Modelling midline shift and ventricle collapse in cerebral oedema following acute ischaemic stroke.

In ischaemic stroke, a large reduction in blood supply can lead to the breakdown of the blood-brain barrier and to cerebral oedema after reperfusion therapy. The resulting fluid accumulation in the brain may contribute to a significant rise in intracranial pressure (ICP) and tissue deformation. Changes in the level of ICP are essential for clinical decision-making and therapeutic strategies. However, the measurement of ICP is constrained by clinical techniques and obtaining the exact values of the ICP has proven challenging. In this study, we propose the first computational model for the simulation of cerebral oedema following acute ischaemic stroke for the investigation of ICP and midline shift (MLS) relationship. The model consists of three components for the simulation of healthy blood flow, occluded blood flow and oedema, respectively. The healthy and occluded blood flow components are utilized to obtain oedema core geometry and then imported into the oedema model for the simulation of oedema growth. The simulation results of the model are compared with clinical data from 97 traumatic brain injury patients for the validation of major model parameters. Midline shift has been widely used for the diagnosis, clinical decision-making, and prognosis of oedema patients. Therefore, we focus on quantifying the relationship between ICP and midline shift (MLS) and identify the factors that can affect the ICP-MLS relationship. Three major factors are investigated, including the brain geometry, blood-brain barrier damage severity and the types of oedema (including rare types of oedema). Meanwhile, the two major types (stress and tension/compression) of mechanical brain damage are also presented and the differences in the stress, tension, and compression between the intraparenchymal and periventricular regions are discussed. This work helps to predict ICP precisely and therefore provides improved clinical guidance for the treatment of brain oedema.

Predicting short-term outcomes in brain-injured patients: a comprehensive approach with transcranial Doppler and intracranial compliance assessment.

Neurocritical patients frequently exhibit abnormalities in cerebral hemodynamics (CH) and/or intracranial compliance (ICC), all of which significantly impact their clinical outcomes. Transcranial Doppler (TCD) and the cranial micro-deformation sensor (B4C) are valuable techniques for assessing CH and ICC, respectively. However, there is a scarcity of data regarding the predictive value of these techniques in determining patient outcomes. We prospectively included neurocritical patients undergoing intracranial pressure (ICP) monitoring within the first 5 days of hospital admission for TCD and B4C assessments. Comprehensive clinical data were collected alongside parameters obtained from TCD (including the estimated ICP [eICP] and estimated cerebral perfusion pressure [eCPP]) and B4C (measured as the P2/P1 ratio). These parameters were evaluated individually as well as in combination. The short-term outcomes (STO) of interest were the therapy intensity levels (TIL) for ICP management recommended by the Seattle International Brain Injury Consensus Conference, as TIL 0 (STO 1), TIL 1-3 (STO 2) and death (STO 3), at the seventh day after last data collection. The dataset was randomly separated in test and training samples, area under the curve (AUC) was used to represent the noninvasive techniques ability on the STO prediction and association with ICP. A total of 98 patients were included, with 67% having experienced severe traumatic brain injury and 15% subarachnoid hemorrhage, whilst the remaining patients had ischemic or hemorrhagic stroke. ICP, P2/P1, and eCPP demonstrated the highest ability to predict early mortality (p = 0.02, p = 0.02, and p = 0.006, respectively). P2/P1 was the only parameter significant for the prediction of STO 1 (p = 0.03). Combining B4C and TCD parameters, the highest AUC was 0.85 to predict death (STO 3), using P2/P1 + eCPP, whereas AUC was 0.72 to identify ICP > 20 mmHg using P2/P1 + eICP. The combined noninvasive neuromonitoring approach using eCPP and P2/P1 ratio demonstrated improved performance in predicting outcomes during the early phase after acute brain injury. The correlation with intracranial hypertension was moderate, by means of eICP and P2/P1 ratio. These results support the need for interpretation of this information in the ICU and warrant further investigations for the definition of therapy strategies using ancillary tests.

Characterization of intracranial compliance in healthy subjects using a noninvasive method - results from a multicenter prospective observational study.

