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Background: Moderate-severe traumatic brain injury (msTBI) carries high morbidity and mortality worldwide. Accurate neuroprognostication is essential in guiding clinical decisions, including patient triage and transition to comfort measures. Here we provide recommendations regarding the reliability of major clinical predictors and prediction models commonly used in msTBI neuroprognostication, guiding clinicians in counseling surrogate decision-makers., Methods: Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, we conducted a systematic narrative review of the most clinically relevant predictors and prediction models cited in the literature. The review involved framing specific population/intervention/comparator/outcome/timing/setting (PICOTS) questions and employing stringent full-text screening criteria to examine the literature, focusing on four GRADE criteria: quality of evidence, desirability of outcomes, values and preferences, and resource use. Moreover, good practice recommendations addressing the key principles of neuroprognostication were drafted., Results: After screening 8125 articles, 41 met our eligibility criteria. Ten clinical variables and nine grading scales were selected. Many articles varied in defining "poor" functional outcomes. For consistency, we treated "poor" as "unfavorable". Although many clinical variables are associated with poor outcome in msTBI, only the presence of bilateral pupillary nonreactivity on admission, conditional on accurate assessment without confounding from medications or injuries, was deemed moderately reliable for counseling surrogates regarding 6-month functional outcomes or in-hospital mortality. In terms of prediction models, the Corticosteroid Randomization After Significant Head Injury (CRASH)-basic, CRASH-CT (CRASH-basic extended by computed tomography features), International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT)-core, IMPACT-extended, and IMPACT-lab models were recommended as moderately reliable in predicting 14-day to 6-month mortality and functional outcomes at 6 months and beyond. When using "moderately reliable" predictors or prediction models, the clinician must acknowledge "substantial" uncertainty in the prognosis., Conclusions: These guidelines provide recommendations to clinicians on the formal reliability of individual predictors and prediction models of poor outcome when counseling surrogates of patients with msTBI and suggest broad principles of neuroprognostication., (© 2024. The Author(s).)

Purpose: To develop and internally validate the MortalitY in Moderate-Severe TBI plus ICU Complications (MYSTIC)-Score to predict in-hospital mortality of msTBI patients without early (<24 h) withdrawal-of-life-sustaining treatments., Methods: We analyzed data from a Neuro-Trauma Intensive Care Unit prospectively collected between 11/2009-5/2019. Consecutive adult msTBI patients were included if Glasgow Coma Scale≤12, and neither died nor had withdrawal-of-life-sustaining treatments within 24 h of admission (n = 485). Using univariate and multivariable logistic regression in a random-split cohort approach (2/3 derivation;1/3 validation), we identified independent predictors of in-hospital mortality while adjusting for validated predictors of mortality (IMPACT-variables). We constructed the MYSTIC-Score and examined discrimination and calibration., Results: The MYSTIC-Score included the ICU complications brain edema, herniation, systemic inflammatory response syndrome, sepsis, acute kidney injury, cardiac arrest, and urinary tract infection. In the derivation cohort(n = 324), discrimination and calibration were excellent (area-under-the-receiver-operating-curve [AUC-ROC] = 0.95;Hosmer-Lemeshow p-value = 0.09, with p > 0.05 indicating good calibration). Internal validation revealed an AUC-ROC = 0.93 and Hosmer-Lemeshow-p-value = 0.76 (n = 161)., Conclusions: Certain ICU complications are independent predictors of in-hospital mortality and strengthen outcome prediction in msTBI when combined with validated admission predictors of mortality. However, external validation is needed to determine robustness and practical applicability of our model given