Neurocritical Care最新文献

{"title":"Ketamine for Critically Ill Patients with Severe Acute Brain Injury: A Systematic Review with Meta-analysis and Trial Sequential Analysis of Randomized Clinical Trials.","authors":"Trine Hjorslev Andreasen, Frederik Andreas Madsen, Marija Barbateskovic, Jane Lindschou, Christian Gluud, Kirsten Møller","doi":"10.1007/s12028-024-02075-2","DOIUrl":"10.1007/s12028-024-02075-2","url":null,"abstract":"<p><strong>Background: </strong>Patients with severe acute brain injury have a high risk of a poor clinical outcome due to primary and secondary brain injury. Ketamine reportedly inhibits cortical spreading depolarization, an electrophysiological phenomenon that has been associated with secondary brain injury, making ketamine potentially attractive for patients with severe acute brain injury. The aim of this systematic review is to explore the current literature regarding ketamine for patients with severe acute brain injury.</p><p><strong>Methods: </strong>We systematically searched international databases for randomized clinical trials comparing ketamine by any regimen versus placebo, no intervention, or any control drug for patients with severe acute brain injury. Two authors independently reviewed and selected trials for inclusion, extracted data, assessed risk of bias, and performed analysis using Review Manager and Trial Sequential Analysis. Evidence certainty was assessed using Grading of Recommendations Assessment, Development and Evaluation. The primary outcomes were the proportion of participants with an unfavorable functional outcome, the proportion of participants with one or more serious adverse events, and quality of life.</p><p><strong>Results: </strong>We identified five randomized trials comparing ketamine versus sufentanil, fentanyl, other sedatives, or saline (total N = 149 participants). All outcomes were at overall high risk of bias. The proportions of participants with one or more serious adverse events did not differ between ketamine and sufentanil or fentanyl (relative risk 1.45, 95% confidence interval 0.81-2.58; very low certainty). Trial sequential analysis showed that further trials are needed.</p><p><strong>Conclusions: </strong>The level of evidence regarding the effects of ketamine on functional outcome and serious adverse events in patients with severe acute brain injury is very low. Ketamine may markedly, modestly, or not at all affect these outcomes. Large randomized clinical trials at low risk of bias are needed.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":"610-621"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Andexanet Alfa Versus Four Factor Prothrombin Complex Concentrate for Emergent Reversal of Factor Xa Inhibitor Associated Intracranial Hemorrhage: A Systematic Review and Meta-Analysis.","authors":"Khalid Sarhan, Rashad G Mohamed, Reem Reda Elmahdi, Youstina Mohsen, Asmaa Elsayed, Dania Mosaad Zayed, Menna A Elkholi, Nagat Gabr, Enjy M El-Bialy, Ibrahim Serag","doi":"10.1007/s12028-024-02130-y","DOIUrl":"10.1007/s12028-024-02130-y","url":null,"abstract":"<p><p>Factor Xa inhibitors (FXaI) are increasingly used for anticoagulation therapy, yet their association with intracranial hemorrhage poses a significant challenge. Although andexanet alfa (AA) and four-factor prothrombin complex concentrate (4F-PCC) have shown promise in reversing FXaI effects, their comparative efficacy and safety remain uncertain. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a literature search on electronic databases to obtain the relevant studies until May 16, 2024. Our primary outcomes were successful anticoagulation reversal, overall mortality (including 30-day and in-hospital mortality), and thromboembolic events. Secondary outcomes were length of hospital and intensive care unit stay and hematoma volume expansion. Data were pooled using a random-effects model. We included 16 eligible studies with a total of 2,977 patients. A statistically significant improvement in hemostatic efficacy rates was in favor of the AA group (risk ratio [RR] 1.10, 95% confidence interval [CI] 1.01-1.20, P = 0.02). Lower overall mortality rates were found in the AA group (RR 