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ABSTRACT: 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.
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.
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.
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.
Journal of Neurosurgery 07/2012; 117(3):579-86. · 2.96 Impact Factor
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ABSTRACT: 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.
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).
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.
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.
European Journal of Intensive Care Medicine 05/2012; 38(9):1497-504. · 5.17 Impact Factor
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Gurpreet S. Kapoor,
Timothy A. Gocke,
Sanjeev Chawla,
Robert G. Whitmore,
Ali Nabavizadeh,
Jaroslaw Krejza,
Joanna Lopinto,
Justin Plaum, Eileen Maloney-Wilensky,
Harish Poptani,
Elias R. Melhem,
Kevin D. Judy,
Donald M. O’Rourke
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ABSTRACT: 1p19q LOH has been shown to predict radio- and chemosensitivity and prolonged survival in oligodendrogliomas (OLs). We have
recently shown that magnetic resonance perfusion-weighted imaging (MR-PWI) may be useful in predicting the histopathological
grade or cytogenetic type of oligodendroglial neoplasms. MR-PWI allows noninvasive determination of relative tumor blood volume
(rTBV), which may reflect the degree of neoplastic angiogenesis and metabolism. The present study was aimed to correlate rTBV
to the angiogenic markers and EGFR expression in oligodendroglial tumors with 1p/19q LOH or 1p LOH (Group 1) and 1p19q intact
alleles or 19q LOH (Group 2), respectively. In WHO grade II neoplasms, Group 1 showed significantly greater rTBV than Group
2 (P=0.013). However, the differences between Group 1 and Group 2 were not significant in grade III tumors. Probe-based real-time
RT-PCR analyses showed that 12% of Group 2 high-grade tumors with intact 1p19q exhibited dramatic EGFR overexpression (designated
EGFR-high). Grade III neoplasms showed a significantly higher rTBV than grade II neoplasms. Group 1 tumors showed significantly higher
rTBV than Group 2 tumors, independent of the EGFR-high subtype. Real-time RT-PCR analyses showed increased expression of VEGF, CD31 and CD105 in Group 1 tumors as compared to Group
2 tumors, excluding the EGFR-high subtype. Multivariable linear regression analysis showed a significant association of rTBV with 1p19q LOH, and expression
of EGFR and VEGF. Therefore, the combined use of extensive molecular profiling and advanced MR imaging modalities may improve
the accuracy of tumor grading, provide prognostic information, and has the potential to influence treatment decisions.
Journal of Neuro-Oncology 04/2012; 92(3):373-386. · 3.21 Impact Factor
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Meeri N. Kim,
Turgut Durduran,
Suzanne Frangos,
Brian L. Edlow,
Erin M. Buckley,
Heather E. Moss,
Chao Zhou,
Guoqiang Yu,
Regine Choe, Eileen Maloney-Wilensky,
Ronald L. Wolf,
M. Sean Grady,
Joel H. Greenberg,
Joshua M. Levine,
Arjun G. Yodh,
John A. Detre,
W. Andrew Kofke
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ABSTRACT: BackgroundThis study assesses the utility of a hybrid optical instrument for noninvasive transcranial monitoring in the neurointensive
care unit. The instrument is based on diffuse correlation spectroscopy (DCS) for measurement of cerebral blood flow (CBF),
and near-infrared spectroscopy (NIRS) for measurement of oxy- and deoxy-hemoglobin concentration. DCS/NIRS measurements of
CBF and oxygenation from frontal lobes are compared with concurrent xenon-enhanced computed tomography (XeCT) in patients
during induced blood pressure changes and carbon dioxide arterial partial pressure variation.
MethodsSeven neurocritical care patients were included in the study. Relative CBF measured by DCS (rCBFDCS), and changes in oxy-hemoglobin (ΔHbO2), deoxy-hemoglobin (ΔHb), and total hemoglobin concentration (ΔTHC), measured by NIRS, were continuously monitored throughout
XeCT during a baseline scan and a scan after intervention. CBF from XeCT regions-of-interest (ROIs) under the optical probes
were used to calculate relative XeCT CBF (rCBFXeCT) and were then compared to rCBFDCS. Spearman’s rank coefficients were employed to test for associations between rCBFDCS and rCBFXeCT, as well as between rCBF from both modalities and NIRS parameters.
