Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP): study protocol for a multicenter, randomized, adaptive allocation clinical trial to identify the optimal duration of induced hypothermia for neuroprotection in comatose, adult survivors of after out-of-hospital cardiac arrest.

Background: Cardiac arrest is a common and devastating emergency of both the heart and brain. More than 380,000 patients suffer out-of-hospital cardiac arrest annually in the United States. Induced cooling of comatose patients markedly improved neurological and functional outcomes in pivotal randomized clinical trials, but the optimal duration of therapeutic hypothermia has not yet been established. Methods: This study is a multi-center randomized, response-adaptive, duration (dose) finding, comparative effectiveness clinical trial with blinded outcome assessment. We investigate two populations of adult comatose survivors of cardiac arrest to ascertain the shortest duration of cooling that provides the maximum treatment effect. The design is based on a statistical model of response as defined by the primary endpoint, a weighted 90-day mRS (modified Rankin Scale, a measure of neurologic disability), across the treatment arms. Subjects will initially be equally randomized between 12, 24, and 48 hours of therapeutic cooling. After the first 200 subjects have been randomized, additional treatment arms between 12 and 48 hours will be opened and patients will be allocated, within each initial cardiac rhythm type (shockable or non-shockable), by response adaptive randomization. As the trial continues, shorter and longer duration arms may be opened. A maximum sample size of 1800 subjects is proposed. Secondary objectives are to characterize: the overall safety and adverse events associated with duration of cooling, the effect on neuropsychological outcomes, and the effect on patient reported quality of life measures. Discussion: In-vitro and in-vivo studies have shown the neuroprotective effects of therapeutic hypothermia for cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having a good outcome. If the treatment effect of cooling is increasing across duration, for at least some set of durations, then this provides evidence of the efficacy of cooling itself versus normothermia, even in the absence of a normothermia control arm, confirming previous RCTs for OHCA survivors of shockable rhythms and provides the first prospective controlled evidence of efficacy in those without initial shockable rhythms. Trial registration: ClinicalTrials.gov (NCT04217551, 2019-12-30).

Methods of Evaluating EEG Reactivity in Adult Intensive Care Units: A Review.

PURPOSE: EEG reactivity (EEG-R) has become widely used in intensive care units for diagnosing and prognosticating patients with disorders of consciousness. Despite efforts toward standardization, including the establishment of terminology for critical care EEG in 2012, the processes of testing and interpreting EEG-R remain inconsistent. METHODS: A review was conducted on PubMed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria consisted of articles published between January 2012, and November 2022, testing EEG-R on adult intensive care unit patients. Exclusion criteria included articles focused on highly specialized stimulation equipment or animal, basic science, or small case report studies. The Quality In Prognostic Studies tool was used to assess risk of bias. RESULTS: One hundred and five articles were identified, with 26 variables collected for each. EEG-R testing varied greatly, including the number of stimuli (range: 1-8; 26 total described), stimulus length (range: 2-30 seconds), length between stimuli (range: 10 seconds-5 minutes), frequency of stimulus application (range: 1-9), frequency of EEG-R testing (range: 1-3 times daily), EEG electrodes (range: 4-64), personnel testing EEG-R (range: neurophysiologists to nonexperts), and sedation protocols (range: discontinuing all sedation to no attempt). EEG-R interpretation widely varied, including EEG-R definitions and grading scales, personnel interpreting EEG-R (range: EEG specialists to nonneurologists), use of quantitative methods, EEG filters, and time to detect EEG-R poststimulation (range: 1-30 seconds). CONCLUSIONS: This study demonstrates the persistent heterogeneity of testing and interpreting EEG-R over the past decade, and contributing components were identified. Further many institutional efforts must be made toward standardization, focusing on the reproducibility and unification of these methods, and detailed documentation in the published literature.

Suspected autoimmune encephalitis: A retrospective study of patients referred for therapeutic plasma exchange.