0.67, 95% CI 0.51-0.88, P = 0.004). However, no difference was found in 30-day mortality rates (RR 0.82, 95% CI 0.58-1.16, P = 0.26). In terms of thromboembolic events, more events were found in the AA group (RR 1.47, 95% CI 1.01-2.15, P = 0.046). AA was associated with a longer duration of hospital stay compared to 4F-PCC (mean difference [MD] 0.64, 95% CI 0.07-1.22, P = 0.03). Neither a significant difference in length of intensive care unit stay (MD 0.25, 95% CI - 0.36 to 0.86, P = 0.41) nor a significant difference in hematoma volume expansion was reported (MD - 0.89, 95% CI - 3.11 to 1.34, P = 0.435). Our results suggest that AA is superior to 4F-PCC in enhancing the hemostatic efficacy and reducing the overall and in-hospital mortality rates. More thromboembolic events are thought to be associated with the use of AA. However, more studies are required to validate whether the better results of AA in improving hemostatic efficacy are enough to make up for their higher cost and their possible risk of thromboembolic events.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":"701-714"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive Models of Long-Term Outcome in Patients with Moderate to Severe Traumatic Brain Injury are Biased Toward Mortality Prediction.","authors":"Florian P Martin, Thomas Goronflot, Jean D Moyer, Olivier Huet, Karim Asehnoune, Raphaël Cinotti, Pierre A Gourraud, Antoine Roquilly","doi":"10.1007/s12028-024-02082-3","DOIUrl":"10.1007/s12028-024-02082-3","url":null,"abstract":"<p><strong>Background: </strong>The prognostication of long-term functional outcomes remains challenging in patients with traumatic brain injury (TBI). Our aim was to demonstrate that intensive care unit (ICU) variables are not efficient to predict 6-month functional outcome in survivors with moderate to severe TBI (msTBI) but are mostly associated with mortality, which leads to a mortality bias for models predicting a composite outcome of mortality and severe disability.</p><p><strong>Methods: </strong>We analyzed the data from the multicenter randomized controlled Continuous Hyperosmolar Therapy in Traumatic Brain-Injured Patients trial and developed predictive models using machine learning methods and baseline characteristics and predictors collected during ICU stay. We compared our models' predictions of 6-month binary Glasgow Outcome Scale extended (GOS-E) score in all patients with msTBI (unfavorable GOS-E 1-4 vs. favorable GOS-E 5-8) with mortality (GOS-E 1 vs. GOS-E 2-8) and binary functional outcome in survivors with msTBI (severe disability GOS-E 2-4 vs. moderate to no disability GOS-E 5-8). We investigated the link between ICU variables and long-term functional outcomes in survivors with msTBI using predictive modeling and factor analysis of mixed data and validated our hypotheses on the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) model.</p><p><strong>Results: </strong>Based on data from 370 patients with msTBI and classically used ICU variables, the prediction of the 6-month outcome in survivors was inefficient (mean area under the receiver operating characteristic 0.52). Using factor analysis of mixed data graph, we demonstrated that high-variance ICU variables were not associated with outcome in survivors with msTBI (p = 0.15 for dimension 1, p = 0.53 for dimension 2) but mostly with mortality (p < 0.001 for dimension 1), leading to a mortality bias for models predicting a composite outcome of mortality and severe disability. We finally identified this mortality bias in the IMPACT model.</p><p><strong>Conclusions: </strong>We demonstrated using machine learning-based predictive models that classically used ICU variables are strongly associated with mortality but not with 6-month outcome in survivors with msTBI, leading to a mortality bias when predicting a composite outcome of mortality and severe disability.