Fewer severe infections with tranexamic acid in patients with hematologic malignancies.

Background: Tranexamic acid (TXA) is an antifibrinolytic agent that reduces bleeding in a multitude of clinical settings from postpartum hemorrhage to trauma. TXA may have clinical effects unrelated to bleeding; plasminogen, the target of TXA, alters immune responses, and TXA appears to decrease the risk of infection in patients undergoing cardiac surgery, as well as joint arthroplasty. Objectives: To address whether TXA alters rates of infection and inflammatory outcomes in patients with hematologic malignancies. Methods: We performed a post hoc analysis of outcomes of patients randomized to receive either TXA or placebo in the double-blinded, multicenter American Trial to Evaluate Tranexamic Acid Therapy in Thrombocytopenia (Clinicaltrials.gov identifier: NCT02578901). Results: TXA did not change the overall rate of infections, but the rate of severe infections (Common Toxicology Criteria for Adverse Events grade 3+) was lower in patients who received TXA compared with the placebo group. Patients who experienced grade 3+ infections had higher rates of World Health Organization grade 2+ bleeding and red blood cell transfusion requirements than patients who did not experience a grade 3+ infection, irrespective of treatment group. TXA did not impact other inflammatory outcomes such as mucositis, rash, or graft vs host disease. Conclusion: Patients with hematologic malignancies who received TXA had less severe infections than those who received placebo with no difference in overall rate of infection or other inflammatory outcomes. Further investigation is needed on the impact of TXA on infections in this population.

Absence of hyperfibrinolysis may explain lack of efficacy of tranexamic acid in hypoproliferative thrombocytopenia.

The American Trial Using Tranexamic Acid (TXA) in Thrombocytopenia (A-TREAT, NCT02578901) demonstrated no superiority of TXA over placebo in preventing World Health Organization (WHO) grade 2 or higher bleeding in patients with severe thrombocytopenia requiring supportive platelet transfusion following myeloablative therapy for hematologic disorders. In this ancillary study, we sought to determine whether this clinical outcome could be explained on the basis of correlative assays of fibrinolysis. Plasma was collected from A-TREAT participants (n = 115) before the initiation of study drug (baseline) and when TXA was at steady-state trough concentration (follow-up). Global fibrinolysis was measured by 3 assays: euglobulin clot lysis time (ECLT), plasmin generation (PG), and tissue-type plasminogen activator (tPA)-challenged clot lysis time (tPA-CLT). TXA was quantified in follow-up samples by tandem mass spectrometry. Baseline samples did not demonstrate fibrinolytic activation by ECLT or tPA-CLT. Furthermore, neither ECLT nor levels of plasminogen activator inhibitor-1, tPA, plasminogen, alpha2-antiplasmin, or plasmin-antiplasmin complexes were associated with a greater risk of WHO grade 2+ bleeding. TXA trough concentrations were highly variable (range, 0.7-10 µg/mL) and did not correlate with bleeding severity, despite the fact that plasma TXA levels correlated strongly with pharmacodynamic assessments by PG (Spearman r, -0.78) and tPA-CLT (r, 0.74). We conclude that (1) no evidence of fibrinolytic activation was observed in these patients with thrombocytopenia, (2) trough TXA concentrations varied significantly between patients receiving the same dosing schedule, and (3) tPA-CLT and PG correlated well with TXA drug levels.

Prophylactic tranexamic acid in patients with hematologic malignancy: a placebo-controlled, randomized clinical trial.

Evidence of the effectiveness of prophylactic use of tranexamic acid (TXA) in thrombocytopenia is lacking. To determine whether TXA safely reduces bleeding incidence in patients undergoing treatment for hematologic malignancies, a randomized, double-blind clinical trial was conducted from June 2016 through June 2020. Of 3120 screened adults, 356 patients were eligible and enrolled, and 337 patients (mean age, 53.9; 141 [41.8%] women), randomized to 1300 mg TXA orally or 1000 mg TXA through IV (n = 168) vs placebo (n = 169) thrice daily for maximum 30 days. Three hundred thirty patients were activated when their platelet counts fell below 30 000 per µL; 279 (83%) had complete outcome ascertainment. World Health Organization (WHO) grade ≥2 bleeding was observed in the 30 days following activation in 50.3% (73/145) and 54.2% (78/144) of patients in the TXA and placebo groups, with an adjusted odds ratio of 0.83 (95% confidence interval [CI], 0.50-1.34; P = .44). There was no statistically significant difference in the mean number of platelet transfusions (mean difference, 0.1; 95% CI, -1.9 to 2.0), mean days alive without grade ≥2 bleeding (mean difference, 0.8; 95% CI, -0.4 to 2.0), thrombotic events (6/163 [3.7%] TXA, 9/163 [5.5%] placebo), or deaths due to serious bleeding. Most common adverse events were: diarrhea (116/164 [70.7%] TXA and 114/163 [69.9%] placebo); febrile neutropenia (111/164 [67.7%] TXA, 105/163 [64.4%] placebo); fatigue (106/164 [64.6%] TXA, 109/163 [66.9%] placebo); and nausea (104/164 [63.4%] TXA, 97/163 [59.5%] placebo). Among patients with hematologic malignancy undergoing chemotherapy or hematopoietic stem cell transplantation, prophylactic treatment with TXA compared with placebo did not significantly reduce the risk of WHO grade ≥2 bleeding.

