Cerebral Performance Category Research Articles

Association between defibrillation-to-adrenaline interval and short-term outcomes in patients with out-of-hospital cardiac arrest and an initial shockable rhythm

AimThe optimal timing of adrenaline administration after defibrillation in patients with out-of-hospital cardiac arrest (OHCA) and an initial shockable rhythm is unknown. We investigated the association between the defibrillation-to-adrenaline interval and clinical outcomes. MethodsBetween 2011 and 2020, we enrolled 1,259,960 patients with OHCA into a nationwide prospective population-based registry in Japan. After applying exclusion criteria, 20,905 patients with an initial shockable rhythm documented at emergency medical services (EMS) arrival who received adrenaline after defibrillation were eligible for this study. Multivariable logistic regression analysis was used to predict favourable short-term outcomes: prehospital return of spontaneous circulation (ROSC), 30-day survival, or a favourable neurological outcome (Cerebral Performance Category 1 or 2) at 30 days. Patients were categorised into 2-minute defibrillation-to-adrenaline intervals up to 18 min, or more than 18 min. ResultsAt 30 days, 1,618 patients (8%) had a favourable neurological outcome. The defibrillation-to-adrenaline interval in these patients was significantly shorter than in patients with an unfavourable neurological outcome [8 (5–12) vs 11 (7–16) minutes; P < 0.001]. The proportion of patients with prehospital ROSC, 30-day survival, or a favourable neurological outcome at 30 days decreased as the defibrillation-to-adrenaline interval increased (P < 0.001 for trend). Multivariable analysis revealed that a defibrillation-to-adrenaline interval of > 6 min was an independent predictor of worse prehospital ROSC, 30-day survival, or neurological outcome at 30 days when compared with an interval of 4–6 min. ConclusionA longer defibrillation-to-adrenaline interval was significantly associated with worse short-term outcomes in patients with OHCA and an initial shockable rhythm.

Higher levels of brain injury biomarker tau are associated with unfavorable outcomes in patients supported with ECMO following cardiac arrest

AimWe sought to determine if higher plasma levels of brain injury biomarkers neurofilament light (NfL), phosphorylated tau 181 (pT181), tau, and ubiquitin C-terminal hydrolase L1 (UCHL1) were associated with unfavorable outcomes in children supported on extracorporeal membrane oxygenation (ECMO) with and without preceding cardiac arrest. MethodsWe conducted a secondary analysis of a two-center prospective observational study of ECMO patients 0-<18 years. Plasma concentrations of NfL, pT181, tau, and UCHL1 were measured on ECMO days 1, 2 and 3. Unfavorable outcome was defined as in-hospital mortality or discharge Pediatric Cerebral Performance Category (PCPC) >2 with decline from baseline PCPC among survivors. ResultsAmong 88 children on ECMO, mean tau levels were significantly higher on each of the first three ECMO days in children who underwent extracorporeal cardiopulmonary resuscitation (ECPR) compared to those with non-ECPR cardiac arrest or with no cardiac arrest preceding ECMO. Higher ECMO day 1 tau levels were significantly associated with increased hazard of unfavorable outcome in unadjusted (HR, 1.35, 95% CI 1.09–1.66) and adjusted (HR, 1.42; 95% CI 1.13–1.79) models. Higher levels of NfL or pT181 were not associated with increased hazard for unfavorable outcome in multivariable models.UCHL1 values were outside of detectable limits and thus deferred from analysis. ConclusionsLevels of tau were significantly associated with increased hazard of death or unfavorable neurologic outcome in unadjusted and adjusted models. Biomarkers of brain injury, particularly tau, may aid in detection of neurologic injury and neuroprognostication in patients on ECMO with and without preceding cardiac arrest.

Non-linear association between the time required to reaching temperature targets and the neurological outcome in patients undergoing targeted temperature management after out-of-hospital cardiac arrest: Observational multicentre cohort study

