Poor Neurological Outcome In Patients Research Articles

Acute kidney injury as a prognostic predictor of in-hospital mortality and neurological outcomes in patients after extracorporeal cardiopulmonary resuscitation.

Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly being applied to patients with refractory cardiac arrest, but the survival rate to hospital discharge is only approximately 29%. Because ECPR requires intensive resources, it is important to predict outcomes. We therefore investigated the prognostic association between acute kidney injury (AKI) and ECPR to confirm the performance of AKI as a prognostic predictor of in-hospital mortality and neurological outcomes in ECPR. We conducted a retrospective observational study on patients undergoing ECPR for cardiac etiology at Chonnam National University Hospital from 2015 to 2021. The group diagnosed with AKI in any KDIGO category within the first 48 h after ECPR was compared to that without AKI, and the primary outcome of the study was in-hospital mortality. Of 138 enrolled patients, 83 were studied. Hospital mortality occurred in 49 patients (59%), and 55 (66.3%) showed poor neurological outcomes. The AKI group displayed significantly elevated in-hospital mortality (77.8% vs 24.1%) and poor neurological outcomes (81.5% vs 37.9%) compared to the non-AKI group (p < 0.001). Regression analysis showed that AKI was associated with significantly higher rates of both in-hospital mortality (odds ratio (OR) range 10.75-12.88) and neurologic outcomes (OR range 5.9-6.22). There was a significant association of AKI with both in-hospital mortality and poor neurologic outcome in patients after ECPR, and AKI can be used as an early prognostic predictor in these patients.

The association between serum free fatty acid levels and neurological outcomes in out-of-hospital cardiac arrest patients: A prospective observational study.

Free fatty acids (FFA) are a known risk factor in the development of sudden cardiac death. However, the relationship between FFA and the outcome of out-of-hospital cardiac arrest (OHCA) patients remains unclear. We aimed to examine the association between FFA and neurological outcomes in OHCA patients. This prospective observational study included adult (≥18 years) OHCA patients between February 2016 and December 2022. We measured serial FFA levels within 1 hour after ROSC and at 6, 12, 24, 48, and 72 hours after the return of spontaneous circulation (ROSC). The primary outcome was neurological outcome at 6 months. A poor neurological outcome was defined by cerebral performance categories 3, 4, and 5. A total of 147 patients were included. Of them, 104 (70.7%) had poor neurological outcomes, whereby the median FFA levels within 1 hour after ROSC (0.72 vs 1.01 mol/L), at 6 hours (1.19 vs 1.90 mol/L), 12 hours (1.20 vs 1.66 mol/L), and 24 hours (1.20 vs 1.95 mol/L) after ROSC were significantly lower than in good outcome group. The FFA levels at 6 hours (odds ratio, 0.583; 95% confidence interval, 0.370-0.919; P = .020), and 12 hours (odds ratio, 0.509; 95% confidence interval, 0.303-0.854; P = .011) after ROSC were independently associated with poor neurological outcomes. The lower FFA levels at 6 hours and 12 hours after ROSC were associated with poor neurological outcomes in patients with OHCA. FFA may reflect oxidative metabolism as well as oxidative stress.

SERUM TRANSACTIVE RESPONSE DNA BINDING PROTEIN 43 ASSOCIATES WITH POOR SHORT-TERM NEUROLOGIC OUTCOME AFTER RETURN OF SPONTANEOUS CIRCULATION FOLLOWING CARDIAC ARREST.

Objective : To explore the association of serum transactive response DNA binding protein 43 (TDP-43) with 28-day poor neurologic outcome in patients with return of spontaneous circulation (ROSC) after cardiac arrest. Methods : We performed a study between January and December 2023. Eligible patients with ROSC following cardiac arrest were enrolled. Their baseline characteristics were collected, and serum levels of TDP-43, tumor necrosis factor-α, interleukin-6 and 10, C-reactive protein, and neuron-specific enolase (NSE) at 24 h after ROSC were measured. The neurologic function was assessed by the cerebral performance category scores on day 28 after ROSC. Results : A total of 92 patients were included, with 51 and 41 patients in the good and poor neurologic outcome groups, respectively. Serum TDP-43 was significantly higher in the poor than the good neurologic outcome group ( P < 0.05). Univariate and multivariate logistic regression analyses showed that TDP-43, Witnessed CA, IL-6, and NSE were associated with poor 28-day neurologic outcome (all P < 0.05). Restricted cubic spline analysis revealed that TDP-43 at the serum level of 11.64 pg/mL might be an ideal cutoff value for distinguishing between good and poor neurologic outcomes. Area under curve of serum TDP-43 (AUC = 0.78) was close to that of serum NSE (AUC = 0.82). A dynamic nomogram prediction model that combined TDP-43, Witnessed CA, IL-6, and NSE was constructed and validated. Conclusion : Elevated serum TDP-43 level was associated with and could be used together with Witnessed CA, IL-6, and NSE to predict poor 28-day neurologic outcome in patients after ROSC following cardiac arrest.

