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Introduction The pupillary examination is an important part of the neurological assessment, especially in the setting of acutely brain-injured patients, and pupillary abnormalities are associated with poor outcomes. Currently, the pupillary examination is based on a visual, subjective and frequently inaccurate estimation. The use of automated infrared pupillometry to measure the pupillary light reflex can precisely quantify subtle changes in pupillary functions. The study aimed to evaluate the association between abnormal pupillary function, assessed by the Neurological Pupil Index (NPi), and long-term outcomes in patients with acute brain injury (ABI).Methods and analysis The Outcome Prognostication of Acute Brain Injury using the Neurological Pupil Index study is a prospective, observational study including adult patients with ABI requiring admission at the intensive care unit. We aimed to recruit at least 420 patients including those suffering from traumatic brain injury or haemorrhagic strokes, over 12 months. The primary aim was to assess the relationship between NPi and 6-month mortality or poor neurological outcome, measured by the Extended Glasgow Outcome Score (GOS-E, poor outcome=GOS-E 1–4). Supervised and unsupervised methods and latent class mixed models will be used to identify patterns of NPi trajectories and Cox and logistic model to evaluate their association with outcome.Ethics and dissemination The study has been approved by the institutional review board (Comitato Etico Brianza) on 16 July 2020. Approved protocol V.4.0 dated 10 March 2020. The results of this study will be published in peer-reviewed journals and presented at conferences.Trial registration number NCT04490005.

Background and Purpose: Cerebral infarction remains an important cause of death or disability in patients with aneurysmal subarachnoid hemorrhage (SAH). The prevalence, trends, and outcomes of cerebral infarction in patients with aneurysmal SAH at a national level are not known., Methods: We identified the proportion of patients who develop cerebral infarction (ascertained using validated methodology) among patients with aneurysmal SAH and annual trends using the Nationwide Inpatient Sample (NIS) from 2016 to 2021. We analyzed the effect of cerebral infarction on in-hospital mortality, routine discharge without palliative care (based on discharge disposition), poor outcome defined by the NIS SAH outcome measure, and length and costs of hospitalization after adjusting for potential confounders., Results: A total of 35,305 (53.6%) patients developed cerebral infarction among 65,840 patients with aneurysmal SAH over a 6-year period. There was a trend toward an increase in the proportion of patients who developed cerebral infarction from 51.5% in 2016 to 56.1% in 2021 (p trend p<.001). Routine discharge was significantly lower (30.5% vs. 37.8%, odds ratio [OR] 0.82, 95% confidence interval [CI] 0.75-0.89, p<.001), and poor outcome defined by NIS-SAH outcome measure was significantly higher among patients with cerebral infarction compared with those without cerebral infarction (67.4% vs. 59.3%, OR 1.29, 95% CI 1.18-1.40, p<.001). There was no difference in in-hospital mortality (13.0% vs. 13.6%, OR 0.94, 95% CI 0.85-1.05, p = .30). The length of stay (median 18 days [interquartile range [IQR] 13-25] vs. 14 days [IQR 9-20]), coefficient 3.04, 95% CI 2.44-3.52 and hospitalization cost (median $96,823 vs. $71,311, coefficient 22,320, 95% CI 20,053-24,587) were significantly higher among patients who developed cerebral infarction compared with those who did not develop cerebral infarction., Conclusions: Cerebral infarction was seen in 54% of the patients with a trend toward an increase in the affected proportion of patients with aneurysmal SAH. Patients with cerebral infarction had higher rates of adverse outcomes and required higher resources during hospitalization., (© 2024 American Society of Neuroimaging.)

Background: Clinical practice recommendations guide healthcare decisions. This study aims to evaluate the strength and quality of evidence supporting the American Heart Association (AHA)/American Stroke Association (ASA) guidelines for aneurysmal subarachnoid hemorrhage (aSAH) and spontaneous intracerebral hemorrhage (ICH)., Methods: We reviewed the current AHA/ASA guidelines for aSAH and spontaneous ICH and compared with previous guidelines. Guidelines were classified based on the Class of recommendation (COR) and Level of evidence (LOE). COR signifies recommendation strength (COR 1: Strong; COR 2a: Moderate; COR 2b: Weak; COR 3: No Benefit/Harm), while LOE denotes evidence quality (LOE A: High-Quality; LOE B-NR: Moderate-Quality, Not Randomized; LOE B-R: Moderate-Quality, Randomized; LOE C-EO: Expert Opinion; LOE C-LD: Limited Data)., Results: For aSAH, we identified 84 recommendations across 15 guideline categories. Of these, 31% were classified as COR I, 30% as COR 2a, 17% as COR 2b, and 18% as COR 3. In terms of LOE, 7% were based on LOE A, 10% on LOE B-R, 65% on LOE B-NR, 14% on LOE C-LD, and 5% on LOE C-EO. Compared to previous guidelines, there was a 46% decrease in LOE A, a 45% increase in LOE B, and an 11% decrease in LOE C. For spontaneous ICH, 124 guidelines were identified across 31 guideline categories. Of these, 28% were COR I, 32% COR 2b, and 9% COR 3. For LOE, 4% were based on LOE A, 35% on LOE B-NR, and 42% on LOE C-LD. Compared to previous guidelines, there was a 78% decrease in LOE A, an 82% increase in LOE B, and a 14% increase in LOE C. This analysis highlights that less than a third of AHA/ASA guidelines are classified as the highest class of recommendation, with less than 10% based on the highest LOE., Conclusion: Less than a third of AHA/ASA guidelines on aSAH and spontaneous ICH are classified as the highest class of recommendation with less than 10% based on highest LOE. There appears to be a decrease in proportion of guidelines based on highest LOE in most recent guidelines., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: To investigate prevalence, risk factors, and in-hospital outcomes of comatose extracorporeal membrane oxygenation (ECMO) patients., Design: Retrospective observational., Setting: Tertiary academic hospital., Participants: Adults received venoarterial (VA) or venovenous (VV) ECMO support between November 2017 and April 022., Interventions: None., Measurements and Main Results: We defined 24-hour off sedation as no sedative infusion (except dexmedetomidine) or paralytics administration over a continuous 24-hour period while on ECMO. Off-sedation coma (coma off ) was defined as a Glasgow Coma Scale score of ≤8 after achieving 24-hour off sedation. On-sedation coma (coma on ) was defined as a Glasgow Coma Scale score of ≤8 during the entire ECMO course without off sedation for 24 hours. Neurological outcomes were assessed at discharge using the modified Rankin scale (good, 0-3; poor, 4-6). We included 230 patients (VA-ECMO 143, 65% male); 24-hour off sedation was achieved in 32.2% VA-ECMO and 26.4% VV-ECMO patients. Among all patients off sedation for 24 hours (n = 69), 56.5% VA-ECMO and 52.2% VV-ECMO patients experienced coma off . Among those unable to be sedation free for 24 hours (n = 161), 50.5% VA-ECMO and 17.2% VV-ECMO had coma on . Coma off was associated with poor outcomes (p < 0.05) in VA-ECMO and VV-ECMO groups, whereas coma on only impacted the VA-ECMO group outcomes. In a multivariable analysis, requirement of renal replacement therapy was an independent risk factor for coma off after adjusting for ECMO configuration, after adjusting for ECMO configuration, acute brain injury, pre-ECMO partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide in arterial blood, pH, and bicarbonate level (worst value within 24 hours before cannulation)., Conclusions: Coma off was common and associated with poor outcomes at discharge. Requirement of renal replacement therapy was an independent risk factor., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cerebral ischemia associated with vasospasm in patients with aneurysmal subarachnoid hemorrhage (aSAH) requires a multifaceted approach. We report the use of the combination of enteral cilostazol and intravenous (IV) high-dose albumin in aSAH patients with cerebral ischemia refractory to other accepted pharmacologic and endovascular treatments. Three aSAH patients who developed cerebral ischemic symptoms despite treatment with oral nimodipine and endovascular measures (i.e., intraarterial vasodilators and balloon angioplasty) were treated with enteral cilostazol (200 mg/day) and one or more doses of IV (25%) albumin (1.25 g per kg over eight hours). The patients were monitored by serial neurological examinations, transcranial Doppler imaging (TCDI) ultrasound, computed tomographic angiography (CTA), and perfusion (CTP) scans. Three patients (ages 58, 67, and 56 years) developed symptomatic cerebral ischemia and vasospasm following an aSAH. Due to limited angiographic response to endovascular treatment, including intraarterial vasodilators with or without balloon angioplasty, IV (25%) albumin and enteral cilostazol were administered. CT angiogram and perfusion 2-3 days post-treatment demonstrated resolution of the perfusion deficits and angiographic vasospasm. Concurrently, TCDI demonstrated improved vasospasm and clinical examination demonstrated resolution of neurological deficits. None of the patients required any additional treatments for cerebral ischemia. A combination of oral cilostazol and IV high dose (25%) albumin was associated with amelioration of angiographic vasospasm, reduction of tissue perfusion deficits, and clinical improvement of aSAH patients with severe refractory cerebral ischemia., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. University of Missouri Institutional Review Board (MU IRB) issued approval 2098328. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Bains et al.)

