Trends in presumed drug overdose out-of-hospital cardiac arrests in San Francisco, 2015-2023.

INTRODUCTION: Estimates of the prevalence of drug-related out of hospital cardiac arrest (OHCA) vary, ranging from 1.8% to 10.0% of medical OHCA. However, studies conducted prior to the recent wave of fentanyl deaths likely underestimate the current prevalence of drug-related OHCA. We evaluated recent trends in drug-related OHCA, hypothesizing that the proportion of presumed drug-related OHCA treated by emergency medical services (EMS) has increased since 2015. METHODS: We conducted a retrospective analysis of OHCA patients treated by EMS providers in San Francisco, California between 2015 and 2023. Participants included OHCA cases in which resuscitation was attempted by EMS. The study exposure was the year of arrest. Our primary outcome was the occurrence of drug-related OHCA, defined as the EMS impression of OHCA caused by a presumed or known overdose of medication(s) or drug(s). RESULTS: From 2015 to 2023, 5044 OHCA resuscitations attended by EMS (average 561 per year) met inclusion criteria. The median age was 65 (IQR 50-79); 3508 (69.6%) were male. The EMS impression of arrest etiology was drug-related in 446/5044 (8.8%) of OHCA. The prevalence of presumed drug-related OHCA increased significantly each year from 1% in 2015 to 17.6% in 2023 (p-value for trend = 0.0001). After adjustment, presumed drug-related OHCA increased by 30% each year from 2015-2023. CONCLUSION: Drug-related OHCA is an increasingly common etiology of OHCA. In 2023, one in six OHCA was presumed to be drug related. Among participants less than 60 years old, one in three OHCA was presumed to be drug related.

The association of clinical, treatment, and demographic characteristics with rearrest in a national dataset.

INTRODUCTION: Following initial resuscitation from out-of-hospital cardiac arrest, rearrest frequently occurs and has been associated with adverse outcomes. We aimed to identify clinical, treatment, and demographic characteristics associated with prehospital rearrest at the encounter and agency levels. METHODS: Adult non-traumatic cardiac arrest patients who achieved ROSC following EMS resuscitation in the 2018-2021 ESO annual datasets were included in this study. Patients were excluded if they had a documented DNR/POLST or achieved ROSC after bystander CPR only. Rearrest was defined as post-ROSC CPR initiation, administration of ≥ 1 milligram of adrenaline, defibrillation, or a documented non-perfusing rhythm on arrival at the receiving hospital. Multivariable logistic regression modeling was used to evaluate the association between rearrest and case characteristics. Linear regression modeling was used to evaluate the association between agency-level factors (ROSC rate, scene time, and scene termination rate), and rearrest rate. RESULTS: Among the 53,027 cases included, 16,116 (30.4%) experienced rearrest. Factors including longer response intervals, longer 'low-flow' intervals, unwitnessed OHCA, and a lack of bystander CPR were associated with rearrest. Among agencies that treated ≥ 30 patients with outcome data, the agency-level rate of rearrest was inversely associated with agency-level rate of survival to discharge to home (R2 = -0.393, p < 0.001). CONCLUSIONS: This multiagency retrospective study found that factors associated with increased ischaemic burden following OHCA were associated with rearrest. Agency-level rearrest frequency was inversely associated with agency-level survival to home. Interventions that decrease the burden of ischemia sustained by OHCA patients may decrease the rate of rearrest and increase survival.

The Association of Prehospital End-Tidal Carbon Dioxide with Survival Following Out-of-Hospital Cardiac Arrest.