Exposure to severe hyperoxemia worsens survival and neurological outcome in patients supported by veno-arterial extracorporeal membrane oxygenation: A meta-analysis

BackgroundVeno-arterial Extracorporeal Membrane Oxygenation (VA-ECMO) is a rescue treatment in refractory cardiogenic shock (CS) or refractory cardiac arrest (CA). Exposure to hyperoxemia is common during VA-ECMO, and its impact on patient’s outcome remains unclear. MethodsWe conducted a systematic review (PubMed and Scopus) and meta-analysis investigating the effects of exposure to severe hyperoxemia on mortality and poor neurological outcome in patients supported by VA-ECMO. When both adjusted and unadjusted Odds Ratio (OR) were provided, we used the adjusted one. Results are reported as OR and 95% confidence interval (CI). Subgroup analyses were conducted according to VA-ECMO indication and hyperoxemia thresholds. ResultsData from 10 observational studies were included. Nine studies reported data on mortality (n = 5 refractory CA, n = 4 CS), and 4 on neurological outcome. As compared to normal oxygenation levels, exposure to severe hyperoxemia was associated with higher mortality (nine studies; OR: 1.80 [1.16–2.78]; p = 0.009; I2 = 83%; low certainty of evidence) and worse neurological outcome (four studies; OR: 1.97 [1.30–2.96]; p = 0.001; I2 = 0%; low certainty of evidence). Magnitude and effect of these findings remained valid in subgroup analyses conducted according to different hyperoxemia thresholds (>200 or >300 mmHg) and VA-ECMO indication, although the association with mortality remained uncertain in the refractory CA population (p = 0.13). Analysis restricted to studies providing adjusted OR data confirmed an increased likelihood of poorer neurological outcome (three studies; OR: 2.11 [1.32–3.38]; p = 0.002) in patients exposed to severe hyperoxemia but did not suggest higher mortality (five studies; OR: 1.68 [0.89–3.18]; p = 0.11). ConclusionsSevere hyperoxemia exposure after initiation of VA-ECMO may be associated with an almost doubled increased probability of poor neurological outcome and mortality. Clinical efforts should be made to avoid severe hyperoxemia during VA-ECMO support.

Machine learning-based predictor for neurologic outcomes in patients undergoing extracorporeal cardiopulmonary resuscitation.

We investigated the predictors of poor neurological outcomes in extracorporeal cardiopulmonary resuscitation (ECPR) patients using machine learning (ML) approaches. This study was a retrospective, single-center, observational study that included adult patients who underwent ECPR while hospitalized between January 2010 and December 2020. The primary outcome was neurologic status at hospital discharge as assessed by the Cerebral Performance Categories (CPC) score (scores range from 1 to 5). We trained and tested eight ML algorithms for a binary classification task involving the neurological outcomes of survivors after ECPR. During the study period, 330 patients were finally enrolled in this analysis; 143 (43.3%) had favorable neurological outcomes (CPC score 1 and 2) but 187 (56.7%) did not. From the eight ML algorithms initially considered, we refined our analysis to focus on the three algorithms, eXtreme Gradient Boosting, random forest, and Stochastic Gradient Boosting, that exhibited the highest accuracy. eXtreme Gradient Boosting models exhibited the highest accuracy among all the machine learning algorithms (accuracy: 0.739, area under the curve: 0.837, Kappa: 0.450, sensitivity: 0.700, specificity: 0.740). Across all three ML models, mean blood pressure emerged as the most influential variable, followed by initial serum lactate, and arrest to extracorporeal membrane oxygenation (ECMO) pump-on-time as important predictors in machine learning models for poor neurological outcomes following successful ECPR. In conclusion, machine learning methods showcased outstanding predictive accuracy for poor neurological outcomes in patients who underwent ECPR.

An innovative MedIcaL dEcision Support tool for neurological ouTcome predictiOn from post-resuscitatioN Electrocardiograms (MILESTONE)

