Traumatic Brain Injured Research Articles

Early management of isolated severe traumatic brain injury patients in a hospital without neurosurgical capabilities: a consensus and clinical recommendations of the World Society of Emergency Surgery (WSES)

BackgroundSevere traumatic brain-injured (TBI) patients should be primarily admitted to a hub trauma center (hospital with neurosurgical capabilities) to allow immediate delivery of appropriate care in a specialized environment. Sometimes, severe TBI patients are admitted to a spoke hospital (hospital without neurosurgical capabilities), and scarce data are available regarding the optimal management of severe isolated TBI patients who do not have immediate access to neurosurgical care.MethodsA multidisciplinary consensus panel composed of 41 physicians selected for their established clinical and scientific expertise in the acute management of TBI patients with different specializations (anesthesia/intensive care, neurocritical care, acute care surgery, neurosurgery and neuroradiology) was established. The consensus was endorsed by the World Society of Emergency Surgery, and a modified Delphi approach was adopted.ResultsA total of 28 statements were proposed and discussed. Consensus was reached on 22 strong recommendations and 3 weak recommendations. In three cases, where consensus was not reached, no recommendation was provided.ConclusionsThis consensus provides practical recommendations to support clinician’s decision making in the management of isolated severe TBI patients in centers without neurosurgical capabilities and during transfer to a hub center.

Head Injury and Pregnancy—Does the Outcome Differ? A Descriptive Analysis of 15 Years from a Single Tertiary Care Center

There are conflicting data about the outcome of head injury in pregnant patients. Since they comprise a small proportion of the traumatic brain-injured (TBI) patients, the literature is sparse on true evidence on this issue. A 15-year observational study to analyze the outcome of TBI in pregnant women admitted to a level 1 trauma center from 2005-2020 was carried out with the approval of institutional review board. Female patients aged 18-50 years admitted with TBI were included. Patients with polytrauma or dead-on arrival to the emergency department were excluded from the study. The vital parameters, Glasgow Coma Scale (GCS) score at admission, Rotterdam computed tomography (CT) scan, severity score, and Glasgow Outcome Score (GOS) at 3 months were collected from the trauma database, discharge summaries, and patient records. During the study period, 5071 patients with head injury were admitted. Among the 228 patients who met inclusion criteria, 31 (13.6%) were pregnant with a mean age of 24.2 ± 3.8 years. The Rotterdam CT severity score, which moderately correlated with outcome in the control group, was found to be a poor predictor in the pregnant group. The outcome measures were compared using GCS score at discharge for immediate and GOS at 3 months for long-term periods. A better functional outcome was observed at 3 months among pregnant patients (P= 0.02). Pregnant TBI patients have better long-term outcomes than their similar-aged counterparts. However, radiologic severity of injury does not seem to predict outcome in this cohort.

Development and validation of a prediction nomogram for a 6-month unfavorable prognosis in traumatic brain-injured patients undergoing primary decompressive craniectomy: An observational study.

ObjectiveThis study was designed to develop and validate a risk-prediction nomogram to predict a 6-month unfavorable prognosis in patients with traumatic brain-injured (TBI) undergoing primary decompressive craniectomy (DC).MethodsThe clinical data of 391 TBI patients with primary DC who were admitted from 2012 to 2020 were reviewed, from which 274 patients were enrolled in the training group, while 117 were enrolled in the internal validation group, randomly. The external data sets containing 80 patients were obtained from another hospital. Independent predictors of the 6-month unfavorable prognosis were analyzed using multivariate logistic regression. Furthermore, a nomogram prediction model was constructed using R software. After evaluation of the model, internal and external validations were performed to verify the efficiency of the model using the area under the receiver operating characteristic curves and the calibration plots.ResultsIn multivariate analysis, age(p = 0.001), Glasgow Score Scale (GCS) (p < 0.001), operative blood loss of >750 ml (p = 0.045), completely effaced basal cisterns (p < 0.001), intraoperative hypotension(p = 0.001), and activated partial thromboplastin time (APTT) of >36 (p = 0.012) were the early independent predictors for 6-month unfavorable prognosis in patients with TBI after primary DC. The AUC for the training, internal, and external validation cohorts was 0.93 (95%CI, 0.89–0.96, p < 0.0001), 0.89 (95%CI, 0.82–0.94, p < 0.0001), and 0.90 (95%CI, 0.84–0.97, p < 0.0001), respectively, which indicated that the prediction model had an excellent capability of discrimination. Calibration of the model was exhibited by the calibration plots, which showed an optimal concordance between the predicted 6-month unfavorable prognosis probability and actual probability in both training and validation cohorts.ConclusionThis prediction model for a 6-month unfavorable prognosis in patients with TBI undergoing primary DC can evaluate the prognosis accurately and enhance the early identification of high-risk patients.

