The time constant of the cerebral arterial bed: exploring age-related implications.

The time constant of the cerebral arterial bed (τ) represents an estimation of the  transit time of flow from the point of insonation at the level of the middle cerebral artery to the arteriolar-capillary boundary, during a cardiac cycle. This study assessed differences in τ among healthy volunteers across different age groups. Simultaneous recordings of transcranial Doppler cerebral blood flow velocity (CBFV) and arterial blood pressure (ABP) were performed on two groups: young volunteers (below 30 years of age), and older volunteers (above 40 years of age). τ was estimated using mathematical transformation of ABP and CBFV pulse waveforms. 77 healthy volunteers [52 in the young group, and 25 in the old group] were included. Pulse amplitude of ABP was higher [16.7 (14.6-19.4) mmHg] in older volunteers as compared to younger ones [12.5 (10.9-14.4) mm Hg; p < 0.001]. CBFV was lower in older volunteers [59 (50-66) cm/s] as compared to younger ones [72 (63-78) cm/s p < 0.001]. τ was longer in the younger volunteers [217 (168-237) ms] as compared to the older volunteers [183 (149-211) ms; p = 0.004]. τ significantly decreased with age (rS = - 0.27; p = 0.018). τ is potentially an integrative marker of the changes occurring in cerebral vasculature, as it encompasses the interplay between changes in compliance and resistance that occur with age.

Relationship between the shape of intracranial pressure pulse waveform and computed tomography characteristics in patients after traumatic brain injury.

BACKGROUND: Midline shift and mass lesions may occur with traumatic brain injury (TBI) and are associated with higher mortality and morbidity. The shape of intracranial pressure (ICP) pulse waveform reflects the state of cerebrospinal pressure-volume compensation which may be disturbed by brain injury. We aimed to investigate the link between ICP pulse shape and pathological computed tomography (CT) features. METHODS: ICP recordings and CT scans from 130 TBI patients from the CENTER-TBI high-resolution sub-study were analyzed retrospectively. Midline shift, lesion volume, Marshall and Rotterdam scores were assessed in the first CT scan after admission and compared with indices derived from the first 24 h of ICP recording: mean ICP, pulse amplitude of ICP (AmpICP) and pulse shape index (PSI). A neural network model was applied to automatically group ICP pulses into four classes ranging from 1 (normal) to 4 (pathological), with PSI calculated as the weighted sum of class numbers. The relationship between each metric and CT measures was assessed using Mann-Whitney U test (groups with midline shift > 5 mm or lesions > 25 cm3 present/absent) and the Spearman correlation coefficient. Performance of ICP-derived metrics in identifying patients with pathological CT findings was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: PSI was significantly higher in patients with mass lesions (with lesions: 2.4 [1.9-3.1] vs. 1.8 [1.1-2.3] in those without; p << 0.001) and those with midline shift (2.5 [1.9-3.4] vs. 1.8 [1.2-2.4]; p < 0.001), whereas mean ICP and AmpICP were comparable. PSI was significantly correlated with the extent of midline shift, total lesion volume and the Marshall and Rotterdam scores. PSI showed AUCs > 0.7 in classification of patients as presenting pathological CT features compared to AUCs ≤ 0.6 for mean ICP and AmpICP. CONCLUSIONS: ICP pulse shape reflects the reduction in cerebrospinal compensatory reserve related to space-occupying lesions despite comparable mean ICP and AmpICP levels. Future validation of PSI is necessary to explore its association with volume imbalance in the intracranial space and a potential complementary role to the existing monitoring strategies.

Association between temporal patterns of baroreflex sensitivity after traumatic brain injury and prognosis: a preliminary study.