Association of Intra-arrest Transport vs Continued On-Scene Resuscitation With Survival to Hospital Discharge Among Patients With Out-of-Hospital Cardiac Arrest.

Importance: There is wide variability among emergency medical systems (EMS) with respect to transport to hospital during out-of-hospital cardiac arrest (OHCA) resuscitative efforts. The benefit of intra-arrest transport during resuscitation compared with continued on-scene resuscitation is unclear. Objective: To determine whether intra-arrest transport compared with continued on-scene resuscitation is associated with survival to hospital discharge among patients experiencing OHCA. Design, Setting, and Participants: Cohort study of prospectively collected consecutive nontraumatic adult EMS-treated OHCA data from the Resuscitation Outcomes Consortium (ROC) Cardiac Epidemiologic Registry (enrollment, April 2011-June 2015 from 10 North American sites; follow-up until the date of hospital discharge or death [regardless of when either event occurred]). Patients treated with intra-arrest transport (exposed) were matched with patients in refractory arrest (at risk of intra-arrest transport) at that same time (unexposed), using a time-dependent propensity score. Subgroups categorized by initial cardiac rhythm and EMS-witnessed cardiac arrests were analyzed. Exposures: Intra-arrest transport (transport initiated prior to return of spontaneous circulation), compared with continued on-scene resuscitation. Main Outcomes and Measures: The primary outcome was survival to hospital discharge, and the secondary outcome was survival with favorable neurological outcome (modified Rankin scale <3) at hospital discharge. Results: The full cohort included 43 969 patients with a median age of 67 years (interquartile range, 55-80), 37% were women, 86% of cardiac arrests occurred in a private location, 49% were bystander- or EMS-witnessed, 22% had initial shockable rhythms, 97% were treated by out-of-hospital advanced life support, and 26% underwent intra-arrest transport. Survival to hospital discharge was 3.8% for patients who underwent intra-arrest transport and 12.6% for those who received on-scene resuscitation. In the propensity-matched cohort, which included 27 705 patients, survival to hospital discharge occurred in 4.0% of patients who underwent intra-arrest transport vs 8.5% who received on-scene resuscitation (risk difference, 4.6% [95% CI, 4.0%- 5.1%]). Favorable neurological outcome occurred in 2.9% of patients who underwent intra-arrest transport vs 7.1% who received on-scene resuscitation (risk difference, 4.2% [95% CI, 3.5%-4.9%]). Subgroups of initial shockable and nonshockable rhythms as well as EMS-witnessed and unwitnessed cardiac arrests all had a significant association between intra-arrest transport and lower probability of survival to hospital discharge. Conclusions and Relevance: Among patients experiencing out-of-hospital cardiac arrest, intra-arrest transport to hospital compared with continued on-scene resuscitation was associated with lower probability of survival to hospital discharge. Study findings are limited by potential confounding due to observational design.

Racial disparities in out-of-hospital cardiac arrest interventions and survival in the Pragmatic Airway Resuscitation Trial.

BACKGROUND: Prior studies have reported racial disparities in survival from out-of-hospital cardiac arrest (OHCA). However, these studies did not evaluate the association of race with OHCA course of care and outcomes. The purpose of this study was to evaluate racial disparities in OHCA airway placement success and patient outcomes in the multicenter Pragmatic Airway Resuscitation Trial (PART). METHOD: We conducted a secondary analysis of adult OHCA patients enrolled in PART. The parent trial randomized subjects to initial advanced airway management with laryngeal tube or endotracheal intubation. For this analysis, the primary independent variable was patient race categorized by emergency medical services (EMS) as white, black, Hispanic, other, and unknown. We used general estimating equations to examine the association of race with airway attempt success, 72-h survival, and survival to hospital discharge, adjusting for sex, age, witness status, bystander cardiopulmonary resuscitation (CPR), initial rhythm, arrest location, and PART randomization cluster. RESULTS: Of 3002 patients, EMS-assessed race as 1537 white, 860 black, 163 Hispanic, 90 other, and 352 unknown. Initial shockable rhythms (13.8% vs. 21.5%, p < 0.001), bystander CPR (35.6% vs. 51.4%, p < 0.001), and survival to hospital discharge (7.6% vs. 10.8%, p = 0.011) were lower for black compared to white patients. After adjustment for confounders, no difference was seen in airway success, 72-h survival, and survival to hospital discharge by race. CONCLUSIONS: In one of the largest studies evaluating differences in prehospital airway interventions and outcomes by EMS-assessed race for OHCA patients, we found no significant adjusted differences between airway success or survival outcomes.