PurposeWe evaluated associations between outcomes and time to achieving temperature targets during targeted temperature management of out-of-hospital cardiac arrest. MethodsUsing Comprehensive Registry of Intensive Care for out-of-hospital cardiac arrest Survival (CRITICAL) study, we enrolled all patients transported to participating hospitals from 1 July 2012 through 31 December 2017 aged ≥ 18 years with out-of-hospital cardiac arrest of cardiac aetiology and who received targeted temperature management in Osaka, Japan. Primary outcome was Cerebral Performance Category scale of 1 or 2 one month after cardiac arrest, designated as “one-month favourable neurological outcome”. Non-linear multivariable logistic regression analyses assessed the primary outcome based on time to reaching temperature targets. In patients subdivided into quintiles based on time to achieving temperature targets, multivariable logistic regression calculated adjusted odds ratios and 95% confidence intervals. ResultsWe analysed 473 patients. In non-linear multivariable logistic regression analysis, p value for non-linearity was < 0.01. In the first quintile (< 26.7 minutes), second quintile (26.8–89.9 minutes), third quintile (90.0–175.1 minutes), fourth quintile (175.2–352.1 minutes), and fifth quintile (≥ 352.2 minutes), one-month favourable neurological outcome was 32.6% (31/95), 40.0% (36/90), 53.5% (53/99), 57.4% (54/94), and 37.9% (36/95), respectively. Adjusted odds ratios with 95% confidence intervals for one-month favourable neurological outcome in the first, second, third, and fifth quintiles compared with the fourth quintile were 0.38 (0.20 to 0.72), 0.43 (0.23 to 0.81), 0.77 (0.41 to 1.44), and 0.46 (0.25 to 0.87), respectively. ConclusionNon-linear multivariable logistic regression analysis could clearly describe the association between neurological outcome in patients with out-of-hospital cardiac arrest and the time from the introduction of targeted temperature management to reaching the temperature targets.

Advantages of bystander-performed conventional cardiopulmonary resuscitation in out-of-hospital cardiac arrest presumably caused by drowning in Japan: a propensity score-matching analysis using an extended nationwide database

ObjectivesThis study aimed to determine whether the association between conventional bystander cardiopulmonary resuscitation (BCPR) and better outcomes in drowning-associated out-of-hospital cardiac arrest (OHCA) differs between young and older people or...

Ferritin Levels on Hospital Admission Predict Hypoxic-Ischemic Encephalopathy in Patients After Out-of-Hospital Cardiac Arrest: A Prospective Observational Single-Center Study.

Out-of-hospital cardiac arrest (OHCA) is a major health concern in Western societies. Poor outcome after OHCA is determined by the extent of hypoxic-ischemic encephalopathy (HIE). Dysregulation of iron metabolism has prognostic relevance in patients with ischemic stroke and sepsis. The aim of this study was to determine whether serum iron parameters help to estimate outcomes after OHCA. In this prospective single-center study, 70 adult OHCA patients were analyzed. Serum ferritin, iron, transferrin (TRF), and TRF saturation (TRFS) were measured in blood samples drawn on day 0 (admission), day 2, day 4, and 6 months after the return of spontaneous circulation (ROSC). The association of 4 iron parameters with in-hospital mortality, neurological outcome (cerebral performance category [CPC]), and HIE was investigated by receiver operating characteristics and multivariate regression analyses. OHCA subjects displayed significantly increased serum ferritin levels on day 0 and lowered iron, TRF, and TRFS on days 2 and 4 after ROSC, as compared to concentrations measured at a 6-month follow-up. Iron parameters were not associated with in-hospital mortality or neurological outcomes according to the CPC. Ferritin on admission was an independent predictor of features of HIE on cranial computed tomography and death due to HIE. OHCA is associated with alterations in iron metabolism that persist for several days after ROSC. Ferritin on admission can help to predict HIE.

Exploratory factor analysis yields grouping of brain injury biomarkers significantly associated with outcomes in neonatal and pediatric ECMO

In this two-center prospective cohort study of children on ECMO, we assessed a panel of plasma brain injury biomarkers using exploratory factor analysis (EFA) to evaluate their interplay and association with outcomes. Biomarker concentrations were measured daily for the first 3 days of ECMO support in 95 participants. Unfavorable composite outcome was defined as in-hospital mortality or discharge Pediatric Cerebral Performance Category > 2 with decline ≥ 1 point from baseline. EFA grouped 11 biomarkers into three factors. Factor 1 comprised markers of cellular brain injury (NSE, BDNF, GFAP, S100β, MCP1, VILIP-1, neurogranin); Factor 2 comprised markers related to vascular processes (vWF, PDGFRβ, NPTX1); and Factor 3 comprised the BDNF/MMP-9 cellular pathway. Multivariable logistic models demonstrated that higher Factor 1 and 2 scores were associated with higher odds of unfavorable outcome (adjusted OR 2.88 [1.61, 5.66] and 1.89 [1.12, 3.43], respectively). Conversely, higher Factor 3 scores were associated with lower odds of unfavorable outcome (adjusted OR 0.54 [0.31, 0.88]), which is biologically plausible given the role of BDNF in neuroplasticity. Application of EFA on plasma brain injury biomarkers in children on ECMO yielded grouping of biomarkers into three factors that were significantly associated with unfavorable outcome, suggesting future potential as prognostic instruments.

