Minimally invasive surgery for intracerebral hemorrhage.

PURPOSE OF REVIEW: Spontaneous intracerebral hemorrhage (ICH) is common, associated with a high degree of mortality and long-term functional impairment, and remains without effective proven treatments. Surgical hematoma evacuation can reduce mass effect and decrease cytotoxic effects from blood product breakdown. However, results from large clinical trials that have examined the role of open craniotomy have not demonstrated a significant outcome benefit over medical management. We review the data on minimally invasive surgery (MIS) that is emerging as a treatment modality for spontaneous ICH. RECENT FINDINGS: The use of MIS for supratentorial ICH has increased significantly in recent years and appears to be associated with decreased mortality and improved functional outcome compared with medical management. The role of MIS for posterior fossa ICH is ill-defined. Currently available MIS devices allow for stereotactic aspiration and thrombolysis, endoport-mediated evacuation, and endoscopic aspiration. Clinical series demonstrate that MIS can facilitate significant hematoma volume reduction and may be associated with less morbidity than conventional open surgical approaches. SUMMARY: MIS is an appealing treatment modality for supratentorial ICH and with careful patient selection and technologic advances has the potential to improve neurologic outcomes and reduce mortality. Early and extensive hematoma evacuation are important therapeutic targets and current studies are underway that have the potential to change the management for ICH patients.

The Incidence and Impact of Secondary Cerebral Insults on Outcome After Aneurysmal Subarachnoid Hemorrhage.

INTRODUCTION: Secondary cerebral insults can adversely affect patients with traumatic brain injury. By contrast, the incidence of secondary cerebral insults after aneurysmal subarachnoid hemorrhage (SAH) and their impact on outcome have been less well studied. METHODS: Four hundred and twenty-one patients with SAH who underwent surgical occlusion of their ruptured aneurysm and who received intensive care unit care for ≥48 hours were retrospectively identified from a prospective observational database. Patients were managed according to standard recommendations for SAH. Three secondary cerebral insults were examined: hypotension (<90 mmHg systolic), hypoxia (Pao2 <60 mm Hg), and hyperglycemia (>200 mg/dL). RESULTS: A secondary cerebral insult was observed in 309 (73.4%) patients including 135 (32.1%) who had multiple insults. There was an association between worse clinical grade and development of secondary insults (P = 0.0002), particularly multiple insults (P < 0.0001). When stratified by clinical grade, single (adjusted odds ratio [OR], 2.23; 95% confidence interval [CI], 1.10-4.51; P = 0.026) and multiple (adjusted OR, 4.37; 95% CI, 2.14-8.93; P < 0.0001) secondary cerebral insults were associated with worse outcome. In multivariate analysis and controlling for age, admission clinical grade, severity of SAH on computed tomography, intracerebral hematoma, increased intracranial pressure (>20 mm Hg), rebleed, intraoperative rupture, and hydrocephalus, secondary cerebral insults were independently associated with poor outcome (adjusted OR, 2.45; 95% CI, 1.20-5.02; P = 0.014). CONCLUSIONS: Secondary cerebral insults (hypoxia, hypotension, and hyperglycemia) are common after SAH, including among patients with a good clinical grade. These insults after SAH are associated with worse outcome. These data suggest that prevention of secondary cerebral insults may provide an opportunity to improve patient outcome after SAH.

Consensus statement from the 2014 International Microdialysis Forum.

Microdialysis enables the chemistry of the extracellular interstitial space to be monitored. Use of this technique in patients with acute brain injury has increased our understanding of the pathophysiology of several acute neurological disorders. In 2004, a consensus document on the clinical application of cerebral microdialysis was published. Since then, there have been significant advances in the clinical use of microdialysis in neurocritical care. The objective of this review is to report on the International Microdialysis Forum held in Cambridge, UK, in April 2014 and to produce a revised and updated consensus statement about its clinical use including technique, data interpretation, relationship with outcome, role in guiding therapy in neurocritical care and research applications.

