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Epinephrine is the most commonly used drug in out-of-hospital cardiac arrest (OHCA) resuscitation, but evidence supporting its efficacy is mixed. What are the comparative efficacy and safety of standard dose epinephrine, high-dose epinephrine, epinephrine plus vasopressin, and placebo or no treatment in improving outcomes after OHCA? In this systematic review and network meta-analysis of randomized controlled trials, we searched six databases from inception through June 2022 for randomized controlled trials evaluating epinephrine use during OHCA resuscitation. We performed frequentist random-effects network meta-analysis and present ORs and 95% CIs. We used the the Grading of Recommendations, Assessment, Development, and Evaluation approach to rate the certainty of evidence. Outcomes included return of spontaneous circulation (ROSC), survival to hospital admission, survival to discharge, and survival with good functional outcome. We included 18 trials (21,594 patients). Compared with placebo or no treatment, high-dose epinephrine (OR, 4.27; 95% CI, 3.68-4.97), standard-dose epinephrine (OR, 3.69; 95% CI, 3.32-4.10), and epinephrine plus vasopressin (OR, 3.54; 95% CI, 2.94-4.26) all increased ROSC. High-dose epinephrine (OR, 3.53; 95% CI, 2.97-4.20), standard-dose epinephrine (OR, 3.00; 95% CI, 2.66-3.38), and epinephrine plus vasopressin (OR, 2.79; 95% CI, 2.27-3.44) all increased survival to hospital admission as compared with placebo or no treatment. However, none of these agents may increase survival to discharge or survival with good functional outcome as compared with placebo or no treatment. Compared with placebo or no treatment, standard-dose epinephrine improved survival to discharge among patients with nonshockable rhythm (OR, 2.10; 95% CI, 1.21-3.63), but not in those with shockable rhythm (OR, 0.85; 95% CI, 0.39-1.85). Use of standard-dose epinephrine, high-dose epinephrine, and epinephrine plus vasopressin increases ROSC and survival to hospital admission, but may not improve survival to discharge or functional outcome. Standard-dose epinephrine improved survival to discharge among patients with nonshockable rhythm, but not those with shockable rhythm. Center for Open Science: https://osf.io/arxwq [Display omitted] [ABSTRACT FROM AUTHOR]

Objectives: Examining the association of time to treatment (drug or placebo) with survival to hospital discharge and neurologic outcome. Design: Post hoc analysis of the Resuscitation Outcomes Consortium Amiodarone, Lidocaine, Placebo randomized controlled trial. Setting: Emergency medical services enrolled patients with out-of-hospital cardiac arrest (OHCA) at multiple North American sites. Patients: Adults with nontraumatic OHCA and an initial rhythm of ventricular fibrillation or pulseless ventricular tachycardia refractory to at least one defibrillation attempt were included. Interventions: None. Measurements and Main Results: We used logistic regression to examine the association of time to treatment with survival to hospital discharge and favorable neurologic status at discharge (modified Rankin Scale ≤ 3) for the three treatment groups including an interaction term between treatment and time to treatment to determine the effect of time on treatment effects. Time to treatment data were available for 2,994 out of 3,026 patients (99%). The proportion of patients who survived to hospital discharge decreased as time to drug administration increased, in amiodarone (odds ratio [OR], 0.91; 95% CI, 0.90–0.93 per min), lidocaine (OR, 0.93; 95% CI, 0.91–0.96), and placebo (OR, 0.91; 95% CI, 0.90–0.93). Comparing amiodarone to placebo, there was improved survival at all times of drug administration (OR, 1.32; 95% CI, 1.05–1.65). Comparing lidocaine to placebo, survival was not different with shorter times to drug administration (< 11 min), whereas survival was higher with lidocaine at longer times to drug administration with an interaction between treatment effect and time to treatment (p = 0.048). Survival with good neurologic outcome showed similar results for all analyses. Conclusions: Survival and favorable neurologic outcomes decreased with longer times to drug administration. Amiodarone improved survival at all time points whereas lidocaine improved survival only at later time points, compared with placebo. [ABSTRACT FROM AUTHOR]

Objective: Clinical trials for patients with shock-refractory out-of-hospital cardiac arrest (OHCA), including the Amiodarone, Lidocaine or Placebo (ALPS) trial, have been unable to demonstrate definitive benefit after treatment with antiarrhythmic drugs. A Bayesian approach, combining the available evidence, may yield additional insights.Methods: We conducted a reanalysis of the ALPS trial comparing treatment with amiodarone or lidocaine with placebo in patients with OHCA following shock-refractory ventricular fibrillation or ventricular tachycardia (VF/VT). We used Bayesian regression to assess the probability of improved survival or improved neurological outcome on the 7-point modified Rankin Scale. We derived weak, moderate and strong priors from a previous clinical trial.Results: The original ALPS trial randomised 3026 adult patients with OHCA to amiodarone (n=974, survival to hospital discharge 24.4%), lidocaine, (n=993, survival 23.7%) or placebo (n=1059, survival 21.0%). In our reanalysis the probability of improved survival from amiodarone ranged from 83% (strong prior) to 95% (weak prior) compared with placebo and from 78% (strong) to 90% (weak) for lidocaine-an estimated improvement in survival of 2.9% (IQR 1.4%-3.8%) for amiodarone and 1.7% (IQR 0.84%-3.2%) for lidocaine over placebo (moderate prior). The probability of improved neurological outcome from amiodarone ranged from 96% (weak) to 99% (strong) compared with placebo and from 88% (weak) to 96% (strong) for lidocaine.Conclusions: In a Bayesian reanalysis of patients with shock-resistant VF/VT OHCA, treatment with amiodarone had high probabilities of improved survival and neurological outcome, while treatment with lidocaine had a more modest benefit. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the provision of bystander interventions and rates of survival after exercise-related sudden cardiac arrest (SCA).Design: Systematic review.Data Sources: MEDLINE, EMBASE, PubMed, CINAHL, SPORTDiscus, Cochrane Library and grey literature sources were searched from inception to November/December 2020.Study Eligibility Criteria: Observational studies assessing a population of exercise-related SCA (out-of-hospital cardiac arrests that occurred during exercise or within 1 hour of cessation of activity), where bystander cardiopulmonary resuscitation (CPR) and/or automated external defibrillator (AED) use were reported, and survival outcomes were ascertained.Methods: Among all included studies, the median (IQR) proportions of bystander CPR and bystander AED use, as well as median (IQR) rate of survival to hospital discharge, were calculated.Results: A total of 29 studies were included in this review, with a median study duration of 78.7 months and a median sample size of 91. Most exercise-related SCA patients were male (median: 92%, IQR: 86%-96%), middle-aged (median: 51, IQR: 39-56 years), and presented with a shockable arrest rhythm (median: 78%, IQR: 62%-86%). Bystander CPR was initiated in a median of 71% (IQR: 59%-87%) of arrests, whereas bystander AED use occurred in a median of 31% (IQR: 19%-42%) of arrests. Among the 19 studies that reported survival to hospital discharge, the median rate of survival was 32% (IQR: 24%-49%). Studies which evaluated the relationship between bystander interventions and survival outcomes reported that both bystander CPR and AED use were associated with survival after exercise-related SCA.Conclusion: Exercise-related SCA occurs predominantly in males and presents with a shockable ventricular arrhythmia in most cases, emphasising the importance of rapid access to defibrillation. Further efforts are needed to promote early recognition and a rapid bystander response to exercise-related SCA. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular magnetic resonance (CMR) is increasingly used in the evaluation of patients who are potential candidates for implantable cardioverter-defibrillator (ICD) therapy to assess left ventricular (LV) ejection fraction (LVEF), myocardial fibrosis, and etiology of cardiomyopathy. It is unclear whether CMR-derived strain measurements are predictive of appropriate shocks and death among patients who receive an ICD. We evaluated the prognostic value of LV strain parameters on feature-tracking (FT) CMR in patients who underwent subsequent ICD implant for primary or secondary prevention of sudden cardiac death. Methods: Consecutive patients from 2 Canadian tertiary care hospitals who underwent ICD implant and had a pre-implant CMR scan were included. Using FT-CMR, a single, blinded, reader measured LV global longitudinal (GLS), circumferential (GCS), and radial (GRS) strain. Cox proportional hazards regression was performed to assess the associations between strain measurements and the primary composite endpoint of all-cause death or appropriate ICD shock that was independently ascertained. Results: Of 364 patients (mean 61 years, mean LVEF 32%), 64(17.6%) died and 118(32.4%) reached the primary endpoint over a median follow-up of 62 months. Univariate analyses showed significant associations between GLS, GCS, and GRS and appropriate ICD shocks or death (all p < 0.01). In multivariable Cox models incorporating LVEF, GLS remained an independent predictor of both the primary endpoint (HR 1.05 per 1% higher GLS, 95% CI 1.01–1.09, p = 0.010) and death alone (HR 1.06 per 1% higher GLS, 95% CI 1.02–1.11, p = 0.003). There was no significant interaction between GLS and indication for ICD implant, presence of ischemic heart disease or late gadolinium enhancement (all p > 0.30). Conclusions: GLS by FT-CMR is an independent predictor of appropriate shocks or mortality in ICD patients, beyond conventional prognosticators including LVEF. Further study is needed to elucidate the role of LV strain analysis to refine risk stratification in routine assessment of ICD treatment benefit. [ABSTRACT FROM AUTHOR]

