Opioid-Associated Out-of-Hospital Cardiac Arrest: Distinctive Clinical Features and Implications for Health Care and Public Responses: A Scientific Statement From the American Heart Association.

Opioid overdose is the leading cause of death for Americans 25 to 64 years of age, and opioid use disorder affects >2 million Americans. The epidemiology of opioid-associated out-of-hospital cardiac arrest in the United States is changing rapidly, with exponential increases in death resulting from synthetic opioids and linear increases in heroin deaths more than offsetting modest reductions in deaths from prescription opioids. The pathophysiology of polysubstance toxidromes involving opioids, asphyxial death, and prolonged hypoxemia leading to global ischemia (cardiac arrest) differs from that of sudden cardiac arrest. People who use opioids may also develop bacteremia, central nervous system vasculitis and leukoencephalopathy, torsades de pointes, pulmonary vasculopathy, and pulmonary edema. Emergency management of opioid poisoning requires recognition by the lay public or emergency dispatchers, prompt emergency response, and effective ventilation coupled to compressions in the setting of opioid-associated out-of-hospital cardiac arrest. Effective ventilation is challenging to teach, whereas naloxone, an opioid antagonist, can be administered by emergency medical personnel, trained laypeople, and the general public with dispatcher instruction to prevent cardiac arrest. Opioid education and naloxone distributions programs have been developed to teach people who are likely to encounter a person with opioid poisoning how to administer naloxone, deliver high-quality compressions, and perform rescue breathing. Current American Heart Association recommendations call for laypeople and others who cannot reliably establish the presence of a pulse to initiate cardiopulmonary resuscitation in any individual who is unconscious and not breathing normally; if opioid overdose is suspected, naloxone should also be administered. Secondary prevention, including counseling, opioid overdose education with take-home naloxone, and medication for opioid use disorder, is important to prevent recurrent opioid overdose.

Implications of a recurrent in-hospital cardiac arrest on survival and neurological outcomes.

BACKGROUND: Despite the high incidence of in-hospital cardiac arrest (IHCA) in US hospitals, the prognosis and end-of-life decision-making patterns of a patient with a recurrent IHCA are unknown. METHODS: Within Get-With-The-Guidelines-Resuscitation, we identified 192,250 patients from 711 hospitals with an IHCA from 2000 to 2015. Patients were categorized as having no recurrent IHCA (only 1 event), recurrent IHCA (≥2 IHCAs), and recurrent out-of-hospital cardiac arrest (OHCA), defined as an IHCA after an OHCA. Using multivariable hierarchical logistic regression, rates of survival to discharge and favorable neurological survival (mild or no disability) between the 3 groups were compared. Rates of de novo "do not attempt resuscitation" (DNAR) and withdrawal of care orders among successfully resuscitated patients were also evaluated. RESULTS: Overall, 165,446 (86.1%) had no recurrent IHCA, 23,643 (12.3%) had recurrent IHCA, and 3162 (1.6%) had recurrent OHCA. Compared with patients with no recurrent IHCA, patients with recurrent IHCA were less than half as likely to survive to discharge (12.7% vs 22.1%; adjusted OR: 0.46 [0.44-0.48], P < .001) and have favorable neurological survival (7.0% vs 13.1%; adjusted OR: 0.44 [0.42-0.47], P < .001). Compared with patients with recurrent OHCA, patients with recurrent IHCA also had lower rates of survival to discharge (12.7% vs 16.1%; adjusted OR: 0.81 [0.71-0.94], P = .005) and favorable neurological survival (7.0% vs 8.9%; adjusted OR: 0.66 [0.54-0.81], P < .001). Despite worse survival outcomes, patients with recurrent IHCA were least likely to adopt DNAR orders within the first 24 hours after successful resuscitation compared with patients with no recurrent IHCA or recurrent OHCA (17.2% vs 18.9% and 26.6%, respectively) or withdraw care at any time (17.7% vs 24.4% and 31.2%, respectively). CONCLUSIONS: Nearly 1 in 8 patients with an IHCA has a recurrent IHCA, and these patients have worse outcomes than patients with only a single IHCA and those with an IHCA after being hospitalized for an OHCA. Despite worse survival, rates of DNAR and withdrawal of care were lowest for patients with recurrent IHCA. These findings provide important prognostic information for clinicians caring for patients with recurrent IHCA and suggest the need to better align resuscitation and end-of-life decisions with patients' prognoses after IHCA.

