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Background: Many randomized controlled trials (RCT) have assessed new treatments in subarachnoid hemorrhage (SAH), yet most show no treatment efficacy. One explanation is the statistical analysis of the primary endpoint was not as efficient as possible. We reanalyzed SAH RCTs with various statistical tests to determine whether the statistical method affects RCT primary outcome.Methods: Individual patient data for the primary outcome (Glasgow outcome scale [GOS]) of two SAH RCTs were analyzed using 15 statistical methods. For tests requiring outcome dichotomization, multiple cut-points in the 5-level GOS were assessed. Next, a synthetic dataset generated using random sampling with replacement from ten SAH RCTs was assessed using the same statistical tests. A Friedman test (two-way non-parametric analysis of variance) determined which tests produced the highest average absolute Z-values. The number of times each test reported significance of pResults: Bootstrapping with replacement produced the best-ranking results, followed by three χ2-tests: one differentiating excellent (GOS=5) from good (GOS=4), poor (GOS=2-3), or dead (GOS=1) outcomes; one differentiating favorable (GOS=4-5) from poor or dead outcomes; and one differentiating favorable (GOS=4-5) from unfavorable outcomes. Each of these reported statistical significance for both RCTs, as did the following ranked tests, respectively: Wilcoxon median test, Student’s t-test, ordinal logistic regression, median test, and a chi-square dichotomizing excellent (GOS≥4) and inferior outcomes. Statistical significance for one or neither RCT was reported by two Cochrane-Armitage tests and two logistic regressions with alternate versions of bucketing, the Kolmogorov-Smirnov test and chi-square test differentiating surviving from dead patients. The synthetic dataset returned similar results, with the same nine most and six least efficient tests.Conclusions: Bootstrapping produced the most efficient results but is time-and resource-intensive. Chi-square tests grouping outcomes into dichotomous or multiple buckets are also efficient, and their ease of use and popularity make them appropriate candidates for statistical analysis in future SAH RCTs.

Author(s): Vitt, Jeffrey R; Sun, Chung-Huan; Le Roux, Peter D; Hemphill, J Claude | Abstract: Purpose of reviewSpontaneous 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 findingsThe 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.SummaryMIS 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.

OBJECTIVES: To estimate the impact of goal-directed therapy on outcome after traumatic brain injury, our team applied goal-directed therapy to standardize care in patients with moderate to severe traumatic brain injury, who were enrolled in a large multicenter clinical trial. DESIGN: Planned secondary analysis of data from Progesterone for the Treatment of Traumatic Brain Injury III, a large, prospective, multicenter clinical trial. SETTING: Forty-two trauma centers within the Neurologic Emergencies Treatment Trials network. PATIENTS: Eight-hundred eighty-two patients were enrolled within 4 hours of injury after nonpenetrating traumatic brain injury characterized by Glasgow Coma Scale score of 4–12. MEASUREMENTS AND MAIN RESULTS: Physiologic goals were defined a priori in order to standardize care across 42 sites participating in Progesterone for the Treatment of Traumatic Brain Injury III. Physiologic data collection occurred hourly; laboratory data were collected according to local ICU protocols and at a minimum of once per day. Physiologic transgressions were predefined as substantial deviations from the normal range of goal-directed therapy. Each hour where goal-directed therapy was not achieved was classified as a “transgression.” Data were adjudicated electronically and via expert review. Six-month outcomes included mortality and the stratified dichotomy of the Glasgow Outcome Scale-Extended. For each variable, the association between outcome and either: 1) the occurrence of a transgression or 2) the proportion of time spent in transgression was estimated via logistic regression model. RESULTS: For the 882 patients enrolled in Progesterone for the Treatment of Traumatic Brain Injury III, mortality was 12.5%. Prolonged time spent in transgression was associated with increased mortality in the full cohort for hemoglobin less than 8 gm/dL (p = 0.0006), international normalized ratio greater than 1.4 (p < 0.0001), glucose greater than 180 mg/dL (p = 0.0003), and systolic blood pressure less than 90 mm Hg (p < 0.0001). In the patient subgroup with intracranial pressure monitoring, prolonged time spent in transgression was associated with increased mortality for intracranial pressure greater than or equal to 20 mm Hg (p < 0.0001), glucose greater than 180 mg/dL (p = 0.0293), hemoglobin less than 8 gm/dL (p = 0.0220), or systolic blood pressure less than 90 mm Hg (p = 0.0114). Covariates inversely related to mortality included: a single occurrence of mean arterial pressure less than 65 mm Hg (p = 0.0051) or systolic blood pressure greater than 180 mm Hg (p = 0.0002). CONCLUSIONS: The Progesterone for the Treatment of Traumatic Brain Injury III clinical trial rigorously monitored compliance with goal-directed therapy after traumatic brain injury. Multiple significant associations between physiologic transgressions, morbidity, and mortality were observed. These data suggest that effective goal-directed therapy in traumatic brain injury may provide an opportunity to improve patient outcomes.