INTRODUCTION: Autoimmune encephalitis (AE) comprises a heterogeneous group of autoantibody-mediated disorders targeting the brain parenchyma. Therapeutic plasma exchange (TPE), one of several first-line therapies for AE, is often initiated when AE is suspected, albeit prior to an established diagnosis. We sought to characterize the role of TPE in the treatment of suspected AE. METHODS: A single-center, retrospective analysis was performed of adults (≥18 years) who underwent at least one TPE procedure for "suspected AE." The following parameters were extracted and evaluated descriptively: clinicopathologic characteristics, treatment course, TPE-related adverse events, outcomes (e.g., modified Rankin scale [mRS]), and diagnosis once investigation was complete. RESULTS: A total of 37 patients (median age 56 years, range 28-77 years, 62.2% male) were evaluated. Autoimmune antibody testing was positive in serum for 43.2% (n = 16) and cerebrospinal fluid for 29.7% (n = 11). Patients underwent a median of five TPE procedures (range 3-16), with 97.3% (n = 36) via a central line and 21.6% (n = 8) requiring at least one unit of plasma as replacement fluid. Fifteen patients (40.5%) experienced at least one TPE-related adverse event. Compared with mRS at admission, the mRS at discharge was improved in 21.6% (n = 8), unchanged in 59.5% (n = 22), or worse in 18.9% (n = 7). Final diagnosis of AE was determined to be definite in 48.6% (n = 18), probable in 8.1% (n = 3) and possible in 27.0% (n = 10). Six (16.2%) patients were ultimately determined to have an alternate etiology. CONCLUSION: Empiric TPE for suspected AE is generally well-tolerated. However, its efficacy remains uncertain in the absence of controlled trials, particularly in the setting of seronegative disease.

Clinicians' approach to predicting post-cardiac arrest outcomes for patients enrolled in a United States clinical trial.

PURPOSE: Perceived poor prognosis can lead to withdrawal of life-sustaining therapies (WLST) in patients who might otherwise recover. We characterized clinicians' approach to post-arrest prognostication in a multicenter clinical trial. METHODS: Semi-structured interviews were conducted with clinicians who treated a comatose post-cardiac arrest patient enrolled in the Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (ICECAP) trial (NCT04217551). Two authors independently analyzed each interview using inductive and deductive coding. The clinician reported how they arrived at a prognosis for the specific patient. We summarized the frequency with which clinicians reported using objective diagnostics to formulate their prognosis, and compared the reported approaches to established guidelines. Each respondent provided demographic information and described local neuroprognostication practices. RESULTS: We interviewed 30 clinicians at 19 US hospitals. Most claimed adherence to local hospital neuroprognostication protocols (n = 19). Prognostication led to WLST for perceived poor neurological prognosis in 15/30 patients, of whom most showed inconsistencies with guidelines or trial recommendations, respectively. In 10/15 WLST cases, clinicians reported relying on multimodal testing. A prevalent theme was the use of "clinical gestalt," defined as prognosticating based on a patient's overall appearance or a subjective impression in the absence of objective data. Many clinicians (21/30) reported using clinical gestalt for initial prognostication, with 9/21 expressing high confidence initially. CONCLUSION: Clinicians in our study state they follow neuroprognostication guidelines in general but often do not do so in actual practice. They reported clinical gestalt frequently informed early, highly confident prognostic judgments, and few objective tests changed initial impressions. Subjective prognostication may undermine well-designed trials.

Continuous Monitoring of Cerebral Autoregulation in Adults Supported by Extracorporeal Membrane Oxygenation.

