Brain Tissue Oxygen Tension Research Articles

Effects of Hypertonic Saline and Sodium Lactate on Cortical Cerebral Microcirculation and Brain Tissue Oxygenation.

Hyperosmolar solutions have been used in neurosurgery to modify brain bulk. The aim of this animal study was to compare the short-term effects of equivolemic, equiosmolar solutions of hypertonic saline (HTS) and sodium lactate (HTL) on cerebral cortical microcirculation and brain tissue oxygenation in a rabbit craniotomy model. Rabbits (weight, 1.5 to 2.0 kg) were anesthetized, ventilated mechanically, and subjected to a craniotomy. The animals were allocated randomly to receive a 3.75 mL/kg intravenous infusion of either 3.2% HTS (group HTS, n=9), half-molar sodium lactate (group HTL, n=10), or normal saline (group C, n=9). Brain tissue partial pressure of oxygen (PbtO2) and microcirculation in the cerebral cortex using sidestream dark-field imaging were evaluated before, 20 and 40 minutes after 15 minutes of hyperosmolar solution infusion. Global hemodynamic data were recorded, and blood samples for laboratory analysis were obtained at the time of sidestream dark-field image recording. No differences in the microcirculatory parameters were observed between the groups before and after the use of osmotherapy. Brain tissue oxygen deteriorated over time in groups C and HTL, this deterioration was not significant in the group HTS. Our findings suggest that equivolemic, equiosmolar HTS and HTL solutions equally preserve perfusion of cortical brain microcirculation in a rabbit craniotomy model. The use of HTS was better in preventing the worsening of brain tissue oxygen tension.

Cerebral Metabolic Changes Related to Oxidative Metabolism in a Model of Bacterial Meningitis Induced by Lipopolysaccharide.

Cerebral mitochondrial dysfunction is prominent in the pathophysiology of severe bacterial meningitis. In the present study, we hypothesize that the metabolic changes seen after intracisternal lipopolysaccharide (LPS) injection in a piglet model of meningitis is compatible with mitochondrial dysfunction and resembles the metabolic patterns seen in patients with bacterial meningitis. Eight pigs received LPS injection in cisterna magna, and four pigs received NaCl in cisterna magna as a control. Biochemical variables related to energy metabolism were monitored by intracerebral microdialysis technique and included interstitial glucose, lactate, pyruvate, glutamate, and glycerol. The intracranial pressure (ICP) and brain tissue oxygen tension (PbtO2) were also monitored along with physiological variables including mean arterial pressure, blood glucose, lactate, and partial pressure of O2 and CO2. Pigs were monitored for 60min at baseline and 240min after LPS/NaCl injection. After LPS injection, a significant increase in cerebral lactate/pyruvate ratio (LPR) compared to control group was registered (p=0.01). This increase was due to a significant increased lactate with stable and normal values of pyruvate. No significant change in PbtO2 or ICP was registered. No changes in physiological variables were observed. The metabolic changes after intracisternal LPS injection is compatible with disturbance in the oxidative metabolism and partly due to mitochondrial dysfunction with increasing cerebral LPR due to increased lactate and normal pyruvate, PbtO2, and ICP. The metabolic pattern resembles the one observed in patients with bacterial meningitis. Metabolic monitoring in these patients is feasible to monitor for cerebral metabolic derangements otherwise missed by conventional intensive care monitoring.

Effects of hyperoxia on 18F-fluoro-misonidazole brain uptake and tissue oxygen tension following middle cerebral artery occlusion in rodents: Pilot studies.