Purpose of review Since the development of intravenous tissue plasminogen activator (tPA) for acute ischemic stroke (AIS), functional outcome has improved when treatment occurs within 4.5 h of stroke onset and treatment benefits are greater with earlier treatment. Endovascular revascularization also is better the sooner it is delivered. Recent findings The Get with the Guidelines Stroke registry found that less than one-third of treatment-eligible AIS patients receive intravenous tPA within 60 min of hospital arrival. Initiatives have tried to improve public education and awareness of stroke symptoms to decrease time to presentation. The mobile stroke unit (MSU) facilitates earlier computed tomography scans, delivery of tPA, proper triage and on-scene goal-directed care. MSUs reduce time from stroke alarm to treatment by 25-40 min and increase the rate of intravenous tPA use without an increase in hemorrhage risk. In addition, three-month favorable outcome is increased. Summary MSUs likely will evolve further and be used for other acute neurologic disorders, help triage patients for endovascular therapy, and be incorporated into systems of care in remote areas. Further studies are awaited to fully understand the overall medical and health-economic benefit of MSUs.

In this chapter we will review anemia in traumatic brain injury (TBI), the pathophysiology of anemia, the effects of anemia on outcome, the physiology of transfusion, and the relationship between red blood cell transfusion (RBCT) and outcome. The role of hematopoiesis-stimulating agents and hemoglobin-based blood substitutes will be briefly considered, and the chapter will conclude with a suggested approach to anemia management in TBI. Coagulation, coagulopathy, and the administration of other blood products (e.g., platelets or coagulation factors) are beyond the scope of this chapter.

A variety of technologies have been developed to assist decision-making during the management of patients with acute brain injury who require intensive care. A large body of research has been generated describing these various technologies. The Neurocritical Care Society (NCS) in collaboration with the European Society of Intensive Care Medicine (ESICM), the Society for Critical Care Medicine (SCCM), and the Latin America Brain Injury Consortium (LABIC) organized an international, multidisciplinary consensus conference to perform a systematic review of the published literature to help develop evidence-based practice recommendations on bedside physiologic monitoring. This supplement contains a Consensus Summary Statement with recommendations and individual topic reviews on physiologic processes important in the care of acute brain injury. In this article we provide the evidentiary tables for select topics including systemic hemodynamics, intracranial pressure, brain and systemic oxygenation, EEG, brain metabolism, biomarkers, processes of care and monitoring in emerging economies to provide the clinician ready access to evidence that supports recommendations about neuromonitoring.

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.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 (PaoA 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 (P0.0001). 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; P0.0001) 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).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.

Background Risk of delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH) with asymptomatic angiographic vasospasm on admission is unclear in the literature. The goal of this study is to identify predictors of clinical DCI in this group of patients. Methods An exploratory subgroup analysis was conducted in the SAHIT (Subarachnoid Hemorrhage International Trialists) data repository to identify predictors of clinical DCI in patients with good-grade aSAH (World Federation of Neurological Surgeons grade I and II) with angiographic vasospasm on admission. Predictors considered include age, sex, systolic blood pressure at presentation, World Federation of Neurological Surgeon grade, Fisher grade, aneurysm size and location, treatment modality, hydrocephalus requiring external ventricular drain insertion, and severity of vasospasm. The predictors were ranked based on dominance analysis with R2 as fit statistics and assessed in a set of logistic regression analysis models. Results Four data sets out of 16 studies in the SAHIT database were analyzed, with a total of 4125 patients. One hundred and ninety-one patients (4.6%) had asymptomatic angiographic vasospasm at admission. Of those, 78 patients (40.8%) developed clinical DCI. Univariate analysis showed significant associations between severe vasospasm on admission and development of clinical DCI (odds ratio, 9.5, 95% confidence interval, 2.07–43.50; P = 0.004). None of the studied predictors was associated with the development of clinical DCI on multivariate analysis. Conclusions Asymptomatic angiographic vasospasm in patients with good-grade aSAH on admission is uncommon. Further studies are needed to identify high-risk patients for the development of DCI in the context of asymptomatic early vasospasm.

Neurocritical care depends, in part, on careful patient monitoring but as yet there are little data on what processes are the most important to monitor, how these should be monitored, and whether monitoring these processes is cost-effective and impacts outcome. At the same time, bioinformatics is a rapidly emerging field in critical care but as yet there is little agreement or standardization on what information is important and how it should be displayed and analyzed. The Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine, and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to begin to address these needs. International experts from neurosurgery, neurocritical care, neurology, critical care, neuroanesthesiology, nursing, pharmacy, and informatics were recruited on the basis of their research, publication record, and expertise. They undertook a systematic literature review to develop recommendations about specific topics on physiologic processes important to the care of patients with disorders that require neurocritical care. This review does not make recommendations about treatment, imaging, and intraoperative monitoring. A multidisciplinary jury, selected for their expertise in clinical investigation and development of practice guidelines, guided this process. The GRADE system was used to develop recommendations based on literature review, discussion, integrating the literature with the participants' collective experience, and critical review by an impartial jury. Emphasis was placed on the principle that recommendations should be based on both data quality and on trade-offs and translation into clinical practice. Strong consideration was given to providing pragmatic guidance and recommendations for bedside neuromonitoring, even in the absence of high quality data.

