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Abstract The INSPIRE randomized clinical trial demonstrated that a high protein diet (HPRO) combined with neuromuscular electrical stimulation (NMES) attenuates muscle atrophy and may improve outcomes after aneurysmal subarachnoid hemorrhage We sought to identify specific metabolites mediating these effects. Blood samples were collected from subjects on admission prior to randomization to either standard of care (SOC; N = 12) or HPRO + NMES (N = 12) and at 7 days. Untargeted metabolomics were performed for each plasma sample. Sparse partial least squared discriminant analysis identified metabolites differentiating each group. Correlation coefficients were calculated between each metabolite and total protein per day and muscle volume. Multivariable models determined associations between metabolites and muscle volume. Unique metabolites (18) were identified differentiating SOC from HPRO + NMES. Of these, 9 had significant positive correlations with protein intake. In multivariable models, N-acetylleucine was significantly associated with preserved temporalis [OR 1.08 (95% CI 1.01, 1.16)] and quadricep [OR 1.08 (95% CI 1.02, 1.15)] muscle volume. Quinolinate was also significantly associated with preserved temporalis [OR 1.05 (95% CI 1.01, 1.09)] and quadricep [OR 1.04 (95% CI 1.00, 1.07)] muscle volume. N-acetylserine and β-hydroxyisovaleroylcarnitine were associated with preserved temporalis or quadricep volume. Metabolites defining HPRO + NMES had strong correlations with protein intake and were associated with preserved muscle volume.

Summary: Background: The inflammatory response in patients with traumatic brain injury (TBI) offers opportunities for stratification and intervention. Previous unselected approaches to immunomodulation in patients with TBI have not improved patient outcomes. Methods: Serum and plasma samples from two prospective, multi-centre observational studies of patients with TBI were used to discover (Collaborative European NeuroTrauma Effectiveness Research [CENTER-TBI], Europe) and validate (Transforming Research and Clinical Knowledge in Traumatic Brain Injury [TRACK-TBI] Pilot, USA) individual variations in the immune response using a multiplex panel of 30 inflammatory mediators. Mediators that were associated with unfavourable outcomes (Glasgow outcome score-extended [GOS-E] ≤ 4) were used for hierarchical clustering to identify patients with similar signatures. Findings: Two clusters were identified in both the discovery and validation cohorts, termed early-inflammatory and pauci-inflammatory. The early-inflammatory phenotype had higher concentrations of interleukin-6 (IL-6), IL-15, and monocyte chemoattractant protein 1 (MCP1). Patients with the early-inflammatory phenotype were older and more likely to have an unfavourable GOS-E at 6 months. There were no differences in the baseline injury severity scores between patients in each phenotype. A combined IL-15 and MCP1 signature identified patients with the early-inflammatory phenotype in both cohorts. Inflammatory processes mediated outcomes in older patients with moderate-severe TBI. Interpretation: Our findings offer a precision medicine approach for future clinical trials of immunomodulation in patients with TBI, by using inflammatory signatures to stratify patients. Funding: CENTER-TBI study was supported by the European Union 7th Framework Programme. TRACK-TBI is supported by the National Institute of Neurological Disorders and Stroke.

We performed a clinical-radiographic association study investigating the hypothesis that paroxysmal sympathetic hyperactivity (PSH) occurs in traumatic brain injury (TBI) patients with structural damage to the central autonomic network (CAN). To this end, we identified critically ill acute TBI patients who underwent magnetic resonance imaging (MRI) of the brain between January 2016 and July 2018. All patients were scored retrospectively according to the PSH-Assessment Measure (PSH-AM), which provides a clinical feature score, a diagnosis likelihood score, and a total score. All MRIs were reviewed for lesions within a priori CAN regions of interest, including the brainstem, ventral diencephalon, thalamus, medial temporal lobes, insula, anterior cingulate/medial prefrontal cortex, corpus callosum, and bilateral hemispheric white matter, on diffusion-weighted imaging (DWI), fluid attenuated inversion recovery (FLAIR), and susceptibility-weighted imaging (SWI) sequences. PSH-AM scores were compared using non-parametric tests according to lesion presence in each region and sequence. Imaging features independently associated with PSH-AM scores were ascertained from multivariable linear regression models using backwards elimination feature selection. The strongest predictive models were adjusted for known PSH risk factors including age, sex, and Glasgow Coma Scale (GCS), to determine the independent contribution of imaging features to PSH-AM scores. We found that of 128 patients meeting inclusion criteria, 60 (47%) were clinically diagnosed with PSH. PSH-AM diagnosis likelihood and total scores and clinical diagnosis were strongly associated with CAN lesions. The strongest multivariable model, adjusted for age, sex, and GCS, identified SWI lesions in the corpus callosum and medial temporal lobes as independent imaging predictors of PSH diagnosis likelihood. This exploratory study supports the hypothesis that structural damage to CAN regions is associated with the clinical syndrome of PSH after TBI, and provides foundational evidence for future data-driven studies.