INTRODUCTION: Traumatic brain injury (TBI) may lead to an increase in intracranial pressure (ICP) as well as impairment of cerebral vascular reactivity and the autonomic nervous system. This study aimed to investigate individual patterns of changes in baroreflex sensitivity (BRS) along with the assessment of pressure reactivity index (PRx) and ICP after TBI. MATERIALS AND METHODS: Twenty-nine TBI patients with continuous arterial blood pressure (ABP) and ICP monitoring were included. BRS was calculated using the sequential cross-correlation method. PRx was estimated using slow-wave oscillations of ABP and ICP. Outcome was assessed using the Glasgow Outcome Scale. RESULTS: Pooled data analysis of the lower breakpoint during the week that followed TBI revealed that BRS reached a minimum about 2 days after TBI. In patients with good outcome, there was a significant increase in BRS during the 7 days following TBI: rp = 0.21; p = 0.008 and the temporal changes in BRS showed either a "U-shaped" pattern or a gradual increase over time. The BRS value after 1.5 days was found to be a significant predictor of mortality (cut-off BRS = 1.8 ms/mm Hg; AUC = 0.83). In patients with poor outcome, ICP and PRx increased while BRS remained low. CONCLUSIONS: We found an association between temporal patterns of BRS and prognosis in the early days following TBI. Further research in a larger cohort of patients is needed to confirm the weight of these preliminary observations for prediction of prognosis in TBI patients.

Brain blood flow pulse analysis may help to recognize individuals who suffer from hydrocephalus.

BACKGROUND: Normal pressure hydrocephalus (NPH) is often associated with altered cerebral blood flow. Recent research with the use of the ultrasonic method suggests specific changes in the shape of cardiac-related cerebral arterial blood volume (CaBV) pulses in NPH patients. Our study aims to provide a quantitative analysis of the shape of CaBV pulses, estimated based on transcranial Doppler ultrasonography (TCD) in NPH patients and healthy individuals. METHODS: The CaBV pulses were estimated using TCD cerebral blood flow velocity signals recorded from probable NPH adults and age-matched healthy individuals at rest. The shape of the CaBV pulses was compared to a triangular shape with 27 similarity parameters calculated for every reliable CaBV pulse and compared between patients and volunteers. The diagnostic accuracy of the most prominent parameter for NPH classification was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: The similarity parameters were calculated for 31 probable NPH patients (age: 59 years (IQR: 47, 67 years), 14 females) and 23 healthy volunteers (age: 54 years (IQR: 43, 61 years), 18 females). Eighteen of 27 parameters were different between healthy individuals and NPH patients (p < 0.05). The most prominent differences were found for the ascending slope of the CaBV pulse with the AUC equal to 0.87 (95% confidence interval: 0.77, 0.97, p < 0.001). CONCLUSIONS: The findings suggest that in NPH, the ascending slope of the CaBV pulse had a slower rise, was more like a straight line, and generally was less convex than in volunteers. Prospective research is required to verify the clinical utility of these findings.

Applying video motion magnification to reveal spontaneous tympanic membrane displacement as an indirect measure of intracranial pressure in patients with brain pathologies.

BACKGROUND: The observation of tympanic membrane displacement (TMD) opens up the possibility of indirect intracranial pressure (ICP) estimation. In this study, we applied a phase-based video motion magnification (VMM) algorithm to reveal spontaneous pulse TMD waveforms (spTMD) and compare them with invasively measured ICP in patients with intracranial pathologies. METHODS: Nine adults (six traumatic brain injury and three aneurysmal subarachnoid haemorrhage; median age 44 (29-53) years admitted to the intensive care unit of Wroclaw Medical University between October 2021 and October 2022 with implanted ICP sensors were included in this retrospective study. Video recordings of the tympanic membrane were performed using a portable otoscope with a video camera and analysed by a custom-written VMM algorithm. ICP was monitored using intraparenchymal sensors and arterial blood pressure (ABP) was measured in the radial arterial lines. ICP, ABP, and spTMD videos were captured simultaneously. The pulse amplitudes of ICP (Amp_ICP), ABP (Amp_ABP) and spTMD (Amp_spTMD) were estimated using fast Fourier transform within the heart rate (HR)-related frequency range. RESULTS: Amp_spTMD was significantly correlated with mean ICP (rS = 0.73; p = 0.025) and with Amp_ICP (rS = 0.88; p = 0.002). Age was not a significant moderator of this association. There were no significant relationships between Amp_spTMD and either mean ABP, HR, or Amp_ABP. CONCLUSIONS: The study suggests that Amp_spTMD increases with the increase in mean ICP and Amp_ICP. Estimation of Amp_spTMD using the VMM algorithm has the potential to allow for non-invasive detection of the risk of elevated ICP; however, further investigation in a larger group of patients is required.

