Development of a piglet model for cerebrovascular autoregulation assessment with altered PaCO2.

Introduction: Cerebrovascular autoregulation (CA) capacity can be impaired in the aftermath of acute brain injuries. Altered physiological states, such as hypo- and hypercapnia, affect CA. Although these effects have been demonstrated in several animal experiments, the exact effect of PaCO2 on the plateau of cerebral blood flow (CBF) across the spectrum of arterial blood pressures has not been fully disclosed. Research question: The aim was to explore pial vasodynamics in response to changing PaCO2 in a porcine cranial window model, as preparation for an experimental setup in which the CBF plateau position is investigated under different PaCO2 conditions. Material and methods: Five piglets were brought under anesthesia, intubated, ventilated and instrumented with a cranial window through which pial arteriolar diameters could be microscopically observed. By changing ventilation to either hyper- or hypoventilation we were able to investigate a range of PaCO2 from 25 till 90 mmHg. Results: Altering the respiratory rate to manipulate PaCO2 by ventilation appeared to be feasible and reliable. Discussion and conclusion: We found that ETCO2 reliably represents PaCO2 in our model. Pial arteriolar diameter changes followed the direction of PaCO2 changes, but the effect of PaCO2 on the diameters was not linear. Only in the hypercapnia setting did we observe a clear and consistent vasodilation of the pial arterioles.

Association between EEG metrics and continuous cerebrovascular autoregulation assessment: a scoping review.

OBJECTIVE: Cerebrovascular autoregulation is defined as the capacity of cerebral blood vessels to maintain stable cerebral blood flow despite changing blood pressure. It is assessed using the pressure reactivity index (the correlation coefficient between mean arterial blood pressure and intracranial pressure). The objective of this scoping review is to describe the existing evidence concerning the association of EEG and cerebrovascular autoregulation in order to identify key concepts and detect gaps in the current knowledge. METHODS: Embase, MEDLINE, SCOPUS, and Web of Science were searched considering articles between their inception up to September 2023. Inclusion criteria were human (paediatric and adult) and animal studies describing correlations between continuous EEG and cerebrovascular autoregulation assessments. RESULTS: Ten studies describing 481 human subjects (67% adult, 59% critically ill) were identified. Seven studies assessed qualitative (e.g. seizures, epileptiform potentials) and five evaluated quantitative (e.g. bispectral index, alpha-delta ratio) EEG metrics. Cerebrovascular autoregulation was evaluated based on intracranial pressure, transcranial Doppler, or near infrared spectroscopy. Specific combinations of cerebrovascular autoregulation and EEG metrics were evaluated by a maximum of two studies. Seizures, highly malignant patterns or burst suppression, alpha peak frequency, and bispectral index were associated with cerebrovascular autoregulation. The other metrics showed either no or inconsistent associations. CONCLUSION: There is a paucity of studies evaluating the link between EEG and cerebrovascular autoregulation. The studies identified included a variety of EEG and cerebrovascular autoregulation acquisition methods, age groups, and diseases allowing for few overarching conclusions. However, the preliminary evidence for the presence of an association between EEG metrics and cerebrovascular autoregulation prompts further in-depth investigations.

Is age or cardiovascular comorbidity the main predictor of reduced cerebrovascular pressure reactivity in older patients with traumatic brain injury?

Introduction: The Pressure Reactivity index (PRx) has been proposed as a surrogate measure for cerebrovascular autoregulation (CA) and it has been described that older age is associated with worse PRx. The etiology for this reduced capacity remains unknown. Research question: To investigate the relation between age and PRx in a cohort of patients with traumatic brain injury (TBI) while correcting for cardiovascular comorbidities. Material and methods: This is a retrospective analysis on prospectively collected data in 151 consecutive TBI patients between 2013 and 2023. PRx was averaged over 5 monitoring days and correlated with demographic, patient and injury data. A multiple regression analysis was performed with PRx as dependent variable and cardiovascular comorbidities, age, Glasgow motor score and pupillary reaction as independent variables. A similar model was constructed without age and compared. Results: Age, sex, thromboembolic history, arterial hypertension, Glasgow motor score and pupillary reaction significantly correlated with PRx in univariate analysis. In multivariate analysis, age had a significant worsening effect on PRx (p = 0.01), while the cardiovascular risk factors and injury severity had no impact. The comparison of the models with and without age yielded a significant difference (p = 0.01), underpinning the independent effect of age. Discussion and conclusion: In the present cohort study in TBI patients it was found that older age independently impaired cerebrovascular pressure reactivity regardless of cardiovascular comorbidity. Pathophysiology of TBI and physiology of ageing seem to line up to synergistically produce a negative effect on brain perfusion.