Outcomes for patients with anterior myocardial infarction and prior cardiac arrest in the home automated external defibrillator trial (HAT).

BACKGROUND: Patients with sudden cardiac arrest occurring in the acute phase of myocardial infarction (MI-SCA) are believed to be at similar risk of death after revascularization compared with MI patients without SCA (MI-no SCA). Among patients with anterior MI, we examined whether those with MI-SCA were at greater risk of all-cause mortality or sudden cardiac death (SCD) than MI-no SCA patients. METHODS: The Home Automated External Defibrillator Trial enrolled patients with anterior MI who had not received or were candidates for an implantable cardioverter defibrillator (ICD). Our cohort included patients with a reported SCA event, in the acute phase of an MI, prior to HAT trial enrollment. Cox proportional hazards models examined the adjusted association between MI-SCA versus MI-no SCA patients and all-cause mortality and sudden cardiac death (SCD). We also determined whether the relationship between prior SCA and outcomes changed with subsequent events (syncope, revascularization, and recurrent MI) during follow-up. RESULTS: Of 6849 patients, 650 (9.5%) had MI-SCA before trial enrollment. Approximately 48% of patients had the MI-SCA event ≤1 year prior to enrollment; 71% of SCA events were in-hospital. MI-SCA patients were younger, more frequently white, and had higher rates of prior PCI versus MI-no SCA patients. There were no differences in adjusted all-cause mortality (hazard ratio [HR 0.95; 95% CI 0.65-1.38]) or SCD (HR 1.12; 95% CI 0.68-1.83) for MI-SCA vs. MI-no SCA. After ICD implantation, MI-SCA patients experienced higher all-cause mortality risk (HR 5.01, 95% CI 1.05-23.79) versus MI-no SCA patients; there was no mortality difference between MI-SCA and MI-no SCA patients without ICD implantation (HR 0.89, 95% CI 0.60-1.31), [interaction p = 0.035]. CONCLUSIONS: Patients with MI-SCA had similar adjusted risk of all-cause mortality and SCD compared with MI-no SCA. After ICD implantation, MI-SCA patients had higher mortality compared with MI-no SCA patients.

Association between patient race and staff resuscitation efforts after cardiac arrest in outpatient dialysis clinics: A study from the CARES surveillance group.

BACKGROUND: Cardiac arrest is the leading cause of death among patients receiving hemodialysis. Despite guidelines recommending CPR training and AED presence in dialysis clinics, rates of CPR and AED use by dialysis staff are suboptimal. Given that racial disparities exist in bystander CPR administration in non-healthcare settings, we examined the relationship between patient race/ethnicity and staff-initiated CPR and AED application within dialysis clinics. METHODS: We analyzed data prospectively collected in the Cardiac Arrest Registry to Enhance Survival across the U.S. from 2013 to 2017 and the Centers for Medicare & Medicaid Services dialysis facility database to identify outpatient dialysis clinic cardiac arrest events. Using multivariable logistic regression models, we examined relationships between patient race/ethnicity and dialysis staff-initiated CPR and AED application. RESULTS: We identified 1568 cardiac arrests occurring in 809 hemodialysis clinics. The racial/ethnic composition of patients was 31.3% white, 32.9% Black, 10.7% Hispanic/Latinx, 2.7% Asian, and 22.5% other/unknown. Overall, 88.0% of patients received CPR initiated by dialysis staff, but rates differed by race: 91% of white patients, 85% of black patients, and 77% of Asian patients (p = 0.005). After adjusting for differences in patient and clinic characteristics, black (OR = 0.41, 95% CI 0.25-0.68) and Asian patients (OR = 0.28, 95% CI 0.12-0.65) were significantly less likely than white patients to receive staff-initiated CPR. No significant difference between staff-initiated CPR rates among white, Hispanic/Latinx, and other/unknown patients was observed. An AED was applied by dialysis staff in 62% of patients. In adjusted models, there was no relationship between patient race/ethnicity and staff AED application. CONCLUSIONS: Black and Asian patients are significantly less likely than white patients to receive CPR from dialysis staff. Further understanding of practices in dialysis clinics and increased awareness of this disparity are necessary to improve resuscitation practices.

