The effect of passive leg raising test on intracranial pressure and cerebral autoregulation in brain injured patients: a physiological observational study.

BACKGROUND: The use of the passive leg raising (PLR) is limited in acute brain injury (ABI) patients with increased intracranial pressure (ICP) since the postural change of the head may impact on ICP and cerebral autoregulation. However, the PLR use may prevent a positive daily fluid balance, which had been recently associated to worse neurological outcomes. We therefore studied early and delayed effects of PLR on the cerebral autoregulation of patients recovering from ABI. MATERIALS AND METHODS: This is a Prospective, observational, single-center study conducted in critically ill patients admitted with stable ABI and receiving invasive ICP monitoring, multimodal neuromonitoring and continuous hemodynamic monitoring. The fluid challenge consisted of 500 mL of crystalloid over 10 min; fluid responsiveness was defined as cardiac index increase ≥ 10%. Comparisons between different variables at baseline and after PLR were made by paired Wilcoxon signed-rank test. The correlation coefficients between hemodynamic and neuromonitoring variables were assessed using Spearman's rank test. RESULTS: We studied 23 patients [12 patients (52.2%) were fluid responders]. The PLR significantly increased ICP [from 13.7 (8.3-16.4) to 15.4 (12.0-19.2) mmHg; p < 0.001], cerebral perfusion pressure (CPP) [from 51.1 (47.4-55.6) to 56.4 (49.6-61.5) mmHg; p < 0.001] and the pressure reactivity index (PRx) [from 0.12 (0.01-0.24) to 0.43 (0.34-0.46) mmHg; p < 0.001]. Regarding Near Infrared Spectroscopy (NIRS)-derived parameters, PLR significantly increased the arterial component of regional cerebral oxygen saturation (O2Hbi) [from 1.8 (0.8-3.7) to 4.3 (2.5-5.6) µM cm; p < 0.001], the deoxygenated hemoglobin (HHbi) [from 1.6 (0.2-2.9) to 2.7 (1.4-4.0) µM cm; p = 0.007] and total hemoglobin (cHbi) [from 3.6 (1.9-5.3) to 7.8 (5.2-10.3): p < 0.001]. In all the patients who had altered autoregulation after PLR, these changes persisted ten minutes afterwards. After the PLR, we observed a significant correlation between MAP and CPP and PRx. CONCLUSIONS: In ABI patient with stable ICP, PLR test increased ICP, but mostly within safety values and thresholds. Despite this, cerebral autoregulation was importantly impaired, and this persisted up to 10 min after the end of the maneuvre. Our results discourage the use of PLR test in ABI even when ICP is stable.

The Effect of Recruitment Maneuvers on Cerebrovascular Dynamics and Right Ventricular Function in Patients with Acute Brain Injury: A Single-Center Prospective Study.

BACKGROUND: Optimization of ventilatory settings is challenging for patients in the neurointensive care unit, requiring a balance between precise gas exchange control, lung protection, and managing hemodynamic effects of positive pressure ventilation. Although recruitment maneuvers (RMs) may enhance oxygenation, they could also exert profound undesirable systemic impacts. METHODS: The single-center, prospective study investigated the effects of RMs (up-titration of positive end-expiratory pressure) on multimodal neuromonitoring in patients with acute brain injury. Our primary focus was on intracranial pressure and secondarily on cerebral perfusion pressure (CPP) and other neurological parameters: cerebral autoregulation [pressure reactivity index (PRx)] and regional cerebral oxygenation (rSO2). We also assessed blood pressure and right ventricular (RV) function evaluated using tricuspid annular plane systolic excursion. Results are expressed as the difference (Δ) from baseline values obtained after completing the RMs. RESULTS: Thirty-two patients were enrolled in the study. RMs resulted in increased intracranial pressure (Δ = 4.8 mm Hg) and reduced CPP (ΔCPP = -12.8 mm Hg) and mean arterial pressure (difference in mean arterial pressure = -5.2 mm Hg) (all p < 0.001). Cerebral autoregulation worsened (ΔPRx = 0.31 a.u.; p < 0.001). Despite higher systemic oxygenation (difference in partial pressure of O2 = 4 mm Hg; p = 0.001) and unchanged carbon dioxide levels, rSO2 marginally decreased (ΔrSO2 = -0.5%; p = 0.031), with a significant drop in arterial content and increase in the venous content. RV systolic function decreased (difference in tricuspid annular plane systolic excursion = -0.1 cm; p < 0.001) with a tendency toward increased RV basal diameter (p = 0.06). Grouping patients according to ΔCPP or ΔPRx revealed that those with poorer tolerance to RMs had higher CPP (p = 0.040) and a larger RV basal diameter (p = 0.034) at baseline. CONCLUSIONS: In patients with acute brain injury, RMs appear to have adverse effects on cerebral hemodynamics. These findings might be partially explained by RM's impact on RV function. Further advanced echocardiography monitoring is required to prove this hypothesis.