BACKGROUND: Impaired cerebral autoregulation (CA) is one of several proposed mechanisms of acute brain injury in patients supported by extracorporeal membrane oxygenation (ECMO). The primary aim of this study was to determine the feasibility of continuous CA monitoring in adult ECMO patients. Our secondary aims were to describe changes in cerebral oximetry index (COx) and other metrics of CA over time and in relation to functional neurologic outcomes. METHODS: This is a single-center prospective observational study. We measured COx, a surrogate measurement of cerebral blood flow measured by near-infrared spectroscopy, which is an index of CA derived from the moving correlation between mean arterial pressure (MAP) and slow waves of regional cerebral oxygen saturation. A COx value that approaches 1 indicates impaired CA. Using COx, we determined the optimal MAP (MAPOPT) and lower and upper limits of autoregulation for individual patients. These measurements were examined in relation to modified Rankin Scale (mRS) scores. RESULTS: Fifteen patients (median age 57 years [interquartile range 47-69]) with 150 autoregulation measurements were included for analysis. Eleven were on veno-arterial ECMO (VA-ECMO), and four were on veno-venous ECMO (VV-ECMO). Mean COx was higher on postcannulation day 1 than on day 2 (0.2 vs. 0.09, p < 0.01), indicating improved CA over time. COx was higher in VA-ECMO patients than in VV-ECMO patients (0.12 vs. 0.06, p = 0.04). Median MAPOPT for the entire cohort was highly variable, ranging from 55 to 110 mm Hg. Patients with mRS scores 0-3 (good outcome) at 3 and 6 months spent less time outside MAPOPT compared with patients with mRS scores 4-6 (poor outcome) (74% vs. 82%, p = 0.01). The percentage of time when observed MAP was outside the limits of autoregulation was higher on postcannulation day 1 than on day 2 (18.2% vs. 3.3%, p < 0.01). CONCLUSIONS: In ECMO patients, it is feasible to monitor CA continuously at the bedside. CA improved over time, most significantly between postcannulation days 1 and 2. CA was more impaired in VA-ECMO patients than in VV-ECMO patients. Spending less time outside MAPOPT may be associated with achieving a good neurologic outcome.

Critical Care Management of Patients After Cardiac Arrest: A Scientific Statement From the American Heart Association and Neurocritical Care Society.

The critical care management of patients after cardiac arrest is burdened by a lack of high-quality clinical studies and the resultant lack of high-certainty evidence. This results in limited practice guideline recommendations, which may lead to uncertainty and variability in management. Critical care management is crucial in patients after cardiac arrest and affects outcome. Although guidelines address some relevant topics (including temperature control and neurological prognostication of comatose survivors, 2 topics for which there are more robust clinical studies), many important subject areas have limited or nonexistent clinical studies, leading to the absence of guidelines or low-certainty evidence. The American Heart Association Emergency Cardiovascular Care Committee and the Neurocritical Care Society collaborated to address this gap by organizing an expert consensus panel and conference. Twenty-four experienced practitioners (including physicians, nurses, pharmacists, and a respiratory therapist) from multiple medical specialties, levels, institutions, and countries made up the panel. Topics were identified and prioritized by the panel and arranged by organ system to facilitate discussion, debate, and consensus building. Statements related to postarrest management were generated, and 80% agreement was required to approve a statement. Voting was anonymous and web based. Topics addressed include neurological, cardiac, pulmonary, hematological, infectious, gastrointestinal, endocrine, and general critical care management. Areas of uncertainty, areas for which no consensus was reached, and future research directions are also included. Until high-quality studies that inform practice guidelines in these areas are available, the expert panel consensus statements that are provided can advise clinicians on the critical care management of patients after cardiac arrest.

Critical Care Management of Patients After Cardiac Arrest: A Scientific Statement from the American Heart Association and Neurocritical Care Society.

The critical care management of patients after cardiac arrest is burdened by a lack of high-quality clinical studies and the resultant lack of high-certainty evidence. This results in limited practice guideline recommendations, which may lead to uncertainty and variability in management. Critical care management is crucial in patients after cardiac arrest and affects outcome. Although guidelines address some relevant topics (including temperature control and neurological prognostication of comatose survivors, 2 topics for which there are more robust clinical studies), many important subject areas have limited or nonexistent clinical studies, leading to the absence of guidelines or low-certainty evidence. The American Heart Association Emergency Cardiovascular Care Committee and the Neurocritical Care Society collaborated to address this gap by organizing an expert consensus panel and conference. Twenty-four experienced practitioners (including physicians, nurses, pharmacists, and a respiratory therapist) from multiple medical specialties, levels, institutions, and countries made up the panel. Topics were identified and prioritized by the panel and arranged by organ system to facilitate discussion, debate, and consensus building. Statements related to postarrest management were generated, and 80% agreement was required to approve a statement. Voting was anonymous and web based. Topics addressed include neurological, cardiac, pulmonary, hematological, infectious, gastrointestinal, endocrine, and general critical care management. Areas of uncertainty, areas for which no consensus was reached, and future research directions are also included. Until high-quality studies that inform practice guidelines in these areas are available, the expert panel consensus statements that are provided can advise clinicians on the critical care management of patients after cardiac arrest.