Study design Retrospective medical record review and literature review. Objective To identify cases where a cerebrospinal fluid (CSF) leak occurred during an anterior cervical discectomy and fusion (ACDF) and to create a management algorithm based on the findings. Summary of background data ACDF is a commonly performed spinal operation. It is effective with very low complication rates. One rare complication of ACDF is a CSF leak. There is limited information on the management of CSF leaks after ACDF and management is on a surgeon-by-surgeon basis. Methods We reviewed 3 surgeons' case logs and identified cases where a CSF leak was encountered during ACDF and reviewed the patients' medical records, operative reports and imaging to determine how these leaks were managed. We also performed a PubMed search for articles about the presentation and management of CSF leaks after ACDF. Results Thirteen CSF leaks were identified in 1223 ACDFs, corresponding to a CSF leak rate of 1%. Of these, 9 were successfully treated with intraoperative repair. Postoperative lumbar drainage was used in the remaining 4 patients and was successful in 1 patient. Three patients underwent neck re-exploration and attempted delayed repair. Three patients, including one who was found to have hydrocephalus, ultimately required continuous CSF diversion via shunting. We identified 7 case reports of CSF leak in ADCF in the literature and 1 article that reviewed the prevalence and management of this complication. Conclusion CSF leak after ACDF is an uncommon complication that can usually be repaired. We provide a stepwise management strategy for CSF leaks in ACDF.

Increased intracranial pressure (ICP) is associated with worse outcome after traumatic brain injury (TBI), but whether its management improves the outcome is unclear. In this review, we will examine the implications of the Benchmark Evidence from South American Trials: Treatment of Intracranial Pressure (BEST TRIP) trial, evidence for an influence of ICP care on outcome, and a need for greater understanding of the pathophysiology than just ICP through multimodal monitoring (MMM) to enhance the outcome.The primary impact of the BEST TRIP trial, a randomized clinical trial that examined two TBI management strategies, one that used an ICP monitor, is in research and should not alter clinical practice. Analyses of large databases suggest TBI care based on the Brain Trauma Foundation guidelines and management of intracranial hypertension can improve patient outcome. However, accumulating evidence demonstrates there are several mechanisms of secondary brain injury (SBI), for example, microvascular dysfunction or alterations in glucose utilization that cannot be detected using an ICP monitor. In these patients, growing clinical evidence suggests that MMM can help manage SBI and improve TBI outcome.ICP-based monitoring and treatment alone may not be enough to enhance TBI outcome, but ICP and cerebral perfusion pressure therapy remain important in TBI care. Although high-quality evidence for MMM is limited, it should be more widely adapted to better understand the complex pathophysiology after TBI, better target care, and identify new therapeutic opportunities.

Widely-varying published and presented analyses of the Benchmark Evidence From South American Trials: Treatment of Intracranial Pressure (BEST TRIP) randomized controlled trial of intracranial pressure (ICP) monitoring have suggested denying trial generalizability, questioning the need for ICP monitoring in severe traumatic brain injury (sTBI), re-assessing current clinical approaches to monitored ICP, and initiating a general ICP-monitoring moratorium. In response to this dissonance, 23 clinically-active, international opinion leaders in acute-care sTBI management met to draft a consensus statement to interpret this study. A Delphi method-based approach employed iterative pre-meeting polling to codify the group's general opinions, followed by an in-person meeting wherein individual statements were refined. Statements required an agreement threshold of more than 70% by blinded voting for approval. Seven precisely-worded statements resulted, with agreement levels of 83% to 100%. These statements, which should be read in toto to properly reflect the group's consensus positions, conclude that the BEST TRIP trial: 1) studied protocols, not ICP-monitoring per se; 2) applies only to those protocols and specific study groups and should not be generalized to other treatment approaches or patient groups; 3) strongly calls for further research on ICP interpretation and use; 4) should be applied cautiously to regions with much different treatment milieu; 5) did not investigate the utility of treating monitored ICP in the specific patient group with established intracranial hypertension; 6) should not change the practice of those currently monitoring ICP; and 7) provided a protocol, used in non-monitored study patients, that should be considered when treating without ICP monitoring. Consideration of these statements can clarify study interpretation.

Outcome of patients with aneurysmal subarachnoid hemorrhage (SAH) has improved over the last decades. Yet, case fatality remains nearly 40% and survivors often have permanent neurological, cognitive and/or behavioural sequelae. Other than nimodipine drug or clinical trials have not consistently improved outcome. We formed a collaboration of SAH investigators to create a resource for prognostic analysis and for studies aimed at optimizing the design and analysis of phase 3 trials in aneurysmal SAH. We identified investigators with data from randomized, clinical trials of patients with aneurysmal SAH or prospectively collected single- or multicentre databases of aneurysmal SAH patients. Data are being collected and proposals to use the data and to design future phase 3 clinical trials are being discussed. This paper reviews some issues discussed at the first meeting of the SAH international trialists (SAHIT) repository meeting. Investigators contributed or have agreed to contribute data from several phase 3 trials including the tirilazad trials, intraoperative hypothermia for aneurysmal SAH trial, nicardipine clinical trials, international subarachnoid aneurysm trial, intravenous magnesium sulphate for aneurysmal SAH, magnesium for aneurysmal SAH and from prospectively-collected data from four institutions. The number of patients should reach 15,000. Some industry investigators refused to provide data and others reported that their institutional research ethics boards would not permit even deidentified or anonymized data to be included. Others reported conflict of interest that prevented them from submitting data. The problems with merging data were related to lack of common definitions and coding of variables, differences in outcome scales used, and times of assessment. Some questions for investigation that arose are discussed. SAHIT demonstrates the possibility of SAH investigators to contribute data for collaborative research. The problems are similar to those already documented in other similar collaborative efforts such as in head injury research. We encourage clinical trial and registry investigators to contact us and participate in SAHIT. Key issues moving forward will be to use common definitions (common data elements), outcomes analysis, and to prioritize research questions, among others.

