Brain Tissue Oxygen Research Articles

Effect of anesthesia induction on cerebral tissue oxygen saturation in hypertensive patients: an observational study

ObjectiveIn hypertensive patients, the autoregulation curve shifts rightward, making these patients more sensitive than normotensive individuals to hypotension. Hypotension following the induction of anesthesia has been studied in normotensive patients to determine its effects on brain tissue oxygenation, but not enough studies have examined the effect of hypotension on brain oxygenation in hypertensive patients. The current study aimed to use near-infrared spectroscopy to evaluate brain tissue oxygen saturation after the induction of anesthesia in hypertensive patients, who may have impaired brain tissue oxygen saturation. MethodsThe study included a total of 200 patients aged > 18 years old with ASA I–III. Measurements were taken while the patient was breathing room air, after the induction of anesthesia, when the lash reflex had disappeared following the induction of anesthesia, after intubation, and in the 5th, 10th, and 15th minutes of surgery. The patients were divided into nonhypertensive and hypertensive groups. ResultsThere was a significant difference in age between the groups (p = 0.000). No correlation was found between cerebral tissue oxygen saturation and age (r = 0.015, p = 0.596). Anesthesia induction was observed to decrease mean arterial blood pressure in both groups (p = 0.000). Given these changes, there was no significant difference in brain tissue oxygen saturation between the nonhypertensive and hypertensive groups (p > 0.05). ConclusionThere was no difference between hypertensive and normotensive groups in terms of the change rates in cSO2 values. However, there was a difference between the groups in terms of cSO2 values.

SARS CoV-2 related microvascular damage and symptoms during and after COVID-19: Consequences of capillary transit-time changes, tissue hypoxia and inflammation.

Corona virus disease 2019 (COVID‐19) causes symptoms from multiple organs after infection by severe acute respiratory syndrome corona virus 2 (SARS CoV‐2). They range from early, low blood oxygen levels (hypoxemia) without breathlessness (“silent hypoxia”), delirium, rashes, and loss of smell (anosmia), to persisting chest pain, muscle weakness and ‐pain, fatigue, confusion, memory problems and difficulty to concentrate (“brain fog”), mood changes, and unexpected onset of hypertension or diabetes. SARS CoV‐2 affects the microcirculation, causing endothelial cell swelling and damage (endotheliitis), microscopic blood clots (microthrombosis), capillary congestion, and damage to pericytes that are integral to capillary integrity and barrier function, tissue repair (angiogenesis), and scar formation. Similar to other instances of critical illness, COVID‐19 is also associated with elevated cytokine levels in the systemic circulation. This review examines how capillary damage and inflammation may contribute to these acute and persisting COVID‐19 symptoms by interfering with blood and tissue oxygenation and with brain function. Undetectable by current diagnostic methods, capillary flow disturbances limit oxygen diffusion exchange in lungs and tissue and may therefore cause hypoxemia and tissue hypoxia. The review analyzes the combined effects of COVID‐19‐related capillary damage, pre‐existing microvascular changes, and upstream vascular tone on tissue oxygenation in key organs. It identifies a vicious cycle, as infection‐ and hypoxia‐related inflammation cause capillary function to deteriorate, which in turn accelerates hypoxia‐related inflammation and tissue damage. Finally, the review addresses the effects of low oxygen and high cytokine levels in brain tissue on neurotransmitter synthesis and mood. Methods to assess capillary functions in human organs and therapeutic means to protect capillary functions and stimulate capillary bed repair may prove important for the individualized management of COVID‐19 patients and targeted rehabilitation strategies.