PURPOSE: An FDA-approved non-invasive intracranial pressure (ICP) monitoring system enables the assessment of ICP waveforms by revealing and analyzing their morphological variations and parameters associated with intracranial compliance, such as the P2/P1 ratio and time-to-peak (TTP). The aim of this study is to characterize intracranial compliance in healthy volunteers across different age groups. METHODS: Healthy participants, both sexes, aged from 9 to 74 years old were monitored for 5 min in the supine position at 0º. Age was stratified into 4 groups: children (≤ 7 years); young adults (18 ≤ age ≤ 44 years); middle-aged adults (45 ≤ age ≤ 64 years); older adults (≥ 65 years). The data obtained was the non-invasive ICP waveform, P2/P1 ratio and TTP. RESULTS: From December 2020 to February 2023, 188 volunteers were assessed, of whom 104 were male, with a median (interquartile range) age of 41 (29-51), and a median (interquartile range) body mass index of 25.09 (22.57-28.04). Men exhibited lower values compared to women for both the P2/P1 ratio and TTP (p < 0.001). There was a relative rise in both P2/P1 and TTP as age increased (p < 0.001). CONCLUSIONS: The study revealed that the P2/P1 ratio and TTP are influenced by age and sex in healthy individuals, with men displaying lower values than women, and both ratios increasing with age. These findings suggest potential avenues for further research with larger and more diverse samples to establish reference values for comparison in various health conditions. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials (RBR-9nv2h42), retrospectively registered 05/24/2022. UTN: U1111-1266-8006.

Short-term mild hyperventilation on intracranial pressure, cerebral autoregulation, and oxygenation in acute brain injury patients: a prospective observational study.

Current guidelines suggest a target of partial pressure of carbon dioxide (PaCO2) of 32-35 mmHg (mild hypocapnia) as tier 2 for the management of intracranial hypertension. However, the effects of mild hyperventilation on cerebrovascular dynamics are not completely elucidated. The aim of this study is to evaluate the changes of intracranial pressure (ICP), cerebral autoregulation (measured through pressure reactivity index, PRx), and regional cerebral oxygenation (rSO2) parameters before and after induction of mild hyperventilation. Single center, observational study including patients with acute brain injury (ABI) admitted to the intensive care unit undergoing multimodal neuromonitoring and requiring titration of PaCO2 values to mild hypocapnia as tier 2 for the management of intracranial hypertension. Twenty-five patients were included in this study (40% female), median age 64.7 years (Interquartile Range, IQR = 45.9-73.2). Median Glasgow Coma Scale was 6 (IQR = 3-11). After mild hyperventilation, PaCO2 values decreased (from 42 (39-44) to 34 (32-34) mmHg, p < 0.0001), ICP and PRx significantly decreased (from 25.4 (24.1-26.4) to 17.5 (16-21.2) mmHg, p < 0.0001, and from 0.32 (0.1-0.52) to 0.12 (-0.03-0.23), p < 0.0001). rSO2 was statistically but not clinically significantly reduced (from 60% (56-64) to 59% (54-61), p < 0.0001), but the arterial component of rSO2 (ΔO2Hbi, changes in concentration of oxygenated hemoglobin of the total rSO2) decreased from 3.83 (3-6.2) µM.cm to 1.6 (0.5-3.1) µM.cm, p = 0.0001. Mild hyperventilation can reduce ICP and improve cerebral autoregulation, with minimal clinical effects on cerebral oxygenation. However, the arterial component of rSO2 was importantly reduced. Multimodal neuromonitoring is essential when titrating PaCO2 values for ICP management.

Assessment of Cerebral Autoregulation Using Invasive and Noninvasive Methods of Intracranial Pressure Monitoring.

BACKGROUND: Pulse amplitude index (PAx), a descriptor of cerebrovascular reactivity, correlates the changes of the pulse amplitude of the intracranial pressure (ICP) waveform (AMP) with changes in mean arterial pressure (MAP). AMP relies on cerebrovascular compliance, which is modulated by the state of the cerebrovascular reactivity. PAx can aid in prognostication after acute brain injuries as a tool for the assessment of cerebral autoregulation and could potentially tailor individual management; however, invasive measurements are required for its calculation. Our aim was to evaluate the relationship between noninvasive PAx (nPAx) derived from a novel noninvasive device for ICP monitoring and PAx derived from gold standard invasive methods. METHODS: We retrospectively analyzed invasive ICP (external ventricular drain) and non-invasive ICP (nICP), via mechanical extensometer (Brain4Care Corp.). Invasive and non-invasive ICP waveform morphology data was collected in adult patients with brain injury with arterial blood pressure monitoring. The time series from all signals were first treated to remove movement artifacts. PAx and nPAx were calculated as the moving correlation coefficients of 10-s averages of AMP or non-invasive AMP (nAMP) and MAP. AMP/nAMP was determined by calculating the fundamental frequency amplitude of the ICP/nICP signal over a 10-s window, updated every 10-s. We then evaluated the relationship between invasive PAx and noninvasive nPAx using the methods of repeated-measures analysis to generate an estimate of the correlation coefficient and its 95% confidence interval (CI). The agreement between the two methods was assessed using the Bland-Altman test. RESULTS: Twenty-four patients were identified. The median age was 53.5 years (interquartile range 40-70), and intracranial hemorrhage (84%) was the most common etiology. Twenty-one (87.5%) patients underwent mechanical ventilation, and 60% were sedated with a median Glasgow Coma Scale score of 8 (7-15). Mean PAx was 0.0296 ± 0.331, and nPAx was 0.0171 ± 0.332. The correlation between PAx and nPAx was strong (R = 0.70, p < 0.0005, 95% CI 0.687-0.717). Bland-Altman analysis showed excellent agreement, with a bias of - 0.018 (95% CI - 0.026 to - 0.01) and a localized regression trend line that did not deviate from 0. CONCLUSIONS: PAx can be calculated by conventional and noninvasive ICP monitoring in a statistically significant evaluation with strong agreement. Further study of the applications of this clinical tool is warranted, with the goal of early therapeutic intervention to improve neurologic outcomes following acute brain injuries.