Cerebral Autoregulation, Cerebral Hemodynamics, and Injury Biomarkers, in Patients with COVID-19 Treated with Veno-Venous Extracorporeal Membrane Oxygenation.

BACKGROUND: This study aimed to describe the cerebrovascular dynamics, in particular cerebral autoregulation (CA), and cerebral biomarkers as neuron-specific enolase (NSE) in patients with a diagnosis of coronavirus disease 2019 and acute respiratory distress syndrome as well as undergoing veno-venous extracorporeal membrane treatment. METHODS: This was a single center, observational study conducted in the intensive care unit of the University Hospital in Wroclaw from October 2020 to February 2022. Transcranial Doppler recordings of the middle cerebral artery conducted for at least 20 min were performed. Cerebral autoregulation (CA) was estimated by using the mean velocity index (Mxa), calculated as the moving correlation coefficient between slow-wave oscillations in cerebral blood flow velocity and arterial blood pressure. Altered CA was defined as a positive Mxa. Blood samples for the measurement of NSE were obtained at the same time as transcranial Doppler measurements. RESULTS: A total of 16 patients fulfilled the inclusion criteria and were enrolled in the study. The median age was 39 (34-56) years. Altered CA was found in 12 patients, and six out of seven patients who died had altered CA. A positive Mxa was a significant predictor of mortality, with a sensitivity of 85.7%. We found that three out of five patients with pathological changes in brain computed tomography and six out of ten patients with neurological complications had altered CA. NSE was a significant predictor of mortality (cutoff value: 28.9 µg/L); area under the curve = 0.83, p = 0.006), with a strong relationship between increased level of NSE and altered CA, χ2 = 6.24; p = 0.035; φ = 0.69. CONCLUSIONS: Patients with coronavirus disease 2019-related acute respiratory distress syndrome, requiring veno-venous extracorporeal membrane treatment, are likely to have elevated NSE levels and altered CA. The CA was associated with NSE values in this group. This preliminary analysis suggests that advanced neuromonitoring and evaluation of biomarkers should be considered in this population.

Cerebrovascular Impedance During Hemodynamic Change in Rabbits: A Pilot Study.

INTRODUCTION: Cerebrovascular impedance describes the relationship between pulsatile changes in arterial blood pressure (ABP) and cerebral blood flow (CBF). It is commonly defined by modulus and phase shift derived from Fourier spectra of ABP and CBF velocity (CBFV) signals under mostly steady-state conditions. The aim of this work was to assess heartbeat-to-heartbeat cerebrovascular impedance at heart rate frequency during controlled changes in mean ABP and intracranial pressure (ICP). MATERIAL AND METHODS: Recordings of ABP in the femoral artery, transcranial Doppler CBFV in the basilar artery, and subarachnoid ICP were obtained from anesthetized rabbits with induced arterial hypotension (n = 8 rabbits), arterial hypertension (n = 5), or intracranial hypertension (n = 7). Modulus of cerebrovascular impedance (|Z|) was estimated from amplitudes of ABP and CBFV. Phase shift of cerebrovascular impedance (PS) was estimated from time-frequency (TF) representations of phase shift between ABP and CBFV overlaid with a time-variant mask based on the fundamental frequency of ABP. RESULTS: Both |Z| and PS increased with increasing mean ABP. |Z| decreased with increasing mean ICP, but no change was observed in PS. CONCLUSIONS: The combined beat-to-beat and TF approach allows for the estimation of cerebrovascular impedance during transient hemodynamic changes. |Z| and PS follow the pattern of changes in CPP.

Analysis of Intracranial Pressure Pulse-Pressure Relationship: Experimental Validation.