IntroductionTraumatic brain injury (TBI) even in the mild form may result in long-lasting post-concussion symptoms. TBI is also a known risk to late-life neurodegeneration. Recent studies suggest that dysfunction in the glymphatic system, responsible for clearing protein waste from the brain, may play a pivotal role in the development of dementia following TBI. Given the diverse nature of TBI, longitudinal investigations are essential to comprehending the dynamic changes in the glymphatic system and its implications for recovery.MethodsIn this prospective study, we evaluated two promising glymphatic imaging markers, namely the enlarged perivascular space (ePVS) burden and Diffusion Tensor Imaging-based ALPS index, in 44 patients with mTBI at two early post-injury time points: approximately 14 days (14Day) and 6–12 months (6–12Mon) post-injury, while also examining their associations with post-concussion symptoms. Additionally, 37 controls, comprising both orthopedic patients and healthy individuals, were included for comparative analysis.ResultsOur key findings include: (1) White matter ePVS burden (WM-ePVS) and ALPS index exhibit significant correlations with age. (2) Elevated WM-ePVS burden in acute mTBI (14Day) is significantly linked to a higher number of post-concussion symptoms, particularly memory problems. (3) The increase in the ALPS index from acute (14Day) to the chronic (6–12Mon) phases in mTBI patients correlates with improvement in sleep measures. Furthermore, incorporating WM-ePVS burden and the ALPS index from acute phase enhances the prediction of chronic memory problems beyond socio-demographic and basic clinical information.ConclusionePVS burden and ALPS index offers distinct values in assessing glymphatic structure and activity. Early evaluation of glymphatic function could be crucial for understanding TBI recovery and developing targeted interventions to improve patient outcomes.

Objectives An estimated 14–23% of patients with traumatic brain injury (TBI) incur multiple lifetime TBIs. The relationship between prior TBI and outcomes in patients with moderate to severe TBI (msTBI) is not well delineated. We examined the associations between prior TBI, in-hospital mortality, and outcomes up to 12 months after injury in a prospective US msTBI cohort.Methods Data from hospitalized subjects with Glasgow Coma Scale score of 3–12 were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (enrollment period: 2014–2019). Prior TBI with amnesia or alteration of consciousness was assessed using the Ohio State University TBI Identification Method. Competing risk regressions adjusting for age, sex, psychiatric history, cranial injury and extracranial injury severity examined the associations between prior TBI and in-hospital mortality, with hospital discharged alive as the competing risk. Adjusted HRs (aHR (95% CI)) were reported. Multivariable logistic regressions assessed the associations between prior TBI, mortality, and unfavorable outcome (Glasgow Outcome Scale-Extended score 1–3 (vs. 4–8)) at 3, 6, and 12 months after injury.Results Of 405 acute msTBI subjects, 21.5% had prior TBI, which was associated with male sex (87.4% vs. 77.0%, p=0.037) and psychiatric history (34.5% vs. 20.7%, p=0.010). In-hospital mortality was 10.1% (prior TBI: 17.2%, no prior TBI: 8.2%, p=0.025). Competing risk regressions indicated that prior TBI was associated with likelihood of in-hospital mortality (aHR=2.06 (1.01–4.22)), but not with hospital discharged alive. Prior TBI was not associated with mortality or unfavorable outcomes at 3, 6, and 12 months.Conclusions After acute msTBI, prior TBI history is independently associated with in-hospital mortality but not with mortality or unfavorable outcomes within 12 months after injury. This selective association underscores the importance of collecting standardized prior TBI history data early after acute hospitalization to inform risk stratification. Prospective validation studies are needed.Level of evidence IV.Trial registration number NCT02119182.

OBJECTIVES:. Accurate classification of disorders of consciousness (DoC) is key in developing rehabilitation plans after brain injury. The Coma Recovery Scale—Revised (CRS-R) is a sensitive measure of consciousness validated in the rehabilitation phase of care. We tested the feasibility, safety, and impact of CRS-R-guided rehabilitation in the ICU for patients with DoC after acute hemorrhagic stroke. DESIGN:. Retrospective cohort study. SETTING:. This single-center study was conducted in the neurocritical care unit at the University of Maryland Medical Center. PATIENTS:. We analyzed records from consecutive patients with subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH), who underwent serial CRS-R assessments during ICU admission from April 1, 2018, to December 31, 2021, where CRS-R less than 8 is vegetative state/unresponsive wakefulness syndrome (VS/UWS); CRS-R greater than or equal to 8 is a minimally conscious state (MCS). INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Outcomes included adverse events during CRS-R evaluations and associations between CRS-R and discharge disposition, therapy-based function, and mobility. We examined the utility of CRS-R compared with other therapist clinical assessment tools in predicting discharge disposition. Seventy-six patients (22 SAH, 54 ICH, median age = 59, 50% female) underwent 276 CRS-R sessions without adverse events. Discharge to acute rehabilitation occurred in 4.4% versus 41.9% of patients with a final CRS-R less than 8 and CRS-R greater than or equal to 8, respectively (odds ratio [OR] 13.4; 95% CI, 2.7–66.1; p < 0.001). Patients with MCS on final CRS-R completed more therapy sessions during hospitalization and had improved mobility and functional performance. Compared with other therapy assessment tools, the CRS-R had the best performance in predicting discharge disposition (area under the curve: 0.83; 95% CI, 0.72–0.94; p < 0.0001). CONCLUSIONS:. Early neurorehabilitation guided by CRS-R appears to be feasible and safe in the ICU following hemorrhagic stroke complicated by DoC and may enhance access to inpatient rehabilitation, with the potential for lasting benefit on recovery. Further research is needed to assess generalizability and understand the impact on long-term outcomes.