Abstract Background The prediction of poor neurological outcome after Out-of-Hospital Cardiac Arrest (OHCA) represents a major challenge in post-resuscitation care. This is currently based on a complex multiparametric prognostication approach and the existing decision support tools are characterized by unsatisfactory performance. Purpose The aim of the present study is to develop a machine learning (ML) tool for clinical decision support in the prediction of neurological outcome in patients who have experienced an OHCA. We present an innovative MedIcaL dEcision Support tool for neurological ouTcome predictiOn from post-resuscitatioN Electrocardiograms (MILESTONE), which can be used in a post-resuscitation setting. Methods MILESTONE uses an ECG image as an input from which it extracts features by computer vision techniques. Those features, used to feed the ML model for the prediction of the neurological outcome, were retrieved from a dataset of 1341 ECGs collected from a Utstein-style OHCA registry: 431 post-ROSC ECGs of patients with poor neurological outcome (defined according to the Cerebral Performance Category &amp;gt; 2) at discharge (class 1); 568 post-ROSC ECGs of patients with good neurological outcome (CPC≤2) and 342 ECGs of healthy subjects (class 0). Image features were extracted by several computer vision algorithms derived from the scale-invariant feature transform (SIFT) method. The extracted features, patient’s age and gender were used to train an XGBoost classifier. Nested cross-validation was applied to optimize the model’s parameters and to test its generalization capability. Class weightage technique was introduced to make our classifier more prone to detect positive cases. Model’s performance was evaluated by the balanced accuracy, the Area Under the Curve of the Receiver Operating Characteristic curve (AUC-ROC), and the F1-score in both the validation and the test sets. Results Our model achieved an AUC-ROC and F1-score of 88.5±4.1% and 78.2±7.3% respectively in the hold-out set (Figure). MILESTONE reached a balanced accuracy of over 80% as a proof of the robustness of the results and the high discrimination capability for both classes, although it has an intended bias towards the identification of patients with worse outcomes. In terms of explainability, MILESTONE has the potential to correlate machine-readable ECG features with more well-known macro features used in clinical practice such as QT intervals, peak shapes, etc. Conclusions We present the first use of computer vision-based ECG features able to predict poor neurological outcome in patients resuscitated from OHCA. Poor neurological outcome represents a major challenge in post-resuscitation care and this innovative and flexible tool showed an extremely promising performance. Moreover, this tool can be re-trained either for different pathologies or on any time length of ECG recording thus continuously improving its performance.

Abstract 246: Consumptive Coagulopathy is Associated With Poor Neurological Outcome in Patients With Refractory VT/VF Cardiac Arrest Requiring Extracorporeal Cardiopulmonary Resuscitation

Introduction: Post cardiac arrest syndrome is associated with altered hemostasis. This is aggravated further by the foreign surface in the extracorporeal circuit leading to a coagulofibrinolytic imbalance. Aim: We examined the serial changes of consumptive coagulopathy markers and their association with neurologic outcomes. Methods: A single-center, retrospective cohort study of consecutive patients with VT/VF cardiac arrest meeting criteria for ECMO-facilitated resuscitation (ECPR) between December 2015 and January 2023 were included. Consumptive coagulopathy markers (INR, D-dimer, platelet count, antithrombin III and fibrinogen) were obtained after VA ECMO cannulation and serially on day 1, 2 and 3. We compared the coagulation profiles of patients who had a neurologically favorable outcome (defined as Cerebral Performance Categories (CPC) 1-2) and those with a neurologically unfavorable outcome (CPC 3-5). Results: Of 258 patients, 82 (32%) survived to hospital discharge. Of these, 87% (71/82) survived with favorable neurological outcome. Prolonged INR, elevated D-dimer levels and decreased ATIII levels were associated (p&lt;0.05) with neurologically unfavorable survival and decreased over time (p&lt;0.05)(Figure1). Platelet count and fibrinogen levels were not associated with neurological outcomes. In adjusted analysis (including age, lactate, CPR time and use of dual antiplatelet therapy), each point increase in the INR on day 1, 2 and 3 was associated with neurologically unfavorable survival (OR 4.4, p=0.01; OR 7.14, p=0.04; OR 8.5, p=0.03 respectively). Conclusion: Markers of consumptive coagulopathy with a prolonged INR are associated with unfavorable neurological outcome.

Abstract 210: The Relationship Between Serum Free Fatty Acid Levels After the Return of Spontaneous Circulation and Neurological Outcomes in Out-of-Hospital Cardiac Arrest Patients

Background: Free fatty acids (FFA) are a known risk factor in the development of sudden cardiac death. However, the relationship between FFA and the outcome of out-of-hospital cardiac arrest (OHCA) patients remains unclear. We aimed to examine the association between FFA and neurological outcomes in OHCA patients. Methods: This prospective observational study included adult (≥ 18 years) OHCA patients between February 2016 and December 2022. We measured serial FFA levels within 1 h after ROSC and at 6 h, 12 h, 24 h, 48 h, and 72 h after the return of spontaneous circulation (ROSC). The primary outcome was neurological outcome at 6 months. A poor neurological outcome was defined by cerebral performance categories 3, 4, and 5. Results: A total of 147 patients were included. Of them, 104 (70.7%) had poor neurological outcomes, whereby the median FFA levels within 1 h after ROSC (0.72 vs. 1.01 mol/L), at 6 h (1.19 vs. 1.90 mol/L), 12 h (1.20 vs. 1.66 mol/L), and 24 h (1.20 vs. 1.95 mol/L) after ROSC were significantly lower than in good outcome group. The FFA levels at 6 h (odds ratio [OR], 0.583; 95% confidence interval [CI], 0.370-0.919; P = 0.020), and 12 h (OR, 0.509; 95% CI, 0.303-0.854; P = 0.011) after ROSC were independently associated with poor neurological outcomes. Conclusions: The lower FFA levels at 6 h and 12 h after ROSC were associated with poor neurological outcomes in patients with OHCA. FFA may reflect oxidative metabolism as well as oxidative stress.