In-Hospital Cardiac Arrest Resuscitation Practices and Outcomes in Maintenance Dialysis Patients.

BACKGROUND AND OBJECTIVES: Patients on maintenance dialysis with in-hospital cardiac arrest have been reported to have worse outcomes relative to those not on dialysis; however, it is unknown if poor outcomes are related to the quality of resuscitation. Using the Get With The Guidelines-Resuscitation (GWTG-R) registry, we examined processes of care and outcomes of in-hospital cardiac arrest for patients on maintenance dialysis compared with nondialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used GWTG-R data linked to Centers for Medicare and Medicaid data to identify patients with ESKD receiving maintenance dialysis from 2000 to 2012. We then case-matched adult patients on maintenance dialysis to nondialysis patients in a 1:3 ratio on the basis of age, sex, race, hospital, and year of arrest. Logistic regression models with generalized estimating equations were used to assess the association of in-hospital cardiac arrest and outcomes by dialysis status. RESULTS: After matching, there were a total of 31,144 GWTG-R patients from 372 sites, of which 8498 (27%) were on maintenance dialysis. Patients on maintenance dialysis were less likely to have a shockable initial rhythm (20% versus 21%) and less likely to be within the intensive care unit at the time of arrest (46% versus 47%) compared with nondialysis patients; they also had lower composite scores for resuscitation quality (89% versus 90%) and were less likely to have defibrillation within 2 minutes (54% versus 58%). After adjustment, patients on maintenance dialysis had similar adjusted odds of survival to discharge (odds ratio [OR], 1.05; 95% confidence interval [95% CI], 0.97 to 1.13), better acute survival (OR, 1.33; 95% CI, 1.26 to 1.40), and were more likely to have favorable neurologic status (OR, 1.12; 95% CI, 1.04 to 1.22) compared with nondialysis patients. CONCLUSIONS: Although there appears to be opportunities to improve the quality of in-hospital cardiac arrest care for among those on maintenance dialysis, survival to discharge was similar for these patients compared with nondialysis patients.

Impact of baseline covariate imbalance on bias in treatment effect estimation in cluster randomized trials: Race as an example.

Individual-level baseline covariate imbalance could happen more frequently in cluster randomized trials, and may influence the observed treatment effect. Using computer and real-data simulations, this paper quantifies the extent and impact of covariate imbalance on the estimated treatment effect for both continuous and binary outcomes, and relates it to the degree of imbalance for different numbers of clusters, cluster sizes, and covariate intraclass correlation coefficients. We focused on the impact of race as a covariate, given the emphasis of regulatory and funding bodies on understanding the influence of demographic characteristics on treatment effectiveness. We found that bias in the treatment effect is proportional to both the degree of baseline covariate imbalance and the covariate effect size. Larger numbers of clusters result in lower covariate imbalance, and increasing cluster size is less effective in reducing imbalance compared to increasing the number of clusters. Models adjusted for important baseline confounders are superior to unadjusted models for minimizing bias in both model-based simulations and an innovative simulation based on real clinical trial data. Higher outcome intraclass correlation coefficients did not affect bias but resulted in greater variance in treatment estimates.

Assessing heterogeneity of treatment effect analyses in health-related cluster randomized trials: A systematic review.