UPLC-Q-TOF/MS-based plasma metabolome to identify biomarkers and time of injury in traumatic brain injured rats.

To identify the potent metabolic biomarkers and time of injury of traumatic brain injured (TBI). A total of 70 Sprague-Dawley rats were used to establish the TBI model in this study. The serum was collected at 3 h, 6 h, 12 h, 24 h, 3 days and 7 days after surgery. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was performed to analyze metabolic changes in the serum of the TBI rats from different groups. The differences between the metabolic profiles of the rats in seven groups were analyzed using partial least squares discriminant analysis. Metabolic profiling revealed significant differences between the sham-operated and other groups. A total of 49 potential TBI metabolite biomarkers were identified between the sham-operated group and the model groups at different time points. Among them, six metabolites (methionine sulfone, kynurenine, 3-hydroxyanthranilic acid, 3-Indolepropionic acid, citric acid and glycocholic acid) were identified as biomarkers of TBI to estimate the injury time. Using metabolomic analysis, we identified new TBI serum biomarkers for accurate detection and determination of the timing of TBI injury.

Management of arterial partial pressure of carbon dioxide in the first week after traumatic brain injury: results from the CENTER-TBI study

PurposeTo describe the management of arterial partial pressure of carbon dioxide (PaCO2) in severe traumatic brain-injured (TBI) patients, and the optimal target of PaCO2 in patients with high intracranial pressure (ICP).MethodsSecondary analysis of CENTER-TBI, a multicentre, prospective, observational, cohort study. The primary aim was to describe current practice in PaCO2 management during the first week of intensive care unit (ICU) after TBI, focusing on the lowest PaCO2 values. We also assessed PaCO2 management in patients with and without ICP monitoring (ICPm), and with and without intracranial hypertension. We evaluated the effect of profound hyperventilation (defined as PaCO2 < 30 mmHg) on long-term outcome.ResultsWe included 1100 patients, with a total of 11,791 measurements of PaCO2 (5931 lowest and 5860 highest daily values). The mean (± SD) PaCO2 was 38.9 (± 5.2) mmHg, and the mean minimum PaCO2 was 35.2 (± 5.3) mmHg. Mean daily minimum PaCO2 values were significantly lower in the ICPm group (34.5 vs 36.7 mmHg, p < 0.001). Daily PaCO2 nadir was lower in patients with intracranial hypertension (33.8 vs 35.7 mmHg, p < 0.001). Considerable heterogeneity was observed between centers. Management in a centre using profound hyperventilation (HV) more frequently was not associated with increased 6 months mortality (OR = 1.06, 95% CI = 0.77–1.45, p value = 0.7166), or unfavourable neurological outcome (OR 1.12, 95% CI = 0.90–1.38, p value = 0.3138).ConclusionsVentilation is manipulated differently among centers and in response to intracranial dynamics. PaCO2 tends to be lower in patients with ICP monitoring, especially if ICP is increased. Being in a centre which more frequently uses profound hyperventilation does not affect patient outcomes.

Variations in Information Flow Patterns Following Intracranial Hypertensive Events in Traumatic Brain Injured Patients

Intracranial hypertension is an acute, life-threatening neurological condition that can lead to high risk of mortality. Its prompt identification and timely management are key to functional recovery and resuscitation of the patient. The objective of the present study is to propose quantitative measures for the early assessment of intracranial hypertensive (IH) episodes in traumatic brain injured (TBI) patients and to explore the association between intra-individual variability and IH events. To achieve this, we identified fifty-nine IH events in twelve TBI patients, and analyzed intracranial pressure (ICP), mean arterial pressure (MAP) and heart rate (HR). The notion of Granger causal (GC) analysis was adopted to quantify the bi-directional information flow patterns among ICP, MAP and HR. Additionally, the coefficient of variations of GC values was estimated to quantify intra-individual variations. The present study shows that GC values of ICP-to-MAP, MAP-to-ICP and HR-to-ICP decrease during an IH event while the GC value of HR-to-MAP increases during an IH event. Moreover, it was also observed that TBI patients show more inconsistency during ICP elevations. Our findings suggest that directional communications across cardiovascular (MAP and HR) and cerebrovascular (ICP) mechanisms are associated with the onset of intracranial hypertension. These derived GC measures may also be utilized as functional bio-markers in physiological diagnostics.