The slope of linear relationship between the amplitude of pulsations in intracranial pressure (ICP) versus mean ICP has recently been suggested as a useful guide for selecting patients for shunt surgery in normal pressure hydrocephalus (NPH). To better understand how the pathophysiology of cerebral circulation influences this parameter, we aimed to study the relationship between mean pressure and pulsation amplitude in a wide range of conditions affecting cerebrovascular tone and ICP in experimental conditions.We retrospectively analysed experimental material collected previously. Three physiological manoeuvres were studied in 29 New Zealand white rabbits: lumbar infusion with an infusion rate ≤0.2 mL/min to induce mild intracranial hypertension (n = 43), sympathetic blockade to induce arterial hypotension (n = 19), and modulation of the ventilator tidal volume, simultaneously influencing arterial carbon dioxide partial pressure (PaCO2) to induce hypocapnia or hypercapnia (n = 17). We investigated whether the slope of the pulse amplitude (AMP)-ICP line depended on PaCO2 and arterial blood pressure (ABP) changes.We found a linear correlation between AMP-ICP and ICP with positive slope. Regression of slope against mean ABP showed a negative dependence (p = 0.03). In contrast, the relationship between slope and PaCO2 was positive, although not reaching statistical significance (p = 0.18).The slope of amplitude-pressure line is strongly modulated by systemic vascular variables and therefore should be taken as a descriptor of cerebrospinal fluid dynamics with great care.

Intracranial pulse pressure waveform analysis using the higher harmonics centroid.

BACKGROUND: The pulse waveform of intracranial pressure (ICP) is its distinctive feature almost always present in the clinical recordings. In most cases, it changes proportionally to rising ICP, and observation of these changes may be clinically useful. We introduce the higher harmonics centroid (HHC) which can be defined as the center of mass of harmonics of the ICP pulse waveform from the 2nd to 10th, where mass corresponds to amplitudes of these harmonics. We investigate the changes in HHC during ICP monitoring, including isolated episodes of ICP plateau waves. MATERIAL AND METHODS: Recordings from 325 patients treated between 2002 and 2010 were reviewed. Twenty-six patients with ICP plateau waves were identified. In the first step, the correlation between HHC and ICP was examined for the entire monitoring period. In the second step, the above relation was calculated separately for periods of elevated ICP during plateau wave and the baseline. RESULTS: For the values averaged over the whole monitoring period, ICP (22.3 ± 6.9 mm Hg) correlates significantly (R = 0.45, p = 0.022) with HHC (3.64 ± 0.46). During the ICP plateau waves (ICP increased from 20.9 ± 6.0 to 53.7 ± 9.7 mm Hg, p < 10-16), we found a significant decrease in HHC (from 3.65 ± 0.48 to 3.21 ± 0.33, p = 10-5). CONCLUSIONS: The good correlation between HHC and ICP supports the clinical application of pressure waveform analysis in addition to the recording of ICP number only. Mean ICP may be distorted by a zero drift, but HHC remains immune to this error. Further research is required to test whether a decline in HHC with elevated ICP can be an early warning sign of intracranial hypertension, whether individual breakpoints of correlation between ICP and its centroid are of clinical importance.

Compliance of the cerebrospinal space: comparison of three methods.

BACKGROUND: Cerebrospinal compliance describes the ability of the cerebrospinal space to buffer changes in volume. Diminished compliance is associated with increased risk of potentially threatening increases in intracranial pressure (ICP) when changes in cerebrospinal volume occur. However, despite various methods of estimation proposed so far, compliance is seldom used in clinical practice. This study aimed to compare three measures of cerebrospinal compliance. METHODS: ICP recordings from 36 normal-pressure hydrocephalus patients who underwent infusion tests with parallel recording of transcranial Doppler blood flow velocity were retrospectively analysed. Three methods were used to calculate compliance estimates during changes in the mean ICP induced by infusion of fluid into the cerebrospinal fluid space: (a) based on Marmarou's model of cerebrospinal fluid dynamics (CCSF), (b) based on the evaluation of changes in cerebral arterial blood volume (CCaBV), and (c) based on the amplitudes of peaks P1 and P2 of ICP pulse waveform (CP1/P2). RESULTS: Increase in ICP caused a significant decrease in all compliance estimates (p < 0.0001). Time courses of compliance estimators were strongly positively correlated with each other (group-averaged Spearman correlation coefficients: 0.94 [0.88-0.97] for CCSF vs. CCaBV, 0.77 [0.63-0.91] for CCSF vs. CP1/P2, and 0.68 [0.48-0.91] for CCaBV vs. CP1/P2). CONCLUSIONS: Indirect methods, CCaBV and CP1/P2, allow for the assessment of relative changes in cerebrospinal compliance and produce results exhibiting good correlation with the direct method of volumetric manipulation. This opens the possibility of monitoring relative changes in compliance continuously.