Perfusion index and mean arterial pressure after return of spontaneous circulation in out-of hospital cardiac arrest (OHCA) and their relationship with perfusion and survival

Abstract Funding Acknowledgements None. Background Current guidelines for post-cardiac arrest care recommend targeting mean arterial pressure (MAP) to restore adequate perfusion indicated by adequate urine output (UO) and normal or decreasing lactate, avoiding hypotension (MAP &amp;lt; 65 mmHg). The peripheral perfusion index (PI) is the ratio of the pulsatile blood flow to the non-pulsatile blood flow measured peripherally by a standard pulse-oximeter, and it represents a promising non-invasive tool to assess perfusion. The goal of this study is to assess whether prehospital PI and MAP measurements are associated with lactate clearance (LC), adequate UO and 30-days survival with good neurological outcome. Methods A retrospective analysis of prospectively collected data (January 2018 - March 2023) in two cardiac arrest registries located in Italy and Belgium was performed. PI was automatically and continuously measured by the manual monitor/defibrillator. The mean PI value of each minute after ROSC was extracted from the monitor data report and the mean value of 30 min of PI monitoring (MPI30) was calculated and categorized in tertiles (MPI30 T1-T3). The lowest prehospital value for MAP recording was considered. LC was defined by a serum lactate level &amp;lt;2 mmol/L at 6 hours. Inadequate UO was defined as &amp;lt; 0.5mL/kg/h averaged at 12 hours. Neurological outcome was assessed with the Cerebral Performance Category (CPC) at 30 days. Results Out of the 397 OHCA patients admitted to the ICU after ROSC enrolled over the study period 206 had a MPI30 value available and were included in this study; MAP value was available in 186 patients. In the subgroup of patients with hypotension, patients with MPI30 in T1 showed higher incidence of inadequate UO at 12 hours (78.9% vs 25.8%, p&amp;lt;0.001). At multivariable logistic regression, after adjusting for MAP, shockable rhythm, age, and dosage of adrenaline administered, MPI30 was independently associated with inadequate UO (OR 0.68, 95% CI 0.50-0.91, p=0.01). Patients with hypotension and MPI30 in T1 showed lower LC at 6h (15.8% vs 43.4%, p=0.02) when compared to the remaining population. At multivariable Cox proportional-hazard regression, after correction for shockable rhythm, age, and total amount of adrenaline administered, patients with hypotension and MPI30 in T1 showed lower survival with CPC 1-2 at 30 days (HR 2.61, 95% CI 1.52-4.51, p=&amp;lt;0.001) when compared to patients without hypotension or with hypotension but MPI30 in T2-T3. No difference in LC, adequate UO and survival with good neurological outcome was found between patients with hypotension and MPI30 in T2-T3 compared to patients without hypotension. Conclusion PI is a useful indicator of perfusion in patients with hypotension after OHCA. Patients with hypotension and reduced PI showed higher incidence of inadequate UO and lower incidence of LC, as well as association with lower survival at 30 days with CPC 1-2.Lactate clearenceSurvival at 30days with CPC 1-2

Post-intensive care syndrome and health-related quality of life in long-term survivors of cardiac arrest: a prospective cohort study

Patients discharged from intensive care are at risk for post-intensive care syndrome (PICS), which consists of physical, psychological, and/or neurological impairments. This study aimed to analyze PICS at 24 months follow-up, to identify potential risk factors for PICS, and to assess health-related quality of life in a long-term cohort of adult cardiac arrest survivors. This prospective cohort study included adult cardiac arrest survivors admitted to the intensive care unit of a Swiss tertiary academic medical center. The primary endpoint was the prevalence of PICS at 24 months follow-up, defined as impairments in physical (measured through the European Quality of Life 5-Dimensions-3-Levels instrument [EQ-5D-3L]), neurological (defined as Cerebral Performance Category Score > 2 or Modified Rankin Score > 3), and psychological (based on the Hospital Anxiety and Depression Scale and the Impact of Event Scale-Revised) domains. Among 107 cardiac arrest survivors that completed the 2-year follow-up, 46 patients (43.0%) had symptoms of PICS, with 41 patients (38.7%) experiencing symptoms in the physical domain, 16 patients (15.4%) in the psychological domain, and 3 patients (2.8%) in the neurological domain. Key predictors for PICS in multivariate analyses were female sex (adjusted odds ratio [aOR] 3.17, 95% CI 1.08 to 9.3), duration of no-flow interval during cardiac arrest (minutes) (aOR 1.17, 95% CI 1.02 to 1.33), post-discharge job-loss (aOR 31.25, 95% CI 3.63 to 268.83), need for ongoing psychological support (aOR 3.64, 95% CI 1.29 to 10.29) or psychopharmacologic treatment (aOR 9.49, 95% CI 1.9 to 47.3), and EQ-visual analogue scale (points) (aOR 0.88, 95% CI 0.84 to 0.93). More than one-third of cardiac arrest survivors experience symptoms of PICS 2 years after resuscitation, with the highest impairment observed in the physical and psychological domains. However, long-term survivors of cardiac arrest report intact health-related quality of life when compared to the general population. Future research should focus on appropriate prevention, screening, and treatment strategies for PICS in cardiac arrest patients.