OBJECTIVE: End tidal carbon dioxide (ETCO2) is often used to assess ventilation and perfusion during cardiac arrest resuscitation. However, few data exist evaluating the relationship between ETCO2 values and mortality in the context of contemporary resuscitation practices. We aimed to explore the association between ETCO2 and mortality following out-of-hospital cardiac arrest (OHCA). METHODS: We used the 2018-2021 ESO annual datasets to query all non-traumatic OHCA patients with attempted resuscitation. Patients with documented DNR/POLST, EMS-witnessed arrest, ROSC after bystander CPR only, or < 2 documented ETCO2 values were excluded. The lowest and highest ETCO2 values recorded during the total prehospital interval, in addition to the pre- and post-ROSC intervals for resuscitated patients, were calculated. Multivariable logistic regression models adjusted for age, sex, initial rhythm, witnessed status, bystander CPR, etiology, OHCA location, sodium bicarbonate administration, number of milligrams of epinephrine administered, and response interval were used to evaluate the association between measures of ETCO2 and mortality. RESULTS: Hospital outcome data were available for 14,122 patients, and 2,209 (15.6%) were classified as surviving to discharge. Compared to patients with maximum prehospital ETCO2 values of 30-40 mmHg, odds of mortality were increased for patients with maximum prehospital ETCO2 values of <20 mmHg (aOR: 3.5 [2.1, 5,9]), 20-29 mmHg (aOR: 1.5 [1.1, 2.1]), and >50 mmHg (aOR: 1.5 [1.2, 1.8]). After 20 minutes of ETCO2 monitoring, <12% of patients had ETCO2 values <10 mmHg. This cutpoint was 96.7% specific and 6.9% sensitive for mortality. CONCLUSION: In this dataset, both high and low ETCO2 values were associated with increased mortality. Contemporary resuscitation practices may make low ETCO2 values uncommon, and field termination decision algorithms should not use ETCO2 values in isolation.

The Association of Combined Prehospital Hypotension and Hypoxia with Outcomes following Out-of-Hospital Cardiac Arrest Resuscitation.

BACKGROUND: Prehospital post-resuscitation hypotension and hypoxia have been associated with adverse outcomes in the context of out-of-hospital cardiac arrest (OHCA). We aimed to investigate the association between clinical outcomes and post-resuscitation hypoxia alone, hypotension alone, and combined hypoxia and hypotension. METHODS: We used the 2018-2021 ESO annual datasets to conduct this study. All EMS-treated non-traumatic OHCA patients who had a documented prehospital return of spontaneous circulation (ROSC) and two or more SpO2 readings and systolic blood pressures recorded were evaluated for inclusion. Patients who were less than 18 years of age, pregnant, had a do-not-resuscitate order or similar, achieved ROSC after bystander CPR only, or had an EMS-witnessed cardiac arrest were excluded. Multivariable logistic regression adjusted for standard Utstein factors and highest prehospital Glasgow Coma Scale (GCS) score was used to investigate the association between hypoxia, hypotension, and outcomes. RESULTS: We analyzed data for 17,943 patients, of whom 3,979 had hospital disposition data. Hypotension and hypoxia were not documented in 1,343 (33.8%) patients, 1,144 (28.8%) had only hypoxia documented, 507 (12.7%) had only hypotension documented, and 985 (24.8%) had both hypoxia and hypotension documented. In comparison to patients who did not have documented hypotension or hypoxia, patients who had documented hypoxia (aOR: 1.76 [1.38, 2.24]), documented hypotension (aOR: 3.00 [2.15, 4.18]), and documented hypoxia and hypotension combined (aOR: 4.87 [3.63, 6.53]) had significantly increased mortality. The relationship between mortality and vital sign abnormalities (hypoxia and hypotension > hypotension > hypoxia) was observed in every evaluated subgroup. CONCLUSIONS: In this large dataset, hypotension and hypoxia were independently associated with mortality both alone and in combination. Compared to patients without documented hypotension and hypoxia, patients with documented hypotension and hypoxia had nearly five-fold greater odds of mortality.

Benefits, key protocol components, and considerations for successful implementation of extracorporeal cardiopulmonary resuscitation: a review of the recent literature.

The application of venoarterial extracorporeal membrane oxygenation (ECMO) in patients unresponsive to conventional cardiopulmonary resuscitation (CPR) has significantly increased in recent years. To date, three published randomized trials have investigated the use of extracorporeal CPR (ECPR) in adults with refractory out-of-hospital cardiac arrest. Although these trials reported inconsistent results, they suggest that ECPR may have a significant survival benefit over conventional CPR in selected patients only when performed with strict protocol adherence in experienced emergency medical services-hospital systems. Several studies suggest that identifying suitable ECPR candidates and reducing the time from cardiac arrest to ECMO initiation are key to successful outcomes. Prehospital ECPR or the rendezvous approach may allow more patients to receive ECPR within acceptable timeframes than ECPR initiation on arrival at a capable hospital. ECPR is only one part of the system of care for resuscitation of cardiac arrest victims. Optimizing the chain of survival is critical to improving outcomes of patients receiving ECPR. Further studies are needed to find the optimal strategy for the use of ECPR.

