Changes In Cerebral Perfusion Pressure Research Articles

Cerebral perfusion pressure and behavior monitoring in freely moving rats.

Cerebral perfusion pressure (CPP) is the net pressure gradient that drives oxygen delivery to cerebral tissue. It is the difference between the mean arterial pressure (MAP) and the intracranial pressure (ICP). As CPP is a calculated value, MAP and ICP must be measured simultaneously. In research models, anesthetized and acute monitoring is incapable of providing a realistic picture of the relationship between ICP and MAP under physiological and/or pathophysiological conditions. For long-term monitoring of both pressures, the principle of telemetry can be used. The aim of this study was to map changes in CPP and spontaneous behavior using continuous pressure monitoring and video recording for 7 days under physiological conditions (group C - 8 intact rats) and under altered brain microenvironment induced by brain edema (group WI - 8 rats after water intoxication) and neuroprotection with methylprednisolone - MP (group WI+MP - 8 rats with MP 100 mg/kg b.w. applicated intraperitoneally during WI). The mean CPP values in all three groups were in the range of 40-60 mm Hg. For each group of rats, the percentage of time that the rats spent during the 7 days in movement pattern A (standard movement stereotype) or B (atypical movement) was defined. Even at very low CPP values, the standard movement stereotype (A) clearly dominated over the atypical movement (B) in all rats. There was no significant difference between control and experimental groups. Chronic CPP values with correlated behavioral type may possibly answer the question of whether there is a specific, universal, optimal CPP at all.

Limitations of prone positioning in patients with aneurysmal subarachnoid hemorrhage and concomitant respiratory failure

ObjectiveProne positioning (PP) is an established treatment modality for respiratory failure. After aneurysmal subarachnoid hemorrhage (aSAH), PP is rarely performed considering the risk of intracranial hypertension. The aim of this study was to analyze the effects of PP on intracranial pressure (ICP), cerebral perfusion pressure (CPP) and cerebral oxygenation following aSAH. Patients and methods: Demographic and clinical data of aSAH patients admitted over a 6-year period and treated with PP due to respiratory insufficiency were retrospectively analyzed. ICP, CPP, brain tissue oxygenation (pBrO2), respiratory parameters and ventilator settings were analyzed before and during PP. ResultsThirty patients receiving invasive multimodal neuromonitoring were included. Overall, 97 PP sessions were performed. Mean arterial oxygenation and pBrO2 increased significantly during PP. We found a significant increase in median ICP compared to the baseline level in supine position. No significant changes in CPP were observed. Five PP sessions had to be terminated early due to medically refractory ICP-crisis. The affected patients were younger (p = 0.02) with significantly higher baseline ICP values (p = 0.009). Baseline ICP correlates significantly (p < 0.001) with ICP 1 h (R: 0.57) and 4 h (R: 0.55) after onset of PP. ConclusionPP in aSAH patients with respiratory insufficiency is an effective therapeutic option improving arterial and global cerebral oxygenation without compromising CPP. The significant increase in ICP was moderate in most sessions. However, as some patients experience intolerable ICP crises during PP, continuous ICP-Monitoring is considered mandatory. Patients with elevated baseline ICP and reduced intracranial compliance should not be considered for PP.

Quantification of Cerebral Vascular Autoregulation Immediately Following Resuscitation from Cardiac Arrest.

Cerebral vascular autoregulation is impaired following resuscitation from cardiac arrest (CA), and its quantification may allow assessing CA-induced brain injury. However, hyperemia occurring immediately post-resuscitation limits the application of most metrics that quantify autoregulation. Therefore, to characterize autoregulation during this critical period, we developed three novel metrics based on how the cerebrovascular resistance (CVR) covaries with changes in cerebral perfusion pressure (CPP): (i)θCVR, which quantifies the CVR vs CPP gradient, (ii) a CVR-based transfer function analysis, and (iii) CVRx, the correlation coefficient between CPP and CVR. We tested these metrics in a model of asphyxia induced CA and resuscitation using seven adult male Wistar rats. Mean arterial pressure (MAP) and cortical blood flow recorded for 30min post-resuscitation via arterial cannulation and laser speckle contrast imaging, were used as surrogates of CPP and cerebral blood flow (CBF), while CVR was computed as the CPP/CBF ratio. Using our metrics, we found that the status of cerebral vascular autoregulation altered substantially during hyperemia, with changes spread throughout the 0-0.05Hz frequency band. Our metrics push the boundary of how soon autoregulation can be assessed, and if validated against outcome markers, may help develop a reliable metric of brain injury post-resuscitation.