Background The optimal red blood cell transfusion (RBCT) trigger for patients with aneurysmal subarachnoid hemorrhage (SAH) is unknown. In patients with cerebral vasospasm, anemia may increase susceptibility to ischemic injury; conversely, RBCT may worsen outcome given known deleterious effects. Objective To examine the association between RBCT, delayed cerebral ischemia (DCI), vasospasm, and outcome after SAH. Methods A total of 421 consecutive patients with SAH, admitted to a neurocritical care unit at a university-affiliated hospital and who underwent surgical occlusion of their ruptured aneurysm were retrospectively identified from a prospective observational database. Propensity score methods were used to reduce the bias associated with treatment selection. Results Two hundred and sixty-one patients (62.0%) received an RBCT. Angiographic vasospasm (odds ratio [OR] 1.6; 95% confidence interval [CI], 1.1–2.3; P = 0.025) but not severe angiographic spasm, DCI, or delayed infarction was associated with RBCT. A total of 283 patients (67.2%) experienced a favorable outcome, defined as good or moderately disabled on the Glasgow Outcome Scale; 47 (11.2%) were severely disabled or vegetative and 91 patients (21.6%) were dead at 6-month follow-up. Among patients who survived ≥2 days, RBCT was associated with unfavorable outcome (OR, 2.6; 95% CI, 1.6–4.1). Transfusion of ≥3 units of blood was associated with an increased incidence of unfavorable outcome. Propensity analysis to control for the probability of exposure to RBCT conditional on observed covariates measured before RBCT indicates that RBCT is associated with unfavorable outcome in the absence of DCI (OR, 2.17; 95% CI, 1.56–3.01; P P = 0.65). Conclusions Blood transfusions are associated with unfavorable outcome after SAH particularly when DCI is absent. Propensity analysis suggests that RBCT may be associated with poor outcome rather than being a marker of disease severity. However, when DCI is present, RBCT may help improve outcome.

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 Hgb11 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), p0.001). 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.

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.

OPINION STATEMENT: Anemia develops in about 50% of patients hospitalized with traumatic brain injury (TBI) and is recognized as a cause of secondary brain injury. This review examines the effects of anemia and transfusion on TBI patients through a literature search to identify original research on anemia and transfusion in TBI, the effects of transfusion on brain physiology, and the role of erythropoietin or hemoglobin-based blood substitutes (HBBSs). However, the amount of high-quality, prospective data available to help make decisions about when TBI patients should be transfused is very small. Randomized transfusion trials have involved far too few TBI patients to reach definitive conclusions. Thus, it is hardly surprising that there is widespread practice variation. In our opinion, a hemoglobin transfusion threshold of 7 g/dL cannot yet be considered safe for TBI patients admitted to hospital, and in particular to the ICU, as it is for other critically ill patients. Red blood cell transfusions often have immediate, seemingly beneficial effects on cerebral physiology, but the magnitude of this effect may depend in part upon how long the cells have been stored before administration. In light of existing physiological data, we generally aim to keep hemoglobin concentrations greater than 9 g/dL during the first several days after TBI. In part, the decision is based on the patient's risk of or development of secondary ischemia or brain injury. An increasing number of centers use multimodal neurologic monitoring, which may help to individualize transfusion goals based on the degree of cerebral hypoxia or metabolic distress. When available, brain tissue oxygen tension values less than 15-20 mm Hg or a lactate:pyruvate ratio greater than 30-40 would influence us to use more aggressive hemoglobin correction (e.g., a transfusion threshold of 10 g/dL). Clinicians can attempt to reduce transfusion requirements by limiting phlebotomy, minimizing hemodilution, and providing appropriate prophylaxis against gastrointestinal hemorrhage. Administration of exogenous erythropoietin may have a small impact in further reducing the need for transfusion, but it also may increase complications, most notably deep venous thrombosis. Erythropoietin is currently of great interest as a potential neuroprotective agent, but until it is adequately evaluated in randomized controlled trials, it should not be used routinely for this purpose. HBBSs are also of interest, but existing preparations have not been shown to be beneficial-or even safe-in the context of TBI.

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.

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 (PbtO2). 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 PbtO2 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 PbtO2 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 PbtO2 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 (PbtO2 < 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 PbtO2.

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 for10 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 for10 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.

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.

Object The object of this study was to determine whether brain tissue oxygen (PbtO2)–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 ≤ 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 PbtO2 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 PbtO2 monitors also had therapy to maintain PbtO2 > 20 mm Hg. Results Data were obtained from 12,148 hours of continuous ICP monitoring and 6,816 hours of continuous PbtO2 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 PbtO2-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 PbtO2–guided management had a favorable short-term outcome (p = 0.01). Among patients who received PbtO2-directed therapy, mortality was associated with lower mean daily PbtO2 (p < 0.05), longer durations of compromised brain oxygen (PbtO2 < 20 mm Hg, p = 0.013) and brain hypoxia (PbtO2 < 15 mm Hg, p = 0.001), more episodes and a longer cumulative duration of compromised PbtO2 (p < 0.001), and less successful treatment of compromised PbtO2 (p = 0.03). Conclusions These results suggest that PbtO2-based therapy, particularly when compromised PbtO2 can be corrected, may be associated with reduced patient mortality and improved patient outcome after severe TBI.

