance, CTA is most useful for diagnosis. Since static imaging alone does not confirm the diagnosis, most cases likely go undiagnosed. Rarely, complications of RCVS include stroke, seizure, cerebral hemorrhage and Posterior Reversible Encephalopathy Syndrome. There is no prophylactic or therapeutic treatment proven effective for RCVS. Recommendations include symptomatic treatment of the headache, blood pressure, and delivery if eclampsia is suspected. Calcium channel blockers are often used for vasodilatory effects, although they have not been proven to improve symptoms or outcome in RCVS. Conclusion: RCVS is a very rarely occurring vascular disorder occasionally seen postpartum. This is the first reported case of associated seizure activity and resultant intraparenchymal and subarachnoid hemorrhage occurring after induction of spinal anesthesia for an uncomplicated C-section. It demonstrates the need for awareness of this disorder as well as knowledgeable hemodynamic anesthesia management specific to its unique features. The RCVS diagnostic and management challenges dictate that case collection and research be continued.

Retraction Note: Release of IL-6 After Stroke Contributes to Impaired Cerebral Autoregulation and Hippocampal Neuronal Necrosis Through NMDA Receptor Activation and Upregulation of ET-1 and JNK.

Retraction Note: Release of IL-6 After Stroke Contributes to Impaired Cerebral Autoregulation and Hippocampal Neuronal Necrosis Through NMDA Receptor Activation and Upregulation of ET-1 and JNK.

Cerebral Autoregulation: A Target for Improving Neurological Outcomes in Extracorporeal Life Support.

Despite improvements in survival after illnesses requiring extracorporeal life support, cerebral injury continues to hinder successful outcomes. Cerebral autoregulation (CA) is an innate protective mechanism that maintains constant cerebral blood flow in the face of varying systemic blood pressure. However, it is impaired in certain disease states and, potentially, following initiation of extracorporeal circulatory support. In this review, we first discuss patient-related factors pertaining to venovenous and venoarterial extracorporeal membrane oxygenation (ECMO) and their potential role in CA impairment. Next, we examine factors intrinsic to ECMO that may affect CA, such as cannulation, changes in pulsatility, the inflammatory and adaptive immune response, intracranial hemorrhage, and ischemic stroke, in addition to ECMO management factors, such as oxygenation, ventilation, flow rates, and blood pressure management. We highlight potential mechanisms that lead to disruption of CA in both pediatric and adult populations, the challenges of measuring CA in these patients, and potential associations with neurological outcome. Altogether, we discuss individualized CA monitoring as a potential target for improving neurological outcomes in extracorporeal life support.

Assessment of Autoregulation of the Cerebral Circulation during Acute Lung Injury in a Neonatal Porcine Model.

In neonates with acute lung injury (ALI), targeting lower oxygenation saturations is suggested to limit oxygen toxicity while maintaining vital organ function. Although thresholds for cerebral autoregulation are studied for the management of premature infants, the impact of hypoxia on hemodynamics, tissue oxygen consumption and extraction is not well understood in term infants with ALI. We examined hemodynamics, cerebral autoregulation and fractional oxygen extraction, as measured by near-infrared spectroscopy (NIRS) and blood gases, in a neonatal porcine oleic acid injury model of moderate ALI. We hypothesized that in ALI animals, cerebral oxygen extraction would be increased to a greater degree than kidney or gut oxygen extraction as indicative of the brain's adaptive efforts to increase cerebral oxygen extraction at the expense of splanchnic end organs. Fifteen anesthetized, ventilated 5-day-old neonatal piglets were divided into moderate lung injury by treatment with oleic acid or control (sham injection). The degree of lung injury was quantified at baseline and after establishment of ALI by blood gases, ventilation parameters and calculated oxygenation deficit, hemodynamic indices by echocardiography and lung injury score by ultrasound. PaCO2 was maintained constant during ventilation. Cerebral, renal and gut oxygenation was determined by NIRS during stepwise decreases in inspired oxygen from 50% to 21%, correlated with PaO2 and PvO2; changes in fractional oxygen extraction (ΔFOE) were calculated from NIRS and from regional blood gas samples. The proportion of cerebral autoregulation impairment attributable to blood pressure, and to hypoxemia, was calculated from autoregulation nomograms. ALI manifested as hypoxemia with increasing intrapulmonary shunt fraction, decreased lung compliance and increased resistance, and marked increase in lung ultrasound score. Brain, gut and renal NIRS, obtained from probes placed over the anterior skull, central abdomen and flank, respectively, correlated with concurrent SVC (brain) or IVC (gut, renal) PvO2 and SvO2. Cerebral autoregulation was impaired after ALI as a function of blood pressure at all FiO2 steps, but predominantly by hypoxemia at FiO2 < 40%. Cerebral ΔFOE was higher in ALI animals at all FiO2 steps. We conclude that in an animal model of neonatal ALI, cerebrovascular blood flow regulation is primarily dependent on oxygenation. There is not a defined oxygenation threshold below which cerebral autoregulation is impaired in ALI. Cerebral oxygen extraction is enhanced in ALI, reflecting compensation for exhausted cerebral autoregulation due to the degree of hypoxemia and/or hypotension, thereby protecting against tissue hypoxia.

A Method to Assess Granger Causality, Isolation and Autonomy in the Time and Frequency Domains: Theory and Application to Cerebrovascular Variability.

Concepts of Granger causality (GC) and Granger autonomy (GA) are central to assess the dynamics of coupled physiologic processes. While causality measures have been already proposed and applied in time and frequency domains, measures quantifying self-dependencies are still limited to the time-domain formulation and lack of clear spectral representation. We embed into the linear parametric framework for computing GC from a driver X to a target process Y a measure of Granger Isolation (GI) quantifying the part of the dynamics of Y not originating from X, and a new spectral measure of GA assessing frequency-specific patterns of self-dependencies in Y. The measures are illustrated in theoretical simulations and applied to time series of arterial pressure and cerebral blood flow obtained in syncope subjects and healthy controls. Simulations show that GI is complementary to GC but not trivially related to it, while GA reflects the regularity of the internal dynamics of the target process. In the application to cerebrovascular interactions, spectral GA quantified the physiological response to postural stress of slow cerebral blood flow oscillations, while spectral GC and GI detected an altered response to orthostasis in syncope subjects, likely related to impaired cerebral autoregulation. The new spectral measures of GI and GA are useful complements to GC for the analysis of interacting oscillatory processes, and detect pathophysiological responses to postural stress which cannot be traced in the time domain. The thorough assessment of causality, isolation and autonomy opens new perspectives for the analysis of coupled processes in both physiological and clinical investigations.