PurposeMapping brain hypoxia is a major goal for stroke diagnosis, pathophysiology and treatment monitoring. 18F-fluoro-misonidazole (FMISO) positron emission tomography (PET) is the gold standard hypoxia imaging method. Normobaric hyperoxia (NBO) is a promising therapy in acute stroke. In this pilot study, we tested the straightforward hypothesis that NBO would markedly reduce FMISO uptake in ischemic brain in Wistar and spontaneously hypertensive rats (SHRs), two rat strains with distinct vulnerability to brain ischemia, mimicking clinical heterogeneity.MethodsThirteen adult male rats were randomized to distal middle cerebral artery occlusion under either 30% O2 or 100% O2. FMISO was administered intravenously and PET data acquired dynamically for 3hrs, after which magnetic resonance imaging (MRI) and tetrazolium chloride (TTC) staining were carried out to map the ischemic lesion. Both FMISO tissue uptake at 2-3hrs and FMISO kinetic rate constants, determined based on previously published kinetic modelling, were obtained for the hypoxic area. In a separate group (n = 9), tissue oxygen partial pressure (PtO2) was measured in the ischemic tissue during both control and NBO conditions.ResultsAs expected, the FMISO PET, MRI and TTC lesion volumes were much larger in SHRs than Wistar rats in both the control and NBO conditions. NBO did not appear to substantially reduce FMISO lesion size, nor affect the FMISO kinetic rate constants in either strain. Likewise, MRI and TTC lesion volumes were unaffected. The parallel study showed the expected increases in ischemic cortex PtO2 under NBO, although these were small in some SHRs with very low baseline PtO2.ConclusionsDespite small samples, the apparent lack of marked effects of NBO on FMISO uptake suggests that in permanent ischemia the cellular mechanisms underlying FMISO trapping in hypoxic cells may be disjointed from PtO2. Better understanding of FMISO trapping processes will be important for future applications of FMISO imaging.

Pressure Autoregulation Measurement Techniques in Adult Traumatic Brain Injury, Part II: A Scoping Review of Continuous Methods.

A scoping review of the literature was performed systematically on commonly described continuous autoregulation measurement techniques in adult traumatic brain injury (TBI) to provide an overview of methodology and comprehensive reference library of the available literature for each technique. Five separate small systematic reviews were conducted for each of the continuous techniques: pressure reactivity index (PRx), laser Doppler flowmetry (LDF), near infrared spectroscopy (NIRS) techniques, brain tissue oxygen tension (PbtO2), and thermal diffusion (TD) techniques. Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library (inception to December 2016), and reference lists of relevant articles were searched. A two-tier filter of references was conducted. The literature base identified from the individual searches was limited, except for PRx. The total number of articles using each of the five searched techniques for continuous autoregulation in adult TBI were: PRx (28), LDF (4), NIRS (9), PbtO2 (10), and TD (8). All continuous techniques described in adult TBI are based on moving correlation coefficients. The premise behind the calculation of these moving correlation coefficients focuses on the impact of slow fluctuations in either mean arterial pressure (MAP) or cerebral perfusion pressure (CPP) on some indirect measure of cerebral blood flow (CBF), such as: intracranial pressure (ICP), LDF, NIRS signals, PbtO2, or TD CBF. The thought is the correlation between a hemodynamic driving factor, such as MAP or CPP, and a surrogate for CBF or cerebral perfusion sheds insight on the state of cerebral autoregulation. Both PRx and NIRS indices were validated experimentally against the "gold standard" static autoregulatory curve (Lassen curve) at least around the lower threshold of autoregulation. The PRx has the largest literature base supporting the association with patient outcome. Various methods of continuous autoregulation assessment are described within the adult TBI literature. Many studies exist on these various indices, suggesting an association between their values and patient morbidity/death.

190 Time Course and Physiological Determinants of Cerebral Lactate/pyruvate Ratio Following Traumatic Brain Injury

Abstract INTRODUCTION Brain lactate/pyruvate ratio (LPR) is an important indicator of cerebral metabolism and an independent predictor of neurological outcome following traumatic brain injury (TBI). This study examined the temporal trends and physiological factors driving fluctuations in LPR following TBI. METHODS This was a retrospective analysis of prospectively collected data on patients with TBI requiring neurocritical care and invasive multi-modality monitoring. Microdialysis parameters (glucose, pyruvate, lactate) were co-registered with continuous recordings of intracranial pressure (ICP), mean arterial pressure (MAP), PRx (a measure of cerebrovascular autoregulation), and brain tissue oxygen tension (PbtO2). Analysis using linear mixed-effects and generalised additive models was conducted in R (v.3.2.5) RESULTS >566 patients were included; median age was 36 years and 76.3% were male. Mortality at 6 months was 21.2% and 32.0% of patient had a poor neurological outcome (extended Glasgow Outcome Scale <4). Mean LPR was higher amongst patients with poor outcome in the first several days following injury. Cerebral glucose was the strongest independent predictor of LPR amongst the monitoring parameters (P < 0.00001), and demonstrated a highly nonlinear relationship with LPR rising rapidly at very low glucose concentrations. Cerebral perfusion pressure (CPP = MAP-ICP; P < 0.0001), ICP (P < 0.01), and PRx (P < 0.0001). Further, there were significant interactive effects on LPR between CPP, glucose, and PbtO2. CONCLUSION Higher LPR is associated with worse outcome following TBI. Brain glucose is a major determinant of LPR, both directly and via interaction with other physiological parameters. These findings suggest potentially modifiable factors that could be employed in therapeutic approaches to correct deranged LPR following TBI.