Ghrelin for Neuroprotection in Post–Cardiac Arrest Coma

Out-of-hospital cardiac arrest survival rates have markedly risen in the last decades, but neurological outcome only improved marginally. Despite research on more than 20 neuroprotective strategies involving patients in comas after cardiac arrest, none have demonstrated unequivocal evidence of efficacy; however, treatment with acyl-ghrelin has shown improved functional and histological brain recovery in experimental models of cardiac arrest and was safe in a wide variety of human study populations. To determine safety and potential efficacy of intravenous acyl-ghrelin to improve neurological outcome in patients in a coma after cardiac arrest. A phase 2, double-blind, placebo-controlled, multicenter, randomized clinical trial, Ghrelin Treatment of Comatose Patients After Cardiac Arrest: A Clinical Trial to Promote Cerebral Recovery (GRECO), was conducted between January 18, 2019, and October 17, 2022. Adult patients 18 years or older who were in a comatose state after cardiac arrest were assessed for eligibility; patients were from 3 intensive care units in the Netherlands. Expected death within 48 hours or unfeasibility of treatment initiation within 12 hours were exclusion criteria. Patients were randomized to receive intravenous acyl-ghrelin, 600 μg (intervention group), or placebo (control group) within 12 hours after cardiac arrest, continued for 7 days, twice daily, in addition to standard care. Primary outcome was the score on the Cerebral Performance Categories (CPC) scale at 6 months. Safety outcomes included any serious adverse events. Secondary outcomes were mortality and neuron-specific enolase (NSE) levels on days 1 and 3. A total of 783 adult patients in a coma after cardiac arrest were assessed for eligibility, and 160 patients (median [IQR] age, 68 [57-75] years; 120 male [75%]) were enrolled. A total of 81 patients (51%) were assigned to the intervention group, and 79 (49%) were assigned to the control group. The common odds ratio (OR) for any CPC improvement in the intervention group was 1.78 (95% CI, 0.98-3.22; P = .06). This was consistent over all CPC categories. Mean (SD) NSE levels on day 1 after cardiac arrest were significantly lower in the intervention group (34 [6] μg/L vs 56 [13] μg/L; P = .04) and on day 3 (28 [6] μg/L vs 52 [14] μg/L; P = .08). Serious adverse events were comparable in incidence and type between the groups. Mortality was 37% (30 of 81) in the intervention group vs 51% (40 of 79) in the control group (absolute risk reduction, 14%; 95% CI, -2% to 29%; P = .08). In patients in a coma after cardiac arrest, intravenous treatment with acyl-ghrelin was safe and potentially effective to improve neurological outcome. Phase 3 trials are needed for conclusive evidence. Clinicaltrialsregister.eu: EUCTR2018-000005-23-NL.

External Validation of Updated Prediction Models for Neurological Outcomes at 90 Days in Patients With Out-of-Hospital Cardiac Arrest.

Few prediction models for individuals with early-stage out-of-hospital cardiac arrest (OHCA) have undergone external validation. This study aimed to externally validate updated prediction models for OHCA outcomes using a large nationwide dataset. We performed a secondary analysis of the JAAM-OHCA (Comprehensive Registry of In-Hospital Intensive Care for Out-of-Hospital Cardiac Arrest Survival and the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest) registry. Previously developed prediction models for patients with cardiac arrest who achieved the return of spontaneous circulation were updated. External validation was conducted using data from 56 institutions from the JAAM-OHCA registry. The primary outcome was a dichotomized 90-day cerebral performance category score. Two models were updated using the derivation set (n=3337). Model 1 included patient demographics, prehospital information, and the initial rhythm upon hospital admission; Model 2 included information obtained in the hospital immediately after the return of spontaneous circulation. In the validation set (n=4250), Models 1 and 2 exhibited a C-statistic of 0.945 (95% CI, 0.935-0.955) and 0.958 (95% CI, 0.951-0.960), respectively. Both models were well-calibrated to the observed outcomes. The decision curve analysis showed that Model 2 demonstrated higher net benefits at all risk thresholds than Model 1. A web-based calculator was developed to estimate the probability of poor outcomes (https://pcas-prediction.shinyapps.io/90d_lasso/). The updated models offer valuable information to medical professionals in the prediction of long-term neurological outcomes for patients with OHCA, potentially playing a vital role in clinical decision-making processes.