ResultsrCBFDCS and rCBFXeCT showed good correlation (r
s=0.73, P=0.010) across the patient cohort. Moderate correlations between rCBFDCS and ΔHbO2/ΔTHC were also observed. Both NIRS and DCS distinguished the effects of xenon inhalation on CBF, which varied among the patients.
ConclusionsDCS measurements of CBF and NIRS measurements of tissue blood oxygenation were successfully obtained in neurocritical care
patients. The potential for DCS to provide continuous, noninvasive bedside monitoring for the purpose of CBF management and
individualized care is demonstrated.
KeywordsNear-infrared spectroscopy-Diffuse correlation spectroscopy-Cerebral blood flow-Xenon CT-Neurocritical care
Neurocritical Care 04/2012; 12(2):173-180. · 2.47 Impact Factor
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ABSTRACT: 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.
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.
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).
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.
Stroke 02/2012; 43(5):1418-21. · 5.73 Impact Factor
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ABSTRACT: 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.
Neurocritical Care 08/2011; 17(1):131-8. · 2.47 Impact Factor
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ABSTRACT: 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.
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).
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.
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.
Neurocritical Care 07/2011; 16(2):286-93. · 2.47 Impact Factor
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ABSTRACT: 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.
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.
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).
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.
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.
Neurosurgery 07/2011; 69(1):53-63; discussion 63. · 2.79 Impact Factor
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Mauro Oddo,
Joshua M Levine,
Larami Mackenzie,
Suzanne Frangos,
François Feihl,
Scott E Kasner,
Michael Katsnelson,
Bryan Pukenas,
Eileen Macmurtrie, Eileen Maloney-Wilensky,
W Andrew Kofke,
Peter D LeRoux
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ABSTRACT: 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.
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.
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.
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).
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.
Neurosurgery 06/2011; 69(5):1037-45; discussion 1045. · 2.79 Impact Factor
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ABSTRACT: 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.
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.
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).
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.
Neurocritical Care 03/2011; 14(3):361-9. · 2.47 Impact Factor
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ABSTRACT: 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.
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.
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).
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.
The Journal of trauma 03/2011; 70(3):535-46. · 2.48 Impact Factor
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ABSTRACT: Follow-up head CT scans are important in neurocritical care but involve intrahospital transport that may be associated with potential hazards including a deleterious effect on brain tissue oxygen pressure (PbtO(2)). Portable head CT (pHCT) scans offer an alternative imaging technique without a need for patient transport. In this study, the investigators examined the effects of pHCT scans on intracranial pressure (ICP), cerebral perfusion pressure (CPP), and PbtO(2) in patients with severe brain injury.
Fifty-seven pHCT scans were obtained in 34 patients (mean age of 42 ± 15 years) who underwent continuous ICP, CPP, and PbtO(2) monitoring in the neuro intensive care unit at a university-based Level I trauma center. Patient ICU records were retrospectively reviewed and physiological data obtained during the 3 hours before and after pHCT scans were examined.
Before pHCT, the mean ICP and CPP were 14.3 ± 7.4 and 78.9 ± 20.2 mm Hg, respectively. Portable HCT had little effect on ICP (mean ICP 14.1 ± 6.6 mm Hg, p = 0.84) and CPP (mean CPP 81.0 ± 19.8 mm Hg, p = 0.59). The mean PbtO(2) was similar before and after pHCT (33.2 ± 17.0 mm Hg and 31.6 ± 15.9 mm Hg, respectively; p = 0.6). Ten episodes of brain hypoxia (PbtO(2) < 15 mm Hg) were observed before pHCT; these episodes prompted scans. Brain hypoxia persisted in 5 patients after pHCT despite treatment. No new episodes of brain hypoxia were observed during or after pHCT.
These data suggest that pHCT scans do not have a detectable effect on a critically ill patient's ICP, CPP, or PbtO(2).
