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Anemia is very common in aneurysmal subarachnoid hemorrhage (aSAH), with approximately half of the aSAH patient population developing moderate anemia during their hospital stay. The available evidence (both physiologic and clinical) generally supports an association of anemia with unfavorable outcomes. Although aSAH shares a number of common mechanisms of secondary insult with other forms of acute brain injury, aSAH also has specific features that make it unique: an early phase (in which early brain injury predominates) and a delayed phase (in which delayed cerebral ischemia and vasospasm predominate). The effects of both anemia and transfusion are potentially variable between these phases, which may have unique considerations and possibly different risk-benefit profiles. Data on transfusion in this population are almost exclusively limited to observational studies, which suffer from significant heterogeneity and risk of bias. Overall, the results are conflicting, with the balance of the studies suggesting that transfusion is associated with unfavorable outcomes. The transfusion targets that are well established in other critically ill populations should not be automatically applied to patients with aSAH because of the unique disease characteristics of this population and the limited representation of aSAH in the clinical trials that established these targets. There are two upcoming clinical trials evaluating transfusion in aSAH that should help clarify specific transfusion targets. Until then, it is reasonable to base transfusion decisions on the current guidelines and use an individualized approach incorporating physiologic and clinical data when available., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Anemia is common in neurocritically ill patients. Considering the limited clinical evidence in this population, preclinical data may provide some understanding of the potential impact of anemia and of red blood cell transfusion in these patients. We aim to estimate the association between different transfusion strategies and neurobehavioral outcome in animal models., Methods: We will conduct a systematic review of comparative studies of red blood cell transfusion strategies using animal models of traumatic brain injury, ischemic stroke or cerebral hemorrhage. We will search MEDLINE, EMBASE, and Web of Science databases for eligible studies from inception onwards. Two independent reviewers will perform study selection and data extraction. We will report our results in a descriptive synthesis focusing on characteristics of included studies, reported outcomes, risk of bias, and construct validity. Our primary outcome is the neurological function (neurobehavioral performance) and our secondary outcomes include mortality, infarct size, intracranial pressure, cerebral perfusion pressure, cerebral blood flow, and brain tissue oxygen tension. If appropriate, we will also perform a quantitative synthesis and pool results using random-effect models. Heterogeneity will be expressed with I 2 statistics. Subgroup analyses are planned according to animal model characteristics, co-interventions, and risks of bias., Discussion: Our study is aligned with the efforts to better understand the level of evidence on the impact of red blood cell transfusion strategies from preclinical studies in animal models of acute brain injury and the potential translation of information from the preclinical to the clinical research field., Systematic Review Registration: PROSPERO CRD42018086662 .

Objectives: To present the recommendations and supporting literature for RBC transfusions in critically ill children with acute brain injury developed by the Pediatric Critical Care Transfusion and Anemia Expertise Initiative., Design: Consensus conference series of international, multidisciplinary experts in RBC transfusion management of critically ill children., Methods: The panel of 38 experts developed evidence-based, and when evidence was lacking, expert-based clinical recommendations as well as research priorities for RBC transfusions in critically ill children. The acute brain injury subgroup included three experts. Electronic searches were conducted using PubMed, EMBASE, and Cochrane Library databases from 1980 to May 2017. Agreement was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method., Results: Transfusion and Anemia Expertise Initiative Consensus Conference experts developed and agreed upon two clinical and two research recommendations focused on RBC transfusion in the critically ill child with acute brain injury. Recommendations include consideration of RBC transfusion for a hemoglobin concentration between 7 and 10 g/dL in patients with acute brain injury and do not support the use of brain tissue PO2 monitoring to guide RBC transfusion decisions. Research is needed to better understand transfusion thresholds and brain tissue monitoring for pediatric patients with acute brain injury., Conclusions: The Transfusion and Anemia Expertise Initiative Consensus Conference developed pediatric-specific clinical and research recommendations regarding RBC transfusion in the critically ill child with acute brain injury. Although agreement among experts was very strong, the available pediatric evidence was extremely limited with major gaps in the literature.

Background: Current guidelines identify the choice of fluid resuscitation as important in minimizing the incidence of secondary brain injury from cerebral edema. It is widely accepted that isotonic crystalloid resuscitation fluids, specifically normal saline (NS), are optimal for resuscitation and that other relatively hypotonic fluids, such as Ringer's lactate (RL), should be avoided in this patient population. The aim of this review is to systematically compare the use of relatively hypotonic versus isotonic crystalloid resuscitation fluids in clinical and pre-clinical models of acute brain injury and their effect on outcomes. In recognition of the potential need for a network meta-analysis (NMA), we have also included all other relevant crystalloid resuscitation fluids as interventions of relevance to potentially inform indirect comparisons., Methods: Systematic searches of MEDLINE, Embase, and Web of Science BIOSIS Previews® will be used to identify eligible clinical and pre-clinical studies, which included studies examining acute brain injury (human and in vivo animal brain injury models) within the first 7 days of therapy. The intervention of interest is the intravenous use of relatively hypotonic crystalloid resuscitation fluids (e.g., Ringer's lactate, Hartmann's or Plasma Lyte® fluids). The main comparator of interest is an isotonic crystalloid resuscitation fluid, specifically normal saline (0.9%). Other crystalloid resuscitation fluids (e.g., hypertonic saline (3-23.4%)) will also be included as an additional intervention of interest. The primary outcome measures of interest are intracranial pressure (ICP) and cerebral perfusion pressure (CPP). Secondary outcomes include the effect of resuscitation on cerebral edema, brain and serum osmolarity, and electrolyte concentrations and clinical outcomes including modified Rankin Scale (mRS), (extended) Glasgow Outcome Scale (GOS/eGOS), and mortality. Separate meta-analyses will be conducted to quantify the effects of the different fluid resuscitation on acute brain injury outcomes in clinical and pre-clinical populations. Network meta-analyses to compare interventions will also be performed to compare the effects of different interventions., Discussion: This systematic review will comprehensively summarize the difference in treatment efficacy of various crystalloid resuscitation fluids in acute brain injury. This review is essential to underscore the evidence, or lack thereof, present in the literature to date to support current preference-driven practice and to direct future study., Systematic Review Registration: PROSPERO #CRD42016042960.