Data collection and interpretation.

Patient monitoring is routinely performed in all patients who receive neurocritical care. The combined use of monitors, including the neurologic examination, laboratory analysis, imaging studies, and physiological parameters, is common in a platform called multi-modality monitoring (MMM). However, the full potential of MMM is only beginning to be realized since for the most part, decision making historically has focused on individual aspects of physiology in a largely threshold-based manner. The use of MMM now is being facilitated by the evolution of bio-informatics in critical care including developing techniques to acquire, store, retrieve, and display integrated data and new analytic techniques for optimal clinical decision making. In this review, we will discuss the crucial initial steps toward data and information management, which in this emerging era of data-intensive science is already shifting concepts of care for acute brain injury and has the potential to both reshape how we do research and enhance cost-effective clinical care.

Neuroprotection in acute brain injury: an up-to-date review.

Neuroprotective strategies that limit secondary tissue loss and/or improve functional outcomes have been identified in multiple animal models of ischemic, hemorrhagic, traumatic and nontraumatic cerebral lesions. However, use of these potential interventions in human randomized controlled studies has generally given disappointing results. In this paper, we summarize the current status in terms of neuroprotective strategies, both in the immediate and later stages of acute brain injury in adults. We also review potential new strategies and highlight areas for future research.

Intracranial pressure and cerebral perfusion pressure monitoring in non-TBI patients: special considerations.

The effect of intracranial pressure (ICP) and the role of ICP monitoring are best studied in traumatic brain injury (TBI). However, a variety of acute neurologic illnesses e.g., subarachnoid hemorrhage, intracerebral hemorrhage, ischemic stroke, meningitis/encephalitis, and select metabolic disorders, e.g., liver failure and malignant, brain tumors can affect ICP. The purpose of this paper is to review the literature about ICP monitoring in conditions other than TBI and to provide recommendations how the technique may be used in patient management. A PubMed search between 1980 and September 2013 identified 989 articles; 225 of which were reviewed in detail. The technique used to monitor ICP in non-TBI conditions is similar to that used in TBI; however, indications for ICP monitoring often are intertwined with the presence of obstructive hydrocephalus and hence the use of ventricular catheters is more frequent. Increased ICP can adversely affect outcome, particularly when it fails to respond to treatment. However, patients with elevated ICP can still have favorable outcomes. Although the influence of ICP-based care on outcome in non-TBI conditions appears less robust than in TBI, monitoring ICP and cerebral perfusion pressure can play a role in guiding therapy in select patients.

Parenchymal brain oxygen monitoring in the neurocritical care unit.

Patients admitted to the neurocritical care unit (NCCU) often have serious conditions that can be associated with high morbidity and mortality. Pharmacologic agents or neuroprotectants have disappointed in the clinical environment. Current NCCU management therefore is directed toward identification, prevention, and treatment of secondary cerebral insults that evolve over time and are known to aggravate outcome. This strategy is based on a variety of monitoring techniques including use of intraparenchymal monitors. This article reviews parenchymal brain oxygen monitors, including the available technologies, practical aspects of use, the physiologic rationale behind their use, and patient management based on brain oxygen.

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.

The relationship between intracranial pressure and brain oxygenation in children with severe traumatic brain injury.