Outcomes With the Use of Bag-Valve-Mask Ventilation During Out-of-hospital Cardiac Arrest in the Pragmatic Airway Resuscitation Trial.

BACKGROUND: While emergency medical services (EMS) often use endotracheal intubation (ETI) or supraglottic airways (SGA), some patients receive only bag-valve-mask (BVM) ventilation during out-of-hospital cardiac arrests (OHCA). Our objective was to compare patient characteristics and outcomes for BVM ventilation to advanced airway management (AAM) in adults with OHCA. METHODS: Using data from the Pragmatic Airway Resuscitation Trial, we identified patients receiving AAM (ETI or a SGA), BVM ventilation only (BVM-only), and BVM ventilation as a rescue after at least one failed attempt at advanced airway placement (BVM-rescue). The outcomes were return of spontaneous circulation (ROSC), 72-hour survival, survival to hospital discharge, neurologically intact survival (Modified Rankin Scale ≤ 3), and the presence of aspiration on a chest radiograph. Comparisons were made using generalized mixed-effects models while adjusting for age, sex, initial rhythm, EMS-witnessed status, bystander cardiopulmonary resuscitation, response time, study cluster, and advanced life support first on scene. RESULTS: Of 3,004 patients enrolled, there were 282 BVM-only, 2,129 AAM, and 156 BVM-rescue patients with complete covariates. Shockable initial rhythms (34% vs. 18.6%) and EMS-witnessed arrests (21.6% vs. 11.3%) were more likely in BVM-only than AAM but similar between BVM-rescue and AAM. Compared to AAM, BVM-only patients had similar ROSC (odds ratio [OR] = 1.29, 95% confidence interval [CI] = 0.96 to 1.73), but higher 72-hour survival (OR = 1.96, 95% CI = 1.42 to 2.69), survival to discharge (OR = 4.47, 95% CI = 3.03 to 6.59), and neurologically intact survival (OR = 7.05, 95% CI = 4.40 to 11.3). Compared to AAM, BVM-rescue patients had similar ROSC (OR = 0.73, 95% CI = 0.47 to 1.12) and 72-hour survival (OR = 1.08, 95% CI = 0.66 to 1.77) but higher survival to discharge (OR = 2.15, 95% CI = 1.17 to 3.95) and neurologically intact survival (OR = 2.64, 95% CI = 1.20 to 5.81). Aspiration incidence was similar. CONCLUSIONS: Bag-valve-mask-only ventilation is associated with improved OHCA outcomes. Despite similar rates of ROSC and 72-hour survival, BVM-rescue ventilation was associated with improved survival to discharge and neurologically intact survival compared to successful AAM.

Variations in the application of exception from informed consent in a multicenter clinical trial.

BACKGROUND: Exception from infor med consent (EFIC) is allowed using federal regulations 21 CFR 50.24 and facilitates research on patients with critical conditions such as cardiac arrest. Little is known regarding the differences in the application of EFIC requirements such as community consultation (CC), public disclosure (PD) and patient notification. We sought to characterize variations in the fulfillment of EFIC requirements in a national multicenter clinical trial in the United States. METHODS: We determined the strategies for fulfillment of EFIC requirements at five regional coordinating centers of the Pragmatic Airway Resuscitation Trial (PART), a cluster-crossover randomized trial comparing airway devices in out-of-hospital cardiac arrest. We collected information from the including site demographics, how CC and PD were implemented, methods undertaken by the site investigative team to meet the local IRB's interpretation, and patient notification timing (post-enrollment). We analyzed the data using descriptive statistics. RESULTS: Sites had multiple approaches to CC, including social media advertising, random digit dialing surveys, working with city officials, and websites with embedded surveys. All sites used more than one approach for conducting CC. Public Disclosure activities included press releases through various means, website documentation, and letters to community members and local officials. Time from CC to study approval ranged from 42 days to 253 days. CONCLUSION: EFIC implementation varies across sites and highlight community and regional variation. Different EFIC approaches may be needed to effectively accomplish the goals of community consultation, public disclosure, and patient notification.

Effect of a Strategy of Initial Laryngeal Tube Insertion vs Endotracheal Intubation on 72-Hour Survival in Adults With Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial.