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 15cmH2O) 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 15cmH2O. Results are expressed as median (interquartile range). Results: Twenty-five patients were included in this study. The median age was 65years (46-73). PEEP increase from 5 to 15cmH2O 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.

Hypertonic Saline Solution versus Mannitol in Children with Intracranial Hypertension: A Systematic Review and Meta-Analysis (P11-7.002)

<h3>Objective:</h3> We aimed to perform a systematic review and meta-analysis on the efficacy of hypertonic saline (HS) versus mannitol (MAN), as hyperosmolar agents, in children with elevated intracranial pressure. <h3>Background:</h3> Hyperosmolar therapy may reduce intracranial hypertension (IH) and act as a lifesaving method in critically ill patients with IH. There is no established superiority of either HS or MAN, the most frequently used agents, in pediatric patients. <h3>Design/Methods:</h3> PubMed, Embase, and Cochrane databases were searched for studies and abstracts published up to October 1st, 2022. Studies were excluded if boluses of HS or MAN were held in patients undergoing elective procedures. The outcomes of interest were mortality; changes in intracranial pressure (ICP); and changes in cerebral perfusion pressure (CPP). <h3>Results:</h3> Six studies with 819 patients were included. The mean patient age ranged from 9 months to 13.5 years. Mortality was not significantly different between the HS (15.6%) and the MAN (21.6%) groups (risk ratio [RR] 0.66; 95% confidence interval [CI] 0.44,0.99; p=0.05). There were also no significant changes in ICP (standardized mean difference −0.25; 95% CI −0.90,0.40; p=0.45) or CPP (standardized mean difference 0.20; 95% CI −0.29,0.68; p=0.42) between patients treated with HS or MAN. <h3>Conclusions:</h3> In this meta-analysis including 819 children with elevated intracranial pressure, there was no difference in mortality, ICP, or CPP between patients treated with HS or MAN. <b>Disclosure:</b> Mr. Menegaz de Almeida has nothing to disclose. Miss Oliveira has nothing to disclose. Miss Viana has nothing to disclose. Dr. Araujo has nothing to disclose. Ms. Oliveira has nothing to disclose. Ms. Dantas has nothing to disclose. Ms. Rodrigues has nothing to disclose. Miss Silva has nothing to disclose. Miss Cordeiro Rocha has nothing to disclose. Dr. Campello Jorge has nothing to disclose. Ms. Godoi has nothing to disclose. Mrs. Reis Marques has nothing to disclose. Mrs. Garcia has nothing to disclose. Miss Barreiros has nothing to disclose. Miss Toguchi has nothing to disclose. Mr. Dos Santos-Bezerra has nothing to disclose. Dr. Polverini has nothing to disclose.

Volatile Sedation With Isoflurane in Neurocritical Care Patients After Poor-grade Aneurysmal Subarachnoid Hemorrhage