Sodium bicarbonate administration is associated with improved survival in asystolic and PEA Out-of-Hospital cardiac arrest.

BACKGROUND: Sodium bicarbonate ("bicarb") administration in out-of-hospital cardiac arrest (OHCA) is intended to counteract acidosis, although there is limited clinical evidence to support its routine administration. We sought to analyze the association of bicarb with resuscitation outcomes in non-traumatic OHCA. METHODS: Records were obtained from the 2019-2020 ESO Data Collaborative prehospital electronic health record database, spanning 1,322 agencies in 50 states. OHCAs with resuscitations lasting 5-40 minutes were stratified by presenting ECG rhythm (VF/VT, pulseless electrical activity (PEA), asystole) for analysis. The outcomes of any prehospital ROSC and survival to discharge were compared by bicarb status using propensity score matching and logistic regressions with/without adjustment. RESULTS: We analyzed 23,567 records, 6,663 (28.3 %) of which included bicarb administration. Most patients presented in asystole (67.4 %), followed by PEA (16.6 %), and VF/VT (15.1 %). In the propensity-matched cohort, ROSC was higher in the bicarb group for the asystole group (bicarb 10.6 % vs control 8.8 %; p = 0.013), without differences in the PEA or VF/VT groups. Survival was higher in the bicarb group for asystole (bicarb 3.3 % vs control 2.4 %; p = 0.020) and for PEA (bicarb 8.1 % vs control 5.4 %; p = 0.034), without differences in the VF/VT group. These results were consistent across adjusted/unadjusted logistic regression analyses: bicarb was associated with ROSC and survival in asystole [uOR (95 % CI): ROSC 1.23 (1.04-1.44), survival 1.40 (1.05-1.87)] and with survival in PEA (1.54 (1.03-2.31). CONCLUSIONS: Bicarb was associated with survival in non-shockable rhythms and ROSC in asystole. Findings from this observational study should be corroborated with prospective randomized work.

Disparities in Out-of-Hospital Cardiac Arrest Treatment and Outcomes of Males and Females.

Background: Previous studies comparing the treatment of males and females during out-of-hospital cardiac arrests (OHCA) have been contradictory. Understanding differences in treatment and outcomes is important to assuring appropriate care to both sexes.Hypothesis: Females with OHCA receive fewer interventions and have lower rates of survival to hospital discharge when compared to males with OHCA.Methods: We conducted a secondary analysis of the Resuscitation Outcomes Consortium (ROC) Cardiac Arrest Epistry 3 data collected from April 2011 to June 2015. We included all OHCA cases treated by emergency medical services (EMS) who had sex recorded. We analyzed 36 treatment and outcome variables. We calculated descriptive statistics and compared treatment and outcomes between males and females using chi-square and t-tests. We performed multivariate regressions adjusting for baseline characteristics.Results: Of 120,306 total subjects, 65,241 were included (23,924 female, 41,317 male). Females were 9.9% less likely to have OHCA in public, 10.9% less likely to have a shockable rhythm, and were a median of 5 years older. In the unadjusted analysis, females were defibrillated by EMS less often (OR 1.81, 95% CI [1.74, 1.88]), received epinephrine less often (OR 1.15, 95% CI [1.10, 1.19]), took an average of 67 seconds longer to achieve first return of spontaneous circulation (ROSC) (coefficient -66.75, 95% CI [-83.98, -49.52]), and had 2.2% lower survival to emergency department (ED) arrival (OR 1.09, 95% CI [1.06, 1.13]). After adjusting for age, bystander CPR, witness status, episode location, and initial rhythm, the odds of surviving to hospital discharge were higher in males (OR 1.12, 95% CI [1.05, 1.21]), and the odds of surviving to ED arrival favored females (OR 0.87, 95% CI [0.84-0.90]). Additionally, odds of receiving epinephrine (OR 1.22, 95% CI [1.16, 1.27]) and odds of receiving defibrillation (OR 1.36, 95% CI [1.29, 1.44]) were both higher in males, and time to achieve first ROSC was no longer associated with sex (p = 0.114, 95% CI [-3.32, 31.11]).Conclusions: After adjusting for case characteristics, females were less likely to receive some key treatments, including epinephrine and defibrillation. Females also had poorer survival to hospital discharge but had higher odds of surviving to ED arrival.