Object Vasospasm is a leading cause of morbidity and death following aneurysmal subarachnoid hemorrhage (SAH). It is important to predict which patients are at risk for vasospasm so that interventions can be made. There are several potential risk factors for vasospasm, one of which is age. However, the effect of age on vasospasm, particularly symptomatic vasospasm, remains controversial. Methods Three hundred ninety-one patients were retrospectively identified from a prospective observational database of patients with SAH who had been admitted to a single center. Demographic and clinical data were recorded, and cerebral angiograms obtained at admission and between 5 and 10 days later were compared. The relationship between age and angiographic and symptomatic vasospasms was examined using logistic regression techniques. Results Mild (86 patients), moderate (69 patients), severe (56 patients), and no angiographic vasospasms (180 patients) were documented by comparing admission and follow-up angiograms in each patient. Symptomatic vasospasm was identified in 69 patients (17.6%). Angiographic vasospasm was more frequent as age decreased. Except in patients < 30 years old, the frequency of symptomatic vasospasm also increased with decreasing age (p = 0.0001). After adjusting for variables known to be associated with vasospasm, an advanced age was associated with a reduced incidence of any angiographic vasospasm (OR 0.96, 95% CI 0.94–0.97), severe angiographic vasospasm (OR 0.96, 95% CI 0.95–0.98), and symptomatic vasospasm (OR 0.98, 95% CI 0.96–0.99). Conclusions Results in this study show that a younger age is associated with an increased incidence of angiographic and symptomatic vasospasm.

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.

Objective - To develop and validate a set of practical prediction tools that reliably estimate the outcome of subarachnoid haemorrhage from ruptured intracranial aneurysms (SAH).Design - Cohort study with logistic regression analysis to combine predictors and treatment modality.Setting - Subarachnoid Haemorrhage International Trialists' (SAHIT) data repository, including randomised clinical trials, prospective observational studies, and hospital registries.Participants - Researchers collaborated to pool datasets of prospective observational studies, hospital registries, and randomised clinical trials of SAH from multiple geographical regions to develop and validate clinical prediction models.Main outcome measure - Predicted risk of mortality or functional outcome at three months according to score on the Glasgow outcome scale.Results - Clinical prediction models were developed with individual patient data from 10 936 patients and validated with data from 3355 patients after development of the model. In the validation cohort, a core model including patient age, premorbid hypertension, and neurological grade on admission to predict risk of functional outcome had good discrimination, with an area under the receiver operator characteristics curve (AUC) of 0.80 (95% confidence interval 0.78 to 0.82). When the core model was extended to a "neuroimaging model," with inclusion of clot volume, aneurysm size, and location, the AUC improved to 0.81 (0.79 to 0.84). A full model that extended the neuroimaging model by including treatment modality had AUC of 0.81 (0.79 to 0.83). Discrimination was lower for a similar set of models to predict risk of mortality (AUC for full model 0.76, 0.69 to 0.82). All models showed satisfactory calibration in the validation cohort.Conclusion - The prediction models reliably estimate the outcome of patients who were managed in various settings for ruptured intracranial aneurysms that caused subarachnoid haemorrhage. The predictor items are readily derived at hospital admission. The web based SAHIT prognostic calculator (http://sahitscore.com) and the related app could be adjunctive tools to support management of patients.

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. 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.

Object Cerebral pressure autoregulation is an important neuroprotective mechanism that stabilizes cerebral blood flow when blood pressure (BP) changes. In this study the authors examined the association between autoregulation and clinical factors, BP, intracranial pressure (ICP), brain tissue oxygen tension (PbtO2), and outcome after pediatric severe traumatic brain injury (TBI). In particular we examined how the status of autoregulation influenced the effect of BP changes on ICP and PbtO2. Methods In this prospective observational study, 52 autoregulation tests were performed in 24 patients with severe TBI. The patients had a mean age of 6.3 ± 3.2 years, and a postresuscitation Glasgow Coma Scale score of 6 (range 3–8). All patients underwent continuous ICP and PbtO2 monitoring, and transcranial Doppler ultrasonography was used to examine the autoregulatory index (ARI) based on blood flow velocity of the middle cerebral artery after increasing mean arterial pressure by 20% of the baseline value. Impaired autoregulation was defined as an ARI < 0.4 and intact autoregulation as an ARI ≥ 0.4. The relationships between autoregulation (measured as both a continuous and dichotomous variable), outcome, and clinical and physiological variables were examined using multiple logistic regression analysis. Results Autoregulation was impaired (ARI < 0.4) in 29% of patients (7 patients). The initial Glasgow Coma Scale score was significantly associated with the ARI (p = 0.02, r = 0.32) but no other clinical factors were associated with autoregulation status. Baseline values at the time of testing for ICP, PbtO2, the ratio of PbtO2/PaO2, mean arterial pressure, and middle cerebral artery blood flow velocity were similar in the patients with impaired or intact autoregulation. There was an inverse relationship between ARI (continuous and dichotomous) with a change in ICP (continuous ARI, p = 0.005; dichotomous ARI, p = 0.02); that is, ICP increased with the BP increase when ARI was low (weak autoregulation). The ARI (continuous and dichotomous) was also inversely associated with a change in PbtO2 (continuous ARI, p = 0.002; dichotomous ARI, p = 0.02). The PbtO2 increased when BP was increased in most patients, even when the ARI was relatively high (stronger autoregulation), but the magnitude of this response was still associated with the ARI. There was no relationship between the ARI and outcome. Conclusions These data demonstrate the influence of the strength of autoregulation on the response of ICP and PbtO2 to BP changes and the variability of this response between individuals. The findings suggest that autoregulation testing may assist clinical decision-making in pediatric severe TBI and help better define optimal BP or cerebral perfusion pressure targets for individual patients.