Volatile sedation after aneurysmal subarachnoid hemorrhage (aSAH) promises several advantages, but there are still concerns regarding intracranial hypertension due to vasodilatory effects. We prospectively analyzed cerebral parameters during the switch from intravenous to volatile sedation with isoflurane in patients with poor-grade (World Federation of Neurosurgical Societies grade 4-5) aSAH. Eleven patients were included in this prospective observational study. Between day 3 and 5 after admission, intravenous sedation was switched to isoflurane using the Sedaconda Anesthetic Conserving Device (Sedana Medical, Danderyd, Sweden). Intracranial pressure (ICP), cerebral perfusion pressure (CPP), brain tissue oxygenation (PBrO2), cerebral mean flow velocities (MFVs; transcranial Doppler ultrasound) and regional cerebral oxygen saturation (rSO2, near-infrared spectroscopy monitoring), as well as cardiopulmonary parameters were assessed before and after the sedation switch (-12 to+12 hours). Additionally, perfusion computed tomography data during intravenous and volatile sedation were analyzed retrospectively for changes in cerebral blood flow. There were no significant changes in mean ICP, CPP, and PBrO2 after the sedation switch to isoflurane. Mean rSO2 showed a non-significant trend towards higher values, and mean MFV in the middle cerebral arteries increased significantly after the initiation of volatile sedation. Isoflurane sedation resulted in a significantly increased norepinephrine administration. Despite an increase in mean inspiratory pressure, we observed a significant increase in mean partial arterial pressure of carbon dioxide. Isoflurane sedation does not compromise ICP or cerebral oxygenation in poor-grade aSAH patients, but the significant depression of CPP could limit the use of volatiles in case of hemodynamic instability or high vasopressor demand.

Cerebrovascular impedance estimation with near-infrared and diffuse correlation spectroscopy.

Cerebrovascular impedance (CVI) is related to cerebral autoregulation (CA), which is the mechanism of the brain to maintain near-constant cerebral blood flow (CBF) despite changes in cerebral perfusion pressure (CPP). Changes in blood vessel impedance enable the stabilization of blood flow. Due to the interplay between CVI and CA, assessment of CVI may enable quantification of CA and may serve as a biomarker for cerebral health. We developed a method to quantify CVI based on a combination of diffuse correlation spectroscopy (DCS) and continuous wave (CW) near-infrared spectroscopy (NIRS). Data on healthy human volunteers were used to validate the method. A combined high-speed DCS-NIRS system was developed, allowing for simultaneous, noninvasive blood flow, and volume measurements in the same tissue compartment. Blood volume was used as a surrogate measurement for blood pressure and CVI was calculated as the spectral ratio of blood volume and blood flow changes. This technique was validated on six healthy human volunteers undergoing postural changes to elicit CVI changes. Averaged across the six subjects, a decrease in CVI was found for a head of bed (HOB) tilting of . These impedance changes were reversed when returning to the horizontal (0deg) HOB baseline. We developed a combined DCS-NIRS system, which measures CBF and volume changes, which we demonstrate can be used to measure CVI. Using CVI as a metric of CA may be beneficial for assessing cerebral health, especially in patients where CPP is altered.

Cerebrovascular Impedance as a Function of Cerebral Perfusion Pressure.

Goal: Cerebrovascular impedance is modulated by a vasoactive autoregulative mechanism in response to changes in cerebral perfusion pressure. Characterization of impedance and the limits of autoregulation are important biomarkers of cerebral health. We developed a method to quantify impedance based on the spectral content of cerebral blood flow and volume at the cardiac frequency, measured with diffuse optical methods. Methods: In three non-human primates, we modulated cerebral perfusion pressure beyond the limits of autoregulation. Cerebral blood flow and volume were measured with diffuse correlation spectroscopy and near-infrared spectroscopy, respectively. Results: We show that impedance can be used to identify the lower and upper limits of autoregulation. Conclusions: This impedance method may be an alternative method to measure autoregulation and a way of assessing cerebral health non-invasively at the clinical bedside.

The contribution of intracranial pressure to human dynamic cerebral autoregulation after acute brain injury.