Neutrophil-to-lymphocyte ratio is an independent predictor for neurological disability in patients with idiopathic transverse myelitis

IntroductionThe neutrophil-to-lymphocyte ratio (NLR) has been found to be useful in the prognostication of immune-mediated neurological disorders because it roughly reflects the systemic innate immune response compared to the adaptive immune response. However, studies on the validity of NLR in demyelinating disorders of the central nervous system have shown conflicting results. Therefore, we aimed to investigate NLR in the idiopathic transverse myelitis (ITM) cohort.MethodsWe retrospectively analyzed the cohort data of patients with ITM between January 2006 and February 2020. The medical data of all patients with myelitis were reviewed to exclude patients with disease-associated myelopathy according to predefined exclusion criteria. The relationship between the natural log-transformed NLR (lnNLR) and the clinical, paraclinical, and imaging data was evaluated. Factors associated with neurological disability were analyzed using a linear mixed-effects model. Predictive factors for moderate-to-severe neurological disability (Expanded Disability Status Scale [EDSS] score ≥ 4) were investigated.ResultsA total of 124 participants were included in the analysis. The lnNLR correlated with EDSS and lesion length. Linear mixed-effects analysis showed that age, lesion length, and lnNLR were independently associated with neurological disabilities. Multivariable logistic regression revealed that lnNLR (odds ratio [OR] = 4.266, 95% confidence interval [CI] = 1.220–14.912, p = 0.023) and lesion length (OR = 1.848, 95% CI = 1.249–2.734, p = 0.002) were independent predictive factors of the worst neurological disability.ConclusionNLR may be used as an independent prognostic factor for predicting poor neurological outcomes in patients with ITM.

Early NSE measurements at the ICU bear prognostic value in patients with and without CPR

Abstract Funding Acknowledgements Type of funding sources: None. Background Neuron-specific enolase (NSE) represents a diagnostic tool for identifying poor neurological outcomes in patients following CPR. As part of multimodal prognostication, NSE values above 60 µg/L after 48h and/or 72h were associated with a worse neurologic outcome (European Resuscitation Council Guidelines 2021). Despite the prognostic value of NSE 48h to 72h after CPR, measurements at admission to the ICU remain the topic of discussion as divergent findings are present in the literature (primarily in small collectives). Purpose Within the proposed study, we aimed to illuminate the prognostic value of NSE measurements on the day of admission to the ICU. Furthermore, we conducted a comparison of patients with and without CPR prior to ICU admission. Due to hemolysis sensitivity, we adjusted NSE values according to a previously published protocol to reveal potential changes in predictive potential through the occurrence of hemolysis. Methods This was a prospective, observational cohort study. 232 consecutive patients admitted to a cardiac ICU were screened over the course of one year. Patients with active malignancies or traumatic brain injuries were excluded. Furthermore, samples with hemolysis index &amp;gt;30 units were excluded to guarantee stable measurements. NSE values were measured on the day of admission to the ICU in a total of 202 patients (154 without previous CPR, 48 with CPR) using specific ELISA kits. According to an earlier publication, hemolysis was considered to account for an artificial increase of 0.29µg/L per unit (range 5-30 units) and was subsequently subtracted. Results Median age was 66.96 (IQR: 55.7-76.9), and 41.1% of the included patients were female. The total 30-day-mortality was calculated to be 27.2%, and 48 patients (23.8%) were admitted following CPR. Interestingly NSE at admission was not higher in patients after CPR (3.23 ± 3.88 µg/L vs 5.43 ± 5.78 µg/L, p = 0.072). However, NSE measurements on the day of admission were significantly elevated in 30-day none-survivors (3.23 ± 3.84 µg/L vs 6.91 ± 6.55 µg/L, p &amp;lt; 0.001). The same findings were made when excluding all patients after CPR (30-day survivors: 3.24 ± 3.99 µg/L vs 30-day none-survivors: 6.15 ± 6.17µg/L, p = 0.001). No statistically significant differences in survival were found when stratifying for the primary cause of admission. Comparing hemolysis-corrected NSE values to raw data showed a slight increase in positive predictive value for 30-day mortality in the total cohort (ROC-AUC: 0.732 vs 0.721) as well as in patients without prior CPR (ROC-AUC: 0.722 vs 0.703). Conclusion We provided evidence for the prognostic value of early NSE measurements at the ICU. In both the total cohort as well as a sub-cohort without patients admitted after CPR, 30-day none-survivors displayed markedly elevated levels of NSE. Moreover, the positive predictive value of these measurements was slightly increased when correcting for hemolysis &amp;gt;5 units.