Importance: Emergency medical services (EMS) commonly perform endotracheal intubation (ETI) or insertion of supraglottic airways, such as the laryngeal tube (LT), on patients with out-of-hospital cardiac arrest (OHCA). The optimal method for OHCA advanced airway management is unknown. Objective: To compare the effectiveness of a strategy of initial LT insertion vs initial ETI in adults with OHCA. Design, Setting, and Participants: Multicenter pragmatic cluster-crossover clinical trial involving EMS agencies from the Resuscitation Outcomes Consortium. The trial included 3004 adults with OHCA and anticipated need for advanced airway management who were enrolled from December 1, 2015, to November 4, 2017. The final date of follow-up was November 10, 2017. Interventions: Twenty-seven EMS agencies were randomized in 13 clusters to initial airway management strategy with LT (n = 1505 patients) or ETI (n = 1499 patients), with crossover to the alternate strategy at 3- to 5-month intervals. Main Outcomes and Measures: The primary outcome was 72-hour survival. Secondary outcomes included return of spontaneous circulation, survival to hospital discharge, favorable neurological status at hospital discharge (Modified Rankin Scale score ≤3), and key adverse events. Results: Among 3004 enrolled patients (median [interquartile range] age, 64 [53-76] years, 1829 [60.9%] men), 3000 were included in the primary analysis. Rates of initial airway success were 90.3% with LT and 51.6% with ETI. Seventy-two hour survival was 18.3% in the LT group vs 15.4% in the ETI group (adjusted difference, 2.9% [95% CI, 0.2%-5.6%]; P = .04). Secondary outcomes in the LT group vs ETI group were return of spontaneous circulation (27.9% vs 24.3%; adjusted difference, 3.6% [95% CI, 0.3%-6.8%]; P = .03); hospital survival (10.8% vs 8.1%; adjusted difference, 2.7% [95% CI, 0.6%-4.8%]; P = .01); and favorable neurological status at discharge (7.1% vs 5.0%; adjusted difference, 2.1% [95% CI, 0.3%-3.8%]; P = .02). There were no significant differences in oropharyngeal or hypopharyngeal injury (0.2% vs 0.3%), airway swelling (1.1% vs 1.0%), or pneumonia or pneumonitis (26.1% vs 22.3%). Conclusions and Relevance: Among adults with OHCA, a strategy of initial LT insertion was associated with significantly greater 72-hour survival compared with a strategy of initial ETI. These findings suggest that LT insertion may be considered as an initial airway management strategy in patients with OHCA, but limitations of the pragmatic design, practice setting, and ETI performance characteristics suggest that further research is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT02419573.

Variation in Survival After Out-of-Hospital Cardiac Arrest Between Emergency Medical Services Agencies.

Importance: Emergency medical services (EMS) deliver essential initial care for patients with out-of-hospital cardiac arrest (OHCA), but the extent to which patient outcomes vary between different EMS agencies is not fully understood. Objective: To quantify variation in patient outcomes after OHCA across EMS agencies. Design, Setting, and Participants: This observational cohort study was conducted in the Resuscitation Outcomes Consortium (ROC) Epistry, a prospective multicenter OHCA registry at 10 sites in North America. Any adult with OHCA treated by an EMS from April 2011 through June 2015 was included. Data analysis occurred from May 2017 to March 2018. Exposure: Treating EMS agency. Main Outcomes and Measures: The primary outcome was survival to hospital discharge. Secondary outcomes were return of spontaneous circulation at emergency department arrival and favorable functional outcome at hospital discharge (defined as a modified Rankin scale score ≤3). Multivariable hierarchical logistic regression models were used to adjust confounders and clustering of patients within EMS agencies, and calculated median odds ratios (MORs) were used to quantify the extent of residual variation in outcomes between EMS agencies. Results: We identified 43 656 patients with OHCA treated by 112 EMS agencies. At EMS agency level, we observed large variations in survival to hospital discharge (range, 0%-28.9%; unadjusted MOR, 1.43 [95% CI, 1.34-1.54]), return of spontaneous circulation on emergency department arrival (range, 9.0%-57.1%; unadjusted MOR, 1.53 [95% CI, 1.43-1.65]), and favorable functional outcome (range, 0%-20.4%; unadjusted MOR, 1.54 [95% CI, 1.40-1.73]). This variation persisted despite adjustment for patient-level and EMS agency-level factors known to be associated with outcomes (adjusted MOR for survival 1.56 [95% CI 1.44-1.73]; adjusted MOR for return of spontaneous circulation at emergency department arrival, 1.50 [95% CI, 1.41-1.62]; adjusted MOR for functionally favorable survival, 1.53 [95% CI, 1.37-1.78]). After restricting analysis to those who survived more than 60 minutes after hospital arrival and including hospital treatment characteristics, the variation persisted (adjusted MOR for survival, 1.49 [95% CI, 1.36-1.69]; adjusted MOR for functionally favorable survival, 1.34 [95% CI, 1.20-1.59]). Conclusions and Relevance: We found substantial variations in patient outcomes after OHCA between a large group of EMS agencies in North America that were not explained by documented patient-level and EMS agency-level variables.