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Background: Advances in resuscitation science have dramatically improved survival rates following cardiac arrest. However, about 60% of adults that regain spontaneous circulation die before leaving the hospital. Recently it has been shown that inducing hypothermia in cardiac arrest survivors immediately following their arrival in hospital can dramatically improve both overall survival and neurological outcomes. Despite the strong evidence for its efficacy and the apparent simplicity of this intervention, recent surveys show that therapeutic hypothermia is delivered inconsistently, incompletely, and often with delay. Methods and design: This study will evaluate a multi-faceted knowledge translation strategy designed to increase the utilization rate of induced hypothermia in survivors of cardiac arrest across a network of 37 hospitals in Southwestern Ontario, Canada. The study is designed as a stepped wedge randomized trial lasting two years. Individual hospitals will be randomly assigned to four different wedges that will receive the active knowledge translation strategy according to a sequential rollout over a number of time periods. By the end of the study, all hospitals will have received the intervention. The primary aim is to measure the effectiveness of a multifaceted knowledge translation plan involving education, reminders, and audit-feedback for improving the use of induced hypothermia in survivors of cardiac arrest presenting to the emergency department. The primary outcome is the proportion of eligible OHCA patients that are cooled to a body temperature of 32 to 34°C within six hours of arrival in the hospital. Secondary outcomes will include process of care measures and clinical outcomes. Discussion: Inducing hypothermia in cardiac arrest survivors immediately following their arrival to hospital has been shown to dramatically improve both overall survival and neurological outcomes. However, this lifesaving treatment is frequently not applied in practice. If this trial is positive, our results will have broad implications by showing that a knowledge translation strategy shared across a collaborative network of hospitals can increase the number of patients that receive this lifesaving intervention in a timely manner. Trial Registration: ClinicalTrials.gov Trial Identifier: NCT00683683 [ABSTRACT FROM AUTHOR]

Background: A recent Cochrane meta-analysis did not confirm the benefits of fish and fish oil in the secondary prevention of cardiac death and myocardial infarction. We performed a meta-analysis of randomized controlled trials that examined the effect of fish-oil supplementation on ventricular fibrillation and ventricular tachycardia to determine the overall effect and to assess whether heterogeneity exists between trials. Methods: We searched electronic databases (MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, CINAHL) from inception to May 2007. We included randomized controlled trials of fish-oil supplementation on ventricular fibrillation or ventricular tachycardia in patients with implantable cardioverter defibrillators. The primary outcome was implantable cardioverter defibrillator discharge. We calculated relative risk [RR] for outcomes at 1-year follow-up for each study. We used the DerSimonian and Laird randomeffects methods when there was significant heterogeneity between trials and the Mantel-Hanzel fixed-effects method when heterogeneity was negligible. Results: We identified 3 trials of 1-2 years' duration. These trials included a total of 573 patients who received fish oil and 575 patients who received a control. Meta-analysis of data collected at 1 year showed no overall effect of fish oil on the relative risk of implantable cardioverter defibrillator discharge. There was significant heterogeneity between trials. The second largest study showed a significant benefit of fish oil (relative risk [RR] 0.74, 95% confidence interval [CI] 0.56-0.98). The smallest showed an adverse tendency at 1 year (RR 1.23, 95% CI 0.92-1.65) and significantly worse outcome at 2 years among patients with ventricular tachycardia at study entry (log rank p = 0.007). Conclusion: These data indicate that there is heterogeneity in the response of patients to fish-oil supplementation. Caution should be used when prescribing fish-oil supplementation for patients with ventricular tachycardia. [ABSTRACT FROM AUTHOR]

Introduction: The slow delayed rectifier K+ current (IKs) contributes little to ventricular repolarization at rest. It is unclear whether IKs plays a role during ventricular fibrillation (VF) or ventricular repolarization at rapid rates during β-adrenergic stimulation. Methods and Results: In an in vivo rabbit model, we evaluated the effects of HMR 1556 (1 mg Kg−1+ 1 mg kg −1 hr −1 i.v.), a selective IKs blocker, on monophasic action potential duration at 90% repolarization (MAPD90), ventricular effective refractory period (VERP), and defibrillation threshold (DFT). In perfused rabbit hearts, the effects of HMR 1556 (10 and 100 nM) in the presence of isoproterenol (5 nM) on MAPD90 and VERP were studied at cycle lengths (CLs) 200–500 msec. In vivo, HMR 1556 prolonged MAPD90 by 6 ± 1 msec at CL 200 msec (P < 0.01, n = 6), lowered DFT from 558 ± 46 V to 417 ± 31 V (P < 0.01), and decreased the coefficient of variation in the VF inter-beat deflection intervals from 8.9 ± 0.6% to 6.5 ± 0.4% (P < 0.05) compared with control. In perfused rabbit hearts, isoproterenol shortened MAPD90 by 5 ± 1 msec at CL 200 msec and 11 ± 4 msec at CL 500 msec (P < 0.05, n = 7). This shortening was reversed by HMR 1556 (P < 0.05), and both effects were rate-independent. Conclusion: IKs block increases VF temporal organization and lowers DFT, and IKs that is activated following β-adrenergic stimulation contributes to ventricular repolarization without rate dependence. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined the effects of rotigaptide, a gap junction modifier on defibrillation energy and resuscitation from after cardiac arrest in rabbits. The substances utilized include xylazine, ketamine and isoflurane. Topics discussed include the effects of rotigaptide on electrophysiological parameters, dose response effect of rotigaptide and limitations of the study.

We appreciate the comments by Dr Madias regarding the study on the incidence of hypertrophic cardiomyopathy (HCM)-related sudden cardiac death in young individuals in Ontario.[1] We entirely agree with Dr Madias that the ECG adds valuable information in HCM and may evolve with disease progression, as previously described.[2] Furthermore, gene carriers without evidence of hypertrophy on echocardiogram and cardiac magnetic resonance can display an abnormal ECG.[3] We agree it would have been interesting to see whether the ECGs of the patients who exhibited no or only mild hypertrophy but had histologic findings consistent with HCM were abnormal and could have been clinically useful for screening before the development of hypertrophy on echocardiogram. In 30 of the 50 individuals who had an autopsy, there was asymmetric septal hypertrophy; in the remaining, the hypertrophy was concentric. Electrocardiogram in apical hypertrophic cardiomyopathy with a speculation as to the mechanism of its features. [Extracted from the article]

Abstract: Epinephrine (adrenaline) and vasopressin have been by far the most commonly studied vasopressors in experimental cardiac arrest. Despite animal experimental studies suggesting improved outcomes in experimental cardiac arrest, clinical trials of pressor agents have failed to show clear cut benefit from either vasopressin or epinephrine, although few, if any, trials compared pressor agents to a placebo. The action of vasopressors in the heart, particularly β1-Adrenergic stimulation, is associated with adverse cardiac effects including post-resuscitation myocardial dysfunction, worsening ventricular arrhythmias, and increasing myocardial oxygen consumption. α2-Adrenergic agonists, in experimental studies, show great promise in improving outcomes in experimental cardiac arrest, but have not been studied in humans. The combination of epinephrine and vasopressin may be effective, but has been incompletely studied. Clinical trials of vasopressor agents, which minimize direct myocardial effects are needed. [Copyright &y& Elsevier]

Abstract: Background:: Although biphasic defibrillation waveforms appear to be superior to monophasic waveforms in terminating VF, their relative benefits in out-of-hospital resuscitation are incompletely understood. Prior comparisons of defibrillation waveform efficacy in out-of-hospital cardiac arrest (OHCA) are confined to patients presenting in a shockable rhythm and resuscitated by first responder (basic life support). This effectiveness study compared monophasic and biphasic defibrillation waveform for conversion of ventricular arrhythmias in all OHCA treated with advance life support (ALS). Methods and results:: This prospective randomized controlled trial compared the rectilinear biphasic (RLB) waveform with the monophasic damped sine (MDS) waveform, using step-up energy levels. The study enrolled OHCA patients requiring at least one shock delivered by ALS providers, regardless of initial presenting rhythm. Shock success was defined as conversion at 5s to organized rhythm after one to three escalating shocks. We report efficacy results for the cohort of patients treated by ALS paramedics who presented with an initially shockable rhythm who had not received a shock from a first responder (MDS: n =83; RLB: n =86). Shock success within the first three ascending energy shocks for RLB (120, 150, 200J) was superior to MDS (200, 300, 360J) for patients initially presenting in a shockable rhythm (52% versus 34%, p =0.01). First shock conversion was 23% and12%, for RLB and MDS, respectively (p =0.07). There were no significant differences in return of spontaneous circulation (47% versus 47%), survival to 24h (31% versus 27%), and survival to discharge (9% versus 7%). Mean 24h survival rates of bystander witnessed events showed differences between waveforms in the early circulatory phase at 4–10min post event (mean (S.D.) RLB 0.45 (0.07) versus MDS 0.31 (0.06), p =0.0002) and demonstrated decline as time to first shock increased to 20min. Conclusion:: Shock success to an organized rhythm comparing step-up protocol for energy settings demonstrated the RLB waveform was superior to MDS in ALS treatment of OHCA. Survival rates for both waveforms are consistent with current theories on the circulatory and metabolic phases of out-of-hospital cardiac arrest. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to compare rate-only detection to enhanced detection in a dual-chamber implantable cardioverter-defibrillator (ICD), to discriminate ventricular tachycardia from supraventricular tachycardia.Background: ICDs are highly effective in treating ventricular tachycardia (VT) or ventricular fibrillation (VF). However, they frequently deliver inappropriate therapy during supraventricular tachycardia (SVT).Methods: We conducted a randomized clinical trial of detection enhancements in a dual-chamber ICD compared to control (rate-only) detection to discriminate VT from SVT. Detection enhancements included a specific standardized protocol identical for all patients for programming rate stability, sudden onset, atrial-to-ventricular relationship (sudden onset = 9% and rate stability = 10 ms; V > A "on"), and "sustained rate duration" (3 minutes). The primary endpoint was the time to first inappropriate therapy classified by a blinded events committee.Results: One hundred forty-nine patients had a history of sustained VT or VF. Mean age (+/- SD) was 60 +/- 13 years; 83% were male, and mean ejection fraction was 35 +/- 15%. Control (n = 70) and "enhanced" (n = 79) groups did not differ with regard to age, sex, ejection fraction, or primary arrhythmia. The proportion of patients free of inappropriate therapy over time was significantly higher in the enhanced versus the control group (hazard ratio = 0.47, P = .011). High-energy shocks were reduced from 0.58 +/- 4.23 shocks/patient/month in the control group to 0.04 +/- 0.15 shocks/patient/month in the enhanced group (P = .0425). No patient programmed per protocol failed to receive therapy for VT detected by the ICD (422 VT episodes).Conclusions: Standardized programming in a dual-chamber ICD leads to a significant and clinically important reduction in inappropriate therapies compared to rate-only detection and does not compromise safety with respect to appropriate treatment of VT. [ABSTRACT FROM AUTHOR]