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 (P0.001). A significant correlation was found between the magnitude of shivering-associated decrease of PbtO(2) (DeltaPbtO(2)) and circulating water temperature (R = 0.82, P0.001).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.

Objectives: Aneurysmal subarachnoid hemorrhage (SAH) is a devastating disorder that still requires much clinical study. However, the decision to participate in a randomized clinical trial, particularly a neuroemergency trial, is a complex one. The purposes of this survey were to determine who would participate in a randomized clinical trial that intended to examine transfusion practices after SAH, to identify who could serve as potential proxy decision-makers, and to find which patient characteristics were associated with the decision to participate. Methods: This was a cross-sectional study using a self-administered questionnaire, composed of a brief description of the proposed trial followed by questions about participation using a 5-point Likert scale. Information sought included potential decision-maker, demographic data, setting and reason for current health care access, and personal or family history of neurologic injury. Results: Nine-hundred five subjects were enrolled during emergency department (ED) visits, office visits, hospital admissions, or online, during a 1-month period: 63% were women and 46% were white. Nonneurologic problems were the leading reason (90%) for health care access, but 45% had a personal or family history of neurologic injury. Overall, 54% (95% confidence interval [CI] = 51% to 57%) of subjects stated they would definitely or probably consent to participate. No subject characteristics were associated with this decision: age (p = 0.28), sex (p = 0.16), race/ethnicity (p = 0.07), education (p = 0.44), religion (p = 0.42), clinical setting (p = 0.14), reason for visit (p = 0.58), and/or history of neurologic injury (p = 0.33). The vast majority (88%) identified a family member as the proxy decision-maker, again without differences among groups. Conclusions: Greater than half of respondents stated they would participate in a proposed emergency treatment trial for SAH. Our survey suggests that the decision to participate is highly individualized, because no demographic, pathologic, historical, or access-related predictors of choice were found. Educational materials designed for this type of trial would need to be broad-based. Family members should be considered as proxy decision-makers where permitted by federal and local regulations.

OBJECTIVE: Tuberculous meningitis (TBM) is a massive global problem. The mortality and morbidity associated with the severe form of the disease are exceptionally high. Even when increased intracranial pressure is treated and full conventional therapy is commenced, cerebral ischemia can develop and is associated with a particularly poor prognosis. We sought to evaluate our experience with two patients with severe TBM and cerebral oxygenation monitoring. DESIGN: Case report. SETTING: Red Cross Children's Hospital, Cape Town. PATIENTS: Two comatose patients with TBM. INTERVENTIONS: Targeted interventions against low cerebral oxygenation in one patient. MEASUREMENTS AND MAIN RESULTS: Cerebral tissue oxygenation (Ptio2) was measured. In both patients, Ptio2 monitoring demonstrated delayed cerebral ischemia despite the institution of full conventional therapy and the control of intracranial pressure. These data confirm that the vascular involvement in TBM is potentially progressive and that failure to diagnose infarction initially is not merely due to a delay in the radiologic appearance. The first patient developed extensive infarction, consistent with Ptio2 readings, and subsequently died after treatment withdrawal. Intervention in the second patient successfully reversed a precipitous decline of the Ptio2 readings and may have prevented infarction in this patient. CONCLUSIONS: The development of delayed cerebral ischemia in TBM despite treatment is confirmed in these two patients. The reversal of a decline in Ptio2 readings suggests a possible benefit for cerebral oxygenation monitoring in selected patients with severe TBM.

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., SCOPUS: re.j, info:eu-repo/semantics/published

Object Control of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) is the foundation of traumatic brain injury (TBI) management. In this study, the authors examined whether conventional ICP- and CPP-guided neurocritical care ensures adequate brain tissue O2 in the first 6 hours after resuscitation. Methods Resuscitated patients with severe TBI (Glasgow Coma Scale score ≤ 8 and Injury Severity Scale score ≥ 16) who were admitted to a Level I trauma center and who underwent brain tissue O2 monitoring within 6 hours of injury were evaluated as part of a prospective observational database. Therapy was directed to maintain an ICP of 25 mm Hg or less and a CPP of 60 mm Hg or higher. Data from a group of 25 patients that included 19 men and six women (mean age 39 ± 20 years) were examined. After resuscitation, ICP was 25 mm Hg or less in 84% and CPP was 60 mm Hg or greater in 88% of the patients. Brain O2 probes were allowed to stabilize; the initial brain tissue O2 level was 25 mm Hg or less in 68% of the patients, 20 mm Hg or less in 56%, and 10 mm Hg or less in 36%. Nearly one third (29%) of patients with ICP readings of 25 mm Hg or less and 27% with CPP levels of 60 mm Hg or greater had severe cerebral hypoxia (brain tissue O2 ≤10 mm Hg). Nineteen patients had both optimal ICP (≤25 mm Hg) and CPP (> 60 mm Hg); brain tissue O2 was 20 mm Hg or less in 47% and 10 mm Hg or less in 21% of these patients. The mortality rate was higher in patients with reduced brain tissue O2. Conclusions Brain resuscitation based on current neurocritical care standards (that is, control of ICP and CPP) does not prevent cerebral hypoxia in some patients. This finding may help explain why secondary neuronal injury occurs in some patients with adequate CPP and suggests that the definition of adequate brain resuscitation after TBI may need to be reconsidered.