Effects of intra-resuscitation antiarrhythmic administration on rearrest occurrence and intra-resuscitation ECG characteristics in the ROC ALPS trial.

BACKGROUND: Intra-resuscitation antiarrhythmic drugs may improve resuscitation outcomes, in part by avoiding rearrest, a condition associated with poor out-of-hospital cardiac arrest (OHCA) outcomes. However, antiarrhythmics may also alter defibrillation threshold. The objective of this study was to investigate the relationship between rearrest and intra-resuscitation antiarrhythmic drugs in the context of the Resuscitation Outcomes Consortium (ROC) amiodarone, lidocaine, and placebo (ALPS) trial. HYPOTHESIS: Rearrest rates would be lower in cases treated with amiodarone or lidocaine, versus saline placebo, prior to first return of spontaneous circulation (ROSC). We also hypothesized antiarrhythmic effects would be quantifiable through analysis of the prehospital electrocardiogram. METHODS: We conducted a secondary analysis of the ROC ALPS trial. Cases that first achieved prehospital ROSC after randomized administration of study drug were included in the analysis. Rearrest, defined as loss of pulses following ROSC, was ascertained from emergency medical services records. Rearrest rate was calculated overall, as well as by ALPS treatment group. Multivariable logistic regression models were constructed to assess the association between treatment group and rearrest, as well as rearrest and both survival to hospital discharge and survival with neurologic function. Amplitude spectrum area, median slope, and centroid frequency of the ventricular fibrillation (VF) ECG were calculated and compared across treatment groups. RESULTS: A total of 1144 (40.4%) cases with study drug prior to first ROSC were included. Rearrest rate was 44.0% overall; 42.9% for placebo, 45.7% for lidocaine, and 43.0% for amiodarone. In multivariable logistic regression models, ALPS treatment group was not associated with rearrest, though rearrest was associated with poor survival and neurologic outcomes. AMSA and median slope measures of the first available VF were associated with rearrest case status, while median slope and centroid frequency were associated with ALPS treatment group. CONCLUSION: Rearrest rates did not differ between antiarrhythmic and placebo treatment groups. ECG waveform characteristics were correlated with treatment group and rearrest. Rearrest was inversely associated with survival and neurologic outcomes.

Time to Epinephrine Administration and Survival From Nonshockable Out-of-Hospital Cardiac Arrest Among Children and Adults.

BACKGROUND: Previous studies have demonstrated that earlier epinephrine administration is associated with improved survival from out-of-hospital cardiac arrest (OHCA) with shockable initial rhythms. However, the effect of epinephrine timing on patients with nonshockable initial rhythms is unclear. The objective of this study was to measure the association between time to epinephrine administration and survival in adults and children with emergency medical services (EMS)-treated OHCA with nonshockable initial rhythms. METHODS: We performed a secondary analysis of OHCAs prospectively identified by the Resuscitation Outcomes Consortium network from June 4, 2011, to June 30, 2015. We included patients of all ages with an EMS-treated OHCA and an initial nonshockable rhythm. We excluded those with return of spontaneous circulation in <10 minutes. We conducted a subgroup analysis involving patients <18 years of age. The primary exposure was time (minutes) from arrival of the first EMS agency to the first dose of epinephrine. Secondary exposure was time to epinephrine dichotomized as early (<10 minutes) or late (≥10 minutes). The primary outcome was survival to hospital discharge. We adjusted for Utstein covariates and Resuscitation Outcomes Consortium study site. RESULTS: From 55 568 EMS-treated OHCAs, 32 101 patients with initial nonshockable rhythms were included. There were 12 238 in the early group, 14 517 in the late group, and 5346 not treated with epinephrine. After adjusting for potential confounders, each minute from EMS arrival to epinephrine administration was associated with a 4% decrease in odds of survival for adults, odds ratio=0.96 (95% confidence interval, 0.95-0.98). A subgroup analysis (n=13 290) examining neurological outcomes showed a similar association (adjusted odds ratio, 0.94 per minute; 95% confidence interval, 0.89-0.98). When epinephrine was given late in comparison with early, odds of survival were 18% lower (odds ratio, 0.82; 95% confidence interval, 0.68-0.98). In a pediatric analysis (n=595), odds of survival were 9% lower (odds ratio, 0.91; 95% confidence interval, 0.81-1.01) for each minute delay in epinephrine. CONCLUSIONS: Among OHCAs with nonshockable initial rhythms, the majority of patients were administered epinephrine >10 minutes after EMS arrival. Each minute delay in epinephrine administration was associated with decreased survival and unfavorable neurological outcomes. EMS agencies should consider strategies to reduce epinephrine administration times in patients with initial nonshockable rhythms.

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.

The association between AHA CPR quality guideline compliance and clinical outcomes from out-of-hospital cardiac arrest.

