Cardiac Arrest Survivors Research Articles

Resting state EEG relates to short- and long-term cognitive functioning after cardiac arrest

BackgroundApproximately half of cardiac arrest survivors have persistent cognitive impairment. Guidelines recommend early screening to identify patients at risk for cognitive impairment, but there is no consensus on the best screening method. We aimed to identify quantitative EEG measures relating with short- and long-term cognitive function after cardiac arrest for potential to cognitive outcome prediction. MethodsWe analyzed data from a prospective longitudinal multicenter cohort study designed to develop a prediction model for cognitive outcome after cardiac arrest. For the current analysis, we used twenty-minute EEG registrations from 80 patients around one week after cardiac arrest. We calculated power spectral density, normalized alpha-to-theta ratio (nATR), peak frequency, and center of gravity (CoG) of this peak frequency. We related these with global cognitive functioning (scores on the Montreal Cognitive Assessment (MoCA)) at one week, three and twelve months follow-up with multivariate mixed effect models, and with performance on standard neuropsychological examination at twelve months using Pearson correlation coefficients. ResultsEach individual EEG parameter related to MoCA at one week (βnATR = 7.36; P < 0.01; βpeak frequency = 1.73, P < 0.01; βCoG = -9.88, P < 0.01). The nATR also related with the MoCA at three months ((βnATR = 2.49; P 0.01). No EEG metrics significantly related to the MoCA score at twelve months. nATR and peak frequency related with memory performance at twelve months. Results were consistent in sensitivity analyses. ConclusionEarly resting-state EEG parameters relate with short-term global cognitive functioning and with memory function at one year after cardiac arrest. Additional predictive values in multimodal prediction models need further study.

Brain network changes and cognitive function after cardiac arrest.

Survival rates after out-of-hospital cardiac arrest have improved over the past two decades. Despite this progress, long-term cognitive impairment remains prevalent even in those with early recovery of consciousness after out-of-hospital cardiac arrest; however, little is known about the determinants and underlying mechanisms. We utilized the REcovery after cardiac arrest surVIVAL cohort of out-of-hospital cardiac arrest survivors who fully regained consciousness to correlate cognition measurements with brain network changes using resting-state functional MRI and the Montreal Cognitive Assessment at hospital discharge and a comprehensive neuropsychological assessment at three-month follow-up. About half of out-of-hospital cardiac arrest survivors displayed cognitive impairments at discharge, and in most, cognitive deficits persisted at three-month follow-up, particularly in the executive and visuospatial functions. Compared to healthy controls, out-of-hospital cardiac arrest survivors exhibited increased connectivity between resting-state networks, particularly involving the frontoparietal network. The increased connectivity between the frontoparietal and visual networks was associated with less favourable cognitive outcomes (β = 14.0, P = 0.01), while higher education seemed to confer some cognitive protection (β = -2.06, P = 0.03). In sum, the data highlight the importance of subtle cognitive impairment, also in out-of-hospital cardiac arrest survivors who are eligible for home discharge, and the potential of functional MRI to identify alterations in brain networks correlating with cognitive outcomes.

Evolution of brain injury and neurological dysfunction after cardiac arrest in the rat – A multimodal and comprehensive model

Cardiac arrest (CA) is one of the leading causes of death worldwide. Due to hypoxic ischemic brain injury, CA survivors may experience variable degrees of neurological dysfunction. This study, for the first time, describes the progression of CA-induced neuropathology in the rat. CA rats displayed neurological and exploratory deficits. Brain MRI revealed cortical and striatal edema at 3 days (d), white matter (WM) damage in corpus callosum (CC), external capsule (EC), internal capsule (IC) at d7 and d14. At d3 a brain edema significantly correlated with neurological score. Parallel neuropathological studies showed neurodegeneration, reduced neuronal density in CA1 and hilus of hippocampus at d7 and d14, with cells dying at d3 in hilus. Microgliosis increased in cortex (Cx), caudate putamen (Cpu), CA1, CC, and EC up to d14. Astrogliosis increased earlier (d3 to d7) in Cx, Cpu, CC and EC compared to CA1 (d7 to d14). Plasma levels of neurofilament light (NfL) increased at d3 and remained elevated up to d14. NfL levels at d7 correlated with WM damage. The study shows the consequences up to 14d after CA in rats, introducing clinically relevant parameters such as advanced neuroimaging and blood biomarker useful to test therapeutic interventions in this model.