Is Lumbar Puncture Needed? - Noninvasive Assessment of ICP Facilitates Decision Making in Patients with Suspected Idiopathic Intracranial Hypertension.

PURPOSE: Idiopathic intracranial hypertension (IIH) usually occurs in obese women of childbearing age. Typical symptoms are headache and sight impairment. Lumbar puncture (LP) is routinely used for both diagnosis and therapy (via cerebrospinal fluid drainage) of IIH. In this study, noninvasively assessed intracranial pressure (nICP) was compared to LP pressure (LPP) in order to clarify its feasibility for the diagnosis of IIH. MATERIALS AND METHODS: nICP was calculated using continuous signals of arterial blood pressure and cerebral blood flow velocity in the middle cerebral artery, a method which has been introduced recently. In 26 patients (f = 24, m = 2; age: 33 ±â€Š11 years), nICP was assessed one hour prior to LPP. If LPP was > 20 cmH2O, lumbar drainage was performed, LPP was measured again, and also nICP was reassessed. RESULTS: In total, LPP and nICP correlated with R = 0.85 (p < 0.001; N = 38). The mean difference of nICP-LPP was 0.45 ±â€Š4.93 cmH2O. The capability of nICP to diagnose increased LPP (LPP > 20 cmH2O) was assessed by ROC analysis. The optimal cutoff for nICP was close to 20 cmH2O with both a sensitivity and specificity of 0.92. Presuming 20 cmH2O as a critical threshold for the indication of lumbar drainage, the clinical implications would coincide in both methods in 35 of 38 cases. CONCLUSION: The TCD-based nICP assessment seems to be suitable for a pre-diagnosis of increased LPP and might eliminated the need for painful lumbar puncture if low nICP is detected.

Prolonged Automated Robotic TCD Monitoring in Acute Severe TBI: Study Design and Rationale.

BACKGROUND: Transcranial Doppler ultrasonography (TCD) is a portable, bedside, noninvasive diagnostic tool used for the real-time assessment of cerebral hemodynamics. Despite the evident utility of TCD and the ability of this technique to function as a stethoscope to the brain, its use has been limited to specialized centers because of the dearth of technical and clinical expertise required to acquire and interpret the cerebrovascular parameters. Additionally, the conventional pragmatic episodic TCD monitoring protocols lack dynamic real-time feedback to guide time-critical clinical interventions. Fortunately, with the recent advent of automated robotic TCD technology in conjunction with the automated software for TCD data processing, we now have the technology to automatically acquire TCD data and obtain clinically relevant information in real-time. By obviating the need for highly trained clinical personnel, this technology shows great promise toward a future of widespread noninvasive monitoring to guide clinical care in patients with acute brain injury. METHODS: Here, we describe a proposal for a prospective observational multicenter clinical trial to evaluate the safety and feasibility of prolonged automated robotic TCD monitoring in patients with severe acute traumatic brain injury (TBI). We will enroll patients with severe non-penetrating TBI with concomitant invasive multimodal monitoring including, intracranial pressure, brain tissue oxygenation, and brain temperature monitoring as part of standard of care in centers with varying degrees of TCD availability and experience. Additionally, we propose to evaluate the correlation of pertinent TCD-based cerebral autoregulation indices such as the critical closing pressure, and the pressure reactivity index with the brain tissue oxygenation values obtained invasively. CONCLUSIONS: The overarching goal of this study is to establish safety and feasibility of prolonged automated TCD monitoring for patients with TBI in the intensive care unit and identify clinically meaningful and pragmatic noninvasive targets for future interventions.

Feasibility of non-invasive neuromonitoring in general intensive care patients using a multi-parameter transcranial Doppler approach.