Background: Survivors of out-of-hospital cardiac arrest are at high risk of recurrent arrests, many of which could be prevented with implantable cardioverter defibrillators (ICDs). We sought to determine the ICD insertion rate among survivors of out-of-hospital cardiac arrest and to determine factors associated with ICD implantation. Methods: The Ontario Prehospital Advanced Life Support (OPALS) study is a prospective, multiphase, before-after study assessing the effectiveness of prehospital interventions for people experiencing cardiac arrest, trauma or respiratory arrest in 19 Ontario communities. We linked OPALS data describing survivors of cardiac arrest with data from all defibrillator im-plantation centres in Ontario. Results: From January 1997 to April 2002, 454 patients in the OPALS study survived to hospital discharge after experiencing an out-of-hospital cardiac arrest. The mean age was 65 (standard deviation 14) years, 122 (26.9%) were women, 398 (87.7%) had a witnessed arrest, 372 (81.9%) had an initial rhythm of ventricular tachycardia or ventricular fibrillation (VT/VF), and 76 (16.7%) had asystole or another arrhythmia. The median cerebral performance category at discharge (range 1-5, 1 = normal) was 1. Only 58 (12.8%) of the 454 patients received an ICD. Patients with an initial rhythm of VT/VF were more likely than those with an initial rhythm of asystole or another rhythm to undergo device insertion (adjusted odds ratio [OR] 9.63, 95% confidence interval [CI] 1.31-71.50). Similarly, patients with a normal cerebral performance score were more likely than those with abnormal scores to undergo ICD insertion (adjusted OR 12.52, 95% CI 1.74-92.12). Interpretation: A minority of patients who survived cardiac arrest underwent ICD insertion. It is unclear whether this low usage rate reflects referral bias, selection bias by electrophysiologists, supply constraint or patient preference. [ABSTRACT FROM AUTHOR]

Patient selection for implantation of a cardioverter-defibrillator for primary prevention of sudden cardiac death is especially difficult in inherited arrhythmia syndromes, owing to a lack of randomized outcome studies in this setting. Two registry studies and the first report of a long-term follow-up of defibrillators in primary prophylaxis have provided some information regarding patient selection, but have important limitations. [ABSTRACT FROM AUTHOR]

Background: Despite high-quality cardiopulmonary resuscitation (CPR), early defibrillation, and antiarrhythmic medications, some patients remain in refractory ventricular fibrillation (VF) during out-of-hospital cardiac arrest. These patients have worse outcomes compared to patients who respond to initial treatment. Double sequential external defibrillation (DSED) and vector change (VC) defibrillation have been proposed as viable options for patients in refractory VF. However, the evidence supporting the use of novel defibrillation strategies is inconclusive. The objective of this study is to compare two novel therapeutic defibrillation strategies (DSED and VC) against standard defibrillation for patients with treatment refractory VF or pulseless ventricular tachycardia (pVT) during out-of-hospital cardiac arrest.Research Question: Among adult (≥ 18 years) patients presenting in refractory VF or pulseless ventricular tachycardia (pVT) during out-of-hospital cardiac arrest, does DSED or VC defibrillation result in greater rates of survival to hospital discharge compared to standard defibrillation?Methods: This will be a three-arm, cluster randomized trial with repeated crossover conducted in six regions of Ontario, Canada (Peel, Halton, Toronto, Simcoe, London, and Ottawa), over 3 years. All adult (≥ 18 years) patients presenting in refractory VF (defined as patients presenting in VF/pVT and remaining in VF/pVT after three consecutive standard defibrillation attempts during out-of-hospital cardiac arrest of presumed cardiac etiology will be treated by one of three strategies: (1) continued resuscitation using standard defibrillation, (2) resuscitation involving DSED, or (3) resuscitation involving VC (change of defibrillation pads from anterior-lateral to anterior-posterior pad position) defibrillation. The primary outcome will be survival to hospital discharge. Secondary outcomes will include return of spontaneous circulation (ROSC), VF termination after the first interventional shock, VF termination inclusive of all interventional shocks, and number of defibrillation attempts to obtain ROSC. We will also perform an a priori subgroup analysis comparing rates of survival for those who receive "early DSED," or first DSED shock is shock 4-6, to those who receive "late DSED," or first DSED shock is shock 7 or later.Discussion: A well-designed randomized controlled trial employing a standardized approach to alternative defibrillation strategies early in the treatment of refractory VF is urgently required to determine if the treatments of DSED or VC defibrillation impact clinical outcomes.Trial Registration: ClinicalTrials.gov NCT04080986 . Registered on 6 September 2019. [ABSTRACT FROM AUTHOR]

Background: Antiarrhythmic drugs have not proven to significantly improve overall survival after out-of-hospital cardiac arrest from shock-refractory ventricular fibrillation/pulseless ventricular tachycardia. How this might be influenced by the route of drug administration is not known.Methods: In this prespecified analysis of a randomized, placebo-controlled clinical trial, we compared the differences in survival to hospital discharge in adults with shock-refractory ventricular fibrillation/pulseless ventricular tachycardia out-of-hospital cardiac arrest who were randomly assigned by emergency medical services personnel to an antiarrhythmic drug versus placebo in the ALPS trial (Resuscitation Outcomes Consortium Amiodarone, Lidocaine or Placebo Study), when stratified by the intravenous versus intraosseous route of administration.Results: Of 3019 randomly assigned patients with a known vascular access site, 2358 received ALPS drugs intravenously and 661 patients by the intraosseous route. Intraosseous and intravenous groups differed in sex, time-to-emergency medical services arrival, and some cardiopulmonary resuscitation characteristics, but were similar in others, including time-to-intravenous/intrasosseous drug receipt. Overall hospital discharge survival was 23%. In comparison with placebo, discharge survival was significantly higher in recipients of intravenous amiodarone (adjusted risk ratio, 1.26 [95% CI, 1.06-1.50]; adjusted absolute survival difference, 5.5% [95% CI, 1.5-9.5]) and intravenous lidocaine (adjusted risk ratio, 1.21 [95% CI, 1.02-1.45]; adjusted absolute survival difference, 4.7% [95% CI, 0.7-8.8]); but not in recipients of intraosseous amiodarone (adjusted risk ratio, 0.94 [95% CI, 0.66-1.32]) or intraosseous lidocaine (adjusted risk ratio, 1.03 [95% CI, 0.74-1.44]). Survival to hospital admission also increased significantly when drugs were given intravenously but not intraosseously, and favored improved neurological outcome at discharge. There were no outcome differences between intravenous and intraosseous placebo, indicating that the access route itself did not demarcate patients with poor prognosis. The study was underpowered to assess intravenous/intraosseous drug interactions, which were not statistically significant.Conclusions: We found no significant effect modification by drug administration route for amiodarone or lidocaine in comparison with placebo during out-of-hospital cardiac arrest. However, point estimates for the effects of both drugs in comparison with placebo were significantly greater for the intravenous than for the intraosseous route across virtually all outcomes and beneficial only for the intravenous route. Given that the study was underpowered to statistically assess interactions, these findings signal the potential importance of the drug administration route during resuscitation that merits further investigation. [ABSTRACT FROM AUTHOR]

Background: Lidocaine has been the initial antiarrhythmic drug treatment recommended for patients with ventricular fibrillation that is resistant to conversion by defibrillator shocks. We performed a randomized trial comparing intravenous lidocaine with intravenous amiodarone as an adjunct to defibrillation in victims of out-of-hospital cardiac arrest. Methods: Patients were enrolled if they had out-of-hospital ventricular fibrillation resistant to three shocks, intravenous epinephrine, and a further shock; or if they had recurrent ventricular fibrillation after initially successful defibrillation. They were randomly assigned in a double-blind manner to receive intravenous amiodarone plus lidocaine placebo or intravenous lidocaine plus amiodarone placebo. The primary end point was the proportion of patients who survived to be admitted to the hospital. Results: In total, 347 patients (mean [±SD] age, 67±14 years) were enrolled. The mean interval between the time at which paramedics were dispatched to the scene of the cardiac arrest and the time of their arrival was 7±3 minutes, and the mean interval from dispatch to drug administration was 25±8 minutes. After treatment with amiodarone, 22.8 percent of 180 patients survived to hospital admission, as compared with 12.0 percent of 167 patients treated with lidocaine (P=0.009; odds ratio, 2.17; 95 percent confidence interval, 1.21 to 3.83). Among patients for whom the time from dispatch to the administration of the drug was equal to or less than the median time (24 minutes), 27.7 percent of those given amiodarone and 15.3 percent of those given lidocaine survived to hospital admission (P=0.05). Conclusions: As compared with lidocaine, amiodarone leads to substantially higher rates of survival to hospital admission in patients with shock-resistant out-of-hospital ventricular fibrillation. (N Engl J Med 2002;346:884-90.) [ABSTRACT FROM AUTHOR]