Relationship between Brain Tissue Oxygen Tension and Transcranial Doppler Ultrasonography

Multimodal monitoring of intracranial pressure and brain tissue oxygen tension (PbtO2) have been increasingly used to detect delayed cerebral ischemia (DCI) after subarachnoid hemorrhage. At our center, patients who cannot be easily assessed clinically will undergo intracranial pressure and PbtO2 monitoring via a NEUROVENT-PTO bolt. We aimed to determine whether the Lindegaard ratios (LRs) computed from transcranial Doppler ultrasonography (TCDU) would correlate with, or can predict, the simultaneously recorded PbtO2 value. Patients with aneurysmal subarachnoid hemorrhage, PbtO2 recordings from the middle cerebral artery territory, and simultaneous TCDU scans available from the ipsilateral middle cerebral artery and internal carotid artery from August 2018 to 2019 were included in the present study. The index test result was vasospasm (LR of ≥3) found on TCDU. The reference standard was the presence of regional hypoxia (PbtO2 <20 mm Hg). The PbtO2 results were compared with those from computed tomography angiography as a radiological standard. The predictive values were calculated using a contingency table and receiver operating characteristic curve. A total of 28 patients (6 men and 22 women; age, 59.04 ± 13.75 years) were identified with simultaneous brain tissue oxygen and TCDU recordings available. Of the 28 patients, 7 had cerebral hypoxia (PbtO2 <20 mm Hg). We found no correlation between the PbtO2 measurements and simultaneously recorded LRs (r2= 0.048; P= 0.26). A LR of ≥3 had high specificity (95.24%) for hypoxia but relatively low sensitivity (42.86%; P= 0.037). We find TCDU to be specific for predicting cerebral hypoxia (measured via an intraparenchymal probe). Therefore, it could be a useful and noninvasive tool in the context of preventative DCI monitoring. However, given the low sensitivity, the lack of vasospasm on TCDU should not preclude the possibility of the presence of evolving DCI.

Prone Position Ventilation in Neurologically Ill Patients: A Systematic Review and Proposed Protocol.

Prone positioning has been shown to be a beneficial adjunctive supportive measure for patients who develop acute respiratory distress syndrome. Studies have excluded patients with reduced intracranial compliance, whereby patients with concomitant neurologic diagnoses and acute respiratory distress syndrome have no defined treatment algorithm or recommendations for management. In this study, we aim to determine the safety and feasibility of prone positioning in the neurologically ill patients. A systematic review of the literature, performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses 2009 guidelines, yielded 10 articles for analysis. Using consensus from these articles, in combination with review of multi-institutional proning protocols for patients with nonneurologic conditions, a proning protocol for patients with intracranial pathology and concomitant acute respiratory distress syndrome was developed. Among 10 studies included in the final analysis, we found that prone positioning is safe and feasible in the neurologically ill patients with acute respiratory distress syndrome. Increased intracranial pressure and compromised cerebral perfusion pressure may occur with prone positioning. We propose a prone positioning protocol for the neurologically ill patients who require frequent neurologic examinations and intracranial monitoring. Although elevations in intracranial pressure and reductions in cerebral perfusion pressure do occur during proning, they may not occur to a degree that would warrant exclusion of prone ventilation as a treatment modality for patients with acute respiratory distress syndrome and concomitant neurologic diagnoses. In cases where intracranial pressure, cerebral perfusion pressure, and brain tissue oxygenation can be monitored, prone position ventilation should be considered a safe and viable therapy.

Absolute quantification of cerebral tissue oxygen saturation with multidistance broadband NIRS in newborn brain.

Tissue oximetry with near-infrared spectroscopy (NIRS) is a technique for the measurement of absolute tissue oxygen saturation (StO2). Offering a real-time and non-invasive assessment of brain oxygenation and haemodynamics, StO2 has potential to be used for the assessment of newborn brain injury. Multiple algorithms have been developed to measure StO2, however, issues with low measurement accuracy or extracranial tissue signal contamination remain. In this work, we present a novel algorithm to recover StO2 in the neonate, broadband multidistance oximetry (BRUNO), based on a measurement of the gradient of attenuation against distance measured with broadband NIRS. The performance of the algorithm was compared to two other published algorithms, broadband fitting (BF) and spatially resolved spectroscopy (SRS). The median error when recovering StO2 in light transport simulations on a neonatal head mesh was 0.4% with BRUNO, 4.2% with BF and 9.5% with SRS. BRUNO was more sensitive to brain tissue oxygenation changes, shown in layered head model simulations. Comparison of algorithm performance during full oxygenation-deoxygenation cycles in a homogeneous dynamic blood phantom showed significant differences in the dynamic range of the algorithms; BRUNO recovered StO2 over 0–100%, BF over 0–90% and SRS over 39–80%. Recovering StO2 from data collected in a neonate treated at the neonatal intensive care showed different baseline values; mean StO2 was 64.9% with BRUNO, 67.2% with BF and 73.2% with SRS. These findings highlight the effect of StO2 algorithm selection on oxygenation recovery; applying BRUNO in the clinical care setting could reveal further insight into complex haemodynamic processes occurring during neonatal brain injury.