Background: The purpose of this study was to assess the prevalence of coma among patients in critical care units in Chile. We also aimed to provide insight into the demographic characteristics, etiologies, and complications associated with coma., Methods: A single day cross-sectional study was conducted through a national survey of public and private hospitals with critical and intensive cardiac care units across Chile. Data were collected using an online questionnaire that contained questions regarding critically ill patients' information, demographic characteristics, etiology and duration of coma, medical complications, and support requirements., Results: A total of 84% of all health facilities answered, accounting for a total of 2,708 patients. The overall coma prevalence was 2.9%. The median age of the comatose patients was 61 years (interquartile range 50-72) and 66.2% were male. The median coma duration was five days (interquartile range 2-9). Cerebral hemorrhage was the most common etiology, followed by severe hypoxic-ischemic encephalopathy, acute ischemic stroke, and traumatic brain injury. A total of 48.1% of coma patients experienced acute and ongoing treatment complications, with pneumonia being the most common complication, and 97.4% required support during comatose management., Conclusions: This study provides an overview of the prevalence of coma in Chilean critical and cardiac care units. Coma is a common condition. Comatose patients frequently experience medical complications during their hospitalization., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Aneurysmal subarachnoid hemorrhage (aSAH) occurs less often than other stroke types but affects younger patients, imposing a disproportionately high burden of long-term disability. Although management advances have improved outcomes over time, relatively few aSAH treatments have been tested in randomized clinical trials (RCTs). One lesson learned from COVID-19 is that trial platforms can facilitate the efficient execution of multicenter RCTs even in complex diseases during challenging conditions. An aSAH trial platform with standardized eligibility criteria, randomization procedures, and end point definitions would enable the study of multiple targeted interventions in a perpetual manner, with treatments entering and leaving the platform based on predefined decision algorithms. An umbrella institutional review board protocol and clinical trial agreement would allow individual arms to be efficiently added as amendments rather than stand-alone protocols. Standardized case report forms using the National Institutes of Health/National Institute of Neurological Disorders and Stroke common data elements and general protocol standardization across arms would create synergies for data management and monitoring. A Bayesian analysis framework would emphasize frequent interim looks to enable early termination of trial arms for futility, common controls, borrowing of information across arms, and adaptive designs. A protocol development committee would assist investigators and encourage pragmatic designs to maximize generalizability, reduce site burden, and execute trials efficiently and cost-effectively. Despite decades of steady clinical progress in the management of aSAH, poor patient outcomes remain common, and despite the increasing availability of RCT data in other fields, it remains difficult to perform RCTs to guide more effective care for aSAH. The development of a platform for pragmatic RCTs in aSAH would help close the evidence gap between aSAH and other stroke types and improve outcomes for this important disease with its disproportionate public health burden., Competing Interests: Dr Kamel reports an ownership stake in TET Medical, compensation from American Medical Association and Javelin Medical for consultant services, compensation from Boehringer Ingelheim for end point review committee services, employment by Weill Cornell Medical College, compensation from Medtronic and Janssen Biotech for other services, and compensation from Novo Nordisk and AstraZeneca for end point review committee services. Dr Suarez reports compensation from Acasti Pharma for data and safety monitoring services and compensation from Cyban for consultant services. Dr Mack reports compensation from Viseon, Inc, for consultant services, compensation from Spartan Micro for consultant services, compensation from Cerebrotech for other services, compensation from Integra LifeSciences for consultant services, stock options in Spartan Micro, compensation from Egret for consultant services, stock options in Stream Biomedical, compensation from Viseon for other services, compensation from Endostream for other services, compensation from Vastrax for other services, stock holdings in Rebound Therapeutics, employment by the University of Southern California, compensation from Q’Apel for consultant services, compensation from Imperative Care, Inc, for consultant services, compensation from Radical Catheters for other services, compensation from Q’Apel for other services, stock options in Egret, compensation from Medtronic for other services, compensation from Stream Biomedical for consultant services, stock holdings in Truvic, compensation from Borvo for other services, and compensation from Stryker for data and safety monitoring services. Dr Chou reports compensation from Acasti for consultant services; employment by Northwestern Medicine; compensation from CSL Behring for consultant services; service as a member of the Board of Directors for the Neurocritical Care Society; grants from the Neurocritical Care Society; compensation from BioVie for consultant services; grants from the National Institute of Neurological Disorders and Stroke; and employment by Northwestern University. Dr Busl reports grants from the National Institutes of Health (NIH). Dr Derdeyn reports compensation from noNO for data and safety monitoring services, compensation from Silk Road Medical, Inc, for data and safety monitoring services, stock options in Euphrates Vascular, and compensation from Penumbra, Inc, for data and safety monitoring services. Dr Dangayach reports employment by Icahn School of Medicine at Mount Sinai, grants from Visionable, compensation from The Jacob’s Institute for consultant services, grants from Ceibahealth, grants from The Aneurysm and AVM Foundation (TAAF), grants from Neurosteer, and grants from American Academy of Neurology. Dr Elm reports compensation from CSL Behring for consultant services and grants from NIH. Dr Beall reports grants from NIH. Dr Ko reports compensation from Route 92 Medical, Inc, for data and safety monitoring services; service on the Board of Directors for TAAF; employment by the School of Medicine, University of California, San Francisco; and funding from the American Heart Association and NIH. The other authors report no conflicts.

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., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cannabinoid use, particularly for recreational purposes, is increasing exponentially across all age groups, especially in younger populations, due to its perceived low risk and legalization. While cannabinoids may be largely considered as safe, there is mounting evidence of increased risk of systemic and neurological complications through their interaction with the poorly understood endocannabinoid receptor network within the central nervous system and other organ systems. Acute cannabinoid exposure can cause neuropsychiatric symptoms in addition to altering cerebral blood flow, leading to cerebrovascular complications such as ischemic stroke, subarachnoid hemorrhage, and reversible cerebral vasoconstriction syndrome (RCVS). Chronic use, particularly among adolescents, may be associated with increased risk of long-term cognitive deficits, schizophrenia, and other neuropsychiatric effects. Synthetic cannabinoids have increased potency, with reports of causing profound neurological complications including coma, seizures, posterior reversible encephalopathy syndrome, and RCVS. Despite increasing evidence, the quality of literature describing neurologic complications with cannabinoids remains limited to case series and retrospective cohort studies, with significant confounding factors such as concomitant use of other illicit drugs, limiting interpretation. In this review, we summarize the effect of cannabinoids on the neurologic system and associated neurological complications., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction: Cerebral infarction from delayed cerebral ischemia (DCI) is a leading cause of poor neurological outcome after aneurysmal subarachnoid hemorrhage (aSAH). We performed an international clinical practice survey to identify monitoring and management strategies for cerebral vasospasm associated with DCI in aSAH patients requiring intensive care unit admission., Methods: The survey questionnaire was available on the European Society of Intensive Care Medicine (May 2021-June 2022) and Neurocritical Care Society (April - June 2022) websites following endorsement by these societies., Results: There were 292 respondents from 240 centers in 38 countries. In conscious aSAH patients or those able to tolerate an interruption of sedation, neurological examination was the most frequently used diagnostic modality to detect delayed neurological deficits related to DCI caused by cerebral vasospasm (278 respondents, 95.2%), while in unconscious patients transcranial Doppler/cerebral ultrasound was most frequently used modality (200, 68.5%). Computed tomography angiography was mostly used to confirm the presence of vasospasm as a cause of DCI. Nimodipine was administered for DCI prophylaxis by the majority of the respondents (257, 88%), mostly by an enteral route (206, 71.3%). If there was a significant reduction in arterial blood pressure after nimodipine administration, a vasopressor was added and nimodipine dosage unchanged (131, 45.6%) or reduced (122, 42.5%). Induced hypertension was used by 244 (85%) respondents as first-line management of DCI related to vasospasm; 168 (59.6%) respondents used an intra-arterial procedure as second-line therapy., Conclusions: This survey demonstrated variability in monitoring and management strategies for DCI related to vasospasm after aSAH. These findings may be helpful in promoting educational programs and future research., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The Curing Coma Campaign (CCC) and its contributing collaborators identified multiple key areas of knowledge and research gaps in coma and disorders of consciousness (DoC). This step was a crucial effort and essential to prioritize future educational and research efforts. These key areas include defining categories of DoC, assessing DoC using multimodal approach (e.g., behavioral assessment tools, advanced neuroimaging studies), discussing optimal clinical trials' design and exploring computational models to conduct clinical trials in patients with DoC, and establishing common data elements to standardize data collection. Other key areas focused on creating coma care registry and educating clinicians and patients and promoting awareness of DoC to improve care in patients with DoC. The ongoing efforts in these key areas are discussed., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction/objectives: The use of non-occupational post-exposure prophylaxis (nPEP) emerges as a strategic intervention to reduce HIV infection risk following sexual encounters in our setting. Notwithstanding, there is a scarcity of contemporary data regarding adherence to this treatment, its effectiveness and tolerance. Our study aims to delve into these factors among individuals who have resorted to nPEP after high-risk sexual encounters., Methods: We conducted a retrospective observational study of cases administered nPEP for HIV from 1 January 2018 to 31 December 2021 at a tertiary hospital in Madrid. The study included all adults over 18 years who sought care at the emergency department of the Fundación Jiménez Díaz Hospital following a risky sexual encounter and were subsequently recommended HIV nPEP treatment., Results: 878 individuals received nPEP for HIV and underwent initial serological tests. Of these, 621 had comprehensive follow-ups. The prescribed regimen for all was raltegravir (RAL) 1200 mg combined with tenofovir/emtricitabine (TDF/FTC) 245/200 mg daily for 28 days. The study revealed a 1.1% rate (n=10) of previously undetected infection and a 0.16% (n=1) failure rate of nPEP. Regarding regimen tolerability, 5.6% (n=35) experienced symptoms linked to the treatment, yet none necessitated discontinuation of the regimen. On the contrary, six per cent (n=53) reported symptoms consistent with an STI during one of the medical visits; specifically, 4.4% had urethritis, and 1.6% had proctitis., Conclusion: nPEP with RAL/TDF/FTC demonstrates high efficacy and safety, contingent on proper adherence. There is an observed increase in STI prevalence in this cohort, with nearly half of the participants not engaging in appropriate follow-up after initiating nPEP., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The Glasgow Coma Scale-Pupils (GCS-P) score has been suggested to better predict patient outcomes compared with GCS alone, while avoiding the need for more complex clinical models. This study aimed to compare the prognostic ability of GCS-P versus GCS in a national cohort of traumatic subdural hematoma (SDH) patients., Methods: Patient data were obtained from the National Trauma Data Bank (2017-2019). Inclusion criteria were traumatic SDH diagnosis with available data on presenting GCS score, pupillary reactivity, and discharge disposition. Patients with severe polytrauma or nonsurvivable head injury at presentation were excluded. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of GCS-P versus GCS scores for inpatient mortality prediction were evaluated across the entire cohort, as well as in subgroups based on age and traumatic brain injury (TBI) type (blunt vs penetrating). Calibration curves were plotted based on predicted probabilities and actual outcomes., Results: A total of 196,747 traumatic SDH patients met the study inclusion criteria. Sensitivity (0.707 vs 0.702), specificity (0.821 vs 0.823), and AUC (0.825 vs 0.814, p < 0.001) of GCS-P versus GCS scores for prediction of inpatient mortality were similar. Calibration curve analysis revealed that GCS scores slightly underestimated inpatient mortality risk, whereas GCS-P scores did not. In patients > 65 years of age with blunt TBI (51.9%, n = 102,148), both GCS-P and GCS scores underestimated inpatient mortality risk. In patients with penetrating TBI (2.4%, n = 4,710), the AUC of the GCS-P score was significantly higher (0.902 vs 0.851, p < 0.001). In this subgroup, both GCS-P and GCS scores underestimated inpatient mortality risk among patients with lower rates of observed mortality and overestimated risk among patients with higher rates of observed mortality. This effect was more pronounced in the GCS-P calibration curve., Conclusions: The GCS-P score provides better short-term prognostication compared with the GCS score alone among traumatic SDH patients with penetrating TBI. The GCS-P score overestimates inpatient mortality risk among penetrating TBI patients with higher rates of observed mortality. For penetrating TBI patients, which comprised 2.4% of our SDH cohort, a low GCS-P score should not justify clinical nihilism or forgoing aggressive treatment.

Objectives: Although delirium is well described in patients with sepsis, there are limited data on other neurologic complications. We aimed to systematically review the prevalence, neuromonitoring tools, and neurocognitive outcomes in sepsis patients with neurologic complications., Data Sources: MEDLINE and six other databases (Embase, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov ) were searched through January 2023., Study Selection: Studies of adult patients with sepsis reported neurologic complications, use of neuromonitoring tools, neuropathology, and cognitive outcomes., Data Extraction: Two independent reviewers extracted the data. Random-effect meta-analyses were used to pool data., Data Synthesis: Seventy-four studies ( n = 146,855) were included. Neurologic complications were reported in 38 studies ( n = 142,193) including septic encephalopathy (36%, 95% CI, 27-46%; I 2 = 99%), ischemic stroke (5%, 95% CI, 2.1-11.5; I 2 = 99%), intracranial hemorrhage (2%, 95% CI, 1.0-4.4%; I 2 = 96%), seizures (1%, 95% CI, 0.2-7%; I 2 = 96%), posterior reversible encephalopathy syndrome (9%), and hypoxic-ischemic brain injury (7%). In the meta-regression analysis, pulmonary infection, sepsis induced by a gram-positive organism, higher sequential organ failure assessment score, acute physiology and chronic health evaluation II score at admission, and longer ICU length of stay were associated with higher risk of developing septic encephalopathy. Three studies ( n = 159) reported postmortem neuropathological findings, acute brain injury was noted in 47% of patients. Twenty-six studies ( n = 1,358) reported the use of neuromonitoring tools, electroencephalogram was the most used tool for seizure detection. Transcranial Doppler and near infrared spectroscopy were used for monitoring cerebral hemodynamic changes to detect early ischemia. Six studies reported cognitive outcomes ( n = 415) up to 12 months postdischarge and cognitive impairment (≥ one domain) was reported in 30%., Conclusions: In-hospital neurologic complications are common in patients with sepsis. However, the mechanism and timing of those sepsis-associated complications are poorly understood and there are limited data on standardized neuromonitoring in this population., Competing Interests: Dr .Cho is funded by National Heart Lung and Blood Institute 1K23HL157610. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objective: Careful hematologic management is required in surgical patients with traumatic acute subdural hematoma (aSDH) taking antithrombotic medications. We sought to compare outcomes between patients with aSDH taking antithrombotic medications at admission who received antithrombotic reversal with patients with aSDH not taking antithrombotics., Methods: Retrospective review identified patients with traumatic aSDH requiring surgical evacuation. The cohort was divided based on antithrombotic use and whether pharmacologic reversal agents or platelet transfusions were administered. A 3-way comparison of outcomes was performed between patients taking anticoagulants who received pharmacologic reversal, patients taking antiplatelets who received platelet transfusion, and patients not taking antithrombotics. Multivariable regressions, adjusted for injury severity, further investigated associations with outcomes., Results: Of 138 patients who met inclusion criteria, 13.0% (n = 18) reported taking anticoagulants, 16.7% (n = 23) reported taking antiplatelets, and 3.6% (n = 5) reported taking both. Patients taking antiplatelets who received platelet transfusion had longer intraoperative times (P = 0.040) and higher rates of palliative care consultations (P = 0.046) compared with patients taking anticoagulants who received pharmacologic reversal and patients not taking antithrombotics. Across groups, no significant differences were found in frequency of in-hospital intracranial hemorrhage and venous thromboembolism, length of hospital stay, rate of inpatient mortality, or follow-up health status. In multivariable analysis, intraoperative time remained longest for the antiplatelets with platelet transfusion group. Other outcomes were not associated with patient group., Conclusions: Among surgical patients with traumatic aSDH, those taking antiplatelet medications who receive platelet transfusions experience longer intraoperative procedure times and higher rates of palliative care consultation. Comparable outcomes were observed between patients receiving antithrombotic reversal and patients not taking antithrombotics., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Limited data exist regarding the optimal clinical trial design for studies involving persons with