Enhanced Fiber Tractography Using Edema Correction: Application and Evaluation in High-Grade Gliomas.

BACKGROUND: A limitation of diffusion tensor imaging (DTI)-based tractography is peritumoral edema that confounds traditional diffusion-based magnetic resonance metrics. OBJECTIVE: To augment fiber-tracking through peritumoral regions by performing novel edema correction on clinically feasible DTI acquisitions and assess the accuracy of the fiber-tracks using intraoperative stimulation mapping (ISM), task-based functional magnetic resonance imaging (fMRI) activation maps, and postoperative follow-up as reference standards. METHODS: Edema correction, using our bi-compartment free water modeling algorithm (FERNET), was performed on clinically acquired DTI data from a cohort of 10 patients presenting with suspected high-grade glioma and peritumoral edema in proximity to and/or infiltrating language or motor pathways. Deterministic fiber-tracking was then performed on the corrected and uncorrected DTI to identify tracts pertaining to the eloquent region involved (language or motor). Tracking results were compared visually and quantitatively using mean fiber count, voxel count, and mean fiber length. The tracts through the edematous region were verified based on overlay with the corresponding motor or language task-based fMRI activation maps and intraoperative ISM points, as well as at time points after surgery when peritumoral edema had subsided. RESULTS: Volume and number of fibers increased with application of edema correction; concordantly, mean fractional anisotropy decreased. Overlay with functional activation maps and ISM-verified eloquence of the increased fibers. Comparison with postsurgical follow-up scans with lower edema further confirmed the accuracy of the tracts. CONCLUSION: This method of edema correction can be applied to standard clinical DTI to improve visualization of motor and language tracts in patients with glioma-associated peritumoral edema.

The Safety of Multimodality Monitoring Using a Triple-Lumen Bolt in Severe Acute Brain Injury.

BACKGROUND: Multimodality monitoring is used frequently to guide care of patients with severe acute brain injury. The aim of this study was to examine the safety and reliability of multimodality monitoring. METHODS: From a prospective observational database at a Level I trauma center, 501 patients, including 300 men and 201 women (mean age 58 ± 39 years) were identified retrospectively. Each patient received a triple-lumen bolt and 3 monitors: intracranial pressure, brain temperature, and brain oxygen. Intensive care unit and hospital records were examined to identify complications, reasons for device replacement, malfunction and infection. Head computed tomography (CT) scans performed before and after the monitors were inserted were examined for evidence of monitor-related adverse effects. RESULTS: A total of 696 triple-lumen bolts were placed. Median duration of monitoring was 78.88 hours (interquartile range, 33.0-133.2 hours). Bilateral monitors were inserted in 22 (3.16%) patients. Ten (1.43%) monitors were replaced to allow magnetic resonance imaging, and 40 (5.74%) monitors were replaced to facilitate additional cranial surgery. Of 35 (5.02%) monitors that were replaced because they were thought to not be functioning properly, 19 (54.29%) were subsequently found to be functioning normally. Follow-up CT scans were compared with CT scans obtained before insertion of monitors; 9 (2.13%) small contusions and 10 (2.36%) extra-axial hematomas associated with the devices were identified. Based on the CT findings, the hematomas were thought to be associated with the insertion technique rather than the device; 4 hematomas required treatment. Twenty-two (3.16%) devices were incorrectly placed (e.g., the probe was in an infarct or an already existing contusion). Only 1 associated infection was identified. CONCLUSIONS: Placement of intracranial monitors for multimodality neuromonitoring using a triple-lumen bolt appears to be safe. The complication rate is similar to published complication rates for single-lumen bolts and single monitors.

Continuous non-invasive optical monitoring of cerebral blood flow and oxidative metabolism after acute brain injury.