BACKGROUND: Intracranial pressure (ICP) monitoring is a cornerstone of care for severe traumatic brain injury (TBI). Management of ICP can help ensure adequate cerebral blood flow and oxygenation. However, studies indicate that brain hypoxia may occur despite normal ICP and the relationship between ICP and brain oxygenation is poorly defined. This is particularly important for children in whom less is known about intracranial dynamics. OBJECTIVE: To examine the relationship between ICP and partial pressure of brain tissue oxygen (PbtO2) in children with severe TBI (Glasgow Coma Scale score ≤ 8) admitted to Red Cross War Memorial Children's Hospital, Cape Town. METHODS: The relationship between time-linked hourly and high-frequency ICP and PbtO2 data was examined using correlation, regression, and generalized estimating equations. Thresholds for ICP were examined against reduced PbtO2 using age bands and receiver-operating characteristic curves. RESULTS: Analysis using more than 8300 hourly (n = 75) and 1 million high-frequency data points (n = 30) demonstrated a weak relationship between ICP and PbtO2 (r = 0.05 and r = 0.04, respectively). No critical ICP threshold for low PbtO2 was identified. Individual patients revealed a strong relationship between ICP and PbtO2 at specific times, but different relationships were evident over longer periods. CONCLUSION: The relationship between ICP and PbtO2 appears complex, and several factors likely influence both variables separately and in combination. Although very high ICP is associated with reduced PbtO2, in general, absolute ICP has a poor relationship with PbtO2. Because reduced PbtO2 is independently associated with poor outcome, a better understanding of ICP and PbtO2 management in pediatric TBI seems to be needed.

Are initial radiographic and clinical scales associated with subsequent intracranial pressure and brain oxygen levels after severe traumatic brain injury?

BACKGROUND: Prediction of clinical course and outcome after severe traumatic brain injury (TBI) is important. OBJECTIVE: To examine whether clinical scales (Glasgow Coma Scale [GCS], Injury Severity Score [ISS], and Acute Physiology and Chronic Health Evaluation II [APACHE II]) or radiographic scales based on admission computed tomography (Marshall and Rotterdam) were associated with intensive care unit (ICU) physiology (intracranial pressure [ICP], brain tissue oxygen tension [PbtO2]), and clinical outcome after severe TBI. METHODS: One hundred one patients (median age, 41.0 years; interquartile range [26-55]) with severe TBI who had ICP and PbtO2 monitoring were identified. The relationship between admission GCS, ISS, APACHE II, Marshall and Rotterdam scores and ICP, PbtO2, and outcome was examined by using mixed-effects models and logistic regression. RESULTS: Median (25%-75% interquartile range) admission GCS and APACHE II without GCS scores were 3.0 (3-7) and 11.0 (8-13), respectively. Marshall and Rotterdam scores were 3.0 (3-5) and 4.0 (4-5). Mean ICP and PbtO2 during the patients' ICU course were 15.5 ± 10.7 mm Hg and 29.9 ± 10.8 mm Hg, respectively. Three-month mortality was 37.6%. Admission GCS was not associated with mortality. APACHE II (P = .003), APACHE-non-GCS (P = .004), Marshall (P < .001), and Rotterdam scores (P < .001) were associated with mortality. No relationship between GCS, ISS, Marshall, or Rotterdam scores and subsequent ICP or PbtO2 was observed. The APACHE II score was inversely associated with median PbtO2 (P = .03) and minimum PbtO2 (P = .008) and had a stronger correlation with amount of time of reduced PbtO2. CONCLUSION: Following severe TBI, factors associated with outcome may not always predict a patient's ICU course and, in particular, intracranial physiology.

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.

Anemia and transfusion after subarachnoid hemorrhage.

Delayed cerebral ischemia after subarachnoid hemorrhage (SAH) may be affected by a number of factors, including cerebral blood flow and oxygen delivery. Anemia affects about half of patients with SAH and is associated with worse outcome. Anemia also may contribute to the development of or exacerbate delayed cerebral ischemia. This review was designed to examine the prevalence and impact of anemia in patients with SAH and to evaluate the effects of transfusion. A literature search was made to identify original research on anemia and transfusion in SAH patients. A total of 27 articles were identified that addressed the effects of red blood cell transfusion (RBCT) on brain physiology, anemia in SAH, and clinical management with RBCT or erythropoietin. Most studies provided retrospectively analyzed data of very low-quality according to the GRADE criteria. While RBCT can have beneficial effects on brain physiology, RBCT may be associated with medical complications, infection, vasospasm, and poor outcome after SAH. The effects may vary with disease severity or the presence of vasospasm, but it remains unclear whether RBCTs are a marker of disease severity or a cause of worse outcome. Erythropoietin data are limited. The literature review further suggests that the results of the Transfusion Requirements in Critical Care Trial and subsequent observational studies on RBCT in general critical care do not apply to SAH patients and that randomized trials to address the role of RBCT in SAH are required.