the high potential for residual confounders., Competing Interests: Declaration of Competing Interest None of the authors have any conflicts of interest. Funded by NIH/NICHD grant 5K23HD080971 (PI Muehlschlegel). This project was additionally supported by the University of Massachusetts Medical School Center for Clinical and Translational Science which is funded by the NIH Clinical and Translational Science Award to the University of Massachusetts Medical School (UL1TR000161)., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Objectives: Breakdowns in clinician-family communication in neurologic intensive care units (neuroICUs) are common, particularly for goals-of-care decisions to continue or withdraw life-sustaining treatments while considering long-term prognoses. Shared decision-making interventions (decision aids [DAs]) may prevent this problem and increase patient-centered care, yet none are currently available. We assessed the feasibility, acceptability, and perceived usefulness of a DA for goals-of-care communication with surrogate decision makers for critically ill patients with severe acute brain injury (SABI) after hemispheric acute ischemic stroke, intracerebral hemorrhage, or traumatic brain injury., Methods: We conducted a parallel-arm, unblinded, patient-level randomized, controlled pilot trial at 2 tertiary care US neuroICUs and randomized surrogate participants 1:1 to a tailored paper-based DA provided to surrogates before clinician-family goals-of-care meetings or usual care (no intervention before clinician-family meetings). The primary outcomes were feasibility of deploying the DA (recruitment, participation, and retention), acceptability, and perceived usefulness of the DA among surrogates. Exploratory outcomes included outcome of surrogate goals-of-care decision, code status changes during admission, patients' 3-month functional outcome, and surrogates' 3-month validated psychological outcomes., Results: We approached 83 surrogates of 58 patients and enrolled 66 surrogates of 41 patients (80% consent rate). Of 66 surrogates, 45 remained in the study at 3 months (68% retention). Of the 33 surrogates randomized to intervention, 27 were able to receive the DA, and 25 subsequently read the DA (93% participation). Eighty-two percent rated the DA's acceptability as good or excellent (median acceptability score 2 [IQR 2-3]); 96% found it useful for goals-of-care decision making. In the DA group, there was a trend toward fewer comfort care decisions (27% vs 56%, p = 0.1) and fewer code status changes (no change, 73% vs 44%, p = 0.02). At 3 months, fewer patients in the DA group had died (33% vs 69%, p = 0.05; median Glasgow Outcome Scale 3 vs1, p = 0.05). Regardless of intervention, 3-month psychological outcomes were significantly worse among surrogates who had chosen continuation of care., Discussion: A goals-of-care DA to support ICU shared decision making for patients with SABI is feasible to deploy and well perceived by surrogates. A larger trial is feasible to conduct, although surrogates who select continuation of care deserve additional psychosocial support., Clinical Trials Registration: Clinicaltrials.gov NCT03833375., Classification of Evidence: This study provides Class IV evidence that the use of a DA explaining the goals-of-care decision and the treatment options is acceptable and useful to surrogates of incapacitated critically ill patients with ischemic stroke, intracerebral hemorrhage, or traumatic brain injury., (© 2022 American Academy of Neurology.)

Palliative care (PC) teams commonly encounter patients with disorders of consciousness (DOC) following anoxic or traumatic brain injury (TBI). Primary teams may consult PC to help surrogates in making treatment choices for these patients. PC clinicians must understand the complexity of predicting neurologic outcomes, address clinical nihilism, and appropriately guide surrogates in making decisions that are concordant with patients' goals. The purpose of this article was to provide PC providers with a better understanding of caring for patients with DOC, specifically following anoxic or TBI. Many of the tips acknowledge the uncertainty of DOC and provide strategies to help tackle this dilemma.