Cerebral perfusion pressure (CPP) is normally expressed by the difference between mean arterial blood pressure (MAP) and intracranial pressure (ICP) but comparison of the separate contributions of MAP and ICP to human cerebral blood flow autoregulation has not been reported. In ABI patients, internal jugular vein compression (IJVC) was performed for 60 s. Dynamic cerebral autoregulation (dCA) was assessed in recordings of middle cerebral artery blood velocity (MCAv, transcranial Doppler), and invasive measurements of MAP and ICP. Patients were separated according to injury severity as having whole/undamaged skull, large fractures or craniotomies, or following decompressive craniectomy. Glasgow coma score was not different for the three groups. IJVC induced changes in MCAv, MAP, ICP, and CPP in all three groups. The MCAv response to step changes in MAP and ICP expressed the dCA response to these two inputs, and was quantified with the autoregulation index (ARI). In 85 patients, ARI was lower for the ICP input as compared to the MAP input (2.25 ± 2.46 vs 3.39 ± 2.28; p<0.0001), and particularly depressed in the DC group (n=24, 0.35 ± 0.62 vs 2.21 ± 1.96; p<0.0005). In patients with ABI, the dCA response to changes in ICP is less efficient than corresponding responses to MAP changes. These results should be taken into consideration in studies aimed to optimize dCA by manipulation of CPP in neurocritical patients.

Non-Invasive Spectroscopy for Measuring Cerebral Tissue Oxygenation and Metabolism as a Function of Cerebral Perfusion Pressure.

Near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) measure cerebral hemodynamics, which in turn can be used to assess the cerebral metabolic rate of oxygen (CMRO2) and cerebral autoregulation (CA). However, current mathematical models for CMRO2 estimation make assumptions that break down for cerebral perfusion pressure (CPP)-induced changes in CA. Here, we performed preclinical experiments with controlled changes in CPP while simultaneously measuring NIRS and DCS at rest. We observed changes in arterial oxygen saturation (~10%) and arterial blood volume (~50%) with CPP, two variables often assumed to be constant in CMRO2 estimations. Hence, we propose a general mathematical model that accounts for these variations when estimating CMRO2 and validate its use for CA monitoring on our experimental data. We observed significant changes in the various oxygenation parameters, including the coupling ratio (CMRO2/blood flow) between regions of autoregulation and dysregulation. Our work provides an appropriate model and preliminary experimental evidence for the use of NIRS- and DCS-based tissue oxygenation and metabolism metrics for non-invasive diagnosis of CA health in CPP-altering neuropathologies.

Long-term effects of multiple concussions on prefrontal cortex oxygenation during repeated squat-stands in retired contact sport athletes

ABSTRACT Background This study investigated the long-term effects of multiple concussions on prefrontal cortex oxygenation using near-infrared spectroscopy (NIRS) during a squat-stand maneuver that activated dynamic cerebral autoregulation. Methods Active male retired contact sport athletes with a history of 3+ concussions (mTBI; n = 55), and active retired athletes with no concussion history (CTRL; n = 29) were recruited. Participants completed a 5-min squat-stand maneuve (10-s squat, 10-s stand, 0.05 Hz; 15 times). Oxygenated (O2Hb), deoxygenated (HHb), total (tHb) hemoglobin, and hemoglobin difference (HbDiff) were analyzed through the change in maximal and minimal values during the test (∆MAX), Z-scores, and standard deviations. Results mTBI group showed left prefrontal cortex O2Hb ∆MAX (p = 0.046) and HbDiff ∆MAX (p = 0.018) were significantly higher. Within-group analyses showed significantly higher left HHb ∆MAX (p = 0.003) and lower left HbDiff Z-scores (p = 0.010) only in the mTBI group. The CTRL group demonstrated significantly lower left HbDiff SD (p = 0.039), tHb Z-scores (p = 0.030), and HbDiff ∆MAX (p = 0.037) compared to right prefrontal cortex response. Conclusion These preliminary results suggest changes in prefrontal cortex oxygenation potentially affecting the brain’s ability to adapt to changing cerebral perfusion pressure after multiple previous concussions.