Treatment strategies for patients with out-of-hospital cardiac arrest associated with traumatic brain injury: A case series

IntroductionCollapse after out-of-hospital cardiac arrest (OHCA) can cause severe traumatic brain injury (TBI). We aimed to investigate the clinical characteristics and treatment strategies for patients with OHCA and TBI. MethodsWe analyzed a consecutive cohort of patients with intrinsic OHCA retrospectively treated between January 2011 and December 2021 at a single critical care center, and presented a case series of seven patients. Patients with collapse-related TBI were examined for the causes and situations of cardiac arrest, laboratory data, radiological images, targeted temperature management (TTM), coronary angiography (CAG), percutaneous coronary intervention (PCI), and extracorporeal cardiopulmonary resuscitation (ECPR). ResultsOf the 197 patients with intrinsic OHCA, 7 (3.6%) had TBI (age range: 49–70 years; 6 men). All seven patients presented with ventricular fibrillation in the initial electrocardiograms, with four refractory cases treated with ECPR. All patients underwent CAG under heparinization, and four underwent PCI with antiplatelet administration. Initial head computed tomography indicated an intracranial hemorrhage (ICH) in three patients. ICH appeared or was exacerbated in six patients after CAG with or without PCI, except in one who underwent delayed PCI. All patients displayed elevated plasma D-dimer levels, and four underwent neurosurgical procedures. Four patients survived (three with cerebral performance category [CPC] 2, one with CPC 3) and three died; two had hypoxic-ischemic brain injury and one had severe TBI. ConclusionDelayed ICH occurred frequently. Individualized management is required based on the extent of brain and cardiac damage, including optimal TTM, PCI procedures, and antiplatelet medications. Early detection of ICH and emergency treatment are critical for multi-disciplinary collaboration.

Factors associated with family decision-making after pediatric out-of-hospital cardiac arrest

AimThis study aims to identify demographic factors, area-based social determinants of health (SDOH), and clinical features associated with medical decision-making after pediatric out-of-hospital cardiac arrest (OHCA). MethodsThis is a retrospective, exploratory, descriptive analysis of patients < 18 years old admitted to the pediatric intensive care unit (ICU) after OHCA from 2011 to 2022 (n = 217) at an urban tertiary care, free-standing children’s hospital. Outcomes of interest included: (1) whether a new advance care plan (ACP) (defined as a written advance directive including do not resuscitate and/or do not intubate) was ordered during hospitalization, and (2) whether the patient was discharged with new medical technology (defined as tracheostomy and/or feeding tube). Logistic regression models identified features associated with these outcomes. ResultsOf the 217 patients, 78 patients (36%) had a new ACP placed during their admission. Of the survivors, 26% (27/102) were discharged home with new medical technology. Factors associated with ACP were greater change in Pediatric Cerebral Performance Category (PCPC) score (aOR = 1.49, 95% CI [1.28–1.73], p-value < 0.001) and palliative care consultation (aOR = 2.39, 95% CI [1.16–4.89], p-value 0.018). Factors associated with new medical technology were lower change in PCPC score (aOR = 0.76, 95% C.I. [0.61–0.95], p-value = 0.015) and palliative care consultation (aOR = 7.07, 95% CI [3.01–16.60], p-value < 0.001). There were no associations between area-based SDOH and outcomes. ConclusionsUnderstanding factors associated with decision-making related to ACP after OHCA is critical to optimize counseling for families. Multi-institutional studies are warranted to identify whether these findings are generalizable.

Survival trends of extracorporeal membrane oxygenation support for pediatric emergency patients in regional and metropolitan areas in Japan

BackgroundTo assess the performance of pediatric extracorporeal membrane oxygenation (ECMO) centers, outcomes were compared between metropolitan and other areas. MethodsA retrospective cohort study was conducted at three regional centers on Kyushu Island and the largest center in the Tokyo metropolitan area of Japan. The clinical outcomes of patients of ≤15 years of age who received ECMO during 2010–2019 were investigated, targeting the survival and performance at discharge from intensive care units (ICUs), using medical charts. ResultsOne hundred and fifty-five patients were analyzed (regional, n = 70; metropolitan, n = 85). Survival rates at ICU discharge were similar between the two areas (64%). In regional centers, deterioration of Pediatric Cerebral Performance Category (PCPC) scores were more frequent (65.7% vs. 49.4%; p = 0.042), but survival rates and ΔPCPC scores (PCPC at ICU discharge–PCPC before admission) improved in the second half of the study period (p = 0.005 and p = 0.046, respectively). Veno-arterial ECMO (odds ratio [OR], 3.00; p < 0.03), extracorporeal cardiopulmonary resuscitation (OR, 8.98; p < 0.01), and absence of myocarditis (OR, 5.47; p < 0.01) were independent risk factors for deterioration of the PCPC score. A sub-analysis of patients with acute myocarditis (n = 51), the main indicator for ECMO, revealed a significantly higher proportion of cases with deteriorated PCPC scores in regional centers (51.9% vs. 25.0%; p = 0.049). ConclusionsThe survival rates of pediatric patients supported by ECMO in regional centers were similar to those in a metropolitan center. However, neurological outcomes must be improved, particularly in patients with acute myocarditis.