disorders of consciousness (DoC), and only a few therapies have been tested in high-quality clinical trials. To address this, the Curing Coma Campaign Clinical Trial Working Group performed a gap analysis on the current state of clinical trials in DoC to identify the optimal clinical design for studies involving persons with DoC., Methods: The Curing Coma Campaign Clinical Trial Working Group was divided into three subgroups to (1) review clinical trials involving persons with DoC, (2) identify unique challenges in the design of clinical trials involving persons with DoC, and (3) recommend optimal clinical trial designs for DoC., Results: There were 3055 studies screened, and 66 were included in this review. Several knowledge gaps and unique challenges were identified. There is a lack of high-quality clinical trials, and most data regarding patients with DoC are based on observational studies focusing on patients with traumatic brain injury and cardiac arrest. There is a lack of a structured long-term outcome assessment with significant heterogeneity in the methodology, definitions of outcomes, and conduct of studies, especially for long-term follow-up. Another major barrier to conducting clinical trials is the lack of resources, especially in low-income countries. Based on the available data, we recommend incorporating trial designs that use master protocols, sequential multiple assessment randomized trials, and comparative effectiveness research. Adaptive platform trials using a multiarm, multistage approach offer substantial advantages and should make use of biomarkers to assess treatment responses to increase trial efficiency. Finally, sound infrastructure and international collaboration are essential to facilitate the conduct of trials in patients with DoC., Conclusions: Conduct of trials in patients with DoC should make use of master protocols and adaptive design and establish international registries incorporating standardized assessment tools. This will allow the establishment of evidence-based practice recommendations and decrease variations in care., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background and Objectives: Growing evidence supports prompt surgical decompression for patients with traumatic spinal cord injury (tSCI). Rates of concomitant tSCI and traumatic brain injury (TBI) range from 10% to 30%. Concomitant TBI may delay tSCI diagnosis and surgical intervention. Little is known about real-world management of this common injury constellation that carries significant clinical consequences. This study aimed to quantify the impact of concomitant TBI on surgical timing in a national cohort of patients with tSCI., Methods: Patient data were obtained from the National Trauma Data Bank (2007-2016). Patients admitted for tSCI and who received surgical intervention were included. Delayed surgical intervention was defined as surgery after 24 hours of admission. Multivariable hierarchical regression models were constructed to measure the risk-adjusted association between concomitant TBI and delayed surgical intervention. Secondary outcome included favorable discharge status., Results: We identified 14 964 patients with surgically managed tSCI across 377 North American trauma centers, of whom 2444 (16.3%) had concomitant TBI and 4610 (30.8%) had central cord syndrome (CCS). The median time to surgery was 20.0 hours for patients without concomitant TBI and 24.8 hours for patients with concomitant TBI. Hierarchical regression modeling revealed that concomitant TBI was independently associated with delayed surgery in patients with tSCI (odds ratio [OR], 1.3; 95% CI, 1.1-1.6). Although CCS was associated with delayed surgery (OR, 1.5; 95% CI, 1.4-1.7), we did not observe a significant interaction between concomitant TBI and CCS. In the subset of patients with concomitant tSCI and TBI, patients with severe TBI were significantly more likely to experience a surgical delay than patients with mild TBI (OR, 1.4; 95% CI, 1.0-1.9)., Conclusion: Concomitant TBI delays surgical management for patients with tSCI. This effect is largest for patients with tSCI with severe TBI. These findings should serve to increase awareness of concomitant TBI and tSCI and the likelihood that this may delay time-sensitive surgery., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background and Objectives: Acute subdural hematoma (aSDH) after traumatic brain injury frequently requires emergent craniotomy (CO) or decompressive craniectomy (DC). We sought to determine the variables associated with either surgical approach and to compare outcomes between matched patients., Methods: A multi-center retrospective review was used to identify traumatic aSDH patients who underwent CO or DC. Patient variables independently associated with surgical approach were used for coarsened exact matching.Multivariate logistic regression and multivariate Cox proportional-hazards regression wereconducted on matched patients to determine independent predictors of mortality., Results: Seventy-six patients underwent CO and sixty-two underwent DC for aSDH evacuation. DC patients were21.4 years younger (P < 0.001), more likely to be male (80.6 % vs 60.5 %,P = 0.011), and present with GCS ≤ 8 (64.5 % vs 36.8 %,P = 0.001). Age (P < 0.001), epidural hematoma (P = 0.01), skull fracture (P = 0.001), and cisternal effacement (P = 0.02) were independently associated with surgical approach. After coarsened exact matching, DC (P = 0.008), older age (P = 0.007), male sex (P = 0.04), and intraventricular hemorrhage (P = 0.02), were independently associated with inpatient mortality. Multivariate Cox proportional-hazards regression demonstrated that DC was independently associated with mortality at 90-days (P = 0.001) and 1-year post-operation (P = 0.003)., Conclusion: aSDH patients who receive surgical evacuation via DC as opposed to CO are younger, more likely to be male, and have worse clinical exam. After controlling for patient differences via coarsened exact matching, DC is independently associated with mortality., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Acute brain injury (ABI) and neuroinflammation is reported in COVID-19 and acute respiratory distress syndrome (ARDS). It remains unclear if COVID-19 plays an independent role in development of ABI compared to those with non-COVID-19 ARDS. We aimed to evaluate if COVID-19 ARDS is associated with higher risk and specific patterns of ABI compared to non-COVID-19 ARDS. We conducted an age and sex matched case-control autopsy study at a tertiary academic center. Ten patients with COVID-19 ARDS were matched to 20 non-COVID-19 ARDS patients. Baseline demographics were comparable between the two groups including severity of ARDS ( p = 0.3). The frequency of overall ABI (70 vs. 60%), infratentorial ABI (40 vs. 25%), ischemic infarct (40 vs. 25%), intracranial hemorrhage (30 vs. 35%), and hypoxic-ischemic brain injury (30 vs. 35%) was similar between COVID-19 and non-COVID-19 ARDS patients, respectively ( p > 0.05). Intracapillary megakaryocytes were exclusively seen in 30% of COVID-19 patients. Overall, frequency and pattern of ABI in COVID-19 ARDS was comparable to non-COVID-19., Competing Interests: LZ was employed by Inova Health System. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Humayun, Zhang, Zaikos, Kannapadi, Suarez, Hager, Troncoso and Cho.)

The convergence of an interdisciplinary team of neurocritical care specialists to organize the Curing Coma Campaign is the first effort of its kind to coordinate national and international research efforts aimed at a deeper understanding of disorders of consciousness (DoC). This process of understanding includes translational research from bench to bedside, descriptions of systems of care delivery, diagnosis, treatment, rehabilitation, and ethical frameworks. The description and measurement of varying confounding factors related to hospital care was thought to be critical in furthering meaningful research in patients with DoC. Interdisciplinary hospital care is inherently varied across geographical areas as well as community and academic medical centers. Access to monitoring technologies, specialist consultation (medical, nursing, pharmacy, respiratory, and rehabilitation), staffing resources, specialty intensive and acute care units, specialty medications and specific surgical, diagnostic and interventional procedures, and imaging is variable, and the impact on patient outcome in terms of DoC is largely unknown. The heterogeneity of causes in DoC is the source of some expected variability in care and treatment of patients, which necessitated the development of a common nomenclature and set of data elements for meaningful measurement across studies. Guideline adherence in hemorrhagic stroke and severe traumatic brain injury may also be variable due to moderate or low levels of evidence for many recommendations. This article outlines the process of the development of common data elements for hospital course, confounders, and medications to streamline definitions and variables to collect for clinical studies of DoC., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Traumatic brain injury (TBI) represents a considerable portion of the global injury burden. The incidence of TBI will continue to increase in view of an increase in population density, an aging population, and the increased use of motor vehicles, motorcycles, and bicycles. The most common causes of TBI are falls and road traffic injuries. Deaths related to road traffic injury are three times higher in low-and middle-income countries (LMIC) than in high-income countries (HIC). The Latin American Caribbean region has the highest incidence of TBI worldwide, primarily caused by road traffic injuries. Data from HIC indicates that road traffic injuries can be successfully prevented through concerted efforts at the national level, with coordinated and multisector responses to the problem. Such actions require implementation of proven measures to address the safety of road users and the vehicles themselves, road infrastructure, and post-crash care. In this