Abstract Determination of prognosis in the triage process after traumatic brain injury (TBI) is difficult to achieve. Current severity measures like the Trauma and injury severity score (TRISS) and revised trauma score (RTS) rely on additional information from the Glasgow Coma Scale (GCS) and the Injury Severity Score (ISS) which may be inaccurate or delayed, limiting their usefulness in the rapid triage setting. We hypothesized that machine learning based estimations of GCS and ISS obtained through modeling of continuous vital sign features could be used to rapidly derive an automated RTS and TRISS. We derived variables from electrocardiograms (ECG), photoplethysmography (PPG), and blood pressure using continuous data obtained in the first 15 min of admission to build machine learning models of GCS and ISS (ML-GCS and ML-ISS). We compared the TRISS and RTS using ML-ISS and ML-GCS and its value using the actual ISS and GCS in predicting in-hospital mortality. Models were tested in TBI with systemic injury (head abbreviated injury scale (AIS) ≥ 1), and isolated TBI (head AIS ≥ 1 and other AIS ≤ 1). The area under the receiver operating characteristic curve (AUROC) was used to evaluate model performance. A total of 21,077 cases (2009–2015) were in the training set. 6057 cases from 2016 to 2017 were used for testing, with 472 (7.8%) severe TBI (GCS 3–8), 223 (3.7%) moderate TBI (GCS 9–12), and 5913 (88.5%) mild TBI (GCS 13–15). In the TBI with systemic injury group, ML-TRISS had similar AUROC (0.963) to TRISS (0.965) in predicting mortality. ML-RTS had AUROC (0.823) and RTS had AUROC 0.928. In the isolated TBI group, ML-TRISS had AUROC 0.977, and TRISS had AUROC 0.983. ML-RTS had AUROC 0.790 and RTS had AUROC 0.957. Estimation of ISS and GCS from machine learning based modeling of vital sign features can be utilized to provide accurate assessments of the RTS and TRISS in a population of TBI patients. Automation of these scores could be utilized to enhance triage and resource allocation during the ultra-early phase of resuscitation.

BackgroundClinicians working in intensive care units (ICUs) are immersed in a cacophony of alarms and a relentless onslaught of data. Within this frenetic environment, clinicians make high-stakes decisions using many data sources and are often oversaturated with information of varying quality. Traditional bedside monitors only depict static vital signs data, and these data are not easily viewable remotely. Clinicians must rely on separate nursing charts—handwritten or electric—to review physiological patterns, including signs of potential clinical deterioration. An automated physiological data viewer has been developed to provide at-a-glance summaries and to assist with prioritizing care for multiple patients who are critically ill. ObjectiveThis study aims to evaluate a novel vital signs viewer system in a level 1 trauma center by subjectively assessing the viewer’s utility in a high-volume ICU setting. MethodsICU attendings were surveyed during morning rounds. Physicians were asked to conduct rounds normally, using data reported from nurse charts and briefs from fellows to inform their clinical decisions. After the physician finished their assessment and plan for the patient, they were asked to complete a questionnaire. Following completion of the questionnaire, the viewer was presented to ICU physicians on a tablet personal computer that displayed the patient’s physiologic data (ie, shock index, blood pressure, heart rate, temperature, respiratory rate, and pulse oximetry), summarized for up to 72 hours. After examining the viewer, ICU physicians completed a postview questionnaire. In both questionnaires, the physicians were asked questions regarding the patient’s stability, status, and need for a higher or lower level of care. A hierarchical clustering analysis was used to group participating ICU physicians and assess their general reception of the viewer. ResultsA total of 908 anonymous surveys were collected from 28 ICU physicians from February 2015 to June 2017. Regarding physicians’ perception of whether the viewer enhanced the ability to assess multiple patients in the ICU, 5% (45/908) strongly agreed, 56.6% (514/908) agreed, 35.3% (321/908) were neutral, 2.9% (26/908) disagreed, and 0.2% (2/908) strongly disagreed. ConclusionsMorning rounds in a trauma center ICU are conducted in a busy environment with many data sources. This study demonstrates that organized physiologic data and visual assessment can improve situation awareness, assist clinicians with recognizing changes in patient status, and prioritize care.