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.

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.

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.

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.

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.

Predictive value of cerebrovascular time constant for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

Time constant of the cerebral arterial bed (τ) is a transcranial Doppler (TCD) based metric that is expected to quantify the transit time of red blood cells from the insonation point to the arteriole-capillary boundary during a cardiac cycle. This study aims to assess the potential of τ as an early predictor of delayed cerebral ischemia (DCI). Consecutive patients (56 ± 15 years) treated for aneurysmal subarachnoid haemorrhage were included in the study. τ was assessed through a modelling approach that involved simultaneous recordings of arterial blood pressure and cerebral blood flow velocity (CBFV) from TCD's first recordings. 71 patients were included. 17 patients experienced DCI. τ was significantly shorter in patients who later developed DCI: 187 ± 64 ms vs. 249 ± 184 ms; p = 0.040 with moderate effect size (rG = 0.24). Logistic regression showed that there was a significant association between increased CBFV, shortened τ, and the development of DCI (χ2 = 11.54; p = 0.003) with AUC for the model 0.75. Patients who had both shortened τ and increased CBFV were 20 times more likely to develop DCI (OR = 20.4 (2.2-187.7)). Our results suggest that early alterations in τ are associated with DCI after aSAH. The highest performance of the model including both CBFV and τ may suggest the importance of both macrovascular and microvascular changes assessment.

The impact of controlled breathing on autonomic nervous system modulation: analysis using phase-rectified signal averaging, entropy and heart rate variability.

Objective.The present study investigated how breathing stimuli affect both non-linear and linear metrics of the autonomic nervous system (ANS).Approach.The analysed dataset consisted of 70 young, healthy volunteers, in whom arterial blood pressure (ABP) was measured noninvasively during 5 min sessions of controlled breathing at three different frequencies: 6, 10 and 15 breaths min-1. CO2concentration and respiratory rate were continuously monitored throughout the controlled breathing sessions. The ANS was characterized using non-linear methods, including phase-rectified signal averaging (PRSA) for estimating heart acceleration and deceleration capacity (AC, DC), multiscale entropy, approximate entropy, sample entropy, and fuzzy entropy, as well as time and frequency-domain measures (low frequency, LF; high-frequency, HF; total power, TP) of heart rate variability (HRV).Main results.Higher breathing rates resulted in a significant decrease in end-tidal CO2concentration (p< 0.001), accompanied by increases in both ABP (p <0.001) and heart rate (HR,p <0.001). A strong, linear decline in AC and DC (p <0.001 for both) was observed with increasing breathing rate. All entropy metrics increased with breathing frequency (p <0.001). In the time-domain, HRV metrics significantly decreased with breathing frequency (p <0.01 for all). In the frequency-domain, HRV LF and HRV HF decreased (p= 0.038 andp= 0.040, respectively), although these changes were modest. There was no significant change in HRV TP with breathing frequencies.Significance.Alterations in CO2levels, a potent chemoreceptor trigger, and changes in HR most likely modulate ANS metrics. Non-linear PRSA and entropy appear to be more sensitive to breathing stimuli compared to frequency-dependent HRV metrics. Further research involving a larger cohort of healthy subjects is needed to validate our observations.

The Role of Early Serum Biomarkers and Clinical Rating Scales in the Prediction of Delayed Cerebral Ischaemia and Short-Term Outcome after Aneurysmal Subarachnoid Haemorrhage: Single Centre Experience.

Considering the variety of complications that arise after aneurysmal subarachnoid haemorrhage (aSAH) and the complex pathomechanism of delayed cerebral ischaemia (DCI), the task of predicting the outcome assumes a profound complexity. Therefore, there is a need to develop early predictive and decision-making models. This study explores the effect of serum biomarkers and clinical scales on patients' outcomes and their interrelationship with DCI and systemic complications in aSAH. This was a retrospective analysis including aSAH patients admitted to the Wroclaw University Hospital (Wroclaw, Poland) from 2011 to 2020. A good outcome was defined as a modified Rankin Scale (mRS) score of 0-2. The prediction of the development of DCI and poor outcome was conducted using logistic regression as a standard model (SM) and random forest as a machine learning method (ML). A cohort of 174 aSAH patients were included in the analysis. DCI was diagnosed in 79 (45%) patients. Significant differences between patients with poor vs. good outcome were determined from their levels of albumin (31 ± 7 vs. 35 ± 5 (g/L); p < 0.001), D-dimer (3.0 ± 4.5 vs. 1.5 ± 2.8 (ng/mL); p < 0.001), procalcitonin (0.2 ± 0.4 vs. 0.1 ± 0.1 (ng/mL); p < 0.001), and glucose (169 ± 69 vs. 137 ± 48 (nmol/L); p < 0.001). SM for DCI prediction included the Apache II scale (odds ratio [OD] 1.05; 95% confidence interval [CI] 1.00-1.09) and albumin level (OD 0.88; CI 0.82-0.95). ML demonstrated that low albumin level, high Apache II scale, increased D-dimer and procalcitonin levels had the highest predictive values for DCI. The integration of clinical parameters and scales with a panel of biomarkers may effectively facilitate the stratification of aSAH patients, identifying those at high risk of secondary complications and poor outcome.