Predictors and outcomes of heart transplantation utilizing donors with different brain death mode: A propensity-score matching study from China

BackgroundHeart transplantation (HTx) of brain-dead donors in China has not been reported, not to mention analysis of donors with different brain death mechanisms. The present study aimed to compare clinical outcomes between HTx of traumatically brain-injured (TBI) and non-TBI donors, as well as to establish a risk-prediction model of mortality. MethodsAll patients undergoing HTx at our institute between January 1st, 2015 and December 31st, 2018 were dichotomized according to cause of donor death, and outcomes between the two groups were compared based on propensity score matching (PSM). The primary endpoint was all-cause mortality. Secondary endpoints included cardiac allograft vasculopathy and other postoperative complications. Results342 eligible HTx recipients were included. TBI grafts accounted for 62.87% (215/342). 121 pairs of candidates were generated from PSM. Actuarial and risk-adjusted survival were similar between TBI and non-TBI groups. Risk factors associated with all-cause mortality included recipient age > 60y (HR = 2.781, p = .002), history of cardiac surgery (HR = 2.186, p = .032), chronic kidney disease (HR = 2.948, p = .033) and smoking (HR = 0.465, p = .041), as well as donor age > 45y (HR = 2.701, p = .003) and BMI > 25 kg/m2 (HR = 2.025, p = .045). The risk-prediction model was established successfully based on specific preoperative variables and high-risk group with a score>10 had nearly fourfold increase in mortality (HR = 3.726, p < 0.001) compared to the low-risk group. ConclusionsIn this largest single-center cohort from China, we found similar survival and rates of complications between HTx recipients with TBI and non-TBI donors. The risk-prediction model may help to identify high-risked recipients and donors and optimize organ-sharing.

Tracheostomy practice and timing in traumatic brain-injured patients: a CENTER-TBI study.

PurposeIndications and optimal timing for tracheostomy in traumatic brain-injured (TBI) patients are uncertain. This study aims to describe the patients’ characteristics, timing, and factors related to the decision to perform a tracheostomy and differences in strategies among different countries and assess the effect of the timing of tracheostomy on patients’ outcomes.MethodsWe selected TBI patients from CENTER-TBI, a prospective observational longitudinal cohort study, with an intensive care unit stay ≥ 72 h. Tracheostomy was defined as early (≤ 7 days from admission) or late (> 7 days). We used a Cox regression model to identify critical factors that affected the timing of tracheostomy. The outcome was assessed at 6 months using the extended Glasgow Outcome Score.ResultsOf the 1358 included patients, 433 (31.8%) had a tracheostomy. Age (hazard rate, HR = 1.04, 95% CI = 1.01–1.07, p = 0.003), Glasgow coma scale ≤ 8 (HR = 1.70, 95% CI = 1.22–2.36 at 7; p < 0.001), thoracic trauma (HR = 1.24, 95% CI = 1.01–1.52, p = 0.020), hypoxemia (HR = 1.37, 95% CI = 1.05–1.79, p = 0.048), unreactive pupil (HR = 1.76, 95% CI = 1.27–2.45 at 7; p < 0.001) were predictors for tracheostomy. Considerable heterogeneity among countries was found in tracheostomy frequency (7.9–50.2%) and timing (early 0–17.6%). Patients with a late tracheostomy were more likely to have a worse neurological outcome, i.e., mortality and poor neurological sequels (OR = 1.69, 95% CI = 1.07–2.67, p = 0.018), and longer length of stay (LOS) (38.5 vs. 49.4 days, p = 0.003).ConclusionsTracheostomy after TBI is routinely performed in severe neurological damaged patients. Early tracheostomy is associated with a better neurological outcome and reduced LOS, but the causality of this relationship remains unproven.Electronic supplementary materialThe online version of this article (10.1007/s00134-020-05935-5) contains supplementary material, which is available to authorized users.