Background: Existing studies have shown conflicting results regarding the relationship of sex with survival after out of hospital cardiac arrest (OHCA). This systematic review evaluates the association of female sex with survival to discharge and survival to 30 days after non-traumatic OHCA.Methods: We searched Medline, Embase, CINAHL, Web of Science, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews from inception through June 2021 for studies evaluating female sex as a predictor of survival in adult patients with non-traumatic cardiac arrest. Random-effects inverse variance meta-analyses were performed to calculate pooled odds ratios (ORs) with 95% confidence intervals (CI). The GRADE approach was used to assess evidence quality.Results: Thirty studies including 1,068,788 patients had female proportion of 41%. There was no association for female sex with survival to discharge (OR 1.03, 95% CI 0.95-1.12; I2 = 89%). Subgroup analysis of low risk of bias studies demonstrated increased survival to discharge for female sex (OR 1.20, 95% CI 1.18-1.23; I2 = 0%) and with high certainty, the absolute increase in survival was 2.2% (95% CI 0.1-3.6%). Female sex was not associated with survival to 30 days post-OHCA (OR 1.02, 95% CI 0.92-1.14; I2 = 79%).Conclusions: In adult patients experiencing OHCA, with high certainty in the evidence from studies with low risk of bias, female sex had a small absolute difference for the outcome survival to discharge and no difference in survival at 30 days. Future models that aim to stratify risk of survival post-OHCA should focus on sex-specific factors as opposed to sex as an isolated prognostic factor. [ABSTRACT FROM AUTHOR]

Objectives: Targeted temperature management has been shown to improve survival with good neurological outcome in patients after out-of-hospital cardiac arrest. The optimal approach to inducing and maintaining targeted temperature management, however, remains uncertain. The objective of this study was to evaluate these processes of care with survival and neurological function in patients after out-of-hospital cardiac arrest. Design: An observational cohort study evaluating the association of targeted temperature management processes with survival and neurological function using bivariate and generalized estimating equation analyses. Setting: Thirty-two tertiary and community hospitals in eight urban and rural regions of southern Ontario, Canada. Patients: Consecutive adult (⩾ 18 yr) patients admitted between November 1, 2007, and January 31, 2012, and who were treated with targeted temperature management following nontraumatic out-of-hospital cardiac arrest. Interventions: Evaluate the association of targeted temperature management processes with survival and neurologic function using bivariate and generalized estimating equation analyses. Measurements and Main Results: There were 5,770 consecutive out-of-hospital cardiac arrest patients, of whom 747 (12.9%) were eligible and received targeted temperature management. Among patients with available outcome data, 365 of 738 (49.5%) survived to hospital discharge and 241 of 675 (35.7%) had good neurological outcomes. After adjusting for the Utstein variables, a higher temperature prior to initiation of targeted temperature management was associated with improved neurological outcomes (odds ratio, 1.27 per °C; 95% CI, 1.08-1.50; p = 0.004) and survival (odds ratio, 1.26 per °C; 95% CI, 1.09-1.46; p = 0.002). A slower rate of cooling was associated with improved neurological outcomes (odds ratio, 0.74 per °C/hr; 95% CI, 0.57-0.97; p = 0.03) and survival (odds ratio, 0.73 per °C/hr; 95% CI, 0.54-1.00; p = 0.049). Conclusions: A higher baseline temperature prior to initiation of targeted temperature management and a slower rate of cooling were associated with improved survival and neurological outcomes. This may reflect a complex relationship between the approach to targeted temperature management and the extent of underlying brain injury causing impaired thermoregulation in out-of-hospital cardiac arrest patients. [ABSTRACT FROM AUTHOR]

Background: Large animal studies are an important step in the translation pathway, but single laboratory experiments do not replicate the variability in patient populations. Our objective was to demonstrate the feasibility of performing a multicenter, preclinical, randomized, double-blinded, placebo-controlled cardiac arrest trial. We evaluated the effect of epinephrine on coronary perfusion pressure (CPP) as previous single laboratory studies have reported mixed results.Methods: Forty-five swine from 5 different laboratories (Ann Arbor, MI; Baltimore, MD; Los Angeles, CA; Pittsburgh, PA; Toronto, ON) using a standard treatment protocol. Ventricular fibrillation was induced and left untreated for 6 min before starting continuous cardiopulmonary resuscitation (CPR). After 2 min of CPR, 9 animals from each lab were randomized to 1 of 3 interventions given over 12 minutes: (1) Continuous IV epinephrine infusion (0.00375 mg/kg/min) with placebo IV normal saline (NS) boluses every 4 min, (2) Continuous placebo IV NS infusion with IV epinephrine boluses (0.015 mg/kg) every 4 min or (3) Placebo IV NS for both infusion and boluses. The primary outcome was mean CPP during the 12 mins of drug therapy.Results: There were no significant differences in mean CPP between the three groups: 14.4 ± 6.8 mmHg (epinephrine Infusion), 16.9 ± 5.9 mmHg (epinephrine bolus), and 14.4 ± 5.5 mmHg (placebo) (p = NS). Sensitivity analysis demonstrated inter-laboratory variability in the magnitude of the treatment effect (p = 0.004).Conclusion: This study demonstrated the feasibility of performing a multicenter, preclinical, randomized, double-blinded cardiac arrest trials. Standard dose epinephrine by bolus or continuous infusion did not increase coronary perfusion pressure during CPR when compared to placebo. [ABSTRACT FROM AUTHOR]

Abstract: Therapeutic hypothermia has become an accepted part of post-resuscitation care. Efforts to shorten the time from return of spontaneous circulation to target temperature have led to the exploration of different cooling techniques. Convective-immersion uses a continuous shower of 2°C water to rapidly induce hypothermia. The primary purpose of this multi-center trial was to evaluate the feasibility and speed of convective-immersion cooling in the clinical environment. The secondary goal was to examine the impact of rapid hypothermia induction on patient outcome. 24 post-cardiac arrest patients from 3 centers were enrolled in the study; 22 agreed to participate until the 6-month evaluations were completed. The median rate of cooling was 3.0°C/h. Cooling times were shorter than reported in previous studies. The median time to cool the patients to target temperature (<34°C) was 37min (range 14–81min); and only 27min in a subset of patients sedated with propofol. Survival was excellent, with 68% surviving to 6 months; 87% of survivors were living independently at 6 months. Conductive-immersion surface cooling using the ThermoSuit® System is a rapid, effective method of inducing therapeutic hypothermia. Although the study was not designed to demonstrate impact on outcomes, survival and neurologic function were superior to those previously reported, suggesting comparative studies should be undertaken. Shortening the delay from return of spontaneous circulation to hypothermic target temperature may significantly improve survival and neurologic outcome and warrants further study. [Copyright &y& Elsevier]

The DOSE VF randomized controlled trial (RCT) employed a pragmatic definition of refractory ventricular fibrillation (VF after three successive shocks). However, it remains unclear whether the underlying rhythm during the first three shocks was shock-refractory or recurrent VF. To explore the relationship between alternate defibrillation strategies employed during the DOSE VF RCT and the type of VF, either shock-refractory VF or recurrent VF, on patient outcomes. We performed a secondary analysis of the DOSE VF RCT. We categorized cases as shock-refractory or recurrent VF based on pre-randomization shocks (shocks 1–3). We then analyzed all subsequent (post-randomization) shocks to assess the impact of standard, vector change (VC) or double sequential external defibrillation (DSED) shocks on clinical outcomes employing logistic regression adjusted for Utstein variables, antiarrhythmics, and epinephrine. We included 345 patients; 60 (17%) shock-refractory VF, and 285 (83%) recurrent VF. Patients in recurrent VF had greater survival than shock-refractory VF (OR: 2.76 95% CI [1.04, 7.27]). DSED was superior to standard defibrillation for survival overall, and for patients with shock-refractory VF (28.6% vs 0%, p = 0.041) but not for those in recurrent VF. DSED was superior to standard defibrillation for return of spontaneous circulation (ROSC) and neurologic survival for shock-refractory and recurrent VF. VC defibrillation was not superior for survival or ROSC overall, for shock-refractory, or recurrent VF groups, but was superior for VF termination across all groups. DSED appears to be the superior defibrillation strategy in the DOSE VF trial, irrespective of whether the preceding VF is shock-refractory or recurrent. [ABSTRACT FROM AUTHOR]