Background: Traumatic brain injury (TBI) is a devastating condition with significant long-term mortality and morbidity. Despite current need for objective indicators to guide initial decision-making, few reliable acute phase prognostic factors have been identified. Early magnetic resonance imaging (MRI) has been investigated as a prognostic tool, but uncertainty remains in both its discriminative predictive value and which acute phase lesion patterns correlate with long-term outcome., Methods: We will conduct a systematic review of observational cohort studies and randomized controlled trials of adult moderate or severe TBI patients who underwent MRI in the acute phase after trauma. A high sensitivity search strategy will be employed in MEDLINE, EMBASE, BIOSIS, and Cochrane CENTRAL to identify citations. Two reviewers will independently screen all identified references for eligibility and extract data into a standardized form. Data will be collected on study design, baseline demographics, trauma characteristics, magnetic resonance (MR) technical specifications, lesion patterns, and outcomes as related to acute MRI imaging. If meta-analysis is possible, quantitative data for each outcome will be pooled per type of lesion pattern using random effects models and expressed as Mantel-Haenszel relative risks in order to determine the prognostic value of lesions detected on acute MRI and their strength as discriminatory predictors of long-term outcome. Statistical heterogeneity will be evaluated with the I (2) statistics, and risk of bias and reporting quality will be assessed with standardized scales. Subgroup analyses are planned as a function of TBI severity, MRI-timing post-TBI, MRI field strength, MRI sequence, timing of outcome assessment, and risk of bias., Discussion: We expect significant clinical heterogeneity, as eligible studies will likely encompass different periods in evolving MRI technology in addition to significant variability of image sequence protocols and timing of acquisition between centers. Based on existing studies in TBI, we expect lesions detected in the brainstem to be of significant predictive value as MRI is particularly sensitive for imaging the brain's posterior fossa. Our systematic review will allow clinicians to more accurately interpret MRI in the context of determining prognosis for moderate and severe TBI patients and inform researchers in this domain to improve the methodology of future studies., Systematic Review Registration: Prospero CRD42015017074.

Our objectives were to evaluate the frequency of red blood cell (RBC) transfusion in patients with traumatic brain injury (TBI) as well as potential determinants and outcomes associated with RBC transfusion in this population. We conducted a systematic review of cohort studies and randomized trials of patients with TBI. We searched Medline, Embase, the Cochrane Library, and BIOSIS databases from their inception up to April 2015. We selected studies of adult patients with acute TBI reporting data on RBC transfusions. Cumulative incidences of transfusion were pooled using random-effect models with a DerSimonian approach. To evaluate the association between RBC transfusion and potential determinants or clinical outcomes, we pooled risk ratios or mean differences with random-effect models and the Mantel-Haenszel method. We identified 24 eligible studies (17414 patients). After pooling data from 23 studies (7524 patients), approximately 36% (95% confidence interval [CI], 28-44; I(2) = 98%) of patients received RBC transfusion at some point during their hospital stay. Hemoglobin thresholds for transfusion were rarely available (reported in 9 studies) and varied from 6 to 10 g/dL. Glasgow Coma Scale scores at admission were lower in patients who were transfused than those who were not (3 cohort studies; 1371 patients; mean difference of 1.38 points [95% CI, 0.86-1.89]; I(2) = 12%). Mortality was not significantly different among transfused and nontransfused patients in univariate and multivariate meta-analyses. Hospital length of stay was longer among patients receiving RBC transfusion compared to those who did not (3 studies; n = 455; mean difference, 9.58 days [95% CI, 3.94-15.22]; I(2) = 74%). Results should be considered cautiously due to the high heterogeneity and high risk of confounding from the observational nature of included studies. Red blood cell transfusion is frequent in patients with TBI, and transfusion practices varied widely between studies. Current published data highlight the lack of clinical evidence guiding transfusion strategies in TBI., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: There is conflicting data on the relationship between anemia and outcomes in patients with traumatic brain injuries (TBI). The objective of this study was to determine if the proportion of time and area under the hemoglobin-time curve of ≥90 g/L are independently associated with 6-month functional outcomes., Methods: Retrospective cohort study of 116 patients with a severe TBI who underwent invasive neuromonitoring between June 2006 and December 2013. Hemoglobin area (HAI) and time (HTI) indices were calculated by dividing the total area, or time, under the hemoglobin-time curve at 90 g/L or above by the total duration of monitoring. Multivariable log-binomial regression was used to model the association between HAI or HTI and 6 month favorable neurologic outcome (Glasgow Outcome Score 4 or 5)., Results: Patients had a mean age of 38 years (SD 16) with a median admission Glasgow Coma Scale of 6 (IQR 4-7). There were 1523 hemoglobin measurements and 523 monitoring days. Patients had a hemoglobin ≥90 g/L for a median of 70 % (IQR 37-100) of the time. Each 10 g/L increase in HAI (RR 1.23, 95 %CI 1.04-1.44, P = 0.011), and 10 % increase in HTI (1.10, 95 %CI 1.04-1.16, P < 0.001) were associated with improved neurologic outcome. Thirty-one patients (27 %) received a transfusion with the median pre-transfusion hemoglobin being 81 g/L (IQR 76-87)., Conclusions: In patients with severe TBI, increased area under the curve and percentage of time that the hemoglobin concentration was ≥90 g/L, were associated with improved neurologic outcomes.