Cortisol total/CRP ratio for the prediction of hospital-acquired pneumonia and initiation of corticosteroid therapy in traumatic brain-injured patients

BackgroundTo propose a combination of blood biomarkers for the prediction of hospital-acquired pneumonia (HAP) and for the selection of traumatic brain-injured (TBI) patients eligible for corticosteroid therapy for the prevention of HAP.MethodsThis was a sub-study of the CORTI-TC trial, a multicenter, randomized, double-blind, controlled trial evaluating the risk of HAP at day 28 in 336 TBI patients treated or not with corticosteroid therapy. Patients were between 15 and 65 years with severe traumatic brain injury (Glasgow coma scale score ≤ 8 and trauma-associated lesion on brain CT scan) and were enrolled within 24 h of trauma. The blood levels of CRP and cortisoltotal&free, as a surrogate marker of the pro/anti-inflammatory response balance, were measured in samples collected before the treatment initiation. Endpoint was HAP on day 28.ResultsOf the 179 patients with available samples, 89 (49.7%) developed an HAP. Cortisoltotal&free and CRP blood levels upon ICU admission were not significantly different between patients with or without HAP. The cortisoltotal/CRP ratio upon admission was 2.30 [1.25–3.91] in patients without HAP and 3.36 [1.74–5.09] in patients with HAP (p = 0.021). In multivariate analysis, a cortisoltotal/CRP ratio > 3, selected upon the best Youden index on the ROC curve, was independently associated with HAP (OR 2.50, CI95% [1.34–4.64] p = 0.004). The HR for HAP with corticosteroid treatment was 0.59 (CI95% [0.34–1.00], p = 0.005) in patients with a cortisoltotal/CRP ratio > 3, and 0.89 (CI95% [0.49–1.64], p = 0.85) in patients with a ratio < 3.ConclusionA cortisoltotal/CRP ratio > 3 upon admission may predict the development of HAP in severe TBI. Among these patients, corticosteroids reduce the occurrence HAP. We suggest that this ratio may select the patients who may benefit from corticosteroid therapy for the prevention of HAP.

The Neutrophil/Lymphocyte Count Ratio Predicts Mortality in Severe Traumatic Brain Injury Patients.

Introduction: Neutrophil-lymphocyte count ratio (NLCR) is a simple and low-cost marker of inflammatory response. NLCR has shown to be a sensitive marker of clinical severity in inflammatory-related tissue injury, and high value of NLCR is associated with poor outcome in traumatic brain injured (TBI) patients. The purpose of this study was to retrospectively analyze NLCR and its association with outcome in a cohort of TBI patients in relation to the type of brain injury. Methods: Adult patients admitted for isolated TBI with Glasgow Coma Score lower than eight were included in the study. NLCR was calculated as the ratio between the absolute neutrophil and lymphocyte count immediately after admission to the hospital, and for six consecutive days after admission to the intensive care unit (ICU). Brain injuries were classified according to neuroradiological findings at the admission computed tomography (CT) as DAI—patients with severe diffuse axonal injury; CE—patients with hemispheric or focal cerebral edema; ICH—patients with intracerebral hemorrhage; S-EH/SAH—patients with subdural and/or epidural hematoma/subarachnoid hemorrhage. Results: NLCR was calculated in 144 patients. Admission NLCR was significantly higher in the non-survivors than in those who survived at 28 days (p < 0.05) from admission. Persisting high NLCR value was associated with poor outcome, and admission NLCR higher than 15.63 was a predictor of 28-day mortality. The highest NLCR value at admission was observed in patients with DAI compared with other brain injuries (p < 0.001). Concussions: NLCR can be a useful marker for predicting outcome in TBI patients. Further studies are warranted to confirm these results.

Heart Transplantation Survival and the Use of Traumatically Brain-Injured Donors: UNOS Registry Propensity-Matched Analysis.