Cerebrovascular Consequences of Elevated Intracranial Pressure After Traumatic Brain Injury.

We compared various descriptors of cerebral hemodynamics in 517 patients with traumatic brain injury (TBI) who had, on average, elevated (>23mmHg) or normal (<15mmHg) intracranial pressure (ICP). In a subsample of 193 of those patients, transcranial Doppler ultrasound (TCD) recordings were made. Arterial blood pressure (ABP), cerebral blood flow velocity (CBFV), cerebral autoregulation indices based on TCD (the mean flow index (Mx; the coefficient of correlation between the the cerebral perfusion pressure CPP and flow velocity) and the autoregulation index (ARI)), and the pressure reactivity index (PRx) were compared between groups. We also analyzed the TCD-based cerebral blood flow (CBF) index (diastolic CBFV/mean CBFV), the spectral pulsatility index (sPI), and the critical closing pressure (CrCP). Finally, we also looked at brain tissue oxygenation (cerebral oxygen partial tension (PbtO2)) in 109 patients. The mean cerebral perfusion pressure (CPP) was lower in the group with elevated ICP (p<0.01), despite a higher mean arterial pressure (MAP) (p<0.005) and worse autoregulation (as assessed with the Mx, ARI, and PRx indices), greater CrCP, a lower CBF index, and a higher sPI (all with p values of <0.001). Neither the mean CBFV nor PbtO2 reached significant differences between groups. Mortality in the group with elevated ICP was almost three times greater than that in the group with normal ICP (45% versus 17%). Elevated ICP affects cerebral autoregulation. When autoregulation is not working properly, the brain is exposed to ischemic insults whenever CPP falls.

The Changes in Brain Oxygenation During Transcranial Alternating Current Stimulation as Consequences of Traumatic Brain Injury: A Near-Infrared Spectroscopy Study.

The aim was to evaluate the changes in brain tissue oxygenation, assessed by near-infrared spectroscopy (NIRS), during transcranial alternating current stimulation (tACS) in patients with mild and moderate traumatic brain injury (TBI). Nineteen patients with diffuse, blunt, non-severe TBI (mean age 32.7±11.4years; 4 women and 15 men; Glasgow Coma Score before tACS 14.1±0.5) were treated by 10 Hz in-phase tACS applied for 30minutes to the left and right lateral prefrontal cortex at 21days after TBI. Regional cerebral tissue oxygen saturation (SctO2) in the frontal lobes was measured simultaneously by the cerebral oximeter. Significance was preset to P<0.05. The SctO2 values before tACS were not different between hemispheres ~65%. After 15minutes of tACS, a significant (p<0.05) decrease in regional SctO2 was observed with the minimum at the eighth minute of 53.4±3.2% and 53.4±3.2% in the left and right hemispheres, respectively. At the end of the stimulation (30minutes), the hemispheric differences in cerebral oxygen saturation became statistically insignificant again (p>0.05). Therefore, tACS causes a significant decrease in SctO2, probably, due to neuronal activation. Our data indicate that tACS may need to be supplemented with oxygen therapy. Further research is required.