Background: Studies examining gender-based differences in outcomes of patients experiencing out-of-hospital cardiac arrest have demonstrated that, despite a higher likelihood of return of spontaneous circulation, women do not have higher survival.Methods: Patients successfully resuscitated from out-of-hospital cardiac arrest enrolled in the CCC trial (Trial of Continuous or Interrupted Chest Compressions during CPR) were included. Hierarchical multivariable logistic regression models were constructed to evaluate the association between gender and survival after adjustment for age, gender, cardiac arrest rhythm, witnessed status, bystander cardiopulmonary resuscitation, episode location, epinephrine dose, emergency medical services response time, and duration of resuscitation. Do not resuscitate (DNR) and withdrawal of life-sustaining therapy (WLST) order status were used to assess whether differences in postresuscitation outcomes were modified by baseline prognosis. The analysis was replicated among ALPS trial (Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest) participants.Results: Among 4875 successfully resuscitated patients, 1825 (37.4%) were women and 3050 (62.6%) were men. Women were older (67.5 versus 65.3 years), received less bystander cardiopulmonary resuscitation (49.1% versus 54.9%), and had a lower proportion of cardiac arrests that were witnessed (55.1% versus 64.5%) or had shockable rhythm (24.3% versus 44.6%, P<0.001 for all). A significantly higher proportion of women received DNR orders (35.7% versus 32.1%, P=0.009) and had WLST (32.8% versus 29.8%, P=0.03). Discharge survival was significantly lower in women (22.5% versus 36.3%, P<0.001; adjusted odds ratio, 0.78 [95% CI, 0.66-0.93]; P=0.005). The association between gender and survival to discharge was modified by DNR and WLST order status such that women had significantly reduced survival to discharge among patients who were not designated DNR (31.3% versus 49.9%, P=0.005; adjusted odds ratio, 0.74 [95% CI, 0.60-0.91]) or did not have WLST (32.3% versus 50.7%, P=0.002; adjusted odds ratio, 0.73 [95% CI, 0.60-0.89]). In contrast, no gender difference in survival was noted among patients receiving a DNR order (6.7% versus 7.4%, P=0.90) or had WLST (2.8% versus 2.4%, P=0.93). Consistent patterns of association between gender and postresuscitation outcomes were observed in the secondary cohort.Conclusions: Among patients resuscitated after experiencing out-of-hospital cardiac arrest, discharge survival was significantly lower in women than in men, especially among patients considered to have a favorable prognosis. [ABSTRACT FROM AUTHOR]

Background: The management of out-of-hospital cardiac arrest (OHCA) patients requires the coordination of prehospital, in-hospital and post-discharge teams. Data reporting a comprehensive analysis of all costs associated with treating OHCA are scarce. We aimed to describe the total costs (and their components) related to the management of OHCA patients.Patient and Methods: We performed an analysis on a merged database of the Toronto Regional RescuNet Epistry database (prehospital data) and administrative population-based databases in Ontario. All non-traumatic OHCA patients over 18 years of age treated by the EMS between January 1, 2006, and March 31, 2014, were included in this study. The primary outcome was per patient longitudinal cumulative healthcare costs, from time of collapse to a maximum follow-up until death or 30 days after the event. We included all available cost sectors, from the perspective of the health system payer. We used multivariable generalized linear models with a logarithmic link and a gamma distribution to determine predictors of healthcare costs.Results: 25,826/44,637 patients were treated by EMS services for an OHCA (mostly male 64.4%, mean age 70.1). 11,727 (45%) were pronounced dead on scene, 8359 (32%) died in the emergency department, 3640 (14%) were admitted to hospital but died before day-30, and 2100 (8.1%) were still alive at day-30. Total cost was $690 [interquartile range (IQR) $308, $1742] per patient; ranging from $290 [IQR $188, $390] for patients who were pronounced on scene to $39,216 [IQR 21,802, 62,093] for patients who were still alive at day-30. In-hospital costs accounted for 93% of total costs. After adjustment for age and gender, rate of patient survival was the main driver of total costs: the rate ratio was 3.88 (95% confidence interval 3.80, 3.95), 49.46 and 148.89 for patients who died in the ED, patients who died after the ED but within 30 days, and patients who were still alive at day-30 compared to patients who were pronounced dead on scene, respectively. Factors independently associated with costs were the number of prehospital teams (rate ratio (RR) 5.50 [5.32, 5.67] for being treated by 4 teams vs. 1), the need for hospital transfer (RR 2.38 [2.01, 2.82]), coronary angiography (RR 1.43 [1.27, 1.62]) and targeted temperature management (RR 1.25 [1.09, 1.44]).Conclusion: Survival is the main driver of total costs of treating OHCA patients in a large Canadian health system. Inpatient costs accounted for the majority of the total costs; potentially modifiable factors include the number of prehospital teams that arrive to the scene of the arrest and the need for between-hospital transfers after successful resuscitation. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have shown significant neighbourhood level variation in out-of-hospital cardiac arrest (OHCA) incidence rates, however, few have provided an explanation for these disparities beyond traditional socioeconomic measures.Methods: This was a retrospective study using data from a large population-based OHCA database (Rescu Epistry). We included adults ≥20 years who experienced a non-traumatic OHCA and were treated by emergency medical services within Toronto, Canada between 2006-2012. The residential address of each OHCA patient was spatially mapped to 1 of 517 Toronto census tracts (CTs). Patient and CT level characteristics were included in multivariate regression models to assess their association with OHCA incidence per 100,000 persons.Results: Of the 7775 OHCAs occurring in the study area, 7692 (98.9%) were eligible for inclusion. OHCA incidence rates varied widely across CT quintiles, with rates differing almost 4-fold (109.1 per 100,000 yearly Q5 most deprived vs. 30.0 per 100,000 yearly Q1 least deprived p < 0.0001). Numerous areas of high incidence adjacent to areas of low incidence were observed. After adjustment, all variables except the Activity Friendly Index showed highly significant linear trends, with increasing age, sex ratio, diabetes prevalence, material deprivation and ethnic concentration being independently associated with increasing OHCA incidence. In contrast, we did not observe a linear relationship between high OHCA incidence and median household income.Conclusions: This study showed almost 4-fold OHCA incidence variability across a large metropolitan area. This variability was partially correlated with population and health data, but not typical socioeconomic predictors, such as median household income. [ABSTRACT FROM AUTHOR]

Animal studies suggest the efficacy of double sequential external defibrillation (DSED) may depend on the interval between the two shocks, or "DSED interval". No human studies have examined this concept. To determine the relationship between DSED interval and termination of ventricular fibrillation (VFT), return of spontaneous circulation (ROSC), survival to hospital discharge, and favourable neurological status (MRS ≤ 2) for patients in refractory VF. We performed a retrospective review of adult (≥18 years) out-of-hospital cardiac arrest between January 2015 and May 2022 with refractory VF who received ≥1 DSED shock. DSED interval was divided into four pre-defined categories. We examined the association between DSED interval and patient outcomes using general estimated equation logistic regression or Fisher's exact test. Among 106 included patients, 303 DSED shocks were delivered (median 2, IQR 1–3). DSED intervals of 75–125 ms (OR 0.39, 95% CI 0.16–0.98), 125–500 ms (OR 0.36, 95% CI 0.16–0.82), and >500 ms (OR 0.27, 95% CI 0.11–0.63) were associated with lower probability of VF termination compared to <75 ms interval. DSED interval of >75 ms was associated with lower probability of ROSC compared to <75 ms interval (OR 0.37, 95% CI 0.14–0.98). No association was noted between DSED interval and survival to hospital discharge or neurologic outcome. Among patients in refractory VF a DSED interval of less than 75 ms was associated with improved rates of VF termination and ROSC. No association was noted between DSED interval and survival to hospital discharge or neurologic outcome. [ABSTRACT FROM AUTHOR]

Background: Hypertrophic cardiomyopathy (HCM) is considered a leading cause of sudden cardiac death (SCD) in younger people. The incidence of HCM-related SCD and its relationship to exercise have not been well studied in large comprehensive studies outside of tertiary care settings. This study sought to estimate the incidence of HCM-related SCD and its association with exercise in a large unselected population.Methods: Using the Office of the Chief Coroner of Ontario database encompassing all deaths attended by the coroner, we identified all HCM-related SCDs in individuals 10 to 45 years of age between 2005 and 2016 (70 million person-years). Confirmation of HCM was based on typical macroscopic and microscopic features (definite HCM-related SCD). Sudden deaths with a prior clinical diagnosis of HCM but no autopsy were considered probable HCM-related SCDs. Cases with typical features but no myofiber disarray were considered possible HCM. The completeness of data was verified in a subset of patients in the Toronto area with the use of a registry of all emergency medical services-attended cardiac arrests, with an autopsy rate of 94%. To estimate the number of HCM-related aborted cardiac arrests and lives potentially saved by implantable cardioverter-defibrillators, all de novo implantations for secondary prevention and all implantations and appropriate shocks for primary prevention in patients with HCM 10 to 45 years of age, respectively, were identified with the use of a registry containing data on implantable cardioverter-defibrillator implantations from all implanting sites throughout Ontario.Results: Forty-four, 3, and 6 cases of definite, probable, and possible HCM-related SCDs, respectively, were identified, corresponding to estimated annual incidence rates of 0.31 per 1000 HCM person-years (95% CI, 0.24-0.44) for definite HCM-related SCD, 0.33 per 1000 HCM person-years (95% CI, 0.34-0.62) for definite or probable HCM-related SCD, and 0.39 per 1000 HCM person-years (95% CI, 0.28-0.49) for definite, probable, or possible HCM-related SCD (estimated 140 740 HCM person-years of observation). The estimated annual incidence rate for HCM-related SCD plus aborted cardiac arrest and HCM-related life-threatening arrhythmia (SCD, aborted cardiac arrest, and appropriate implantable cardioverter-defibrillator shocks) was 0.84 per 1000 HCM person-years (95% CI, 0.70-1.0). The majority (70%) of SCDs occurred in previously undiagnosed individuals. Most SCDs occurred during rest (64.8%) or light activity (18.5%).Conclusions: The incidence of HCM-related SCD in the general population 10 to 45 years of age is substantially lower than previously reported, with most cases occurring in previously undiagnosed individuals. SCDs are infrequently related to exercise. [ABSTRACT FROM AUTHOR]