Association of prehospital hypotension depth and dose with survival following out-of-hospital cardiac arrest.

INTRODUCTION: Hypotension following resuscitation from out-of-hospital cardiac arrest (OHCA) may cause harm by exacerbating secondary brain injury; however, limited research has explored this relationship. Our objective was to examine the association between duration and depth of prehospital post return of spontaneous circulation (ROSC) hypotension and survival. METHODS: We utilized the 2019 and 2020 ESO Data Collaborative public use research data sets for this study (ESO, Austin, TX). Hypotension dose (mmHg*min.), average prehospital systolic blood pressure (SBP), and lowest recorded prehospital SBP were calculated. The association of these measures with survival to home (STH) and rearrest were explored using multivariable logistic regression. Time to hypotension resolution analyses by hypotension management strategy (push dose vasopressors, vasopressor infusion, or fluid only) were conducted using adjusted Cox proportional hazards models. RESULTS: 17,280 OHCA patients met inclusion criteria, of which 3,345 had associated hospital outcome data. Over one-third (37.8%; 6,526/17,280) of all patients had at least one recorded SBP below 90 mmHg. When modeled continuously, average prehospital SBP (1.19 [1.15, 1.23] per 10 mmHg), lowest prehospital SBP (1.20 [1.17, 1.24] per 10 mmHg), and hypotension dose (0.995 [0.993, 0.996] per mmHg*min.) were independently associated with STH. Differences in hypotension management were not associated with differences in survival or time to hypotension resolution. CONCLUSION: Severity and duration of hypotension were significantly associated with worse outcomes in this dataset. Defining a threshold for hypotension requiring treatment above the classical SBP threshold of 90 mmHg may be warranted in the setting of prehospital post-resuscitation care.

Association of prehospital post-resuscitation peripheral oxygen saturation with survival following out-of-hospital cardiac arrest.

BACKGROUND: Hypoxia and hyperoxia following resuscitation from out-of-hospital cardiac arrest (OHCA)may cause harm by exacerbating secondary brain injury. Our objective was to retrospectively examine theassociationof prehospital post-ROSC hypoxia and hyperoxia with the primary outcome of survival to discharge home. METHODS: We utilized the 2019-2021 ESO Data Collaborative public use research datasets for this study (ESO, Austin, TX). Average prehospital SpO2, lowest recorded prehospital SpO2, and hypoxia dose were calculated for each patient. Theassociationof these measures with survival was explored using multivariable logistic regression. We also evaluated theassociationof American Heart Association (AHA) and European Resuscitation Council (ERC) recommended post-ROSC SpO2 target ranges with outcome. RESULTS: After application of exclusion criteria, 19,023 patients were included in this study. Of these, 52.3% experienced at least one episode of post-ROSC hypoxia (lowest SpO2 < 90%) and 19.6% experienced hyperoxia (average SpO2 > 98%). In comparison to normoxic patients, patients who were hypoxic on average (AHA aOR: 0.31 [0.25, 0.38]; ERC aOR: 0.34 [0.28, 0.42]) and patients who had a hypoxic lowest recorded SpO2 (AHA aOR: 0.48 [0.39, 0.59]; ERC aOR: 0.52 [0.42, 0.64]) had lower adjusted odds of survival. Patients who had a hyperoxic average SpO2 (AHA aOR: 0.75 [0.59, 0.96]; ERC aOR: 0.68 [0.53, 0.88]) and patients who had a hyperoxic lowest recorded SpO2 (AHA aOR: 0.66 [0.48, 0.92]; ERC aOR: 0.65 [0.46, 0.92]) also had lower adjusted odds of survival. CONCLUSION: Prehospital post-ROSC hypoxia and hyperoxia were associated with worse outcomes in this dataset.

Sudden Electrocardiogram Rhythm Changes after Return of Spontaneous Circulation in Porcine Models of Out-of-Hospital Cardiac Arrest: A Phenomenological Report.