Regional brain net water uptake in computed tomography after cardiac arrest – A novel biomarker for neuroprognostication

BackgroundSelective water uptake by neurons and glial cells and subsequent brain tissue oedema are key pathophysiological processes of hypoxic-ischemic encephalopathy (HIE) after cardiac arrest (CA). Although brain computed tomography (CT) is widely used to assess the severity of HIE, changes of brain radiodensity over time have not been investigated. These could be used to quantify regional brain net water uptake (NWU), a potential prognostic biomarker. MethodsWe conducted an observational prognostic accuracy study including a derivation (single center cardiac arrest registry) and a validation (international multicenter TTM2 trial) cohort. Early (<6 h) and follow-up (>24 h) head CTs of CA patients were used to determine regional NWU for grey and white matter regions after co-registration with a brain atlas. Neurological outcome was dichotomized as good versus poor using the Cerebral Performance Category Scale (CPC) in the derivation cohort and Modified Rankin Scale (mRS) in the validation cohort. ResultsWe included 115 patients (81 derivation, 34 validation) with out-of-hospital (OHCA) and in-hospital cardiac arrest (IHCA). Regional brain water content remained unchanged in patients with good outcome. In patients with poor neurological outcome, we found considerable regional water uptake with the strongest effect in the basal ganglia. NWU >8% in the putamen and caudate nucleus predicted poor outcome with 100% specificity (95%-CI: 86–100%) and 43% (moderate) sensitivity (95%-CI: 31–56%). ConclusionThis pilot study indicates that NWU derived from serial head CTs is a promising novel biomarker for outcome prediction after CA. NWU >8% in basal ganglia grey matter regions predicted poor outcome while absence of NWU indicated good outcome. NWU and follow-up CTs should be investigated in larger, prospective trials with standardized CT acquisition protocols.

Quantitative analysis of apparent diffusion coefficients to predict neurological prognosis in cardiac arrest survivors: an observational derivation and internal–external validation study

BackgroundThis study aimed to validate apparent diffusion coefficient (ADC) values and thresholds to predict poor neurological outcomes in out-of-hospital cardiac arrest (OHCA) survivors by quantitatively analysing the ADC values via brain magnetic resonance imaging (MRI).MethodsThis observational study used prospectively collected data from two tertiary academic hospitals. The derivation cohort comprised 70% of the patients randomly selected from one hospital, whereas the internal validation cohort comprised the remaining 30%. The external validation cohort used the data from another hospital, and the MRI data were restricted to scans conducted at 3 T within 72–96 h after an OHCA experience. We analysed the percentage of brain volume below a specific ADC value at 50-step intervals ranging from 200 to 1200 × 10–6 mm2/s, identifying thresholds that differentiate between good and poor outcomes. Poor neurological outcomes were defined as cerebral performance categories 3–5, 6 months after experiencing an OHCA.ResultsA total of 448 brain MRI scans were evaluated, including a derivation cohort (n = 224) and internal/external validation cohorts (n = 96/128, respectively). The proportion of brain volume with ADC values below 450, 500, 550, 600, and 650 × 10–6 mm2/s demonstrated good to excellent performance in predicting poor neurological outcomes in the derivation group (area under the curve [AUC] 0.89–0.91), and there were no statistically significant differences in performances among the derivation, internal validation, and external validation groups (all P > 0.5). Among these, the proportion of brain volume with an ADC below 600 × 10–6 mm2/s predicted a poor outcome with a 0% false-positive rate (FPR) and 76% (95% confidence interval [CI] 68–83) sensitivity at a threshold of > 13.2% in the derivation cohort. In both the internal and external validation cohorts, when using the same threshold, a specificity of 100% corresponded to sensitivities of 71% (95% CI 58–81) and 78% (95% CI 66–87), respectively.ConclusionsIn this validation study, by consistently restricting the MRI types and timing during quantitative analysis of ADC values in brain MRI, we observed high reproducibility and sensitivity at a 0% FPR. Prospective multicentre studies are necessary to validate these findings.

