Severe Acute Brain Injury Research Articles

Delayed Withdrawal of Life-Sustaining Treatment in Disorders of Consciousness: Practical and Theoretical Considerations.

Disorders of consciousness (DoC) resulting from severe acute brain injuries may prompt clinicians and surrogate decision makers to consider withdrawal of life-sustaining treatment (WLST) if the neurologic prognosis is poor. Recent guidelines suggest, however, that clinicians should avoid definitively concluding a poor prognosis prior to 28days post injury, as patients may demonstrate neurologic recovery outside the acute time period. This practice may increase the frequency with which clinicians consider the option of delayed WLST (D-WLST), namely, WLST that would occur after hospital discharge, if the patient's recovery trajectory ultimately proves inconsistent with an acceptable quality of life. However acute care clinicians are often uncertain about what D-WLST entails and therefore find it difficult to properly counsel surrogates about this option. Here, we describe practical and theoretical considerations relevant to D-WLST. We first identify post-acute-care facilities to which patients with DoC are likely to be discharged and where D-WLST may be considered. Second, we describe how clinicians and surrogates may determine the appropriate timing of D-WLST. Third, we outline how D-WLST is practically implemented. And finally, we discuss psychosocial barriers to D-WLST, including the regret paradox, in which surrogates of patients who do not recover to meet preestablished goals frequently choose not to ultimately pursue D-WLST. Together, these practical, logistic, and psychosocial factors must be considered when potentially deferring WLST to the post-acute-care setting to optimize neurologic recovery for patients, avoid prolonged undue suffering, and promote informed and shared decision-making between clinicians and surrogates.

Pre- and post-therapy functional MRI connectivity in severe acute brain injury with suppression of consciousness: a comparative analysis to epilepsy features.

Severe acute brain injury (SABI) with suppressed consciousness is a major societal burden, with early prognosis being crucial for life-and-death treatment decisions. Resting-state functional MRI (rs-fMRI) is promising for prognosis and identifying epileptogenic activity in SABI. While established for SABI prognosis and seizure networks (SzNET) identification in epilepsy, the rs-fMRI use for SzNET detection in SABI is limited. This study compared evolution of SzNET and resting-state networks (RSN) pre-to-post treatment in SABI and epilepsy, hypothesizing that changes would align with clinical evolution. Therapies included epilepsy surgery for the epilepsy group and antiseizure medication for the SABI group. Independent component analysis (ICA) was used to identify SzNET and RSNs in all rs-fMRI. High-frequency BOLD (HF-BOLD), an ICA power spectrum-based index, quantified RSN and SzNET changes by the patient. Confidence intervals measured HF-BOLD changes pre-to-post-therapy. Baseline HF-BOLD and HF-BOLD changes were compared using linear-mixed models and interaction tests. Five SABI and ten epilepsy patients were included. SzNET were identified in all SABI's pre-therapy rs-fMRI. The clinical changes in SABI and epilepsy were consistent with rs-fMRI findings across groups. HF-BOLD reduced in the epilepsy group RSN post-therapy (-0.78, 95% CI -3.42 to -0.33), but the evidence was insufficient to determine an HF-BOLD reduction in SABI patients or SzNET. The HF-BOLD change trend in pre-to-post epilepsy surgery scans paralleled the clinical improvement, suggesting that the power spectrum may quantify the degree of abnormality on ICA-derived networks. Despite limitations such as small sample sizes, this exploratory study provides valuable insights into network dysfunction in SABI and epilepsy.

Lung-Protective Mechanical Ventilation in Patients with Severe Acute Brain Injury: A Multicenter Randomized Clinical Trial (PROLABI).