Incidence and Survival of Out-of-Hospital Cardiac Arrest in Public Housing Areas in 3 European Capitals.

Strategies to reach out-of-hospital cardiac arrests (called cardiac arrest) in residential areas and reduce disparities in care and outcomes are warranted. This study investigated incidences of cardiac arrests in public housing areas. This register-based cohort study included cardiac arrest patients from Amsterdam (the Netherlands) from 2016 to 2021, Copenhagen (Denmark) from 2016 to 2021, and Vienna (Austria) from 2018 to 2021. Using Poisson regression adjusted for spatial correlation and city, we compared cardiac arrest incidence rates (number per square kilometer per year and number per 100 000 inhabitants per year) in public housing and other residential areas and examined the proportion of cardiac arrests within public housing and adjacent areas (100-m radius). Overall, 9152 patients were included of which 3038 (33.2%) cardiac arrests occurred in public housing areas and 2685 (29.3%) in adjacent areas. In Amsterdam, 635/1801 (35.3%) cardiac arrests occurred in public housing areas; in Copenhagen, 1036/3077 (33.7%); and in Vienna, 1367/4274 (32.0%). Public housing areas covered 42.4 (12.6%) of 336.7 km2 and 1 024 470 (24.6%) of 4 164 700 inhabitants. Across the capitals, we observed a lower probability of 30-day survival in public housing versus other residential areas (244/2803 [8.7%] versus 783/5532 [14.2%]). The incidence rates and rate ratio of cardiac arrest in public housing versus other residential areas were incidence rate, 16.5 versus 4.1 n/km2 per year; rate ratio, 3.46 (95% CI, 3.31-3.62) and incidence rate, 56.1 versus 36.8 n/100 000 inhabitants per year; rate ratio, 1.48 (95% CI, 1.42-1.55). The incidence rates and rate ratios in public housing versus other residential areas were consistent across the 3 capitals. Across 3 European capitals, one-third of cardiac arrests occurred in public housing areas, with an additional third in adjacent areas. Public housing areas exhibited consistently higher cardiac arrest incidences per square kilometer and 100 000 inhabitants and lower survival than other residential areas. Public housing areas could be a key target to improve cardiac arrest survival in countries with a public housing sector.

Cost of out-of-hospital cardiac arrest survivors compared with matched control groups

IntroductionSocietal costs of out-of-hospital cardiac arrest (OHCA) survivors may be extensive due to high health care utilization and sick leave. Knowledge of the costs of OHCA survivors may guide decision-makers to prioritize health resources. AimThe aims of the study were to evaluate the costs of OHCA survivors from a societal perspective, and to compare these costs to the costs of individuals with non-cardiac arrest myocardial infarction (MI) and individuals with no cardiac disease (non-CD). MethodsFrom the Danish OHCA Registers, survivors, with a cardiac arrest between 2005–2018 were identified. Each case was assigned one MI control and one non-CD control, matched on gender and age. Based on register data, costs of healthcare utilization, sick leave, vocational rehabilitation, disability pension and other social benefits one year before event and five years after, were estimated. ResultsIn total 5,646 OHCA survivors were identified with associated control groups. The mean costs for OHCA survivors during the 6-year period were €119,106 (95%CI: 116,297–121,916), with €83,472 (95%CI: 81,392–85,552) being healthcare costs. Mean costs of OHCA survivors were €49,132 higher than the MI-control group and €100,583 higher than the non-CD control group. ConclusionsTotal costs of OHCA survivors were considerably higher than costs of MI- and non-CD controls. Hospital costs were highest during the first year after event, and work inability during the second to fifth year with sick leave and later disability pension as main burdens.

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.

Ketone Bodies after Cardiac Arrest: A Narrative Review and the Rationale for Use.