Rapid detection of ischemic conditions at the bedside can improve treatment of acute brain injury. In this observational study of 11 critically ill brain-injured adults, we employed a monitoring approach that interleaves time-resolved near-infrared spectroscopy (TR-NIRS) measurements of cerebral oxygen saturation and oxygen extraction fraction (OEF) with diffuse correlation spectroscopy (DCS) measurement of cerebral blood flow (CBF). Using this approach, we demonstrate the clinical promise of non-invasive, continuous optical monitoring of changes in CBF and cerebral metabolic rate of oxygen (CMRO2). In addition, the optical CBF and CMRO2 measures were compared to invasive brain tissue oxygen tension (PbtO2), thermal diffusion flowmetry CBF, and cerebral microdialysis measures obtained concurrently. The optical CBF and CMRO2 information successfully distinguished between ischemic, hypermetabolic, and hyperemic conditions that arose spontaneously during patient care. Moreover, CBF monitoring during pressor-induced changes of mean arterial blood pressure enabled assessment of cerebral autoregulation. In total, the findings suggest that this hybrid non-invasive neurometabolic optical monitor (NNOM) can facilitate clinical detection of adverse physiological changes in brain injured patients that are otherwise difficult to measure with conventional bedside monitoring techniques.

Relative Deficiency of Plasma A Disintegrin and Metalloprotease with Thrombospondin Type 1 Repeats 13 Activity and Elevation of Human Neutrophil Peptides in Patients with Traumatic Brain Injury.

Traumatic microvascular injury (tMVI) is a universal endophenotype of traumatic brain injury (TBI) that is responsible for significant neurological morbidity and mortality. The mechanism underlying tMVI is not fully understood. The present study aims to determine plasma levels of von Willebrand factor (VWF), a disintegrin and metalloprotease with thrombospondin type 1 repeats (ADAMTS) 13 activity, and human neutrophil peptides (HNP) 1-3 and to correlate these biomarkers with functional outcomes after moderate-severe TBI. Thirty-one consecutive TBI patients (Glasgow Coma Scale [GCS] range, 3-12) were enrolled into the study between February 2010 and November 2014. Blood samples were collected on 0, 1, 2, 3, and 5 days after admission and analyzed for plasma levels of VWF antigen (VWFAg), collagen-binding activity (VWFAc), ADAMTS13 activity, and HNP1-3 proteins. Mean values of plasma VWFAg, VWFAc, and HNP1-3 were significantly increased in TBI patients compared to those in healthy controls (n = 30). Conversely, mean plasma values of ADAMTS13 activity in TBI patients were significantly decreased during the first 2 days after admission. This resulted in a dramatic reduction in the ratio of ADAMTS13 activity to VWFAg or ADAMTS13 to VWFAc in all 5 post-TBI days. Cluster analysis demonstrated that high median plasma levels of VWFAg and HNP1-3 were observed in the cluster with a high mortality rate. These results demonstrate that a relative deficiency of plasma ADAMTS13 activity, resulting from activation of neutrophils and endothelium, may contribute to the formation of microvascular thrombosis and mortality after moderate-severe TBI.

Elevated Red Cell Distribution Width is Associated with Cerebral Infarction in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Elevated red blood cell distribution width (RDW) has been associated with thrombotic disorders including myocardial infarction, venous thromboembolism, and ischemic stroke, independent of other inflammatory and coagulation biomarkers. The purpose of this study was to determine whether elevated RDW is associated with cerebral infarction and poor outcome after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: In this retrospective single-center cohort of aSAH patients (October 2009-September 2014), elevated RDW was defined as a mean RDW >14.5 % during the first 14 days after aSAH. Outcomes included cerebral infarction (CI) by any mechanism and poor functional outcome, defined as discharge modified Rankin Scale (mRS) >4, indicating severe disability or death. RESULTS: Of 179 patients, 27 % had a high Hunt-Hess grade (IV-V), and 76 % were women. Twenty-four patients (13.4 %) underwent red blood cell (RBC) transfusion and compared to patients with normal RDW, patients with an elevated RDW were at greater odds of RBC transfusion (OR 2.56 [95 % CI, 1.07-6.11], p = 0.035). In univariate analysis, more patients with elevated RDW experienced CI (30.8 vs. 13.7 %, p = 0.017). In the multivariable model, elevated RDW was significantly associated with CI (OR 3.08 [95 % CI, 1.30-7.32], p = 0.011), independent of known confounders including but not limited to age, sex, race, high Hunt-Hess grade, and RBC transfusion. In multivariable analysis, RDW elevation was also associated with poor functional outcome (mRS > 4) at discharge (OR 2.59 [95 % CI, 1.04-629], p = 0.040). CONCLUSIONS: RDW elevation is associated with cerebral infarction and poor outcome after aSAH. Further evaluation of this association is warranted as it may shed light on mechanistic relations between anemia, inflammation, and thrombosis after aSAH.