The comparative effects of desflurane and isoflurane on intraoperative cerebral hemodynamics, cardiovascular changes, and post-operative recovery in patients undergoing craniotomy for supratentorial tumors

Background: Preserving hemodynamic stability, providing a slack brain, and enabling early recovery are the main criteria of neuroanesthesia. The most commonly used volatile anesthetic for neurosurgeries is isoflurane due to its favorable effects on cerebral blood flow and intracranial pressure. On the other hand, desflurane, having lower blood gas partition coefficient, favors rapid recovery from anesthesia. Aims and Objectives: This study was conducted for comparing the effects of desflurane and isoflurane on intraoperative cerebral and cardiovascular hemodynamics and post-operative recovery among patients with supratentorial neoplasms posted for craniotomy. Materials and Methods: A total of 52 patients aged 20–60, ASA I and II, scheduled for craniotomy under general anesthesia, were randomized into Group I (isoflurane) and Group D (desflurane). All patients received standardized anesthetic protocol and anesthesia was maintained either with isoflurane or desflurane (≤1 MAC). Lumbar cerebrospinal fluid pressure (LCSFP) and cerebral perfusion pressure (CPP) were monitored every 5 min till dura was opened and the degree of dural tension and brain swelling were assessed by neurosurgeons, blinded to the study, at the time of dural opening. Perioperative heart rate, mean arterial pressure, and post-operative recovery time were also noted. Results: No statistically significant changes were observed among two groups regarding change in LCSFP, CPP, dural tension, brain swelling, and cardiovascular changes. Post-operative recovery time was significantly shorter in desflurane group (P&lt;0.001) than isoflurane group. Conclusion: Desflurane and isoflurane both can be used safely in maintaining neuroanesthesia. However, due to a significantly faster recovery which facilitates early post-operative neurological assessment, desflurane may be considered a better alternative to isoflurane.

Optimal Cerebral Perfusion Pressure During Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

The recommendation of induced hypertension for delayed cerebral ischemia treatment after aneurysmal subarachnoid hemorrhage has been challenged recently and ideal pressure targets are missing. A new concept advocates an individual cerebral perfusion pressure where cerebral autoregulation functions best to ensure optimal global perfusion. We characterized optimal cerebral perfusion pressure at time of delayed cerebral ischemia and tested the conformity of induced hypertension with this target value. Retrospective analysis of prospectively collected data. University hospital neurocritical care unit. Thirty-nine aneurysmal subarachnoid hemorrhage patients with invasive neuromonitoring (20 with delayed cerebral ischemia, 19 without delayed cerebral ischemia). Induced hypertension greater than 180 mm Hg systolic blood pressure. Changepoint analysis was used to calculate significant changes in cerebral perfusion pressure, optimal cerebral perfusion pressure, and the difference of cerebral perfusion pressure and optimal cerebral perfusion pressure 48 hours before delayed cerebral ischemia diagnosis. Optimal cerebral perfusion pressure increased 30 hours before the onset of delayed cerebral ischemia from 82.8 ± 12.5 to 86.3 ± 11.4 mm Hg (p < 0.05). Three hours before delayed cerebral ischemia, a changepoint was also found in the difference of cerebral perfusion pressure and optimal cerebral perfusion pressure (decrease from -0.2 ± 11.2 to -7.7 ± 7.6 mm Hg; p < 0.05) with a corresponding increase in pressure reactivity index (0.09 ± 0.33 to 0.19 ± 0.37; p < 0.05). Cerebral perfusion pressure at time of delayed cerebral ischemia was lower than in patients without delayed cerebral ischemia in a comparable time frame (cerebral perfusion pressure delayed cerebral ischemia 81.4 ± 8.3 mm Hg, no delayed cerebral ischemia 90.4 ± 10.5 mm Hg; p < 0.05). Inducing hypertension resulted in a cerebral perfusion pressure above optimal cerebral perfusion pressure (+12.4 ± 8.3 mm Hg; p < 0.0001). Treatment response (improvement of delayed cerebral ischemia: induced hypertension+ [n = 15] or progression of delayed cerebral ischemia: induced hypertension- [n = 5]) did not correlate to either absolute values of cerebral perfusion pressure or optimal cerebral perfusion pressure, nor the resulting difference (cerebral perfusion pressure [p = 0.69]; optimal cerebral perfusion pressure [p = 0.97]; and the difference of cerebral perfusion pressure and optimal cerebral perfusion pressure [p = 0.51]). At the time of delayed cerebral ischemia occurrence, there is a significant discrepancy between cerebral perfusion pressure and optimal cerebral perfusion pressure with worsening of autoregulation, implying inadequate but identifiable individual perfusion. Standardized induction of hypertension resulted in cerebral perfusion pressures that exceeded individual optimal cerebral perfusion pressure in delayed cerebral ischemia patients. The potential benefit of individual blood pressure management guided by autoregulation-based optimal cerebral perfusion pressure should be explored in future intervention studies.