A 12-Year Audit of Neurological Outcomes Associated with Core Body Temperature >37.5°C in Children with Severe Traumatic Brain Injury.

Hyperthermia exposure is associated with poor neurological outcomes in patients with severe traumatic brain injury (TBI). Our aim was to describe fever in children with severe TBI admitted to a pediatric intensive care unit (PICU) for at least 72 hours and to evaluate associations between fever using a novel approach to describe thermal exposure and neurobehavioral outcomes. The cohort included children from birth to 17 years of age admitted to the PICU between 2000 and 2012 for at least 72 hours who had severe TBI with intracranial pressure monitoring. Patients with non-accidental TBI or pre-existing developmental delays were excluded. Hyperthermia was defined as a core temperature >37.5°C. Hourly temperature measurements were used to calculate the area under the curve (AUC) using the linear trapezoidal rule. Each participant was followed up at the Brain Injury Clinic 6 and 18 months postinjury. Neurobehavioral outcome scores were analyzed against AUC using standard statistical methods. Ninety-eight patients admitted with severe TBI met the study inclusion criteria. Hyperthermia/fever was common (89.7%), and patients remained hyperthermic for a median of 9.4 hours. However, no statistically significant association was found between AUC and abnormal neurological outcomes. The follow-up rates were good at 6 (86.7%) and 18 months (83.7%). The neurological deficit improved with time, with "favorable outcomes" increasing from 72% to 94% at the respective follow-up months. Our study used a novel method to describe patients' fever, providing a different indicator of thermal exposure than that previously reported. In addition, the AUC was well correlated with the maximum temperature recorded and the proportion of time >37.5°C, indicating that it is a good surrogate for thermal exposure. Interestingly, the neurological disabilities of the patients improved over time.

Abstract 320: Gray-white Matter Ratio Under 1.12 Could Predict Poor Neurological Outcomes, Even When Measured Within Two Hours After Return Of Spontaneous Circulation

Introduction: Literature on neuroprognostication suggests that gray-white matter ratio (GWR) measured from head computed tomography (CT) within two hours after return of spontaneous circulation (ROSC) can’t adequately predict neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients. However, severe cerebral edema may predict poor outcomes within two hours after ROSC. Hypothesis: We evaluated if GWR measurements obtained early after OHCA (≤ 2 hours) indicated poor neurological outcomes in patients with severe cerebral edema. Methods: We conducted a multicenter, retrospective cohort study using data from five hospitals collected between 2007 and 2019 in Japan. Inclusion criteria: adult comatose OHCA survivors with head CT within two hours after ROSC. Exclusion criteria was trauma, stroke, or pre-existing neurological disorders. Primary outcome was poor neurological outcome, defined as Cerebral Performance Category (CPC) score ≥ 3 at one month after admission. GWR was measured at the levels of the basal ganglia (BG), corpus callosum (CC), and posterior internal capsule (PIC). The prognostic value of GWR for predicting poor outcome was assessed using a receiver operating characteristic (ROC) curve analysis, area under the curve (AUC) with sensitivity/specificity. Results: A total of 377 patients were included. Of those, 281 (74.6%) exhibited poor neurological outcome at one month after admission. GWR values did not alter by the time of obtaining head CT: 1.22 (0-30 min: n=194); 1.22 (31-60 min: n=127); 1.22 (61-120 min: n=56). Using a cut-off GWR value of &lt;1.2, ROC analysis demonstrated AUC for GWR-BG (0.69, 95% CI 0.65-0.73), GWR-CC (0.77, 95% CI 0.69-0.76), and GWR-PIC (0.76, 95% CI 0.72-0.79) with sensitivities/specificities of 45.5%/92.7%, 47.6%/97.9%, 55.8%/96.8%, and 46.2%/97.9%, respectively for poor outcomes. However, GWR values &lt;1.12 demonstrated 100% specificity for poor outcomes: GWR-BG (AUC 0.56, sensitivity/specificity 13.5%/100%), GWR-CC (AUC 0.56, sensitivity/specificity 13.5%/100%), and GWR-PIC (AUC 0.59, sensitivity/specificity 19.5%/100%). Conclusion: GWR (&lt;1.12) obtained even within two hours after ROSC could be used as a threshold for poor neurological outcome in OHCA patients.