Thromboelastography Parameter Predicts Outcome After Subarachnoid Hemorrhage: An Exploratory Analysis.

OBJECTIVE: Hypercoagulability after subarachnoid hemorrhage (SAH) is well described and may be platelet mediated. Thromboelastography (TEG) provides a global assessment of coagulation. We sought to determine whether the maximum amplitude (MA) parameter of TEG, a measure of platelet strength and function, is associated with outcome after SAH. METHODS: One hundred ten TEG analyses were performed for patients with moderate-to-severe SAH and compared with 6 healthy age- and sex-matched controls. TEG indices included MA, G value (G), alpha angle, and thrombus generation and were correlated to functional outcomes and laboratory tests including complete blood count, erythrocyte sedimentation rate, high sensitivity C-reactive protein, fibrinogen, and d-dimer, obtained on post-bleed days (PBDs) 1, 3, 5, 7, and 10. RESULTS: MA was significantly elevated compared with controls on PBD 3 (70.0 mm ± 4.5 mm vs. 64.1 mm ± 6.5 mm; P = 0.02), PBD 5 (72.6 mm ± 5.3 mm vs. 64.1 mm ± 6.5 mm; P = 0.003), PBD 7 (73.0 mm ± 5.4 mm vs. 64.1 mm ± 6.5 mm; P = 0.003), and PBD 10 (73.4 mm ± 6.0 mm vs. 64.1 mm ± 6.5 mm; P = 0.005). G was significantly elevated compared with controls on PBD 3 (P = 0.03), PBD 5 (P = 0.01), PBD 7 (P = 0.01), and PBD 10 (P = 0.02). The only biomarker associated with poor outcome was CRP. Multivariate logistic regression demonstrated an association between elevated MA and outcome (odds ratio 39.1, P = 0.006) independent of CRP, age, Hunt Hess grade, and transfusion. CONCLUSIONS: TEG indices are associated with poor outcome after SAH and may identify a platelet-mediated hypercoagulable state. The association between MA and outcome was stronger than that between traditional biomarkers and was independent of age and Hunt Hess grade.

Cerebral Microdialysis.

A variety of neuromonitoring techniques are available to aid in the care of neurocritically ill patients. However, traditional monitors lack the ability to measure brain biochemistry and may provide inadequate warning of potentially reversible deleterious conditions. Cerebral microdialysis (CMD) is a safe, novel method of monitoring regional brain biochemistry. Analysis of CMD analytes as part of a multimodal approach may help inform clinical decision making, guide medical treatments, and aid in prognostication of patient outcome. Its use is most frequently documented in traumatic brain injury and subarachnoid hemorrhage. Incorporating CMD into clinical practice is a multidisciplinary effort.

Thromboelastography defines late hypercoagulability after TBI: a pilot study.

INTRODUCTION: Traumatic brain injury (TBI) is associated with a hypercoagulable state, the mechanism and duration of which remain unclear. We sought to determine whether thromboelastography (TEG) analysis could identify the hypercoagulable state after TBI, as defined by elevations in maximal amplitude (MA), thrombus generation (TG), G value (G), and alpha angle (αA). METHODS: Patients with moderate-severe TBI, defined primarily as a GCS <12, admitted between 1/2012 and 8/2013 were eligible for enrolment in this prospective cohort study. TEG profiles were obtained between 0-24 h (T1), 24-48 h (T2), 48-72 h (T3), 72-96 h (T4), and 96-120 h (T5) after admission. Early TEG was defined as 0-48 h, and late TEG was defined as >48 h. RESULTS: Twenty five patients (80 % men) and 7 age- and sex-matched control subjects were studied. Median age was 38 years (range 18-85). Early MA was [63.6 mm (60.5, 67.4)] versus late MA [69.9 mm (65.2,73.9); p = 0.02], early TG was [763.3 mm/min (712.8, 816.2)] versus late TG [835.9 mm/min (791.2,888.3); p = 0.02], and early G was [8.8 d/cm(2) (7.7,10.4)] versus late G [11.6 d/cm(2) (9.4,14.1); p = 0.02]. Study patients had higher MA (p = 0.02), TG (p = 0.03), and G (p = 0.02) values at T5 compared to controls. There was a linear increase per day of MA by 2.6 mm (p = 0.001), TG 31.9 mm/min (p ≤ 0.001), and G value by 1.3 d/cm(2) (p ≤ 0.001) when clustered by pairs in regression analysis. Lower MA values trended toward home discharge (p = 0.08). CONCLUSION: The data suggest a progressive and delayed hypercoagulable state observed days after initial TBI. The hypercoagulable state may reflect excess platelet activity.

