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.

Analysis of phase shift between pulse oscillations of macro- and microvascular cerebral blood flow in patients with traumatic brain injury.

PURPOSE: After a traumatic brain injury (TBI), monitoring of both macrovascular and microvascular blood circulation can potentially yield a better understanding of pathophysiology of potential secondary brain lesions. We investigated the changes in phase shift (PS) between cardiac-induced oscillations of cerebral blood flow (CBF) measured at macro (ultrasound Doppler) and microvascular (laser Doppler) level. Further we assessed the impact of intracranial pressure (ICP) on PS in TBI patients. A secondary aim was to compare PS to TCD-derived cerebral arterial time constant (τ), a parameter that reflects the circulatory transit time. METHODS: TCD blood flow velocities (FV) in the middle cerebral artery, laser Doppler blood microcirculation flux (LDF), arterial blood pressure (ABP), and ICP were monitored in 29 consecutive patients with TBI. Eight patients were excluded because of poor-quality signals. For the remaining 21 patients (median age = 23 (Q1: 20-Q3: 33); men:16,) data were retrospectively analysed. PS between the fundamental harmonics of FV and LDF signals was determined using spectral analysis. τ was estimated as a product of cerebrovascular resistance and compliance, based on the mathematical transformation of FV and ABP, ICP pulse waveforms. RESULTS: PS was negative (median: -26 (Q1: -38-Q3: -15) degrees) indicating that pulse LDF at a heart rate frequency lagged behind TCD pulse. With rising mean ICP, PS became more negative (R = -0.51, p < 0.019) indicating that delay of LDF pulse increases. There was a significant correlation between PS and cerebrovascular time constant (R = -0.47, p = 0.03). CONCLUSIONS: Pulse divergence between FV and LDF became greater with elevated ICP, likely reflecting prolonged circulatory travel time.

Quantitative analysis of similarity between cerebral arterial blood volume and intracranial pressure pulse waveforms during intracranial pressure plateau waves.

Introduction: Both intracranial pressure (ICP) and cerebral arterial blood volume (CaBV) have a pulsatile character related to the cardiac cycle. The evolution of the shape of ICP pulses under increasing ICP or decreasing intracranial compliance is well documented. Nevertheless, the exact origin of the alterations in the ICP morphology remains unclear. Research question: Does ICP pulse waveform become similar to non-invasively estimated CaBV pulse during ICP plateau waves. Material and methods: A total of 15 plateau waves recorded in 15 traumatic brain injured patients were analyzed. CaBV pulse waveforms were calculated using global cerebral blood flow model from transcranial Doppler cerebral blood flow velocity (CBFV) signals. The difference index (DI) was used to quantify the similarity between ICP and CaBV waveforms. DI was calculated as the sum of absolute sample-by-sample differences between ICP and CaBV waveforms, representing the area between the pulses. Results: ICP increased (19.4 mm Hg [Q1-Q3: 18.2-23.4 mm Hg] vs. 42.7 mm Hg [Q1-Q3: 36.5-45.1 mm Hg], p < 0.001) while CBFV decreased (44.2 cm/s [Q1-Q3: 34.8-69.5 cm/s] vs. 32.9 cm/s [Q1-Q3: 24.7-68.2 cm/s], p = 0.002) during plateau waves. DI was smaller during the plateau waves (20.4 [Q1-Q3: 15.74-23.0]) compared to the baselines (26.3 [Q1-Q3: 24.2-34.7], p < 0.001). Discussion and conclusion: The area between corresponding ICP and CaBV pulse waveforms decreased during the plateau waves which suggests they became similar in shape. CaBV may play a significant role in determining the shape of ICP pulses during the plateau waves and might be a driving force in formulating ICP elevation.

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.

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.

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.

Analysis of intracranial pressure pulse waveform in studies on cerebrospinal compliance: a narrative review.

Continuous monitoring of mean intracranial pressure (ICP) has been an essential part of neurocritical care for more than half a century. Cerebrospinal pressure-volume compensation, i.e. the ability of the cerebrospinal system to buffer changes in volume without substantial increases in ICP, is considered an important factor in preventing adverse effects on the patient's condition that are associated with ICP elevation. However, existing assessment methods are poorly suited to the management of brain injured patients as they require external manipulation of intracranial volume. In the 1980s, studies suggested that spontaneous short-term variations in the ICP signal over a single cardiac cycle, called the ICP pulse waveform, may provide information on cerebrospinal compensatory reserve. In this review we discuss the approaches that have been proposed so far to derive this information, from pulse amplitude estimation and spectral techniques to most recent advances in morphological analysis based on artificial intelligence solutions. Each method is presented with focus on its clinical significance and the potential for application in standard clinical practice. Finally, we highlight the missing links that need to be addressed in future studies in order for ICP pulse waveform analysis to achieve widespread use in the neurocritical care setting.

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.

Effects of positive end-expiratory pressure on cerebral hemodynamics in acute brain injury patients.