Changes in neurovascular coupling with cerebral perfusion pressure indicate a link to cerebral autoregulation

Cerebral autoregulation ensures a stable average blood supply to brain tissue across steady state cerebral perfusion pressure (CPP) levels. Neurovascular coupling, in turn, relies on sufficient blood flow to meet neuronal demands during activation. These mechanisms break down in pathologies where extreme levels of CPP can cause dysregulation in cerebral blood flow. Here, we experimentally tested the influence of changes in CPP on neurovascular coupling in a hydrocephalus-type non-human primate model (n = 3). We recorded local neural and vascular evoked responses to a checkerboard visual stimulus, non-invasively, using electroencephalography and near-infrared spectroscopy respectively. The evoked signals showed changes in various waveform features in the visual evoked potentials and the hemodynamic responses, with CPP. We further used these signals to fit for a hemodynamic response function (HRF) to describe neurovascular coupling. We estimated n = 26 distinct HRFs at a subset of CPP values ranging from 40–120 mmHg across all subjects. The HRFs, when compared to a subject dependent healthy baseline (CPP 70–90 mmHg) HRF, showed significant changes in shape with increasing CPP (ρCPP = −0.55, p-valueCPP = 0.0049). Our study provides preliminary experimental evidence on the relationship between neurovascular coupling and CPP changes, especially when beyond the limits of static autoregulation.

Assessment of Optimal Arterial Pressure with Near-Infrared Spectroscopy in Traumatic Brain Injury Patients.

In patients with severe traumatic brain injury (TBI), simultaneous measurement of intracranial and arterial blood pressure (ICP and ABP, respectively) allows monitoring of cerebral perfusion pressure (CPP) and the assessment of cerebral autoregulation (CA). CPP, a difference between ICP and ABP, is the pressure gradient that drives oxygen delivery to cerebral tissue. CA is the ability of cerebral vasculature to maintain stable blood flow despite changes in CPP and thus, is an important homeostatic mechanism. Pressure reactivity index (PRx), a moving Pearson's correlation between slow waves in ICP and ABP, has been most frequently cited in literature over the past two decades as a tool for CA evaluation. However, in some clinical situations, ICP monitoring may be unavailable or contraindicated. In such cases, simultaneous mean arterial pressure (MAP) monitoring and near-infrared spectroscopy (NIRS) can be used for CA assessment by cerebral oximetry index (COx), allowing calculation of the optimal blood pressure (MAPOPT). The purpose of this study was to compare regional oxygen saturation (rSO2)-based CA (COx) with ICP/ABP-based CA (PRx) in TBI patients and to compare MAPOPT derived from both technologies. Three TBI patients were monitored at the bedside to measure CA using both PRx and COx. Patients were monitored daily for up to 3days from TBI. Averaged PRx and COx-, and PRx and COx-based MAPOPT were compared using Pearson's correlation. Bias analysis was performed between these same CA metrics. Correlation between averaged values of COx and PRx was R=0.35, p=0.15. Correlation between optimal MAP calculated for COx and PRx was R=0.49, p<0.038. Bland-Altman analysis showed moderate agreement with a bias of 0.16±0.23 for COx versus PRx and good agreement with a bias of 0.39±7.89 for optimal MAP determined by COx versus PRx. Non-invasive measurement of CA by NIRS (COx) is not correlated with invasive ICP/ABP-based CA (PRx). However, the determination of MAPOPT using COx is correlated with MAPOPT derived from PRx. Obtained results demonstrate that COx is not an acceptable substitute for PRx in TBI patients. However, in some TBI cases, NIRS may be useful in determining MAP determination.