Neurological outcome of cardiac arrest patients in mountain areas: An analysis of the Northern French Alps Emergency Network

BackgroundMountainous areas pose a challenge for the out-of-hospital cardiac arrest (OHCA) chain of survival. Survival rates for OHCAs in mountainous areas may differ depending on the location. Increased survival has been observed compared to standard location when OHCA occurred on ski slopes. Limited data is available about OHCA in other mountainous areas. The objective was to compare the survival rates with a good neurological outcome of OHCAs occurring on ski slopes (On-S) and off the ski slopes (OffS) compared to other locations (OL). MethodsAnalysis of prospectively collected data from the cardiac arrest registry of the Northern French Alps Emergency Network (RENAU) from 2015 to 2021. The RENAU corresponding to an Emergency Medicine Network between all Emergency Medical Services and hospitals of 3 counties (Isère, Savoie, Haute-Savoie). The primary outcome was survival at 30 days with a Cerebral Performance Category scale (CPC) of 1 or 2 (1: Good Cerebral Performance, 2: Moderate Cerebral Disability). ResultsA total of 9589 OHCAs were included: 213 in the On-S group, 141 in the Off-S group, and 9235 in the OL group. Cardiac etiology was more common in On-S conditions (On-S: 68.9% vs OffS: 51.1% vs OL: 66.7%, p < 0.001), while Off-S cardiac arrests were more often due to traumatic circumstances (OffS: 39.7% vs On-S: 21.7% vs OL: 7.7%, p < 0.001). Automated external defibrillator (AED) use before rescuers' arrival was lower in the Off-S group than in the other two groups (On-S: 15.2% vs OL: 4.5% vs OffS: 3.7%; p < 0.002). The first AED shock was longer in the Off-S group (median time in minutes: OffS: 22.0 (9.5–35.5) vs On-S: 10.0 (3.0–19.5) vs OL: 16.0 (11.0–27.0), p = 0.03). In multivariate analysis, on-slope OHCA remained a positive factor for 30-day survival with a CPC score of 1 or 2 with a 1.96 adjusted odds ratio (95% confidence interval (CI), 1.02–3.75, p = 0.04), whereas off-slope OHCA had an 0.88 adjusted odds ratio (95% CI, 0.28–2.72, p = 0.82). ConclusionsOHCAs in ski-slopes conditions were associated with an improvement in neurological outcomes at 30 days, whereas off-slopes OHCAs were not. Ski-slopes rescue patrols are efficient in improving outcomes.

Biomarkers for neuroprognostication after standard versus extracorporeal cardiopulmonary resuscitation – A sub-analysis of Prague-OHCA study

BackgroundLimited evidence exists for prognostic performance of biomarkers in patients resuscitated from out-of-hospital cardiac arrest (OHCA) with extracorporeal CPR (ECPR). We hypothesized that (1) the time course and (2) prognostic performance of biomarkers might differ between CPR and ECPR in a sub-analysis of Prague-OHCA study. MethodsPatients received either CPR (n = 164) or ECPR (n = 92). The primary outcome was favorable neurologic survival at 180 days [cerebral performance category (CPC) 1–2]. Secondary outcomes included biomarkers of neurologic injury, inflammation and hemocoagulation. ResultsFavorable neurologic outcome was not different between groups: CPR 29.3% vs. ECPR 21.7%; p = 0.191. Biomarkers exhibited similar trajectories in both groups, with better values in patients with CPC 1–2. Procalcitonin (PCT) was higher in ECPR group at 24–72 h (all p < 0.01). Neuron-specific enolase (NSE), C-reactive protein and neutrophil-to-lymphocyte ratio did not differ between groups. Platelets, D-dimers and fibrinogen were lower in ECPR vs. CPR groups at 24–72 h (all p < 0.001). ROC analysis (24–48–72 h) showed the best performance of NSE in both CPR and ECPR groups (AUC 0.89 vs. 0.78; 0.9 vs. 0.9; 0.91 vs. 0.9). PCT showed good performance specifically in ECPR (0.72 vs. 0.84; 0.73 vs. 0.87; 0.73 vs. 0.86). Optimal cutoff points of NSE and PCT were higher in ECPR vs. CPR. ConclusionsBiomarkers exhibited similar trajectories although absolute values tended to be higher in ECPR. NSE had superior performance in both groups. PCT showed a good performance specifically in ECPR. Additional biomarkers may have modest incremental value. Prognostication algorithms should reflect the resuscitation method.