Background: Cerebral autoregulation is the mechanism that allows to maintain the stability of cerebral blood flow despite changes in cerebral perfusion pressure. Maneuvers which increase intrathoracic pressure, such as the application of positive end-expiratory pressure (PEEP), have been always challenged in brain injured patients for the risk of increasing intracranial pressure (ICP) and altering autoregulation. The primary aim of this study is to assess the effect of PEEP increase (from 5 to 15 cmH2O) on cerebral autoregulation. Secondary aims include the effect of PEEP increase on ICP and cerebral oxygenation. Material and Methods: Prospective, observational study including adult mechanically ventilated patients with acute brain injury requiring invasive ICP monitoring and undergoing multimodal neuromonitoring including ICP, cerebral perfusion pressure (CPP) and cerebral oxygenation parameters obtained with near-infrared spectroscopy (NIRS), and an index which expresses cerebral autoregulation (PRx). Additionally, values of arterial blood gases were analyzed at PEEP of 5 and 15 cmH2O. Results are expressed as median (interquartile range). Results: Twenty-five patients were included in this study. The median age was 65 years (46-73). PEEP increase from 5 to 15 cmH2O did not lead to worsened autoregulation (PRx, from 0.17 (-0.003-0.28) to 0.18 (0.01-0.24), p = 0.83). Although ICP and CPP changed significantly (ICP: 11.11 (6.73-15.63) to 13.43 (6.8-16.87) mm Hg, p = 0.003, and CPP: 72.94 (59.19-84) to 66.22 (58.91-78.41) mm Hg, p = 0.004), these parameters did not reach clinically relevant levels. No significant changes in relevant cerebral oxygenation parameters were observed. Conclusion: Slow and gradual increases of PEEP did not alter cerebral autoregulation, ICP, CPP and cerebral oxygenation to levels triggering clinical interventions in acute brain injury patients.

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.

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.

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.

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.

Changes in autonomic nervous system during cerebral desaturation episodes in aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Little evidence is available on the effect of regional cerebral desaturation (rCD) episodes that occur in the first days after aneurysm subarachnoid haemorrhage (aSAH) on the autonomic nervous system activity and on cardiovascular hemodynamics. In this study, we aimed to determine the impact of rCD episodes, developed within 5 days of aSAH, on the autonomic nervous system based on the assessment of baroreflex sensitivity (BRS) and on cardiac output (CO) and cardiac index (CI), and on cerebral autoregulation (CA). MATERIALS AND METHODS: Of 96 patients with aSAH, 36 patients (aged 57 (48-69)) met the inclusion criteria and were included in the study. Regional cerebral oxygen saturation and rCD episodes were evaluated using near-infrared spectroscopy. CA was quantified by the correlation coefficient (TOxa). Cardiac output (CO) and cardiac index (CI) were monitored using the FloTrack®/EV1000. Baroreflex sensitivity (BRS) was assessed using the cross-correlation method. Scores of 1 to 3 in Glasgow Outcome Scale were classified as a poor outcome. RESULTS: During episodes of rCD, BRS decreased significantly compared to baseline (p = 0.027) in patients who had a total duration of rCD episodes of more than 10 hours. During rCD episodes, CA improved slightly in comparison to baseline (p = 0.027). The threshold associated with poor outcome was: rSO2 < 62% (p = 0.002). CONCLUSIONS: BRS decreased in patients who had a total duration rCD episodes of more than 10 hours within the 5 days of aSAH. These results might partly explain the relationship between lower BRS and worse prognosis.

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.

Awake craniotomy with dexmedetomidine during resection of brain tumours located in eloquent regions.

INTRODUCTION: An awake craniotomy (AC) is the gold standard for the resection of supra-tentorial brain tumours in eloquent areas. Intraoperative monitoring "on-demand" of essential eloquent brain functions and the increasing need to preserve higher intellectual functions during surgery requires a unique anaesthetic approach during AC. Dexmedetomidine is considered the first-choice pharmacological agent for sedation during AC. MATERIAL AND METHODS: Twenty-six patients with a single brain tumour located in areas of eloquent brain function were enrolled in this prospective study. The patients underwent AC under conscious sedation. Motor-evoked potentials and brainstem-evoked auditory potentials were measured using neurophysiological tests during surgery to assess brain potentials. Intraoperative brain relaxation was reached using a modified Bristow scale. Neuromonitoring and psychological tests were maintained until meningeal closure. RESULTS: All operations were carried out successfully, and no reoperations were needed. No significant impact on circulatory and respiratory parameters was observed during conscious sedation based on dexmedetomidine. Neither instrumental airway support nor conversion to general anaesthesia was necessary. Brain relaxation was good in 84% of cases. Intraoperative epileptic episodes were observed in 15% of the patients. Neuro-logical and psychological monitoring was satisfactory. Unaltered muscle force was observed postoperatively in 88% of the patients. CONCLUSIONS: AC performed under conscious sedation, and dexmedetomidine infusion without instrumental airway support, was safe and well-tolerated by patients with comfortable physiological sleep for most of the procedure. This approach to AC was associated with minimal risk of perioperative adverse events and may be particularly beneficial in patients with severe comorbidities.

Analysis of the Shape of Intracranial Pressure Pulse Waveform in Traumatic Brain Injury Patients.

Intracranial pressure (ICP) pulse waveform, i.e., the shape of the ICP signal over a single cardiac cycle, is regarded as a potential source of information about intracranial compliance. In this study we aimed to compare the results of automatic classification of ICP pulse shapes on a scale from normal to pathological with other ICP pulse-derived metrics. Additionally, identification of artifacts was performed simultaneously with pulse classification to assess the effect of artifact removal on the results. Data from 35 traumatic brain injury (TBI) patients were analyzed retrospectively in terms of dominant waveform shape, mean ICP, mean amplitude of ICP (AmpICP), mean index of compensatory reserve (RAP index), and their association with the patient's clinical outcome. Our results show that patients with poor outcome exhibit more pathological waveform shape than patients with good outcome. More pathological ICP pulse shape is associated with higher mean ICP, mean AmpICP, and RAP.Clinical relevance- In the clinical setting, ICP pulse waveform analysis could potentially be used to complement the commonly monitored mean ICP and improve the assessment of intracranial compliance in TBI patients. Artifact removal from the ICP signal could reduce the frequency of false positive detection of clinically adverse events.