Endotracheal intubation, frequently required during management of refractory status epilepticus (RSE), can be facilitated by anesthetic medications; however, their effectiveness for RSE control is unknown. We performed a single-center retrospective review of patients admitted to a neurocritical care unit (NCCU) who underwent in-hospital intubation during RSE management. Patients intubated with propofol, ketamine, or benzodiazepines, termed anti-seizure induction (ASI), were compared to patients who received etomidate induction (EI). The primary endpoint was clinical or electrographic seizures within 12 h post-intubation. We estimated the association of ASI on post-intubation seizure using logistic regression. A sub-group of patients undergoing electroencephalography during intubation was identified to evaluate the immediate effect of ASI on RSE. We screened 697 patients admitted to the NCCU for RSE and identified 148 intubated in-hospital (n = 90 ASI, n = 58 EI). There was no difference in post-intubation seizure (26 % (n = 23) ASI, 29 % (n = 17) EI) in the cohort, however, there was increased RSE resolution with ASI in 24 patients with electrographic RSE during intubation (ASI: 61 % (n = 11/18) vs EI: 0 % (n = 0/6), p =.016). While anti-seizure induction did not appear to affect post-intubation seizure occurrence overall, a sub-group of patients undergoing electroencephalography during intubation had a higher incidence of seizure cessation, suggesting potential benefit in an enriched population.

OBJECTIVES/GOALS: Super refractory status epilepticus (SRSE) is associated with high mortality, often due to withdrawal of life sustaining therapy (WLST) based on perceived poor neurological prognosis. Factors influencing decision making are underreported and poorly understood. We surveyed clinicians who treat SRSE to identify factors that influence WLST. METHODS/STUDY POPULATION: Health care providers (HCP), including physicians, pharmacists, and advanced practice providers, who treat SRSE answered a 51-question survey on respondent demographics, institutional characteristics and SRSE management that was distributed though professional societies. Respondents described approaches to prognostication and rated the importance of clinical factors in the management of two hypothetical clinical cases followed by their prediction of recovery potential for the same two cases. Neurointensivists and other HCP responses were compared using descriptive statistics to differentiate group characteristics; a p-value

The relationship between systemic inflammation and secondary injury in traumatic brain injury (TBI) is complex. We investigated associations between inflammatory markers and clinical confirmation of TBI diagnosis and prognosis. The prospective TRACK-TBI Pilot (Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot) study enrolled TBI patients triaged to head computed tomography (CT) and received blood draw within 24?h of injury. Healthy controls (HCs) and orthopedic controls (OCs) were included. Thirty-one inflammatory markers were analyzed from plasma. Area under the receiver operating characteristic curve (AUC) was used to evaluate discriminatory ability. AUC >0.7 was considered acceptable. Criteria included: TBI diagnosis (vs. OC/HC); moderate/severe vs. mild TBI (Glasgow Coma Scale; GCS); radiographic TBI (CT positive vs. CT negative); 3- and 6-month Glasgow Outcome Scale-Extended (GOSE) dichotomized to death/greater relative disability versus less relative disability (GOSE 1?4/5?8); and incomplete versus full recovery (GOSE

The use of UCH-L1 detection with point-of-care (POC) assay alone has not been characterized for clinical use. This study compares the accuracies of POC UCH-L1 and Neuron-Specific Enolase (NSE) Elecsys® levels for identifying TBI patients with structural abnormalities on neuroimaging.The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Phase 1 Cohort, enrolled 1375 TBI patients (GCS 3–15) presenting to one of 18 US Level I trauma centers within 24 h of injury who had an admission head CT; blood samples were collected, along with 122 orthopedic and 209 healthy controls. The TBI cohort consisted of 810 CT-negative (CT-) and 549 CT-positive (CT+) subjects. Of the CT- subjects who had MRIs, 121 were MRI-positive (MRI+) and 333 were MRI-negative (MRI-). UCH-L1 POC showed best diagnostic performance for CT + versus CT-, 0–8 h post-injury with an AUC of 0·779 [0·708–0.850] when compared to the 0–25 h interval, with an AUC of 0.684 [0.655–0.712]. NSE assay has an AUC of 0.695 [0.619–0.770] for the 0–8 h interval and 0.634 [0.603–0.665] for the 0–25 h interval. During the first 8 after injury, POC UCH-L1 outperforms NSE in identifying TBI patients with structural abnormalities on neuroimaging.

Abstract Secondary neurologic decline (ND) after traumatic brain injury (TBI) is independently associated with outcome, but robust predictors of ND are lacking. In this retrospective analysis of consecutive isolated TBI admissions to the R. Adams Cowley Shock Trauma Center between November 2015 and June 2018, we aimed to develop a triage decision support tool to quantify risk for early ND. Three machine learning models based on clinical, physiologic, or combined characteristics from the first hour of hospital resuscitation were created. Among 905 TBI cases, 165 (18%) experienced one or more ND events (130 clinical, 51 neurosurgical, and 54 radiographic) within 48 h of presentation. In the prediction of ND, the clinical plus physiologic data model performed similarly to the physiologic only model, with concordance indices of 0.85 (0.824–0.877) and 0.84 (0.812–0.868), respectively. Both outperformed the clinical only model, which had a concordance index of 0.72 (0.688–0.759). This preliminary work suggests that a data-driven approach utilizing physiologic and basic clinical data from the first hour of resuscitation after TBI has the potential to serve as a decision support tool for clinicians seeking to identify patients at high or low risk for ND.