Cervical laminoforaminotomy for radiculopathy: Symptomatic and functional outcomes in a large cohort with long-term follow-up.

BACKGROUND: The efficacy and safety of cervical laminoforaminotomy (FOR) in the treatment of cervical radiculopathy has been demonstrated in several series with follow-up less than a decade. However, there is little data analyzing the relative effectiveness of FOR for radiculopathy due to soft disc versus osteophyte disease. In the present study, we review our experience with FOR in a single-center cohort, with long-term follow-up. METHODS: We examined the charts of patients who underwent 1085 FORs between 1990 and 2009. A cohort of these patients participated in a telephone interview designed to assess improvement in symptoms and function. RESULTS: A total of 338 interviews were completed with a mean follow-up of 10 years. Approximately 90% of interviewees reported improved pain, weakness, or function following FOR. Ninety-three percent of patients were able to return to work after FOR. The overall complication rate was 3.3%, and the rate of recurrent radiculopathy requiring surgery was 6.2%. Soft disc subtypes compared to osteophyte disease by operative report were associated with improved symptoms (P < 0.05). The operative report of these pathologic subtypes was associated with the preoperative magnetic resonance imaging (MRI) interpretation (P < 0.001). CONCLUSIONS: These results suggest that FOR is a highly effective surgical treatment for cervical radiculopathy with a low incidence of complications. Radiculopathy due to soft disc subtypes may be associated with a better prognosis compared to osteophyte disease, although osteophyte disease remains an excellent indication for FOR.

Brief report: a comparison of clinical and research practices in measuring cerebral perfusion pressure: a literature review and practitioner survey.

BACKGROUND: Our objective was to determine whether there is variability in the foundational literature and across centers in how mean arterial blood pressure is measured to calculate cerebral perfusion pressure. METHODS: We reviewed foundational literature and sent an e-mail survey to members of the Neurocritical Care Society. RESULTS: Of 32 articles reporting cerebral perfusion pressure data, the reference point for mean arterial blood pressure was identified in 16: 10 heart and 6 midbrain. The overall survey response rate was 14.3%. Responses from 31 of 34 (91%) United Council for Neurologic Subspecialties fellowship-accredited Neurointensive Care Units indicated the reference point was most often the heart (74%), followed by the midbrain (16%). Conflicting answers were received from 10%. CONCLUSIONS: There is substantive heterogeneity in both research reports and clinical practice in how mean arterial blood pressure is measured to determine cerebral perfusion pressure.

Temporal dynamics of microparticle elevation following subarachnoid hemorrhage.