Developing a porcine model of severe traumatic brain injury induced by high amplitude rotational acceleration.

Introduction: It is unclear which pathophysiological processes initiate and drive dynamic cerebrovascular autoregulation (CA) impairment as seen in traumatic brain injury (TBI). This is not solely attributable to raised intracranial pressure (ICP), but also results from local tissue damage. Research question: In order to investigate CA disturbing processes, a porcine model is needed that mimics severe TBI as seen in humans. This model requires high amplitude rotational acceleration. Material and methods: A customized device was built to produce a rotational impulse with high amplitude and short pulse duration. Following preparatory tests on cadaver piglets, six piglets of six weeks old were sedated, ventilated and subjected to rotational impulses of different magnitudes. The impulse was immediately followed by installment of invasive monitoring of ICP, PbO2, Laser Doppler Flowmetry and arterial blood pressure. TBI was further characterized by magnetic resonance brain imaging. Results: The current setup enabled to reach sagittal head rotational maximal acceleration magnitudes up to 30 krad/s2. Half of the animals had an increase in ICP, measured shortly after the impulse. It has proved impossible so far to produce a sustained rise in ICP as seen in human severe TBI. MRI showed no anatomical abnormalities which would confirm severe TBI. Discussion and conclusion: The challenge to build a porcine model in which severe TBI with ICP raise and MRI changes as seen in humans can be reliably reproduced is still ongoing. It might be that higher peak rotational accelerations are needed.

Nervous System Response to Neurotrauma: A Narrative Review of Cerebrovascular and Cellular Changes After Neurotrauma.

Neurotrauma is a significant cause of morbidity and mortality worldwide. For instance, traumatic brain injury (TBI) causes more than 30% of all injury-related deaths in the USA annually. The underlying cause and clinical sequela vary among cases. Patients are liable to both acute and chronic changes in the nervous system after such a type of injury. Cerebrovascular disruption has the most common and serious effect in such cases because cerebrovascular autoregulation, which is one of the main determinants of cerebral perfusion pressure, can be effaced in brain injuries even in the absence of evident vascular injury. Disruption of the blood-brain barrier regulatory function may also ensue whether due to direct injury to its structure or metabolic changes. Furthermore, the autonomic nervous system (ANS) can be affected leading to sympathetic hyperactivity in many patients. On a cellular scale, the neuroinflammatory cascade medicated by the glial cells gets triggered in response to TBI. Nevertheless, cellular and molecular reactions involved in cerebrovascular repair are not fully understood yet. Most studies were done on animals with many drawbacks in interpreting results. Therefore, future studies including human subjects are necessarily needed. This review will be of relevance to clinicians and researchers interested in understanding the underlying mechanisms in neurotrauma cases and the development of proper therapies as well as those with a general interest in the neurotrauma field.

Conductivity reactivity index for monitoring of cerebrovascular autoregulation in early cerebral ischemic rabbits.