Background: Anemia is a prevalent condition in critically ill patients and red blood cell transfusions are frequent. Although transfusions at low hemoglobin levels have been shown to be associated with equivalent or better outcomes than higher hemoglobin thresholds, clinical equipoise persists in patients with traumatic brain injury considering their susceptibility to secondary cerebral insults such as those from hypoxemia., Methods: Our objectives are to estimate the frequency of red blood cell transfusion in patients with traumatic brain injury and to evaluate transfusion thresholds, determinants and outcomes associated with transfusion strategies.We will conduct a systematic review of cohort studies and randomized controlled trials of patients with traumatic brain injury. We will search MEDLINE, Embase, BIOSIS and the Cochrane Library for eligible studies. Two independent reviewers will screen all identified references. Studies including adult patients with traumatic brain injury reporting data on red blood cell transfusions will be eligible. We will collect data on baseline demographics, trauma characteristics, hemoglobin thresholds, blood transfusions and clinical outcomes (mortality, length of stay, complications, and so on). Two independent reviewers will extract data using a standardized form. We will pool cumulative incidences using DerSimonian and Lair random-effect models after a Freeman-Tukey transformation to stabilize variances. We will pool risk ratios or mean differences with random-effect models and Mantel-Haenszel or inverse variance methods in order to evaluate the association between red blood cell transfusion and potential determinants or outcomes. Sensitivity and subgroup analysis according to timing of red blood cell transfusion, traumatic brain injury severity, year of conduction of the study, risk of bias, notably, are planned., Discussion: We expect to observe high heterogeneity in the proportion of transfused patients across studies and that the global proportion will be similar to the frequency observed in the general medical critically ill population. Our systematic review will allow us to better describe and understand current transfusion practices in patients with traumatic brain injury, a clinical population in which liberal transfusions are still advocated in the absence of evidence-based data., Systematic Review Registration Prospero: CRD42014007402.

Introduction: Worldwide, severe traumatic brain injury is a frequent pathology and is associated with high morbidity and mortality. Mannitol and hypertonic saline are therapeutic options for intracranial hypertension occurring in the acute phase of care. However, current practices of emergency physicians are unknown., Methods: We conducted a self-administered survey of emergency physicians in the province of Québec, Canada, to understand their attitudes surrounding the use of hyperosmolar solutions in patients with severe traumatic brain injury. Using information from a systematic review of hypertonic saline solutions and experts' opinion, we developed a questionnaire following a systematic approach (items generation and reduction). We tested the questionnaire for face and content validity, and test-retest reliability. Physicians were identified through the department head of each eligible level I and II trauma centers. We administered the survey using a web-based interface and planned email reminders., Results: We received 210 questionnaires out of 429 potentials respondents (response rate 49%). Most respondents worked in level II trauma centers (69%). Fifty-three percent (53%) of emergency physicians stated using hypertonic saline to treat severe traumatic brain injury. Most reported using hyperosmolar therapy in the presence of severe traumatic brain injury and unilateral reactive mydriasis, midline shift or cistern compression on brain computed tomography., Conclusion: Hyperosmolar therapy is believed being broadly used by emergency physicians in Quebec following severe traumatic brain injury. Despite the absence of clinical practice guidelines promoting the use of hypertonic saline, a majority of them said to use these solutions in specific clinical situations.

Objectives: To assess the clinical outcomes, predictors, and prevalence of anterior pituitary disorders following traumatic brain injury., Data Sources: We searched Medline, Embase, Cochrane Registry, BIOSIS, and Trip Database up to February 2012 and consulted bibliographies of narrative reviews and selected articles., Study Selection: We included cohort, case-control, cross-sectional studies and randomized trials enrolling at least five adults with blunt traumatic brain injury in whom at least one anterior pituitary axis was assessed. We excluded case series and studies in which other neurological conditions were indistinguishable from traumatic brain injury., Data Extraction: Two independent reviewers selected citations, extracted data, and assessed the risk of bias using a standardized form., Data Synthesis: We performed meta-analyses using random effect models and assessed heterogeneity using the I index., Results: We included 66 studies (5,386 patients) evaluating prevalence, 14 evaluating clinical outcomes, and 27 evaluating predictors. Thirty studies were at low risk of bias. Anterior pituitary disorders were associated with a trend toward increased ICU mortality (risk ratio, 1.79; 95% CI, 0.99-3.21; four studies) and no difference in Glasgow Outcome Scale score (mean difference, -0.45; 95% CI, -1.10 to 0.20; three studies). Age (mean difference, 3.19; 95% CI, 0.31-6.08; 19 studies), traumatic brain injury severity (risk ratio, 2.15; 95% CI, 1.20-3.86 for patients with severe vs nonsevere traumatic brain injury; seven studies), and skull fractures (risk ratio, 1.73; 95% CI, 1.03-2.91; six studies) predicted anterior pituitary disorders. Over the long term, 31.6% (95% CI, 23.6-40.1%; 27 studies) of patients had at least one anterior pituitary disorder. We observed significant heterogeneity that was not solely explained by the risk of bias or traumatic brain injury severity., Conclusions: Approximately one third of traumatic brain injury patients have persistent anterior pituitary disorder. Older age, traumatic brain injury severity, and skull fractures predict anterior pituitary disorders, which in turn may be associated with higher ICU mortality. Further high-quality studies are warranted to better define the burden of anterior pituitary disorders and to identify high-risk patients.