Rationale: Lung-protective strategies using low Vt and moderate positive end-expiratory pressure (PEEP) are considered best practice in critical care, but interventional trials have never been conducted in patients with acute brain injuries because of concerns about carbon dioxide control and the effect of PEEP on cerebral hemodynamics. Objectives: To test the hypothesis that ventilation with lower VT and higher PEEP compared to conventional ventilation would improve clinical outcomes in patients with acute brain injury. Methods: In this multicenter, open-label, controlled clinical trial, 190 adult patients with acute brain injury were assigned to receive either a lung-protective or a conventional ventilatory strategy. The primary outcome was a composite endpoint of death, ventilator dependency, and acute respiratory distress syndrome (ARDS) at Day 28. Neurological outcome was assessed at ICU discharge by the Oxford Handicap Scale and at 6 months by the Glasgow Outcome Scale. Measurements and Main Results: The two study arms had similar characteristics at baseline. In the lung-protective and conventional strategy groups, using an intention-to-treat approach, the composite outcome at 28 days was 61.5% and 45.3% (relative risk [RR], 1.35; 95% confidence interval [CI], 1.03-1.79; P = 0.025). Mortality was 28.9% and 15.1% (RR, 1.91; 95% CI, 1.06-3.42; P = 0.02), ventilator dependency was 42.3% and 27.9% (RR, 1.52; 95% CI, 1.01-2.28; P = 0.039), and incidence of ARDS was 30.8% and 22.1% (RR, 1.39; 95% CI, 0.85-2.27; P = 0.179), respectively. The trial was stopped after enrolling 190 subjects because of termination of funding. Conclusions: In patients with acute brain injury without ARDS, a lung-protective ventilatory strategy, as compared with a conventional strategy, did not reduce mortality, percentage of patients weaned from mechanical ventilation, or incidence of ARDS and was not beneficial in terms of neurological outcomes. Because of the early termination, these preliminary results require confirmation in larger trials. Clinical trial registered with www.clinicaltrials.gov (NCT01690819).

Ketamine for Critically Ill Patients with Severe Acute Brain Injury: A Systematic Review with Meta-analysis and Trial Sequential Analysis of Randomized Clinical Trials.

Patients with severe acute brain injury have a high risk of a poor clinical outcome due to primary and secondary brain injury. Ketamine reportedly inhibits cortical spreading depolarization, an electrophysiological phenomenon that has been associated with secondary brain injury, making ketamine potentially attractive for patients with severe acute brain injury. The aim of this systematic review is to explore the current literature regarding ketamine for patients with severe acute brain injury. We systematically searched international databases for randomized clinical trials comparing ketamine by any regimen versus placebo, no intervention, or any control drug for patients with severe acute brain injury. Two authors independently reviewed and selected trials for inclusion, extracted data, assessed risk of bias, and performed analysis using Review Manager and Trial Sequential Analysis. Evidence certainty was assessed using Grading of Recommendations Assessment, Development and Evaluation. The primary outcomes were the proportion of participants with an unfavorable functional outcome, the proportion of participants with one or more serious adverse events, and quality of life. We identified five randomized trials comparing ketamine versus sufentanil, fentanyl, other sedatives, or saline (total N = 149 participants). All outcomes were at overall high risk of bias. The proportions of participants with one or more serious adverse events did not differ between ketamine and sufentanil or fentanyl (relative risk 1.45, 95% confidence interval 0.81-2.58; very low certainty). Trial sequential analysis showed that further trials are needed. The level of evidence regarding the effects of ketamine on functional outcome and serious adverse events in patients with severe acute brain injury is very low. Ketamine may markedly, modestly, or not at all affect these outcomes. Large randomized clinical trials at low risk of bias are needed.

Comparison of Continuous Intracortical and Scalp Electroencephalography in Comatose Patients with Acute Brain Injury.

Depth electroencephalography (dEEG) is a recent invasive monitoring technique used in patients with acute brain injury. This study aimed to describe in detail the clinical manifestations of nonconvulsive seizures (NCSzs) with and without a surface EEG correlate, analyze their long-standing effects, and provide data that contribute to understanding the significance of certain scalp EEG patterns observed in critically ill patients. We prospectively enrolled a cohort of 33 adults with severe acute brain injury admitted to the neurological intensive care unit. All of them underwent multimodal invasive monitoring, including dEEG. All patients were scanned on a 3T magnetic resonance imaging scanner at 6months after hospital discharge, and mesial temporal atrophy (MTA) was calculated using a visual scale. In 21 (65.6%) of 32 study participants, highly epileptiform intracortical patterns were observed. A total of 11 (34.3%) patients had electrographic or electroclinical seizures in the dEEG, of whom 8 had both spontaneous and stimulus-induced (SI) seizures, and 3 patients had only spontaneous intracortical seizures. An unequivocal ictal scalp correlate was observed in only 3 (27.2%) of the 11 study participants. SI-NCSzs occurred during nursing care, medical procedures, and family visits. Subtle clinical manifestations, such as restlessness, purposeless stereotyped movements of the upper limbs, ventilation disturbances, jerks, head movements, hyperextension posturing, chewing, and oroalimentary automatisms, occurred during intracortical electroclinical seizures. MTA was detected in 18 (81.8%) of the 22 patients. There were no statistically significant differences between patients with MTA with and without seizures or status epilepticus. Most NCSzs in critically ill comatose patients remain undetectable on scalp EEG. SI-NCSzs frequently occur during nursing care, medical procedures, and family visits. Semiology of NCSzs included ictal minor signs and subtle symptoms, such as breathing pattern changes manifested as patient-ventilator dyssynchrony.