review, we focus on the epidemiology of TBI in Latin America and the implementation of solutions and preventive measures to decrease mortality and long-term disability., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: 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., Methods: 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., Findings: 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)., Interpretation: 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., Funding: NeurOptics., Competing Interests: Declaration of interests GC reports institutional research grants from Integra and NeurOptics; and received personal fees as a speakers’ bureau member and advisory board member from Integra, NeurOptics, Biogen, Idorsia, and Invex Therapeutics, all outside the submitted work; and is the Editor-in-Chief of Intensive Care Medicine. FST received consulting and lecture fees from NeurOptics; and received personal fees as an Advisory Board Member from NeurOptics, all outside the submitted work. MO received fee payments for consultancy roles for NeurOptics and honoraria for lectures by NeurOptics; received personal fees as an advisory board member from NeurOptics, all unrelated to the submitted work; and received institutional grants from the Swiss National Science Foundation. JIS reported personal fees as a member of the Clinical Endpoint Committee for the REACT Study funded by Idorsia; is member of the data safety and monitoring board for the INTREPID study; is a member of the board of directors of the Neurocritical Care Foundation and the Neurocritical Care Society; and is member of the editorial board of Stroke. NB-H received honoraria for lectures from ORION Pharma. ABO received honoraria for educational events from BD, support for attending meetings from Pfizer, and received equipment from NeurOptics. PB received honoraria for lectures from LFB Company and equipment from NeurOptics. RMC received institutional grants from the National Institutes of Health (National Institute of Child Health and Human Development; Fogarty International Centre). SG participated as a data safety and monitoring board member at Division of Cell Matrix Biology and Regenerative Medicine, University of Manchester, without payment. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Paediatric early warning systems (PEWS) aid in the early identification of clinical deterioration events in children admitted to hospital. We aimed to investigate the effect of PEWS implementation on mortality due to clinical deterioration in children with cancer in 32 resource-limited hospitals across Latin America., Methods: Proyecto Escala de Valoración de Alerta Temprana (Proyecto EVAT) is a quality improvement collaborative to implement PEWS in hospitals providing childhood cancer care. In this prospective, multicentre cohort study, centres joining Proyecto EVAT and completing PEWS implementation between April 1, 2017, and May 31, 2021, prospectively tracked clinical deterioration events and monthly inpatient-days in children admitted to hospital with cancer. De-identified registry data reported between April 17, 2017, and Nov 30, 2021, from all hospitals were included in analyses; children with limitations on escalation of care were excluded. The primary outcome was clinical deterioration event mortality. Incidence rate ratios (IRRs) were used to compare clinical deterioration event mortality before and after PEWS implementation; multivariable analyses assessed the correlation between clinical deterioration event mortality and centre characteristics., Findings: Between April 1, 2017, and May 31, 2021, 32 paediatric oncology centres from 11 countries in Latin America successfully implemented PEWS through Proyecto EVAT; these centres documented 2020 clinical deterioration events in 1651 patients over 556 400 inpatient-days. Overall clinical deterioration event mortality was 32·9% (664 of 2020 events). The median age of patients with clinical deterioration events was 8·5 years (IQR 3·9-13·2), and 1095 (54·2%) of 2020 clinical deterioration events were reported in male patients; data on race or ethnicity were not collected. Data were reported per centre for a median of 12 months (IQR 10-13) before PEWS implementation and 18 months (16-18) after PEWS implementation. The mortality rate due to a clinical deterioration event was 1·33 events per 1000 patient-days before PEWS implementation and 1·09 events per 1000 patient-days after PEWS implementation (IRR 0·82 [95% CI 0·69-0·97]; p=0·021). In the multivariable analysis of centre characteristics, higher clinical deterioration event mortality rates before PEWS implementation (IRR 1·32 [95% CI 1·22-1·43]; p<0·0001), being a teaching hospital (1·18 [1·09-1·27]; p<0·0001), not having a separate paediatric haematology-oncology unit (1·38 [1·21-1·57]; p<0·0001), and having fewer PEWS omissions (0·95 [0·92-0·99]; p=0·0091) were associated with a greater reduction in clinical deterioration event mortality after PEWS implementation; no association was found with country income level (IRR 0·86 [95% CI 0·68-1·09]; p=0·22) or clinical deterioration event rates before PEWS implementation (1·04 [0·97-1·12]; p=0·29)., Interpretation: PEWS implementation was associated with reduced clinical deterioration event mortality in paediatric patients with cancer across 32 resource-limited hospitals in Latin America. These data support the use of PEWS as an effective evidence-based intervention to reduce disparities in global survival for children with cancer., Funding: American Lebanese Syrian Associated Charities, US National Institutes of Health, and Conquer Cancer Foundation., Translations: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The neurointensive care management of patients with aneurysmal subarachnoid hemorrhage (aSAH) is one of the most critical components contributing to short-term and long-term patient outcomes. Previous recommendations for the medical management of aSAH comprehensively summarized the evidence based on consensus conference held in 2011. In this report, we provide updated recommendations based on appraisal of the literature using the Grading of Recommendations Assessment, Development, and Evaluation methodology., Methods: The Population/Intervention/Comparator/Outcome (PICO) questions relevant to the medical management of aSAH were prioritized by consensus from the panel members. The panel used a custom-designed survey instrument to prioritize clinically relevant outcomes specific to each PICO question. To be included, the study design qualifying criteria were as follows: prospective randomized controlled trials (RCTs), prospective or retrospective observational studies, case-control studies, case series with a sample larger than 20 patients, meta-analyses, restricted to human study participants. Panel members first screened titles and abstracts, and subsequently full text review of selected reports. Data were abstracted in duplicate from reports meeting inclusion criteria. Panelists used the Grading of Recommendations Assessment, Development, and Evaluation Risk of Bias tool for assessment of RCTs and the "Risk of Bias In Nonrandomized Studies - of Interventions" tool for assessment of observational studies. The summary of the evidence for each PICO was presented to the full panel, and then the panel voted on the recommendations., Results: The initial search retrieved 15,107 unique publications, and 74 were included for data abstraction. Several RCTs were conducted to test pharmacological interventions, and we found that the quality of evidence for nonpharmacological questions was consistently poor. Five PICO questions were supported by strong recommendations, one PICO question was supported by conditional recommendations, and six PICO questions did not have sufficient evidence to provide a recommendation., Conclusions: These guidelines provide recommendations for or against interventions proven to be effective, ineffective, or harmful in the medical management of patients with aSAH based on a rigorous review of the available literature. They also serve to highlight gaps in knowledge that should guide future research priorities. Despite improvements in the outcomes of patients with aSAH over time, many important clinical questions remain unanswered., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background Cigarette smoking is a well-known risk factor for ischemic and hemorrhagic stroke. We evaluated the impact of smoking status on hematoma expansion and clinical outcome in patients with primary intracerebral hemorrhage. Methods and Results This is a post hoc exploratory analysis of the ATACH (Antihypertensive Treatment at Acute Cerebral Hemorrhage)-2 trial. Patients with intracerebral hemorrhage were randomized into intensive blood pressure lowering (systolic blood pressure, <139 mm Hg) versus standard blood pressure lowering (systolic blood pressure, 140-179 mm Hg) in this study. We compared the demographic characteristics; hematoma size, location, and expansion rate; and clinical outcome based on subjects' smoking status. Of a total of 914 patients in the trial with known smoking status, 439 (48%) patients were ever smokers (264 current smokers and 175 former smokers). Current and former smokers were younger and more likely to be men. Baseline Glasgow Coma Scale score and initial hematoma size did not vary based on smoking status. Ever smokers had higher rates of thalamic hemorrhage (42% versus 34%) and intraventricular hemorrhage (29% versus 23%); this rate was highest among former smokers versus current smokers (49% versus 35%, respectively). Ever smokers had a higher rate of hematoma expansion in 24 hours (adjusted relative risk [RR] [95% CI], 1.46 [1.08-1.96]) compared with nonsmokers on multivariate analysis. There was no significant difference in the rate of death and disability at 90 days between the 2 groups (adjusted RR [95% CI], 1.18 [0.998-1.40]). Conclusions Our analysis demonstrates cigarette smoking as an independent predictor for hematoma expansion. There was no significant difference in death and disability based on smoking status.