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.

Red blood cell transfusion in patients with subarachnoid hemorrhage: a multidisciplinary North American survey.

INTRODUCTION: Anemia is associated with poor outcomes in patients with aneurysmal subarachnoid hemorrhage (SAH). It remains unclear whether this association can be modified with more aggressive use of red blood cell (RBC) transfusions. The degree to which restrictive thresholds have been adopted in neurocritical care patients remains unknown. METHODS: We performed a survey of North American academic neurointensivists, vascular neurosurgeons and multidisciplinary intensivists who regularly care for patients with SAH to determine hemoglobin (Hb) concentrations which commonly trigger a decision to initiate transfusion. We also assessed minimum and maximum acceptable Hb goals in the context of a clinical trial and how decision-making is influenced by advanced neurological monitoring, clinician characteristics and patient-specific factors. RESULTS: The survey was sent to 531 clinicians, of whom 282 (53%) responded. In a hypothetical patient with high-grade SAH (WFNS 4), the mean Hb concentration at which clinicians administered RBCs was 8.19 g/dL (95% CI, 8.07 to 8.30 g/dL). Transfusion practices were comparatively more restrictive in patients with low-grade SAH (mean Hb 7.85 g/dL (95% CI, 7.73 to 7.97 g/dL)) (P < 0.0001) and more liberal in patients with delayed cerebral ischemia (DCI) (mean Hb 8.58 g/dL (95% CI, 8.45 to 8.72 g/dL)) (P < 0.0001). In each setting, there was a broad range of opinions. The majority of respondents expressed a willingness to study a restrictive threshold of ≤8 g/dL (92%) and a liberal goal of ≥10 g/dl (75%); in both cases, the preferred transfusion thresholds were significantly higher for patients with DCI (P < 0.0001). Neurosurgeons expressed higher minimum Hb goals than intensivists, especially for patients with high-grade SAH (ß = 0.46, P = 0.003), and were more likely to administer two rather than one unit of RBCs (56% vs. 19%; P < 0.0001). Institutional use of transfusion protocols was associated with more restrictive practices. More senior clinicians preferred higher Hb goals in the context of a clinical trial. Respondents were more likely to transfuse patients with brain tissue oxygen tension values <15 mmHg and lactate-to-pyruvate ratios >40. CONCLUSIONS: There is widespread variation in the use of RBC transfusions in SAH patients. Practices are heavily influenced by the specific dynamic clinical characteristics of patients and may be further modified by clinician specialty and seniority, the use of protocols and advanced neurological monitoring.

Portable head CT scan and its effect on intracranial pressure, cerebral perfusion pressure, and brain oxygen.

OBJECT: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: These data suggest that pHCT scans do not have a detectable effect on a critically ill patient's ICP, CPP, or PbtO(2).

Community views on neurologic emergency treatment trials.

STUDY OBJECTIVE: We improve our understanding of the community consultation process for acute neurologic emergency trials conducted under the federal regulations for Exception From Informed Consent (EFIC) for emergency research. METHODS: We performed a qualitative study using focus groups to collect data from patients with a previous stroke or brain injury and their families and from young men at risk for traumatic brain injury. Discussions were transcribed, coded, and analyzed for major themes and subthemes. RESULTS: Five focus groups, involving 40 participants, were convened. Major themes included the awareness and understanding of key clinical trial concepts, including prominent concerns about placebo and therapeutic misconception; inability to obtain informed consent and acceptable surrogate decision-making; EFIC in emergency research and whether existing regulations are acceptable; specific trial design problems, including comparison to standard of care versus 2 competing active therapies; and community consultation and representation. CONCLUSION: In this study sample, EFIC trials were deemed appropriate and acceptable for acute neurologic emergency research. Education, along with open discussion about basic clinical research concepts, disease- and trial-specific information, and potential surrogate decision-making, was essential to determine the acceptability of an EFIC trial. Approval by institutional review boards was highly regarded as a means of human protection and effective community consultation for such trials. A data repository of information gained from similar qualitative research may help investigators and regulators who wish to plan, conduct, review, and provide oversight for acute neurologic emergency trials under EFIC regulations.