Objectives: To determine the ability and accuracy of the S-100β protein in predicting prognosis after a moderate or severe traumatic brain injury., Design: Systematic review and meta-analysis of randomised controlled trials and observational studies., Data Sources: Medline, Embase, Cochrane Central Register of Controlled Trials, BIOSIS (from their inception to April 2012), conference abstracts, bibliographies of eligible articles, and relevant narrative reviews., Study Selection: Two reviewers independently reviewed citations and selected eligible studies, defined as cohort studies or randomised control trials including patients with moderate or severe traumatic brain injury and evaluating the prognostic value of S-100β protein. Outcomes evaluated were mortality, score on the Glasgow outcome scale, or brain death., Data Extraction: Two independent reviewers extracted data using a standardised form and evaluated the methodological quality of included studies. Pooled results were presented with geometric means ratios and analysed with random effect models. Prespecified sensitivity analyses were performed to explain heterogeneity., Results: The search strategy yielded 9228 citations. Two randomised controlled trials and 39 cohort studies were considered eligible (1862 patients). Most studies (n=23) considered Glasgow outcome score ≤ 3 as an unfavourable outcome. All studies reported at least one measurement of S-100β within 24 hours after traumatic brain injury. There was a significant positive association between S-100β protein concentrations and mortality (12 studies: geometric mean ratio 2.55, 95% confidence interval 2.02 to 3.21, I(2)=56%) and score ≤ 3 (18 studies: 2.62, 2.01 to 3.42, I(2)=79%). Sensitivity analysis based on sampling time, sampling type, blinding of outcome assessors, and timing of outcome assessment yielded similar results. Thresholds for serum S-100β protein values with 100% specificity ranged from 1.38 to 10.50 µg/L for mortality (six studies) and from 2.16 to 14.00 µg/L for unfavourable neurological prognosis as defined by the Glasgow outcome score., Conclusions: After moderate or severe traumatic brain injury, serum S-100β protein concentrations are significantly associated with unfavourable prognosis in the short, mid, or long term. Optimal thresholds for discrimination remain unclear. Measuring the S-100β protein could be useful in evaluating the severity of traumatic brain injury and in the determination of long term prognosis in patients with moderate and severe injury.

Objectives: Accurate prognostic information in patients with severe traumatic brain injury remains limited, but mortality following the withdrawal of life-sustaining therapies is high and variable across centers. We designed a survey to understand attitudes of physicians caring for patients with severe traumatic brain injury toward the determination of prognosis and clinical decision making on the level of care., Design, Setting, and Participants: We conducted a cross-sectional study of intensivists, neurosurgeons, and neurologists that participate in the care of patients with severe traumatic brain injury at all Canadian level 1 and level 2 trauma centers., Intervention: None., Measurements: The main outcome measure was physicians' perceptions of prognosis and recommendations on the level of care., Main Results: Our response rate was 64% (455/712). Most respondents (65%) reported that an accurate prediction of prognosis would be most helpful during the first 7 days. Most respondents (>80%) identified bedside monitoring, clinical exam, and imaging to be useful for evaluating prognosis, whereas fewer considered electrophysiology tests (<60%) and biomarkers (<15%). In a case-based scenario, approximately one-third of respondents agreed, one-third were neutral, and one-third disagreed that the patient prognosis would be unfavorable at one year. About 10% were comfortable recommending withdrawal of life-sustaining therapies., Conclusions: A significant variation in perceptions of neurologic prognosis and in clinical decision making on the level of care was found among Canadian intensivists, neurosurgeons, and neurologists. Improved understanding of the factors that can accurately predict prognosis for patients with traumatic brain injury is urgently needed.

To examine clinical trials and observational studies that compared use of management protocols (MPs) versus usual care for adult intensive care unit (ICU) patients with acute severe traumatic brain injury (TBI) on 6-month neurologic outcome (Glasgow Outcome Scale, GOS) and mortality, major electronic databases were searched from 1950 to April 18, 2011. Abstracts from major international meetings were searched to identify gray literature. A total of 6,151 articles were identified; 488 were reviewed in full and 13 studies were included. Data on patient and MP characteristics, outcomes and methodological quality were extracted. All 13 included studies were observational. A random effects model showed that use of MPs was associated with a favorable neurologic outcome (GOS 4 or 5) at 6 months (odds ratio [OR] and 95 % confidence interval [CI] 3.84 (2.47-5.96)) but not 12 months (OR, 95 % CI 0.87 (0.56-1.36)). Use of MPs was associated with reduced mortality at hospital discharge and 6 months (OR and 95 % CI 0.72 (0.45-1.14) and 0.33 (0.13-0.82) respectively), but not 12 months (OR, 95 % CI 0.79 (0.5-1.24)). Sources of heterogeneity included variation in study design, methodological quality, MP design, MP neurophysiologic endpoints, and type of ICU. MPs for severe TBI were associated with reductions in death and improved neurologic outcome. Although no definitive conclusions about the efficacy of MPs for severe TBI can be drawn from our study, these results should encourage the conduct of randomized controlled trials to more rigorously examine the efficacy of MPs for severe TBI.

Purpose: To identify factors associated with decisions to withdraw life-sustaining therapies in patients with severe traumatic brain injury (TBI)., Materials and Methods: We conducted a 2-year multicenter retrospective cohort study (2005-2006) in mechanically ventilated patients aged 16 years and older admitted to the intensive care units (ICUs) of six Canadian level I trauma centers following severe TBI. One hundred and twenty charts were randomly selected at each center (n = 720). Data on ICU management strategies, patients' clinical condition, surgical procedures, diagnostic imaging, and decision to withdraw life-sustaining therapies were collected. The association of factors pertaining to the injury, interventions, and management strategies with decisions to withdraw life-sustaining therapies was evaluated among non-survivors., Results: Among the 228 non-survivors, 160 died following withdrawal of life-sustaining therapies. Patients were predominantly male (69.7 %) with a mean age of 50.7 (±21.7) years old. Brain herniation was more often reported in patients who died following decisions to withdraw life-sustaining therapies (odds ratio [OR] 2.91, 95 % confidence interval [CI] 1.16-7.30, p = 0.02) compared to those who died due to other causes (e.g., cardiac arrest, shock, etc.). Epidural hematomas (OR 0.18, 95 % CI 0.06-0.56, p < 0.01), craniotomies (OR 0.12, 95 % CI 0.02-0.68, p = 0.02), and other non-neurosurgical procedures (OR 0.08, 95 % CI 0.02-0.43, p < 0.01) were less often associated with death following withdrawal of life-sustaining therapies than death from other causes., Conclusions: Death following decisions to withdraw life-sustaining therapies is associated with specific patient and clinical factors, and the intensity of care.