Continuous Monitoring of Cerebral Autoregulation in Adults Supported by Extracorporeal Membrane Oxygenation.

Background: Impaired cerebral autoregulation (CA) is one of several proposed mechanisms of acute brain injury in patients supported by extracorporeal membrane oxygenation (ECMO). The primary aim of this study was to determine the feasibility of continuous CA monitoring in adult ECMO patients. Our secondary aims were to describe changes in cerebral oximetry index (COx) and other metrics of CA over time and in relation to functional neurologic outcomes. Methods: This is a single-center prospective observational study. We measured Cox, a surrogate measurement of cerebral blood flow, measured by near-infrared spectroscopy, which is an index of CA derived from the moving correlation between mean arterial pressure and slow waves of regional cerebral oxygen saturation. A COx value that approaches 1 indicates impaired CA. Using COx, we determined the optimal MAP (MAPOPT), lower and upper limits of autoregulation for individual patients. These measurements were examined in relation to modified Rankin Scale (mRS) scores. Results: Fifteen patients (median age=57 years [IQR=47-69]) with 150 autoregulation measurements were included for analysis. Eleven were on veno-arterial ECMO and 4 on veno-venous. Mean COx was higher on post-cannulation day 1 than on day 2 (0.2 vs 0.09, p<0.01), indicating improved CA over time. COx was higher in VA-ECMO patients than in VV-ECMO (0.12 vs 0.06, p=0.04). Median MAPOPT for entire cohort was highly variable, ranging 55-110 mmHg. Patients with mRS 0-3 (good outcome) at 3 and 6 months spent less time outside of MAPOPT compared to patients with mRS 4-6 (poor outcome) (74% vs 82%, p=0.01). The percentage of time when observed MAP was outside the limits of autoregulation was higher on post-cannulation day 1 than on day 2 (18.2% vs 3.3%, p<0.01). Conclusions: In ECMO patients, it is feasible to monitor CA continuously at the bedside. CA improved over time, most significantly between post-cannulation days 1 and 2. CA was more impaired in VA-ECMO than VV-ECMO. Spending less time outside of MAPOPT may be associated with achieving a good neurologic outcome.

Hyperacute autonomic and cortical function recovery following cardiac arrest resuscitation in a rodent model.

OBJECTIVE: There is a complex interaction between nervous and cardiovascular systems, but sparse data exist on brain-heart electrophysiological responses to cardiac arrest resuscitation. Our aim was to investigate dynamic changes in autonomic and cortical function during hyperacute stage post-resuscitation. METHODS: Ten rats were resuscitated from 7-min cardiac arrest, as indicators of autonomic response, heart rate (HR), and its variability (HRV) were measured. HR was monitored through continuous electrocardiography, while HRV was assessed via spectral analysis, whereby the ratio of low-/high-frequency (LF/HF) power indicates the balance between sympathetic/parasympathetic activities. Cortical response was evaluated by continuous electroencephalography and quantitative analysis. Parameters were quantified at 5-min intervals over the first-hour post-resuscitation. Neurological outcome was assessed by Neurological Deficit Score (NDS, range 0-80, higher = better outcomes) at 4-h post-resuscitation. RESULTS: A significant increase in HR was noted over 15-30 min post-resuscitation (p < 0.01 vs.15-min, respectively) and correlated with higher NDS (rs = 0.56, p < 0.01). LF/HF ratio over 15-20 min was positively correlated with NDS (rs = 0.75, p < 0.05). Gamma band power surged over 15-30 min post-resuscitation (p < 0.05 vs. 0-15 min, respectively), and gamma band fraction during this period was associated with NDS (rs ≥0.70, p < 0.05, respectively). Significant correlations were identified between increased HR and gamma band power during 15-30 min (rs ≥0.83, p < 0.01, respectively) and between gamma band fraction and LF/HF ratio over 15-20 min post-resuscitation (rs = 0.85, p < 0.01). INTERPRETATIONS: Hyperacute recovery of autonomic and cortical function is associated with favorable functional outcomes. While this observation needs further validation, it presents a translational opportunity for better autonomic and neurologic monitoring during early periods post-resuscitation to develop novel interventions.