BACKGROUND: Cerebrovascular autoregulation (CVAR) is the mechanism that maintains constant cerebral blood flow by adjusting the caliber of the cerebral vessels. It is important to have an effective, contactless way to monitor and assess CVAR in patients with ischemia. METHODS: The adjustment of cerebral blood flow leads to changes in the conductivity of the whole brain. Here, whole-brain conductivity measured by the magnetic induction phase shift method is a valuable alternative to cerebral blood volume for non-contact assessment of CVAR. Therefore, we proposed the correlation coefficient between spontaneous slow oscillations in arterial blood pressure and the corresponding magnetic induction phase shift as a novel index called the conductivity reactivity index (CRx). In comparison with the intracranial pressure reactivity index (PRx), the feasibility of the conductivity reactivity index to assess CVAR in the early phase of cerebral ischemia has been preliminarily confirmed in animal experiments. RESULTS: There was a significant difference in the CRx between the cerebral ischemia group and the control group (p = 0.002). At the same time, there was a significant negative correlation between the CRx and the PRx (r = - 0.642, p = 0.002) after 40 min after ischemia. The Bland-Altman consistency analysis showed that the two indices were linearly related, with a minimal difference and high consistency in the early ischemic period. The sensitivity and specificity of CRx for cerebral ischemia identification were 75% and 20%, respectively, and the area under the ROC curve of CRx was 0.835 (SE = 0.084). CONCLUSION: The animal experimental results preliminarily demonstrated that the CRx can be used to monitor CVAR and identify CVAR injury in early ischemic conditions. The CRx has the potential to be used for contactless, global, bedside, and real-time assessment of CVAR of patients with ischemic stroke.

Association between time-dependent changes in cerebrovascular autoregulation after cardiac arrest and outcomes: A prospective cohort study.

This prospective observational single-center cohort study aimed to determine an association between cerebrovascular autoregulation (CVAR) and outcomes in hypoxic-ischemic brain injury post-cardiac arrest (CA), and assessed 100 consecutive post-CA patients in Japan between June 2017 and May 2020 who experienced a return of spontaneous circulation. Continuous monitoring was performed for 96 h to determine CVAR presence. A moving Pearson correlation coefficient was calculated from the mean arterial pressure and cerebral regional oxygen saturation. The association between CVAR and outcomes was evaluated using the Cox proportional hazard model; non-CVAR time percent was the time-dependent, age-adjusted covariate. The non-linear effect of target temperature management (TTM) was assessed using a restricted cubic spline. Of the 100 participants, CVAR was detected using the cerebral performance category (CPC) in all patients with a good neurological outcome (CPC 1-2) and in 65 patients (88%) with a poor outcome (CPC 3-5). Survival probability decreased significantly with increasing non-CVAR time percent. The TTM versus the non-TTM group had a significantly lower probability of a poor neurological outcome at 6 months with a non-CVAR time of 18%-37% (p < 0.05). Longer non-CVAR time may be associated with significantly increased mortality in hypoxic-ischemic brain injury post-CA.

Secondary hyperperfusion injury following surgical evacuation for acute isolated epidural hematoma with concurrent cerebral herniation.

Objective: Hemispherical cerebral swelling or even encephalocele after head trauma is a common complication and has been well elucidated previously. However, few studies have focused on the secondary brain hemorrhage or edema occurring regionally but not hemispherically in the cerebral parenchyma just underneath the surgically evacuated hematoma during or at a very early stage post-surgery. Methods: In order to explore the characteristics, hemodynamic mechanisms, and optimized treatment of a novel peri-operative complication in patients with isolated acute epidural hematoma (EDH), clinical data of 157 patients with acute-isolated EDH who underwent surgical intervention were reviewed retrospectively. Risk factors including demographic characteristics, admission Glasgow Coma Score, preoperative hemorrhagic shock, anatomical location, and morphological parameters of epidural hematoma, as well as the extent and duration of cerebral herniation on physical examination and radiographic evaluation were considered. Results: It suggested that secondary intracerebral hemorrhage or edema was determined in 12 of 157 patients within 6 h after surgical hematoma evacuation. It was featured by remarkable, regional hyperperfusion on the computed tomography (CT) perfusion images and associated with a relatively poor neurological prognosis. In addition to concurrent cerebral herniation, which was found to be a prerequisite for the development of this novel complication, multivariate logistic regression further showed four independent risk factors contributing to this type of secondary hyperperfusion injury: cerebral herniation that lasted longer than 2 h, hematomas that were located in the non-temporal region, hematomas that were thicker than 40 mm, and hematomas occurring in pediatric and elderly patients. Conclusion: Secondary brain hemorrhage or edema occurring within an early perioperative period of hematoma-evacuation craniotomy for acute-isolated EDH is a rarely described hyperperfusion injury. Because it plays an important prognostic influence on patients' neurological recovery, optimized treatment should be given to block or reduce the consequent secondary brain injuries.