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":"573-586"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of N-Methyl-D-Aspartate (NMDA) Receptor Antagonists in Treating Traumatic Brain Injury-Induced Brain Edema: A Systematic Review and Meta-analysis of Animal Studies.","authors":"Fernanda Cristina Poscai Ribeiro, Nadine Vieira de Oliveira, Gabriela Regonha Coral, Alcântara Ramos de Assis César, Moisés Willian Aparecido Gonçalves, Erika Said Abu Egal, Kleber Fernando Pereira","doi":"10.1007/s12028-024-02079-y","DOIUrl":"10.1007/s12028-024-02079-y","url":null,"abstract":"<p><p>Traumatic brain injury leads to glutamate release, which overstimulates N-methyl-D-aspartate (NMDA) receptors, leading to neurotoxicity and cytotoxic edema. NMDA receptor antagonists may offer neuroprotection by blocking this pathway. The objective of this systematic review is to assess the efficacy of NMDA receptor antagonists for traumatic brain injury-induced brain edema in rodent models. This systematic review followed Cochrane Handbook guidelines and registered its protocol in PROSPERO (ID: CRD42023440934). Here, we included controlled rodent animal models comparing NMDA antagonist use with a placebo treatment. Outcome measures included the reduction of cerebral edema, Neurobehavioral Severity Scale, and adverse effects. The search strategy used Medical Subject Headings terms related to traumatic brain injury and NMDA receptor antagonists. The Collaborative Approach to Meta Analysis and Review of Animal Experimental Studies (CAMARADES) checklist and Systematic Review Centre for Laboratory Animal Experimentation's (SYRCLE's) tools were used to measure the quality and bias of included studies. The synthesis of results was presented in a meta-analysis of standard mean difference. Sixteen studies were included, with the predominant drugs being ifenprodil, MK-801, magnesium, and HU-211. The subjects consisted of Sprague-Dawley or Sabra rats. The analysis showed a significant reduction in brain edema with NMDA antagonist treatment (Standardized mean difference [SMD] - 1.17, 95% confidence interval [CI] - 1.59 to - 0.74, p < 0.01), despite high heterogeneity (I² = 72%). Neurobehavioral Severity Scale also significantly improved (mean difference - 3.32, 95% CI - 4.36 to - 2.28, p < 0.01) in animals receiving NMDA antagonists. Administration within 1 h after injury showed a modest enhancement in reducing brain edema compared with the baseline (SMD - 1.23, 95% CI - 1.69 to - 0.77, p < 0.01). Studies met standards for animal welfare and model appropriateness. Although baseline comparability and selective reporting bias were generally addressed, key biases such as randomization, allocation concealment, and blinding were often unreported. Overall, NMDA antagonists exhibit promising efficacy in the treatment of traumatic brain injury. Notably, our systematic review consistently demonstrated a significant reduction in brain edema with compounds including HU-211 and NPS 150.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":"622-634"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Robotic Assisted Transcranial Doppler Monitoring in Acute Neurovascular Care: A Feasibility and Safety Study.","authors":"Alvise Fattorello Salimbeni, Caterina Kulyk, Francesco Favruzzo, Ludovica De Rosa, Federica Viaro, Alessio Pieroni, Stefano Mozzetta, Milan R Vosko, Claudio Baracchini","doi":"10.1007/s12028-024-02121-z","DOIUrl":"10.1007/s12028-024-02121-z","url":null,"abstract":"<p><strong>Background: </strong>Transcranial color Doppler (TCD) is currently the only noninvasive bedside tool capable of providing real-time information on cerebral hemodynamics. However, being operator dependent, TCD monitoring is not feasible in many institutions. Robotic assisted TCD (ra-TCD) was recently developed to overcome these constraints. The aim of this study was to evaluate the safety and feasibility of cerebral monitoring with a novel ra-TCD in acute neurovascular care.</p><p><strong>Methods: </strong>This is a two-center prospective study conducted between August 2021 and February 2022 at Padua University Hospital (Padua, Italy) and Kepler University Hospital (Linz, Austria). Adult patients with conditions impacting cerebral hemodynamics or patients undergoing invasive procedures affecting cerebral hemodynamics were recruited for prolonged monitoring (> 30 min) of the middle cerebral artery with a novel ra-TCD (NovaGuide Intelligent Ultrasound, NeuraSignal, Los Angeles, CA). Manual TCD was also performed for comparison by an experienced operator. Feasibility and safety rates were recorded.