Journal of Neurosurgery 12/2010; 114(5):1479-84. · 2.96 Impact Factor
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ABSTRACT: How body position influences brain tissue oxygen (PbtO2) and intracranial pressure (ICP) in critically ill neurosurgical patients remains poorly defined. In a prospective observational repeated measures study, we examined the effects of 12 different body positions on neurodynamic and hemodynamic outcomes. Thirty-three consecutive patients (mean +/- SD, age = 48.3 +/- 16.6 years; 22 men), admitted after traumatic brain injury, subarachnoid hemorrhage, or craniotomy for tumor, were evaluated in a neurocritical care unit at a level 1 academic trauma center. Patients were eligible if the admission score in the Glasgow Coma Scale was < or =8 and they had a Licox CMP Monitoring System (Integra Neurosciences, Plainsboro, NJ). Patients were exposed to all 12 positions in random order. Changes from baseline to the 15-minute postposition assessment mean change scores showed a downward trend for PbtO2 for all positions with statistically significant decreases observed for supine head of bed (HOB) elevated 30 degrees and 45 degrees (p < .01) and right and left lateral positioning HOB 30 degrees (p < .05). ICP decreased with supine HOB 45 degrees (p < .01) and knee elevation, HOB 30 degrees and 45 degrees (p < .05), and increased (p < .05) with right and left lateral HOB 15 degrees. Hemodynamic parameters were similar in the various positions. Positioning practices can positively or negatively affect PbtO2 and ICP and fluctuate with considerable variability among patients. Nurses must consider potential effects of turning, evaluate changes with positioning on the basis of monitoring feedback from multimodality devices, and make independent clinical judgments about optimal positions to maintain or improve cerebral oxygenation.
Journal of Neuroscience Nursing 10/2010; 42(5):280-7. · 0.81 Impact Factor
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ABSTRACT: Pulmonary complications are frequently observed after severe traumatic brain injury (TBI), but little is known about the consequences of lung injury on brain tissue oxygenation and metabolism.
We examined the association between lung function and brain tissue oxygen tension (PbtO2) in patients with severe TBI.
We analyzed data from 78 patients with severe, nonpenetrating TBI who underwent continuous PbtO2 and intracranial pressure monitoring. Acute lung injury was defined by the presence of pulmonary infiltrates with a PaO2/FiO2 (PF) ratio less than 300 and the absence of left ventricular failure. A total of 587 simultaneous measurements of PbtO2 and PF ratio were examined using longitudinal data analysis.
PbtO2 correlated strongly with PaO2 and PF ratio (P < .05) independent of PaCO2, brain temperature, cerebral perfusion pressure, and hemoglobin. Acute lung injury was associated with lower PbtO2 (34.6 +/- 13.8 mm Hg at PF ratio >300 vs 30.2 +/- 10.8 mm Hg [PF ratio 200-300], 28.9 +/- 9.8 mm Hg [PF ratio 100-199], and 21.1 +/- 7.4 mm Hg [PF ratio <100], all P values <.01). After adjusting for intracranial pressure, Marshall computed tomography score, and APACHE II (Acute Physiology and Chronic Health Evaluation) score, acute lung injury was an independent risk factor for compromised PbtO2 (PbtO2 <20 mm Hg; adjusted odds ratio: 2.13, 95% confidence interval: 1.21-3.77; P < .01).
After severe TBI, PbtO2 correlates with PF ratio. Acute lung injury is associated with an increased risk of compromised PbtO2, independent from intracerebral and systemic injuries. Our findings support the use of lung-protective strategies to prevent brain hypoxia in TBI patients.
Neurosurgery 08/2010; 67(2):338-44. · 2.79 Impact Factor
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ABSTRACT: The object of this study was to determine whether brain tissue oxygen (PbtO(2))-based therapy or intracranial pressure (ICP)/cerebral perfusion pressure (CPP)-based therapy is associated with improved patient outcome after severe traumatic brain injury (TBI).
Seventy patients with severe TBI (postresuscitation GCS score < or = 8), admitted to a neurosurgical intensive care unit at a university-based Level I trauma center and tertiary care hospital and managed with an ICP and PbtO(2) monitor (mean age 40 +/- 19 years [SD]) were compared with 53 historical controls who received only an ICP monitor (mean age 43 +/- 18 years). Therapy for both patient groups was aimed to maintain ICP < 20 mm Hg and CPP > 60 mm Hg. Patients with PbtO(2) monitors also had therapy to maintain PbtO(2) > 20 mm Hg.