Hyperoxemia is Associated With Poor Neurological Outcomes in Patients With Out-of-Hospital Cardiac Arrest Rescued by Extracorporeal Cardiopulmonary Resuscitation: Insight From the Nationwide Multicenter Observational JAAM-OHCA (Japan Association for Acute Medicine) Registry

BackgroundPrevious studies have shown an association between hyperoxemia and mortality in patients with out-of-hospital cardiac arrest (OHCA) after cardiopulmonary resuscitation (CPR); however, evidence is lacking in the extracorporeal CPR (ECPR) setting. ObjectiveThe aim of this study was to test the hypothesis that hyperoxemia is associated with poor neurological outcomes in patients treated by ECPR. MethodsThe Japanese Association for Acute Medicine OHCA Registry is a multicenter, prospective, observational registry of patients from 2014 to 2017. Adult (18 years or older) patients who had undergone ECPR after OHCA were included. Eligible patients were divided into two groups based on the partial pressure of oxygen in arterial blood (PaO2) levels at 24 h after ECPR: the high-PaO2 group (n = 242) defined as PaO2 ≥ 157 mm Hg (median) and the low-PaO2 group (n = 211) defined as PaO2 60 to < 157 mm Hg. The primary outcome was the favorable neurological outcome, defined as a Cerebral Performance Categories Scale score of 1 to 2 at 30 days after OHCA. ResultsOf 34,754 patients with OHCA, 453 patients were included. The neurological outcome was significantly lower in the high-PaO2 group than in the low-PaO2 group (15.9 vs. 33.5%; p < 0.001). After adjusting for potential confounders, high PaO2 was negatively associated with favorable neurological outcomes (adjusted odds ratio [aOR] 0.48; 95% confidence interval [CI] 0.24–0.97; p = 0.040). In a multivariate analysis with multiple imputation, high PaO2 was also negatively associated with favorable neurological outcomes (aOR 0.63; 95% CI 0.49–0.81; p < 0.001). ConclusionsHyperoxemia was associated with worse neurological outcomes in OHCA patients with ECPR.

The impact of antihypertensive use in the treatment of acute ischemic stroke in patients receiving alteplase.

Treatment of acute ischemic stroke (AIS) with intravenous alteplase within 4.5 h of symptom onset is associated with neurologic improvement. High baseline blood pressure (BP) and BP variability during the first 24 h of AIS is associated with increased early adverse events and death. The purpose of this study is to characterize the incidence of poor neurologic outcome in patients treated with alteplase for AIS who received antihypertensive medications prior to and within the first 24 h following alteplase administration compared with patients who did not. This was a multicenter, retrospective cohort of patients >18 years diagnosed with AIS from January 1, 2011 through December 31, 2015 who received one or more antihypertensive medication in the first 24 h of AIS in patients receiving alteplase compared to controls. The primary endpoint was poor neurologic outcome at 90 days, according to modified Rankin Scale ≥3. Univariate analysis was conducted using Chi-square, Fisher's exact test, or Mann-Whitney U test. Multivariable logistic regression was conducted to determine independent predictors of poor outcome. Of the 587 patients evaluated, 351 (59.7%) were included, of which 127 (36.2%) received antihypertensive(s). More patients in the antihypertensive treatment group had a history of hypertension (88.2% vs. 69.6%, p < 0.01), diabetes (37% vs. 25.5%, p = 0.03) and chronic kidney disease (19.7% vs. 8.5%, p < 0.01). Intravenous push labetalol was most commonly administered (81.2%), followed by nicardipine (44.1%), and hydralazine (22%). More patients in the antihypertensive treatment group experienced poor neurologic outcome at 90 days (53.5% vs. 38.8%, p < 0.01), however, this finding was not observed after multivariable logistic regression. Antihypertensive treatment in the first 24 h of AIS was associated with poor neurologic outcomes at 90 days. However, after controlling for other clinical factors in a multivariable logistic regression, this association was no longer observed.

Brain Kynurenine Pathway and Functional Outcome of Rats Resuscitated From Cardiac Arrest.

BackgroundBrain injury and neurological deficit are consequences of cardiac arrest (CA), leading to high morbidity and mortality. Peripheral activation of the kynurenine pathway (KP), the main catabolic route of tryptophan metabolized at first into kynurenine, predicts poor neurological outcome in patients resuscitated after out‐of‐hospital CA. Here, we investigated KP activation in hippocampus and plasma of rats resuscitated from CA, evaluating the effect of KP modulation in preventing CA‐induced neurological deficit.Methods and ResultsEarly KP activation was first demonstrated in 28 rats subjected to electrically induced CA followed by cardiopulmonary resuscitation. Hippocampal levels of the neuroactive metabolites kynurenine, 3‐hydroxy‐anthranilic acid, and kynurenic acid were higher 2 hours after CA, as in plasma. Further, 36 rats were randomized to receive the inhibitor of the first step of KP, 1‐methyl‐DL‐tryptophan, or vehicle, before CA. No differences were observed in hemodynamics and myocardial function. The CA‐induced KP activation, sustained up to 96 hours in hippocampus (and plasma) of vehicle‐treated rats, was counteracted by the inhibitor as indicated by lower hippocampal (and plasmatic) kynurenine/tryptophan ratio and kynurenine levels. 1‐Methyl‐DL‐tryptophan reduced the CA‐induced neurological deficits, with a significant correlation between the neurological score and the individual kynurenine levels, as well as the kynurenine/tryptophan ratio, in plasma and hippocampus.ConclusionsThese data demonstrate the CA‐induced lasting activation of the first step of the KP in hippocampus, showing that this activation was involved in the evolving neurological deficit. The degree of peripheral activation of KP may predict neurological function after CA.