OBJECT: Microparticles (MPs), small membrane fragments shed from various cell types, have been implicated in thrombosis, inflammation, and endothelial dysfunction. Their involvement in subarachnoid hemorrhage (SAH) and the development of cerebral infarction and clinical deterioration caused by delayed cerebral ischemia (DCI) remain ill defined. The authors sought to quantify the magnitude of elevations in MPs, delineate the temporal dynamics of elevation, and analyze the correlation between MPs and DCI in patients with SAH. METHODS: On the day of hemorrhage and on Days 1, 3, 5, 7, and 10 after hemorrhage, peripheral blood samples were drawn from 22 patients with SAH. Plasma samples were labeled with Annexin V and CD142, CD41a, CD235a, CD146, CD66b, or von Willebrand factor (vWF) and were quantified by flow cytometry. Clinical data, including the 3-month extended Glasgow Outcome Scale (GOS-E) scores, infarction as measured on MRI at 14 days after SAH, and vasospasm as measured by transcranial Doppler ultrasonography and angiography, were collected and compared with the MP burden. RESULTS: When averaged over time, all MP subtypes were elevated relative to controls. The CD235a+(erythrocyte)-, CD66b+(neutrophil)-, and vWF-associated MPs peaked on the day of hemorrhage and quickly declined. The CD142+(tissue factor [TF])-associated MPs and CD146+(endothelial cell)-associated MPs were significantly elevated throughout the study period. There was a strong negative correlation between TF-expressing and endothelial-derived MPs at Day 1 after SAH and the risk of infarction at Day 14 after SAH. CONCLUSIONS: Microparticles of various subtypes are elevated following SAH; however, the temporal profile of this elevation varies by subtype. Those subtypes closely associated with thrombosis and endothelial dysfunction, for example, CD145+(TF)-associated MPs and CD146+(endothelial cell)-associated MPs, had the most durable response and demonstrated a significant negative correlation with radiographic infarction at 14 days after SAH. Levels of these MPs predict infarction as early as Day 1 post-SAH.

Anemia and brain oxygen after severe traumatic brain injury.

PURPOSE: To investigate the relationship between hemoglobin (Hgb) and brain tissue oxygen tension (PbtO(2)) after severe traumatic brain injury (TBI) and to examine its impact on outcome. METHODS: This was a retrospective analysis of a prospective cohort of severe TBI patients whose PbtO(2) was monitored. The relationship between Hgb-categorized into four quartiles (≤9; 9-10; 10.1-11; >11 g/dl)-and PbtO(2) was analyzed using mixed-effects models. Anemia with compromised PbtO(2) was defined as episodes of Hgb ≤ 9 g/dl with simultaneous PbtO(2) < 20 mmHg. Outcome was assessed at 30 days using the Glasgow outcome score (GOS), dichotomized as favorable (GOS 4-5) vs. unfavorable (GOS 1-3). RESULTS: We analyzed 474 simultaneous Hgb and PbtO(2) samples from 80 patients (mean age 44 ± 20 years, median GCS 4 (3-7)). Using Hgb > 11 g/dl as the reference level, and controlling for important physiologic covariates (CPP, PaO(2), PaCO(2)), Hgb ≤ 9 g/dl was the only Hgb level that was associated with lower PbtO(2) (coefficient -6.53 (95 % CI -9.13; -3.94), p < 0.001). Anemia with simultaneous PbtO(2) < 20 mmHg, but not anemia alone, increased the risk of unfavorable outcome (odds ratio 6.24 (95 % CI 1.61; 24.22), p = 0.008), controlling for age, GCS, Marshall CT grade, and APACHE II score. CONCLUSIONS: In this cohort of severe TBI patients whose PbtO(2) was monitored, a Hgb level no greater than 9 g/dl was associated with compromised PbtO(2). Anemia with simultaneous compromised PbtO(2), but not anemia alone, was a risk factor for unfavorable outcome, irrespective of injury severity.

Brain lactate metabolism in humans with subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Lactate is central for the regulation of brain metabolism and is an alternative substrate to glucose after injury. Brain lactate metabolism in patients with subarachnoid hemorrhage has not been fully elucidated. METHODS: Thirty-one subarachnoid hemorrhage patients monitored with cerebral microdialysis (CMD) and brain oxygen (PbtO(2)) were studied. Samples with elevated CMD lactate (>4 mmol/L) were matched to PbtO(2) and CMD pyruvate and categorized as hypoxic (PbtO(2) <20 mm Hg) versus nonhypoxic and hyperglycolytic (CMD pyruvate >119 µmol/L) versus nonhyperglycolytic. RESULTS: Median per patient samples with elevated CMD lactate was 54% (interquartile range, 11%-80%). Lactate elevations were more often attributable to cerebral hyperglycolysis (78%; interquartile range, 5%-98%) than brain hypoxia (11%; interquartile range, 4%-75%). Mortality was associated with increased percentage of samples with elevated lactate and brain hypoxia (28% [interquartile range 9%-95%] in nonsurvivors versus 9% [interquartile range 3%-17%] in survivors; P=0.02) and lower percentage of elevated lactate and cerebral hyperglycolysis (13% [interquartile range, 1%-87%] versus 88% [interquartile range, 27%-99%]; P=0.07). Cerebral hyperglycolytic lactate production predicted good 6-month outcome (odds ratio for modified Rankin Scale score, 0-3 1.49; CI, 1.08-2.05; P=0.016), whereas increased lactate with brain hypoxia was associated with a reduced likelihood of good outcome (OR, 0.78; CI, 0.59-1.03; P=0.08). CONCLUSIONS: Brain lactate is frequently elevated in subarachnoid hemorrhage patients, predominantly because of hyperglycolysis rather than hypoxia. A pattern of increased cerebral hyperglycolytic lactate was associated with good long-term recovery. Our data suggest that lactate may be used as an aerobic substrate by the injured human brain.