Introduction: Although out-of-hospital cardiac arrest (OHCA) is thought of as a sudden event, recent studies suggest that many patients have symptoms or have sought medical attention prior to their arrest. Our objective was to evaluate patterns of healthcare utilization before OHCA.Methods: We conducted a population-based cohort study in Ontario, Canada, which included all patients ≥20 years, who suffered out-of-hospital cardiac arrest and transferred to an emergency department (ED) from 2007 to 2018. Measurements included emergency room assessments, hospitalizations and physician visits prior to arrest.Results: The cohort comprised 38,906 patients, their mean age was 66.5 years, and 32.7% were women. Rates of ED assessments and hospital admissions were relatively constant until 90 days prior to arrest where they markedly increased to the time before arrest. Within 90 days, rates of ED assessment, hospitalization, and primary care physician visit were 29.5%, 16.4%, and 70.1%, respectively. Cardiovascular conditions were diagnosed in 14.4% of ED visits, and 33.7% of hospitalizations in this time period. The largest age-difference was the mental and behavioural disorders within 90 days of OHCA in the ED, where rates were 12.2% among patients <65 years vs. 1.9% for patients ≥65 years.Conclusions: In contrast to the conventional wisdom that OHCA occurs without prior contacts to the health care system, we found that more than 1 in 4 patients were assessed in the ED prior within 90 days of their arrest. Identification of warning signs of OHCA may allow future development of prevention strategies. [ABSTRACT FROM AUTHOR]

Objectives: Epinephrine is routinely administered to sudden cardiac arrest patients during resuscitation, but the neurologic effects on patients treated with epinephrine are not well understood. This study aims to assess the cerebral oxygenation and metabolism during ventricular fibrillation cardiac arrest, cardiopulmonary resuscitation, and epinephrine administration.Design: To investigate the effects of equal dosages of IV epinephrine administrated following sudden cardiac arrest as a continuous infusion or successive boluses during cardiopulmonary resuscitation, we monitored cerebral oxygenation and metabolism using hyperspectral near-infrared spectroscopy.Settings: A randomized laboratory animal study.Subjects: Nine healthy pigs.Interventions: None.Measurements and Main Results: Our study showed that although continuous epinephrine administration had no significant impact on overall cerebral hemodynamics, epinephrine boluses transiently improved cerebral oxygenation (oxygenated hemoglobin) and metabolism (cytochrome c oxidase) by 15% ± 6.7% and 49% ± 18%, respectively (p < 0.05) compared with the baseline (untreated) ventricular fibrillation. Our results suggest that the effects of epinephrine diminish with successive boluses as the impact of the third bolus on brain oxygen metabolism was 24.6% ± 3.8% less than that of the first two boluses.Conclusions: Epinephrine administration by bolus resulted in transient improvements in cerebral oxygenation and metabolism, whereas continuous epinephrine infusion did not, compared with placebo. Future studies are needed to evaluate and optimize the use of epinephrine in cardiac arrest resuscitation, particularly the dose, timing, and mode of administration. [ABSTRACT FROM AUTHOR]

Aims: Although the prevention and treatment of cardiovascular conditions have significantly improved over the past decade, whether they have reduced the incidence of sudden cardiac death (SCD) is not known. We sought to evaluate the temporal trends of SCD in a large unselected population.Methods: We conducted a population-based cohort study using multiple linked longitudinal data in Ontario Canada. We included patients aged 35-74 years who had SCD from April 1st 2003 to March 31st 2014. SCD was defined as those who died of cardiac causes outside of the hospital or the emergency department, and had no recent hospitalization, no serious illness, and who were not residing in long-term care facilities.Results: We identified 36,334 patients who fulfilled criteria for SCD. The overall age and sex-standardized rate of SCD declined from 57.9/100,000 in fiscal year 2003 to 42.4/100,000 in 2013. Men and women had similar declining trends in SCD incidence. Larger reductions were seen among the older age groups. Patients who had prior heart failure experienced the largest decline in SCD incidence from 829/100,000 to 533/100,000 from 2003 to 2013. Patients who had prior myocardial infarction also had significant reduction from 484/100,000 to 381/100,000. In contrast, individuals with cardiac risk factors without disease had much smaller declines in SCD incidence.Conclusions: Although significant progress to reduce SCD among patients with cardiac conditions was made in the past decade, additional effort should focus on the prevention of SCD in individuals without heart disease. [ABSTRACT FROM AUTHOR]

Background: The incidence of sudden cardiac arrest during participation in sports activities remains unknown. Preparticipation screening programs aimed at preventing sudden cardiac arrest during sports activities are thought to be able to identify at-risk athletes; however, the efficacy of these programs remains controversial. We sought to identify all sudden cardiac arrests that occurred during participation in sports activities within a specific region of Canada and to determine their causes.Methods: In this retrospective study, we used the Rescu Epistry cardiac arrest database (which contains records of every cardiac arrest attended by paramedics in the network region) to identify all out-of-hospital cardiac arrests that occurred from 2009 through 2014 in persons 12 to 45 years of age during participation in a sport. Cases were adjudicated as sudden cardiac arrest (i.e., having a cardiac cause) or as an event resulting from a noncardiac cause, on the basis of records from multiple sources, including ambulance call reports, autopsy reports, in-hospital data, and records of direct interviews with patients or family members.Results: Over the course of 18.5 million person-years of observation, 74 sudden cardiac arrests occurred during participation in a sport; of these, 16 occurred during competitive sports and 58 occurred during noncompetitive sports. The incidence of sudden cardiac arrest during competitive sports was 0.76 cases per 100,000 athlete-years, with 43.8% of the athletes surviving until they were discharged from the hospital. Among the competitive athletes, two deaths were attributed to hypertrophic cardiomyopathy and none to arrhythmogenic right ventricular cardiomyopathy. Three cases of sudden cardiac arrest that occurred during participation in competitive sports were determined to have been potentially identifiable if the athletes had undergone preparticipation screening.Conclusions: In our study involving persons who had out-of-hospital cardiac arrest, the incidence of sudden cardiac arrest during participation in competitive sports was 0.76 cases per 100,000 athlete-years. The occurrence of sudden cardiac arrest due to structural heart disease was uncommon during participation in competitive sports. (Funded by the National Heart, Lung, and Blood Institute and others.). [ABSTRACT FROM AUTHOR]

Background: Sodium bicarbonate (SB) is widely used for resuscitation in out-of- hospital cardiac arrest (OHCA); however, its effect on long term outcomes is unclear.Methods: From 2005-2016, we prospectively conducted a province-wide population-based observational study including adult non-traumatic OHCA patients managed by paramedics. SB was administered by paramedics based on their clinical assessments. To examine the association of SB administration and survival and favorable neurological outcome to hospital discharge, defined as modified Rankin scale of 3 or less, we performed a multivariable logistic regression analysis: (1) within propensity score matched comparison groups, and; (2) within the full cohort with missing variables addressed by multiple imputation techniques.Results: Of 15 601 OHCA patients, 13,865 were included in this study with 5165 (37.3%) managed with SB. In the SB treated group, 118 (2.3%) patients survived and 62 (1.2%) had favorable neurological outcomes to hospital discharge, compared to 1699 (19.8%) and 831 (10.6%) in the non-SB treated group, respectively. In the 1:1 propensity matched cohort including 5638 OHCA patients, SB was associated with decreased probability of outcomes (adjusted OR for survival: 0.64, 95% CI 0.45-0.91, and adjusted OR for favorable neurological outcome: 0.59, 95% CI 0.39-0.88, respectively). The association remained consistent in the multiply imputed cohort (adjusted OR 0.48, 95 CI 0.36-0.64, and adjusted OR 0.54, 95% CI 0.38-0.76, respectively).Conclusions: In OHCA patients, prehospital SB administration was associated with worse survival rate and neurological outcomes to hospital discharge. [ABSTRACT FROM AUTHOR]

Aim: To use a novel methodology to assess the incidence and specific causes of Out-of-Hospital Cardiac Arrest (OHCA) within a young urban cohort.Methods: All EMS attended OHCA patients in a large urban area, between 2009 and 2012, aged 2-45 years, treated or untreated, who died or survived, and that were designated as "no obvious cause" etiology by trained data abstractors were included. Using multisource (medical and coroner) records, an expert panel adjudicated the causes of the OHCAs as: confirmed cardiac causes, confirmed non- cardiac causes, and other causes.Results: Of a total of 1993 cases EMS designated as "no obvious cause", only 29.9% (595/1993) were due to confirmed cardiac causes; the rest were due to other causes (non-cardiac etiologies): confirmed drug overdose (n=624), trauma (n=108), cancer (n=69), complex chronic care (n=65) and non-cardiac acute illness - mostly vascular, infectious, and metabolic (n=376). The annual incidence rate of "no obvious cause" OHCAs after initial field classification was 12.97/100,000 pt. years (95% CI 12.40, 13.50), compared to 3.87/100,000 pt. years (95% CI 3.56, 4.18) for the confirmed cardiac OHCAs after adjudication. The predominant underlying etiologies of confirmed cardiac OHCAs were coronary heart disease and structural heart disease.Conclusions: In young adults with OHCA, confirmed cardiac causes were responsible in a minority of cases, and they differed in presentation from those with confirmed non- cardiac causes. Establishing rigorous case ascertainment strategies with linkage to multiple data sources will facilitate a more reliable evaluation of the causes of these events. [ABSTRACT FROM AUTHOR]