Cardiac arrest survivors suffer the repercussions of anoxic brain injury, a critical factor influencing long-term prognosis. This injury is characterised by profound and enduring metabolic impairment. Ketone bodies, an alternative energetic resource in physiological states such as exercise, fasting, and extended starvation, are avidly taken up and used by the brain. Both the ketogenic diet and exogenous ketone supplementation have been associated with neuroprotective effects across a spectrum of conditions. These include refractory epilepsy, neurodegenerative disorders, cognitive impairment, focal cerebral ischemia, and traumatic brain injuries. Beyond this, ketone bodies possess a plethora of attributes that appear to be particularly favourable after cardiac arrest. These encompass anti-inflammatory effects, the attenuation of oxidative stress, the improvement of mitochondrial function, a glucose-sparing effect, and the enhancement of cardiac function. The aim of this manuscript is to appraise pertinent scientific literature on the topic through a narrative review. We aim to encapsulate the existing evidence and underscore the potential therapeutic value of ketone bodies in the context of cardiac arrest to provide a rationale for their use in forthcoming translational research efforts.

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.

Return to work after out of hospital cardiac arrest, insights from a prospective multicentric French cohort

Rationale: About 60 to 70% of out-of-hospital cardiac arrest (OHCA) survivors who worked before cardiac arrest return to work within one year but the precise conditions for this resumption of professional activity remain little known. The objective of this study was to assess components of return to work among OHCA survivors. Patients and MethodsWe used the French national multicentric cohort AfterRosc to include OHCA survivors admitted between April 1st 2021 and March 31st 2022, discharged alive from the Intensive Care Unit (ICU), and who were less than 65 years old. A phone-call interview was performed one year after OHCA to assess return to work, level of education, former level of occupation as well as neurological recovery. Geographic and socio-economic data from the patient’s residential neighborhoods were also collected. Comparisons were performed between patients who returned to work and those who did not, using non-parametric tests. ResultsOf the 251 patients included in the registry, 86 were alive at ICU discharge and 31 patients that worked prior to the OHCA were included for analysis. Seventeen survivors returned to work after a median delay of 112 days [92–157] Among them, nine (53%) had required initial work adjustments. Overall, only 6 patients (19%) had returned to work ad integrum. Higher educational level, work which required higher competence-level, higher income, living in a better socio-economical neighborhood, as well as better scores on all three standardized MPAI-4 score components (abilities, adjustment and participation) were significantly associated with return to work. Participants that had not returned to work had a significant drop of income (p = 0.0025). ConclusionIn this prospective study regarding French OHCA survivors, return to work is associated with better socio-economical individual and environmental status, as well as better scores on all MPAI-4 components.

Integrating rSO2 and EEG monitoring in cardiopulmonary resuscitation: A novel methodology

Despite improvements in cardiopulmonary resuscitation (CPR), survival and neurologic recovery after cardiac arrest remain poor due to ischemia and subsequent reperfusion injury. As the likelihood of survival and favorable neurologic outcome decreases with increasing severity of ischemia during CPR, developing methods to measure the magnitude of ischemia during resuscitation is critical for improving overall outcomes. Cerebral oximetry, which measures regional cerebral oxygen saturation (rSO2) by near‐infrared spectroscopy, has emerged as a potentially beneficial marker of cerebral ischemia during CPR. In numerous preclinical and clinical studies, higher rSO2during CPR has been associated with improved cardiac arrest survival and neurologic outcome. There is also emerging evidence that this can be integrated with electroencephalogram (EEG) monitoring to provide a bimodal system of brain monitoring during CPR. In this method’s review, we discuss the feasibility, application, and implications of this integrated monitoring approach, highlighting its significance for improving clinical outcomes in cardiac arrest management and guiding future research directions.

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.

The Dutch Idiopathic Ventricular Fibrillation Registry: progress report on the quest to identify the unidentifiable.