The relationship between the time of cerebral desaturation episodes and outcome in aneurysmal subarachnoid haemorrhage: a preliminary study.

In this preliminary study we investigated the relationship between the time of cerebral desaturation episodes (CDEs), the severity of the haemorrhage, and the short-term outcome in patients with aneurysmal subarachnoid haemorrhage (aSAH). Thirty eight patents diagnosed with aneurysmal subarachnoid haemorrhage were analysed in this study. Regional cerebral oxygenation (rSO2) was assessed using near infrared spectroscopy (NIRS). A CDE was defined as rSO2 < 60% with a duration of at least 30 min. The severity of the aSAH was assessed using the Hunt and Hess scale and the short-term outcome was evaluated utilizing the Glasgow Outcome Scale. CDEs were found in 44% of the group. The total time of the CDEs and the time of the longest CDE on the contralateral side were longer in patients with severe versus moderate aSAH [h:min]: 8:15 (6:26-8:55) versus 1:24 (1:18-4:18), p = 0.038 and 2:05 (2:00-5:19) versus 0:48 (0:44-2:12), p = 0.038. The time of the longest CDE on the ipsilateral side was longer in patients with poor versus good short-term outcome [h:min]: 5:43 (3:05-9:36) versus 1:47 (0:42-2:10), p = 0.018. The logistic regression model for poor short-term outcome included median ABP, the extent of the haemorrhage in the Fisher scale and the time of the longest CDE. We have demonstrated that the time of a CDE is associated with the severity of haemorrhage and short-term outcome in aSAH patients. A NIRS measurement may provide valuable predictive information and could be considered as additional method of neuromonitoring of patients with aSAH.

Hypocapnia after traumatic brain injury: how does it affect the time constant of the cerebral circulation?

The time constant of the cerebral arterial bed ("tau") estimates how fast the blood entering the brain fills the arterial vascular sector. Analogous to an electrical resistor-capacitor circuit, it is expressed as the product of arterial compliance (Ca) and cerebrovascular resistance (CVR). Hypocapnia increases the time constant in healthy volunteers and decreases arterial compliance in head trauma. How the combination of hyocapnia and trauma affects this parameter has yet to be studied. We hypothesized that in TBI patients the intense vasoconstrictive action of hypocapnia would dominate over the decrease in compliance seen after hyperventilation. The predominant vasoconstrictive response would maintain an incoming blood volume in the arterial circulation, thereby lengthening tau. We retrospectively analyzed recordings of intracranial pressure (ICP), arterial blood pressure (ABP), and blood flow velocity (FV) obtained from a cohort of 27 severe TBI patients [(39/30 years (median/IQR), 5 women; admission GCS 6/5 (median/IQR)] studied during a standard clinical CO2 reactivity test. The reactivity test was performed by means of a 50-min increase in ventilation (20% increase in respiratory minute volume). CVR and Ca were estimated from these recordings, and their product calculated to find the time constant. CVR significantly increased [median CVR pre-hypocapnia/during hypocapnia: 1.05/1.35 mmHg/(cm3/s)]. Ca decreased (median Ca pre-hypocapnia/during hypocapnia: 0.130/0.124 arbitrary units) to statistical significance (p = 0.005). The product of these two parameters resulted in a significant prolongation of the time constant (median tau pre-hypocapnia/during hypocapnia: 0.136 s/0.152 s, p ˂ .001). Overall, the increase in CVR dominated over the decrease in compliance, hence tau was longer. We demonstrate a significant increase in the time constant of the cerebral circulation during hypocapnia after severe TBI, and attribute this to an increase in cerebrovascular resistance which outweighs the decrease in cerebral arterial bed compliance.

Feasibility of Hidden Markov Models for the Description of Time-Varying Physiologic State After Severe Traumatic Brain Injury.