Challenges in determining death by neurologic criteria in extracorporeal membrane oxygenation - A single center experience.

INTRODUCTION: Apnea test (AT) in patients on extracorporeal membrane oxygenation (ECMO) support is challenging, leading to variation in determining death by neurologic criteria (DNC). We aim to describe the diagnostic criteria and barriers for DNC in adults on ECMO in a tertiary care center. METHODS: A retrospective review of a prospective observational standardized neuromonitoring study was conducted in adult VA- and VV-ECMO patients at a tertiary center from June 2016 to March 2022. Brain death was defined according to the 2010 American Academy of Neurology guidelines and following the 2020 World Brain Death Project recommendations for performing AT in ECMO patients. RESULTS: Eight (2.7%) ECMO patients (median age = 44 years, 75% male, 50% VA-ECMO) met criteria for DNC, six (75%) of whom were determined with AT. In the other two patients who did not undergo AT due to safety concerns, ancillary tests (transcranial doppler and electroencephalography) were consistent with DNC. An additional seven (2.3%) patients (median age = 55 years, 71% male, 86% VA-ECMO) were noted to have absent brainstem reflexes but failed to complete determination of DNC as they underwent withdrawal of life-sustaining treatment (WLST) before a full evaluation was completed. In these patients, AT was never performed, and ancillary tests were inconsistent with either neurological exam findings and/or neuroimaging supporting DNC, or with each other. CONCLUSION: AT was used safely and successfully in 6 of the 8 ECMO patients diagnosed with DNC and was always consistent with the neurological exam and imaging findings, as opposed to ancillary tests alone.

Hypoxic-Ischemic Brain Injury in ECMO: Pathophysiology, Neuromonitoring, and Therapeutic Opportunities.

Extracorporeal membrane oxygenation (ECMO), in conjunction with its life-saving benefits, carries a significant risk of acute brain injury (ABI). Hypoxic-ischemic brain injury (HIBI) is one of the most common types of ABI in ECMO patients. Various risk factors, such as history of hypertension, high day 1 lactate level, low pH, cannulation technique, large peri-cannulation PaCO2 drop (∆PaCO2), and early low pulse pressure, have been associated with the development of HIBI in ECMO patients. The pathogenic mechanisms of HIBI in ECMO are complex and multifactorial, attributing to the underlying pathology requiring initiation of ECMO and the risk of HIBI associated with ECMO itself. HIBI is likely to occur in the peri-cannulation or peri-decannulation time secondary to underlying refractory cardiopulmonary failure before or after ECMO. Current therapeutics target pathological mechanisms, cerebral hypoxia and ischemia, by employing targeted temperature management in the case of extracorporeal cardiopulmonary resuscitation (eCPR), and optimizing cerebral O2 saturations and cerebral perfusion. This review describes the pathophysiology, neuromonitoring, and therapeutic techniques to improve neurological outcomes in ECMO patients in order to prevent and minimize the morbidity of HIBI. Further studies aimed at standardizing the most relevant neuromonitoring techniques, optimizing cerebral perfusion, and minimizing the severity of HIBI once it occurs will improve long-term neurological outcomes in ECMO patients.

Perceived Utility of Intracranial Pressure Monitoring in Traumatic Brain Injury: A Seattle International Brain Injury Consensus Conference Consensus-Based Analysis and Recommendations.