Idiopathic ventricular fibrillation (iVF) is arare cause of sudden cardiac arrest and, by definition, adiagnosis of exclusion. Due to the rarity of the disease, previous and current studies are limited by their retrospective design and small patient numbers. Even though the incidence of iVF has declined owing to the identification of new disease entities, an important subgroup of patients remains. To expand the existing Dutch iVF Registry into alarge nationwide cohort of patients initially diagnosed with iVF, to reveal the underlying cause of iVF in these patients, and to improve arrhythmia management. The Dutch iVF Registry includes sudden cardiac arrest survivors with an initial diagnosis of iVF. Clinical data and outcomes are collected. Outcomes include subsequent detection of adiagnosis other than 'idiopathic', arrhythmia recurrence and death. Non-invasive electrocardiographic imaging is used to investigate electropathological substrates and triggers of VF. To date, 432 patients have been included in the registry (median age at event 40years (interquartile range 28-52)), 61% male. During amedian follow-up of 6(2-12) years, 38patients (9%) received adiagnosis other than 'idiopathic'. Eleven iVF patients were characterised with electrocardiographic imaging. The Dutch iVF Registry is currently the largest of its kind worldwide. In this heterogeneous population of index patients, we aim to identify common functional denominators associated with iVF. With the implementation of non-invasive electrocardiographic imaging and other diagnostic modalities (e.g. echocardiographic deformation, cardiac magnetic resonance), we advance the possibilities to reveal pro-fibrillatory substrates.

Resuscitation for out-of-hospital cardiac arrest in Ireland 2012–2020: Modelling national temporal developments and survival predictors

AimTo explore potential predictors of national out-of-hospital cardiac arrest (OHCA) survival, including health system developments and the COVID pandemic in Ireland. MethodsNational level OHCA registry data from 2012 through to 2020, relating to unwitnessed, and bystander witnessed OHCA were interrogated. Logistic regression models were built by including predictors through stepwise variable selection and enhancing the models by adding pairwise interactions that improved fit. Missing data sensitivity analyses were conducted using multiple imputation. ResultsThe data included 18,177 cases. The final model included seventeen variables. Of these nine variables were involved in pairwise interactions. The COVID-19 period was associated with reduced survival (OR 0.61, 95%CI 0.43, 0.87), as were increasing age in years (OR 0.96, 95% CI 0.96, 0.97) and call response interval in minutes (OR 0.97, 95% CI 0.96, 0.99). Amiodarone administration (OR 3.91, 95% CI 2.80, 5.48), urban location (OR 1.40, 95% CI 1.12, 1.77), and chronological year over time (OR 1.14, 95% CI 1.08, 1.20) were associated with increased survival. ConclusionsNational survival from OHCA has significantly increased incrementally over time in Ireland. The COVID-19 pandemic was associated with decreased survival even after accounting for potential disruption to key elements of bystander and EMS care. Further research is needed to understand and address the discrepancy between urban and rural OHCA survival. Information concerning pre-event patient health status and inpatient care process may yield important additional insights in future.

Age and sex-related differences in outcomes of OHCA patients after adjustment for sex-based in-hospital management disparities

ObjectivesOut-of-hospital cardiac arrest (OHCA) survival differences due to sex remain controversial. Previous studies adjusted for prehospital variables, but not sex-based in-hospital management disparities. We aimed to investigate age and sex-related differences in survival outcomes in OHCA patients after adjustment for sex-based in-hospital management disparities. MethodsThis retrospective observational study used a prospective multicenter OHCA registry to review data of patients from October 2015 to December 2020. The primary outcome was good neurological outcome defined as cerebral performance category score 1 or 2. We performed multivariable logistic regression and restricted cubic spline analysis according to age. ResultsTotally, 8988 patients were analyzed. Women showed poorer prehospital characteristics and received fewer coronary angiography, percutaneous coronary interventions, targeted temperature management, and extracorporeal membrane oxygenation than men. Good neurological outcomes were lower in women than in men (5.8% vs. 12.2%, p < 0.001). After adjustment for age, prehospital variables, and in-hospital management, women were more likely to have good neurological outcomes than men (adjusted odds ratio [aOR] 1.37, 95% confidence interval [CI] 1.07–1.74, p = 0.012). The restricted cubic spline curve showed a reverse sigmoid pattern of adjusted predicted probability of outcomes and dynamic associations of sex and age-based outcomes. ConclusionsWomen with OHCA were more likely to have good neurological outcome after adjusting for age, prehospital variables, and sex-based in-hospital management disparities. There were non-linear associations between sex and survival outcomes according to age and age-related sex-based differences.