OBJECTIVES: Continuous assessment of physiology after traumatic brain injury is essential to prevent secondary brain insults. The present work aims at the development of a method for detecting physiologic states associated with the outcome from time-series physiologic measurements using a hidden Markov model. DESIGN: Unsupervised clustering of hourly values of intracranial pressure/cerebral perfusion pressure, the compensatory reserve index, and autoregulation status was attempted using a hidden Markov model. A ternary state variable was learned to classify the patient's physiologic state at any point in time into three categories ("good," "intermediate," or "poor") and determined the physiologic parameters associated with each state. SETTING: The proposed hidden Markov model was trained and applied on a large dataset (28,939 hr of data) using a stratified 20-fold cross-validation. PATIENTS: The data were collected from 379 traumatic brain injury patients admitted to Addenbrooke's Hospital, Cambridge between 2002 and 2016. INTERVENTIONS: Retrospective observational analysis. MEASUREMENTS AND MAIN RESULTS: Unsupervised training of the hidden Markov model yielded states characterized by intracranial pressure, cerebral perfusion pressure, compensatory reserve index, and autoregulation status that were physiologically plausible. The resulting classifier retained a dose-dependent prognostic ability. Dynamic analysis suggested that the hidden Markov model was stable over short periods of time consistent with typical timescales for traumatic brain injury pathogenesis. CONCLUSIONS: To our knowledge, this is the first application of unsupervised learning to multidimensional time-series traumatic brain injury physiology. We demonstrated that clustering using a hidden Markov model can reduce a complex set of physiologic variables to a simple sequence of clinically plausible time-sensitive physiologic states while retaining prognostic information in a dose-dependent manner. Such states may provide a more natural and parsimonious basis for triggering intervention decisions.

Assessment of cerebral hemodynamic parameters using pulsatile versus non-pulsatile cerebral blood outflow models.

BACKGROUND: Prior methods evaluating the changes in cerebral arterial blood volume (∆CaBV) assumed that brain blood transport distal to big cerebral arteries can be approximated with a non-pulsatile flow (CFF) model. In this study, a modified ∆CaBV calculation that accounts for pulsatile blood flow forward (PFF) from large cerebral arteries to resistive arterioles was investigated. The aim was to assess cerebral hemodynamic indices estimated by both CFF and PFF models while changing arterial blood carbon dioxide concentration (EtCO2) in healthy volunteers. MATERIALS AND METHODS: Continuous recordings of non-invasive arterial blood pressure (ABP), transcranial Doppler blood flow velocity (CBFVa), and EtCO2 were performed in 53 young volunteers at baseline and during both hypo- and hypercapnia. The time constant of the cerebral arterial bed (τ) and critical closing pressure (CrCP) were estimated using mathematical transformations of the pulse waveforms of ABP and CBFVa, and with both pulsatile and non-pulsatile models of ∆CaBV estimation. Results are presented as median values ± interquartile range. RESULTS: Both CrCP and τ gave significantly lower values with the PFF model when compared with the CFF model (p ≪ 0.001 for both). In comparison to normocapnia, both CrCP and τ determined with the PFF model increased during hypocapnia [CrCPPFF (mm Hg): 5.52 ± 8.78 vs. 14.36 ± 14.47, p = 0.00006; τPFF (ms): 47.4 ± 53.9 vs. 72.8 ± 45.7, p = 0.002] and decreased during hypercapnia [CrCPPFF (mm Hg): 5.52 ± 8.78 vs. 2.36 ± 7.05, p = 0.0001; τPFF (ms): 47.4 ± 53.9 vs. 29.0 ± 31.3, p = 0.0003]. When the CFF model was applied, no changes were found for CrCP during hypercapnia or in τ during hypocapnia. CONCLUSION: Our results suggest that the pulsatile flow forward model better reflects changes in CrCP and in τ induced by controlled alterations in EtCO2.

Cerebral arterial time constant calculated from the middle and posterior cerebral arteries in healthy subjects.