PURPOSE: To assess the feasibility of Transcranial Doppler ultrasonography (TCD) neuromonitoring in a general intensive care environment, in the prognosis and outcome prediction of patients who are in coma due to a variety of critical conditions. METHODS: The prospective trial was performed between March 2017 and March 2019 Addenbrooke's Hospital, Cambridge, UK. Forty adult patients who failed to awake appropriately after resuscitation from cardiac arrest or were in coma due to conditions such as meningitis, seizures, sepsis, metabolic encephalopathies, overdose, multiorgan failure or transplant were eligible for inclusion. Gathered data included admission diagnosis, duration of ventilation, length of stay in the ICU, length of stay in hospital, discharge status using Cerebral Performance Categories (CPC). All patients received intermittent extended TCD monitoring following inclusion in the study. Parameters of interest included TCD-based indices of cerebral autoregulation, non-invasive intracranial pressure, autonomic system parameters (based on heart rate variability), critical closing pressure, the cerebrovascular time constant and indices describing the shape of the TCD pulse waveform. RESULTS: Thirty-seven patients were included in the final analysis, with 21 patients classified as good outcome (CPC 1-2) and 16 as poor neurological outcomes (CPC 3-5). Three patients were excluded due to inadequacies identified in the TCD acquisition. The results indicated that irrespective of the primary diagnosis, non-survivors had significantly disturbed cerebral autoregulation, a shorter cerebrovascular time constant and a more distorted TCD pulse waveform (all p<0.05). CONCLUSIONS: Preliminary results from the trial indicate that multi-parameter TCD neuromonitoring increases outcome-predictive power and TCD-based indices can be applied to general intensive care monitoring.

Early effects of ventilatory rescue therapies on systemic and cerebral oxygenation in mechanically ventilated COVID-19 patients with acute respiratory distress syndrome: a prospective observational study.

BACKGROUND: In COVID-19 patients with acute respiratory distress syndrome (ARDS), the effectiveness of ventilatory rescue strategies remains uncertain, with controversial efficacy on systemic oxygenation and no data available regarding cerebral oxygenation and hemodynamics. METHODS: This is a prospective observational study conducted at San Martino Policlinico Hospital, Genoa, Italy. We included adult COVID-19 patients who underwent at least one of the following rescue therapies: recruitment maneuvers (RMs), prone positioning (PP), inhaled nitric oxide (iNO), and extracorporeal carbon dioxide (CO2) removal (ECCO2R). Arterial blood gas values (oxygen saturation [SpO2], partial pressure of oxygen [PaO2] and of carbon dioxide [PaCO2]) and cerebral oxygenation (rSO2) were analyzed before (T0) and after (T1) the use of any of the aforementioned rescue therapies. The primary aim was to assess the early effects of different ventilatory rescue therapies on systemic and cerebral oxygenation. The secondary aim was to evaluate the correlation between systemic and cerebral oxygenation in COVID-19 patients. RESULTS: Forty-five rescue therapies were performed in 22 patients. The median [interquartile range] age of the population was 62 [57-69] years, and 18/22 [82%] were male. After RMs, no significant changes were observed in systemic PaO2 and PaCO2 values, but cerebral oxygenation decreased significantly (52 [51-54]% vs. 49 [47-50]%, p < 0.001). After PP, a significant increase was observed in PaO2 (from 62 [56-71] to 82 [76-87] mmHg, p = 0.005) and rSO2 (from 53 [52-54]% to 60 [59-64]%, p = 0.005). The use of iNO increased PaO2 (from 65 [67-73] to 72 [67-73] mmHg, p = 0.015) and rSO2 (from 53 [51-56]% to 57 [55-59]%, p = 0.007). The use of ECCO2R decreased PaO2 (from 75 [75-79] to 64 [60-70] mmHg, p = 0.009), with reduction of rSO2 values (59 [56-65]% vs. 56 [53-62]%, p = 0.002). In the whole population, a significant relationship was found between SpO2 and rSO2 (R = 0.62, p < 0.001) and between PaO2 and rSO2 (R0 0.54, p < 0.001). CONCLUSIONS: Rescue therapies exert specific pathophysiological mechanisms, resulting in different effects on systemic and cerebral oxygenation in critically ill COVID-19 patients with ARDS. Cerebral and systemic oxygenation are correlated. The choice of rescue strategy to be adopted should take into account both lung and brain needs. Registration The study protocol was approved by the ethics review board (Comitato Etico Regione Liguria, protocol n. CER Liguria: 23/2020).

Spectral Cerebral Blood Volume Accounting for Noninvasive Estimation of Changes in Cerebral Perfusion Pressure in Patients with Traumatic Brain Injury.