Brain tissue oxygen-based therapy and outcome after severe traumatic brain injury: a systematic literature review.

Observational clinical studies demonstrate that brain hypoxia is associated with poor outcome after severe traumatic brain injury (TBI). In this study, available medical literature was reviewed to examine whether brain tissue oxygen (PbtO2)-based therapy is associated with improved patient outcome after severe TBI. Clinical studies published between 1993 and 2010 that compared PbtO2-based therapy combined with intracranial and cerebral perfusion pressure (ICP/CPP)-based therapy to ICP/CPP-based therapy alone were identified from electronic databases, Index Medicus, bibliographies of pertinent articles, and expert consultation. For analysis, each selected paper had to have adequate data to determine odds ratios (ORs) and confidence intervals (CIs) of outcome described by the Glasgow outcome score (GOS). Seven studies that compared ICP/CPP and PbtO2- to ICP/CPP-based therapy were identified. There were no randomized studies and no comparison studies in children. Four studies, published in 2003, 2009, and 2010 that included 491 evaluable patients were used in the final analysis. Among patients who received PbtO2-based therapy, 121(38.8%) had unfavorable and 191 (61.2%) had a favorable outcome. Among the patients who received ICP/CPP-based therapy 104 (58.1%) had unfavorable and 75 (41.9%) had a favorable outcome. Overall PbtO2-based therapy was associated with favorable outcome (OR 2.1; 95% CI 1.4-3.1). Summary results suggest that combined ICP/CPP- and PbtO2-based therapy is associated with better outcome after severe TBI than ICP/CPP-based therapy alone. Cross-organizational practice variances cannot be controlled for in this type of review and so we cannot answer whether PbtO2-based therapy improves outcome. However, the potentially large incremental value of PbtO2-based therapy provides justification for a randomized clinical trial.

Obesity is associated with reduced brain tissue oxygen tension after severe brain injury.

BACKGROUND: Obesity has been associated with compromised tissue oxygenation and reduced organ perfusion. The brain is critically dependent on oxygen delivery, and reduced brain tissue oxygen tension (P(bt)O(2)) may result in poor outcome after brain injury. We tested the hypothesis that obesity is associated with compromised P(bt)O(2) after severe brain injury. METHODS: Patients with severe brain injury (GCS score ≤ 8) who underwent continuous P(bt)O(2) monitoring were retrospectively identified from a prospective single-center database. Patients, were classified by body mass index (BMI = weight (kg)/m(2)) and were included if they were obese (BMI ≥ 30) or non-obese (BMI = < 30). RESULTS: Sixty-nine patients (mean age 46.4 ± 17.0 years) were included. Mean daily P(bt)O(2) was 25.8 (9.6) mmHg for the 28 obese and 31.8 (12.3) mmHg for the 41 non-obese patients (P = 0.03). Initial P(bt)O(2) and mean daily maximum P(bt)O(2) measurements also were significantly lower in obese patients than in non-obese patients. Univariate predictors of compromised P(bt)O(2) (defined as minutes P(bt)O(2) < 20 mmHg) included elevated BMI (P = 0.02), presence of ARDS (P < 0.01), mean PaO(2) (P < 0.01), maximum FiO(2) (P < 0.01), mean PaO(2):FiO(2) (P < 0.01), and mean CVP (P < 0.01). In multivariable analysis, BMI was significantly associated with compromised P(bt)O(2) (P = 0.02). Sex, age, and mean CVP were also identified as significant predictors of compromised P(bt)O(2); ARDS and PF ratio were not. CONCLUSIONS: In patients with severe brain injury, obesity was found to be an independent predictor of compromised P(bt)O(2). This effect may be mediated through obesity-related pulmonary dysfunction and inadequate compensatory mechanisms.