Aspects on the Physiological and Biochemical Foundations of Neurocritical Care.

Neurocritical care (NCC) is a branch of intensive care medicine characterized by specific physiological and biochemical monitoring techniques necessary for identifying cerebral adverse events and for evaluating specific therapies. Information is primarily obtained from physiological variables related to intracranial pressure (ICP) and cerebral blood flow (CBF) and from physiological and biochemical variables related to cerebral energy metabolism. Non-surgical therapies developed for treating increased ICP are based on knowledge regarding transport of water across the intact and injured blood–brain barrier (BBB) and the regulation of CBF. Brain volume is strictly controlled as the BBB permeability to crystalloids is very low restricting net transport of water across the capillary wall. Cerebral pressure autoregulation prevents changes in intracranial blood volume and intracapillary hydrostatic pressure at variations in arterial blood pressure. Information regarding cerebral oxidative metabolism is obtained from measurements of brain tissue oxygen tension (PbtO2) and biochemical data obtained from intracerebral microdialysis. As interstitial lactate/pyruvate (LP) ratio instantaneously reflects shifts in intracellular cytoplasmatic redox state, it is an important indicator of compromised cerebral oxidative metabolism. The combined information obtained from PbtO2, LP ratio, and the pattern of biochemical variables reveals whether impaired oxidative metabolism is due to insufficient perfusion (ischemia) or mitochondrial dysfunction. Intracerebral microdialysis and PbtO2 give information from a very small volume of tissue. Accordingly, clinical interpretation of the data must be based on information of the probe location in relation to focal brain damage. Attempts to evaluate global cerebral energy state from microdialysis of intraventricular fluid and from the LP ratio of the draining venous blood have recently been presented. To be of clinical relevance, the information from all monitoring techniques should be presented bedside online. Accordingly, in the future, the chemical variables obtained from microdialysis will probably be analyzed by biochemical sensors.

Advanced monitoring in traumatic brain injury: microdialysis.

Here, we review the present state-of-the-art of microdialysis for monitoring patients with severe traumatic brain injury, highlighting the newest developments. Microdialysis has evolved in neurocritical care to become an established bedside monitoring modality that can reveal unique information on brain chemistry. A major advance is recent consensus guidelines for microdialysis use and interpretation. Other advances include insight obtained from microdialysis into the complex, interlinked traumatic brain injury disorders of electrophysiological changes, white matter injury, inflammation and metabolism. Microdialysis has matured into being a standard clinical monitoring modality that takes its place alongside intracranial pressure and brain tissue oxygen tension measurement in specialist neurocritical care centres, as well as being a research tool able to shed light on brain metabolism, inflammation, therapeutic approaches, blood-brain barrier transit and drug effects on downstream targets. Recent consensus on microdialysis monitoring is paving the way for improved neurocritical care protocols. Furthermore, there is scope for future improvements both in terms of the catheters and microdialysate analyser technology, which may further enhance its applicability.

Brain Multimodality Monitoring: A New Tool in Neurocritical Care of Comatose Patients.

Neurocritical care patients are at risk of developing secondary brain injury from inflammation, ischemia, and edema that follows the primary insult. Recognizing clinical deterioration due to secondary injury is frequently challenging in comatose patients. Multimodality monitoring (MMM) encompasses various tools to monitor cerebral metabolism, perfusion, and oxygenation aimed at detecting these changes to help modify therapies before irreversible injury sets in. These tools include intracranial pressure (ICP) monitors, transcranial Doppler (TCD), Hemedex™ (thermal diffusion probe used to measure regional cerebral blood flow), microdialysis catheter (used to measure cerebral metabolism), Licox™ (probe used to measure regional brain tissue oxygen tension), and continuous electroencephalography. Although further research is needed to demonstrate their impact on improving clinical outcomes, their contribution to illuminate the black box of the brain in comatose patients is indisputable. In this review, we further elaborate on commonly used MMM parameters, tools used to measure them, and the indications for monitoring per current consensus guidelines.