Post-Intensive Care Syndrome in Neurocritical Care Patients.

Post-intensive care syndrome (PICS) refers to unintended consequences of critical care that manifest as new or worsening impairments in physical functioning, cognitive ability, or mental health. As intensive care unit (ICU) survival continues to improve, PICS is becoming increasingly recognized as a public health problem. Studies that focus on PICS have typically excluded patients with acute brain injuries and chronic neurodegenerative problems. However, patients who require neurocritical care undoubtedly suffer from impairments that overlap substantially with those encompassed by PICS. A major challenge is to distinguish between impairments related to brain injury and those that occur as a consequence of critical care. The general principles for the prevention and management of PICS and multidomain impairments in patients with moderate and severe neurological injuries are similar including the ICU liberation bundle, multidisciplinary team-based care throughout the continuum of care, and increasing awareness regarding the challenges of critical care survivorship among patients, families, and multidisciplinary team members. An extension of this concept, PICS-Family (PICS-F) refers to the mental health consequences of the intensive care experience for families and loved ones of ICU survivors. A dyadic approach to ICU survivorship with an emphasis on recognizing families and caregivers that may be at risk of developing PICS-F after neurocritical care illness can help improve outcomes for ICU survivors. In this review, we will summarize our current understanding of PICS and PICS-F, emerging literature on PICS in severe acute brain injury, strategies for preventing and treating PICS, and share our recommendations for future directions.

Prognostication in Neurocritical Care.

This article synthesizes the current literature on prognostication in neurocritical care, identifies existing challenges, and proposes future research directions to reduce variability and enhance scientific and patient-centered approaches to neuroprognostication. Patients with severe acute brain injury often lack the capacity to make their own medical decisions, leaving surrogate decision makers responsible for life-or-death choices. These decisions heavily rely on clinicians' prognostication, which is still considered an art because of the previous lack of specific guidelines. Consequently, there is significant variability in neuroprognostication practices. This article examines various aspects of neuroprognostication. It explores the cognitive approach to prognostication, highlights the use of statistical modeling such as Bayesian models and machine learning, emphasizes the importance of clinician-family communication during prognostic disclosures, and proposes shared decision making for more patient-centered care. This article identifies ongoing challenges in the field and emphasizes the need for future research to ameliorate variability in neuroprognostication. By focusing on scientific methodologies and patient-centered approaches, this research aims to provide guidance and tools that may enhance neuroprognostication in neurocritical care.

Temperature Control in Acute Brain Injury: An Update.

Temperature control in severe acute brain injury (SABI) is a key component of acute management. This manuscript delves into the complex role of temperature management in SABI, encompassing conditions like traumatic brain injury (TBI), acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), aneurysmal subarachnoid hemorrhage (aSAH), and hypoxemic/ischemic brain injury following cardiac arrest. Fever is a common complication in SABI and is linked to worse neurological outcomes due to increased inflammatory responses and intracranial pressure (ICP). Temperature management, particularly hypothermic temperature control (HTC), appears to mitigate these adverse effects primarily by reducing cerebral metabolic demand and dampening inflammatory pathways. However, the effectiveness of HTC varies across different SABI conditions. In the context of post-cardiac arrest, the impact of HTC on neurological outcomes has shown inconsistent results. In cases of TBI, HTC seems promising for reducing ICP, but its influence on long-term outcomes remains uncertain. For AIS, clinical trials have yet to conclusively demonstrate the benefits of HTC, despite encouraging preclinical evidence. This variability in efficacy is also observed in ICH, aSAH, bacterial meningitis, and status epilepticus. In pediatric and neonatal populations, while HTC shows significant benefits in hypoxic-ischemic encephalopathy, its effectiveness in other brain injuries is mixed. Although the theoretical basis for employing temperature control, especially HTC, is strong, the clinical outcomes differ among various SABI subtypes. The current consensus indicates that fever prevention is beneficial across the board, but the application and effectiveness of HTC are more nuanced, underscoring the need for further research to establish optimal temperature management strategies. Here we provide an overview of the clinical evidence surrounding the use of temperature control in various types of SABI.

