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.

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.

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.

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.

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.

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.

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.

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.

Inflammation-induced preterm birth alters neuronal morphology in the mouse fetal brain.

Adverse neurological outcome is a major cause of long-term morbidity in ex-preterm children. To investigate the effect of parturition and inflammation on the fetal brain, we utilized two in vivo mouse models of preterm birth. To mimic the most common human scenario of preterm birth, we used a mouse model of intrauterine inflammation by intrauterine infusion of lipopolysaccharide (LPS). To investigate the effect of parturition on the immature fetal brain, in the absence of inflammation, we used a non-infectious model of preterm birth by administering RU486. Pro-inflammatory cytokines (IL-10, IL-1beta, IL-6 and TNF-alpha) in amniotic fluid and inflammatory biomarkers in maternal serum and amniotic fluid were compared between the two models using ELISA. Pro-inflammatory cytokine expression was evaluated in the whole fetal brains from the two models. Primary neuronal cultures from the fetal cortex were established from the different models and controls in order to compare the neuronal morphology. Only the intrauterine inflammation model resulted in an elevation of inflammatory biomarkers in the maternal serum and amniotic fluid. Exposure to inflammation-induced preterm birth, but not non-infectious preterm birth, also resulted in an increase in cytokine mRNA in whole fetal brain and in disrupted fetal neuronal morphology. In particular, Microtubule-associated protein 2 (MAP2) staining was decreased and the number of dendrites was reduced (P < 0.001, ANOVA between groups). These results suggest that inflammation-induced preterm birth and not the process of preterm birth may result in neuroinflammation and alter fetal neuronal morphology.

The effect of blood transfusion on brain oxygenation in children with severe traumatic brain injury.

OBJECTIVE: The indications for blood transfusion in traumatic brain injury are controversial. In particular, little is known about the effect of blood transfusion in childhood traumatic brain injury. This study aimed to examine the influence of blood transfusion on brain tissue oxygen tension in children with severe traumatic brain injury. DESIGN: A retrospective analysis of a prospective observational database of children with severe traumatic brain injury who received brain tissue oxygen tension monitoring and a blood transfusion. SETTING: University-affiliated pediatric hospital. PATIENTS: Children with severe traumatic brain injury and blood transfusion. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Brain tissue oxygen tension was measured in normal-appearing white matter with a commercially available polarographic Clarke-type electrode. Brain tissue oxygen tension values after blood transfusion were compared with pre-transfusion values in hemodynamically stable patients. Limited interventions were allowed during the studied period. Brain tissue oxygen tension values were examined for early (1-4 hrs) and late (24 hrs) changes after blood transfusion, controlling for multiple clinical and physiologic variables with regression techniques. Further comparison was made with matched non-transfused controls to examine the influence of time after injury. Nineteen blood transfusions in 17 patients were evaluated. Brain tissue oxygen tension increased significantly in the early period after blood transfusion (p = .0018; 79% increased, 21% decreased) in comparison with baseline values and matched controls, but the overall changes were small and, in part, influenced by accompanying cerebral perfusion pressure changes. Also, this effect was limited to the early period after blood transfusion and was not significant after 24 hrs. In general, the brain tissue oxygen tension increase was larger in patients with higher baseline brain tissue oxygen tension and lower initial hemoglobin; however, no factors associated with the magnitude of the brain tissue oxygen tension change were significant in multivariate analysis. Increased age of blood did not appear to impair brain tissue oxygen tension changes, but most blood transfusion were <14 days old. CONCLUSIONS: Brain tissue oxygen tension increased transiently in 79% of blood transfusion in pediatric traumatic brain injury patients, and decreased transiently in 21%. Brain tissue oxygen tension returned to baseline within 24 hrs. Reliable predictors of this brain tissue oxygen tension response to blood transfusion, however, remain elusive.

Effect of shivering on brain tissue oxygenation during induced normothermia in patients with severe brain injury.