Data were obtained from 12,148 hours of continuous ICP monitoring and 6,816 hours of continuous PbtO(2) monitoring. The mean daily ICP and CPP and the frequency of elevated ICP (> 20 mm Hg) or suboptimal CPP (< 60 mm Hg) episodes were similar in each group. The mortality rate was significantly lower in patients who received PbtO(2)-directed care (25.7%) than in those who received conventional ICP and CPP-based therapy (45.3%, p < 0.05). Overall, 40% of patients receiving ICP/CPP-guided management and 64.3% of those receiving PbtO(2)-guided management had a favorable short-term outcome (p = 0.01). Among patients who received PbtO(2)-directed therapy, mortality was associated with lower mean daily PbtO(2) (p < 0.05), longer durations of compromised brain oxygen (PbtO(2) < 20 mm Hg, p = 0.013) and brain hypoxia (PbtO(2) < 15 mm Hg, p = 0.001), more episodes and a longer cumulative duration of compromised PbtO(2) (p < 0.001), and less successful treatment of compromised PbtO(2) (p = 0.03).
These results suggest that PbtO(2)-based therapy, particularly when compromised PbtO(2) can be corrected, may be associated with reduced patient mortality and improved patient outcome after severe TBI.
Journal of Neurosurgery 04/2010; 113(3):571-80. · 2.96 Impact Factor
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ABSTRACT: Transport of critically ill intensive care unit (ICU) patients may be hazardous. In this study, we examined the use of a portable head CT scanner (CereTom) in the ICU to assess its feasibility, safety, and radiological quality. Two hundred and twenty-five portable head CT scans were obtained from 114 patients (mean age = 57 +/- 18 years) treated in a neurosurgical intensive care unit at a university-based Level I trauma center. Patient radiological and ICU records were retrospectively reviewed. The vast majority of portable CT scans were performed after an intracranial procedure (24%) due to neurological deterioration (16%) or in routine follow-up (16%). Diagnostic quality was judged to be adequate, and no scans needed to be repeated because of poor quality. No scans were complicated by accidental disconnection of an intravenous line. In ventilated patients, there were no interruptions in mechanical ventilation and no inadvertent extubations. In addition, continuous intracranial monitoring, when in use, remained connected. The average total time to perform a portable head CT scan was 19.5 +/- 3.5 min. The actual scan time was 2.5 +/- 0.7 min. These results suggest that the portable CT scanner (CereTom) is feasible, easy to use, and safe and provides adequate radiological quality for diagnostic decisions.
Journal of Neuroscience Nursing 04/2010; 42(2):109-16. · 0.81 Impact Factor
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ABSTRACT: INTRODUCTION: Secondary neuronal injury is implicated in poor outcome after acute neurological insults. Outcome can be improved with protocol-driven therapy. These therapies have largely been based on monitoring and control of intracranial pressure and the maintenance of an adequate cerebral perfusion pressure. DISCUSSION: In recent years, brain tissue oxygen partial pressure (PbtO2) monitoring has emerged as a clinically useful modality and a complement to intracranial pressure monitors. This review examines the physiology of PbtO2 monitors and practical aspects of their use.
Child s Nervous System 11/2009; 26(4):419-30. · 1.54 Impact Factor
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ABSTRACT: We analyzed the impact of shivering on brain tissue oxygenation (PbtO(2)) during induced normothermia in patients with severe brain injury.
We studied patients with severe brain injury who developed shivering during induced normothermia. Induced normothermia was applied to treat refractory fever (body temperature [BT] > or =38.3 degrees C, refractory to conventional treatment) using a surface cooling device with computerized adjustment of patient BT target to 37 +/- 0.5 degrees C. PbtO(2), intracranial pressure, mean arterial pressure, cerebral perfusion pressure, and BT were monitored continuously. Circulating water temperature of the device system was measured to assess the intensity of cooling.
Fifteen patients (10 with severe traumatic brain injury, 5 with aneurysmal subarachnoid hemorrhage) were treated with induced normothermia for an average of 5 +/- 2 days. Shivering caused a significant decrease in PbtO(2) levels both in SAH and TBI patients. Compared to baseline, shivering was associated with an overall reduction of PbtO(2) from 34.1 +/- 7.3 to 24.4 +/- 5.5 mmHg (P < 0.001). A significant correlation was found between the magnitude of shivering-associated decrease of PbtO(2) (DeltaPbtO(2)) and circulating water temperature (R = 0.82, P < 0.001).
In patients with severe brain injury treated with induced normothermia, shivering was associated with a significant decrease of PbtO(2), which correlated with the intensity of cooling. Monitoring of therapeutic cooling with computerized thermoregulatory systems may help prevent shivering and optimize the management of induced normothermia. The clinical significance of shivering-induced decrease in brain tissue oxygenation remains to be determined.