Multimodality Monitoring: Illuminating the Comatose Human Brain.

The field of neurocritical care has evolved tremendously in recent years, a development explained vastly by the advent of neurophysiological monitoring. From basic intracranial pressure measurements to brain tissue oxygenation, microdialysis, cerebral blood flow (CBF), and surface and intracortical electroencephalography (EEG), our ability to detect and control physiologic endpoints of brain function in comatose patients has grown substantially. The integration of these data gave birth to the concept of multimodality monitoring (MMM). Real-time data acquisition and analysis systems are crucial for fully understanding the relationship between physiologic drivers such as blood pressure, temperature and end-tidal CO2, and end-point measures of brain metabolism such as brain tissue oxygen tension, CBF, lactate/pyruvate ratio, and EEG. Multimodality monitoring provides an early warning system for detecting physiological derangements that can be corrected before secondary brain injury occurs. Multimodality monitoring also allows for the creation of an optimized physiological environment for the injured brain, with the goal of preventing secondary injury events. The authors review the basic ideas and technical aspects of MMM, and therefore provide a unique window of illumination into the comatose human brain.

Monitoring of brain oxygenation during hypothermic CPR – A prospective porcine study

Background and aimLimited data are available concerning the impact of CPR interventions on cerebral oxygenation during hypothermic cardiac arrest. We therefore studied cerebral perfusion pressure (CPP), brain tissue oxygen tension (PbtO2), cerebral venous oxygen saturation (ScvO2) and regional cerebral oxygen saturation (rSO2) in an animal model of hypothermic CPR. We also assessed the correlation between rSO2 and CPP, PbtO2 and ScvO2 to clarify whether near-infrared spectroscopy (NIRS) may be used to non-invasively monitor changes in cerebral oxygenation during hypothermic CPR. MethodsNine pigs were surface-cooled to a core temperature of 28°C and underwent a period of asphyxia before cardiac arrest was induced. After 2min of untreated cardiac arrest they were resuscitated for 45min. CPP, PbtO2, ScvO2 and rSO2 were monitored after periods of stable external chest compression, a short interruption of CPR and after epinephrine administration. ResultsDuring external chest-compressions before adrenalin administration CPP, PbtO2, ScvO2 and rSO2 increased in parallel and changes in rSO2 closely correlated with changes in CPP (r=.844; p<.001) and ScvO2 (r=.868; p<.001). After adrenaline administration CPP and PbtO2 increased, ScvO2 decreased and rSO2 values did not change and there was no significant correlation between rSO2 and CPP, PbtO2, or ScvO2. ConclusionIn this animal model of hypothermic cardiac arrest adrenaline was associated with an increase in global cerebral oxygen extraction despite an increase in CPP. Discrepancies in the time course of PbtO2 and ScvO2 suggest differences in regional oxygen metabolism after adrenalin. rSO2 values correlated closely with CPP and ScvO2 only during periods of external chest compression without adrenaline administration.

Myogenic and metabolic feedback in cerebral autoregulation: Putative involvement of arachidonic acid-dependent pathways

The present paper presents a mechanistic model of cerebral autoregulation, in which the dual effects of the arachidonic acid metabolites 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs) on vascular smooth muscle mediate the cerebrovascular adjustments to a change in cerebral perfusion pressure (CPP). 20-HETE signalling in vascular smooth muscle mediates myogenic feedback to changes in vessel wall stretch, which may be modulated by metabolic feedback through EETs released from astrocytes and endothelial cells in response to changes in brain tissue oxygen tension. The metabolic feedback pathway is much faster than 20-HETE-dependent myogenic feedback, and the former thus initiates the cerebral autoregulatory response, while myogenic feedback comprises a relatively slower mechanism that functions to set the basal cerebrovascular tone. Therefore, assessments of dynamic cerebral autoregulation, which may provide information on the response time of the cerebrovasculature, may specifically be used to yield information on metabolic feedback mechanisms, while data based on assessments of static cerebral autoregulation represent the integrated functionality of myogenic and metabolic feedback.