Trajectories of Care and Missed Opportunities for Survivors of Severe Acute Brain Injury (P7-11.015)

Trajectories of Care and Missed Opportunities for Survivors of Severe Acute Brain Injury (P7-11.015)

A nomogram for predicting the necessity of tracheostomy after severe acute brain injury in patients within the neurosurgery intensive care unit: A retrospective cohort study

ObjectiveThis retrospective study was aimed to develop a predictive model for assessing the necessity of tracheostomy (TT) in patients admitted to the neurosurgery intensive care unit (NSICU). MethodWe analyzed data from 1626 NSICU patients with severe acute brain injury (SABI) who were admitted to the Department of NSICU at the Affiliated People's Hospital of Jiangsu University between January 2021 and December 2022. Data of the patients were retrospectively obtained from the clinical research data platform. The patients were randomly divided into training (70%) and testing (30%) cohorts. The least absolute shrinkage and selection operator (LASSO) regression identified the optimal predictive features. A multivariate logistic regression model was then constructed and represented by a nomogram. The efficacy of the model was evaluated based on discrimination, calibration, and clinical utility. ResultsThe model highlighted six predictive variables, including the duration of NSICU stay, neurosurgery, orotracheal intubation time, Glasgow Coma Scale (GCS) score, systolic pressure, and respiration rate. Receiver operating characteristic (ROC) analysis of the nomogram yielded area under the curve (AUC) values of 0.854 (95% confidence interval [CI]: 0.822–0.886) for the training cohort and 0.865 (95% CI: 0.817–0.913) for the testing cohort, suggesting commendable differential performance. The predictions closely aligned with actual observations in both cohorts. Decision curve analysis demonstrated that the numerical model offered a favorable net clinical benefit. ConclusionWe developed a novel predictive model to identify risk factors for TT in SABI patients within the NSICU. This model holds the potential to assist clinicians in making timely surgical decisions concerning TT.

Amantadine as an Aid to Extubation in Severe Acute Brain Injury: A Case Series.

For a subset of patients with severe acute brain injury (SABI) undergoing invasive mechanical ventilation, the primary barrier to successful extubation is depressed mental status. Amantadine is a neurostimulant that has been demonstrated to increase arousal and improve functional outcomes in patients with SABI. In this case series, we describe 5 patients with SABI and invasive mechanical ventilation who received amantadine as an agent to improve mental status to allow extubation. The primary barrier to extubation for all patients was depressed mental status. Median age was 77 (range 32 to 82). Primary diagnoses were ischemic stroke (n = 1), subdural hemorrhage (n = 2), intracerebral hemorrhage (n = 1), and traumatic brain injury (n = 1). Median Glasgow Coma Score was 7T prior to administration of amantadine and 10T on the day after amantadine was initiated, with improvements in eye-opening and motor response. Four patients displayed improvement in arousal and attention and were successfully extubated 1 to 4days after initiation of amantadine (median 2days). The fifth patient only displayed marginal improvement in mental status after starting amantadine, but was ultimately able to be extubated 7days later. Amantadine may improve the likelihood of or reduce the time to successful extubation in patients with SABI.

Public and Clinician Perspectives on Ventilator Withdrawal in Vegetative State Following Severe Acute Brain Injury: A Vignette Survey.