Cerebral oxygenation monitoring in patients during and after cardiac arrest -- a narrative review of current methods and evidence

Hypoxic-ischemic brain injury (HIBI) is a leading cause of mortality in post-cardiac arrest (post-CA) patients who successfully survive the initial cardiopulmonary resuscitation (CPR) but later die in the Intensive Care Unit (ICU). Therefore, a key priority of post-resuscitation ICU care is to prevent and limit the impact of HIBI by optimizing the balance between cerebral oxygen delivery and demand. Traditionally, an optimal systemic oxygen balance is considered to ensure the brain’s oxygen balance. However, the validity of this assumption is uncertain, as the brain constitutes only 2%of the body mass while accounting for approximately 20% of basal oxygen consumption at rest. Hence, there is a real need to monitor cerebral oxygenation realistically. Several imaging and bedside monitoring methods are available for cerebral oxygenation monitoring in post-CA patients. Unfortunately, each of them has its limitations. Imaging methods require transporting a critically ill unstable patient to the scanner. Moreover, they provide an assessment of the oxygenation state only at a particular moment, while brain oxygenation is dynamic. Bedside methods, specifically near-infrared spectroscopy (NIRS), brain tissue oxygen tension (PbtO2), and jugular venous oxygen saturation monitoring (SjvO2), have not often been used in studies involving post-CA patients. Hence there is ambiguity regarding clear recommendations for using these bedside monitors. Presently, the most promising option seems to be using the NIRS as an indicator of effective CPR. We present a narrative review focusing on bedside methods and discuss the evidence for their use in adult patients after cardiac arrest.

Use of Direct Intracranial Pressure and Brain Tissue Oxygen Monitoring in Perioperative Management of Patients with Moyamoya Disease.

Intracranial pressure monitoring and brain tissue oxygen monitoring are commonly used in head injury for goal-directed therapies, but there may be more indications for its use. Moyamoya disease involves progressive stenosis of the arterial circulation and formation of collateral vessels that are at risk of hemorrhage. The risk of ischemic events during revascularization surgery and postoperatively is high. Impaired cerebral autoregulation may be one of the factors that are implicated. We present our experience with monitoring of cerebral oxygenation and autoregulation in the pathological hemisphere during the perioperative period in four patients with moyamoya disease.

Systems Biology Model of Cerebral Oxygen Delivery and Metabolism During Therapeutic Hypothermia: Application to the Piglet Model.

Hypoxic ischaemic encephalopathy (HIE) is a significant cause of death and disability. Therapeutic hypothermia (TH) is the only available standard of treatment, but 45-55% of cases still result in death or neurodevelopmental disability following TH. This work has focussed on developing a new brain tissue physiology and biochemistry systems biology model that includes temperature effects, as well as a Bayesian framework for analysis of model parameter estimation. Through this, we can simulate the effects of temperature on brain tissue oxygen delivery and metabolism, as well as analyse clinical and experimental data to identify mechanisms to explain differing behaviour and outcome. Presented here is an application of the model to data from two piglets treated with TH following hypoxic-ischaemic injury showing different responses and outcome following treatment. We identify the main mechanism for this difference as the Q10 temperature coefficient for metabolic reactions, with the severely injured piglet having a median posterior value of 0.133 as opposed to the mild injury value of 5.48. This work demonstrates the use of systems biology models to investigate underlying mechanisms behind the varying response to hypothermic treatment.

Analysis of the Association Between Lung Function and Brain Tissue Oxygen Tension in Severe Traumatic Brain Injury.

Low brain tissue oxygen tension (PbtO2) has been shown to be an independent factor associated with unfavourable outcomes in traumatic brain injury (TBI). Although PbtO2 provides clinicians with an understanding of ischaemic and non-ischaemic derangements of brain physiology, the value alone can be the result of several factors, including partial arterial oxygenation pressure (PaO2), haemoglobin levels (Hb) and cerebral perfusion pressure (CPP). This chapter presents a single-centre, retrospective cohort study of 70 adult patients with severe TBI who were admitted to the Neurocritical Care Unit (NCCU) at Addenbrooke's Hospital (Cambridge, UK) between October 2014 and December 2017. A total of 303 simultaneous measurements of different variables that included (but were not limited to) intracranial pressure (ICP), PaO2, PbtO2, CPP and the fraction of inspired oxygen (FiO2) were considered in this work. We conducted a correlation analysis between all of the variables. We also implemented a longitudinal data analysis of the PbtO2 and PaO2/FiO2 ratio (PF ratio). There were strong and independent correlations between PbtO2 and the PF ratio, and between PbtO2 and PaO2, with adjusted p values of <0.001 for both correlations. After adjustment for ICP, age, sex and the Glasgow Coma Scale (GCS) score, a PF ≤ 330 was shown to be an independent risk factor for a compromised PbtO2 value of <20, with an adjusted odds ratio of 1.94 (95% confidence interval 1.12-3.34) and a p value of 0.02. Brain and lung interactions in patients with TBI patients have complex interrelationships. Our results confirm the importance of employing lung-protective strategies to prevent brain hypoxia in patients with TBI.