BackgroundThe transplantation of hearts from traumatically brain‐injured (TBI) donors has been associated with inferior long‐term survival in single‐center analyses. However, in a more recent analysis, death caused by cerebrovascular accident was associated with worse posttransplant survival in recipients. The purpose of this study was to explore the outcomes of heart transplantation in recipients receiving donor hearts from TBI and non‐TBI donors in a large national registry.Methods and ResultsWe performed a retrospective cohort analysis of the UNOS (United Network of Organ Sharing) Registry Organ Procurement and Transplantation Network between 2006 and 2018 for adult candidates wait‐listed for isolated heart transplantation. Recipients were stratified into 2 groups, TBI and non‐TBI donors. Propensity score matching was performed. Kaplan‐Meier analysis was used to estimate survival posttransplant. A total of 24 894 candidates met inclusion criteria. TBI was the leading cause of death in the donor population. Recipients of TBI donor hearts (N=13 07) were younger (median age, 55 versus 57 years; P<0.001) and less likely women (21.6% versus 29.8%; P<0.001). At 10 years, the TBI group had better long‐term survival compared with the non‐TBI group (62.8% versus 59.9%; P<0.001). After propensity group matching, the 10‐year survival was similar between groups.ConclusionsIn the largest analysis of heart transplants and their survival, according to the type of donor injury (TBI versus non‐TBI), we found similar survival in heart transplant recipients. Future studies should address specific subpopulations (eg, hemorrhagic stroke) in the non‐TBI group to address concerns about reduced posttransplant survival.

Da-Cheng-Qi Decoction () Combined with Lactobacillus Acidophilus Improves Gastrointestinal Function of Traumatic Brain-Injured Model Mice.

To investigate the effects of Da-Cheng-Qi Decoction (DCQD, ) combined with Lactobacillus acidophilus (LA) on the recovery of gastrointestinal (GI) function in traumatic brain-injured (TBI) mice. A total of 150 male C57BL/6 mice were randomly divided into sham-injury, normal saline (NS), DCQD (0.4 mL/day), LA (⩾1 × 1010 cfu/day LA), DCQD+LA (LA administration at the same dosage after 4 h of feeding DCQD), and ½ DCQD+LA groups (LA administration at the same dosage after 4 h of feeding ½ DCQD dose) by a random number table, 5-8 mice in each group. The sever TBI model was constructed according to Feeney's enhanced gravitational forces of free falling. On days 1, 3, and 7 post-TBI, plasma diamine oxidase (DAO) and D-lactic acid levels were assessed by enzyme-linked immunosorbent assay (ELISA). Occludin expression in the intestinal epithelium was assessed by Western blot analysis. Transmission electron microscopy (TEM) was used to observe the morphological changes in the network structure of interstitial cells of Cajal (ICC) and change of enteric nervous system-ICC-smooth muscle cell (ENS-ICC-SMC). Immunofluorescence staining was used to detect changes in the network structure of the ICC. Compared with the NS group, occludin expression in the DCQD+LA group significantly increased on Day 1, 3, and 7 post-TBI (P<0.05 or P<0.01). The concentration of DAO significantly decreased in the LA, DCQD, and DCQD+LA groups on Day 3 and 7, whilst the D-lactate concentrations in the LA and ½ DCQD+LA groups decreased on Day 1 and 3 post-injury (P<0.05 or P<0.01). The NS group experienced a great damage on the ENS-ICC-SMC network morphology and ICC network structure, and all treatment groups had some improvements, among which the DCQD+LA group presented relatively intact network morphology. DCQD combined with LA treatment could effectively repair the intestinal mucosal barrier and improve GI motility in mice after TBI. The combination of DCQD and LA was more effective than their respective monotherapies.

Abstracts from The 37th Annual National Neurotrauma Symposium June 29–July 3, 2019 Pittsburgh, Pennsylvania

Abstracts from The 37^th Annual National Neurotrauma Symposium June 29–July 3, 2019 Pittsburgh, Pennsylvania

Impact of Traumatically Brain-Injured Donors on Outcomes After Heart Transplantation

BackgroundHeart transplant recipients of traumatically brain-injured (TBI) donors have been reported to have inferior survival and increased rates of cardiac allograft vasculopathy in single-center studies. This study sought to examine the impact of TBI donors on outcomes after heart transplantation across all transplantation centers. MethodsWe identified all adult heart transplants performed during 2007-2016 in the OPTN database. Recipients were dichotomized based on donor cause of death (TBI versus non-TBI), propensity-scored across 22 variables with known associations with mortality, and matched 1:1 without replacement. The primary endpoint was all-cause mortality. Secondary endpoints were conditional survival and rates of cardiac allograft vasculopathy. ResultsIn total, 20,244 patients underwent heart transplantation. TBI was the primary cause of death in 53.4% of donors (10,816/20,244), and among TBI donors, blunt injury (59.6%; 6443/10,816) and gunshot wound (35%; 3781/10,816) were the most common mechanisms of injury. Propensity matching generated 6919 pairs (all absolute mean differences < 0.07). Risk-adjusted survival was similar between recipients of TBI donors and non-TBI donors at 5 y (78.1% versus 77.5%, log-rank P = 0.34). Risk-adjusted survival conditional on 1-y survival was also similar at 5 y (86.2% versus 86.1%, log-rank P = 0.74). The 5-y risk-adjusted rates of cardiac allograft vasculopathy did not differ either (30.6% versus 30.4%; log-rank P = 0.78). ConclusionsIn the largest analysis of TBI donors in heart transplantation, we found similar survival and rates of cardiac allograft vasculopathy to those who received hearts from non-TBI donors out to 5 y. These findings should allay concerns over continued transplantation with this unique donor population.