Intraoperative monitoring of cerebrovascular autoregulation in infants and toddlers receiving major elective surgery to determine the individually optimal blood pressure - a pilot study.

Introduction: Inducing general anesthesia (GA) in children can considerably affect blood pressure, and the rate of severe critical events owing to this remains high. Cerebrovascular autoregulation (CAR) protects the brain against blood-flow-related injury. Impaired CAR may contribute to the risk of cerebral hypoxic-ischemic or hyperemic injury. However, blood pressure limits of autoregulation (LAR) in infants and children are unclear. Materials and methods: In this pilot study CAR was monitored prospectively in 20 patients aged <4 years receiving elective surgery under GA. Cardiac- or neurosurgical procedures were excluded. The possibility of calculating the CAR index hemoglobin volume index (HVx), by correlating near-infrared-spectroscopy (NIRS)-derived relative cerebral tissue hemoglobin and invasive mean arterial blood pressure (MAP) was determined. Optimal MAP (MAPopt), LAR, and the proportion of time with a MAP outside LAR were determined. Results: The mean patient age was 14 ± 10 months. MAPopt could be determined in 19 of 20 patients, with an average of 62 ± 12 mmHg. The required time for a first MAPopt depended on the extent of spontaneous MAP fluctuations. The actual MAP was outside the LAR in 30% ± 24% of the measuring time. MAPopt significantly differed among patients with similar demographics. The CAR range averaged 19 ± 6 mmHg. Using weight-adjusted blood pressure recommendations or regional cerebral tissue saturation, only a fraction of the phases with inadequate MAP could be identified. Conclusion: Non-invasive CAR monitoring using NIRS-derived HVx in infants, toddlers, and children receiving elective surgery under GA was reliable and provided robust data in this pilot study. Using a CAR-driven approach, individual MAPopt could be determined intraoperatively. The intensity of blood pressure fluctuations influences the initial measuring time. MAPopt may differ considerably from recommendations in the literature, and the MAP range within LAR in children may be smaller than that in adults. The necessity of manual artifact elimination represents a limitation. Larger prospective and multicenter cohort studies are necessary to confirm the feasibility of CAR-driven MAP management in children receiving major surgery under GA and to enable an interventional trial design using MAPopt as a target.

Post-ischemic hyperemia following endovascular therapy for acute stroke is associated with lesion growth.

A substantial proportion of acute stroke patients fail to recover following successful endovascular therapy (EVT) and injury to the brain and vasculature secondary to reperfusion may be a contributor. Acute stroke patients were included with: i) large vessel occlusion of the anterior circulation, ii) successful recanalization, and iii) evaluable MRI early after EVT. Presence of hyperemia on MRI perfusion was assessed by consensus using a modified ASPECTS. Three different approaches were used to quantify relative cerebral blood flow (rCBF). Sixty-seven patients with median age of 66 [59-76], 57% female, met inclusion criteria. Hyperemia was present in 35/67 (52%) patients early post-EVT, in 32/65 (49%) patients at 24 hours, and in 19/48 (40%) patients at 5 days. There were no differences in incomplete reperfusion, HT, PH-2, HARM, severe HARM or symptomatic ICH rates between those with and without early post-EVT hyperemia. A strong association (R2 = 0.81, p < 0.001) was found between early post-EVT hyperemia (p = 0.027) and DWI volume at 24 hours after adjusting for DWI volume at 2 hours (p < 0.001) and incomplete reperfusion at 24 hours (p = 0.001). Early hyperemia is a potential marker for cerebrovascular injury and may help select patients for adjunctive therapy to prevent edema, reperfusion injury, and lesion growth.