Evaluating the impact of ELSO guideline adherence on favorable neurological outcomes among patients requiring extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest

AimSelecting the appropriate candidates for extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA) is challenging. Previously, the Extracorporeal Life Support Organization (ELSO) guidelines suggested the example of inclusion criteria. However, it is unclear whether patients who meet the inclusion criteria of the ELSO guidelines have more favorable outcomes. We aimed to evaluate the relationship between the outcomes and select inclusion criteria of the ELSO guidelines. MethodsWe conducted a post-hoc analysis of a multicenter prospective study conducted between 2019 and 2021. Adult patients with OHCA treated with ECPR were included. The primary outcome was a favorable neurological outcome (Cerebral Performance Category of 1 or 2) at 30 days. An ELSO criteria score was assigned based on four criteria: (i) age < 70 years; (ii) witness; (iii) bystander CPR; and (iv) low-flow time (<60 min). Subgroup analysis based on initial cardiac rhythm was performed. ResultsAmong 9,909 patients, 227 with OHCA were included. The proportion of favorable neurological outcomes according to the number of ELSO criteria met were: 0.0% (0/3), 0 points; 0.0% (0/23), 1 point; 3.0% (2/67), 2 points; 7.3% (6/82), 3 points; and 16.3% (7/43), 4 points. A similar tendency was observed in patients with an initial shockable rhythm. However, no such relationship was observed in those with an initial non-shockable rhythm. ConclusionPatients who adhered more closely to specific inclusion criteria of the ELSO guidelines demonstrated a tendency towards a higher rate of favorable neurological outcomes. However, the relationship was heterogeneous according to initial rhythm.

Fluid balance during acute phase extracorporeal cardiopulmonary resuscitation and outcomes in OHCA patients: a retrospective multicenter cohort study.

The association between fluid balance and outcomes in patients who underwent out-of-hospital cardiac arrest (OHCA) and received extracorporeal cardiopulmonary resuscitation (ECPR) remains unknown. We aimed to examine the above relationship during the first 24 h following intensive care unit (ICU) admission. We performed a secondary analysis of the SAVE-J II study, a retrospective multicenter study involving OHCA patients aged ≥ 18 years treated with ECPR between 2013 and 2018 and who received fluid therapy following ICU admission. Fluid balance was calculated based on intravenous fluid administration, blood transfusion, and urine output. The primary outcome was in-hospital mortality. The secondary outcomes included unfavorable outcome (cerebral performance category scores of 3-5 at discharge), acute kidney injury (AKI), and need for renal replacement therapy (RRT). Overall, 959 patients met our inclusion criteria. In-hospital mortality was 63.6%, and the proportion of unfavorable outcome at discharge was 82.0%. The median fluid balance in the first 24 h following ICU admission was 3673 mL. Multivariable analysis revealed that fluid balance was significantly associated with in-hospital mortality (odds ratio (OR), 1.04; 95% confidence interval (CI), 1.02-1.06; p < 0.001), unfavorable outcome (OR, 1.03; 95% CI, 1.01-1.06; p = 0.005), AKI (OR, 1.04; 95% CI, 1.02-1.05; p < 0.001), and RRT (OR, 1.05; 95% CI, 1.03-1.07; p < 0.001). Excessive positive fluid balance in the first day following ICU admission was associated with in-hospital mortality, unfavorable outcome, AKI, and RRT in ECPR patients. Further investigation is warranted.

A national multi centre pre-hospital ECPR stepped wedge study; design and rationale of the ON-SCENE study

BackgroundThe likelihood of return of spontaneous circulation with conventional advanced life support is known to have an exponential decline and therefore neurological outcome after 20 min in patients with a cardiac arrest is poor. Initiation of venoarterial ExtraCorporeal Membrane Oxygenation (ECMO) during resuscitation might improve outcomes if used in time and in a selected patient category. However, previous studies have failed to significantly reduce the time from cardiac arrest to ECMO flow to less than 60 min. We hypothesize that the initiation of Extracorporeal Cardiopulmonary Resuscitation (ECPR) by a Helicopter Emergency Medical Services System (HEMS) will reduce the low flow time and improve outcomes in refractory Out of Hospital Cardiac Arrest (OHCA) patients.MethodsThe ON-SCENE study will use a non-randomised stepped wedge design to implement ECPR in patients with witnessed OHCA between the ages of 18–50 years old, with an initial presentation of shockable rhythm or pulseless electrical activity with a high suspicion of pulmonary embolism, lasting more than 20, but less than 45 min. Patients will be treated by the ambulance crew and HEMS with prehospital ECPR capabilities and will be compared with treatment by ambulance crew and HEMS without prehospital ECPR capabilities. The primary outcome measure will be survival at hospital discharge. The secondary outcome measure will be good neurological outcome defined as a cerebral performance categories scale score of 1 or 2 at 6 and 12 months.DiscussionThe ON-SCENE study focuses on initiating ECPR at the scene of OHCA using HEMS. The current in-hospital ECPR for OHCA obstacles encompassing low survival rates in refractory arrests, extended low-flow durations during transportation, and the critical time sensitivity of initiating ECPR, which could potentially be addressed through the implementation of the HEMS system. When successful, implementing on-scene ECPR could significantly enhance survival rates and minimize neurological impairment.Trial registrationClinicaltyrials.gov under NCT04620070, registration date 3 November 2020.