The vegetative state (VS) after severe acute brain injury (SABI) is associated with significant prognostic uncertainty and poor long-term functional outcomes. However, it is generally distinguished from imminent death and is exempt from the Life-Sustaining Treatment (LST) Decisions Act in Korea. Here, we aimed to examine the perspectives of the general population (GP) and clinicians regarding decisions on mechanical ventilator withdrawal in patients in a VS after SABI. A cross-sectional survey was undertaken, utilizing a self-reported online questionnaire based on a case vignette. Nationally selected by quota sampling, the GP comprised 500 individuals aged 20 to 69 years. There were 200 doctors from a tertiary university hospital in the clinician sample. Participants were asked what they thought about mechanical ventilator withdrawal in patients in VS 2 months and 3 years after SABI. Two months after SABI in the case, 79% of the GP and 83.5% of clinicians had positive attitudes toward mechanical ventilator withdrawal. In the GP, attitudes were associated with spirituality, household income, religion, the number of household members. On the other hand, clinicians' attitudes were related to their experience of completing advance directives (AD) and making decisions about LST. In this case, 3 years after SABI, 92% of the GP and 94% of clinicians were more accepting of ventilator withdrawal compared to previous responses, based on the assumption that the patient had written AD. However, it appeared that the proportion of positive responses to ventilator withdrawal decreased when the patients had only verbal expressions (82% of the GP; 75.5% of clinicians) or had not previously expressed an opinion regarding LST (58% of the GP; 39.5% of clinicians). More than three quarters of both the GP and clinicians had positive opinions regarding ventilator withdrawal in patients in a VS after SABI, which was reinforced with time and the presence of AD. Legislative adjustments are needed to ensure that previous wishes for those patients are more respected and reflected in treatment decisions.

Resting-State Functional Magnetic Resonance Imaging Network Association With Mortality, Epilepsy, Cognition, and Motor Two-Year Outcomes in Suspected Severe Neonatal Acute Brain Injury

Background and ObjectivesIn acute brain injury of neonates, resting-state functional magnetic resonance imaging (MRI) (RS) showed incremental association with consciousness, mortality, cognitive and motor development, and epilepsy, with correction for multiple comparisons, at six months postgestation in neonates with suspected acute brain injury (ABI). However, there are relatively few developmental milestones at six months to benchmark against, thus, we extended this cohort study to evaluate two-year outcomes. MethodsIn 40 consecutive neonates with ABI and RS, ordinal scores of resting-state networks; MRI, magnetic resonance spectroscopy, and electroencephalography; and up to 42-month outcomes of mortality, general and motor development, Pediatric Cerebral Performance Category Scale (PCPC), and epilepsy informed associations between tests and outcomes. ResultsMean gestational age was 37.8 weeks, 68% were male, and 60% had hypoxic-ischemic encephalopathy. Three died in-hospital, four at six to 42 months, and five were lost to follow-up. Associations included basal ganglia network with PCPC (P = 0.0003), all-mortality (P = 0.005), and motor (P = 0.0004); language/frontoparietal network with developmental delay (P = 0.009), PCPC (P = 0.006), and all-mortality (P = 0.01); default mode network with developmental delay (P = 0.003), PCPC (P = 0.004), neonatal intensive care unit mortality (P = 0.01), and motor (P = 0.009); RS seizure onset zone with epilepsy (P = 0.01); and anatomic MRI with epilepsy (P = 0.01). ConclusionFor the first time, at any age, resting state functional MRI in ABI is associated with long-term epilepsy and RSNs predicted mortality in neonates. Severity of RSN abnormality was associated with incrementally worsened neurodevelopment including cognition, language, and motor function over two years.

An Update on Palliative Care in Neurocritical Care: Providing Goal‑Concordant Care in the Face of Prognostic Uncertainty.

We investigate the complexities and interplay between the concepts of prognostic uncertainty and patient preferences as they relate to the delivery of goal-concordant care to patients with severe acute brain injuries (SABI) in the Neurological Intensive Care Unit (Neuro-ICU). Patients with SABI in the Neuro-ICU have unique palliative care needs due to sudden, often unexpected changes in personhood and quality of life. A substantial amount of uncertainty is inherent and poses a challenge to both the patient's prognosis and treatment preferences. The delivery of goal-concordant care can be difficult to achieve.

A Mindfulness-Based Resiliency Program for Caregivers of Patients With Severe Acute Brain Injury Transitioning Out of Critical Care: Protocol for an Open Pilot Trial.