Aims: Improvement in resuscitation efforts has translated to an increasing number of survivors after out-of-hospital cardiac arrest (OHCA). Our objectives were to assess the long-term outcomes and predictors of mortality for patients who survived OHCA.Methods: We conducted a population-based cohort study linking the Toronto RescuNET cardiac arrest database with administrative databases in Ontario, Canada. We included patients with non-traumatic OHCA from December 1, 2005 to December 31, 2014. The primary outcomes were mortality at 1 year and 3 years. Cox proportional hazard models were constructed to evaluate the predictors of mortality.Results: Among the 28,611 OHCA patients who received treatment at the scene of arrest, 1591 patients survived to hospital discharge. During hospitalization, 36% received coronary revascularizations and 27% received an implantable cardioverter defibrillator. At one year after discharge, 12.6% of patients had died and 37.3% were readmitted. At 3 years, mortality rate was 20% and all-cause readmission rate was 54.1%. Older age and a history of cancer were associated with higher risk of 3-year mortality. Shockable rhythm at presentation (hazard ratio [HR] 0.62, 95% CI 0.45-0.85), use of coronary revascularization (HR 0.37, 95% CI 0.28-0.51) or implantable cardioverter defibrillator (HR 0.28, 95% CI 0.20-0.41) was associated with substantially lower 3-year mortality. Prior cardiac conditions and other arrest characteristics were not associated with long-term mortality.Conclusions: Survivors of OHCA face significant morbidity and mortality after hospital discharge. Clinical trials are needed to evaluate the potential benefits of invasive cardiac procedures in OHCA survivors. [ABSTRACT FROM AUTHOR]

Background: The role of Troponin (Tn) levels in the management of patients post out-of-hospital cardiac arrest (OHCA) is unclear.Methods: All OHCA patients enrolled in the Resuscitation Outcomes Consortium Prehospital Resuscitation using an IMpedance valve and Early versus Delayed analysis trial and admitted to hospital with a Tn level and a 12-lead electrocardiogram were stratified by ST elevation (STE) or no STE in a regression model for survival to discharge adjusted for Utstein predictors and site.Results: Of the 15,617 enrolled OHCA patients, 4118 (26%) survived to admission to hospital; 17% (693) were STE and 77% (3188) were no STE with 6% unknown; 83% (3460) had at least one Tn level. Reperfusion rates were higher when Tn level >2ng/ml (p>0.1ng/ml) improved with a diagnostic cardiac catheterization (p<0.001).Conclusions: Elevated Tn levels >2ng/ml were associated with improved survival to discharge in patients post OHCA with STE. Survival in patients with no STE and Tn values >0.1ng/ml was higher when associated with diagnostic cardiac catheterization or treated with reperfusion or revascularization. [ABSTRACT FROM AUTHOR]

Objective: Patient volume as a surrogate for institutional experience has been associated with quality of care indicators for a variety of illnesses. We evaluated the association between hospital experience with comatose out-of-hospital cardiac arrest (OHCA) patients and important care processes.Methods: This was a population-based, retrospective cohort study using data from 37 hospitals in Southern Ontario from 2007 to 2013. We included adults with atraumatic OHCA who were comatose on emergency department arrival and survived at least 6h. We excluded patients with a Do-Not-Resuscitate order or severe bleeding within 6h of hospital arrival. Multi-level logistic regression models estimated the association between average annual hospital volume of OHCA patients and outcomes. The primary outcome was successful targeted temperature management (TTM) and secondary outcomes included TTM initiation, premature withdrawal of life-sustaining therapy, and survival with good neurologic function.Results: Our analysis included 2723 patients. For every increase of 10 in the average annual volume of eligible patients, the adjusted odds increased by 30% for successful TTM (OR 1.29, 95% CI 1.03-1.62) and by 38% for initiating TTM (OR 1.38, 95% CI 1.11-1.72). No significant association between patient volume and other secondary outcomes was observed.Conclusions: Patients arriving at hospitals with more experience treating comatose post cardiac arrest patients are more likely to have TTM initiated and to successfully reach target temperature. Our findings have implications for regional systems of care and knowledge translation efforts aiming to improve quality of care for this patient population. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether a Post-Arrest Consult Team improved care and outcomes for patients with out-of-hospital cardiac arrest.Design: Prospective cohort study of Post-Arrest Consult Team implementation at two hospitals, with concurrent controls from 27 others.Setting: Twenty-nine hospitals within the Strategies for Post-Arrest Care Network of Southern Ontario, Canada.Patients: We included comatose adult nontraumatic out-of-hospital cardiac arrest patients surviving more than or equal to 6 hours after emergency department arrival who had no contraindications to targeted temperature management.Intervention: The Post-Arrest Consult Team was an advisory consult service to improve 1) targeted temperature management, 2) assessment for percutaneous coronary intervention, 3) electrophysiology assessment, and 4) appropriately delayed neuroprognostication.Measurements and Main Results: We used generalized linear mixed models to explore the association between Post-Arrest Consult Team implementation and performance of targeted processes. We included 1,006 patients. The Post-Arrest Consult Team was associated with a significant reduction over time in rates of withdrawal of life-sustaining therapy within 72 hours of emergency department arrival on the basis of predictions of poor neurologic prognosis (ratio of odds ratios, 0.13; 95% CI, 0.02-0.98). Post-Arrest Consult Team was not associated with improved successful targeted temperature management (ratio of odds ratios, 0.91; 95% CI, 0.31-2.65), undergoing angiography (ratio of odds ratios, 1.91; 95% CI, 0.17-21.04), receiving electrophysiology consultation (ratio of odds ratios, 0.93; 95% CI, 0.11-8.16), or functional survival (ratio of odds ratios, 0.75; 95% CI, 0.19-2.94).Conclusions: Implementation of a Post-Arrest Consult Team reduced premature withdrawal of life-sustaining therapy but did not improve rates of successful targeted temperature management, coronary angiography, formal electrophysiology assessments, or functional survival for comatose patients after out-of-hospital cardiac arrest. [ABSTRACT FROM AUTHOR]

Rationale: International guidelines recommend use of targeted temperature management following resuscitation from out-of-hospital cardiac arrest. This treatment, however, is often neglected or delayed. Objective: To determine whether multifaceted quality improvement interventions would increase the proportion of eligible patients receiving successful targeted temperature management. Setting: A network of 6 regional emergency medical services systems and 32 academic and community hospitals serving a population of 8.8 million people providing post arrest care to out-of- hospital cardiac arrest. Interventions: Comparing interventions improve the implementation of targeted temperature management post out-of-hospital cardiac arrest through passive (education, generic protocol, order set, local champions) versus additional active quality improvement interventions (nurse specialist providing site-specific interventions, monthly audit-feedback, network educational events, internet blog) versus no intervention (baseline standard of care). Measurements and Main Results: The primary process outcome was proportion of eligible patients receiving successful targeted temperature management, defined as a target temperature of 32-34°C within 6 hours of emergency department arrival. Secondary clinical outcomes included survival and neurological outcome at hospital discharge. Four thousand three hundred seventeen out-of-hospital cardiac arrests were transported to hospital; 1,737 (40%) achieved spontaneous circulation, and 934 (22%) were eligible for targeted temperature management. After accounting for secular trends, patients admitted during the passive quality improvement phase were more likely to achieve successful targeted temperature management compared with those admitted during the baseline period (25.7% passive vs 9.0% baseline; odds ratio, 2.76; 95% CI, 1.76-4.32; p < 0.001). Active quality improvement interventions conferred no additional improvements in rates of successful targeted temperature management (26.9% active vs 25.7% passive; odds ratio, 0.96; 95% CI, 0.63-1.45; p = 0.84). Despite a significant increase in rates of successful targeted temperature management, survival to hospital discharge was unchanged. Conclusion: Simple quality improvement interventions significantly increased the rates of achieving successful targeted temperature management following out-of-hospital cardiac arrest in a large network of hospitals but did not improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Background--Out-of-hospital cardiac arrest (OHCA) is associated with a poor prognosis and poses a significant burden to the healthcare system, but few studies have evaluated whether OHCA incidence and survival have changed over time. Methods and Results--A population-based cohort study was conducted, including 34 291 OHCA patients >20 years of age who were transported alive to the emergency department of an acute-care hospital from April 1, 2002, to March 31, 2012, in Ontario, Canada. Patients with life-threatening trauma and those who died before hospital arrival were excluded. The overall age- and sex-standardized incidence of OHCA patients who were transported alive was 36 cases per 100 000 persons and did not significantly change over the study period. Cardiac risk factor prevalence increased significantly, whereas the rate of most cardiovascular conditions decreased significantly. The 30-day survival improved from 9.4% in 2002 to 13.6% in 2011; 1-year survival improved from 7.7% to 11.8% (P<0.001). Patients hospitalized in 2011 were significantly more likely to survive 30 days (adjusted odds ratio, 1.47 [95% CI, 1.22--1.77]) and 1 year (adjusted odds ratio, 1.55 [95% CI, 1.27--1.91]) compared with 2002. A significant interaction between temporal trends in survival improvement and age group was observed in which the improvement in survival was largest in the youngest age groups. Conclusions--OHCA patients who were transported alive are increasingly likely to have cardiovascular risk factors but less likely to have previous cardiovascular conditions. The overall incidence of OHCA patients transported to hospital alive did not change over the past decade. Short- and longer-term survival after OHCA has substantially improved, with younger patients experiencing the greatest improvement. [ABSTRACT FROM AUTHOR]