The cerebral arterial blood volume changes (∆CaBV) during a single cardiac cycle can be estimated using transcranial Doppler ultrasonography (TCD) by assuming pulsatile blood inflow, constant, and pulsatile flow forward from large cerebral arteries to resistive arterioles [continuous flow forward (CFF) and pulsatile flow forward (PFF)]. In this way, two alternative methods of cerebral arterial compliance (Ca) estimation are possible. Recently, we proposed a TCD-derived index, named the time constant of the cerebral arterial bed (τ), which is a product of Ca and cerebrovascular resistance and is independent of the diameter of the insonated vessel. In this study, we aim to examine whether the τ estimated by either the CFF or the PFF model differs when calculated from the middle cerebral artery (MCA) and the posterior cerebral artery (PCA). The arterial blood pressure and TCD cerebral blood flow velocity (CBFVa) in the MCA and in the PCA were non-invasively measured in 32 young, healthy volunteers (median age: 24, minimum age: 18, maximum age: 31). The τ was calculated using both the PFF and CFF models from the MCA and the PCA and compared using a non-parametric Wilcoxon signed-rank test. Results are presented as medians (25th-75th percentiles). The cerebrovascular time constant estimated in both arteries using the PFF model was shorter than when using the CFF model (ms): [64.83 (41.22-104.93) vs. 178.60 (160.40-216.70), p < 0.001 in the MCA, and 44.04 (17.15-81.17) vs. 183.50 (153.65-204.10), p < 0.001 in the PCA, respectively]. The τ obtained using the PFF model was significantly longer from the MCA than from the PCA, p = 0.004. No difference was found in the τ when calculated using the CFF model. Longer τ from the MCA might be related to the higher Ca of the MCA than that of the PCA. Our results demonstrate MCA-PCA differences in the τ, but only when the PFF model was applied.

Critical Closing Pressure During a Controlled Increase in Intracranial Pressure.

OBJECTIVES: The objectives were to compare three methods of estimating critical closing pressure (CrCP) in a scenario of a controlled increase in intracranial pressure (ICP) induced during an infusion test in patients with suspected normal pressure hydrocephalus (NPH). METHODS: We retrospectively analyzed data from 37 NPH patients who underwent infusion tests. Computer recordings of directly measured intracranial pressure (ICP), arterial blood pressure (ABP) and transcranial Doppler cerebral blood flow velocity (CBFV) were used. The CrCP was calculated using three methods: first harmonics ratio of the pulse waveforms of ABP and CBFV (CrCPA) and two methods based on a model of cerebrovascular impedance, as a function of cerebral perfusion pressure (CrCPinv), and as a function of ABP (CrCPninv). RESULTS: There is good agreement among the three methods of CrCP calculation, with correlation coefficients being greater than 0.8 (p < 0.0001). For the CrCPA method, negative values were found for about 20% of all results. Negative values of CrCP were not observed in estimators based on cerebrovascular impedance. During the controlled rise of ICP, all three estimators of CrCP increased significantly (p < 0.05). The strongest correlation between ICP and CrCP was found for CrCPinv (median R = 0.41). CONCLUSION: Invasive CrCP is most sensitive to variations in ICP and can be used as an indicator of the status of the cerebrovascular system during infusion tests.

Changes in the level of cardiac troponine and disorders in pulmonary gas exchange as predictors of short- and long-term outcomes of patients with aneurysm subarachnoid haemorrhage.

SUBJECT: Cardiopulmonary abnormalities are common after aneurysmal subarachnoid haemorrhage (aSAH). However, the relationship between short- and long-term outcome is poorly understood. In this paper, we present how cardiac troponine elevations (cTnI) and pulmonary disorders are associated with short- and long-term outcomes assessed by the Glasgow Outcome Scale (GOS) and Extended Glasgow Outcome Scale (GOSE). METHODS: A total of 104 patients diagnosed with aSAH were analysed in the study. The non-parametric U Mann-Whitney test was used to evaluate the difference between good (GOS IV-V, GOSE V-VIII) and poor (GOS I-III, GOSE I-IV) outcomes in relation to cTnI elevation and pulmonary disorders. Outcome was assessed at discharge from the hospital, and then followed up 6 and 12 months later. Pulmonary disorders were determined by the PaO2/FiO2 ratio and radiography. The areas under the ROC curves (AUCs) were used to determine the predictive power of these factors. RESULTS: In the group with good short-term outcomes cTnI elevation on the second day after aSAH was significantly lower (p = .00007) than in patients with poor short-term outcomes. The same trend was observed after 6 months, although there were different results 12 months from the onset (p = .024 and n.s., respectively). A higher peak of cTnI was observed in the group with a pathological X-ray (p = .008) and pathological PaO2/FiO2 ratio (p ≪ .001). cTnI was an accurate predictor of short-term outcomes (AUC = 0.741, p ≪ .001) and the outcome after 6 months (AUC = 0.688, p = .015). CONCLUSION: The results showed that cardiopulmonary abnormalities perform well as predictive factors for short- and long-term outcomes after aSAH.