Effect of body position on cerebral oxygenation and physiologic parameters in patients with acute neurological conditions.

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.

Dendritic alterations after dynamic axonal stretch injury in vitro.

Traumatic axonal injury (TAI) is the most common and important pathology of traumatic brain injury (TBI). However, little is known about potential indirect effects of TAI on dendrites. In this study, we used a well-established in vitro model of axonal stretch injury to investigate TAI-induced changes in dendrite morphology. Axons bridging two separated rat cortical neuron populations plated on a deformable substrate were used to create a zone of isolated stretch injury to axons. Following injury, we observed the formation of dendritic alterations or beading along the dendrite shaft. Dendritic beading formed within minutes after stretch then subsided over time. Pharmacological experiments revealed a sodium-dependent mechanism, while removing extracellular calcium exacerbated TAI's effect on dendrites. In addition, blocking ionotropic glutamate receptors with the N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 prevented dendritic beading. These results demonstrate that axon mechanical injury directly affects dendrite morphology, highlighting an important bystander effect of TAI. The data also imply that TAI may alter dendrite structure and plasticity in vivo. An understanding of TAI's effect on dendrites is important since proper dendrite function is crucial for normal brain function and recovery after injury.

Patient transport and brain oxygen in comatose patients.

OBJECTIVE: Transport of critically ill intensive care unit patients may be hazardous. We examined whether brain oxygen (brain tissue oxygen partial pressure [PbtO2]) is influenced by transport to and from a follow-up head computed tomography (transport head computed tomography [tHCT]) scan. METHODS: Forty-five patients (24 men, 21 women; Glasgow Coma Scale score < or =8; mean age, 47.3 +/- 19.0 years) who had a traumatic brain injury (n = 26) or subarachnoid hemorrhage (n = 19) were retrospectively identified from a prospective observational cohort of PbtO2 monitoring in a neurosurgical intensive care unit at a university-based level I trauma center. PbtO2, intracranial pressure, and cerebral perfusion pressure were monitored continuously and compared during the 3 hours before and after 100 tHCT scans. RESULTS: The mean PbtO2 before and after the tHCT scans for all 100 scans was 37.9 +/- 19.8 mm Hg and 33.9 +/- 17.2 mm Hg, respectively (P = .0001). A decrease in PbtO2 (>5%) occurred after 54 tHCTs (54%) and in 36 patients (80%). In instances in which a decrease occurred, the average decrease in mean, minimum, and maximum PbtO2 was 23.6%, 29%, and 18.1%, respectively. This decrease was greater when PbtO2 was compromised (<25 mm Hg) before tHCT. An episode of brain hypoxia (<15 mm Hg) was identified in the 3 hours before tHCT in 9 and after tHCT in 19 instances. On average, an episode of brain hypoxia was 46.6 +/- 16.0 (standard error) minutes longer after tHCT than before tHCT (P = .008). Multivariate analysis suggests that changes in lung function (PaO2/fraction of inspired oxygen [FiO2] ratio) may account for the reduced PbtO2 after tHCT (parameter estimate 0.45, 95% confidence interval: 0.024-0.871; P = .04). CONCLUSION: These data suggest that transport to and from the intensive care unit may adversely affect PbtO2. This deleterious effect is greater when PbtO2 is already compromised and may be associated with lung function.

Brain tissue oxygen-directed management and outcome in patients with severe traumatic brain injury.

OBJECT: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.