Race and Sex Differences in the Association of Bystander CPR for Cardiac Arrest.

BACKGROUND: Bystander cardiopulmonary resuscitation (CPR) is associated with higher survival for out-of-hospital cardiac arrest, but whether its association with survival differs by patients' sex and race and ethnicity is less clear. METHODS: Within a large US registry, we identified 623 342 nontraumatic out-of-hospital cardiac arrests during 2013 to 2022 for this observational cohort study. Using hierarchical logistic regression, we examined whether there was a differential association between bystander CPR and survival outcomes by patients' sex and race and ethnicity, overall and by neighborhood strata. RESULTS: Mean age was 62.1±17.1 years, and 35.9% were women. Nearly half of patients (49.8%) were non-Hispanic White; 20.6% were non-Hispanic Black; 7.3% were Hispanic; 2.9% were Asian; and 0.4% were Native American. Overall, 58 098 (9.3%) survived to hospital discharge. Although bystander CPR was associated with higher survival in each race and ethnicity group, the association of bystander CPR compared with patients without bystander CPR in each racial and ethnic group was highest in individuals who were White (adjusted odds ratio [OR], 1.33 [95% CI, 1.30-1.37]) and Native American (adjusted OR, 1.40 [95% CI, 1.02-1.90]) and lowest in individuals who were Black (adjusted OR, 1.09 [95% CI, 1.04-1.14]; Pinteraction<0.001). The adjusted OR for bystander CPR compared with those without bystander CPR for Hispanic patients was 1.29 (95% CI, 1.20-1.139), for Asian patients, it was 1.27 (95% CI, 1.12-1.42), and for those of unknown race, it was 1.31 (95% CI, 1.25-1.36). Similarly, bystander CPR was associated with higher survival in both sexes, but its association with survival was higher in men (adjusted OR, 1.35 [95% CI, 1.31-1.38]) than women (adjusted OR, 1.15 [95% CI, 1.12-1.19]; Pinteraction<0.001). The weaker association of bystander CPR in Black individuals and women was consistent across neighborhood race and ethnicity and income strata. Similar results were observed for the outcome of survival without severe neurological deficits. CONCLUSIONS: Although bystander CPR was associated with higher survival in all patients, its association with survival was weakest for Black individuals and women with out-of-hospital cardiac arrest.

Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP): study protocol for a multicenter, randomized, adaptive allocation clinical trial to identify the optimal duration of induced hypothermia for neuroprotection in comatose, adult survivors of after out-of-hospital cardiac arrest.

Background: Cardiac arrest is a common and devastating emergency of both the heart and brain. More than 380,000 patients suffer out-of-hospital cardiac arrest annually in the United States. Induced cooling of comatose patients markedly improved neurological and functional outcomes in pivotal randomized clinical trials, but the optimal duration of therapeutic hypothermia has not yet been established. Methods: This study is a multi-center randomized, response-adaptive, duration (dose) finding, comparative effectiveness clinical trial with blinded outcome assessment. We investigate two populations of adult comatose survivors of cardiac arrest to ascertain the shortest duration of cooling that provides the maximum treatment effect. The design is based on a statistical model of response as defined by the primary endpoint, a weighted 90-day mRS (modified Rankin Scale, a measure of neurologic disability), across the treatment arms. Subjects will initially be equally randomized between 12, 24, and 48 hours of therapeutic cooling. After the first 200 subjects have been randomized, additional treatment arms between 12 and 48 hours will be opened and patients will be allocated, within each initial cardiac rhythm type (shockable or non-shockable), by response adaptive randomization. As the trial continues, shorter and longer duration arms may be opened. A maximum sample size of 1800 subjects is proposed. Secondary objectives are to characterize: the overall safety and adverse events associated with duration of cooling, the effect on neuropsychological outcomes, and the effect on patient reported quality of life measures. Discussion: In-vitro and in-vivo studies have shown the neuroprotective effects of therapeutic hypothermia for cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having a good outcome. If the treatment effect of cooling is increasing across duration, for at least some set of durations, then this provides evidence of the efficacy of cooling itself versus normothermia, even in the absence of a normothermia control arm, confirming previous RCTs for OHCA survivors of shockable rhythms and provides the first prospective controlled evidence of efficacy in those without initial shockable rhythms. Trial registration: ClinicalTrials.gov (NCT04217551, 2019-12-30).

Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP): study protocol for a multicenter, randomized, adaptive allocation clinical trial to identify the optimal duration of induced hypothermia for neuroprotection in comatose, adult survivors of after out-of-hospital cardiac arrest.

BACKGROUND: Cardiac arrest is a common and devastating emergency of both the heart and brain. More than 380,000 patients suffer out-of-hospital cardiac arrest annually in the USA. Induced cooling of comatose patients markedly improved neurological and functional outcomes in pivotal randomized clinical trials, but the optimal duration of therapeutic hypothermia has not yet been established. METHODS: This study is a multi-center randomized, response-adaptive, duration (dose) finding, comparative effectiveness clinical trial with blinded outcome assessment. We investigate two populations of adult comatose survivors of cardiac arrest to ascertain the shortest duration of cooling that provides the maximum treatment effect. The design is based on a statistical model of response as defined by the primary endpoint, a weighted 90-day mRS (modified Rankin Scale, a measure of neurologic disability), across the treatment arms. Subjects will initially be equally randomized between 12, 24, and 48 h of therapeutic cooling. After the first 200 subjects have been randomized, additional treatment arms between 12 and 48 h will be opened and patients will be allocated, within each initial cardiac rhythm type (shockable or non-shockable), by response adaptive randomization. As the trial continues, shorter and longer duration arms may be opened. A maximum sample size of 1800 subjects is proposed. Secondary objectives are to characterize: the overall safety and adverse events associated with duration of cooling, the effect on neuropsychological outcomes, and the effect on patient-reported quality of life measures. DISCUSSION: In vitro and in vivo studies have shown the neuroprotective effects of therapeutic hypothermia for cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having a good outcome. If the treatment effect of cooling is increasing across duration, for at least some set of durations, then this provides evidence of the efficacy of cooling itself versus normothermia, even in the absence of a normothermia control arm, confirming previous RCTs for OHCA survivors of shockable rhythms and provides the first prospective controlled evidence of efficacy in those without initial shockable rhythms. TRIAL REGISTRATION: ClinicalTrials.gov NCT04217551. Registered on 30 December 2019.

Prehospital Ground and Helicopter-Based Extracorporeal Cardiopulmonary Resuscitation (ECPR) Reduce Barriers to ECPR: A GIS Model.

INTRODUCTION: Evidence suggests that Extracorporeal Cardiopulmonary Resuscitation (ECPR) can improve survival rates for nontraumatic out-of-hospital cardiac arrest (OHCA). However, when ECPR is indicated over 50% of potential candidates are unable to qualify in the current hospital-based system due to geographic limitations. This study employs a Geographic Information System (GIS) model to estimate the number of ECPR eligible patients within the United States in the current hospital-based system, a prehospital ECPR ground-based system, and a prehospital ECPR Helicopter Emergency Medical Services (HEMS)-based system. METHODS: We constructed a GIS model to estimate ground and helicopter transport times. Time-dependent rates of ECPR eligibility were derived from the Resuscitation Outcome Consortium (ROC) database, while the Cardiac Arrest Registry to Enhance Survival (CARES) registry determined the number of OHCA patients meeting ECPR criteria within designated transportation times. Emergency Medical Services (EMS) response time, ECPR candidacy determination time, and on-scene time were modeled based on data from the EROCA trial. The combined model was used to estimate the total ECPR eligibility in each system. RESULTS: The CARES registry recorded 736,066 OHCA patients from 2013 to 2021. After applying clinical criteria, 24,661 (3.4%) ECPR-indicated OHCA were identified. When considering overall ECPR eligibility within 45 min from OHCA to initiation, only 11.76% of OHCA where ECPR was indicated were eligible in the current hospital-based system. The prehospital ECPR HEMS-based system exhibited a four-fold increase in ECPR eligibility (49.3%), while the prehospital ground-based system showed a more than two-fold increase (28.4%). CONCLUSIONS: The study demonstrates a two-fold increase in ECPR eligibility for a prehospital ECPR ground-based system and a four-fold increase for a prehospital ECPR HEMS-based system compared to the current hospital-based ECPR system. This novel GIS model can inform future ECPR implementation strategies, optimizing systems of care.