Immediate Platelet Inhibition Strategy for Comatose Out-of-Hospital Cardiac Arrest Survivors Undergoing Percutaneous Coronary Intervention and Mild Therapeutic Hypothermia.

Background: Comatose survivors of out-of-hospital cardiac arrest (OHCA) undergoing percutaneous coronary intervention (PCI) and target temperature management (TTM) are at increased risk of stent thrombosis (ST), partly due to delayed platelet inhibition even with more potent P2Y12 agents. We hypothesized that periprocedural cangrelor would induce immediate platelet inhibition, bridging the "P2Y12 inhibition gap". Methods: In our pilot study, we randomized 30 comatose OHCA patients undergoing PCI and TTM (32-34 °C) into cangrelor and control groups. Both groups received unfractioned heparin, acetylsalicylic acid, and ticagrelor via enteral tube. The cangrelor group also received an intravenous bolus of cangrelor followed by a 4 h infusion. Platelet inhibition was measured using VerifyNow® and Multiplate® ADP at baseline and 1, 3, 5, and 8 h post PCI. Results: Patient characteristics did not differ between groups. VerifyNow® showed significantly decreased platelet reactivity with cangrelor at 1 h (30 vs. 221 PRU; p < 0.001) and 3 h (24 vs. 180 PRU; p < 0.001), with differences at 5 and 8 h. Similarly, the proportion of patients with high on-treatment platelet reactivity (HPR) in the cangrelor group was significantly lower at 1 h (0% vs. 67%; p < 0.001) and 3 h (0% vs. 47%; p = 0.007). Multiplate® ADP was also decreased at 1 h (14 vs. 48 U; p < 0.001) and 3 h (11 vs. 42 U; p = 0.001), with no difference at 5 and 8 h. The occurrence of bleeding events was similar in both groups. Conclusions: Cangrelor safely induced immediate and profound platelet inhibition. We observed no significant drug-drug interaction with ticagrelor.

Effects of a Serious Smartphone Game on Nursing Students' Theoretical Knowledge and Practical Skills in Adult Basic Life Support: Randomized Wait List-Controlled Trial.

Retention of adult basic life support (BLS) knowledge and skills after professional training declines over time. To combat this, the European Resuscitation Council and the American Heart Association recommend shorter, more frequent BLS sessions. Emphasizing technology-enhanced learning, such as mobile learning, aims to increase out-of-hospital cardiac arrest (OHCA) survival and is becoming more integral in nursing education. The aim of this study was to investigate whether playing a serious smartphone game called MOBICPR at home can improve and retain nursing students' theoretical knowledge of and practical skills in adult BLS. This study used a randomized wait list-controlled design. Nursing students were randomly assigned in a 1:1 ratio to either a MOBICPR intervention group (MOBICPR-IG) or a wait-list control group (WL-CG), where the latter received the MOBICPR game 2 weeks after the MOBICPR-IG. The aim of the MOBICPR game is to engage participants in using smartphone gestures (eg, tapping) and actions (eg, talking) to perform evidence-based adult BLS on a virtual patient with OHCA. The participants' theoretical knowledge of adult BLS was assessed using a questionnaire, while their practical skills were evaluated on cardiopulmonary resuscitation quality parameters using a manikin and a checklist. In total, 43 nursing students participated in the study, 22 (51%) in MOBICPR-IG and 21 (49%) in WL-CG. There were differences between the MOBICPR-IG and the WL-CG in theoretical knowledge (P=.04) but not in practical skills (P=.45) after MOBICPR game playing at home. No difference was noted in the retention of participants' theoretical knowledge and practical skills of adult BLS after a 2-week break from playing the MOBICPR game (P=.13). Key observations included challenges in response checks with a face-down manikin and a general neglect of safety protocols when using an automated external defibrillator. Playing the MOBICPR game at home has the greatest impact on improving the theoretical knowledge of adult BLS in nursing students but not their practical skills. Our findings underscore the importance of integrating diverse scenarios into adult BLS training. ClinicalTrials.gov (NCT05784675); https://clinicaltrials.gov/study/NCT05784675.