Simultaneous external validation of various cardiac arrest prognostic scores: a single-center retrospective study

BackgroundThis study aimed to compare and validate the out-of-hospital cardiac arrest (OHCA); cardiac arrest hospital prognosis (CAHP); non-shockable rhythm, unwitnessed arrest, long no-flow or long low-flow period, blood pH < 7.2, lactate > 7.0 mmol/L, end-stage chronic kidney disease, age ≥ 85 years, still resuscitation, and extracardiac cause (NULL-PLEASE) clinical; post-cardiac arrest syndrome for therapeutic hypothermia (CAST); and revised CAST (rCAST) scores in OHCA patients treated with recent cardiopulmonary resuscitation strategies.MethodsWe retrospectively collected data on adult OHCA patients admitted to our emergency department between February 2015 and July 2018. OHCA, CAHP, NULL-PLEASE clinical, CAST, and rCAST scores were calculated based on the data collected. The predictive abilities of each score were tested using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve.ResultsWe identified 236 OHCA patients from computer-based medical records and analyzed 189 without missing data. In OHCA patients without bystander witnesses, CAHP and OHCA scores were not calculated. Although the predictive abilities of the scores were not significantly different, the NULL-PLEASE score had a large AUC of ROC curve in various OHCA patients. Furthermore, in patients with bystander-witnessed OHCA, the NULL-PLEASE score had large partial AUCs of ROC from sensitivity 0.8–1.0 and specificity 0.8–1.0.ConclusionsThe NULL-PLEASE score had a high, comprehensive predictive ability in various OHCA patients. Furthermore, the NULL-PLEASE score had a high predictive ability for good and poor neurological outcomes in patients with bystander-witnessed OHCA.

Association between age and neurological outcomes in out-of-hospital cardiac arrest patients resuscitated with extracorporeal cardiopulmonary resuscitation: a nationwide multicentre observational study.

Little is known about the difference in outcomes between young and old patients who received extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA). Therefore, we aimed to investigate the differences in outcomes between those aged ≥75 years and <75 years who experienced OHCA and were resuscitated with ECPR. We performed a secondary analysis of a nationwide prospective cohort study using the Japanese Association for Acute Medicine OHCA registry. We identified patients aged ≥18 years with OHCA who received ECPR. The patients were classified into three age groups (18-59 years, 60-74 years, and ≥75 years). The primary outcome was a 1-month neurological outcome. To examine the association between age and 1-month neurological outcome, we performed logistic regression analyses fitted with generalized estimating equations. From 2014 to 2017, we identified 875 OHCA patients aged ≥18 years who received ECPR. The proportion of patients who survived with favourable neurological outcome in the patients aged 18-59 years, 60-74 years, and ≥75 years were 15% (64/434), 8.9% (29/326), and 1.7% (2/115), respectively. In the multivariable analysis, compared with the age of 18-59 years, the proportions of favourable neurological outcomes were significantly lower in patients aged 60-74 years [adjusted odds ratio (OR), 0.44; 95% confidence interval (CI), 0.32-0.61] and those aged ≥75 years (adjusted OR, 0.26; 95% CI, 0.11-0.59). Advanced age (age ≥75 years in particular) was significantly associated with poor neurological outcomes in patients with OHCA who received ECPR.

Stereotactic cisternal lavage in patients with aneurysmal subarachnoid hemorrhage with urokinase and nimodipine for the prevention of secondary brain injury (SPLASH): study protocol for a randomized controlled trial