In the intensive care unit, dopamine agonists (DA) have been used in traumatic brain injury (TBI) patients to augment or accelerate cognitive recovery and rehabilitation. However, the efficacy and safety of DA in this population is not well established. We conducted a systematic review of randomized controlled trials (RCTs) examining the clinical efficacy and safety of DA in patients with TBI. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, comparing DA to either placebo, standard treatment, or another active comparator. There was no restriction for age, date, or language of publication. Sensitivity analyses were planned to evaluate the potential effect of timing of TBI, age, drugs, and year of publication on efficacy. Among the 790 citations identified, 20 RCTs evaluating methylphenidate, amantadine, and bromocriptine were eligible. Significant clinical heterogeneity was observed between and within studies, which precluded any pooling of data. Efficacy outcomes included mainly neuropsychological measures of cognitive functioning. A total of 76 different neuropsychological tests were used, but most of them (59%) only once. Only 5 studies systematically assessed safety. No trend could be drawn from the analysis of efficacy and safety. Important sources of bias in the studies were of major concern. Considering the absence of consensus regarding clinical outcome, the lack of safety assessment, and the high risk of bias in the included trials, more research is warranted before DA can be recommended in critically ill TBI patients.

Background: Severe traumatic brain injury often leads to death from withdrawal of life-sustaining therapy, although prognosis is difficult to determine., Methods: To evaluate variation in mortality following the withdrawal of life-sustaining therapy and hospital mortality in patients with critical illness and severe traumatic brain injury, we conducted a two-year multicentre retrospective cohort study in six Canadian level-one trauma centres. The effect of centre on hospital mortality and withdrawal of life-sustaining therapy was evaluated using multivariable logistic regression adjusted for baseline patient-level covariates (sex, age, pupillary reactivity and score on the Glasgow coma scale)., Results: We randomly selected 720 patients with traumatic brain injury for our study. The overall hospital mortality among these patients was 228/720 (31.7%, 95% confidence interval [CI] 28.4%-35.2%) and ranged from 10.8% to 44.2% across centres (χ(2) test for overall difference, p < 0.001). Most deaths (70.2% [160/228], 95% CI 63.9%-75.7%) were associated with withdrawal of life-sustaining therapy, ranging from 45.0% (18/40) to 86.8% (46/53) (χ(2) test for overall difference, p < 0.001) across centres. Adjusted odd ratios (ORs) for the effect of centre on hospital mortality ranged from 0.61 to 1.55 (p < 0.001). The incidence of withdrawal of life-sustaining therapy varied by centre, with ORs ranging from 0.42 to 2.40 (p = 0.001). About one half of deaths that occurred following the withdrawal of life-sustaining therapies happened within the first three days of care., Interpretation: We observed significant variation in mortality across centres. This may be explained in part by regional variations in physician, family or community approaches to the withdrawal of life-sustaining therapy. Considering the high proportion of early deaths associated with the withdrawal of life-sustaining therapy and the limited accuracy of current prognostic indicators, caution should be used regarding early withdrawal of life-sustaining therapy following severe traumatic brain injury.

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Copyright of Canadian Journal of Surgery is the property of CMA Impact Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Most deaths in critically ill patients with severe traumatic brain injury are associated with a decision to withdraw life-sustaining treatments. We aimed to identify the behavioural determinants that influence recommendations by critical care physicians to consider the withdrawal of life-sustaining treatments in this population.Methods: We conducted a descriptive qualitative study based on the Theoretical Domains Framework of critical care physicians caring for patients with severe traumatic brain injury across Canada. We stratified critical care physicians by regions and used a purposive sampling strategy. We conducted semistructured phone interviews using a piloted and pretested interview guide. We transcribed the interviews verbatim and verified the content for accuracy. We performed the analysis using a 3-step approach: coding, generation of specific beliefs and generation of specific themes.Results: We recruited 20 critical care physicians across 4 geographic regions. After reaching saturation, we identified 7 core themes across 4 Theoretical Domains Framework domains for factors relevant to the decision to withdraw life-sustaining treatments. Four factors (i.e., clinical triggers, social triggers, interaction with families and intentions with medical decisions) were identified before the decision is made and 3 were identified during the decision-making process (i.e., considerations, priorities and knowledge needs). We identified multiple themes reflecting internal (n = 18, 8 Theoretical Domains Framework domains) and external (n = 15, 6 Theoretical Domains Framework domains) influences on the decision to withdraw life-sustaining treatments.Interpretation: We identified several core themes and domains considered by critical care physicians in Canada in the decision to withdraw life-sustaining treatments in critically ill patients with severe traumatic brain injury. Future research should aim at identifying the factors influencing surrogate decision-makers in the decision to withdraw life-sustaining treatments in these patients. [ABSTRACT FROM AUTHOR]