Caregivers of patients with severe acute brain injuries (SABI) that lead to coma and require intensive care unit (ICU) treatment often experience chronic emotional distress. To address this need, we developed the Coma Family (COMA-F) program, a mindfulness-based resiliency intervention for these caregivers. We will conduct an open pilot trial of COMA-F (National Institutes of Health Stage IA). Here we describe our study protocol and proposed intervention content. We will enroll 15 caregivers of patients with SABIs during their loved one's hospital course from 3 enrollment centers. A clinical psychologist will deliver the COMA-F intervention (6 sessions) over Zoom (Zoom Video Communications, Inc) or in person. We will iterate COMA-F after each caregiver completes the intervention and an exit interview. English-speaking adults who have emotional distress confirmed by the clinical team and are the primary caregivers of a patient with SABI are eligible. The adult patient must have been admitted to the neuro-ICU for SABI and (1) have had a Glasgow Coma Scale score below 9 while not intubated or an inability to follow meaningful commands while intubated at any point during their hospitalization for >24 hours due to SABI; (2) will be undergoing either tracheostomy or percutaneous endoscopic or surgical gastrostomy tube placement or have already received one or both; and (3) have a prognosis of survival >3 months. We will identify eligible caregivers through screening patients' medical records and through direct referrals from clinicians in the neuro-ICU. During the intervention we will teach caregivers mind-body and resilience skills, including deep breathing, mindfulness, meditation, dialectical thinking, acceptance, cognitive restructuring, effective communication, behavioral activation, and meaning-making. Caregivers will complete self-report assessments (measures of emotional distress and resilience) before and after the intervention. Primary outcomes are feasibility (recruitment, quantitative measures, adherence, and therapist fidelity) and acceptability (treatment satisfaction, credibility, and expectancy). We will conduct brief qualitative exit interviews to gather feedback on refining the program and study procedures. We will examine frequencies and proportions to determine feasibility and acceptability and will analyze qualitative exit interview data using thematic analysis. We will also conduct 2-tailed t tests to explore signals of improvement in emotional distress and treatment targets. We will then conduct an explanatory-sequential mixed methods analysis to integrate quantitative and qualitative data to refine the COMA-F manual and study procedures. This study has been approved by the institutional review board at 1 of the 3 enrollment centers (2023P000536), with approvals at the other 2 centers pending. We anticipate that the study will be completed by late 2024. We will use our findings to refine the COMA-F intervention and prepare for a feasibility randomized controlled trial. ClinicalTrials.gov NCT05761925; https://clinicaltrials.gov/study/NCT05761925. PRR1-10.2196/50860.

Cognitive Biases and Shared Decision Making in Acute Brain Injury.

Many patients hospitalized after severe acute brain injury are comatose and require life-sustaining therapies. Some of these patients make favorable recoveries with continued intensive care, while others do not. In addition to providing medical care, clinicians must guide surrogate decision makers through high-stakes, emotionally charged decisions about whether to continue life-sustaining therapies. These consultations require clinicians first to assess a patient's likelihood of recovery given continued life-sustaining therapies (i.e., prognosticate), then to communicate that prediction to surrogates, and, finally, to elicit and interpret the patient's preferences. At each step, both clinicians and surrogates are vulnerable to flawed decision making. Clinicians can be imprecise, biased, and overconfident when prognosticating after brain injury. Surrogates can misperceive the choice and misunderstand or misrepresent a patient's wishes, which may never have been communicated clearly. These biases can undermine the ability to reach choices congruent with patients' preferences through shared decision making (SDM). Decision science has extensively studied these biases. In this article, we apply that research to improving SDM for patients who are comatose after acute brain injury. After introducing SDM and the medical context, we describe principal decision science results as they relate to neurologic prognostication and end-of-life decisions, by both clinicians and surrogates. Based on research regarding general processes that can produce imprecise, biased, and overconfident prognoses, we propose interventions that could improve SDM, supporting clinicians and surrogates in making these challenging decisions.

Predicting neurologic recovery after severe acute brain injury using resting-state networks.