OBJECTIVES:. We aimed to 1) describe patterns of beta-blocker utilization among critically ill patients following moderate–severe traumatic brain injury (TBI) and 2) examine the association of early beta-blocker exposure with functional and clinical outcomes following injury. DESIGN:. Retrospective cohort study. SETTING:. ICUs at 18 level I, U.S. trauma centers in the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study. PATIENTS:. Greater than or equal to 17 years enrolled in the TRACK-TBI study with moderate–severe TBI (Glasgow Coma Scale of

Mild (mTBI) traumatic brain injury (TBI) accounts for the majority of all TBI cases. Evidence has suggested that patients with mTBI can suffer from long-lasting cognitive deficits, persistent symptoms, and decreased quality of life. Sleep disorders are commonly observed after TBI, with the prevalence rate of sleep disturbances in persons with TBI being much higher than that in the general population. Poor sleep quality can impair cognitive functions in the general population. This effect of sleep disturbances may impede the recovery processes in the population with TBI. The objective of this study is to add to our understanding of the relationship between self-reported sleep problems and other post-concussion symptoms and look at the association between early sleep problems and long-term outcomes in mTBI. Post-concussion symptoms, neurocognitive functions, level of global outcomes, and rating of satisfaction of life were assessed in 64 patients with mTBI. The results revealed that the presence of sleep disturbances co-occur with an increased level of overall post-concussion symptoms at the subacute stage of mTBI, particularly with symptoms including poor concentration, memory problems, and irritability. In addition, sleep disturbance at the subacute stage is associated with persistent poor concentration and memory problems, as well as worse neurocognitive function, slower overall recovery, and lower satisfactory of life at the long term. Our findings suggest that sleep disturbance can be a prognostic factor of long-term outcomes after mTBI. Early interventions to improve sleep quality can have potential benefits to facilitate the recovery process from mTBI.

Introduction: Targeted temperature management plays an important role in the treatment of myriad critical illnesses. Non-invasive, quick-onset options for isolated brain temperature control remain lacking. The goal of this study was to assess the safety and efficacy of a novel intranasal high flow cooled air device using a large animal model. Methods: Yorkshire swine were instrumented with temperature probes in the rectum, brain, ear, and snout, and a novel intranasal cooled air device was applied to half. The primary outcome was effectiveness of brain and snout cooling by the study device. Secondary outcomes included tympanic cooling and absence of rectal cooling, CT, CT perfusion, and histologic evidence of injury in the short- and medium-term. Results: 10 animals (54.7 kgs.+/- 19.4 SD) underwent non-survival evaluation, 3 underwent delayed evaluation (56.1 kgs.+/-6.4). From baseline to cooling period, intranasal (38.1 °C vs. 34.9 °C, p = 0.01), intracranial (38.6 °C vs. 37.2 °C, p = 0.01) and tympanic temperatures (38.3 °C vs. 37.5 °C, p = 0.01) decreased, while rectal temperature remained unchanged.After cooling, nasal temperature (34.9 °C vs. 37.6 °C, p = 0.004) and intracranial temperatures (37.2 °C vs. 37.9 °C, p = 0.01) increased. Rectal temperatures remained unchanged. A mixed effects model showed association between temperature and study period (p

OBJECTIVES/GOALS: Multiple induction agents can facilitate rapid sequence intubation (RSI) in management of refractory status epilepticus (rSE), many which have anti-seizure properties. We examine the anti-seizure efficacy and safety of induction agents used during RSI in the management of rSE. METHODS/STUDY POPULATION: We conducted a single-center retrospective review of patients admitted to the neuro-ICU intubated for management of rSE. Propofol, ketamine and benzodiazepines were considered anti-seizure medication (ASMs), etomidate was not. Patients were treated with propofol or midazolam following intubation. Our primary outcome was clinical or electrographic recurrence of SE within 12 hours of intubation. Exploratory outcomes included time to recover command following, duration of mechanical ventilation (MV) and complications related to intubation. We used multivariable logistical regression to evaluate outcomes between patients induced with ASMs and etomidate. A Fisher exact test was used to compare rSE cessation in a subset of patients with continuous electroencephalography (cEEG) at the time of intubation. RESULTS/ANTICIPATED RESULTS: We identified 149 induced for RSI in management of rSE: 88 patients intubated using ASMs (propofol,n=56; ketamine,n=14; benzodiazepines,n=18) and 61 patients intubated with etomidate. Forty-one patients had recurrence (29.9% ASMS, 24.6% etomidate). The induction agent was not associated with recurrence of SE, time to command following, or duration of MV. Twenty-seven patients had cEEG monitoring at the time of intubation. Sixteen of the 22 patients induced with ASMs had cessation of rSE with induction, while 1 of 5 intubated with etomidate had cessation (Fisher exact test, p=0.047). There were 34 patients with post-induction hypotension (22.9% ASMs, 22.9% etomidate (Fisher exact test, p=1)). DISCUSSION/SIGNIFICANCE: Induction with an anti-seizure medication during intubation was more likely to halt rSE, but did not decrease the likelihood of clinical or electrographic recurrence of rSE and may not affect time to recovery of command following or duration of MV.