</p><p><strong>Results: </strong>A total of 92 patients (age: mean 68.5 years, range 36-91; sex: male 57 [62%]) were enrolled in the two centers: 54 in Padua, 38 in Linz. The examination was feasible in the majority of patients (85.9%); the head cradle design and its radiopacity hindered its use during carotid endarterectomy and mechanical thrombectomy. Regarding safety, only one patient (1.1%) reported a minor local edema due to prolonged probe pressure. Velocity values were similar between ra-TCD and manual TCD.</p><p><strong>Conclusions: </strong>This novel ra-TCD showed an excellent safety and feasibility and proved to be as reliable as manual TCD in detecting blood flow velocities. These findings support its wider use for cerebral hemodynamics monitoring in acute neurovascular care. However, further technical improvements are needed to expand the range of applicable settings.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":"457-464"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contribution of an Automatic Algorithm for Quantifying the Volume of Aneurysmal Subarachnoid Hemorrhage to the Evaluation of the Risk of Occurrence of Delayed Cerebral Ischemia: A Cohort Study.","authors":"Pierre Simeone, Thomas Corrias, Nicolas Bruder, Salah Boussen, Dan Cardoso, Audrey Alonzo, Anthony Reyre, Hervé Brunel, Nadine Girard, Thomas Graillon, Henry Dufour, David Couret, Lionel Velly","doi":"10.1007/s12028-024-02135-7","DOIUrl":"10.1007/s12028-024-02135-7","url":null,"abstract":"<p><strong>Background: </strong>This study focuses on aneurysmal subarachnoid hemorrhage (aSAH) with a high risk of delayed cerebral ischemia (DCI) and acute hydrocephalus (AH). The aim was to compare the performance of an automatic algorithm for quantifying the volume of intracranial blood with the reference radiological scales to predict DCI, AH, and neurological outcome.</p><p><strong>Methods: </strong>This was a single-center retrospective observational study of a cohort of patients with aSAH. We developed an automated blood detection algorithm based on the specific density of the blood clot. The blood clot was segmented on the first brain scan (total, supratentorial, cisternal, intraventricular). The predictive value of our model was compared, using the area under the receiver operating characteristic curve (ROC_AUC), to eight radiological scales: Fisher, modified Fisher, Claassen, Barrow Neurological Institute, Hijdra, Graeb, LeRoux scales, and intraventricular hemorrhage score.</p><p><strong>Results: </strong>We analyzed the scans of 145 patients with aSAH. In our cohort, 51 patients (43%) had DCI and 70 patients (54%) had AH. At 3 months, 22% of patients had died and 19% had poor outcome (Glasgow Outcome Scale extended 2-4). Cisternal blood volume was significantly correlated with cisternal Hijdra scale (R² = 0.79; P < 0.001). The ROC_AUC of cisternal blood volume was comparable to the ROC_AUC of the Hijdra scale in predicting the occurrence of DCI (ROC_AUC = 0.83 [95% confidence interval {CI} 0.75-0.89] vs. 0.86 [95% CI 0.79-0.9]; P = 0.23). The ROC_AUC of intraventricular blood volume was not significantly different from the intraventricular hemorrhage score in predicting the occurrence of AH (ROC_AUC = 0.78 [95% CI 0.70-0.84] vs. 0.79 [95% CI 0.72-0.85]; P = 0.28). The ROC_AUC and supratentorial blood volumes were not significantly different from the Simplified Acute Physiology Score II in predicting the occurrence of poor neurological outcome at 3 months (ROC_AUC = 0.75 [95% CI 0.67-0.82] vs. 0.81 [95% CI 0.74-0.87]; P = 0.073).</p><p><strong>Conclusions: </strong>With no manual intervention, our algorithm performed as well as the best radiological scores in predicting the occurrence of DCI, AH, and neurological outcome.