Cerebrospinal Fluid and Serum Biomarker Insights in Aneurysmal Subarachnoid Haemorrhage: Navigating the Brain-Heart Interrelationship for Improved Patient Outcomes.

The pathophysiological mechanisms underlying severe cardiac dysfunction after aneurysmal subarachnoid haemorrhage (aSAH) remain poorly understood. In the present study, we focused on two categories of contributing factors describing the brain-heart relationship. The first group includes brain-specific cerebrospinal fluid (CSF) and serum biomarkers, as well as cardiac-specific biomarkers. The secondary category encompasses parameters associated with cerebral autoregulation and the autonomic nervous system. A group of 15 aSAH patients were included in the analysis. Severe cardiac complications were diagnosed in seven (47%) of patients. In the whole population, a significant correlation was observed between CSF S100 calcium-binding protein B (S100B) and brain natriuretic peptide (BNP) (rS = 0.62; p = 0.040). Additionally, we identified a significant correlation between CSF neuron-specific enolase (NSE) with cardiac troponin I (rS = 0.57; p = 0.025) and BNP (rS = 0.66; p = 0.029), as well as between CSF tau protein and BNP (rS = 0.78; p = 0.039). Patients experiencing severe cardiac complications exhibited notably higher levels of serum tau protein at day 1 (0.21 ± 0.23 [ng/mL]) compared to those without severe cardiac complications (0.03 ± 0.04 [ng/mL]); p = 0.009. Impaired cerebral autoregulation was noted in patients both with and without severe cardiac complications. Elevated serum NSE at day 1 was related to impaired cerebral autoregulation (rS = 0.90; p = 0.037). On the first day, a substantial, reciprocal correlation between heart rate variability low-to-high frequency ratio (HRV LF/HF) and both GFAP (rS = -0.83; p = 0.004) and S100B (rS = -0.83; p = 0.004) was observed. Cardiac and brain-specific biomarkers hold the potential to assist clinicians in providing timely insights into cardiac complications, and therefore they contribute to the prognosis of outcomes.

Analysis of intracranial pressure pulse waveform in traumatic brain injury patients: a CENTER-TBI study.

OBJECTIVE: Intracranial pressure (ICP) pulse waveform analysis may provide valuable information about cerebrospinal pressure-volume compensation in patients with traumatic brain injury (TBI). The authors applied spectral methods to analyze ICP waveforms in terms of the pulse amplitude of ICP (AMP), high frequency centroid (HFC), and higher harmonics centroid (HHC) and also used a morphological classification approach to assess changes in the shape of ICP pulse waveforms using the pulse shape index (PSI). METHODS: The authors included 184 patients from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) High-Resolution Sub-Study in the analysis. HFC was calculated as the average power-weighted frequency within the 4- to 15-Hz frequency range of the ICP power density spectrum. HHC was defined as the center of mass of the ICP pulse waveform harmonics from the 2nd to the 10th. PSI was defined as the weighted sum of artificial intelligence-based ICP pulse class numbers from 1 (normal pulse waveform) to 4 (pathological waveform). RESULTS: AMP and PSI increased linearly with mean ICP. HFC increased proportionally to ICP until the upper breakpoint (average ICP of 31 mm Hg), whereas HHC slightly increased with ICP and then decreased significantly when ICP exceeded 25 mm Hg. AMP (p < 0.001), HFC (p = 0.003), and PSI (p < 0.001) were significantly greater in patients who died than in patients who survived. Among those patients with low ICP (< 15 mm Hg), AMP, PSI, and HFC were greater in those with poor outcome than in those with good outcome (all p < 0.001). CONCLUSIONS: Whereas HFC, AMP, and PSI could be used as predictors of mortality, HHC may potentially serve as an early warning sign of intracranial hypertension. Elevated HFC, AMP, and PSI were associated with poor outcome in TBI patients with low ICP.