BACKGROUND: We analyzed the impact of shivering on brain tissue oxygenation (PbtO(2)) during induced normothermia in patients with severe brain injury. METHODS: 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. RESULTS: Fifteen patients (10 with severe traumatic brain injury, 5 with aneurysmal subarachnoid hemorrhage) were treated with induced normothermia for an average of 5 +/- 2 days. Shivering caused a significant decrease in PbtO(2) levels both in SAH and TBI patients. Compared to baseline, shivering was associated with an overall reduction of PbtO(2) from 34.1 +/- 7.3 to 24.4 +/- 5.5 mmHg (P < 0.001). A significant correlation was found between the magnitude of shivering-associated decrease of PbtO(2) (DeltaPbtO(2)) and circulating water temperature (R = 0.82, P < 0.001). CONCLUSION: 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.

The effect of increased inspired fraction of oxygen on brain tissue oxygen tension in children with severe traumatic brain injury.

BACKGROUND: This study examines the effect of an increase in the inspired fraction of oxygen (FiO2) on brain tissue oxygen (PbO2) in children with severe traumatic brain injury (TBI). METHODS: A prospective observational study of patients who underwent PbO2 monitoring and an oxygen challenge test (temporary increase of FiO2 for 15 min) was undertaken. Pre- and post-test values for arterial partial pressure of oxygen (PaO2), PbO2, and arterial oxygen content (CaO2) were examined while controlling for any changes in arterial carbon dioxide tension and cerebral perfusion pressure during the test. Baseline transcranial Doppler studies were done. Outcome was assessed at 6 months. RESULTS: A total of 43 tests were performed in 28 patients. In 35 tests in 24 patients, the PbO2 monitor was in normal-appearing white matter and in eight tests in four patients, the monitor was in a pericontusional location. When catheters were pericontusional or in normal white matter the baseline PbO2/PaO2 ratio was similar. PaO2 (P < 0.0001) and PbO2 (P < 0.0001) significantly increased when FiO2 was increased. The magnitude of the PbO2 response (PbO2) was correlated with PaO2 (P < 0.0001, R(2) = 0.37) and CaO2 (P = 0.001, R(2) = 0.23). The PbO2/PaO2 ratio (oxygen reactivity) varied between patients, was related to the baseline PbO2 (P = 0.001, r = 0.54) and was inversely related to outcome (P = 0.02, confidence interval 0.03-0.78). CONCLUSION: Normobaric hyperoxia increases PbO2 in children with severe TBI, but the response is variable. The magnitude of this response is related to the change in PaO2 and the baseline PbO2. A greater response appears to be associated with worse outcome.

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.

The use of a portable head CT scanner in the intensive care unit.

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.

Hemoglobin concentration and cerebral metabolism in patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The optimal hemoglobin (Hgb) target after aneurysmal subarachnoid hemorrhage is not precisely known. We sought to examine the threshold of Hgb concentration associated with an increased risk of cerebral metabolic dysfunction in patients with poor-grade subarachnoid hemorrhage. METHODS: Twenty consecutive patients with poor-grade subarachnoid hemorrhage who underwent multimodality neuromonitoring (intracranial pressure, brain tissue oxygen tension, cerebral microdialysis) were studied prospectively. Brain tissue oxygen tension and extracellular lactate/pyruvate ratio were used as markers of cerebral metabolic dysfunction and the relationship between Hgb concentrations and the incidence of brain hypoxia (defined by a brain tissue oxygen tension <20 mm Hg) and cell energy dysfunction (defined by a lactate/pyruvate ratio >40) was analyzed. RESULTS: Compared with higher Hgb concentrations, a Hgb concentration <9 g/dL was associated with lower brain tissue oxygen tension (27.2 [interquartile range, 21.2 to 33.1] versus 19.9 [interquartile range, 7.1 to 33.1] mm Hg, P=0.02), higher lactate/pyruvate ratio (29 [interquartile range, 25 to 38] versus 36 [interquartile range, 26 to 59], P=0.16), and an increased incidence of brain hypoxia (21% versus 52%, P<0.01) and cell energy dysfunction (23% versus 43%, P=0.03). On multivariable analysis, a Hgb concentration <9 g/dL was associated with a higher risk of brain hypoxia (OR, 7.92; 95% CI, 2.32 to 27.09; P<0.01) and cell energy dysfunction (OR, 4.24; 95% CI, 1.33 to 13.55; P=0.02) after adjusting for cerebral perfusion pressure, central venous pressure, PaO(2)/FIO(2) ratio, and symptomatic vasospasm. CONCLUSIONS: A Hgb concentration <9 g/dL is associated with an increased incidence of brain hypoxia and cell energy dysfunction in patients with poor-grade subarachnoid hemorrhage.