We present the application of a new method for non-invasive cerebral perfusion pressure estimation (spectral nCPP or nCPPs) accounting for changes in transcranial Doppler-derived pulsatile cerebral blood volume. Primarily, we analysed cases in which CPP was changing (delta [∆],magnitude of changes]): (1) rise during vasopressor-induced augmentation of ABP (N = 16); and (2) spontaneous changes in intracranial pressure (ICP) during plateau waves (N = 14). Secondarily, we assessed nCPPs in a larger cohort in which CPP presented a wider range of values. The average correlation in the time domain between CPP and nCPPs for patients undergoing an induced rise in arterial blood pressure (ABP) was 0.95 ± 0.07. For the greater traumatic brain injury (TBI) cohort, this correlation was 0.63 ± 0.37. ∆ correlations between mean values of CPP and nCPPs were 0.73 (p = 0.002) and 0.78 (p < 0.001) respectively for induced rise in ABP and ICP plateau wave cohorts. The area under the curve (AUC) for ∆CPP was of 0.71 with a 95% confidence interval of 0.54-0.88. To detect low CPP, AUC was 0.817 with a 95% confidence interval of 0.79-0.85. nCPPs can reliably identify changes in direct CPP across time and the magnitude of these changes in absolute values. The ability to detect changes in CPP is reasonable but stronger for detecting low CPP, ≤70 mmHg.

Noninvasive Intracranial Pressure Assessment in Patients with Suspected Idiopathic Intracranial Hypertension.

INTRODUCTION: Idiopathic intracranial hypertension (IIH) usually occurs in obese women of childbearing age. Typical symptoms are headache and sight disorders. Besides ophthalmoscopy, lumbar puncture is used for both diagnosis and therapy of IIH. In this study, noninvasively-assessed intracranial pressure (nICP) was compared to lumbar pressure (LP) to clarify its suitability for diagnosis of IIH. METHODS: nICP was calculated using continuous signals of arterial blood pressure and cerebral blood flow velocity, a method previously introduced by the authors. In thirteen patients (f = 11, m = 2; age: 36 ± 10 years), nICP was assessed 1 h prior to LP. If LP was >20 cmH2O (~15 mmHg), lumbar drainage was performed, LP was measured again, and nICP was reassessed. RESULTS: In six patients, LP and nICP were compared after lumbar drainage. In three patients, assessment of nICP versus LP was repeated. In total, LP and nICP correlated with R = 0.82 (p < 0.001; N = 22). Mean difference of ICP-nICP was 0.8 ± 3.7 mmHg. Presuming 15 mmHg as critical threshold for indication of lumbar drainage in 20 of 22 cases, the clinical implications would have been the same in both methods. CONCLUSION: TCD-based ICP assessment seems to be a promising method for pre-diagnosis of increased LP and might prevent the need for lumbar puncture if nICP is low.

Arterial and Venous Cerebral Blood Flow Velocities in Healthy Volunteers.

Transcranial Doppler ultrasound (TCD) enables assessment of brain hemodynamics through insonation of cerebral arteries and veins. Few studies have investigated whether the normal ranges of flow velocities in both arterial and venous compartments may be affected by age and sex.The purpose of this study was to determine the normal blood flow velocities across different sex and age subgroups in a cohort of healthy volunteers by studying the middle cerebral arteries (MCAs) and the straight sinus (SS).A total of 122 healthy volunteers undergoing preanesthetic assessment were recruited at Galliera Hospital in Genoa, Italy. The cohort was stratified for sex (males and females) and for age (18-44 years, 45-64 years, and ≥65 years). Data on systolic, diastolic, and mean flow velocities (FVs, FVd, and FVm, respectively) in the MCA and peak venous flow velocity in the SS (FVVs) were collected from each volunteer.The arterial FVs and FVm were significantly higher in males than in females; FVs, FVm, FVd, and FVVs increased across the age spectrum, especially in the elderly female population.Our findings suggest that there are differences in cerebrovascular flow velocities due to age and sex, which may be correlated to hormonal variations during the lifespan.

Variability of the Optic Nerve Sheath Diameter on the Basis of Sex and Age in a Cohort of Healthy Volunteers.

Many studies have demonstrated that the optic nerve sheath diameter (ONSD) is a good indicator of intracranial pressure (ICP). There are uncertainties regarding the optimal ONSD threshold, considering age and sex differences in the healthy population, and these differences could lead to uncertainties in evaluation of ONSD in pathological conditions.The aim of this prospective observational study was to investigate if age and sex could influence ONSD in a cohort of healthy Italian volunteers recruited during preanesthetic assessment for low-risk surgical procedures.The population was stratified for sex (males versus females) and for age (18-44 years, 45-64 years, and ≥65 years). The axial and longitudinal ONSD diameters were measured by two trained investigators.A significant difference in ONSD between males and females was found (median 4.2 (interquartile range 3.9-4.6) versus 4.1 (interquartile range 3.6-4.2) mm, P = 0.01), and a positive correlation between ONSD and age was found (R = 0.50, P < 0.0001).It was concluded that ONSD increases with age and is significantly larger in the healthy male population. These discrepancies should be taken into consideration when ONSD measurement is performed.