Brain multimodality monitoring in patients suffering from acute aneurysmal subarachnoid hemorrhage: clinical value and complications.

Brain multimodality monitoring measuring brain tissue oxygen pressure, cerebral blood flow, and cerebral near-infrared spectroscopy may help optimize the neurocritical care of patients with aneurysmal subarachnoid hemorrhage and delayed cerebral ischemia. We retrospectively looked for complications associated with the placement of the probes and checked the reliability of the different tools used for multimodality monitoring. In addition, we screened for therapeutic measures derived in cases of pathological values in multimodality monitoring in 26 patients with acute aneurysmal subarachnoid hemorrhage. Computed tomography scans showed minor hemorrhage along with the probes in 12 patients (46.2%). Missing transmission of values was observed in 34.1% of the intended time of measurement for cerebral blood flow probes and 15.5% and 16.2%, respectively, for the two kinds of probes measuring brain tissue oxygen pressure. We identified 744 cumulative alarming values transmitted from multimodality monitoring. The most frequent intervention was modifying minute ventilation (29%). Less frequent interventions were escalating the norepinephrine dosage (19.9%), elevating cerebral perfusion pressure (14.9%) or inspiratory fraction of inspired oxygen (7.5%), transfusing red blood cell concentrates (1.2%), initiating further diagnostics (2.3%) and neurosurgical interventions (1.9%). As well, 355 cases of pathological values had no therapeutic consequence. The reliability of the measuring tools for multimodality monitoring regarding a continuous transmission of values must be improved, particularly for cerebral blood flow monitoring. The overall high rate of missing therapeutic responses to pathological values derived from multimodality monitoring in patients with aneurysmal subarachnoid hemorrhage underlines the need for structured tiered algorithms. In addition, such algorithms are the basic requirement for prospective multicenter studies, which are urgently needed to evaluate the role of multimodality monitoring in treating these patients.

How do we identify the crashing traumatic brain injury patient - the neurosurgeon's view.

To provide an overview on recent advances in the field of assessment and monitoring of patients with severe traumatic brain injury (sTBI) in neurocritical care from a neurosurgical point of view. In high-income countries, monitoring of patients with sTBI heavily relies on multimodal neurocritical parameters, nonetheless clinical assessment still has a solid role in decision-making. There are guidelines and consensus-based treatment algorithms that can be employed in both absence and presence of multimodal monitoring in the management of patients with sTBI. Additionally, novel dynamic monitoring options and machine learning-based prognostic models are introduced. Currently, the acute management and treatment of secondary injury/insults is focused on dealing with the objective evident pathology. An ongoing paradigm shift is emerging towards more proactive treatment of neuroworsening as soon as premonitory signs of deterioration are detected. Based on the current evidence, serial clinical assessment, neuroimaging, intracranial and cerebral perfusion pressure and brain tissue oxygen monitoring are key components of sTBI care. Clinical assessment has a crucial role in identifying the crashing patient with sTBI, especially from a neurosurgical standpoint. Multimodal monitoring and clinical assessment should be seen as complementary evaluation methods that support one another.