Detection of cerebral compromise with multimodality monitoring in patients with subarachnoid hemorrhage.

BACKGROUND: Studies in traumatic brain injury suggest that monitoring techniques such as brain tissue oxygen (P(BTO2)) and cerebral microdialysis may complement conventional intracranial pressure (ICP) and cerebral perfusion pressure (CPP) measurements. OBJECTIVE: In this study of poor-grade (Hunt and Hess grade IV and V) subarachnoid hemorrhage (SAH) patients, we examined the prevalence of brain hypoxia and brain energy dysfunction in the presence of normal and abnormal ICP and CPP. METHODS: SAH patients who underwent multimodal neuromonitoring and cerebral microdialysis were studied. We examined the frequency of brain hypoxia and energy dysfunction in different ICP and CPP ranges and the relationship between P(BTO2) and the lactate/pyruvate ratio (LPR). RESULTS: A total of 2394 samples from 19 patients were analyzed. There were 149 samples with severe brain hypoxia (P(BTO2) ≤10 mm Hg) and 347 samples with brain energy dysfunction (LPR >40). The sensitivities of abnormal ICP or CPP for elevated LPR and reduced P(BTO2) were poor (21.2% at best), and the LPR or P(BTO2) was abnormal in many instances when ICP or CPP was normal. Severe brain hypoxia was often associated with an LPR greater than 40 (86% of samples). In contrast, mild brain hypoxia (≤20 mm Hg) and severe brain hypoxia were observed in only 53% and 36% of samples with brain energy dysfunction, respectively. CONCLUSION: Our data demonstrate that ICP and CPP monitoring may not always detect episodes of cerebral compromise in SAH patients. Our data suggest that several complementary monitors may be needed to optimize the care of poor-grade SAH patients.

Brain hypoxia is associated with short-term outcome after severe traumatic brain injury independently of intracranial hypertension and low cerebral perfusion pressure.

BACKGROUND: Brain hypoxia (BH) can aggravate outcome after severe traumatic brain injury (TBI). Whether BH or reduced brain oxygen (Pbto(2)) is an independent outcome predictor or a marker of disease severity is not fully elucidated. OBJECTIVE: To analyze the relationship between Pbto(2), intracranial pressure (ICP), and cerebral perfusion pressure (CPP) and to examine whether BH correlates with worse outcome independently of ICP and CPP. METHODS: We studied 103 patients monitored with ICP and Pbto(2) for > 24 hours. Durations of BH (Pbto(2) < 15 mm Hg), ICP > 20 mm Hg, and CPP < 60 mm Hg were calculated with linear interpolation, and their associations with outcome within 30 days were analyzed. RESULTS: Duration of BH was longer in patients with unfavorable (Glasgow Outcome Scale score, 1-3) than in those with favorable (Glasgow Outcome Scale, 4-5) outcome (8.3 ± 15.9 vs 1.7 ± 3.7 hours; P < .01). In patients with intracranial hypertension, those with BH had fewer favorable outcomes (46%) than those without (81%; P < .01); similarly, patients with low CPP and BH were less likely to have favorable outcome than those with low CPP but normal Pbto(2) (39% vs 83%; P < .01). After ICP, CPP, age, Glasgow Coma Scale score, Marshall computed tomography grade, and Acute Physiology and Chronic Health Evaluation II score were controlled for, BH was independently associated with poor prognosis (adjusted odds ratio for favorable outcome, 0.89 per hour of BH; 95% confidence interval, 0.79-0.99; P = .04). CONCLUSION: Brain hypoxia is associated with poor short-term outcome after severe traumatic brain injury independently of elevated ICP, low CPP, and injury severity. Pbto(2) may be an important therapeutic target after severe traumatic brain injury.