Delayed cerebral ischemia (DCI) is one of the most important complications of subarachnoid hemorrhage. Despite lack of prospective evidence, medical rescue interventions for DCI include hemodynamic augmentation using vasopressors or inotropes, with limited guidance on specific blood pressure and hemodynamic parameters. For DCI refractory to medical interventions, endovascular rescue therapies (ERTs), including intraarterial (IA) vasodilators and percutaneous transluminal balloon angioplasty, are the cornerstone of management. Although there are no randomized controlled trials assessing the efficacy of ERTs for DCI and their impact on subarachnoid hemorrhage outcomes, survey studies suggest that they are widely used in clinical practice with significant variability worldwide. IA vasodilators are first line ERTs, with better safety profiles and access to distal vasculature. The most commonly used IA vasodilators include calcium channel blockers, with milrinone gaining popularity in more recent publications. Balloon angioplasty achieves better vasodilation compared with IA vasodilators but is associated with higher risk of life-threatening vascular complications and is reserved for proximal severe refractory vasospasm. The existing literature on DCI rescue therapies is limited by small sample sizes, significant variability in patient populations, lack of standardized methodology, variable definitions of DCI, poorly reported outcomes, lack of long-term functional, cognitive, and patient-centered outcomes, and lack of control groups. Therefore, our current ability to interpret clinical results and make reliable recommendations regarding the use of rescue therapies is limited. This review summarizes existing literature on rescue therapies for DCI, provides practical guidance, and identifies future research needs., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Aim: The "2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage" replaces the 2012 "Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage." The 2023 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with aneurysmal subarachnoid hemorrhage., Methods: A comprehensive search for literature published since the 2012 guideline, derived from research principally involving human subjects, published in English, and indexed in MEDLINE, PubMed, Cochrane Library, and other selected databases relevant to this guideline, was conducted between March 2022 and June 2022. In addition, the guideline writing group reviewed documents on related subject matter previously published by the American Heart Association. Newer studies published between July 2022 and November 2022 that affected recommendation content, Class of Recommendation, or Level of Evidence were included if appropriate. Structure: Aneurysmal subarachnoid hemorrhage is a significant global public health threat and a severely morbid and often deadly condition. The 2023 aneurysmal subarachnoid hemorrhage guideline provides recommendations based on current evidence for the treatment of these patients. The recommendations present an evidence-based approach to preventing, diagnosing, and managing patients with aneurysmal subarachnoid hemorrhage, with the intent to improve quality of care and align with patients' and their families' and caregivers' interests. Many recommendations from the previous aneurysmal subarachnoid hemorrhage guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

Background: Intracranial pressure (ICP) monitoring and its management in aneurysmal subarachnoid hemorrhage (aSAH) is variable worldwide. The present study aimed to explore the practice of ICP monitoring, its variability across countries, and the association with 6-month outcomes in aSAH., Methods: This was a preplanned subanalysis of SYNAPSE-ICU, a multicenter, international, prospective, observational cohort study focused on patients diagnosed with aSAH. We evaluated the variability in ICP monitoring across countries through a logistic regression model adjusted for case-mix and considered countries as a random effect. The association between ICP probe insertion and 6-month mortality and a poor neurological outcome, defined as an Glasgow Outcome Score Extended ≤ 4, was assessed by using a propensity score approach., Results: A total of 423 patients with aSAH from 92 centers across 32 countries were included in this analysis. ICP monitoring was used in 295 (69.7%) patients. Significant between-country variability in ICP insertion was observed, with an incidence ranging between 4.7% and 79.9% (median odd ratio 3.04). The median duration of ICP monitoring was 12 days (first quartile [Q1] through third quartile [Q3] range 8-18), with an overall daily median ICP value of 14 mm Hg (Q1-Q3 10-19) and a median maximum value of 21 mm Hg (Q1-Q3 16-30). Patients monitored with ICP received more aggressive therapy treatments compared with non-monitored patients (therapy intensity level, TIL, score 10.33 [standard deviation 3.61] vs. 6.3 [standard deviation 4.19], p < 0.001). In more severe patients, ICP monitoring was significantly associated with better 6-month outcome (poor neurological outcome: odds ratio 0.14, 95% confidence interval 0.02-0.53, p = 0.0113; mortality: hazard ratio 0.25, 95% confidence interval 0.13-0.49, p < 0.0001). However, no significant effect was observed in patients with both reactive pupils., Conclusions: Our cohort demonstrated high variability in ICP insertion practice among countries. A more aggressive treatment approach was applied in ICP-monitored patients. In patients with severe aSAH, ICP monitoring might reduce unfavorable outcomes and mortality at 6 months., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Cilostazol, a phosphodiesterase III inhibitor, appears to be a promising agent for preventing cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage. Here, the authors perform a systematic review and meta-analysis to quantitatively assess the effects of cilostazol on brain structural and functional outcomes in animal models of cerebral ischemia and subarachnoid hemorrhage-induced cerebral vasospasm., Methods: By using the PRISMA guidelines, a search of the PubMed, Scopus, and Web of Science was conducted to identify relevant studies. Study quality of each included study for both systematic reviews were scored by using an adapted 15-item checklist from the Collaborative Approach to Meta-Analysis of Animal Data from Experimental Studies. We calculated a standardized mean difference as effect size for each comparison. For each outcome, comparisons were combined by using random-effects modeling to account for heterogeneity, with a restricted maximum likelihood estimate of between-study variance., Results: A total of 22 (median [Q1, Q3] quality score of 7 [5, 8]) and 6 (median [Q1, Q3] quality score of 6 [6, 6]) studies were identified for cerebral ischemia and subarachnoid hemorrhage-induced cerebral vasospasm, respectively. Cilostazol significantly reduced the infarct volume in cerebral ischemia models with a pooled standardized mean difference estimate of - 0.88 (95% confidence interval [CI] [- 1.07 to - 0.70], p < 0.0001). Cilostazol significantly reduced neurofunctional deficits in cerebral ischemia models with a pooled standardized mean difference estimate of - 0.66 (95% CI [- 1.06 to - 0.28], p < 0.0001). Cilostazol significantly improved the basilar artery diameter in subarachnoid hemorrhage-induced cerebral vasospasm with a pooled standardized mean difference estimate of 2.30 (95% CI [0.94 to 3.67], p = 0.001). Cilostazol also significantly improved the basilar artery cross-section area with a pooled standardized mean estimate of 1.88 (95% CI [0.33 to 3.43], p < 0.05). Overall, there was between-study heterogeneity and asymmetry in the funnel plot observed in all comparisons., Conclusions: Published animal data support the overall efficacy of cilostazol in reducing infarct volume and neurofunctional deficits in cerebral ischemia models and cerebral vasospasm in subarachnoid hemorrhage models., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Platelet to lymphocyte ratio (PLR) is a prognostic marker in human hepatocellular carcinoma (HCC) however, its utility in canine HCC has not been explored. The aim of the study was to determine if PLR could predict survival outcomes in 42 dogs with HCC. PLR was not a significant predictive factor ( p = 0.15) but lymphopenia alone was significantly correlated with a reduced probability of survival ( p = 0.024). Further studies are needed to evaluate if peripheral lymphocyte count mirrors that of the tumor microenvironment in canine HCC., Competing Interests: Conceptualization: Johnston AN; Data curation: Suarez-Rodriguez JI; Formal analysis: Liu CC; Investigation: Suarez-Rodriguez JI; Methodology: Suarez-Rodriguez JI; Project administration: Johnston AN; Software: Liu CC; Supervision: Johnston AN; Validation: Liu CC, Dehghanpir SD Johnston AN; Visualization: Liu CC, Johnston AN; Writing - original draft: Suarez-Rodriguez JI; Writing - review & editing: Liu CC, Dehghanpir SD, Johnston AN., (© 2023 The Korean Society of Veterinary Science.)

Background: Stroke patients requiring mechanical ventilation often have a poor prognosis. The optimal timing of tracheostomy and its impact on mortality in stroke patients remains uncertain. We performed a systematic review and meta-analysis of tracheostomy timing and its association with reported all-cause overall mortality. Secondary outcomes were the effect of tracheostomy timing on neurological outcome (modified Rankin Scale, mRS), hospital length of stay (LOS), and intensive care unit (ICU) LOS., Methods: We searched 5 databases for entries related to acute stroke and tracheostomy from inception to 25 November 2022. We adhered to PRISMA guidance for reporting systematic reviews and meta-analyses. Selected studies included (1) ICU-admitted patients who had stroke (either acute ischaemic stroke, AIS or intracerebral haemorrhage, ICH) and received a tracheostomy (with known timing) during their stay and (2) > 20 tracheotomised. Studies primarily reporting sub-arachnoid haemorrhage (SAH) were excluded. Where this was not possible, adjusted meta-analysis and meta-regression with study-level moderators were performed. Tracheostomy timing was analysed continuously and categorically, where early (< 5 days from initiation of mechanical ventilation to tracheostomy) and late (> 10 days) timing was defined per the protocol of SETPOINT2, the largest and most recent randomised controlled trial on tracheostomy timing in stroke patients., Results: Thirteen studies involving 17,346 patients (mean age = 59.8 years, female 44%) met the inclusion criteria. ICH, AIS, and SAH comprised 83%, 12%, and 5% of known strokes, respectively. The mean time to tracheostomy was 9.7 days. Overall reported all-cause mortality (adjusted for follow-up) was 15.7%. One in five patients had good neurological outcome (mRS 0-3; median follow-up duration was 180 days). Overall, patients were ventilated for approximately 12 days and had an ICU LOS of 16 days and a hospital LOS of 28 days. A meta-regression analysis using tracheostomy time as a continuous variable showed no statistically significant association between tracheostomy timing and mortality (β = - 0.3, 95% CI = - 2.3 to 1.74, p = 0.8). Early tracheostomy conferred no mortality benefit when compared to late tracheostomy (7.8% vs. 16.4%, p = 0.7). Tracheostomy timing was not associated with secondary outcomes (good neurological outcome, ICU LOS and hospital LOS)., Conclusions: In this meta-analysis of over 17,000 critically ill stroke patients, the timing of tracheostomy was not associated with mortality, neurological outcomes, or ICU/hospital LOS., Trial Registration: PROSPERO-CRD42022351732 registered on 17th of August 2022., (© 2023. The Author(s).)