Individualized Brain Tissue Oxygen-Monitoring Probe Placement Helps to Guide Therapy and Optimizes Outcome in Neurocritical Care

Background/ObjectiveIn order to monitor tissue oxygenation in patients with acute neurological disorders, probes for measurement of brain tissue oxygen tension (ptO2) are often placed non-specifically in a right frontal lobe location. To improve the value of ptO2 monitoring, placement of the probe into a specific area of interest is desirable. We present a technique using CT-guidance to place the ptO2 probe in a particular area of interest based on the individual patient’s pathology.MethodsIn this retrospective cohort study, we analyzed imaging and clinical data from all patients who underwent CT-guided ptO2 probe placement at our institution between October 2017 and April 2019. Primary endpoint was successful placement of the probe in a particular area of interest rated by two independent reviewers. Secondary outcomes were complications from probe insertion, clinical consequences from ptO2 measurements, clinical outcome according to the modified Rankin Scale (mRS) as well as development of ischemia on follow-up imaging. A historical control group was selected from patients who underwent conventional ptO2 probe placement between January 2010 and October 2017.ResultsEleven patients had 16 CT-guided probes inserted. In 15 (93.75%) probes, both raters agreed on the correct placement in the area of interest. Each probe triggered on average 0.48 diagnostic or therapeutic adjustments per day. Only one infarction within the vascular territory of a probe was found on follow-up imaging. Eight out of eleven patients (72.73%) reached a good outcome (mRS ≤ 3). In comparison, conventionally placed probes triggered less diagnostic and therapeutic adjustment per day (p = 0.007). Outcome was worse in the control group (p = 0.024).ConclusionCT-guided probe insertion is a reliable and easy technique to place a ptO2 probe in a particular area of interest in patients with potentially reduced cerebral oxygen supply. By adjusting treatment aggressively according to this individualized monitoring data, clinical outcome may improve.

Multimodal brain monitoring following traumatic brain injury: A primer for intensive care practitioners.

Traumatic brain injury (TBI) is common and potentially devastating. Traditional examination-based patient monitoring following TBI may be inadequate for frontline clinicians to reduce secondary brain injury through individualized therapy. Multimodal neurologic monitoring (MMM) offers great potential for detecting early injury and improving outcomes. By assessing cerebral oxygenation, autoregulation and metabolism, clinicians may be able to understand neurophysiology during acute brain injury, and offer therapies better suited to each patient and each stage of injury. Hence, we offer this primer on brain tissue oxygen monitoring, pressure reactivity index monitoring and cerebral microdialysis. This narrative review serves as an introductory guide to the latest clinically-relevant evidence regarding key neuromonitoring techniques.

The Effect of Temperature Increases on Brain Tissue Oxygen Tension in Patients with Traumatic Brain Injury: A Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Substudy.

Fever may aggravate secondary brain injury after traumatic brain injury (TBI). The aim of this study was to identify episodes of temperature increases through visual plot analysis and algorithm supported detection, and to describe associated patterns of changes in on brain tissue oxygen tension (PbtO2). Data derive from the high-resolution cohort of the multicenter prospective Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study. Temperature increases (≥0.5°C) were visually identified in 33 patients within the first 11 days of monitoring. Generalized estimating equations were used to detect significant changes of systemic and neuromonitoring parameters from baseline to the highest temperature. Patients were median 50 (interquartile range [IQR], 35-62) years old, and presented with a Glasgow Coma Scale (GCS) of 8 (IQR, 4-10). In 202 episodes of temperature increases, mean temperature rose by 1.0°C ± 0.5°C within 4 hours. Overall, PbtO2 slightly increased (ΔPbtO2 = 0.9 ± 6.1 mmHg, p = 0.022) during temperature increases. PbtO2 increased in 35% (p < 0.001), was stable in 49% (p = 0.852), and decreased in 16% (p < 0.001) of episodes. During episodes of temperature increases and simultaneous drops in PbtO2, cerebral perfusion pressure (CPP) decreased (ΔCPP -6.3 ± 11.5 mmHg; p < 0.001). Brain tissue hypoxia (PbtO2 <20 mmHg) developed during 27/164 (17%) episodes of effervescences, in the remaining 38/202 episodes baseline PbtO2 was already <20 mmHg. Comparable results were found when using algorithm-supported detection of temperature increases. In conclusion, during effervescences, PbtO2 was mostly stable or slightly increased. A decrease of PbtO2 was observed in every sixth episode, where it was associated with a decrease in CPP. Our data highlight the need for special attention to CPP monitoring and maintenance during episodes of fever.