BACKGROUND: Measures of chest compression fraction (CCF), compression rate, compression depth and pre-shock pause have all been independently associated with improved outcomes from out-of-hospital (OHCA) cardiac arrest. However, it is unknown whether compliance with American Heart Association (AHA) guidelines incorporating all the aforementioned metrics, is associated with improved survival from OHCA. METHODS: We performed a secondary analysis of prospectively collected data from the Resuscitation Outcomes Consortium Epistry-Cardiac Arrest database. As per the 2015 American Heart Association (AHA) guidelines, guideline compliant cardiopulmonary resuscitation (CPR) was defined as CCF >0.8, chest compression rate 100-120/minute, chest compression depth 50-60mm, and pre-shock pause <10s. Multivariable logistic regression models controlling for Utstein variables were used to assess the relationship between global guideline compliance and survival to hospital discharge and neurologically intact survival with MRS ≤3. Due to potential confounding between CPR quality metrics and cases that achieved early ROSC, we performed an a priori subgroup analysis restricted to patients who obtained ROSC after ≥10min of EMS resuscitation. RESULTS: After allowing for study exclusions, 19,568 defibrillator records were collected over a 4-year period ending in June 2015. For all reported models, the reference standard included all cases who did not meet all CPR quality benchmarks. For the primary model (CCF, rate, depth), there was no significant difference in survival for resuscitations that met all CPR quality benchmarks (guideline compliant) compared to the reference standard (OR 1.26; 95% CI: 0.80, 1.97). When the dataset was restricted to patients obtaining ROSC after ≥10min of EMS resuscitation (n=4,158), survival was significantly higher for those resuscitations that were guideline compliant (OR 2.17; 95% CI: 1.11, 4.27) compared to the reference standard. Similar findings were obtained for neurologically intact survival with MRS ≤3 (OR 3.03; 95% CI: 1.12, 8.20). CONCLUSIONS: In this observational study, compliance with AHA guidelines for CPR quality was not associated with improved outcomes from OHCA. Conversely, when restricting the cohort to those with late ROSC, compliance with guidelines was associated with improved clinical outcomes. Strategies to improve overall guideline compliance may have a significant impact on outcomes from OHCA.

Compression-to-ventilation ratio and incidence of rearrest-A secondary analysis of the ROC CCC trial.

BACKGROUND: Previous work has demonstrated that when out-of-hospital cardiac arrest (OHCA) patients achieve return of spontaneous circulation (ROSC), but subsequently have another cardiac arrest prior to hospital arrival (rearrest), the probability of survival to hospital discharge is significantly decreased. Additionally, few modifiable factors for rearrest are known. We sought to examine the association between rearrest and compression-to-ventilation ratio during cardiopulmonary resuscitation (CPR) and to confirm the association between rearrest and outcomes. HYPOTHESIS: Rearrest incidence would be similar between cases treated with 30:2 or continuous chest compression (CCC) CPR, but inversely related to survival and good neurological outcome. METHODS: We conducted a secondary analysis of a large randomized-controlled trial of CCC versus 30:2 CPR for the treatment of OHCA between 2011 and 2015 among 8 sites of the Resuscitation OUTCOMES: Consortium (ROC). Patients were randomized through an emergency medical services (EMS) agency-level cluster randomization design to receive either 30:2 or CCC CPR. Case data were derived from prehospital patient care reports, digital defibrillator files, and hospital records. The primary analysis was an as-treated comparison of the proportion of patients with a rearrest for patients who received 30:2 versus those who received CCC. In addition, we assessed the association between rearrest and both survival to hospital discharge and favorable neurological outcome (Modified Rankin Score≤3) in patients with and without ROSC upon ED arrival using multivariable logistic regression adjusting for age, sex, initial rhythm and measures of CPR quality. RESULTS: There were 14,109 analyzable cases that were determined to have definitively received either CCC or 30:2 CPR. Of these, 4713 had prehospital ROSC and 2040 (43.2%) had at least one rearrest. Incidence of rearrest was not significantly different between patients receiving CCC and 30:2 (44.1% vs 41.8%; adjusted OR: 1.01; 95% CI: 0.88, 1.16). Rearrest was significantly associated with lower survival (23.3% vs 36.9%; adjusted OR: 0.46; 95%CI: 0.36-0.51) and worse neurological outcome (19.4% vs 30.2%; adjusted OR: 0.46; 95%CI: 0.38, 0.55). CONCLUSION: Rearrest occurrence was not significantly different between patients receiving CCC and 30:2, and was inversely associated with survival to hospital discharge and MRS.

A comparison of the universal TOR Guideline to the absence of prehospital ROSC and duration of resuscitation in predicting futility from out-of-hospital cardiac arrest.