Brain Hypoxia Secondary to Diffusion Limitation in Hypoxic Ischemic Brain Injury Postcardiac Arrest.

OBJECTIVES: We sought to characterize 1) the difference in the diffusion gradient of cellular oxygen delivery and 2) the presence of diffusion limitation physiology in hypoxic-ischemic brain injury patients with brain hypoxia, as defined by parenchymal brain tissue oxygen tension less than 20 mm Hg versus normoxia (brain tissue oxygen tension > 20 mm Hg). DESIGN: Post hoc subanalysis of a prospective study in hypoxic-ischemic brain injury patients dichotomized into those with brain hypoxia versus normoxia. SETTING: Quaternary ICU. PATIENTS: Fourteen adult hypoxic-ischemic brain injury patients after cardiac arrest. INTERVENTIONS: Patients underwent monitoring with brain oxygen tension, intracranial pressure, cerebral perfusion pressure, mean arterial pressure, and jugular venous bulb oxygen saturation. Data were recorded in real time at 300Hz into the ICM+ monitoring software (Cambridge University Enterprises, Cambridge, United Kingdom). Simultaneous arterial and jugular venous bulb blood gas samples were recorded prospectively. MEASUREMENTS AND MAIN RESULTS: Both the normoxia and hypoxia groups consisted of seven patients. In the normoxia group, the mean brain tissue oxygen tension, jugular venous bulb oxygen tension, and cerebral perfusion pressure were 29 mm Hg (SD, 9), 45 mm Hg (SD, 9), and 80 mm Hg (SD, 7), respectively. In the hypoxia group, the mean brain tissue oxygen tension, jugular venous bulb oxygen to brain tissue oxygen tension gradient, and cerebral perfusion pressure were 14 mm Hg (SD, 4), 53 mm Hg (SD, 8), and 72 mm Hg (SD, 6), respectively. There were significant differences in the jugular venous bulb oxygen tension-brain oxygen tension gradient (16 mm Hg [sd, 6] vs 39 mm Hg SD, 11]; p < 0.001) and in the relationship of jugular venous bulb oxygen tension-brain oxygen tension gradient to cerebral perfusion pressure (p = 0.004) when comparing normoxia to hypoxia. Each 1 mm Hg increase in cerebral perfusion pressure led to a decrease in the jugular venous bulb oxygen tension-brain oxygen tension gradient by 0.36 mm Hg (95% CI, -0.54 to 0.18; p < 0.001) in the normoxia group, but no such relation was demonstrable in the hypoxia group. CONCLUSIONS: In hypoxic-ischemic brain injury patients with brain hypoxia, there is an elevation in the jugular venous bulb oxygen tension-brain oxygen tension gradient, which is not modulated by changes in cerebral perfusion pressure.

Transcranial Doppler as a non-invasive method to estimate cerebral perfusion pressure in children with severe traumatic brain injury.

INTRODUCTION: Cerebral perfusion pressure (CPP) is one of the most important parameters in preventing ischemic brain insults. Guidelines have used CPP values to guide treatment of traumatic brain injury (TBI) for many years. We tested the feasibility of a novel non-invasive method for CPP estimation (nCPP) in children with severe TBI. METHODS: Retrospective analysis of prospectively monitored pediatric TBI patients with invasive intracranial pressure (ICP) monitoring, arterial blood pressure, and Transcranial Doppler (TCD) studies was performed daily. A novel estimator of CPP (nCPP) was calculated using TCD-spectral accounting method. We analyzed the correlation coefficient and correlation in time domain between CPP and nCPP, prediction ability of nCPP to detect low CPP, and the confidence intervals for CPP prediction (95% CI). RESULTS: We retrospectively analyzed 69 TCD recordings from 19 children (median age 15 years, range 3-16 years). There was a good correlation between CPP and nCPP (Spearman correlation coefficient, R = 0.67 (p < 0.0001), and a good mean correlation in time domain (R = 0.55 ± 0.42). The ability of nCPP to predict values of CPP below 70 mmHg was excellent as demonstrated by an area under the curve of 0.908 (95% CI = 0.83-0.98) using a receiver operating curve analysis. Bland-Altman analysis revealed that nCPP overestimated CPP by 19.61 mmHg with a wide 95% CI of ± 40.4 mmHg. CONCLUSIONS: nCPP monitoring with TCD appears to be a feasible method for CPP assessment in pediatric TBI. The novel spectral CPP tested in this study has a decent correlation with invasive CPP and can predict low CPP with excellent accuracy at the 70-mmHg threshold.