Intracranial Pressure Pulse Morphology-based Definition of Life-threatening Intracranial Hypertension Episodes.

Intracranial hypertension (IH) is associated with poor outcome in traumatic brain injury (TBI) patients and must be avoided to prevent secondary brain injury. In clinical practice the most common method of IH detection is the calculation of the mean value of intracranial pressure (ICP) and the therapeutic intervention is usually introduced when the mean exceeds a certain threshold. This threshold, however, is rather individual for each patient than universal for all. Impaired cerebrovascular reactivity and reduced intracranial compliance are associated with raised ICP. This work explores a new definition of life-threatening hypertension (LTH) which accounts for the state of cerebral compliance. In the proposed method, changes in compliance are analysed through identification of likely pathological and/or pathological shapes of ICP pulse waveforms using a neural network. In terms of predictive power for mortality in TBI, detection of both shape clasess of ICP pulse waveforms during raised ICP offers similar results to previously proposed LTH definition accounting for the state of cerebrovascular reactivity (77.8% vs 76.9% accuracy, respectively). On the other hand, the fully pathological shapes of ICP pulses are present during ICP rises almost only in recordings of patients who died: out of 216 analysed patients only 6% of surviving and as many as 42% of deceased patients developed this type of LTH event. The stricter definition of LTH events including only pathological shape of ICP pulses presents the highest accuracy among the analysed approaches for mortality prediction (87.9%). Clinical relevance-Reliable detection of potentially life-threatening episodes of ICP elevation offers the possibility of improving clinical management of TBI by identifying the patients at risk of unfavourable outcome.

End-to-End Automatic Morphological Classification of Intracranial Pressure Pulse Waveforms Using Deep Learning.

OBJECTIVE: Mean intracranial pressure (ICP) is commonly used in the management of patients with intracranial pathologies. However, the shape of the ICP signal over a single cardiac cycle, called ICP pulse waveform, also contains information on the state of the craniospinal space. In this study we aimed to propose an end-to-end approach to classification of ICP waveforms and assess its potential clinical applicability. METHODS: ICP pulse waveforms obtained from long-term ICP recordings of 50 neurointensive care unit (NICU) patients were manually classified into four classes ranging from normal to pathological. An additional class was introduced to simultaneously identify artifacts. Several deep learning models and data representations were evaluated. An independent testing dataset was used to assess the performance of final models. Occurrence of different waveform types was compared with the patients' clinical outcome. RESULTS: Residual Neural Network using 1-D ICP signal as input was identified as the best performing model with accuracy of 93% in the validation and 82% in the testing dataset. Patients with unfavorable outcome exhibited significantly lower incidence of normal waveforms compared to the favorable outcome group even at ICP levels below 20 mm Hg (median [first-third quartile]: 9 [1-36]% vs. 63 [52-88] %, p = 0.002). CONCLUSIONS: Results of this study confirm the possibility of analyzing ICP pulse waveform morphology in long-term recordings of NICU patients. Proposed approach could potentially be used to provide additional information on the state of patients with intracranial pathologies beyond mean ICP.

Peak appearance time in pulse waveforms of intracranial pressure and cerebral blood flow velocity.

The shape of the pulse waveforms of intracranial pressure (ICP) and cerebral blood flow velocity (CBFV) typically contains three characteristic peaks. It was reported that alterations in cerebral hemodynamics may influence the shape of the pulse waveforms by changing peaks' configuration. However, the changes in peak appearance time (PAT) in ICP and CBFV pulses are only described superficially. We analyzed retrospectively ICP and CBFV signals recorded in traumatic brain injury patients during decrease in ICP induced by hypocapnia (n = 11) and rise in ICP during episodes of ICP plateau waves (n = 8). All three peaks were manually annotated in over 48 thousand individual pulses. The changes in PAT were compared between periods of vasoconstriction (expected during hypocapnia) and vasodilation (expected during ICP plateau waves) and their corresponding baselines. Correlation coefficient (rS) analysis between mean ICP and mean PATs was performed in each individual recording. Vasodilation prolonged PAT of the first peaks of ICP and CBFV pulses and the third peak of CBFV pulse. It also accelerated PAT of the third peak of ICP pulse. In contrast, vasoconstriction shortened appearance time of the first peaks of ICP and CBFV pulses and the second peak of ICP pulses. Analysis of individual recordings demonstrated positive association between changes in PAT of all three peaks in the CBFV pulse and mean ICP (rS range: 0.32-0.79 for significant correlations). Further study is needed to test whether PAT of the CBFV pulse may serve as an indicator of changes in ICP-this may open a perspective for non-invasive monitoring of alterations in mean ICP.