INTRODUCTION: The Universal Termination of Resuscitation (TOR) Guideline accurately identifies potential out-of-hospital cardiac arrest (OHCA) survivors. However, implementation is inconsistent with some Emergency Medical Service (EMS) agencies using absence of return of spontaneous circulation (ROSC) as sole criterion for termination. OBJECTIVE: To compare the performance of the Universal TOR Guideline with the single criterion of no prehospital ROSC. Second, to determine factors associated with survival for patients transported without a ROSC. Lastly, to compare the impact of time to ROSC as a marker of futility to the Universal TOR Guideline. DESIGN: Retrospective, observational cohort study. PARTICIPANTS: Non-traumatic, adult (≥18 years) OHCA patients of presumed cardiac etiology treated by EMS providers. SETTING: ROC-PRIMED and ROC-Epistry post ROC-PRIMED databases between 2007 and 2011. OUTCOMES: Primary outcome was survival to hospital discharge and the secondary outcome was functional survival. We used multivariable regression to evaluate factors associated with survival in patients transported without a ROSC. RESULTS: 36,543 treated OHCAs occurred of which 9467 (26%) were transported to hospital without a ROSC. Patients transported without a ROSC who met the Universal TOR Guideline for transport had a survival of 3.0% (95% CI 2.5-3.4%) compared to 0.7% (95% CI 0.4-0.9%) in patients who met the Universal TOR Guideline for termination. The Universal TOR Guideline identified 99% of survivors requiring continued resuscitation and transportation to hospital including early identification of survivors who sustained a ROSC after extended durations of CPR. CONCLUSION: Using absence of ROSC as a sole predictor of futility misses potential survivors. The Universal TOR Guideline remains a strong predictor of survival.

Unchanged pediatric out-of-hospital cardiac arrest incidence and survival rates with regional variation in North America.

AIM: Outcomes for pediatric out-of-hospital cardiac arrest (OHCA) are poor. Our objective was to determine temporal trends in incidence and mortality for pediatric OHCA. METHODS: Adjusted incidence and hospital mortality rates of pediatric non-traumatic OHCA patients from 2007-2012 were analyzed using the 9 region Resuscitation Outcomes Consortium-Epidemiological Registry (ROC-Epistry) database. Children were divided into 4 age groups: perinatal (<3 days), infants (3days-1year), children (1-11 years), and adolescents (12-19 years). ROC regions were analyzed post-hoc. RESULTS: We studied 1738 children with OHCA. The age- and sex-adjusted incidence rate of OHCA was 8.3 per 100,000 person-years (75.3 for infants vs. 3.7 for children and 6.3 for adolescents, per 100,000 person-years, p<0.001). Incidence rates differed by year (p<0.001) without overall linear trend. Annual survival rates ranged from 6.7-10.2%. Survival was highest in the perinatal (25%) and adolescent (17.3%) groups. Stratified by age group, survival rates over time were unchanged (all p>0.05) but there was a non-significant linear trend (1.3% increase) in infants. In the multivariable logistic regression analysis, infants, unwitnessed event, initial rhythm of asystole, and region were associated with worse survival, all p<0.001. Survival by region ranged from 2.6-14.7%. Regions with the highest survival had more cases of EMS-witnessed OHCA, bystander CPR, and increased EMS-defibrillation (all p<0.05). CONCLUSIONS: Overall incidence and survival of children with OHCA in ROC regions did not significantly change over a recent 5year period. Regional variation represents an opportunity for further study to improve outcomes.

Association of early withdrawal of life-sustaining therapy for perceived neurological prognosis with mortality after cardiac arrest.

BACKGROUND: Withdrawing life-sustaining therapy because of perceived poor neurological prognosis (WLST-N) is a common cause of hospital death after out-of-hospital cardiac arrest (OHCA). Although current guidelines recommend against WLST-N before 72h (WLST-N<72), this practice is common and may increase mortality. We sought to quantify these effects. METHODS: In a secondary analysis of a multicenter OHCA trial, we evaluated survival to hospital discharge and survival with favorable functional status (modified Rankin Score ≤3) in adults alive >1h after hospital admission. Propensity score modeling the probability of exposure to WLST-N<72 based on pre-exposure covariates was used to match unexposed subjects with those exposed to WLST-N<72. We determined the probability of survival and functionally favorable survival in the unexposed matched cohort, fit adjusted logistic regression models to predict outcomes in this group, and then used these models to predict outcomes in the exposed cohort. Combining these findings with current epidemiologic statistics we estimated mortality nationally that is associated with WLST-N<72. RESULTS: Of 16,875 OHCA subjects, 4265 (25%) met inclusion criteria. WLST-N<72 occurred in one-third of subjects who died in-hospital. Adjusted analyses predicted that exposed subjects would have 26% survival and 16% functionally favorable survival if WLST-N<72 did not occur. Extrapolated nationally, WLST-N<72 may be associated with mortality in approximately 2300 Americans each year of whom nearly 1500 (64%) might have had functional recovery. CONCLUSIONS: After OHCA, death following WLST-N<72 may be common and is potentially avoidable. Reducing WLST-N<72 has national public health implications and may afford an opportunity to decrease mortality after OHCA.