MRI of brain tissue oxygen tension under hyperbaric conditions

The brain depends on a continuous supply of oxygen to maintain its structural and functional integrity. This study measured T1 from MRI under normobaric air, normobaric oxygen, hyperbaric air, and hyperbaric oxygen (HBO) conditions as a marker of tissue pO2 since dissolved molecular oxygen acts as an endogenous contrast agent. Brain tissue T1 decreased corresponding to increased pO2 with increasing inhaled oxygen concentrations, and tissue oxygenation was estimated from the T1 changes between different inhaled oxygen levels. Tissue pO2 difference maps between different oxygen conditions showed heterogeneous pO2 changes in the brain. MRI-derived tissue pO2 was markedly lower than the arterial pO2 but was slightly higher than venous pO2. Additionally, for comparison with published extracellular tissue pO2 data obtained using oxygen electrodes and other invasive techniques, a model was used to estimate extracellular and intracellular pO2 from the MRI-derived mean tissue pO2. This required multiple assumptions, and so the effects of the assumptions and parameters used in modeling brain pO2 were evaluated. MRI-derived pO2 values were strongly dependent on assumptions about the extra- and intracellular compartments but were relatively less sensitive to variations in the relaxivity constant of oxygen and contribution from oxygen in the cerebral blood compartment. This approach may prove useful in evaluating tissue oxygenation in disease states such as stroke.

Electrocorticographic(ECoG) monitoring in spontaneous intracerebral hemorrhage(sICH): Metabolic profile of cortical spreading depolarizations(CSD)

Objective Metabolic changes accompany CSDs in clinical secondary brain injury. This was investigated for the first time after sICH. Methods Patients with sICH were enrolled in COSBID (Co-operative Study on Brain Injury Depolarisations). Prolonged depressions of ECoG was used to detect CSDs. Brain tissue oxygen tension (PbtO2), cerebral blood flow (CBF), and cerebral metabolism (microdialysis) were monitored in the region of perihematomal edema (PHE). Results 18 patients (38% female, 55–67 years) had an ICH volume of 33–69 ml. Hematoma evacuation (n = 17) or craniectomy only (n = 1) was performed. During monitoring for 10 (6–14) days, a total of 129 CSDs were observed in 66.7% (n = 12) of patients. CSDs occurred in 73% (N = 11) of patients with PHE expansion. CSDs were directly associated with a significant decrease of PbtO2 (−4mmHg [−3;−7]) in 68% (52/77), CBF changes in 95% (19/20), and metabolic derangement in 80% (80/100) of events. PHE expansion was observed in all patients with spreading convulsions (N = 2) and patients with repetitive CSDs. Conclusions CSDs are associated with local PbtO2 decreases. Clusters of CSDs in particular seems to be associated with detrimental metabolic changes of the perihematomal brain tissue. Key Message ECoG reveals brain pathophysiology of sICH: CSDs are frequent and accompanied by metabolic derangement.

Brain tissue oxygen tension and its response to physiological manipulations: influence of distance from injury site in a swine model of traumatic brain injury.

OBJECTIVE The optimal site for placement of tissue oxygen probes following traumatic brain injury (TBI) remains unresolved. The authors used a previously described swine model of focal TBI and studied brain tissue oxygen tension (PbtO2) at the sites of contusion, proximal and distal to contusion, and in the contralateral hemisphere to determine the effect of probe location on PbtO2 and to assess the effects of physiological interventions on PbtO2 at these different sites. METHODS A controlled cortical impact device was used to generate a focal lesion in the right frontal lobe in 12 anesthetized swine. PbtO2 was measured using Licox brain tissue oxygen probes placed at the site of contusion, in pericontusional tissue (proximal probe), in the right parietal region (distal probe), and in the contralateral hemisphere. PbtO2 was measured during normoxia, hyperoxia, hypoventilation, and hyperventilation. RESULTS Physiological interventions led to expected changes, including a large increase in partial pressure of oxygen in arterial blood with hyperoxia, increased intracranial pressure (ICP) with hypoventilation, and decreased ICP with hyperventilation. Importantly, PbtO2 decreased substantially with proximity to the focal injury (contusion and proximal probes), and this difference was maintained at different levels of fraction of inspired oxygen and partial pressure of carbon dioxide in arterial blood. In the distal and contralateral probes, hypoventilation and hyperventilation were associated with expected increased and decreased PbtO2 values, respectively. However, in the contusion and proximal probes, these effects were diminished, consistent with loss of cerebrovascular CO2 reactivity at and near the injury site. Similarly, hyperoxia led to the expected rise in PbtO2 only in the distal and contralateral probes, with little or no effect in the proximal and contusion probes, respectively. CONCLUSIONS PbtO2 measurements are strongly influenced by the distance from the site of focal injury. Physiological alterations, including hyperoxia, hyperventilation, and hypoventilation substantially affect PbtO2 values distal to the site of injury but have little effect in and around the site of contusion. Clinical interpretations of brain tissue oxygen measurements should take into account the spatial relation of probe position to the site of injury. The decision of where to place a brain tissue oxygen probe in TBI patients should also take these factors into consideration.