Ultrasound non-invasive intracranial pressure assessment in paediatric neurocritical care: a pilot study.

BACKGROUND: The assessment of intracranial pressure (ICP) is essential in the management of neurocritical care paediatric patients. The gold standard for invasive ICP is an intraventricular catheter or intraparenchymal microsensor but is invasive and carries some risks. Therefore, a non-invasive method for measuring ICP (nICP) would be desirable especially in the paediatric population. The aim of this study is to assess the relationship between ICP and different ultrasound-based methods in neurocritical care paediatric patients. METHODS: Children aged < 16 years with indication for invasive ICP monitoring were prospectively enrolled. The following non-invasive methods were compared with the invasive gold standard: optic nerve sheath diameter ultrasound (ONSD)-derived nICP (nICPONSD); arterial TCD-derived pulsatility index (PIa) and a method based on the diastolic component of the TCD cerebral blood flow velocity and mean arterial blood pressure (nICPFVd). RESULTS: We analysed 107 measurements from 10 paediatric patients. Results from linear regression demonstrated that, among the nICP methods, ONSD has the best correlation with ICP (r = 0.852 (p < 0.0001)). Results from receiving operator curve analysis demonstrated that using a threshold of 15 mmHg, ONSD has and area under the curve (AUC) of 0.94 (95% CI = 0.892-0.989), with best threshold at 3.85 mm (sensitivity = 0.811; specificity = 0.939). CONCLUSIONS: Our preliminary results suggested that ONSD ultrasonography presents the best accuracy to assess ICP among the methods studied. Given its non-invasiveness, repeatability and safety, this technique has the potential of representing a valid option as non-invasive tool to assess the risk of intracranial hypertension in the paediatric population.

Observations on the Cerebral Effects of Refractory Intracranial Hypertension After Severe Traumatic Brain Injury.

BACKGROUND: Raised intracranial pressure (ICP) is a prominent cause of morbidity and mortality after severe traumatic brain injury (TBI). However, in the clinical setting, little is known about the cerebral physiological response to severe and prolonged increases in ICP. METHODS: Thirty-three severe TBI patients from a single center who developed severe refractory intracranial hypertension (ICP > 40 mm Hg for longer than 1 h) with ICP, arterial blood pressure, and brain tissue oxygenation (PBTO2) monitoring (subcohort, n = 9) were selected for retrospective review. Secondary parameters reflecting autoregulation (including pressure reactivity index-PRx, which was available in 24 cases), cerebrospinal compensatory reserve (RAP), and ICP pulse amplitude were calculated. RESULTS: PRx deteriorated from 0.06 ± 0.26 a.u. at baseline levels of ICP to 0.57 ± 0.24 a.u. (p < 0.0001) at high levels of ICP (> 50 mm Hg). In 4 cases, PRx was impaired (> 0.25 a.u.) before ICP was raised above 25 mm Hg. Concurrently, PBTO2 decreased from 27.3 ± 7.32 mm Hg at baseline ICP to 12.68 ± 7.09 mm Hg at high levels of ICP (p < 0.001). The pulse amplitude of the ICP waveform increased with increasing ICP but showed an 'upper breakpoint'-whereby further increases in ICP lead to decreases in pulse amplitude-in 6 out of the 33 patients. DISCUSSION: Severe intracranial hypertension after TBI leads to decreased brain oxygenation, impaired pressure reactivity, and changes in the pulse amplitude of ICP. Impaired pressure reactivity may denote increased risk of developing refractory intracranial hypertension in some patients.

The Burden of Brain Hypoxia and Optimal Mean Arterial Pressure in Patients With Hypoxic Ischemic Brain Injury After Cardiac Arrest.