Neurocritical Care 10/2009; 12(1):10-6. · 2.47 Impact Factor
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Gurpreet S Kapoor,
Timothy A Gocke,
Sanjeev Chawla,
Robert G Whitmore,
Ali Nabavizadeh,
Jaroslaw Krejza,
Joanna Lopinto,
Justin Plaum, Eileen Maloney-Wilensky,
Harish Poptani,
Elias R Melhem,
Kevin D Judy,
Donald M O'Rourke
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ABSTRACT: 1p19q LOH has been shown to predict radio- and chemosensitivity and prolonged survival in oligodendrogliomas (OLs). We have recently shown that magnetic resonance perfusion-weighted imaging (MR-PWI) may be useful in predicting the histopathological grade or cytogenetic type of oligodendroglial neoplasms. MR-PWI allows noninvasive determination of relative tumor blood volume (rTBV), which may reflect the degree of neoplastic angiogenesis and metabolism. The present study was aimed to correlate rTBV to the angiogenic markers and EGFR expression in oligodendroglial tumors with 1p/19q LOH or 1p LOH (Group 1) and 1p19q intact alleles or 19q LOH (Group 2), respectively. In WHO grade II neoplasms, Group 1 showed significantly greater rTBV than Group 2 (P = 0.013). However, the differences between Group 1 and Group 2 were not significant in grade III tumors. Probe-based real-time RT-PCR analyses showed that 12% of Group 2 high-grade tumors with intact 1p19q exhibited dramatic EGFR overexpression (designated EGFR-high). Grade III neoplasms showed a significantly higher rTBV than grade II neoplasms. Group 1 tumors showed significantly higher rTBV than Group 2 tumors, independent of the EGFR-high subtype. Real-time RT-PCR analyses showed increased expression of VEGF, CD31 and CD105 in Group 1 tumors as compared to Group 2 tumors, excluding the EGFR-high subtype. Multivariable linear regression analysis showed a significant association of rTBV with 1p19q LOH, and expression of EGFR and VEGF. Therefore, the combined use of extensive molecular profiling and advanced MR imaging modalities may improve the accuracy of tumor grading, provide prognostic information, and has the potential to influence treatment decisions.
Journal of Neuro-Oncology 06/2009; 92(3):373-86. · 3.21 Impact Factor
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ABSTRACT: In this study, available medical literature were reviewed to determine whether brain hypoxia as measured by brain tissue oxygen (Bto2) levels is associated with increased risk of poor outcome after traumatic brain injury (TBI). A secondary objective was to examine the safety profile of a direct BtO2 probe. DATA SOURCE AND EXTRACTION: Clinical studies published between 1993 and 2008 were identified from electronic databases, Index Medicus, bibliographies of pertinent articles, and expert consultation. The following inclusion criteria were applied for outcome analysis: 1) more than 10 patients described, 2) use of a direct Bto2 monitor, 3) brain hypoxia defined as Bto2 <10 mm Hg for >15 or 30 minutes, 4) 6-month outcome data, and 5) clear reporting of patient outcome associated with Bto2. For the analysis, each selected article had to have adequate data to determine odds ratios (ORs) and confidence intervals (CIs). Thirteen studies met the initial inclusion criteria and three were included in the final outcome analysis. Safety data were abstracted from any report where it was mentioned.
The three studies included 150 evaluable patients with severe TBI (Glasgow Coma Scale <or=8). Brain hypoxia was identified in 71 (47%) of these patients. Among the patients with brain hypoxia, 52 (73%) had unfavorable outcome including 39 (55%) who died. In the absence of brain hypoxia, 34 (43%) patients had an unfavorable outcome, including 17 (22%) who died. Overall brain hypoxia (Bto2 <10 mm Hg >15 minutes) was associated with worse outcome (OR 4.0; 95% CI 1.9-8.2) and increased mortality (OR 4.6; 95% CI 2.2-9.6). We reviewed published safety data; in 292 patients monitored with a Bto2 probe, only two adverse events were reported.
Summary results indicate that brain hypoxia (<10 mm Hg) is associated with worse outcome after severe TBI and that Bto2 probes are safe. These results imply that treating patients to increase Bto2 may improve outcome after severe TBI. This question will require further study.
Critical care medicine 05/2009; 37(6):2057-63. · 6.37 Impact Factor