Background: Prognostic uncertainty is frequently cited as a barrier to communication between physicians and patients and is particularly burdensome for surrogate decision-makers, who must make choices on behalf of their incapacitated family members. The Conceptual Taxonomy of Uncertainty is one model through which physician and surrogate communication can be analyzed to identify strategies for reducing uncertainty in surrogate decision-making. Our objective was to examine themes of uncertainty in physician communication of prognosis and surrogate goals-of-care decision-making for critically ill patients with traumatic brain injury (TBI)., Methods: We performed a secondary analysis of a previous qualitative study that involved semistructured interviews of 16 surrogates of critically ill patients with TBI from two level 1 trauma centers and 20 TBI expert physicians from seven trauma centers. Open-ended questions about prognostic uncertainty were asked. We identified major themes with an inductive approach. The Conceptual Taxonomy of Uncertainty was applied to further characterize these themes as data-centered, system-centered, and patient-centered issues of uncertainty., Results: Nearly all surrogates (15 of 16) and physicians (19 of 20) recognized the emotional burden of uncertainty in the decision-making process for surrogates. More than three quarters of surrogates (13 of 16) described instances in which a lack of information regarding their loved one's disease or prognosis created uncertainty in their decision-making process, identifying both positive and negative instances of prognostic communication by physicians. We found that physicians used one of three strategies to communicate prognostic uncertainty to surrogates: leaving no room for uncertainty, honesty about uncertainty, and range of possibilities. These strategies did not meet the communication preferences of the majority of surrogates, with more than a third of decision-makers (6 of 15) being frustrated by too much ambiguity about prognosis as well as the failure to acknowledge the existence of uncertainty., Conclusions: We found that physician communication strategies rarely addressed surrogate needs regarding uncertainty adequately, suggesting an urgent need for future research into improved communication of prognostic uncertainty., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Hypernatremia has been associated with mortality in neurocritically ill patients, with and without traumatic brain injury (TBI). These studies, however, lack concomitant adjustment for hyperchloremia as a physiologically co-occurring finding despite the associations with hyperchloremia and worse outcomes after trauma, sepsis, and intracerebral hemorrhage. The objective of our study was to examine the association of concomitant hypernatremia and hyperchloremia with in-hospital mortality in moderate-severe TBI (msTBI) patients., Methods: We retrospectively analyzed prospectively collected data from the OPTIMISM-study and included all msTBI patients consecutively enrolled between 11/2009 and 1/2017. Time-weighted average (TWA) sodium and chloride values were calculated for all patients to examine the unadjusted mortality rates associated with the burden of hypernatremia and hyperchloremia over the entire duration of the intensive care unit stay. Multivariable logistic regression modeling predicting in-hospital mortality adjusted for validated confounders of msTBI mortality was applied to evaluate the concomitant effects of hypernatremia and hyperchloremia. Internal bootstrap validation was performed., Results: Of the 458 patients included for analysis, 202 (44%) died during the index hospitalization. Fifty-five patients (12%) were excluded due to missing data. Unadjusted mortality rates were nearly linearly increasing for both TWA sodium and TWA chloride, and were highest for patients with a TWA sodium > 160 mmol/L (100% mortality) and TWA chloride > 125 mmol/L (94% mortality). When evaluated separately in the multivariable analysis, TWA sodium (per 10 mmol/L change: adjusted OR 4.0 [95% CI 2.1-7.5]) and TWA chloride (per 10 mmol/L change: adjusted OR 3.9 [95% CI 2.2-7.1]) independently predicted in-hospital mortality. When evaluated in combination, TWA chloride remained independently associated with in-hospital mortality (per 10 mmol/L change: adjusted OR 2.9 [95% CI 1.1-7.8]), while this association was no longer observed with TWA sodium values (per 10 mmol/L change: adjusted OR 1.5 [95% CI 0.51-4.4])., Conclusions: When concomitantly adjusting for the burden of hyperchloremia and hypernatremia, only hyperchloremia was independently associated with in-hospital mortality in our msTBI cohort. Pending validation, our findings may provide the rationale for future studies with targeted interventions to reduce hyperchloremia and improve outcomes in msTBI patients.