Incidence and characteristics of cerebral hypoxia after craniectomy in brain-injured patients: a cohort study.

After craniectomy, although intracranial pressure (ICP) is controlled, episodes of brain hypoxia might still occur. Cerebral hypoxia is an indicator of poor outcome independently of ICP and cerebral perfusion pressure. No study has systematically evaluated the incidence and characteristics of brain hypoxia after craniectomy. The authors' objective was to describe the incidence and characteristics of brain hypoxia after craniectomy. The authors included 25 consecutive patients who underwent a craniectomy after traumatic brain injury or intracerebral hemorrhage and who were monitored afterward with a brain tissue oxygen pressure monitor. The frequency of hypoxic values after surgery was 14.6% despite ICP being controlled. Patients had a mean of 18 ± 23 hypoxic episodes. Endotracheal (ET) secretions (17.4%), low cerebral perfusion pressure (10.3%), and mobilizing the patient (8.6%) were the most common causes identified. Elevated ICP was rarely identified as the cause of hypoxia (4%). No cause of cerebral hypoxia could be determined 31.2% of the time. Effective treatments that were mainly used included sedation/analgesia (20.8%), ET secretion suctioning (15.4%), and increase in fraction of inspired oxygen or positive end-expiratory pressure (14.1%). Cerebral hypoxia is common after craniectomy, despite ICP being controlled. ET secretion and patient mobilization are common causes that are easily treatable and often not identified by standard monitoring. These results suggest that monitoring should be pursued even if ICP is controlled. The authors' findings might provide a hypothesis to explain the poor functional outcome in the recent randomized controlled trials on craniectomy after traumatic brain injury where in which brain tissue oxygen pressure was not measured.

Mutant G2019S-LRRK2 Induces Abnormalities in Arteriolar Cerebral Blood Volume in Mouse Brains: An MRI Study

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disease and the most common movement disorder characterized by motor impairments resulting from midbrain dopamine neuron loss. Abnormalities in small pial arteries and arterioles, which are the primary pathways of local delivery of nutrients and oxygen in brain tissue, have been reported in many neurodegenerative diseases including PD. Mutations in LRRK2 cause genetic PD and contribute to sporadic PD. The most common PD-linked mutation LRRK2 G2019S contributes 20–47% of genetic forms of PD in Caucasian populations. The human LRRK2 G2019S transgenic mouse model displays PD-like movement impairment and was used to identify novel LRRK2 inhibitors, which provides a useful model for studying microvascular abnormalities in PD. Objectives: To investigate abnormalities in arteriolar cerebral blood volume (CBVa) in various brain regions using the inflow-based vascular-space occupancy (iVASO) MRI technique in LRRK2 mouse models of PD. Methods: Anatomical and iVASO MRI scans were performed in 5 female and 7 male nontransgenic (nTg), 3 female and 4 male wild-type (WT) LRRK2, and 5 female and 7 male G2019S-LRRK2 mice of 9 months of age. CBVa was calculated and compared in the substantia nigra (SN), olfactory cortex, and prefrontal cortex. Results: Compared to nTg mice, G2019S-LRRK2 mice showed decreased CBVa in the SN, but increased CBVa in the olfactory and prefrontal cortex in both male and female groups, whereas WT-LRRK2 mice showed no change in CBVa in the SN (male and female), the olfactory (female), and prefrontal (female) cortex, but a slight increase in CBVa in the olfactory and prefrontal cortex in the male group only. Conclusions: Alterations in the blood volume of small arteries and arterioles (CBVa) were detected in the G2019S-LRRK2 mouse model of PD. The opposite changes in CBVa in the SN and the cortex indicate that PD pathology may have differential effects in different brain regions. Our results suggest the potential value of CBVa as a marker for clinical PD studies.