Brain Temperature Influences Intracranial Pressure and Cerebral Perfusion Pressure After Traumatic Brain Injury: A CENTER-TBI Study

BackgroundAfter traumatic brain injury (TBI), fever is frequent. Brain temperature (BT), which is directly linked to body temperature, may influence brain physiology. Increased body and/or BT may cause secondary brain damage, with deleterious effects on intracranial pressure (ICP), cerebral perfusion pressure (CPP), and outcome.MethodsCollaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI), a prospective multicenter longitudinal study on TBI in Europe and Israel, includes a high resolution cohort of patients with data sampled at a high frequency (from 100 to 500 Hz). In this study, simultaneous BT, ICP, and CPP recordings were investigated. A mixed-effects linear model was used to examine the association between different BT levels and ICP. We additionally focused on changes in ICP and CPP during the episodes of BT changes (Δ BT ≥ 0.5 °C lasting from 15 min to 3 h) up or downward. The significance of ICP and CPP variations was estimated with the paired samples Wilcoxon test (also known as Wilcoxon signed-rank test).ResultsTwenty-one patients with 2,435 h of simultaneous BT and ICP monitoring were studied. All patients reached a BT of 38 °C and experienced at least one episode of ICP above 20 mm Hg. The linear mixed-effects model revealed an association between BT above 37.5 °C and higher ICP levels that was not confirmed for lower BT. We identified 149 episodes of BT changes. During BT elevations (n = 79) ICP increased, whereas CPP was reduced; opposite ICP and CPP variations occurred during episodes of BT reduction (n = 70). All these changes were of moderate clinical relevance (increase of ICP of 4.5 and CPP decrease of 7.5 mm Hg for BT rise, and ICP reduction of 1.7 and CPP elevation of 3.7 mm Hg during BT defervescence), even if statistically significant (p < 0.0001). It has to be noted, however, that a number of therapeutic interventions against intracranial hypertension was documented during those episodes.ConclusionsPatients after TBI usually develop BT > 38 °C soon after the injury. BT may influence brain physiology, as reflected by ICP and CPP. An association between BT exceeding 37.5 °C and a higher ICP was identified but not confirmed for lower BT ranges. The relationship between BT, ICP, and CPP become clearer during rapid temperature changes. During episodes of temperature elevation, BT seems to have a significant impact on ICP and CPP.

Trans-Ocular Brain Impedance Indices Predict Pressure Reactivity Index Changes in a Porcine Model of Hypotension and Cerebral Autoregulation Perturbation.

Cerebrovascular autoregulation (CA) is a protective mechanism that enables the cerebral vasculature to automodulate tone in response to changes in cerebral perfusion pressure to ensure constant levels of cerebral blood flow (CBF) and oxygen delivery. CA can be impaired after neurological injury and contributes to secondary brain injury. In this study, we report novel impedance indices using trans-ocular brain impedance (TOBI) during controlled systemic hemorrhage and hypotension to assess CA in comparison with pressure reactivity index (PRx). Yorkshire swine were instrumented to record intracranial pressure (ICP), mean arterial pressure (MAP), and CBF. TOBI was recorded using electrocardiographic electrodes placed on the closed eyelids. Impedance changes (dz) were recorded in response to introducing an alternating current (0.4mA) through the electrodes. MAP, ICP, and CBF were also measured. Animals were subjected to a controlled hemorrhage to remove 30-40% of each animal's total blood volume over 25-35min. Hemorrhage was titrated to reach an MAP of approximately 35mm Hg and end-tidal carbon dioxide above 28mm Hg. PRx was calculated as a moving Pearson correlation between MAP and ICP. TOBI indices were calculated as the amplitude of the respiratory-induced changes in dz. DZx was calculated as a moving Pearson correlation between dz and MAP. TOBI indices (dz and DZx) were compared with hemodynamic indicators and PRx. dz was shown to be highly correlated with MAP, ICP, cerebral perfusion pressure, and CBF (r = - 0.823, - 0.723, - 0.813, and - 0.726), respectively (p < 0.0001). During hemorrhage, cerebral perfusion pressure and CBF had a mean percent decrease (standard deviation) from baseline of - 54.2% (12.5%) and - 28.3% (14.7%), respectively, whereas dz increased by 277% (268%). Receiver operator characteristics and precision-recall curves demonstrated high predictive performance of DZx when compared with PRx with an area under the curve above 0.82 and 0.89 for receiver operator characteristic and precision-recall curves, respectively, with high sensitivity and positive predictive power. TOBI indices appear to track changes in PRx and hemodynamics that affect CA during hemorrhage-induced hypotension. TOBI may offer a suitable, less invasive surrogate to PRx for monitoring and assessing CA.