Background: Most deaths following severe traumatic brain injury follow decisions to withdraw life-sustaining therapies. However, the incidence of the withdrawal of life-sustaining therapies and its potential impact on research data interpretation have been poorly characterized. The aim of this systematic review was to assess the reporting and the impact of withdrawal of life-sustaining therapies in randomized clinical trials of patients with severe traumatic brain injury. Methods: We searched Medline, Embase, Cochrane Central, BIOSIS, and CINAHL databases and references of included trials. All randomized controlled trials published between January 2002 and August 2015 in the six highest impact journals in general medicine, critical care medicine, and neurocritical care (total of 18 journals) were considered for eligibility. Randomized controlled trials were included if they enrolled adult patients with severe traumatic brain injury (Glasgow Coma Scale ≤ 8) and reported data on mortality. Our primary objective was to assess the proportion of trials reporting the withdrawal of life-sustaining therapies in a publication. Our secondary objectives were to describe the overall mortality rate, the proportion of deaths following the withdrawal of life-sustaining therapies, and to assess the impact of the withdrawal of life-sustaining therapies on trial results. Results: From 5987 citations retrieved, we included 41 randomized trials (n = 16,364, ranging from 11 to 10,008 patients). Overall mortality was 23% (range = 3%-57%). Withdrawal of life-sustaining therapies was reported in 20% of trials (8/41, 932 patients in trials) and the crude number of deaths due to the withdrawal of life-sustaining therapies was reported in 17% of trials (7/41, 884 patients in trials). In these trials, 63% of deaths were associated with the withdrawal of life-sustaining therapies (105/168). An analysis carried out by imputing a 4% differential rate in instances of withdrawal of life-sustaining therapies between study groups yielded different results and conclusions in one third of the trials. Conclusion: Data on the withdrawal of life-sustaining therapies are incompletely reported in randomized controlled trials of patients with severe traumatic brain injury. Given the high proportion of deaths due to the withdrawal of life-sustaining therapies in severe traumatic brain injury patients, and the potential of this medical decision to influence the results of clinical trials, instances of withdrawal of life-sustaining therapies should be systematically reported in clinical trials in this group of patients. [ABSTRACT FROM AUTHOR]

Background: Prognosis is difficult to establish early after moderate or severe traumatic brain injury despite representing an important concern for patients, families and medical teams. Biomarkers, such as neuron-specific enolase, have been proposed as potential early prognostic indicators. Our objective was to determine the association between neuron-specific enolase and clinical outcomes, and the prognostic value of neuron-specific enolase after a moderate or severe traumatic brain injury. Methods: We searched MEDLINE, Embase, The Cochrane Library and Biosis Previews, and reviewed reference lists of eligible articles to identify studies. We included cohort studies and randomized controlled trials that evaluated the prognostic value of neuron-specific enolase to predict mortality or Glasgow Outcome Scale score in patients with moderate or severe traumatic brain injury. Two reviewers independently collected data. The pooled mean differences were analyzed using random-effects models. We assessed risk of bias using a customized Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Subgroup and sensitivity analyses were performed based on a priori hypotheses. Results: We screened 5026 citations from which 30 studies (involving 1321 participants) met our eligibility criteria. We found a significant positive association between neuron-specific enolase serum levels and mortality (10 studies, n = 474; mean difference [MD] 18.46 µg/L, 95% confidence interval [CI] 10.81 to 26.11 µg/L; I2 = 83%) and a Glasgow Outcome Scale ≤ 3 (14 studies, n = 603; MD 17.25 µg/L, 95% CI 11.42 to 23.07 µg/L; I2 = 82%). We were unable to determine a clinical threshold value using the available patient data. Interpretation: In patients with moderate or severe traumatic brain injury, increased neuron-specific enolase serum levels are associated with unfavourable outcomes. The optimal neuron-specific enolase threshold value to predict unfavourable prognosis remains unknown and clinical decision-making is currently not recommended until additional studies are made available. [ABSTRACT FROM AUTHOR]

Background: Severe traumatic brain injury often leads to death from withdrawal of life-sustaining therapy, although prognosis is difficult to determine. Methods: To evaluate variation in mortality following the withdrawal of life-sustaining therapy and hospital mortality in patients with critical illness and severe traumatic brain injury, we conducted a two-year multicentre retrospective cohort study in six Canadian level-one trauma centres. The effect of centre on hospital mortality and withdrawal of life-sustaining therapy was evaluated using multivariable logistic regression adjusted for baseline patient-level covariates (sex, age, pupillary reactivity and score on the Glasgow coma scale). Results: We randomly selected 720 patients with traumatic brain injury for our study. The overall hospital mortality among these patients was 228/720 (31.7%, 95% confidence interval [CI] 28.4%-35.2%) and ranged from 10.8% to 44.2% across centres (X2 test for overall difference, p < 0.001). Most deaths (70.2% [160/228], 95% CI 63.9%-75.7%) were associated with withdrawal of life-sustaining therapy, ranging from 45.0% (18/40) to 86.8% (46/53) (X2 test for overall difference, p < 0.001) across centres. Adjusted odd ratios (ORs) for the effect of centre on hospital mortality ranged from 0.61 to 1.55 (p < 0.001). The incidence of withdrawal of life-sustaining therapy varied by centre, with ORs ranging from 0.42 to 2.40 (p = 0.001). About one half of deaths that occurred following the withdrawal of life-sustaining therapies happened within the first three days of care. Interpretation: We observed significant variation in mortality across centres. This may be explained in part by regional variations in physician, family or community approaches to the withdrawal of life-sustaining therapy. Considering the high proportion of early deaths associated with the withdrawal of life-sustaining therapy and the limited accuracy of current prognostic indicators, caution should be used regarding early withdrawal of life-sustaining therapy following severe traumatic brain injury. [ABSTRACT FROM AUTHOR]

The author reflects differences in the medical and surgical management of older patients with severe traumatic brain injury (TBI) compared with younger patients with the same brain injuries. It mentions epidemiologic patterns of severe TBI are in fact shifting toward a more balanced bimodal distribution aspects such as chronic medical conditions, polypharmacy, and premorbid disabilities. It also mentions anticoagulant agents and platelet aggregation inhibitors prescribed to patients.