There is a lack of reliable tools used to predict functional recovery in unresponsive patients following a severe brain injury. The objective of the study is to evaluate the prognostic utility of resting-state functional magnetic resonance imaging for predicting good neurologic recovery in unresponsive patients with severe brain injury in the intensive-care unit. Each patient underwent a 5.5-min resting-state scan and ten resting-state networks were extracted via independent component analysis. The Glasgow Outcome Scale was used to classify patients into good and poor outcome groups. The Nearest Centroid classifier used each patient's ten resting-state network values to predict best neurologic outcome within 6months post-injury. Of the 25 patients enrolled (mean age = 43.68, range = [19-69]; GCS ≤ 9; 6 females), 10 had good and 15 had poor outcome. The classifier correctly and confidently predicted 8/10 patients with good and 12/15 patients with poor outcome (mean = 0.793, CI = [0.700, 0.886], Z = 2.843, p = 0.002). The prediction performance was largely determined by three visual (medial: Z = 3.11, p = 0.002; occipital pole: Z = 2.44, p = 0.015; lateral: Z = 2.85, p = 0.004) and the left frontoparietal network (Z = 2.179, p = 0.029). Our approach correctly identified good functional outcome with higher sensitivity (80%) than traditional prognostic measures. By revealing preserved networks in the absence of discernible behavioral signs, functional connectivity may aid in the prognostic process and affect the outcome of discussions surrounding withdrawal of life-sustaining measures.

The Neurological Pupil index for outcome prognostication in people with acute brain injury (ORANGE): a prospective, observational, multicentre cohort study

Improving the prognostication of acute brain injury is a key element of critical care. Standard assessment includes pupillary light reactivity testing with a hand-held light source, but findings are interpreted subjectively; automated pupillometry might be more precise and reproducible. We aimed to assess the association of the Neurological Pupil index (NPi)-a quantitative measure of pupillary reactivity computed by automated pupillometry-with outcomes of patients with severe non-anoxic acute brain injury. ORANGE is a multicentre, prospective, observational cohort study at 13 hospitals in eight countries in Europe and North America. Patients admitted to the intensive care unit after traumatic brain injury, aneurysmal subarachnoid haemorrhage, or intracerebral haemorrhage were eligible for the study. Patients underwent automated infrared pupillometry assessment every 4 h during the first 7 days after admission to compute NPi, with values ranging from 0 to 5 (with abnormal NPi being <3). The co-primary outcomes of the study were neurological outcome (assessed with the extended Glasgow Outcome Scale [GOSE]) and mortality at 6 months. We used logistic regression to model the association between NPi and poor neurological outcome (GOSE ≤4) at 6 months and Cox regression to model the relation of NPi with 6-month mortality. This study is registered with ClinicalTrials.gov, NCT04490005. Between Nov 1, 2020, and May 3, 2022, 514 patients (224 with traumatic brain injury, 139 with aneurysmal subarachnoid haemorrhage, and 151 with intracerebral haemorrhage) were enrolled. The median age of patients was 61 years (IQR 46-71), and the median Glasgow Coma Scale score on admission was 8 (5-11). 40 071 NPi measurements were taken (median 40 per patient [20-50]). The 6-month outcome was assessed in 497 (97%) patients, of whom 160 (32%) patients died, and 241 (47%) patients had at least one recording of abnormal NPi, which was associated with poor neurological outcome (for each 10% increase in the frequency of abnormal NPi, adjusted odds ratio 1·42 [95% CI 1·27-1·64]; p<0·0001) and in-hospital mortality (adjusted hazard ratio 5·58 [95% CI 3·92-7·95]; p<0·0001). NPi has clinically and statistically significant prognostic value for neurological outcome and mortality after acute brain injury. Simple, automatic, repeat automated pupillometry assessment could improve the continuous monitoring of disease progression and the dynamics of outcome prediction at the bedside. NeurOptics.

Thematic Analysis of Psychosocial Stressors and Adaptive Coping Strategies Among Informal Caregivers of Patients Surviving ICU Admission for Coma.