Perfluorocarbon NVX-108 increased cerebral oxygen tension after traumatic brain injury in rats

BackgroundHypoxia is a critical secondary injury mechanism in traumatic brain injury (TBI), and early intervention to alleviate post-TBI hypoxia may be beneficial. NVX-108, a dodecafluoropentane perfluorocarbon, was screened for its ability to increase brain tissue oxygen tension (PbtO2) when administered soon after TBI. MethodsKetamine-acepromazine anesthetized rats ventilated with 40% oxygen underwent moderate controlled cortical impact (CCI)-TBI at time 0 (T0). Rats received either no treatment (NON, n=8) or 0.5ml/kg intravenous (IV) NVX-108 (NVX, n=9) at T15 (15min after TBI) and T75. ResultsBaseline cortical PbtO2 was 28±3mm Hg and CCI-TBI resulted in a 46±6% reduction in PbtO2 at T15 (P<0.001). Significant differences in time-group interactions (P=0.013) were found when comparing either absolute or percentage change of PbtO2 to post-injury (mixed-model ANOVA) suggesting that administration of NVX-108 increased PbtO2 above injury levels while it remained depressed in the NON group. Specifically in the NVX group, PbtO2 increased to a peak 143% of T15 (P=0.02) 60min after completion of NVX-108 injection (T135). Systemic blood pressure was not different between the groups. ConclusionNVX-108 caused an increase in PbtO2 following CCI-TBI in rats and should be evaluated further as a possible immediate treatment for TBI.

Multimodal brain monitoring in fulminant hepatic failure.

Acute liver failure, also known as fulminant hepatic failure (FHF), embraces a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction, and hepatic encephalopathy. Cerebral edema and intracranial hypertension are common causes of mortality in patients with FHF. The management of patients who present acute liver failure starts with determining the cause and an initial evaluation of prognosis. Regardless of whether or not patients are listed for liver transplantation, they should still be monitored for recovery, death, or transplantation. In the past, neuromonitoring was restricted to serial clinical neurologic examination and, in some cases, intracranial pressure monitoring. Over the years, this monitoring has proven insufficient, as brain abnormalities were detected at late and irreversible stages. The need for real-time monitoring of brain functions to favor prompt treatment and avert irreversible brain injuries led to the concepts of multimodal monitoring and neurophysiological decision support. New monitoring techniques, such as brain tissue oxygen tension, continuous electroencephalogram, transcranial Doppler, and cerebral microdialysis, have been developed. These techniques enable early diagnosis of brain hemodynamic, electrical, and biochemical changes, allow brain anatomical and physiological monitoring-guided therapy, and have improved patient survival rates. The purpose of this review is to discuss the multimodality methods available for monitoring patients with FHF in the neurocritical care setting.

Long-Term, Continuous Intra-Arterial Nimodipine Treatment of Severe Vasospasm After Aneurysmal Subarachnoid Hemorrhage

Secondary vasospasm and disturbances in cerebrovascular autoregulation are associated with the development of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. An intra-arterial application of nimodipine has been shown to increase the vessel diameter, although this effect is transient. The feasibility of long-term, continuous, intra-arterial nimodipine treatment and its effects on macrovasospasm, autoregulation parameters, and outcome were evaluated in patients with refractory severe macrovasospasm. Ten patients were included with refractory macrovasospasm despite bolus nimodipine application (n= 4) or with primary severe vasospasm (n= 6). The patients were assessed with continuous multimodal neuromonitoring (mean arterial pressure, intraceranial pressure, cerebral perfusion pressure, brain tissue oxygen tension probe), daily transcranial Doppler examinations, and computed tomography angiography/perfusion. Autoregulation indices, the pressure reactivity index, and oxygen reactivity index were calculated. Indwelling microcatheters were placed in the extracranial internal carotid arteries and 0.4 mg nimodipine was continuously infused at 50 mL/hour. The duration of continuous, intra-arterial nimodipine ranged from 9 to 15 days. During treatment intracranial pressure remained stable, transcranial Doppler flow velocity decreased, and brain tissue oxygen tension improved by 37%. Macrovasospasm, as assessed via computed tomography angiography, had improved (n= 5) or disappeared (n= 5) at the end of treatment. Cerebrovascular autoregulation according to the pressure reactivity index and oxygen reactivity index significantly worsened during treatment. All patients showed a favorable outcome (median Glasgow Outcome Scale 5) at 3 months. In well-selected patients with prolonged severe macrovasospasm, continuous intra-arterial nimodipine treatment can be applied as a rescue therapy with relative safety for more than 2 weeks to prevent secondary cerebral ischemia. The induced impairment of cerebrovascular autoregulation during treatment seems to have no negative effects.