BACKGROUND: Intracranial pressure (ICP) monitoring is widely practiced, but the indications are incompletely developed, and guidelines are poorly followed. OBJECTIVE: To study the monitoring practices of an established expert panel (the clinical working group from the Seattle International Brain Injury Consensus Conference effort) to examine the match between monitoring guidelines and their clinical decision-making and offer guidance for clinicians considering monitor insertion. METHODS: We polled the 42 Seattle International Brain Injury Consensus Conference panel members' ICP monitoring decisions for virtual patients, using matrices of presenting signs (Glasgow Coma Scale [GCS] total or GCS motor, pupillary examination, and computed tomography diagnosis). Monitor insertion decisions were yes, no, or unsure (traffic light approach). We analyzed their responses for weighting of the presenting signs in decision-making using univariate regression. RESULTS: Heatmaps constructed from the choices of 41 panel members revealed wider ICP monitor use than predicted by guidelines. Clinical examination (GCS) was by far the most important characteristic and differed from guidelines in being nonlinear. The modified Marshall computed tomography classification was second and pupils third. We constructed a heatmap and listed the main clinical determinants representing 80% ICP monitor insertion consensus for our recommendations. CONCLUSION: Candidacy for ICP monitoring exceeds published indicators for monitor insertion, suggesting the clinical perception that the value of ICP data is greater than simply detecting and monitoring severe intracranial hypertension. Monitor insertion heatmaps are offered as potential guidance for ICP monitor insertion and to stimulate research into what actually drives monitor insertion in unconstrained, real-world conditions.

Quantification of Cerebral Vascular Autoregulation Immediately Following Resuscitation from Cardiac Arrest.

Cerebral vascular autoregulation is impaired following resuscitation from cardiac arrest (CA), and its quantification may allow assessing CA-induced brain injury. However, hyperemia occurring immediately post-resuscitation limits the application of most metrics that quantify autoregulation. Therefore, to characterize autoregulation during this critical period, we developed three novel metrics based on how the cerebrovascular resistance (CVR) covaries with changes in cerebral perfusion pressure (CPP): (i) Î¸CVR, which quantifies the CVR vs CPP gradient, (ii) a CVR-based transfer function analysis, and (iii) CVRx, the correlation coefficient between CPP and CVR. We tested these metrics in a model of asphyxia induced CA and resuscitation using seven adult male Wistar rats. Mean arterial pressure (MAP) and cortical blood flow recorded for 30 min post-resuscitation via arterial cannulation and laser speckle contrast imaging, were used as surrogates of CPP and cerebral blood flow (CBF), while CVR was computed as the CPP/CBF ratio. Using our metrics, we found that the status of cerebral vascular autoregulation altered substantially during hyperemia, with changes spread throughout the 0-0.05 Hz frequency band. Our metrics push the boundary of how soon autoregulation can be assessed, and if validated against outcome markers, may help develop a reliable metric of brain injury post-resuscitation.

Prognostication and Goals of Care Decisions in Severe Traumatic Brain Injury: A Survey of The Seattle International Severe Traumatic Brain Injury Consensus Conference Working Group.

Abstract Best practice guidelines have advanced severe traumatic brain injury (TBI) care; however, there is little that currently informs goals of care decisions and processes despite their importance and frequency. Panelists from the Seattle International severe traumatic Brain Injury Consensus Conference (SIBICC) participated in a survey consisting of 24 questions. Questions queried use of prognostic calculators, variability in and responsibility for goals of care decisions, and acceptability of neurological outcomes, as well as putative means of improving decisions that might limit care. A total of 97.6% of the 42 SIBICC panelists completed the survey. Responses to most questions were highly variable. Overall, panelists reported infrequent use of prognostic calculators, and observed variability in patient prognostication and goals of care decisions. They felt that it would be beneficial for physicians to improve consensus on what constitutes an acceptable neurological outcome as well as what chance of achieving that outcome is acceptable. Panelists felt that the public should help to define what constitutes a good outcome and expressed some support for a "nihilism guard." More than 50% of panelists felt that if it was certain to be permanent, a vegetative state or lower severe disability would justify a withdrawal of care decision, whereas 15% felt that upper severe disability justified such a decision. Whether conceptualizing an ideal or existing prognostic calculator to predict death or an unacceptable outcome, on average a 64-69% chance of a poor outcome was felt to justify treatment withdrawal. These results demonstrate important variability in goals of care decision making and a desire to reduce this variability. Our panel of recognized TBI experts opined on the neurological outcomes and chances of those outcomes that might prompt consideration of care withdrawal; however, imprecision of prognostication and existing prognostication tools is a significant impediment to standardizing the approach to care-limiting decisions.