Background--Resistant ventricular fibrillation, refibrillation, and diminished myocardial contractility are important factors leading to poor survival after cardiac arrest. We hypothesized that dantrolene improves survival after ventricular fibrillation (VF) by rectifying the calcium dysregulation caused by VE Methods and Results--VF was induced in 26 Yorkshire pigs for 4 minutes. Cardiopulmonary resuscitation was then commenced for 3 minutes, and dantrolene or isotonic saline was infused at the onset of cardiopulmonary resuscitation. Animals were defibrillated and observed for 30 minutes. To study the effect of VF on calcium handling and its modulation by dantrolene, hearts from 14 New Zealand rabbits were Langendorff-perfused. The inducibility of VF after dantrolene administration was documented. Optical mapping was performed to evaluate diastolic spontaneous calcium elevations as a measure of cytosolic calcium leak. The sustained return of spontaneous circulation (systolic blood pressure ≥60 mm Hg) was achieved in 85% of the dantrolene group in comparison with 39% of controls (P=0.02). return of spontaneous circulation was achieved earlier in dantrolene-treated pigs after successful defibrillation (21±6 s versus 181±57 s in controls, P=0.005). The median number of refibrillation episodes was lower in the dantrolene group (0 versus 1, P=0.04). In isolated rabbit hearts, the successful induction of VF was achieved in 83% of attempts in controls versus 41% in dantrolene-treated hearts (P=0.007). VF caused diastolic calcium leaks in the form of spontaneous calcium elevations. Administration of 20 µmol/L dantrolene significantly decreased spontaneous calcium elevation amplitude versus controls. (0.024±0.013 versus 0.12±0.02 arbitrary unit [200-ms cycle length], P=0.001 ). Conclusions--Dantrolene infusion during cardiopulmonary resuscitation facilitates successful defibrillation, improves hemodynamics postdefibrillation, decreases refibrillation, and thus improves survival after cardiac arrest. The effects are mediated through normalizing VF-induced dysfunctional calcium cycling. [ABSTRACT FROM AUTHOR]

Background: Cardiac arrest is an important cause of mortality. Cardiopulmonary resuscitation (CPR) improves survival, however, delivery of effective CPR can be challenging and combining effective chest compressions with ventilation, while avoiding over-ventilation is difficult. We hypothesized that ventilation with a pneumatically powered, automatic ventilator (Oxylator®) can provide adequate ventilation in a model of cardiac arrest and improve the consistency of ventilations during CPR. Methods/results: Twelve pigs (∼40kg, either sex) underwent 3 episodes each of cardiac arrest and resuscitation consisting of 30s of untreated ventricular fibrillation, followed by 5min of CPR, defibrillation, and ∼30min of recovery. During CPR in each episode, pigs were ventilated in 1 of 3 ways in random balanced order: manual ventilation using AMBU bag (12breaths/min), low pressure Oxylator® (maximum airway pressure 15cmH2O with 20L/min constant flow in automatic mode [Ox15/20]), or high pressure Oxylator® (maximum airway pressure 20cmH2O with 30L/min constant flow in automatic mode [Ox20/30]). During CPR, both Ox15/20 and Ox20/30 resulted in higher levels of positive end expiratory pressure than manual ventilation. Ox15/20 ventilation also resulted in higher arterial pCO2 than manual ventilation. Ox20/30 ventilation yielded higher arterial pO2 and a lower arterial–alveolar gradient than manual ventilation. All pigs were successfully defibrillated, and no measured haemodynamic variables were different between the groups. Conclusion: Ventilation with an automatic ventilation device during CPR is feasible and provides adequate ventilation and comparable haemodynamics when compared to manual bag ventilation. [ABSTRACT FROM AUTHOR]

Objectives: We developed and tested a training method for basic life support incorporating defibrillator feedback during simulated cardiac arrest (CA) to determine the impact on the quality and retention of CPR skills. Methods: 298 subjects were randomized into 3 groups. All groups received a 2h training session followed by a simulated CA test scenario, immediately after training and at 3 months. Controls used a non-feedback defibrillator during training and testing. Group 1 was trained and tested with an audiovisual feedback defibrillator. During training, Group 1 reviewed quantitative CPR data from the defibrillator. Group 2 was trained as per Group 1, but was tested using the non-feedback defibrillator. The primary outcome was difference in compression depth between groups at initial testing. Secondary outcomes included differences in rate, depth at retesting, compression fraction, and self-assessment. Results: Groups 1 and 2 had significantly deeper compressions than the controls (35.3±7.6mm, 43.7±5.8mm, 42.2±6.6mm for controls, Groups 1 and 2, P =0.001 for Group 1 vs. controls; P =0.001 for Group 2 vs. controls). At three months, CPR depth was maintained in all groups but remained significantly higher in Group 1 (39.1±9.9mm, 47.0±7.4mm, 42.2±8.4mm for controls, Groups 1 and 2, P =0.001 for Group 1 vs. control). No significant differences were noted between groups in compression rate or fraction. Conclusions: A simplified 2h training method using audiovisual feedback combined with quantitative review of CPR performance improved CPR quality and retention of these skills. [ABSTRACT FROM AUTHOR]

Abstract: Background: Despite the publication and dissemination of the Advanced Cardiac Life Support guidelines, variability in the use of drugs during resuscitation from out-of-hospital cardiac arrest may exist between different Emergency Medical Services throughout North America. The purpose of this study was to characterize the use of such drugs and evaluate their relationship to cardiac arrest outcomes. Methods and results: The Resuscitation Outcomes Consortium Registry-Cardiac Arrest collects out-of-hospital cardiac arrest data from 264 Emergency Medical Services agencies in 11 geographical locations in the US and Canada. Multivariable logistic regression was used to assess the association between drug use, characteristics of the cardiac arrest and a pulse at emergency department arrival and survival to discharge. A total of 16,221 out-of-hospital cardiac arrests were attended by 74 Emergency Medical Services agencies. There was a considerable variability in the administration of amiodarone and lidocaine for the treatment of shock resistant ventricular tachycardia/ventricular fibrillation. For non-shockable rhythms, atropine use ranged from 29 to 95% and sodium bicarbonate use ranged from 0.2 to 73% across agencies in the 89% of agencies that used the drug. Epinephrine use ranged from 57 to 98% within agencies. Neither lidocaine nor amiodarone was associated with a survival benefit while there was an inverse relationship between the administration of epinephrine, atropine and sodium bicarbonate and survival to hospital discharge. Conclusions: There is considerable variability among Emergency Medical Services agencies in their use of pharmacological therapy for out-of-hospital cardiac arrests which may be resolved by performing large randomized trials examining effects on survival. [Copyright &y& Elsevier]

Background: The impedance threshold device (ITD) is designed to enhance venous return and cardiac output during cardiopulmonary resuscitation (CPR) by increasing the degree of negative intrathoracic pressure. Previous studies have suggested that the use of an ITD during CPR may improve survival rates after cardiac arrest. Methods: We compared the use of an active ITD with that of a sham ITD in patients with out-of-hospital cardiac arrest who underwent standard CPR at 10 sites in the United States and Canada. Patients, investigators, study coordinators, and all care providers were unaware of the treatment assignments. The primary outcome was survival to hospital discharge with satisfactory function (i.e., a score of ≤3 on the modified Rankin scale, which ranges from 0 to 6, with higher scores indicating greater disability). Results: Of 8718 patients included in the analysis, 4345 were randomly assigned to treatment with a sham ITD and 4373 to treatment with an active device. A total of 260 patients (6.0%) in the sham-ITD group and 254 patients (5.8%) in the active-ITD group met the primary outcome (risk difference adjusted for sequential monitoring, −0.1 percentage points; 95% confidence interval, −1.1 to 0.8; P=0.71). There were also no significant differences in the secondary outcomes, including rates of return of spontaneous circulation on arrival at the emergency department, survival to hospital admission, and survival to hospital discharge. Conclusions: Use of the ITD did not significantly improve survival with satisfactory function among patients with out-of-hospital cardiac arrest receiving standard CPR. (Funded by the National Heart, Lung, and Blood Institute and others; ROC PRIMED ClinicalTrials.gov number, NCT00394706.) [ABSTRACT FROM PUBLISHER]

Abstract: Introduction: We examined the effect of the 2005 American Heart Association guidelines on survival in the Resuscitation Outcomes Consortium (ROC) Cardiac Arrest Epistry. Methods: We surveyed 174 EMS agencies from 8 of 10 ROC sites to determine 2005 AHA guideline implementation, or crossover, date. Two sites with 2005 compatible treatment algorithms prior to guideline release, and agencies that did not adopt the new guidelines during the study period were excluded. Non-traumatic adult cardiac arrests that were not witnessed by EMS, and did not have do not resuscitate orders were included. A linear mixed effects model was applied for survival controlling for time and agency. The “crossover” date was added to the model to determine the effect of the 2005 guidelines. Results: Of 174 agencies, 85 contributed cases to both cohorts during the 18 month period between 2005/12/01 and 2007/05/31. Of 7779 cases, 5054 occurred during the 13 month (median) interval before crossover and 2725 occurred in the five month (median) interval after crossover. The overall survival rate was 6.1%; 5.8% in the old cohort vs. 6.5%, p =0.23. For VF/VT patients, survival was 14.6% vs. 18.0%, p =0.063. Our model estimated no increase in survival over time (monthly OR 1.014, 95% CI 0.988, 1.041, p =0.28). Conclusion: This study found no significant change in survival rate over time in the early months after implementation. Further longitudinal study is needed to determine the full impact of the guidelines on survival and methods to translate knowledge quickly and effectively in EMS. [Copyright &y& Elsevier]