The Impact of Intra-Arterial Papaverine-Hydrochloride on Cerebral Metabolism and Oxygenation for Treatment of Delayed-Onset Post-Subarachnoid Hemorrhage Vasospasm

Delayed posthemorrhagic vasospasm remains among the major complications after aneurysmal subarachnoid hemorrhage (SAH) and can result in devastating ischemic strokes. As rescue therapy, neurointerventional procedures are used for selective vasodilatation. To investigate the effects of intra-arterial papaverine-hydrochloride on cerebral metabolism and oxygenation. A total of 10 consecutive patients, suffering from severe aneurysmal SAH were prospectively included. Patients were under continuous multimodality neuromonitoring and required intra-arterial papaverine-hydrochloride for vasospasm unresponsive to hypertensive therapy. Cerebral metabolism (microdialysis), brain tissue oxygen tension (ptiO2), intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were analyzed for a period of 12 h following intervention. A median dose of 125 mg papaverine-hydrochloride was administered ipsilateral to the multimodality probe. Angiographic improvement of cerebral vasospasm was observed in 80% of patients. During intervention, a significant elevation of ICP (13.7±5.2 mmHg) and the lactate-pyruvate ratio (LPR) (54.2±15.5) was observed, whereas a decrease in cerebral glucose (0.9±0.5 mmol/L) occurred. Within an hour, an increase of cerebral lactate (5.0±2.0 mmol/L) and glycerol (104.4±89.8 μmol/L) as well as a decrease of glucose (0.9±0.4 mmol/L) were measured. In 2 to 5 h after treatment, the LPR significantly decreased (pretreatment: 39.3±15.3, to lowest 30.5±6.7). Cerebral pyruvate levels increased in 1 to 10 h (pretreatment: 100.1± 33.1 μmol/L, to highest 141.4±33.7 μmol/L) after intervention. No significant changes in ptiO2 or CPP occurred. The initial detrimental effects of the endovascular procedure itself were outweighed by an improved cerebral metabolism within 10 h thereafter. As the effect was very limited, repeated interventions or continuous application should be considered.

Mild hypercapnia improves brain tissue oxygen tension but not diffusion limitation in asphyxial cardiac arrest: an experimental study in pigs

BackgroundWe sought to evaluate the effect of mild hypercapnia on brain tissue oxygen tension (Pbto2) and diffusion limitation (impaired ability of oxygen extraction) in a porcine post asphyxial cardiac arrest model.MethodsIn 16 Bama pigs, asphyxial cardiac arrest was induced by endotracheal tube clamping and remained untreated for another 4 min. After return of spontaneous circulation (ROSC), animals were randomly assigned to mild hypercapnia (end-tidal carbon dioxide (EtCO2): 45 ~ 50 mmHg) and normocapnia (EtCO2: 35 ~ 40 mmHg) groups for 12 h. Intracranial pressure (ICP), Pbto2, and brain tissue temperature were invasively measured by multimodality monitors. Blood gas analysis, neuron specific enolase (NSE), and S100β were tested at baseline, ROSC 1 h, 6 h, and 12 h. Generalized mixed model with a compound symmetry covariance matrix was used to compare the time-variables of the two groups.ResultsTwelve (75%) pigs had ROSC and 11 pigs survived for the study period, with 6 pigs in mild hypercapnia group and 5 in the normocapnia group. The mean EtCO2 in the mild hypercapnia was significantly higher than normocapnia group (48 vs 38 mmHg, p < 0.001). Compared with normocapnia, mild hypercapnia group had higher Pbto2 (p < 0.001), slightly higher mean arterial pressure (p = 0.012) and ICP (p = 0.009). There were no differences in cerebral perfusion pressure (p = 0.106), gradient of partial pressure of jugular venous bulb oxygen (Pjvo2) and Pbto2 (p = 0.262), difference of partial pressure of jugular venous CO2 and arterial CO2 (p = 0.546), cardiac output (p = 0.712), NSE (p = 0.822), and S100β (p = 0.759) between the two groups.ConclusionsShort term mild hypercapnia post-resuscitation could improve Pbto2. However, no corresponding improvements in the gradient of Pjvo2 to Pbto2 and biomarkers of neurological recovery were observed in the porcine asphyxial cardiac arrest model.