Intra-arrest blood-based biomarkers for out-of-hospital cardiac arrest: A scoping review.

Objective: Blood-based biomarkers play a central role in the diagnosis and treatment of critically ill patients, yet none are routinely measured during the intra-arrest phase of out-of-hospital cardiac arrest (OHCA). Our objective was to describe methodological aspects, sources of evidence, and gaps in research surrounding intra-arrest blood-based biomarkers for OHCA. Methods: We used scoping review methodology to summarize existing literature. The protocol was designed a priori following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews. Inclusion criteria were peer-reviewed scientific studies on OHCA patients with at least one blood draw intra-arrest. We excluded in-hospital cardiac arrest and animal studies. There were no language, date, or study design exclusions. We conducted an electronic literature search using PubMed and Embase and hand-searched secondary literature. Data charting/synthesis were performed in duplicate using standardized data extraction templates. Results: The search strategy identified 11,834 records, with 118 studies evaluating 105 blood-based biomarkers included. Only eight studies (7%) had complete reporting. The median number of studies per biomarker was 2 (interquartile range 1-4). Most studies were conducted in Asia (63 studies, 53%).  Only 22 studies (19%) had blood samples collected in the prehospital setting, and only six studies (5%) had samples collected by paramedics. Pediatric patients were included in only three studies (3%). Out of eight predefined biomarker categories of use, only two were routinely assessed: prognostic (97/105, 92%) and diagnostic (61/105, 58%). Conclusions: Despite a large body of literature on intra-arrest blood-based biomarkers for OHCA, gaps in methodology and knowledge are widespread.

Statewide implementation of the cardiac arrest registry to enhance survival in Ohio.

Objective: Public health surveillance is essential for improving community health. The Cardiac Arrest Registry to Enhance Survival (CARES) is a surveillance system for out-of-hospital cardiac arrest (OHCA). We describe results of the organized statewide implementation of Ohio CARES. Methods: We performed a retrospective analysis of CARES enactment in Ohio. Key elements included: establishment of statewide leadership, appointment of a dedicated coordinator, conversion to a statewide subscription, statewide dissemination of information, fundraising from internal and external stakeholders, and conduct of resuscitation academies. We identified all adult (≥18 years) OHCA reported in the registry during 2013-2020. We evaluated OHCA characteristics before (2013-2015) and after (2016-2019) statewide implementation using chi-square test. We evaluated trends in OHCA outcomes using the Cochran-Armitage test of trend. Results: Statewide CARES promotion increased participation from 2 (urban) to 136 (129 urban, 7 rural) EMS agencies. Covered population increased from 1.2 M (10% of state) to 4.8 M (41% of state). After statewide implementation, OHCA populations increased male (58.1% vs 60.8%, p < 0.01), white (50.1% vs 63.7%, p < 0.01), bystander witnessed (26.9% vs 32.9%, p < 0.01) OHCAs. Bystander CPR (34.7% vs 33.2%, p = 0.22), bystander AED (13.5% vs 12.3%, p = 0.55) and initial rhythm (shockable 18.0% vs 18.3%, p = 0.32) did not change. From 2013 to 2019 there were temporal increases in ROSC (29.7% to 31.9%, p-trend = 0.028), survival (7.4% to 12.3%, p-trend < 0.001) and survival with good neurologic outcome (5.6% to 8.6%, p-trend = 0.047). Conclusion: The organized statewide implementation of CARES in Ohio was associated with marked increases in community uptake and concurrent observed improvements in patient outcomes. These results highlight key lessons for community-wide fostering of OHCA surveillance.