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":"363-373"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Futurology: What Would Future Historians of Neurocritical Care Write About?","authors":"Eelco F M Wijdicks","doi":"10.1007/s12028-024-02155-3","DOIUrl":"10.1007/s12028-024-02155-3","url":null,"abstract":"","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":"722-725"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aneurysmal Subarachnoid Hemorrhage Risk Assessment Model Identifies Patients for Safe Early Discharge at Day 15-The SAFE-SaH Score.","authors":"Eric E Kennison, Nick M Murray, Dave S Collingridge, Daniel Knox, Gabriel V Fontaine","doi":"10.1007/s12028-025-02236-x","DOIUrl":"https://doi.org/10.1007/s12028-025-02236-x","url":null,"abstract":"<p><strong>Background: </strong>Patients with aneurysmal subarachnoid hemorrhage (aSAH) are often hospitalized for 21 days after aneurysm rupture due to the risk of complications. However, some never experience complications and are unlikely to benefit from a prolonged hospitalization. The aim of this study is to derive a risk assessment model (RAM) using data from the first 14 days of hospitalization to identify low-risk patients for early discharge, at day 15 or after.</p><p><strong>Methods: </strong>Patients ≥ 18 years old with an acute aSAH at a Comprehensive Stroke Center from 2017 to 2024 were included. Baseline demographics, aSAH grading scales, and in-hospital complications requiring intervention were characterized. Complications included: vasospasm, delayed cerebral ischemia (DCI), cerebral salt wasting (CSW), cerebral edema, seizures, arrhythmias, respiratory failure, and hydrocephalus. Binary logistic regression with leave-one-out cross validation (LOOCV) was used to identify an optimal RAM.</p><p><strong>Results: </strong>Of 165 patients, the mean Hunt Hess Score (HHS) was 2.5 (standard deviation, SD 1.2), modified Fisher Score (mFS) was 3.1 (SD 1), endovascular therapy was used for aneurysm securement in 73% of patients, and 54.5% of patients experienced complications during days 15-21. In bivariate analyses, days 0-14 variables associated with days 15 + complications were the following: HHS, mFS, middle cerebral artery (MCA) aneurysm, clinical or radiologic vasospasm, endovascular therapies, intraventricular hemorrhage, hydrocephalus, presence of external ventricular drain (EVD), mechanical ventilation, vasopressors, hypertonic solutions, antiseizure medications, milrinone, and fludrocortisone (all p < 0.05). LOOCV regression for a best fit RAM included six variables: Sum of Vasopressors, Artery (MCA aneurysm), Fludrocortisone, EVD, Scale (mFS and HHS), \"SAFE-SaH\" and had an area under the receiver operator characteristics curve of 0.90 (95% confidence interval 0.85-0.95), sensitivity of 0.94, specificity of 0.69, positive predictive value of 79%, and negative predictive value of 91% for predicting complications on day 15 + .</p><p><strong>Conclusions: </strong>This is the first ever RAM to incorporate clinical data from the first 14 days of hospitalization to identify patients with an aSAH at low risk for complications after day 14. With 94% sensitivity, the RAM classifies patients who will not have complications and may assist in earlier disposition on day 15 or after.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel, Interpretable Machine Learning Model to Predict Neurological Outcomes Following Venoarterial Extracorporeal Membrane Oxygenation.","authors":"Benjamin L Shou, Albert Leng, Preetham Bachina, Andrew Kalra, Alice L Zhou, Glenn Whitman, Sung-Min Cho","doi":"10.1007/s12028-025-02233-0","DOIUrl":"https://doi.org/10.1007/s12028-025-02233-0","url":null,"abstract":"<p><strong>Background: </strong>We used machine learning models incorporating rich electronic medical record (EMR) data to predict neurological outcomes after venoarterial extracorporeal membrane oxygenation (VA-ECMO).</p><p><strong>Methods: </strong>This was a retrospective review of adult (≥ 18 years) patients undergoing VA-ECMO between 6/2016 and 4/2022 at a single center. The primary outcome was good neurological outcome, defined as a modified Rankin Scale score of 0 to 3, evaluated at hospital discharge. We extracted every measurement of 74 vital and laboratory values, as well as circuit and ventilator settings, from 24 h before cannulation through the entire duration of ECMO. An XGBoost model with Shapley Additive Explanations was developed and evaluated with leave-one-out cross-validation.