Prognostic assessment in traumatic brain injury (TBI) is embedded deeply in clinical care. Considering the limitations of current prognostic indicators, there is increasing interest in understanding the role of new biomarkers, and in finding other prognostic indicators of long-term outcomes following TBI. New prognostic indicators may result in the development of more accurate prediction models that could be useful for both risk stratification and clinical decision making. We aimed to review methodological issues and provide tentative guidelines for prognostic research in TBI. Prognostic factor research focuses on the role of a specific patient or disease-related characteristic in relation to outcome. Typically, univariable relations of the prognostic factor are studied, followed by analyses adjusting for other variables related to the outcome. Following existing guidelines, we emphasize the importance of transparent reporting of patient and specimen characteristics, study design, clinical end-points, and statistical analysis. Prognostic model research considers combinations of predictors, with challenges for model specification, estimation, evaluation, validation, and presentation. We highlight modern approaches and opportunities related to missing values, exploration of non-linear effects, and assessing between-study heterogeneity. Prognostic research in TBI can be improved if key methodological principles are adhered to and when research is performed in collaboration among multiple centers to ensure generalizability. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is the leading cause of death and disability in children. Many clinical practice guidelines (CPGs) have addressed pediatric TBI in the last decade but significant variability in the use of these guidelines persists. Here, we systematically review CPGs recommendations for pediatric moderate-to-severe TBI, evaluate the quality of CPGs, synthesize the quality of evidence and strength of included recommendations, and identify knowledge gaps. A systematic search was conducted in MEDLINE®, Embase, Cochrane CENTRAL, Web of Science, and Web sites of organizations publishing recommendations on pediatric injury care. We included CPGs developed in high-income countries from January 2012 to May 2023, with at least one recommendation targeting pediatric (≤ 19 years old) moderate-to-severe TBI populations. The quality of included clinical practice guidelines was assessed using the AGREE II tool. We synthesized evidence on recommendations using a matrix based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. We identified 15 CPGs of which 9 were rated moderate to high quality using AGREE II. We identified 90 recommendations, of which 40 (45%) were evidence based. Eleven of these were based on moderate to high quality evidence and were graded as moderate or strong by at least one guideline. These included transfer, imaging, intracranial pressure control, and discharge advice. We identified gaps in evidence-based recommendations for red blood cell transfusion, plasma and platelet transfusion, thromboprophylaxis, surgical antimicrobial prophylaxis, early diagnosis of hypopituitarism, and mental health mangement. Many up-to-date CPGs are available, but there is a paucity of evidence to support recommendations, highlighting the urgent need for robust clinical research in this vulnerable population. Our results may be used by clinicians to identify recommendations based on the highest level of evidence, by healthcare administrators to inform guideline implementation in clinical settings, by researchers to identify areas where robust evidence is needed, and by guideline writing groups to inform the updating of existing guidelines or the development of new ones. [ABSTRACT FROM AUTHOR]

The article presents a study analyzing the amount of S-100 beta proteins in patients suffering from moderate or severe traumatic brain injury. It states that these proteins are associated with unfavorable prognosis after brain injury. According to the results of the study, these proteins causes mortality and brain stem death. It further mentions that sensitivity analysis was conducted during the study.

A letter to the editor is presented in response to an article on variability in withdrawal of life-sustaining therapies in severe traumatic brain injury in a previous issue.

Objectives: To develop a hospital indicator of resource use for injury admissions.Methods: We focused on resource use for acute injury care and therefore adopted a hospital perspective. We included patients ≥16 years old with an Injury Severity Score >9 admitted to any of the 57 trauma centers of an inclusive Canadian trauma system from 2014 to 2018. We extracted data from the trauma registry and hospital financial reports and estimated resource use with activity-based costing. We developed risk-adjustment models by trauma center designation level (I/II and III/IV) for the whole sample, traumatic brain injuries, thoraco-abdominal injuries, orthopedic injuries, and patients ≥65 years old. Candidate variables were selected using bootstrap resampling. We performed benchmarking by comparing the adjusted mean cost in each center, obtained using shrinkage estimates, to the provincial mean.Results: We included 38 713 patients. The models explained between 12% and 36% (optimism-corrected r2) of the variation in resource use. In the whole sample and in all subgroups, we identified centers with higher- or lower-than-expected resource use across level I/II and III/IV centers.Conclusions: We propose an algorithm to produce the indicator using data routinely collected in trauma registries to prompt targeted exploration of potential areas for improvement in resource use for injury admissions. The r2 of our models suggest that between 64% and 88% of the variation in resource use for injury care is dictated by factors other than patient baseline risk. [ABSTRACT FROM AUTHOR]

Despite numerous interventions and treatment options, the outcomes of traumatic brain injury (TBI) have improved little over the last 3 decades, which raises concern about the value of care in this patient population. We aimed to synthesize the evidence on 14 potentially low-value clinical practices in TBI care. Using umbrella review methodology, we identified systematic reviews evaluating the effectiveness of 14 potentially low-value practices in adults with acute TBI. We present data on methodological quality (Assessing the Methodological Quality of Systematic Reviews), reported effect sizes, and credibility of evidence (I to IV). The only clinical practice with evidence of benefit was therapeutic hypothermia (credibility of evidence II to IV). However, the most recent meta-analysis on hypothermia based on high-quality trials suggested harm (credibility of evidence IV). Meta-analyses on platelet transfusion for patients on antiplatelet therapy were all consistent with harm but were statistically non-significant. For the following practices, effect estimates were consistently close to the null: computed tomography (CT) in adults with mild TBI who are low-risk on a validated clinical decision rule; repeat CT in adults with mild TBI on anticoagulant therapy with no clinical deterioration; antibiotic prophylaxis for external ventricular drain placement; and decompressive craniectomy for refractory intracranial hypertension. We identified five clinical practices with evidence of lack of benefit or harm. However, evidence could not be considered to be strong for any clinical practice as effect measures were imprecise and heterogeneous, systematic reviews were often of low quality, and most included studies had a high risk of bias. [ABSTRACT FROM AUTHOR]