A novel wireless optical technique for quantitative evaluation of cerebral perfusion pressure in a fluid percussion animal model of traumatic brain injury.

Cerebral perfusion pressure (CPP) calculated by mean arterial pressure (MAP) minus intracranial pressure (ICP) is related to blood flow into the brain and reflects cerebral ischemia and oxygenation indirectly. Near-infrared spectroscopy (NIRS) can assess cerebral ischemia and hypoxia non-invasively and has been widely used in neuroscience. However, the correlation between CPP and NIRS, and its potential application in traumatic brain injury, has seldom been investigated. We used a novel wireless NIRS system and commercial ICP and MAP devices to assess the trauma to rat brains using different impact intensity. The relationship between CPP and NIRS parameters with increasing impact strength were investigated. The results showed that changes in CPP (∆CPP), oxy-hemoglobin {∆[HbO2]}, total-hemoglobin {∆[HbT]}, and deoxy-hemoglobin were inversely proportional to the increase in impact intensity, and the correlations between ∆CPP, NIRS parameters {∆[HbO2], and ∆[HbT]} were significant. The NIRS system can assess cerebral ischemia and oxygenation non-invasively and changes of HbO2 and HbT may be used as reference parameters to assess the level of CPP in an animal model of traumatic brain injury.

Effects of circulatory arrest and cardiopulmonary bypass on cerebral autoregulation in neonatal swine

BackgroundCerebral autoregulation mechanisms help maintain adequate cerebral blood flow (CBF) despite changes in cerebral perfusion pressure. Impairment of cerebral autoregulation, during and after cardiopulmonary bypass (CPB), may increase risk of neurologic injury in neonates undergoing surgery. In this study, alterations of cerebral autoregulation were assessed in a neonatal swine model probing four perfusion strategies.MethodsNeonatal swine (n = 25) were randomized to continuous deep hypothermic cardiopulmonary bypass (DH-CPB, n = 7), deep hypothermic circulatory arrest (DHCA, n = 7), selective cerebral perfusion (SCP, n = 7) at deep hypothermia, or normothermic cardiopulmonary bypass (control, n = 4). The correlation coefficient (LDx) between laser Doppler measurements of CBF and mean arterial blood pressure was computed at initiation and conclusion of CPB. Alterations in cerebral autoregulation were assessed by the change between initial and final LDx measurements.ResultsCerebral autoregulation became more impaired (LDx increased) in piglets that underwent DH-CPB (initial LDx: median 0.15, IQR [0.03, 0.26]; final: 0.45, [0.27, 0.74]; p = 0.02). LDx was not altered in those undergoing DHCA (p > 0.99) or SCP (p = 0.13). These differences were not explained by other risk factors.ConclusionsIn a validated swine model of cardiac surgery, DH-CPB had a significant effect on cerebral autoregulation, whereas DHCA and SCP did not.ImpactApproximately half of the patients who survive neonatal heart surgery with cardiopulmonary bypass (CPB) experience neurodevelopmental delays. This preclinical investigation takes steps to elucidate and isolate potential perioperative risk factors of neurologic injury, such as impairment of cerebral autoregulation, associated with cardiac surgical procedures involving CPB.We demonstrate a method to characterize cerebral autoregulation during CPB pump flow changes in a neonatal swine model of cardiac surgery.Cerebral autoregulation was not altered in piglets that underwent deep hypothermic circulatory arrest (DHCA) or selective cerebral perfusion (SCP), but it was altered in piglets that underwent deep hypothermic CBP.

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, ≤70mmHg.