Objective: To develop and demonstrate early feasibility of a goals-of-care decision aid for surrogates of patients who are critically ill with traumatic brain injury (ciTBI) that meets accepted international decision aid guidelines., Methods: We developed the decision aid in 4 stages: (1) qualitative study of goals-of-care communication and decision needs of 36 stakeholders of ciTBI (surrogates and physicians), which informed (2) development of paper-based decision aid with iterative revisions after feedback from 52 stakeholders; (3) acceptability and usability testing in 18 neurologic intensive care unit (neuroICU) family members recruited from 2 neuroICU waiting rooms using validated scales; and (4) open-label, randomized controlled feasibility trial in surrogates of ciTBI. We performed an interim analysis of 16 surrogates of 12 consecutive patients who are ciTBI to confirm early feasibility of the study protocol and report recruitment, participation, and retention rates to date., Results: The resultant goals-of-care decision aid achieved excellent usability (median System Usability Scale 87.5 [possible range 0-100]) and acceptability (97% graded the tool's content as "good" or "excellent"). Early feasibility of the decision aid and the feasibility trial protocol was demonstrated by high rates of recruitment (73% consented), participation (100%), and retention (100% both after the goals-of-care clinician-family meeting and at 3 months) and complete data for the measurements of all secondary decision-related and behavioral outcomes to date., Conclusions: Our systematic development process resulted in a novel goals-of-care decision aid for surrogates of patients who are ciTBI with excellent usability, acceptability, and early feasibility in the neuroICU environment, and meets international decision aid standards. This methodology may be a development model for other decision aids in neurology to promote shared decision-making., (© 2020 American Academy of Neurology.)

Purpose: To describe the frequency of cardiovascular complications and cardiac dysfunction in critically-ill patients with moderate-severe traumatic brain injury (msTBI) and cardiac factors associated with in-hospital survival., Methods: Retrospective analysis of a prospective cohort study at a single Level-1 trauma center with a dedicated neuro-trauma intensive care unit (ICU). Adult patients admitted to the ICU with msTBI were consecutively enrolled in the prospective OPTIMISM study between November 2009 and January 2017. Cardiac dysfunction was measured using a combination of EKG parameters, echocardiography abnormalities, and peak serum troponin-I levels during the index hospitalization. These items were combined into a cardiac dysfunction index (CDI), ranging from 0 to 3 points and modeled in a Cox regression analysis., Results: A total of 326 patients with msTBI were included. For every one-point increase in the CDI, the multivariable adjusted risk of dying during the patient's acute hospitalization more than doubled (adjusted HR 2.41; 95% CI 1.29-4.53)., Conclusion: Cardiac dysfunction was common in patients with msTBI and independently associated with more severe brain injury and a reduction in hospital survival in this population. Further research is needed to validate the CDI and create more precise scoring tools., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Two randomised trials assessing the effectiveness of decompressive craniectomy (DC) following traumatic brain injury (TBI) were published in recent years: DECRA in 2011 and RESCUEicp in 2016. As the results have generated debate amongst clinicians and researchers working in the field of TBI worldwide, it was felt necessary to provide general guidance on the use of DC following TBI and identify areas of ongoing uncertainty via a consensus-based approach., Methods: The International Consensus Meeting on the Role of Decompressive Craniectomy in the Management of Traumatic Brain Injury took place in Cambridge, UK, on the 28th and 29th September 2017. The meeting was jointly organised by the World Federation of Neurosurgical Societies (WFNS), AO/Global Neuro and the NIHR Global Health Research Group on Neurotrauma. Discussions and voting were organised around six pre-specified themes: (1) primary DC for mass lesions, (2) secondary DC for intracranial hypertension, (3) peri-operative care, (4) surgical technique, (5) cranial reconstruction and (6) DC in low- and middle-income countries., Results: The invited participants discussed existing published evidence and proposed consensus statements. Statements required an agreement threshold of more than 70% by blinded voting for approval., Conclusions: In this manuscript, we present the final consensus-based recommendations. We have also identified areas of uncertainty, where further research is required, including the role of primary DC, the role of hinge craniotomy and the optimal timing and material for skull reconstruction.