Careful patient monitoring using a variety of techniques including clinical and laboratory evaluation, bedside physiological monitoring with continuous or non-continuous techniques and imaging is fundamental to the care of patients who require neurocritical care. How best to perform and use bedside monitoring is still being elucidated. To create a basic platform for care and a foundation for further research the Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to develop recommendations about physiologic bedside monitoring. This supplement contains a Consensus Summary Statement with recommendations and individual topic reviews as a background to the recommendations. In this article, we highlight the recommendations and provide additional conclusions as an aid to the reader and to facilitate bedside care.

To determine a) whether packed red blood cell transfusion (RBCT) increases local brain tissue oxygen partial pressure (Pbto2) in a neurocritical care population; and b) what (if any) demographic, clinical, or physiologic variables mediate the assumed change.Prospective observational study.A neurosurgical intensive care unit at a university-based level I trauma center and tertiary care hospital.Thirty-five consecutive volume-resuscitated patients with subarachnoid hemorrhage or traumatic brain injury, without cardiac disease, requiring Pbto2 monitoring and receiving RBCT were studied between October 2001 and December 2003.None.The following physiologic variables were measured and compared 1 hr before and after RBCT: Pbto2, intracranial pressure, cerebral perfusion pressure, hemoglobin oxygen saturation (Sao2), Fio2, hemoglobin, and hematocrit. An increase in Pbto2 was observed in 26 of the 35 patients (74%). In nine patients, Pbto2 decreased after RBCT. The mean (+/-sd) increase in Pbto2 for all patients was 3.2 +/- 8.8 mm Hg (p = .02), a 15% change from baseline (1 hr before RCBT). This Pbto2 increase was associated with a significant mean increase in hemoglobin and hematocrit after RBCT (1.4 +/- 1.1 g/dL and 4.2% +/- 3.3%, respectively; both p.001). Cerebral perfusion pressure, Sao2, and Fio2 were similar before and after RBCT. Among the 26 patients whose Pbto2 increased, the mean increase in Pbto2 was 5.1 +/- 9.4 mm Hg or a 49% mean increase (p.01).RBCT is associated with an increase in Pbto2 in most patients with subarachnoid hemorrhage or traumatic brain injury. This mean increase appears to be independent of cerebral perfusion pressure, Sao2, and Fio2. Further study is required to determine why Pbto2 decreases in some patients after RBCT.

INTRODUCTION Increasing costs and concerns about blood supply safety have led to a reevaluation of blood transfusion practices. This study was undertaken to examine blood use during aneurysm surgery. METHODS We performed a retrospective analysis of hospital records including operative, anesthetic, and nursing notes, computed tomographic scans, and four-vessel angiographic films of 547 patients undergoing surgery for ruptured and unruptured cerebral aneurysms at Harborview Medical Center in Seattle. During the review period, the transfusion threshold was not altered. RESULTS A total of 134 patients (24.5%) received an intraoperative blood transfusion (median number of units, 2; range, 1–17). Preoperative factors associated with intraoperative blood use included older patient age (P < 0.001), lower hematocrit level on admission (P = 0.007), ruptured rather than unruptured aneurysm (P = 0.004), severe intraventricular hemorrhage (P = 0.03), and larger aneurysm size (P = 0.004). Factors not associated with intraoperative blood transfusion included past medical history (including cardiac or pulmonary disease), admission clinical grade after aneurysm rupture, findings such as hydrocephalus on computed tomographic scanning, and aneurysm location and aneurysm neck-to-fundus ratio. Also associated with blood transfusion during surgery were intraoperative aneurysm rupture (P < 0.0001), intracerebral hematoma evacuation (P = 0.02), and obliteration of multiple aneurysms (P = 0.002). Among patients who received an intraoperative transfusion, those who experienced an aneurysm rupture required an average of 3.6 ± 0.35 units, whereas patients who did not have a rupture required 1.9 ± 0.12 units (P = 0.001). Postoperatively, a total of 244 patients (44.6%), including 77 who received blood intraoperatively, required a blood transfusion (median number of units, 2; range, 1–31). Postoperative blood transfusion was associated with the treatment of patients with subarachnoid hemorrhage (P < 0.0001), particularly among poor-grade patients who developed medical complications. CONCLUSION Blood transfusion can be expected in one in five patients undergoing aneurysm surgery. Reducing intraoperative rupture may reduce the need for blood products.