Reduced brain tissue oxygen in traumatic brain injury: are most commonly used interventions successful?

BACKGROUND: Brain tissue oxygenation (PbtO2)-guided management facilitates treatment of reduced PbtO2 episodes potentially conferring survival and outcome advantages in severe traumatic brain injury (TBI). To date, the nature and effectiveness of commonly used interventions in correcting compromised PbtO2 in TBI remains unclear. We sought to identify the most common interventions used in episodes of compromised PbtO2 and to analyze which were effective. METHODS: A retrospective 7-year review of consecutive severe TBI patients with a PbtO2 monitor was conducted in a Level I trauma center's intensive care unit or neurosurgical registry. Episodes of compromised PbtO2 (defined as <20 mm Hg for 0.25-4 hours) were identified, and clinical interventions conducted during these episodes were analyzed. Response to treatment was gauged on how rapidly (ΔT) PbtO2 normalized (>20 mm Hg) and how great the PbtO2 increase was (ΔPbtO2). Intracranial pressure (ΔICP) and cerebral perfusion pressure (ΔCPP) also were examined for these episodes. RESULTS: Six hundred twenty-five episodes of reduced PbtO2 were identified in 92 patients. Patient characteristics were: age 41.2 years, 77.2% men, and Injury Severity Score and head or neck Abbreviated Injury Scale score of 34.0 ± 9.2 and 4.9 ± 0.4, respectively. Five interventions: narcotics or sedation, pressors, repositioning, FIO2/PEEP increases, and combined sedation or narcotics + pressors were the most commonly used strategies. Increasing the number of interventions resulted in worsening the time to PbtO2 correction. Triple combinations resulted in the lowest ΔICP and dual combinations in the highest ΔCPP (p < 0.05). CONCLUSION: Clinicians use a limited number of interventions when correcting compromised PbtO2. Using strategies employing many interventions administered closely together may be less effective in correcting PbO2, ICP, and CPP deficits. Some PbtO2 deficits may be self-limited.

Medical management of compromised brain oxygen in patients with severe traumatic brain injury.

BACKGROUND: Brain tissue oxygen (PbtO(2)) monitoring is used in severe traumatic brain injury (TBI) patients. How brain reduced PbtO(2) should be treated and its response to treatment is not clearly defined. We examined which medical therapies restore normal PbtO(2) in TBI patients. METHODS: Forty-nine (mean age 40 ± 19 years) patients with severe TBI (Glasgow Coma Scale [GCS] ≤ 8) admitted to a University-affiliated, Level I trauma center who had at least one episode of compromised brain oxygen (PbtO(2) <25 mmHg for >10 min), were retrospectively identified from a prospective observational cohort study. Intracranial pressure (ICP), cerebral perfusion pressure (CPP), and PbtO(2) were monitored continuously. Episodes of compromised PbtO(2) and brain hypoxia (PbtO(2) <15 mmHg for >10 min) and the medical interventions that improved PbtO(2) were identified. RESULTS: Five hundred and sixty-four episodes of compromised PbtO2 were identified from 260 days of PbtO2 monitoring. Medical management used in a "cause-directed" manner successfully reversed 72% of the episodes of compromised PbtO(2), defined as restoration of a "normal" PbtO(2) (i.e. ≥ 25 mmHg). Ventilator manipulation, CPP augmentation, and sedation were the most frequent interventions. Increasing FiO(2) restored PbtO(2) 80% of the time. CPP augmentation and sedation were effective in 73 and 66% of episodes of compromised brain oxygen, respectively. ICP reduction using mannitol was effective in 73% of treated episodes, though was used only when PbtO(2) was compromised in the setting of elevated ICP. Successful medical treatment of brain hypoxia was associated with decreased mortality. Survivors (n = 38) had a 71% rate of response to treatment and non-survivors (n = 11) had a 44% rate of response (P = 0.01). CONCLUSION: Reduced PbtO(2) may occur in TBI patients despite efforts to maintain CPP. Medical interventions other than those to treat ICP and CPP can improve PbtO(2). This may increase the number of therapies for severe TBI in the ICU.