Background: Determine the prognostic impact of magnetic resonance imaging (MRI)-defined diffuse axonal injury (DAI) after traumatic brain injury (TBI) on functional outcomes, quality of life, and 3-year mortality., Methods: This retrospective single center cohort included adult trauma patients (age > 17 years) admitted from 2006 to 2012 with TBI. Inclusion criteria were positive head computed tomography with brain MRI within 2 weeks of admission. Exclusion criteria included penetrating TBI or prior neurologic condition. Separate ordinal logistic models assessed DAI's prognostic value for the following scores: (1) hospital-discharge Functional Independence Measure, (2) long-term Glasgow Outcome Scale-Extended, and (3) long-term Quality of Life after Brain Injury-Overall Scale. Cox proportional hazards modeling assessed DAI's prognostic value for 3-year survival. Covariates included age, sex, race, insurance status, Injury Severity Score, admission Glasgow Coma Scale Score, Marshall Head computed tomography Class, clinical DAI on MRI (Y/N), research-level anatomic DAI Grades I-III (I, cortical; II, corpus callosum; III, brainstem), ventilator days, time to follow commands, and time to long-term follow-up (for logistic models)., Results: Eligibility criteria was met by 311 patients, who had a median age of 40 years (interquartile range [IQR], 23-57 years), Injury Severity Score of 29 (IQR, 22-38), intensive care unit stay of 6 days (IQR, 2-11 days), and follow-up of 5 years (IQR, 3-6 years). Clinical DAI was present on 47% of MRIs. Among 300 readable MRIs, 56% of MRIs had anatomic DAI (25% Grade I, 18% Grade II, 13% Grade III). On regression, only clinical (not anatomic) DAI was predictive of a lower Functional Independence Measure score (odds ratio, 2.5; 95% confidence interval, 1.28-4.76], p = 0.007). Neither clinical nor anatomic DAI were related to survival, Glasgow Outcome Scale-Extended, or Quality of Life after Brain Injury-Overall Scale scores., Conclusion: In this longitudinal cohort, clinical evidence of DAI on MRI may only be useful for predicting short-term in-hospital functional outcome. Given no association of DAI and long-term TBI outcomes, providers should be cautious in attributing DAI to future neurologic function, quality of life, and/or survival., Level of Evidence: Epidemiological, level III; Therapeutic, level IV.

Background: Diffuse axonal injury (DAI) on magnetic resonance imaging has been associated with poor functional outcome after moderate-severe traumatic brain injury (msTBI). Yet, DAI assessment with highly sensitive magnetic resonance imaging techniques is unfeasible in the acute trauma setting, and computed tomography (CT) remains the key diagnostic modality despite its lower sensitivity. We sought to determine whether CT-defined hemorrhagic DAI (hDAI) is associated with discharge and favorable 3- and 12-month functional outcome (Glasgow Coma Scale score ≥4) after msTBI., Methods: We analyzed 361 msTBI patients from the single-center longitudinal Outcome Prognostication in Traumatic Brain Injury study collected over 6 years (November 2009 to November 2015) with prospective outcome assessments at 3 months and 12 months. Patients with microhemorrhages on CT were designated "CT-hDAI-positive" and those without as "CT-hDAI-negative." For secondary analyses "CT-hDAI-positive" was stratified into two phenotypes according to presence ("associated") versus absence ("predominant") of concomitant large acute traumatic lesions to determine whether presence versus absence of additional focal mass lesions portends a different prognosis., Results: Seventy (19%) patients were CT-hDAI-positive (n = 36 predominant; n = 34 associated hDAI). In univariate analyses, CT-hDAI-positive status was associated with discharge survival (p = 0.004) and favorable outcome at 3 months (p = 0.003) and 12 months (p = 0.005). After multivariable adjustment, CT-hDAI positivity was no longer associated with discharge survival and functional outcome (all ps > 0.05). Stratified by hDAI phenotype, predominant hDAI patients had worse trauma severity, longer intensive care unit stays, and more systemic medical complications. Predominant hDAI, but not associated hDAI, was an independent predictor of discharge survival (adjusted odds ratio, 24.7; 95% confidence interval [CI], 3.2-192.6; p = 0.002) and favorable 12-month outcome (adjusted odds ratio, 4.7; 95% CI, 1.5-15.2; p = 0.01). Sensitivity analyses using Cox regression confirmed this finding for 1-year survival (adjusted hazard ratio, 5.6; 95% CI, 1.3-23; p = 0.048)., Conclusion: The CT-defined hDAI was not an independent predictor of unfavorable short- and long-term outcomes and should not be used for acute prognostication in msTBI patients. Predominant hDAI patients had good clinical outcomes when supported to intensive care unit discharge and beyond., Level of Evidence: Prognostic study, level III.