</p><p><strong>Results: </strong>Overall, 194 patients undergoing VA-ECMO (median age 58 years, 63% male) were included. We extracted more than 14 million individual data points from the EMR. Of 194 patients, 39 patients (20%) had good neurological outcomes. Three models were generated: model A, which contained only pre-ECMO data; model B, which added data from the first 48 h of ECMO; and model C, which included data from the entire ECMO run. The leave-one-out cross-validation area under the receiver operator characteristics curves for models A, B, and C were 0.72, 0.81, and 0.90, respectively. The inclusion of on-ECMO physiologic, laboratory, and circuit data greatly improved model performance. Both modifiable and nonmodifiable variables, such as lower body mass index, lower age, higher mean arterial pressure, and higher hemoglobin, were associated with good neurological outcome.</p><p><strong>Conclusions: </strong>An interpretable machine learning model from EMR-extracted data was able to predict neurological outcomes for patients undergoing VA-ECMO with excellent accuracy.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Consequences of Disproportionate Free Valproate Elevation in Critically Ill Adult Patients: A Multicenter Retrospective Cohort Study.","authors":"Andrew J Webb, David J Gagnon, Caitlin S Brown, Richard R Riker, Natasha D Lopez, Melanie Z Goodberlet, Michael J Schontz, Kaylee K Marino, Sahar F Zafar, Eric S Rosenthal","doi":"10.1007/s12028-025-02243-y","DOIUrl":"https://doi.org/10.1007/s12028-025-02243-y","url":null,"abstract":"<p><strong>Background: </strong>Valproate has a narrow therapeutic index and unpredictable protein binding, and critically ill patients may experience unexpectedly elevated free concentrations. We sought to identify the clinical consequences and determinants of disproportionate free valproate concentration elevation in critically ill adults.</p><p><strong>Methods: </strong>This was a retrospective observational cohort study conducted at two academic medical centers from December 2015 to December 2023. Adult patients admitted to an intensive care unit who were receiving valproate and had concurrent total and free valproate concentrations measured were eligible for inclusion. We examined whether valproate concentrations were independently associated with adverse effects (AEs), including thrombocytopenia, hepatotoxicity, hyperammonemia, and pancreatic injury. Secondarily, determinants of disproportionate free valproate elevation, defined as a free valproate concentration that was greater than expected and out of proportion to the total concentration (e.g., free valproate above reference range but total valproate below reference range), were also identified.</p><p><strong>Results: </strong>A total of 311 patients (mean age 58 [SD ± 17] years, 36% female, 31% non-White, and 29% on valproate prior to admission) with 550 concurrent free valproate and total valproate pairs were included. The median total valproate concentration was 46 μg/mL (interquartile range [IQR] 34-63), and the median free valproate concentration was 17 μg/mL (IQR 11-23); the median free fraction was 35% (IQR 25-63%). Disproportionate free valproate elevation was observed in 462 (84%) samples. Each 2.5-μg/mL increase in free valproate concentration was associated with thrombocytopenia (adjusted odds ratio [aOR] 1.15, 95% confidence interval [CI] 1.05-1.26) and hepatotoxicity (aOR 1.11, 95% CI 1.05-1.18). Albumin concentration (aOR 0.17, 95% CI 0.08-0.36), blood urea nitrogen (aOR 1.36, 95% CI 1.09-1.70), and propofol exposure (aOR 3.06, 95% CI 1.38-6.79) were associated with disproportionate free valproate elevation.</p><p><strong>Conclusions: </strong>Elevated free valproate concentrations were associated with hepatotoxicity and thrombocytopenia; free valproate concentrations should be directly measured in critically ill patients because it is underrepresented by total valproate. Most critically ill patients are at risk, especially those with hypoalbuminemia, uremia, and propofol exposure.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}