Family caregivers of patients with severe acute brain injury (SABI) admitted to intensive care units (ICUs) with coma experience heightened emotional distress stemming from simultaneous stressors. Stress and coping frameworks can inform psychosocial intervention development by elucidating common challenges and ways of navigating such experiences but have yet to be employed with this population. The present study therefore sought to use a stress and coping framework to characterize the stressors and coping behaviors of family caregivers of patients with SABI hospitalized in ICUs and recovering after coma. Our qualitative study recruited a convenience sample from 14 US neuroscience ICUs. Participants were family caregivers of patients who were admitted with ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, traumatic brain injury, or hypoxic-ischemic encephalopathy; had experienced a comatose state for > 24h; and completed or were scheduled for tracheostomy and/or gastrostomy tube placement. Participants were recruited < 7days after transfer out of the neuroscience ICU. We conducted live online video interviews from May 2021 to January 2022. One semistructured interview per participant was recorded and subsequently transcribed. Recruitment was stopped when thematic saturation was reached. We deductively derived two domains using a stress and coping framework to guide thematic analysis. Within each domain, we inductively derived themes to comprehensively characterize caregivers' experiences. We interviewed 30 caregivers. We identified 18 themes within the two theory-driven domains, including ten themes describing practical, social, and emotional stressors experienced by caregivers and eight themes describing the psychological and behavioral coping strategies that caregivers attempted to enact. Nearly all caregivers described using avoidance or distraction as an initial coping strategy to manage overwhelming emotions. Caregivers also expressed awareness of more adaptive strategies (e.g., cultivation of positive emotions, acceptance, self-education, and soliciting social and medical support) but had challenges employing them because of their heightened emotional distress. In response to substantial stressors, family caregivers of patients with SABI attempted to enact various psychological and behavioral coping strategies. They described avoidance and distraction as less helpful than other coping strategies but had difficulty engaging in alternative strategies because of their emotional distress. These findings can directly inform the development of additional resources to mitigate the long-term impact of acute psychological distress among this caregiver population.

Clinical Trajectories in Patients with Severe Acute Brain Injury Requiring Mechanical Ventilation: A Descriptive Analysis of a Single-Center Prospective Observational Cohort Study (P5-7.005)

<h3>Objective:</h3> To describe outcomes for patients with severe acute brain injury (SABI) who require mechanical ventilation (MV). <h3>Background:</h3> Patients with SABI often require MV due to impaired consciousness and insufficient airway protection, reflecting a substantial neurological injury. Outcomes for this high-acuity population have been insufficiently explored. <h3>Design/Methods:</h3> In this single-center prospective, observational cohort study at a level-1 trauma and comprehensive stroke center, we included consecutive adult patients with SABI, including traumatic brain injury (TBI), spontaneous intracranial hemorrhage (sICH), acute ischemic stroke (AIS), and subarachnoid hemorrhage (SAH), who required MV on admission between September-November 2021. We assessed in-hospital and 6–12 months mortality, tracheostomy and percutaneous gastrostomy tube (PEG) placement, and Extended Glasgow Outcome Score (GOS-E) at 6–12 months. <h3>Results:</h3> Overall, 90 patients (age 55 [SD 19], 73% male; median Glasgow Coma Scale on admission 7 [IQR 3,11]; 50% TBI, 20% sICH, 18% AIS, 12% SAH) were included. Median duration of MV was 2 days (IQR 1,7), with 40% requiring MV for £ 24 hours (G1), 37% 1–7 days (G2), and 23% &gt;7 days (G3). In-hospital mortality was 47% (n=42), 79% (33/42) died after withdrawal of life-sustaining treatments (30% £24 hours, 24% 1–7 days, 45% &gt;7 days). One third of survivors (30%, n=13) underwent PEG, 16% (n=7) tracheostomy. At 6–12 months, 51% (n=46) had died (51% TBI, 67% sICH, 44% AIS, 36% SAH; 44% G1, 55% G2, 57% G3); 57% of survivors (64% TBI, 50% sICH, 33% AIS, 71% SAH; 60% G1, 67% G2, 22% G3) had a GOS-E of 5–8. Among survivors who underwent PEG and tracheostomy, 54% and 29% had a GOS-E 5–8; all survivors who initially underwent tracheostomy were decannulated at 6–12 months. <h3>Conclusions:</h3> Mortality and long-term disability in patients with SABI who required MV were high and varied based on SABI subtype and duration of MV. <b>Disclosure:</b> Ms. Smith has nothing to disclose. Ms. JAMES has nothing to disclose. Dr. Matin has nothing to disclose. Dr. Sarhadi has nothing to disclose. Dr. Town has nothing to disclose. The institution of Dr. Creutzfeldt has received research support from NINDS. The institution of Dr. Creutzfeldt has received research support from NINR. Chiara Robba has nothing to disclose. Giuseppe Citerio has nothing to disclose. Dr. Lele has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for LifeCenter Northwest . Dr. Wahlster has nothing to disclose.