Severe traumatic brain injury (sTBI) is a major contributor to long-term disability and a leading cause of death worldwide. Medical management of the sTBI patient, beginning with prehospital triage, is aimed at preventing secondary brain injury. This review discusses prehospital and emergency department management of sTBI, as well as aspects of TBI management in the intensive care unit where advances have been made in the past decade. Areas of emphasis include intracranial pressure management, neuromonitoring, management of paroxysmal sympathetic hyperactivity, neuroprotective strategies, prognostication, and communication with families about goals of care. Where appropriate, differences between the third and fourth editions of the Brain Trauma Foundation guidelines for the management of severe traumatic brain injury are highlighted.

Background: Surrogate decision-makers ("surrogates") and physicians of incapacitated patients have different views of prognosis and how it should be communicated, but this has not been investigated in neurocritically ill patients. We examined surrogates' communication preferences and physicians' practices during the outcome prognostication for critically ill traumatic brain injury (ciTBI) patients in two level-1 trauma centers and seven academic medical centers in the USA., Methods: We used qualitative content analysis and descriptive statistics of transcribed interviews to identify themes in surrogates (n = 16) and physicians (n = 20)., Results: The majority of surrogates (82%) preferred numeric estimates describing the patient's prognosis, as they felt it would increase prognostic certainty, and limit the uncertainty perceived as frustrating. Conversely, 75% of the physicians reported intentionally omitting numeric estimates during prognostication meetings due to low confidence in family members' abilities to appropriately interpret probabilities, worry about creating false hope, and distrust in the accuracy and data quality of existing TBI outcome models. Physicians felt that these models are for research only and should not be applied to individual patients. Surrogates valued compassion during prognostication discussions, and acceptance of their goals-of-care decision by clinicians. Physicians and surrogates agreed on avoiding false hope., Conclusion: We identified fundamental differences in the communication preferences of prognostic information between ciTBI patient surrogates and physicians. These findings inform the content of a future decision aid for goals-of-care discussions in ciTBI patients. If validated, these findings may have important implications for improving communication practices in the neurointensive care unit independent of whether a formal decision aid is used.

The Glasgow Coma Scale (GCS) has limited utility in intubated patients due to the inability to assign verbal subscores. The verbal subscore can be derived from the eye and motor subscores using a mathematical model, but the advantage of this method and its use in outcome prognostication in traumatic brain injury (TBI) patients remains unknown. We compared the validated "Core+CT"-IMPACT-model performance in 251 intubated TBI patients prospectively enrolled in the longitudinal OPTIMISM study between November 2009 and May 2015 when substituting the original motor GCS (mGCS) with the total estimated GCS (teGCS; with estimated verbal subscore). We hypothesized that model performance would improve with teGCS. Glasgow Outcome Scale (GOS) scores were assessed at 3 and 12 months by trained interviewers. In the complete case analysis, there was no statistically or clinically significant difference in the discrimination (C-statistic) at either time-point using the mGCS versus the teGCS (3 months: 0.893 vs. 0.871;12 months: 0.926 vs. 0.92). At 3 months, IMPACT-model calibration was excellent with mGCS and teGCS (Hosmer-Lemeshow "goodness-of-fit" chi square p value 0.9293 and 0.9934, respectively); it was adequate at 12 months with teGCS (0.5893) but low with mGCS (0.0158), possibly related to diminished power at 12 months. At both time-points, motor GCS contributed more to the variability of outcome (Nagelkerke ΔR 2 ) than teGCS (3 months: 5.8% vs. 0.4%; 12 months: 5% vs. 2.6%). The sensitivity analysis with imputed missing outcomes yielded similar results, with improved calibration for both GCS variants. In our cohort of intubated TBI patients, there was no statistically or clinically meaningful improvement in the IMPACT-model performance by substituting the original mGCS with teGCS.