Background and purposeTherapeutic hypothermia (TH), or targeted temperature management (TTM), is a classic treatment option for reducing inflammation and potentially other destructive processes across a wide range of pathologies, and has been successfully used in numerous disease states. The ability for TH to improve neurological outcomes seems promising for inflammatory injuries but has yet to demonstrate clinical benefit in the intracerebral hemorrhage (ICH) patient population. Minimally invasive ICH evacuation also presents a promising option for ICH treatment with strong preclinical data but has yet to demonstrate functional improvement in large randomized trials. The biochemical mechanisms of action of ICH evacuation and TH appear to be synergistic, and thus combining hematoma evacuation with cooling therapy could provide synergistic benefits. The purpose of this working group was to develop consensus recommendations on optimal clinical trial design and outcomes for the use of therapeutic hypothermia in ICH in conjunction with minimally invasive ICH evacuation.MethodsAn international panel of experts on the intersection of critical-care TH and ICH was convened to analyze available evidence and form a consensus on critical elements of a focal cooling protocol and clinical trial design. Three focused sessions and three full-group meetings were held virtually from December 2020 to February 2021. Each meeting focused on a specific subtopic, allowing for guided, open discussion.ResultsThese recommendations detail key elements of a clinical cooling protocol and an outline for the roll-out of clinical trials to test and validate the use of TH in conjunction with hematoma evacuation as well as late-stage protocols to improve the cooling approach. The combined use of systemic normothermia and localized moderate (33.5°C) hypothermia was identified as the most promising treatment strategy.ConclusionsThese recommendations provide a general outline for the use of TH after minimally invasive ICH evacuation. More research is needed to further refine the use and combination of these promising treatment paradigms for this patient population.

OBJECTIVES/GOALS: Accurate classification of disorders of consciousness (DoC) is key in developing rehabilitation plans following brain injury. The Coma Recovery Scale-Revised (CRS-R) is a sensitive measure of consciousness. We explore feasibility, safety and impact of CRS-R guided rehab in hemorrhagic stroke patients with DoC and evaluate predictors of recovery. METHODS/STUDY POPULATION: Consecutive patients with non-traumatic hemorrhagic stroke, defined as subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH), receiving serial CRS-R assessments during their ICU stay at University of Maryland Medical Center from 2017-2021 were retrospectively identified. Outcomes of interest included the association with CRS-R and discharge disposition, therapy-based function and mobility and occurrence of safety events during CRS assessment. We also examined the association between CRS-R and physiological and anatomical injury pattern on electroencephalography (EEG) and magnetic resonance imaging (MRI), respectively. CRS-R RESULTS/ANTICIPATED RESULTS: 76 patients with≥2 CRS-R assessments were identified (22 SAH, 54 ICH, median age = 59, 50% female). Median CRS-R completed was 3 with no SAEs identified during sessions. We identified 4 patterns: persistent VS/UWS (49%), persistent MCS or better (13%), emergence from VS/UWS to MCS or better (27%) and regression from MCS or better to VS/UWS (11%). Persistent low CRS-R correlated with older age in SAH (p=0.01), female gender in ICH (p=0.04), and history of diabetes (p=0.01). 2% of patients with final CRS-R DISCUSSION/SIGNIFICANCE: Early neurorehabilitation guided by CRS-R appears to be feasible and safe acutely following hemorrhagic stroke complicated by prolonged DoC and may enhance access to inpatient rehabilitation with a lasting benefit on recovery. Further characterization of DoC patterns and their correlation to clinical markers, including EEG and MRI is needed.

Objectives: To assess trainees’ performance in managing a patient with post-cardiac arrest complicated by status epilepticus. Methods: In this prospective, observational, single-center simulation-based study, trainees ranging from sub interns to critical care fellows evaluated and managed a post cardiac arrest patient, complicated by status epilepticus. Critical action items were developed by a modified Delphi approach based on American Heart Association guidelines and the Neurocritical Care Society’s Emergency Neurological Life Support protocols. The primary outcome measure was the critical action item sum score. We sought validity evidence to support our findings by including attending neurocritical care physicians and comparing performance across four levels of training. Results: Forty-nine participants completed the simulation. The mean sum of critical actions completed by trainees was 10/21 (49%). Eleven (22%) trainees verbalized a differential diagnosis for the arrest. Thirty-two (65%) reviewed the electrocardiogram, recognized it as abnormal, and consulted cardiology. Forty trainees (81%) independently decided to start temperature management, but only 20 (41%) insisted on it when asked to reconsider. There was an effect of level of training on critical action checklist sum scores (novice mean score [standard deviation (SD)] = 4.8(1.8) vs. intermediate mean score (SD) = 10.4(2.1) vs. advanced mean score (D) = 11.6(3.0) vs. expert mean score (SD) = 14.7(2.2)) Conclusions: High-fidelity manikin-based simulation holds promise as an assessment tool in the performance of post-cardiac arrest care.