Induced normothermia attenuates cerebral metabolic distress in patients with aneurysmal subarachnoid hemorrhage and refractory Fever.

BACKGROUND AND PURPOSE: The purpose of this study was to analyze whether fever control attenuates cerebral metabolic distress after aneurysmal subarachnoid hemorrhage (SAH). METHODS: Eighteen SAH patients, who underwent intracranial pressure (ICP) and cerebral microdialysis monitoring and were treated with induced normothermia for refractory fever (body temperature >or=38.3 degrees C, despite antipyretics), were studied. Levels of microdialysate lactate/pyruvate ratio (LPR) and episodes of cerebral metabolic crisis (LPR >40) were analyzed during fever and induced normothermia, at normal and high ICP (>20 mm Hg). RESULTS: Compared to fever, induced normothermia resulted in lower LPR (40+/-24 versus 32+/-9, P<0.01) and a reduced incidence of cerebral metabolic crisis (13% versus 5%, P<0.05) at normal ICP. During episodes of high ICP, induced normothermia was associated with a similar reduction of LPR, fewer episodes of cerebral metabolic crisis (37% versus 8%, P<0.01), and lower ICP (32+/-11 versus 28+/-12 mm Hg, P<0.05). CONCLUSIONS: Fever control is associated with reduced cerebral metabolic distress in patients with SAH, irrespective of ICP.

Beyond white matter damage: fetal neuronal injury in a mouse model of preterm birth.

OBJECTIVE: The purpose of this study was to elucidate possible mechanisms of fetal neuronal injury in inflammation-induced preterm birth. STUDY DESIGN: With the use of a mouse model of preterm birth, the following primary cultures were prepared from fetal brains: (1) control neurons (CNs), (2) lipopolysaccharide-exposed neurons (LNs), (3) control coculture (CCC) that consisted of neurons and glia, and (4) lipopolysaccharide-exposed coculture (LCC) that consisted of lipopolysaccharide-exposed neurons and glia. CNs and LNs were treated with culture media from CN, LN, CCC, and LCC after 24 hours in vitro. Immunocytochemistry was performed for culture characterization and neuronal morphologic evidence. Quantitative polymerase chain reaction was performed for neuronal differentiation marker, microtubule-associated protein 2, and for cell death mediators, caspases 1, 3, and 9. RESULTS: Lipopolysaccharide exposure in vivo did not influence neuronal or glial content in cocultures but decreased the expression of microtubule-associated protein 2 in LNs. Media from LNs and LCCs induced morphologic changes in control neurons that were comparable with LNs. The neuronal damage caused by in vivo exposure (LNs) could not be reversed by media from control groups. CONCLUSION: Lipopolysaccharide-induced preterm birth may be responsible for irreversible neuronal injury.

Brain tissue oxygen tension monitoring in pediatric severe traumatic brain injury. Part 1: Relationship with outcome.