Cerebral Arterial Time Constant Recorded from the MCA and PICA in Normal Subjects.

Cerebral arterial time constant (τ) estimates how quickly the cerebral arterial bed distal to the point of insonation is filled with arterial blood following a cardiac contraction. It is not known how τ behaves in different vascular territories in the brain. We therefore investigated the differences in τ of two cerebral arteries: the posterior inferior cerebellar artery (PICA) and the middle cerebral artery (MCA).Transcranial Doppler cerebral blood flow velocity (CBFV) in the PICA and left MCA along with Finapres arterial blood pressure (ABP) were simultaneously recorded in 35 young healthy volunteers. τ was estimated using mathematical transformations of pulse waveforms of ABP and the CBFV of the MCA and the PICA. Since τ is independent from the vessel radius, its comparison in different cerebral arteries was feasible. Mean ABP was 76.1 ± 9.6 mmHg. The CBFV of the MCA was higher than that of the PICA (59.7 ± 7.7 vs. 41.0 ± 4.5 cm/s; p < 0.000001). τ of the PICA was shorter than that of the MCA (0.15 ± 0.03 vs. 0.18 ± 0.03 s; p < 0.000001). The MCA-supplied vascular bed has a longer distal average length, measured from the place of insonation up to the small arterioles, than the PICA-supplied vascular bed. Therefore, a longer time is needed to fill it with arterial blood volume. This study thus confirms the physiological validity of the τ concept.

Plateau Waves of Intracranial Pressure and Partial Pressure of Cerebral Oxygen.

This study investigates 55 intracranial pressure (ICP) plateau waves recorded in 20 patients after severe traumatic brain injury (TBI) with a focus on a moving correlation coefficient between mean arterial pressure (ABP) and ICP, called PRx, which serves as a marker of cerebrovascular reactivity, and a moving correlation coefficient between ABP and cerebral partial pressure of oxygen (pbtO2), called ORx, which serves as a marker for cerebral oxygen reactivity. ICP and ICPamplitude increased significantly during the plateau waves, whereas CPP and pbtO2 decreased significantly. ABP, ABP amplitude, and heart rate remained unchanged. In 73 % of plateau waves PRx increased during the wave. ORx showed an increase during and a decrease after the plateau waves, which was not statistically significant. Our data show profound cerebral vasoparalysis on top of the wave and, to a lesser extent, impairment of cerebral oxygen reactivity. The different behavior of the indices may be due to the different latencies of the cerebral blood flow and oxygen level control mechanisms. While cerebrovascular reactivity is a rapidly reacting mechanism, cerebral oxygen reactivity is slower.

Outcome, Pressure Reactivity and Optimal Cerebral Perfusion Pressure Calculation in Traumatic Brain Injury: A Comparison of Two Variants.

This study investigates the outcome prediction and calculation of optimal cerebral perfusion pressure (CPPopt) in 307 patients after severe traumatic brain injury (TBI) based on cerebrovascular reactivity calculation of a moving correlation correlation coefficient, named PRx, between mean arterial pressure (ABP) and intracranial pressure (ICP). The correlation coefficient was calculated from simultaneously recorded data using different frequencies. PRx was calculated from oscillations between 0.008 and 0.05Hz and the longPRx (L-PRx) was calculated from oscillations between 0.0008 and 0.016 Hz. PRx was a significant mortality predictor, whereas L-PRx was not. CPPopt for pooled data was higher for L-PRx than for PRx, with no statistical difference. Mortality was associated with mean CPP below CPPopt. Severe disability was associated with CPP above CPPopt (PRx). These relationships were not statistically significant for CPPopt (L-PRx). We conclude that PRx and L-PRx cannot be used interchangeably.