Heart Transplantation Survival and the Use of Traumatically Brain-Injured Donors

Purpose The transplantation of hearts from traumatically brain-injured (TBI) donors has been associated with inferior long-term survival. The purpose of this study was to explore the outcomes of heart transplantation using TBI donors in a large national registry. Methods We performed a retrospective cohort analysis of the OPTN/UNOS registry encompassing years 1987 to 2018 for adult candidates (>18 years) waitlisted for isolated heart transplantation. Recipients were stratified into two groups, TBI and non-TBI donors. Propensity score matching was performed across key baseline demographic variables and a 1:1 match was done. Kaplan-Meier analysis was used to estimate survival post-transplant. Cox Proportional Hazards modeling was performed to identify independent predictors of survival. Results A total of 58,474 candidates met inclusion criteria. TBI was the leading cause of death in the donor population. Non-TBI donors (N=27,483) were more likely female (41.6% vs 18.8%, p Conclusion In the largest analysis of heart transplants and their survival according to the type of donor injury: TBI vs non-TBI, we found similar survival in heart transplant recipients. These findings should relieve concerns regarding using this unique donor population in heart transplantation.

Time estimation: Close your eyes and tell me when a minute goes by

The 1-minute estimation test is a relatively new task. This article is an initial offering showing normative data for children from age six up through adulthood (age =76). The task is quite simple, the individual was simply asked to estimate the passage of time for 1 minute. The normative data indicate that children’s data needs to be stratified by age, whereas adult data did not need to be stratified by age. Demographic variables such as handedness, gender and ethnicity were not significantly related to 1-minute estimation performance. In looking at a comparison between Traumatic Brain Injured (TBI) patients and Normal Controls, there was a significant effect suggesting that the 1-minute estimation is sensitive to cognitive impairment. Further investigation is needed; however, investigation must begin with the availability of adequate norms so that comparisons can be made. This article provides the needed normative data.

Forewarning of hypotensive events using a Bayesian artificial neural network in neurocritical care.

Traumatically brain injured (TBI) patients are at risk from secondary insults. Arterial hypotension, critically low blood pressure, is one of the most dangerous secondary insults and is related to poor outcome in patients. The overall aim of this study was to get proof of the concept that advanced statistical techniques (machine learning) are methods that are able to provide early warning of impending hypotensive events before they occur during neuro-critical care. A Bayesian artificial neural network (BANN) model predicting episodes of hypotension was developed using data from 104 patients selected from the BrainIT multi-center database. Arterial hypotension events were recorded and defined using the Edinburgh University Secondary Insult Grades (EUSIG) physiological adverse event scoring system. The BANN was trained on a random selection of 50% of the available patients (n = 52) and validated on the remaining cohort. A multi-center prospective pilot study (Phase 1, n = 30) was then conducted with the system running live in the clinical environment, followed by a second validation pilot study (Phase 2, n = 49). From these prospectively collected data, a final evaluation study was done on 69 of these patients with 10 patients excluded from the Phase 2 study because of insufficient or invalid data. Each data collection phase was a prospective non-interventional observational study conducted in a live clinical setting to test the data collection systems and the model performance. No prediction information was available to the clinical teams during a patient's stay in the ICU. The final cohort (n = 69), using a decision threshold of 0.4, and including false positive checks, gave a sensitivity of 39.3% (95% CI 32.9-46.1) and a specificity of 91.5% (95% CI 89.0-93.7). Using a decision threshold of 0.3, and false positive correction, gave a sensitivity of 46.6% (95% CI 40.1-53.2) and specificity of 85.6% (95% CI 82.3-88.8). With a decision threshold of 0.3, > 15min warning of patient instability can be achieved. We have shown, using advanced machine learning techniques running in a live neuro-critical care environment, that it would be possible to give neurointensive teams early warning of potential hypotensive events before they emerge, allowing closer monitoring and earlier clinical assessment in an attempt to prevent the onset of hypotension. The multi-centre clinical infrastructure developed to support the clinical studies provides a solid base for further collaborative research on data quality, false positive correction and the display of early warning data in a clinical setting.