BackgroundDelayed cerebral infarction (DCI) is a major cause of death and poor neurological outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Direct intrathecal therapies with fibrinolytic and spasmolytic drugs have appeared promising in clinical trials. However, access to the subarachnoid space for intrathecal drug administration is an unsolved problem so far, especially in patients with endovascular aneurysm securing. We investigate a therapy protocol based on stereotactic catheter ventriculocisternostomy (STX-VCS), a new approach to overcome this problem. The primary objective of this study is to assess whether cisternal lavage with urokinase, nimodipine, and Ringer’s solution administered via a stereotactically implanted catheter into the basal cisterns (= investigational treatment (IT)) is safe and improves neurological outcome in patients with aSAH.MethodsThis is a randomized, controlled, parallel-group, open-label phase II trial. Fifty-four patients with severe aSAH (WFNS grade ≥ 3) will be enrolled at one academic tertiary care center in Southern Germany. Patients will be randomized at a ratio of 1:1 to receive either standard of care only or standard of care plus the IT. The primary endpoint is the proportion of subjects with a favorable outcome on the Modified Rankin Scale (defined as mRS 0–3) at 6 months after aSAH. Further clinical and surrogate outcome parameters are defined as secondary endpoints.DiscussionNew approaches for the prevention and therapy of secondary brain injury in patients with aSAH are urgently needed. We propose this RCT to assess the clinical safety and efficacy of a novel therapy protocol for intrathecal administration of urokinase, nimodipine, and Ringer’s solution.Trial registrationDeutsches Register Klinischer Studien (German Clinical Trials Register), DRKS00015645. Registered on 8 May 2019

Serum neurofilament measurement improves clinical risk scores for outcome prediction after cardiac arrest: results of a prospective study

BackgroundA recent study found serum neurofilament light chain (NfL) levels to be strongly associated with poor neurological outcome in patients after cardiac arrest. Our aim was to confirm these findings in an independent validation study and to investigate whether NfL improves the prognostic value of two cardiac arrest-specific risk scores.MethodsThis prospective, single-center study included 164 consecutive adult after out-of-hospital cardiac arrest (OHCA) patients upon intensive care unit admission. We calculated two clinical risk scores (OHCA, CAHP) and measured NfL on admission within the first 24 h using the single molecule array NF-light® assay. The primary endpoint was neurological outcome at hospital discharge assessed with the cerebral performance category (CPC) score.ResultsPoor neurological outcome (CPC > 3) was found in 60% (98/164) of patients, with 55% (91/164) dying within 30 days of hospitalization. Compared to patients with favorable outcome, NfL was 14-times higher in patients with poor neurological outcome (685 ± 1787 vs. 49 ± 111 pg/mL), with an adjusted odds ratio of 3.4 (95% CI 2.1 to 5.6, p < 0.001) and an area under the curve (AUC) of 0.82. Adding NfL to the clinical risk scores significantly improved discrimination of both the OHCA score (from AUC 0.82 to 0.89, p < 0.001) and CAHP score (from AUC 0.89 to 0.92, p < 0.05). Adding NfL to both scores also resulted in significant improvement in reclassification statistics with a Net Reclassification Index (NRI) of 0.58 (p < 0.001) for OHCA and 0.83 (p < 0.001) for CAHP.ConclusionsAdmission NfL was a strong outcome predictor and significantly improved two clinical risk scores regarding prognostication of neurological outcome in patients after cardiac arrest. When confirmed in future outcome studies, admission NfL should be considered as a standard laboratory measures in the evaluation of OHCA patients.

NSE as a predictor of death or poor neurological outcome after non-shockable cardiac arrest due to any cause: Ancillary study of HYPERION trial data

PurposePrognostication of hypoxic-ischaemic brain injury after resuscitation from cardiac arrest is based on a multimodal approach including biomarker assays. Our goal was to assess whether plasma NSE helps to predict day-90 death or poor neurological outcome in patients resuscitated from cardiac arrest in non-shockable rhythm. MethodsAll included patients participated in the randomised multicentre HYPERION trial. Serum blood samples were taken 24, 48, and 72 h after randomisation; pre-treated, aliquoted, and frozen at −80 °C at the study sites; and shipped to a central biology laboratory, where the NSE assays were performed. Primary outcome was neurological status at day 90 assessed by Cerebral Performance Category (1 or 2 versus. 3, 4 or 5). ResultsNSE was assayed in 235 assessable blood samples from 101 patients. In patients with good versus poor outcomes, median NSE values at 24, 48, and 72 h were 22.6 [95%CI, 14.6;27.3] ng/mL versus 33.6 [20.5;90.0] ng/mL (p < 0.04), 18.1 [11.7;29.7] ng/mL versus 76.8 [21.5;206.6] ng/mL (p < 0.0029), and 9 [6.1;18.6] ng/mL versus 80.5 [22.9;236.1] ng/mL (p < 0.001), respectively. NSE at 48 and 72 h predicted the neurological outcome with areas under the receiver-operating curve of 0.79 [95%CI, 0.69;0.96] and 0.9 [0.81;0.96], respectively. NSE levels did not differ significantly between the groups managed at 33°C and 37°C (p = 0.59). ConclusionsData from a multicentre trial on cardiac arrest with a non-shockable rhythm due to any cause confirm that NSE values at 72 h are associated with 90-day outcome. NSE levels did not differ significantly according to the targeted temperature. Registration IdentifierClinicalTrial NCT02722473.