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.

Association Between Chest Compression Pause Duration and Survival After Pediatric In-Hospital Cardiac Arrest.

The association between chest compression (CC) pause duration and pediatric in-hospital cardiac arrest survival outcomes is unknown. The American Heart Association has recommended minimizing pauses in CC in children to <10 seconds, without supportive evidence. We hypothesized that longer maximum CC pause durations are associated with worse survival and neurological outcomes. In this cohort study of index pediatric in-hospital cardiac arrests reported in pediRES-Q (Quality of Pediatric Resuscitation in a Multicenter Collaborative) from July of 2015 through December of 2021, we analyzed the association in 5-second increments of the longest CC pause duration for each event with survival and favorable neurological outcome (Pediatric Cerebral Performance Category ≤3 or no change from baseline). Secondary exposures included having any pause >10 seconds or >20 seconds and number of pauses >10 seconds and >20 seconds per 2 minutes. We identified 562 index in-hospital cardiac arrests (median [Q1, Q3] age 2.9 years [0.6, 10.0], 43% female, 13% shockable rhythm). Median length of the longest CC pause for each event was 29.8 seconds (11.5, 63.1). After adjustment for confounders, each 5-second increment in the longest CC pause duration was associated with a 3% lower relative risk of survival with favorable neurological outcome (adjusted risk ratio, 0.97 [95% CI, 0.95-0.99]; P=0.02). Longest CC pause duration was also associated with survival to hospital discharge (adjusted risk ratio, 0.98 [95% CI, 0.96-0.99]; P=0.01) and return of spontaneous circulation (adjusted risk ratio, 0.93 [95% CI, 0.91-0.94]; P<0.001). Secondary outcomes of any pause >10 seconds or >20 seconds and number of CC pauses >10 seconds and >20 seconds were each significantly associated with adjusted risk ratio of return of spontaneous circulation, but not survival or neurological outcomes. Each 5-second increment in longest CC pause duration during pediatric in-hospital cardiac arrest was associated with lower chance of survival with favorable neurological outcome, survival to hospital discharge, and return of spontaneous circulation. Any CC pause >10 seconds or >20 seconds and number of pauses >10 seconds and >20 seconds were significantly associated with lower adjusted probability of return of spontaneous circulation, but not survival or neurological outcomes.

Association between early lactate-related variables and 6-month neurological outcome in out-of-hospital cardiac arrest patients

IntroductionThe role of lactate measurement in out-of-hospital cardiac arrest (OHCA) survivors remains controversial. We assessed the association between early lactate-related variables, OHCA characteristics, and long-term neurological outcome. MethodsIn OHCA patients who received targeted temperature management, lactate levels were measured at 0, 12, and 24 h after the return of spontaneous circulation. We calculated lactate clearance and time-weighted cumulative lactate (TWCL), which represent the area under the time-lactate curve. The area under the receiver operating characteristic curve (AUC) and the adjusted odds ratios (AORs) of lactate-related variables for predicting 6-month poor outcome (Cerebral Performance Category 3–5) were evaluated. Interactions between lactate variables and characteristics of OHCA were evaluated by a multivariable logistic model with interaction terms and subgroup analysis. ResultsA total of 347 OHCA patients were included. After adjustment, higher lactate levels at the three time points were associated with a poor outcome (AOR 1.10 [95% CI, 1.03–1.18], AOR 1.15 [95% CI, 1.02–1.29], and AOR 1.36 [95% CI, 1.15–1.60], respectively), while TWCL was the only lactate kinetics variable associated with a poor outcome (AOR 1.29 [95% CI, 1.12–1.49]). We identified several interactions between lactate-related variables and OHCA characteristics. In particular, the AUC of TWCL was excellent in cases of noncardiac etiology (AUC 0.92 [95% CI, 0.86–0.96] but only moderate in cardiac etiology (AUC 0.69 [95% CI, 0.62–0.75]). ConclusionsEarly lactate levels, especially at 24 h, and TWCL were independent predictors of neurologic outcome in these patients, whereas lactate clearance was not. The prognostic ability of lactate-related variables varied depending on the OHCA characteristics.