Rupture of cerebral aneurysms is a complex and devastating pathophysiologic event. The successful management of aneurysm rupture requires a dedicated multidisciplinary team. This article reviews pathophysiology; clinical grading that can be used to predict outcome and guide therapy; factors that may affect outcome such as rebleeding, poor clinical grade, intracerebral hemorrhage, intraventricular hemorrhage, and acute hydrocephalus; preoperative care and assessment; pharmacological therapy; anesthetic, surgical, and endovascular considerations; and postoperative care following aneurysm rupture.

Future clinical or scientific innovations may bring about improvements in the management of intracranial aneurysms and subarachnoid hemorrhage. However, there are several potential avenues for improvement in the care of, and present management of, patients with cerebral aneurysms. These opportunities for improvement exist in areas of prevention, systems approach and organization of cerebrovascular centers, physician and patient education, screening and treatment of unruptured aneurysms, and advances in surgical and endovascular therapy. All such advances, however, will depend on rigorous academic evaluation.

Subarachnoid hemorrhage (SAH) is a complex pathophysiological event that results in a number of intracranial and systemic alterations. The effective management of SAH has its foundation in the prevention, early diagnosis, and correction of complications. Successful outcome in these compromised patients requires close monitoring and intensive care. This article will review the pathophysiology of SAH, identify the most common medical and neurological events that complicate SAH, examine the impact of secondary cerebral insults after aneurysm rupture, and outline current ICU care for SAH.

Parenchymal brain tissue oxygen (PbtO2) monitoring is a safe and reliable technique for continuous bedside evaluation of patients with severe brain injury. Two techniques, a modified Clark electrode that uses the electrochemical properties of noble metals or optical fluorescence technology, can be used to measure PbtO2. PbtO2 indicates the balance between regional oxygen supply and cellular oxygen consumption and may be described by the equation PbtO2 5 CBF AVTO2, where CBF is cerebral blood flow, PvO2 is partial oxygen pressure in mixed venous blood, and AVTO2 is PaO2 PvO2. PbtO2 values less than 20 mm Hg are considered worth treating and values less than 15 mm Hg are consistent with brain hypoxia or ischemia. Reduced PbtO2 is associated with worse outcome in acute brain injury in adults and children, although the strength of this relationship may depend on probe location. When severe traumatic brain injury care is based on data from both a PbtO2 and intracranial pressure (ICP) monitor, some (but not all) observational series suggest that outcome is better than when just ICP-based care is provided.

Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. Despite encouraging animal research, pharmacological agents and neuroprotectants have disappointed in the clinical environment. Current TBI management therefore is directed towards identification, prevention, and treatment of secondary cerebral insults that are known to exacerbate outcome after injury. This strategy is based on a variety of monitoring techniques that include the neurological examination, imaging, laboratory analysis, and physiological monitoring of the brain and other organ systems used to guide therapeutic interventions. Recent clinical series suggest that TBI management informed by multimodality monitoring is associated with improved patient outcome, in part because care is provided in a patient-specific manner. In this review we discuss physiological monitoring of the brain after TBI and the emerging field of neurocritical care bioinformatics.

Patients admitted to the neurocritical care unit (NCCU) are at risk for secondary brain injury that frequently can exacerbate outcome. Consequently, current NCCU management strategies focus on the identification, prevention, and management of secondary brain injury, since there are few pharmacological agents that demonstrate efficacy in these patients. In the last decade, techniques to monitor brain function have evolved and, in the modern NCCU, play an important role in patient care and in particular in a patient-specific targeted approach. Monitors include radiologic techniques that provide information about a specific point in time or bedside monitors that provide continuous or noncontinuous physiologic information. In turn, these bedside techniques may be subdivided into invasive or noninvasive monitors. In this review we will discuss invasive intracranial monitors including (1) intracranial pressure; (2) monitors of cerebral oxygenation (direct measurement of brain oxygen [PbtO2] and jugular venous catheters); (3) metabolic monitors, i.e., cerebral microdialysis; and (4) cerebral blood flow monitors such as thermal diffusion flowmetry and laser Doppler flowmetry.

Clinical prediction models can enhance clinical decision-making and research. However, available prediction models in aneurysmal subarachnoid hemorrhage (aSAH) are rarely used. We evaluated the methodological validity of SAH prediction models and the relevance of the main predictors to identify potentially reliable models and to guide future attempts at model development. We searched the EMBASE, MEDLINE, and Web of Science databases from January 1995 to June 2012 to identify studies that reported clinical prediction models for mortality and functional outcome in aSAH. Validated methods were used to minimize bias. Eleven studies were identified; 3 developed models from datasets of phase 3 clinical trials, the others from single hospital records. The median patient sample size was 340 (interquartile range 149–733). The main predictors used were age (n = 8), Fisher grade (n = 6), World Federation of Neurological Surgeons grade (n = 5), aneurysm size (n = 5), and Hunt and Hess grade (n = 3). Age was consistently dichotomized. Potential predictors were prescreened by univariate analysis in 36 % of studies. Only one study was penalized for model optimism. Details about model development were often insufficiently described and no published studies provided external validation. While clinical prediction models for aSAH use a few simple predictors, there are substantial methodological problems with the models and none have had external validation. This precludes the use of existing models for clinical or research purposes. We recommend further studies to develop and validate reliable clinical prediction models for aSAH.

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.