BACKGROUND: Cluster-randomized trials (CRTs) are being increasingly used to test a range of interventions, including medical interventions commonly used in clinical practice. Policies created by the NIH and the Food and Drug Administration (FDA) require the reporting of demographics and the examination of demographic heterogeneity of treatment effect (HTE) for individually randomized trials. Little is known about how frequent demographics are reported and HTE analyses are conducted in CRTs. OBJECTIVES: We sought to understand the prevalence of HTE analyses and the statistical methods used to conduct them in CRTs focused on treating cardiovascular disease, cancer, and chronic lower respiratory diseases. Additionally, we also report on the proportion of CRTs that reported on baseline demographics of its populations and conducted demographic HTE analyses. DATA SOURCES: We searched PubMed and Embase for CRTs published between 1/1/2010 and 3/29/2016 that focused on treating the top 3 Center for Disease Control causes of death (cardiovascular disease, chronic lower respiratory disease, and cancer). Evidence Screening And Review: Of 1,682 unique titles, 117 abstracts were screened. After excluding 53 articles, we included 64 CRT publications and abstracted information on study characteristics and demographic information, statistical analysis, HTE analysis, and study quality. RESULTS: Age and sex were reported in greater than 95.3% of CRTs, while race and ethnicity were reported in only 20.3% of CRTs. HTE analyses were conducted in 28.1% (n = 18) of included CRTs and 77.8% (n = 12) were prespecified analyses. Four CRTs conducted a demographic subgroup analysis. Only 6/18 CRTs used interaction testing to determine whether HTE existed. CONCLUSIONS: Baseline demographic reporting was high for age and sex in CRTs, but was uncommon for race and ethnicity. HTE analyses were uncommon and was rare for demographic subgroups, which limits the ability to examine the extent of benefits or risks for treatments tested with CRT designs.

Association of Neighborhood Demographics With Out-of-Hospital Cardiac Arrest Treatment and Outcomes: Where You Live May Matter.

Importance: We examined whether resuscitation care and outcomes vary by the racial composition of the neighborhood where out-of-hospital cardiac arrests (OHCAs) occur. Objective: To evaluate the association between bystander treatments (cardiopulmonary resuscitation and automatic external defibrillation) and timing of emergency medical services personnel on OHCA outcomes according to the racial composition of the neighborhood where the OHCA event occurred. Design, Setting, and Participants: This retrospective observational cohort study examined patients with OHCA from January 1, 2008, to December 31, 2011, using data from the Resuscitation Outcomes Consortium. Neighborhoods where OHCA occurred were classified by census tract, based on percentage of black residents: less than 25%, 25% to 50%, 51% to 75%, or more than 75%. Multilevel mixed-effects logistic regression modeling examined the association between racial composition of neighborhoods and OHCA survival, adjusting for patient, neighborhood, and treatment characteristics. Main Outcomes and Measures: Survival to discharge, return of spontaneous circulation on emergency department arrival, and favorable neurologic status at discharge. Results: We examined 22 816 adult patients with nontraumatic OHCA at Resuscitation Outcomes Consortium sites in the United States. The median age of patients with OHCA was 64 years (interquartile range [IQR], 51-78). Compared with patients who experienced OHCA in neighborhoods with a lower proportion of black residents, those in neighborhoods with more than 75% black residents were slightly younger, were more frequently women, had lower rates of initial shockable rhythm, and less frequently experienced OHCA in a public location. The percentage of patients with OHCA receiving bystander cardiopulmonary resuscitation or a lay automatic external defibrillation was inversely associated with the percentage of black residents in neighborhoods. Compared with OHCA in predominantly white neighborhoods (<25% black), those with OHCA in mixed to majority black neighborhoods had lower adjusted survival rates to hospital discharge (25%-50% black: odds ratio, 0.76; 95% CI, 0.61-0.93; 51%-75% black: odds ratio, 0.67; 95% CI, 0.49-0.90; >75% black: odds ratio, 0.63; 95% CI, 0.50-0.79; P < .001). There was similar mortality risk for black and white patients with OHCA in each neighborhood racial quantile. When the primary model included geographic site, there was an attenuated nonsignificant association between racial composition in a neighborhood and survival. Conclusions and Relevance: Those with OHCA in predominantly black neighborhoods had the lowest rates of bystander cardiopulmonary resuscitation and automatic external defibrillation use and significantly lower likelihood for survival compared with predominantly white neighborhoods. Improving bystander treatments in these neighborhoods may improve cardiac arrest survival.