Objectives: Biomarkers have been suggested as potential prognostic predictors following a moderate or severe traumatic brain injury but their prognostic accuracy is still uncertain. The objective of this systematic review is to assess the ability of the glial fibrillary acidic protein to predict prognosis in patients with moderate or severe traumatic brain injury.Data Sources: MEDLINE, Embase, CENTRAL, and BIOSIS electronic databases and conference abstracts, bibliographies of selected studies, and narrative reviews were searched.Study Selection: Pairs of reviewers identified eligible studies. Cohort studies including greater than or equal to four patients with moderate or severe traumatic brain injury and reporting glial fibrillary acidic protein levels according to the outcomes of interest, namely Glasgow Outcome Scale or Extended Glasgow Outcome Scale, and mortality, were eligible.Data Extraction: Pairs of reviewers independently extracted data from the selected studies using a standardized case report form. Mean levels were log-transformed, and their differences were pooled with random effect models. Results are presented as geometric mean ratios. Methodologic quality, risk of bias, and applicability concerns of the included studies were assessed.Data Synthesis: Seven-thousand seven-hundred sixty-five citations were retrieved of which 15 studies were included in the systematic review (n = 1,070), and nine were included in the meta-analysis (n = 701). We found significant associations between glial fibrillary acidic protein serum levels and Glasgow Outcome Scale score less than or equal to 3 or Extended Glasgow Outcome Scale score less than or equal to 4 (six studies: geometric mean ratio 4.98 [95% CI, 2.19-11.13]; I = 94%) and between mortality (seven studies: geometric mean ratio 8.13 [95% CI, 3.89-17.00]; I = 99%).Conclusions: Serum glial fibrillary acidic protein levels were significantly higher in patients with an unfavorable prognosis. Glial fibrillary acidic protein has a potential for clinical bedside use in helping for prognostic assessment. Further research should focus on multimodal approaches including tissue biomarkers for prognostic evaluation in critically ill patients with traumatic brain injury. [ABSTRACT FROM AUTHOR]

The aims of this study were to document the frequency of major and minor depressive episodes in the first year after traumatic brain injury (TBI), taking into account TBI severity and pre-morbid history of major depression, and to describe trajectories of depressive episodes. Participants were 227 adults who were hospitalized post-TBI (76% male; mean age = 41 years; 50% mild, 33% moderate, and 17% severe TBI). Major and minor depressive episodes were assessed with the Mini International Neuropsychiatric Interview at three time points (4, 8, and 12 months after TBI). Overall, 29% of participants had a major depressive episode in at least one of the three assessments, with fairly stable rates across assessments. Participants with mild TBI were more likely than those with moderate/severe TBI to be diagnosed with major depression, as were individuals with a positive pre-morbid history of depression compared to those without such history. In addition, 13% of participants had a minor depressive episode in at least one of the three assessments. Rates of minor depression significantly decreased from 4 to 8–12 months post-injury. Results also revealed a wide variety of trajectories of depressive episodes across assessments. Of note, 52% of major depression cases still fulfilled diagnostic criteria 4 months later, whereas 38% of minor depression cases deteriorated to major depression at the following assessment. These findings suggest that depression is highly prevalent after TBI, and monitoring of patients with subthreshold depressive symptoms is warranted in order to prevent the development of full-blown major depressive episodes. [ABSTRACT FROM AUTHOR]

Objectives: Traumatic brain injury is a major cause of death and disability, yet many predictors of outcome are not precise enough to guide initial clinical decision-making. Although increasingly used in the early phase following traumatic brain injury, the prognostic utility of MRI remains uncertain. We thus undertook a systematic review and meta-analysis of studies evaluating the predictive value of acute MRI lesion patterns for discriminating clinical outcome in traumatic brain injury.Data Sources: MEDLINE, EMBASE, BIOSIS, and CENTRAL from inception to November 2015.Study Selection: Studies of adults who had MRI in the acute phase following moderate or severe traumatic brain injury. Our primary outcomes were all-cause mortality and the Glasgow Outcome Scale.Data Extraction: Two authors independently performed study selection and data extraction. We calculated pooled effect estimates with a random effects model, evaluated the risk of bias using a modified version of Quality in Prognostic Studies and determined the strength of evidence with the Grading of Recommendations, Assessment, Development, and Evaluation.Data Synthesis: We included 58 eligible studies, of which 27 (n = 1,652) contributed data to meta-analysis. Brainstem lesions were associated with all-cause mortality (risk ratio, 1.78; 95% CI, 1.01-3.15; I = 43%) and unfavorable Glasgow Outcome Scale (risk ratio, 2.49; 95% CI, 1.72-3.58; I = 81%) at greater than or equal to 6 months. Diffuse axonal injury patterns were associated with an increased risk of unfavorable Glasgow Outcome Scale (risk ratio, 2.46; 95% CI, 1.06-5.69; I = 74%). MRI scores based on lesion depth demonstrated increasing risk of unfavorable neurologic outcome as more caudal structures were affected. Most studies were at high risk of methodological bias.Conclusions: MRI following traumatic brain injury yields important prognostic information, with several lesion patterns significantly associated with long-term survival and neurologic outcome. Given the high risk of bias in the current body of literature, large well-controlled studies are necessary to better quantify the prognostic role of early MRI in moderate and severe traumatic brain injury. [ABSTRACT FROM AUTHOR]