INTRODUCTION: Intracranial pressure (ICP) monitoring and cerebral perfusion pressure (CPP) management are the current standards to guide care of severe traumatic brain injury (TBI). However, brain hypoxia and secondary brain injury can occur despite optimal ICP and CPP. In this study, we used brain tissue oxygen tension (PbtO(2)) monitoring to examine the association between multiple patient factors, including PbtO(2), and outcome in pediatric severe TBI. MATERIALS AND METHODS: In this prospective observational study, 52 children (less than 15 years) with severe TBI were managed with continuous PbtO(2) and ICP monitoring. The relationships between outcome [Glasgow Outcome Score (GOS) and Pediatric Cerebral Performance Category Scale] and clinical, radiologic, treatment, and physiological variables, including PbtO(2), were examined using multiple logistic regression analysis. RESULTS: Outcome was favorable in 40 patients (77%) and unfavorable (mortality, 9.6%; n = 5) in 12 (23%). In univariate analysis, the following variables had a significant association with unfavorable outcome: initial GCS, computed tomography classification, ICP(peak), mICP(24), mICP, CPP(low), CPP(<40), pupil reactivity, PbtO(2)(low), PbtO(2) < 5 mmHg, PbtO(2) < 10 mmHg, mPbtO(2)(24), and time-severity product. PbtO(2) parameters had the strongest independent association with poor outcome in multiple regression analysis. In particular, when PbtO(2) was <5 mmHg for >1 h, the adjusted OR for poor outcome was 27.4 (95% confidence interval, 1.9-391). No variables apart from PbtO(2) were independently associated with mortality when controlled for PbtO(2). CONCLUSION: Reduced PbtO(2) is shown to be an independent factor associated with poor outcome in pediatric severe TBI in the largest study to date. It appears to have a stronger association with outcome than conventionally evaluated measures.

Brain tissue oxygen tension monitoring in pediatric severe traumatic brain injury. Part 2: Relationship with clinical, physiological, and treatment factors.

INTRODUCTION: Brain tissue oxygen tension (PbtO(2)) monitoring is used increasingly in adult severe traumatic brain injury (TBI) management. Several factors are known to influence PbtO(2) in adults, but the variables that affect PbtO(2) in pediatric TBI are not well described. This study examines the relationships between PbtO(2) and (1) physiological markers of potential secondary insults commonly used in pediatric TBI, in particular intracranial pressure (ICP), cerebral perfusion pressure (CPP), and systemic hypoxia, and (2) other clinical factors and treatment received that may influence PbtO(2). MATERIALS AND METHODS: In this prospective observational study, 52 children (mean age, 6.5 +/- 3.4 years; range, 9 months to 14 years old) with severe TBI and a median post-resuscitation Glasgow Coma Score (GCS) of 5 were managed with continuous PbtO(2) monitoring. The relationships between PbtO(2) parameters (Pbt)(2)(low), PbtO(2) < 5, PbtO(2) < 10, and mPbtAO(2)(24)) and clinical, physiological, and treatment factors were explored using time-linked data and Spearman's correlation coefficients. RESULTS: No clinical, physiological, or treatment variable was significantly associated with all PbtO(2) parameters, but individual associations were found with initial GCS (PbtO(2) < 5, p = 0.0113), admission Pediatric Trauma Score (PbtO(2) < 10, 0.0175), mICP > 20 (mPbtO(2)(24), p = 0.0377), CPP(low) (PbtO(2)(low), p = 0.0065), CPP < 40 (PbtO(2)(low), p = 0.0269; PbtO(2) < 5, p = 0.0212), P(a)O(2) < 60 (mPbtO(2)(24), p = 0.0037), S(a)O(2) < 90 (PbtO(2)(low), p = 0.0438), and use of inotropes during ICU care (PbtO(2)(low), p = 0.0276; PbtO(2) < 10, p = 0.0277; p = mPbtO(2)(24)). CONCLUSION: Delivery of oxygen to the brain is important to limit secondary neuronal injury after severe TBI. Our data show that PbtO(2) is poorly predicted by clinical and physiological factors commonly measured in the pediatric ICU. Multimodality monitoring may be needed to detect all secondary cerebral insults in pediatric TBI.