Changes in Optic Nerve Sheath Diameter in Response to Various Levels of End-Tidal Carbon Dioxide in Healthy Patients under General Anesthesia

Abstract Background Intracranial pressure (ICP) monitoring is an essential component in management of traumatic brain-injured (TBI) patients. While invasive techniques are associated with many complications, noninvasive nature of ultrasonographic measurement of optic nerve sheath diameter (ONSD) is now becoming popular. Carbon dioxide (CO2) alters the ICP by changing the size of cerebral vasculature. We aimed to assess the effect of (hypercarbia and hypocarbia) different levels of end-tidal carbon dioxide (EtCO2) on ONSD. Methods Thirty adult patients aged between 18 and 65 years, undergoing brachial plexus injury surgery under general anesthesia, were enrolled. Following standard anesthetic protocol, ONSD was measured at different time points of EtCO2. ONSD was measured at EtCO2 of 40 and then 30 mm Hg to assess change in ONSD due to hypocarbia (Thypocarbia). Similarly, ONSD was measured at EtCO2 of 50 mm Hg to assess change in ONSD due to hypercarbia (Thypercarbia). The mean of three ONSD values at each time point was taken as the final value. The generalized estimating equation (GEE) was used to analyze correlation between different levels of EtCO2 and ONSD. Results The calculated 95% confidence interval (CI) for the difference of two measures (Thypocarbia, EtCO2 40 and 30 mm Hg) on ONSD was −0.056 to −0.036, and the calculated CI for the difference of other two measures (Thypercarbia, EtCO2 40 and 50 mm Hg) on ONSD was 0.044 to 0.077, and thus were observed to be significant. Conclusions ONSD changes significantly in response to different EtCO2 levels in healthy non-neurosurgical patients under general anesthesia.

Albeit nocturnal, rats subjected to traumatic brain injury do not differ in neurobehavioral performance whether tested during the day or night.

Behavioral assessments in rats are overwhelmingly conducted during the day, albeit that is when they are least active. This incongruity may preclude optimal performance. Hence, the goal of this study was to determine if differences in neurobehavior exist in traumatic brain injured (TBI) rats when assessed during the day vs. night. The hypothesis was that the night group would perform better than the day group on all behavioral tasks. Anesthetized adult male rats received either a cortical impact or sham injury and then were randomly assigned to either Day (1:00-3:00p.m.) or Night (7:30-9:30p.m.) testing. Motor function (beam-balance/walk) was conducted on post-operative days 1-5 and cognitive performance (spatial learning) was assessed on days 14-18. Corticosterone (CORT) levels were quantified at 24h and 21days after TBI. No significant differences were revealed between the TBI rats tested during the Day vs. Night for motor or cognition (p's<0.05). CORT levels were higher in the Night-tested TBI and sham groups at 24h (p<0.05), but returned to baseline and were no longer different by day 21 (p>0.05), suggesting an initial, but transient, stress response that did not affect neurobehavioral outcome. These data suggest that the time rats are tested has no noticeable impact on their performance, which does not support the hypothesis. The finding validates the interpretations from numerous studies conducted when rats were tested during the day vs. their natural active period.

Automated subdural hematoma segmentation for traumatic brain injured (TBI) patients.

Traumatic brain injury is a serious public health problem in the U.S. contributing to a large portion of permanent disability. However, its early management and treatment could limit the impact of the injury, save lives and reduce the burden of cost for patients as well as healthcare systems. Subdural hematoma is one of the most common types of TBI, which its visual detection and quantitative evaluation are time consuming and prone to error. In this study, we propose a fully auto-mated machine learning based approach for 3D segmentation of convexity subdural hematomas. Textural, statistical and geometrical features of sample points from intracranial region are extracted based on head Computed Tomography (CT) images. Then, a tree bagger classifier is implemented to classify each pixel as hematoma or no-hematoma. Our method yields sensitivity, specificity and area under the receiver operating curve (AUC) of 85:02%, 73:74% and 0:87 respectively.