Introduction: Traumatic Brain Injury (TBI) has been shown to be associated with altered hemostasis and coagulopathy, that correlates with worsening secondary injury and clinical outcomes. Isolated Traumatic Brain Injury (iTBI), that is TBI without significant extracranial injuries, has also been shown to be associated with systemic coagulopathy and derangements in hemostasis., Methods: Literature Review., Results: Present your results in logical sequence in the text, tables, and figures, giving the main or most important findings first. Do not repeat all the data in the tables or figures in the text; emphasize or summarize only the most important observations. Provide data on all primary and secondary outcomes identified in the Methods section. Give numeric results not only as derivatives (e.g. percentages) but also as the absolute numbers from which the derivatives were calculated, and specify the statistical significance attached to them, if any., Discussion: In this review, we provide an overview of the pathophysiology of the hemostatic disturbances caused by iTBI, review key clinical findings and discrepancies in the way this question has been approached, describe the use and role of global viscoelastic assays such as the thromboelastrogram, and detail principles for reversal of pre-injury blood thinners., Conclusions: iTBI is clearly associated with the development of coagulopathy, but the extent to which it occurs is confounded by the fact that many of the studies have included patients with moderate extracranial trauma into the iTBI category. The coagulopathy itself has been better studied in preclinical models, and the mechanisms driving it suggest a pattern consistent with disseminated intravascular coagulation with hyperfibrinolysis. We provide pragmatic clinical takeaways and suggestions for future research., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

This proceedings article presents the scope of pediatric coma and disorders of consciousness based on presentations and discussions at the First Pediatric Disorders of Consciousness Care and Research symposium held on September 14th, 2021. Herein we review the current state of pediatric coma care and research opportunities as well as shared experiences from seasoned researchers and clinicians. Salient current challenges and opportunities in pediatric and neonatal coma care and research were identified through the contributions of the presenters, who were Jose I. Suarez, MD, Nina F. Schor, MD, PhD, Beth S. Slomine, PhD Erika Molteni, PhD, and Jan-Marino Ramirez, PhD, and moderated by Varina L. Boerwinkle, MD, with overview by Mark Wainwright, MD, and subsequent audience discussion. The program, executively planned by Varina L. Boerwinkle, MD, Mark Wainwright, MD, and Michelle Elena Schober, MD, drove the identification and development of priorities for the pediatric neurocritical care community., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Improving neurosurgical quality metrics necessitates the analysis of patient safety indicator (PSI) 04, a measure of failure to rescue (FTR)., Objective: To demonstrate that PSI 04 is not an appropriate measure for capturing FTR within neurosurgery., Methods: We conducted a single-center retrospective cohort study. Patients from January 1, 2017 to June 1, 2021, who sustained a PSI 04-attributed complication (pneumonia, deep vein thrombosis/pulmonary embolism, sepsis, shock/cardiac arrest, or gastrointestinal hemorrhage/acute ulcer), underwent a neurosurgical procedure, had inpatient mortality, and were identified using patient safety indicator 04 (PSI 04) tracking algorithm. The primary outcome was whether the attributed PSI 04 designation was the primary driver of mortality., Results: We identified 67 patients who met the PSI 04 criteria (median age, 61 years; female sex, 43.4%). Nearly 20% of patients met the PSI complication criteria before admission. Patients who underwent emergent bedside procedures were more likely to present with a poor Glasgow Coma Scale ( P = .016), more likely to be intubated before admission ( P = .016), and less likely to have mortality due to a PSI 04-related complication ( P = .002). PSI 04-related complications were identified as the cause of death in only 43.2% of cases. Procedures occurring in the interventional radiology suite (odds ratio, 23.2; 95% CI, 3.5-229.3; P = .003) or the operating room (odds ratio, 6.2; 95% CI, 1.25-39.5; P = .03) were more likely to have mortality because of a PSI 04-related complication compared with bedside procedures., Conclusion: In total, 65.7% of patients were inappropriately flagged as meeting PSI 04 criteria. PSI 04 currently identifies patients with complications unrelated to operating room procedures. Improvement in patient safety within neurosurgery necessitates the development of a subspecialty specific measure to capture FTR., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

To ensure neuronal survival after severe traumatic brain injury, oxygen supply is essential. Cerebral tissue oxygenation represents the balance between oxygen supply and consumption, largely reflecting the adequacy of cerebral perfusion. Multiple physiological parameters determine the oxygen delivered to the brain, including blood pressure, hemoglobin level, systemic oxygenation, microcirculation and many factors are involved in the delivery of oxygen to its final recipient, through the respiratory chain. Brain tissue hypoxia occurs when the supply of oxygen is not adequate or when for some reasons it cannot be used at the cellular level. The causes of hypoxia are variable and can be analyzed pathophysiologically following "the oxygen route." The current trend is precision medicine, individualized and therapeutically directed to the pathophysiology of specific brain damage; however, this requires the availability of multimodal monitoring. For this purpose, we developed the acronym "THE MANTLE," a bundle of therapeutical interventions, which covers and protects the brain, optimizing the components of the oxygen transport system from ambient air to the mitochondria., (© 2023. The Author(s).)

To investigate the effect of the occurrence of early hyperchloremia on death or severe disability at 180 days in patients with severe traumatic brain injury (TBI)., Design: Post hoc analysis of Resuscitation Outcomes Consortium Hypertonic Saline (ROC HS)-TBI trial., Setting: A total of 114 North American emergency medical services agencies in the ROC., Patients: A total of 991 patients with severe TBI and Glasgow Coma Scale score of less than or equal to 8., Interventions: Prehospital resuscitation with single IV dose (250 cc) of 7.5% saline in 6% dextran-70, 7.5% saline (no dextran), or crystalloid., Measurements and Main Results: Patients with increased serum chloride concentrations (110 mmol/L or greater) 24 hours after randomization were identified. Hyperchloremia was graded into one or greater than or equal to 2 occurrences in the first 24 hours. Logistic regression analyses were performed to determine the effects of hyperchloremia on: 1) death or severe disability at 180 days and 2) death within 180 days after adjusting for confounders. Compared with patients without hyperchloremia, patients with greater than or equal to 2 occurrences of hyperchloremia had significantly higher odds of death or severe disability at 180 days (odds ratio [OR], 1.81; 95% CI, 1.19-2.75) and death within 180 days (OR, 1.89; 95% CI, 1.14-3.08) after adjustment for confounders. However, the total volume of fluids administered during the first 24 hours was an independent predictor of death within 180 days; therefore, after adding an interaction term between the total volume of fluids administered during the first 24 hours and greater than or equal to 2 occurrences of hyperchloremia, patients with greater than or equal to 2 occurrences of hyperchloremia had significantly higher odds of death within 180 days (OR, 2.35; 95% CI, 1.21-4.61 d) but not of composite outcome of death or severe disability at 180 days., Conclusions: After modifying for the effect of the total volume of fluids administered during the first 24 hours, multiple occurrences of hyperchloremia in the first 24 hours were associated with higher odds of death within 180 days in patients with severe TBI., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Objective: The aim of this study was to better define the shape of association between the degree ("magnitude") of early (< 1 h) reduction in systolic blood pressure (SBP) and outcomes in patients with acute intracerebral hemorrhage (ICH) through pooled analysis of the second Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) and second Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-II) datasets., Methods: Association of the continuous magnitude of SBP reduction described using cubic splines and an ordinal measure of the functional outcome on the modified Rankin scale (mRS) scores at 90 days were analyzed in generalized linear mixed models. Models were adjusted for achieved (mean) and variability (standard deviation, SD) of SBP between 1 and 24 h, various baseline covariates, and trial as a random effect., Results: Among 3796 patients (mean age 63.1 (SD = 13.0) years; female 37.4%), with a mean magnitude (< 1 h) of SBP reduction of 28.5 (22.8) mmHg, those with larger magnitude were more often non-Asian and female, had higher baseline SBP, received multiple blood pressure (BP) lowering agents, and achieved lower SBP levels in 1-24 h. Compared to those patients with no SBP reduction within 1 h (reference), the adjusted odds of unfavorable functional outcome, according to a shift in mRS scores, were lower for SBP reductions up to 60 mmHg with an inflection point between 32 and 46 mmHg, but significantly higher for SBP reductions > 70 mmHg. Similar J-shape associations were evident across various time epochs across 24 h and consistent according to baseline hematoma volume and SBP and history of hypertension., Interpretation: A moderate degree of rapid SBP lowering is associated with improved functional outcome after ICH, but large SBP reductions over 1 h (e.g. from > 200 to target < 140 mmHg) were associated with reduction, or reversal, of any such benefit.