Limited data exist on the effect of continuous renal replacement therapy (CRRT) methods on anti‐epileptic drug pharmacokinetics (PK). This prospective practice‐based PK study aims to assess the impact of continuous venovenous hemofiltration (CVVH), a modality of CRRT, on levetiracetam PK in critically ill patients and to derive individualized dosing recommendations. Eleven patients receiving oral or intravenous levetiracetam and CVVH in various intensive care units at a large academic medical center were enrolled to investigate the need for dosing adjustments. Prefilter, postfilter, and ultrafiltrate samples were obtained before dosing, after the completion of the infusion or 1‐hour postoral dose, and up to 6 additional time points postinfusion or postoral administration. Patient‐specific blood and ultrafiltrate flow rates and laboratory values were also collected at the time of sampling. The average sieving coefficient (SC) for levetiracetam was 0.89 ± 0.1, indicating high filter efficiency. Six of the 11 patients experienced concentrations outside the reported therapeutic range (12–46 mg/L). The average volume of distribution was 0.73 L/kg. CVVH clearance contributes a major fraction of the total levetiracetam clearance (36–73%) in neurocritically ill patients. The average bias and precision of the estimated vs. observed total clearance value was ~ 10.6% and 21.5%. Major dose determinants were identified to be SC and effluent flow rate. Patients with higher ultrafiltrate rates will have increased drug clearance and, therefore, will require higher doses in order to match exposures seen in patients with normal renal function.

Background Variation exists in outcomes following out‐of‐hospital cardiac arrest (OHCA), but whether racial and ethnic disparities exist in post‐arrest provision of targeted temperature management (TTM) is unknown. Methods and Results We performed a retrospective analysis of a prospectively collected cohort of patients who survived to admission following OHCA from the Cardiac Arrest Registry to Enhance Survival, whose catchment area represents ~50% of the United States from 2013‐2019. Our primary exposure was race/ethnicity and primary outcome was utilization of TTM. We built a mixed‐effects model with both state of arrest and admitting hospital modeled as random intercepts to account for clustering. Among 96,695 patients (24.6% Black, 8.0% Hispanic/Latino, 63.4% White), a smaller percentage of Hispanic/Latino patients received TTM than Black or White patients (37.5% vs. 45.0 % vs 43.3%, P < .001) following OHCA. In the mixed‐effects model, Black patients (Odds Ratio [OR] 1.153, 95% Confidence Interval [CI] 1.102‐1.207, P < .001) and Hispanic/Latino patients (OR 1.086, 95% CI 1.017‐1.159, P < .001) were slightly more likely to receive TTM compared to White patients, perhaps due to worse admission neurological status. We did find community level disparity as Hispanic/Latino‐serving hospitals (defined as the top decile of hospitals that cared for the highest proportion of Hispanic/Latino patients) provided less TTM (OR 0.587, 95% CI 0.474 to 0.742, P < .001). Conclusions Reassuringly, we did not find evidence of intrahospital or interpersonal racial or ethnic disparity in the provision of TTM. However, we did find inter‐hospital, community level disparity. Hispanic/Latino‐serving hospitals provided less guideline‐recommended TTM after OHCA.