Design and implementation of the Resuscitation Outcomes Consortium Pragmatic Airway Resuscitation Trial (PART).

Airway management is an important component of resuscitation from out-of-hospital cardiac arrest (OHCA). The optimal approach to advanced airway management is unknown. The Pragmatic Airway Resuscitation Trial (PART) will compare the effectiveness of endotracheal intubation (ETI) and Laryngeal Tube (LT) insertion upon 72-h survival in adult OHCA. Encompassing United States Emergency Medical Services agencies affiliated with the Resuscitation Outcomes Consortium (ROC), PART will use a cluster-crossover randomized design. Participating subjects will include adult, non-traumatic OHCA requiring bag-valve-mask ventilation. Trial interventions will include (1) initial airway management with ETI and (2) initial airway management with LT. The primary and secondary trial outcomes are 72-h survival and return of spontaneous circulation. Additional clinical outcomes will include airway management process and adverse events. The trial will enroll a total of 3000 subjects. Results of PART may guide the selection of advanced airway management strategies in OHCA.

A quantitative analysis of out-of-hospital pediatric and adolescent resuscitation quality--A report from the ROC epistry-cardiac arrest.

AIM: High-quality cardiopulmonary resuscitation (CPR) may improve survival. The quality of CPR performed during pediatric out-of-hospital cardiac arrest (p-OHCA) is largely unknown. The main objective of this study was to describe the quality of CPR performed during p-OHCA resuscitation attempts. METHODS: Prospective observational multi-center cohort study of p-OHCA patients ≥ 1 and < 19 years of age registered in the Resuscitation Outcomes Consortium (ROC) Epistry database. The primary outcome was an a priori composite variable of compliance with American Heart Association (AHA) guidelines for both chest compression (CC) rate and CC fraction (CCF). Event compliance was defined as a case with 60% or more of its minute epochs compliant with AHA targets (rate 100-120 min(-1); depth ≥ 38 mm; and CCF ≥ 0.80). In a secondary analysis, multivariable logistic regression was used to evaluate the association between guideline compliance and return of spontaneous circulation (ROSC). RESULTS: Between December 2005 and December 2012, 2564 pediatric events were treated by EMS providers, 390 of which were included in the final cohort. Of these events, 22% achieved AHA compliance for both rate and CCF, 36% for rate alone, 53% for CCF alone, and 58% for depth alone. Over time, there was a significant increase in CCF (p < 0.001) and depth (p = 0.03). After controlling for potential confounders, there was no significant association between AHA guideline compliance and ROSC. CONCLUSIONS: In this multi-center study, we have established that there are opportunities for professional rescuers to improve prehospital CPR quality. Encouragingly, CCF and depth both increased significantly over time.

Classification of cardiopulmonary resuscitation chest compression patterns: manual versus automated approaches.

OBJECTIVES: New chest compression detection technology allows for the recording and graphical depiction of clinical cardiopulmonary resuscitation (CPR) chest compressions. The authors sought to determine the inter-rater reliability of chest compression pattern classifications by human raters. Agreement with automated chest compression classification was also evaluated by computer analysis. METHODS: This was an analysis of chest compression patterns from cardiac arrest patients enrolled in the ongoing Resuscitation Outcomes Consortium (ROC) Continuous Chest Compressions Trial. Thirty CPR process files from patients in the trial were selected. Using written guidelines, research coordinators from each of eight participating ROC sites classified each chest compression pattern as 30:2 chest compressions, continuous chest compressions (CCC), or indeterminate. A computer algorithm for automated chest compression classification was also developed for each case. Inter-rater agreement between manual classifications was tested using Fleiss's kappa. The criterion standard was defined as the classification assigned by the majority of manual raters. Agreement between the automated classification and the criterion standard manual classifications was also tested. RESULTS: The majority of the eight raters classified 12 chest compression patterns as 30:2, 12 as CCC, and six as indeterminate. Inter-rater agreement between manual classifications of chest compression patterns was κ = 0.62 (95% confidence interval [CI] = 0.49 to 0.74). The automated computer algorithm classified chest compression patterns as 30:2 (n = 15), CCC (n = 12), and indeterminate (n = 3). Agreement between automated and criterion standard manual classifications was κ = 0.84 (95% CI = 0.59 to 0.95). CONCLUSIONS: In this study, good inter-rater agreement in the manual classification of CPR chest compression patterns was observed. Automated classification showed strong agreement with human ratings. These observations support the consistency of manual CPR pattern classification as well as the use of automated approaches to chest compression pattern analysis.