OBJECTIVES: In patients at risk of hypoxic ischemic brain injury following cardiac arrest, we sought to: 1) characterize brain oxygenation and determine the prevalence of brain hypoxia, 2) characterize autoregulation using the pressure reactivity index and identify the optimal mean arterial pressure, and 3) assess the relationship between optimal mean arterial pressure and brain tissue oxygenation. DESIGN: Prospective interventional study. SETTING: Quaternary ICU. PATIENTS: Adult patients with return of spontaneous circulation greater than 10 minutes and a postresuscitation Glasgow Coma Scale score under 9 within 72 hours of cardiac arrest. INTERVENTIONS: All patients underwent multimodal neuromonitoring which included: 1) brain tissue oxygenation, 2) intracranial pressure, 3) jugular venous continuous oximetry, 4) regional saturation of oxygen using near-infrared spectroscopy, and 5) pressure reactivity index-based determination of optimal mean arterial pressure, lower and upper limit of autoregulation. We additionally collected mean arterial pressure, end-tidal CO2, and temperature. All data were captured at 300 Hz using ICM+ (Cambridge Enterprise, Cambridge, United Kingdom) brain monitoring software. MEASUREMENTS AND MAIN RESULTS: Ten patients (7 males) were included with a median age 47 (range 20-71) and return to spontaneous circulation 22 minutes (12-36 min). The median duration of monitoring was 47 hours (15-88 hr), and median duration from cardiac arrest to inclusion was 15 hours (6-44 hr). The mean brain tissue oxygenation was 23 mm Hg (SD 8 mm Hg), and the mean percentage of time with a brain tissue oxygenation below 20 mm Hg was 38% (6-100%). The mean pressure reactivity index was 0.23 (0.27), and the percentage of time with a pressure reactivity index greater than 0.3 was 50% (12-91%). The mean optimal mean arterial pressure, lower and upper of autoregulation were 89 mm Hg (11), 82 mm Hg (8), and 96 mm Hg (9), respectively. There was marked between-patient variability in the relationship between mean arterial pressure and indices of brain oxygenation. As the patients' actual mean arterial pressure approached optimal mean arterial pressure, brain tissue oxygenation increased (p < 0.001). This positive relationship did not persist when the actual mean arterial pressure was above optimal mean arterial pressure. CONCLUSIONS: Episodes of brain hypoxia in hypoxic ischemic brain injury are frequent, and perfusion within proximity of optimal mean arterial pressure is associated with increased brain tissue oxygenation. Pressure reactivity index can yield optimal mean arterial pressure, lower and upper limit of autoregulation in patients following cardiac arrest.

Changes in hemodynamics, cerebral oxygenation and cerebrovascular reactivity during the early transitional circulation in preterm infants.

BACKGROUND: Changes in systemic and cerebral hemodynamics in preterm infants during early transitional circulation are complex and may differ between infants with or without intraventricular hemorrhage (IVH). METHOD: In total, 43 infants born at median (range) 25 + 5 (23 + 3-31) had continuous near-infrared spectroscopy (NIRS) monitoring of tissue oxygenation index (TOI) and cerebrovascular reactivity within the first 48 h of life. Measurements of left and right cardiac outputs (LVO, RVO) and patent ductus arteriosus (PDA) were collected at 6, 12, 24, and 48 h of life. RESULTS: LVO increased within the first 48 h in the IVH (P = 0.007) and no-IVH (P < 0.001) groups. The pattern of change in LVO and RVO was not different between these two groups. TOI was lower in the IVH (P < 0.001) group. A positive correlation between TOI and LVO (P = 0.003) and a negative correlation between the tissue oxygen reactivity index (TOx) and LVO (P = 0.04) were observed at 24 h of life in the IVH group. PDA diameter was not different between IVH groups at any time interval. CONCLUSION: Cerebral oxygenation was lower and cerebrovascular reactivity was passive to systemic blood flow at 24 h in infants who developed an IVH.

Cerebrovascular assessment of patients undergoing shoulder surgery in beach chair position using a multiparameter transcranial Doppler approach.

Although the beach-chair position (BCP) is widely used during shoulder surgery, it has been reported to associate with a reduction in cerebral blood flow, oxygenation, and risk of brain ischaemia. We assessed cerebral haemodynamics using a multiparameter transcranial Doppler-derived approach in patients undergoing shoulder surgery. 23 anaesthetised patients (propofol (2 mg/kg)) without history of neurologic pathology undergoing elective shoulder surgery were included. Arterial blood pressure (ABP, monitored with a finger-cuff plethysmograph calibrated at the auditory meatus level) and cerebral blood flow velocity (FV, monitored in the middle cerebral artery) were recorded in supine and in BCP. All subjects underwent interscalene block ipsilateral to the side of FV measurement. We evaluated non-invasive intracranial pressure (nICP) and cerebral perfusion pressure (nCPP) calculated with a black-box mathematical model; critical closing pressure (CrCP); diastolic closing margin (DCM-pressure reserve available to avoid diastolic flow cessation); cerebral autoregulation index (Mxa); pulsatility index (PI). Significant changes occured for DCM [mean decrease of 6.43 mm Hg (p = 0.01)] and PI [mean increase of 0.11 (p = 0.05)]. ABP, FV, nICP, nCPP and CrCP showed a decreasing trend. Cerebral autoregulation was dysfunctional (Mxa > 0.3) and PI deviated from normal ranges (PI > 0.8) in both phases. ABP and nCPP values were low (< 60 mm Hg) in both phases. Changes between phases did not result in CrCP reaching diastolic ABP, therefore DCM did not reach critical values (≤ 0 mm Hg). BCP resulted in significant cerebral haemodynamic changes. If left untreated, reduction in cerebral blood flow may result in brain ischaemia and post-operative neurologic deficit.