Early brain injury after aneurysmal subarachnoid hemorrhage: a multimodal neuromonitoring study.

IntroductionThere is a substantial amount of evidence from animal models that early brain injury (EBI) may play an important role for secondary brain injury after aneurysmal subarachnoid hemorrhage (aSAH). Cerebral microdialysis (CMD) allows online measurement of brain metabolites, including the pro-inflammatory cytokine interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9), which is indicative for disruption of the blood-brain barrier.MethodsTwenty-six consecutive poor-grade aSAH patients with multimodal neuromonitoring were analyzed for brain hemodynamic and metabolic changes, including CMD-IL-6 and CMD-MMP-9 levels. Statistical analysis was performed by using a generalized estimating equation with an autoregressive function.ResultsThe baseline cerebral metabolic profile revealed brain metabolic distress and an excitatory response which improved over the following 5 days (P <0.001). Brain tissue hypoxia (brain tissue oxygen tension of less than 20 mm Hg) was common (more than 60% of patients) in the first 24 hours of neuromonitoring and improved thereafter (P <0.05). Baseline CMD-IL-6 and CMD-MMP-9 levels were elevated in all patients (median = 4,059 pg/mL, interquartile range (IQR) = 1,316 to 12,456 pg/mL and median = 851 pg/mL, IQR = 98 to 25,860 pg/mL) and significantly decreased over days (P <0.05). A higher pro-inflammatory response was associated with the development of delayed cerebral ischemia (P = 0.04), whereas admission disease severity and early brain tissue hypoxia were associated with higher CMD-MMP-9 levels (P <0.03). Brain metabolic distress and increased IL-6 levels were associated with poor functional outcome (modified Rankin Scale of more than 3, P ≤0.01). All models were adjusted for probe location, aneurysm securing procedure, and disease severity as appropriate.ConclusionsMultimodal neuromonitoring techniques allow insight into pathophysiologic changes in the early phase after aSAH. The results may be used as endpoints for future interventions targeting EBI in poor-grade aSAH patients.

Continuous-wave near-infrared spectroscopy is not related to brain tissue oxygen tension.

Near-infrared spectroscopy (NIRS) has gained acceptance for cerebral monitoring, especially during cardiac surgery, though there are few data showing its validity. We therefore aimed to correlate invasive brain tissue oxygen measurements (PtiO2) with the corresponding NIRS-values (regional oxygen saturation, rSO2). We also studied whether NIRS was able to detect ischemic events, defined as a PtiO2-value of <15mmHg. Eleven patients were studied with invasive brain tissue oxygen monitoring and continuous-wave NIRS. PtiO2-correlation with corresponding NIRS-values was calculated. We found no correlation between PtiO2- and NIRS-readings. Measurement of rSO2 was no better than flipping a coin in the detection of cerebral ischemia when a commonly agreed ischemic PtiO2 cut-off value of <15mmHg was chosen. Continuous-wave-NIRS was unable to reliably detect ischemic cerebral episodes, defined as a PtiO2 value <15mmHg. Displayed NIRS-values did not correlate with invasively measured PtiO2-values. CW-NIRS should not be used for the detection of cerebral ischemia.

179 Brain Tissue Oxygen Tension and Its Response to Physiological Manipulations Is Dependent on Distance From Injury Site in a Swine Model of Traumatic Brain Injury

179 Brain Tissue Oxygen Tension and Its Response to Physiological Manipulations Is Dependent on Distance From Injury Site in a Swine Model of Traumatic Brain Injury