Background: Regional cerebral oxygen saturation (rScO2) measured by near-infrared spectroscopy (NIRS) can be used to monitor brain oxygenation in extracorporeal membrane oxygenation (ECMO). ECMO patients that develop acute brain injuries (ABIs) are observed to have worse outcomes. We evaluated the association between rScO2 and ABI in venoarterial (VA) ECMO patients.Methods: We retrospectively reviewed prospectively-collected NIRS data from patients undergoing VA ECMO from April 2016 to October 2016. Baseline demographics, ECMO and clinical characteristics, cerebral oximetry data, neuroradiographic images, and functional outcomes were reviewed for each patient. rScO2 desaturations were defined as a >25% decline from baseline or an absolute value < 40% and quantified by frequency, duration, and area under the curve per hour of NIRS monitoring (AUC rate, rScO2*min/h). The primary outcome was ABI, defined as abnormalities noted on brain computerized tomography (CT) or magnetic resonance imaging (MRI) obtained during or after ECMO therapy.Results: Eighteen of Twenty patients who underwent NIRS monitoring while on VA ECMO were included in analysis. Eleven patients (61%) experienced rScO2 desaturations. Patients with desaturations were more frequently female (73 vs. 14%, p = 0.05), had acute liver dysfunction (64 vs. 14%, p = 0.05), and higher peak total bilirubin (5.2 mg/dL vs. 1.4 mg/dL, p = 0.02). Six (33%) patients exhibited ABI, and had lower pre-ECMO Glasgow Coma Scale (GCS) scores (5 vs. 10, p = 0.03) and higher peak total bilirubin levels (7.3 vs. 1.4, p = 0.009). All ABI patients experienced rScO2 desaturation while 42% of patients without ABI experienced desaturation (p = 0.04). ABI patients had higher AUC rates than non-ABI patients (right hemisphere: 5.7 vs. 0, p = 0.01, left hemisphere: 119 vs. 0, p = 0.06), more desaturation events (13 vs. 0, p = 0.05), longer desaturation duration (2:33 vs. 0, p = 0.002), and more severe desaturation events with rScO2 < 40 (9 vs. 0, p = 0.05). Patients with ABI had lower GCS scores (post-ECMO initiation) before care withdrawal or discharge than those without ABI (10 vs. 15, p = 0.02).Conclusions: The presence and burden of cerebral desaturations noted on NIRS cerebral oximetry are associated with secondary neurologic injury in adults undergoing VA ECMO.

Background: In the acute resuscitation period after traumatic brain injury (TBI), one of the goals is to identify those at risk for secondary neurological decline (ND), represented by a constellation of clinical signs that can be identified as objective events related to secondary brain injury and independently impact outcome. We investigated whether continuous vital sign variability and waveform analysis of the electrocardiogram (ECG) or photoplethysmogram (PPG) within the first hour of resuscitation may enhance the ability to predict ND in the initial 48 hours after traumatic brain injury (TBI).Methods: Retrospective analysis of ND in TBI patients enrolled in the prospective Oximetry and Noninvasive Predictors Of Intervention Need after Trauma (ONPOINT) study. ND was defined as any of the following occurring in the first 48 h: new asymmetric pupillary dilatation (>2 mm), 2 point GCS decline, interval worsening of CT scan as assessed by the Marshall score, or intervention for cerebral edema. Beat-to-beat variation of ECG or PPG, as well as waveform features during the first 15 and 60 min after arrival in the TRU were analyzed to determine physiologic parameters associated with future ND. Physiologic and admission clinical variables were combined in multivariable logistic regression models predicting ND and inpatient mortality.Results: There were 33 (17%) patients with ND among 191 patients (mean age 43 years old, GCS 13, ISS 12, 69% men) who met study criteria. ND was associated with ICU admission (P < 0.001) and inpatient mortality (P < 0.001). Both ECG (AUROC: 0.84, 95% CI: 0.76,0.93) and PPG (AUROC: 0.87, 95% CI: 0.80, 0.93) analyses during the first 15 min of resuscitation demonstrated a greater ability to predict ND then clinical characteristics alone (AUROC: 0.69, 95% CI: 0.59, 0.8). Age (P = 0.02), Marshall score (P = 0.001), penetrating injury (P = 0.02), and predictive probability for ND by PPG analysis at 15 min (P = 0.03) were independently associated with inpatient mortality.Conclusions: Analysis of variability and ECG or PPG waveform in the first minutes of resuscitation may represent a non-invasive early marker of future ND.

IntroductionWe sought to determine whether compliance with scheduled nimodipine in subarachnoid hemorrhage patients impacted patient outcomes, with the intent of guiding future nimodipine management in patients who experience nimodipine-induced hypotension.MethodsWe performed a retrospective analysis of 118 consecutive aneurysmal subarachnoid hemorrhage patients treated with the Maryland Low-Dose IV Heparin Infusion Protocol. Patients were categorized into three independent nimodipine compliance groups: ≥1 dose held, ≥1 dose split, and no missed or split-doses. A split-dose was defined as 30 mg of nimodipine administered every 2 h. Our primary outcome was discharge to home. Bivariate and multivariable logistic regression analyses were used to assess predictors of discharge disposition as a function of nimodipine compliance.ResultsOf the 118 patients, 20 (17%) received all nimodipine doses, 6 (5%) received split-doses but never had a full dose held, and 92 (78%) had ≥1 dose held. Forty-five percent of patients were discharged to home, including 75% who received all doses, 67% who received ≥1 split-doses, and 37% with ≥1 missed doses (p = 0.003). Multivariable analysis showed that, along with age and World Federation of Neurosurgical Societies grade, nimodipine compliance was an independent predictor of clinical outcome; compared to missing one or more nimodipine doses, full dosing compliance was associated with increased odds of discharge to home (odds ratio 5.20; 95% confidence intervals 1.46–18.56).ConclusionIn aneurysmal subarachnoid hemorrhage patients with modified Fisher scores 2 through 4 who are cotreated with a low-dose heparin infusion, full compliance with nimodipine dosing was associated with increased odds of discharge to home.