Background: Individuals who are dehydrated, volume contracted or both at the time of hospitalization for acute ischemic stroke have worse clinical outcomes than do individuals with optimal volume status. Currently, there is no gold standard method for measuring hydration status, except indirect markers of a volume contracted state (VCS) including elevated blood urea nitrogen (BUN)/creatinine ratio. We sought to test the feasibility and acceptability of a non-invasive cardiac output monitor (NICOM) for the measurement of hydration status in a group of hospitalized ischemic stroke patients, and explore the relationship with a common indirect laboratory-based measure of VCS., Methods: We performed a prospective observational feasibility study of hospitalized acute ischemic stroke patients. We collected hemodynamic parameters using the NICOM device before and after fluid auto-bolus via passive leg raise and BUN/creatinine ratio. Successful acquisition of relevant hemodynamic data was the primary objective of this study. We explored agreement between the NICOM results and BUN/creatinine ratio using Cohen's kappa statistic., Results: Thirty patients hospitalized with acute ischemic stroke were enrolled. We found that 29/30 patients tolerated assessment with NICOM. Hemodynamic data were collected in all 30 patients. Data capture took an average of 10 min(SD ± 112 s). Agreement between NICOM and BUN/creatinine ratio was 70%; (expected agreement 51%; kappa 0.38). Agreement was stronger in the cohort without history of diabetes (81% agreement, kappa 0.61)., Conclusions: NICOM assessment was feasible in hospitalized stroke patients. The identification of an objective, real-time measure of hydration status would be clinically useful, and could allow precise, goal-directed care., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: On the basis of increased mortality associated with hyperchloremia among critically ill patients, we investigated the effect of occurrence of early hyperchloremia on death or disability at 90 days in patients with intracerebral hemorrhage (ICH)., Methods: We analyzed the data from Antihypertensive Treatment of Cerebral Hemorrhage 2 trial, which recruited patients with spontaneous ICH within 4.5 h of symptom onset. Patients with increased serum chloride levels (110 mmol/L or greater) at either baseline or 24, 48, or 72 h after randomization were identified. We further graded hyperchloremia into one occurrence or two or more occurrences within the first 72 h. Two logistic regression analyses were performed to determine the effects of hyperchloremia on (1) death within 90 days and (2) death or disability at 90 days after adjustment for potential confounders., Results: Among the total of 1,000 patients analyzed, hyperchloremia within 72 h was seen in 114 patients with one occurrence and in 154 patients with two or more occurrences. Patients with one occurrence of hyperchloremia (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.1-5.5) and those with two or more occurrences (OR 2.6, 95% CI 1.3-5.0) had significantly higher odds of death within 90 days after adjustment for age, race and ethnicity, National Institutes of Health Stroke Scale score strata, hematoma volume, presence or absence of intraventricular hemorrhage, cigarette smoking, previous stroke, and maximum hourly dose of nicardipine. Patients with two or more occurrences of hyperchloremia (OR 3.4, 95% CI 2.1-5.6) had significantly higher odds of death or disability at 90 days compared with patients without hyperchloremia after adjustment for the abovementioned potential confounders., Conclusions: The independent association between hyperchloremia and death or disability at 90 days suggests that avoidance of hyperchloremia may reduce the observed death or disability in patients with ICH., Clinical Trial Registration: ClinicalTrials.gov: NCT01176565., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Objectives: The standard-of-care for postoperative care following elective craniotomy has historically been ICU admission. However, recent literature interrogating complications and interventions during this postoperative ICU stay suggests that all patients may not require this level of care. Thus, hospitals began implementing non-ICU postoperative care pathways for elective craniotomy. This systematic review aims to summarize and evaluate the existing literature regarding outcomes and costs for patients receiving non-ICU care after elective craniotomy., Data Sources: A systematic review of the PubMed database was performed following PRISMA guidelines from database inception to August 2021., Study Selection: Included studies were published in peer-reviewed journals, in English, and described outcomes for patients undergoing elective craniotomies without postoperative ICU care., Data Extraction: Data regarding study design, patient characteristics, and postoperative care pathways were extracted independently by two authors. Quality and risk of bias were evaluated using the Oxford Centre for Evidence-Based Medicine Levels of Evidence tool and Risk Of Bias In Non-Randomized Studies-of Interventions tool, respectively., Data Synthesis: In total, 1,131 unique articles were identified through the database search, with 27 meeting inclusion criteria. Included articles were published from 2001 to 2021 and included non-ICU inpatient care and same-day discharge pathways. Overall, the studies demonstrated that postoperative non-ICU care for elective craniotomies led to length of stay reduction ranging from 6 hours to 4 days and notable cost reductions. Across 13 studies, 53 of the 2,469 patients (2.1%) intended for postoperative management in a non-ICU setting required subsequent care escalation., Conclusions: Overall, these studies suggest that non-ICU care pathways for appropriately selected postcraniotomy patients may represent a meaningful opportunity to improve care value. However, included studies varied greatly in patient selection, postoperative care protocol, and outcomes reporting. Standardization and multi-institutional collaboration are needed to draw definitive conclusions regarding non-ICU postoperative care for elective craniotomy., Competing Interests: Dr. Rincon-Torroella’s institution received funding from the National Institute of Neurological Disorders and Stroke (R25 grant holder [5R25NS065729]); she received support for article research from the National Institutes of Health (NIH). Dr. Jackson received funding from Boehringer Laboratories and Egret Therapeutics. Dr. Brem received funding from the NIH, Johns Hopkins University, Arbor Pharmaceuticals, and Bristol-Myers Squibb; he disclosed that he is a consultant for AcuityBio Corp., InSightec, Accelerating Combination Therapies, Catalio Nexus Fund II, CraniUS, Candel Therapeutics, LikeMinds, Galen Robotics, Nurami Medical, AsclepiX Therapeutics, and StemGen. Dr. Bettegowda disclosed that he is a consultant for Depuy-Synthes, Bionaut Labs, and Galectin Therapeutics. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Big data (BD) and artificial intelligence (AI) have increasingly been used in neurocritical care. "BD" can be operationally defined as extremely large datasets that are so large and complex that they cannot be analyzed by using traditional statistical modeling. "AI" means the ability of machines to perform tasks similar to those performed by human intelligence. We present a brief overview of the most commonly applied AI techniques to perform BD analytics and discuss some of the recent promising examples in the field of neurocritical care. The latter include the following: cognitive motor dissociation in disorders of consciousness, hypoxic-ischemic injury following cardiac arrest, delayed cerebral ischemia and vasospasm after subarachnoid hemorrhage, and monitoring of intracranial pressure. It is imperative that we develop multicenter collaborations to tackle BD. These collaborations will allow us to share data, combine predictive algorithms, and analyze multiple and cumulative sources of data retrospectively and prospectively. Once AI algorithms are validated at multiple centers, they should be tested in randomized controlled trials investigating their impact on clinical outcome. The neurocritical care community must work to ensure that AI incorporates standards to ensure fairness and health equity rather than reflect our biases present in our collective conscience., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Objective: Based on the relationship between hyperchloremia and mortality in critically ill patients, we investigated the effect of early hyperchloremia on 90-day outcomes in acute ischemic stroke patients., Materials and Methods: Acute ischemic stroke patients recruited within 5 h of symptom onset were analyzed. Hyperchloremia (defined as 110 mmol/L or greater) at either baseline, or 24, or 48 h after randomization was identified and classified as one occurrence or two or more occurrences. Logistic regression analyses were performed to determine the effects of hyperchloremia on: favorable outcomes (defined by a National Institutes of Health Stroke Scale and/or modified Rankin scale scores of 0-1) at 90-day, death or disability at 90-day, and death within 90-day after accounting for potential confounders., Results: Among the total of 1275 patients, one and two or more occurrence of hyperchloremia within 48 h were seen in 191 patients and 108 patients, respectively. Compared with patients without hyperchloremia, patients with two or more occurrences of hyperchloremia at significantly higher odds of lack of favorable outcomes (odds ratio 3.0, 95% confidence interval 1.8-5.1) and death or disability (odds ratio 2.6, 95% confidence interval 1.6-4.1) at 90-day after adjustment for age, National Institutes of Health Stroke Scale score strata (6-9, 10-19, ≥ 20), study intervention, initial SBP, and intra-arterial treatment., Conclusions: The independent association between sustained hyperchloremia and lack of favorable outcomes at 90-day suggest that avoidance of hyperchloremia may reduce the rate of lack of favorable outcomes and death or disability in patients with acute ischemic stroke., Competing Interests: Declaration of Competing Interest Dr. Qureshi has received consultation fees from AstraZeneca., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: External ventricular drains (EVD) are commonly used in aneurysmal subarachnoid hemorrhage (aSAH) patients and can be life-saving by diverting cerebrospinal fluid. However, the overall relationship between EVD use and outcome is poorly understood., Methods: In an exploratory analysis of an aSAH patient cohort, we examined EVD use in relation to modified Rankin Scale (mRS) at hospital discharge and at 6 months (unfavorable outcome = mRS > 2) using univariable and multivariable analyses., Results: EVDs were placed in 31 of 56 (55.4%) patients and more often in women than men (66.7% vs 35.0%, p = 0.022) despite similar rates of hydrocephalus. Women had greater ICU [18 (13.5-25) vs 11.5 (6.5-18.5) days, p = 0.014] and hospital lengths of stay (LOS) [20.5 (16.5-34) vs 13.5 (10.5-27) days, p = 0.015] than men and greater mRS at discharge [4 (3-5) vs 3 (2-3.5), p = 0.011] although mRS at 6 months was similar. Patients with EVDs had longer ICU and hospital LOS and greater mRS at discharge [5 (3-6) vs 2 (2-3), p < 0.001] and at 6 months [4 (2-6) vs 1 (0-2), p = 0.001] than those without an EVD. In multivariable models, EVD use was associated with unfavorable 6-month outcome accounting for age, sex, and admission modified Fisher scale, but not in models adjusting for Hunt and Hess scale and World Federation of Neurological Surgeons scale., Conclusion: In an aSAH cohort, the use of EVDs was associated with female sex and longer LOS, and may be linked to functional outcomes at discharge and at 6 months, although these associations warrant further investigation., (© 2022. The Author(s).)