Cardiac Arrest and Neurologic Recovery: Insights from the Case of Mr. Damar Hamlin.

The association between brain injury after cardiac arrest and poor survival outcomes has led to longstanding pessimism. However, the publicly witnessed cardiac arrest, resuscitation, and acute management of Mr. Damar Hamlin and his favorable neurologic recovery provides some optimism. Mr. Hamlin's case highlights the neurologic advances of the last 2 decades and presents the opportunity to improve outcomes for all cardiac arrest patients in key areas: (1) effectively implementing the American Heart Association "Chain of Survival" to prevent initial brain injury and promote neuroprotection; (2) revisiting the process of neurologic prognostication and re-defining the brain recovery during the early periods, and (3) incorporating neurorehabilitation into existing cardiac rehabilitation models to support holistic recovery. ANN NEUROL 2023;93:871-876.

Approach to acute encephalitis in the intensive care unit.

PURPOSE OF REVIEW: Recent years have seen a dramatic increase in the identification of autoimmune encephalitis (AE) and the emergence of new causes of infectious encephalitis (IE). However, management of these patients remains challenging, with many requiring care in intensive care units. Here, we describe recent advances in the diagnosis and management of acute encephalitis. RECENT FINDINGS: Advances in the identification of clinical presentations, neuroimaging biomarkers, and electroencephalogram patterns have enabled more rapid diagnosis of encephalitis. Newer modalities such as meningitis/encephalitis multiplex PCR panels, metagenomic next-generation sequencing, and phage display-based assays are being evaluated in an effort to improve detection of autoantibodies and pathogens. Specific advances in the treatment of AE include establishment of a systematic approach to first-line therapies and the development of newer second-line modalities. The role of immunomodulation and its applications in IE are actively being investigated. In the ICU, particular attention to status epilepticus, cerebral edema, and dysautonomia may improve outcomes. SUMMARY: Substantial diagnostic delays still occur, with many cases left without an identified etiology. Antiviral therapies remain scarce, and optimal treatment regimens for AE still need to be clarified. Nevertheless, our understanding of diagnostic and therapeutic approaches to encephalitis is rapidly evolving.

Management of Anticoagulation Therapy in ECMO-Associated Ischemic Stroke and Intracranial Hemorrhage.

OBJECTIVE: Despite the common occurrence of extracorporeal membrane oxygenation (ECMO)-associated acute ischemic stroke (AIS) and intracranial hemorrhage (ICH), there are little data to guide optimal anticoagulation management. We sought to describe antithrombotic therapy management after stroke and outcomes. METHODS: A retrospective analysis was conducted of venoarterial (VA) and venovenous (VV) ECMO patients treated at a tertiary care center from June 2016 to February 2021. Patients with image-confirmed diagnosis of AIS or ICH while receiving ECMO were included for study with data collected regarding anticoagulation management and clinical outcomes. RESULTS: Overall, 216 patients (153 VA-ECMO, 63 VV-ECMO) were included in this study. Of the 153 patients on VA-ECMO, 13 (8.4%) had AIS and 6 (3.9%) had ICH. Of the 63 patients on VV-ECMO, none had AIS and 5 (7.9%) had ICH. One patient (9%) received anticoagulation reversal after ICH. Anticoagulation was discontinued and later resumed in all 5 ICH survivors (median cessation time, 30 h) and 1 of 2 (50%) AIS survivors (median cessation time, 96 h). While off anticoagulation, 2 of 11 patients (18%) had thromboembolic events and none had new AIS. Upon resumption, there were no cases of hemorrhagic transformation of AIS or ICH expansion. There was no difference in in-hospital mortality between patients with ICH and those without in both the VA-ECMO and VV-ECMO cohorts nor between VA-ECMO patients with AIS and those without. CONCLUSIONS: Early cessation and judicious resumption of anticoagulation appeared feasible in the cohort of patients with ECMO-associated AIS and ICH.