BACKGROUND: Observation of the electrocardiogram (ECG) immediately following return of spontaneous circulation (ROSC) in resuscitated swine has revealed the interesting phenomenon of sudden ECG rhythm changes (SERC) that occur in the absence of pharmacological, surgical, or other medical interventions. OBJECTIVE: We sought to identify, quantify, and characterize post-ROSC SERC in successfully resuscitated swine. METHODS: We reviewed all LabChart data from resuscitated approximately 4- to 6-month-old swine used for various experimental protocols from 2006 to 2019. We identified those that achieved sustained ROSC and analyzed their entire post-ROSC periods for evidence of SERC in the ECG, and arterial and venous pressure tracings. Presence or absence of SERC was confirmed independently by two reviewers (ACK, DDS). We measured the interval from ROSC to first SERC, analyzed the following metrics, and calculated the change from 60 sec pre-SERC (or from ROSC if less than 60 sec) to 60 sec post-SERC: heart rate, central arterial pressure (CAP), and central venous pressure (CVP). RESULTS: A total of 52 pigs achieved and sustained ROSC. Of these, we confirmed at least one SERC in 25 (48.1%). Two pigs (8%) each had two unique SERC events. Median interval from ROSC to first SERC was 3.8 min (inter-quartile range 1.0-6.9 min; range 16 sec to 67.5 min). We observed two distinct types of SERC: type 1) the post-SERC heart rate and arterial pressure increased (72% of cases); and type 2) the post-SERC heart rate and arterial pressure decreased (28% of cases). For type 1 cases, the mean (standard deviation [SD]) heart rate increased by 33.6 (45.7) beats per minute (bpm). The mean (SD) CAP increased by 20.6 (19.2) mmHg. For type 2 cases, the mean (SD) heart rate decreased by 39.7 (62.3) bpm. The mean (SD) CAP decreased by 21.9 (15.6) mmHg. CONCLUSIONS: SERC occurred in nearly half of all cases with sustained ROSC and can occur multiple times per case. First SERC most often occurred within the first 4 minutes following ROSC. Heart rate, CAP, and CVP changed at the moment of SERC. We are proceeding to examine whether this phenomenon occurs in humans post-cardiac arrest and ROSC.

Establishing a multicenter, preclinical consortium in resuscitation: A pilot experimental trial evaluating epinephrine in cardiac arrest.

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.

Injury characteristics and hemodynamics associated with guideline-compliant CPR in a pediatric porcine cardiac arrest model.

BACKGROUND: Guidelines for depth of chest compressions in pediatric cardiopulmonary resuscitation (CPR) are based on sparse evidence. OBJECTIVE: We sought to evaluate the performance of the two most widely recommended chest compression depth levels for pediatric CPR (1.5 in. and 1/3 the anterior-posterior diameter- APd) in a controlled swine model of asphyxial cardiac arrest. METHODS: We executed a 2-group, randomized laboratory study with an adaptive design allowing early termination for overwhelming injury or benefit. Forty mixed-breed domestic swine (mean weight = 26 kg) were sedated, anesthetized and paralyzed along with endotracheal intubation and mechanical ventilation. Asphyxial cardiac arrest was induced with fentanyl overdose. Animals were untreated for 9 min followed by mechanical CPR with a target depth of 1.5 in. or 1/3 the APd. Advanced life support drugs were administered IV after 4 min of basic resuscitation followed by defibrillation at 14 min. The primary outcomes were return of spontaneous circulation (ROSC), hemodynamics and CPR-related injury severity. RESULTS: Enrollment in the 1/3 APd group was stopped early due to overwhelming differences in injury. Twenty-three animals were assigned to the 1.5 in. group and 15 assigned to the 1/3 APd group, per an adaptive group design. The 1/3 APd group had increased frequency of rib fracture (6.7 vs 1.7, p < 0.001) and higher proportions of several anatomic injury markers than the 1.5 in. group, including sternal fracture, hemothorax and blood in the endotracheal tube (p < 0.001). ROSC and hemodynamic measures were similar between groups. CONCLUSION: In this pediatric model of cardiac arrest, chest compressions to 1/3APd were more harmful without a concurrent benefit for resuscitation outcomes compared to the 1.5 in. compression group.

Early cytotoxic lymphocyte localization to the brain following resuscitation in a porcine model of asphyxial cardiac arrest: A pilot study.

INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) is a major cause of morbidity and mortality in the US. Of major concern is a lack of therapies to mitigate associated brain injury. Immune cell infiltration (ICI) into the brain, which may exacerbate injury post-resuscitation, is one possible therapeutic target, although the post-OHCA immune response has not been fully characterized. OBJECTIVE: In this pilot study, we aimed to detect early post-resuscitation cytotoxic lymphocyte ICI in porcine brain using a model of opioid-mediated asphyxial OHCA. METHODS: Ten young, healthy swine (26.7+/-3.4 kg) were sedated, anaesthetized and paralyzed. In eight of the animals, this was followed by induction of asphyxial OHCA via fentanyl bolus and concurrent airway occlusion. The remaining two 'sham' animals were instrumented but did not undergo asphyxia. After nine minutes of asphyxia, mechanical CPR and manual ventilations were started, in an initial BLS followed by ALS configuration. At termination of resuscitation or euthanasia, the whole brain was removed. Immune cells were extracted and analyzed via flow cytometry. RESULTS: 304 +/- 62.2 cells/g were discovered to be CD8 single positive cells in animals that achieved ROSC, 481 +/- 274.4 cells/g in animals that did not achieve ROSC, and 40 +/- 11.31 cells/g in sham animals. CD8 single positive cells made up 0.473 +/- 0.24% of detected cells in animals that achieved ROSC, 0.395 +/- 0.062% in animals that did not achieve ROSC, and 0.19 +/- 0.014% in sham animals (No ROSC vs Sham, p = 0.012). CONCLUSIONS: These data suggest that cytotoxic lymphocytes may be localizing to the brain during cardiac arrest resuscitation.

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.

The impact of increased chest compression fraction on survival for out-of-hospital cardiac arrest patients with a non-shockable initial rhythm.

OBJECTIVE: We evaluated the effect of chest compression fraction (CCF) on survival to hospital discharge and return of spontaneous circulation (ROSC) in out-of-hospital cardiac arrest (OHCA) patients with non-shockable rhythms. METHODS: This is a retrospective analysis (completed in 2016) of a prospective cohort study which included OHCA patients from ten U.S. and Canadian sites (Resuscitation Outcomes Consortium Epistry and PRIMED study (2007-2011)). We included all OHCA victims of presumed cardiac aetiology, not witnessed by emergency medical services (EMS), without automated external defibrillator shock prior to EMS arrival, receiving > 1 min of CPR with CPR process measures available, and initial non-shockable rhythm. We measured CCF using the first 5 min of electronic CPR records. RESULTS: Demographics of 12,928 adult patients were: mean age 68; male 59.9%; public location 8.5%; bystander witnessed 35.2%; bystander CPR 39.3%; median interval from 911 to defibrillator turned on 10 min:04 s; initial rhythm asystole 64.8%, PEA 26.0%, other non-shockable 9.2%; compression rate 80-120/min (69.1%); median CCF 74%; ROSC 25.6%; survival to hospital discharge 2.4%. Adjusted odds ratio (OR); 95% confidence intervals (95%CI) of survival for each CCF category were: 0-40% (2.00; 1.16, 3.32); 41-60% (0.83; 0.54, 1.24); 61-80% (1.02; 0.77, 1.35); and 81-100% (reference group). Adjusted (OR; 95%CI) of ROSC for each CCF category were: 0-40% (1.02; 0.79, 1.30); 41-60% (0.83; 0.72, 0.95); 61-80% (0.85; 0.77, 0.94); and 81-100% (reference group). CONCLUSIONS: We observed an incremental benefit from higher CCF on the incidence of ROSC, but not survival, among non-shockable OHCA patients with CCF higher than 40%.

Ventricular fibrillation waveform characteristics in out-of-hospital cardiac arrest and cardiovascular medication use.

BACKGROUND: Ventricular fibrillation (VF) waveform analyses are considered a reliable proxy for OHCA characteristics in out-of-hospital cardiac arrest (OHCA), but patient characteristics such as cardiovascular medication use might also be associated with changes in VF waveform measures. OBJECTIVES: To assess associations between cardiovascular medication use and amplitude spectrum area (AMSA) of VF, while correcting for the presence of cardiovascular disease (CVD), CVD risk factors, and OHCA characteristics. METHODS: We included 990 VF patients from an OHCA registry in the Netherlands, with available information on medical history and cardiovascular medication use. Associations between cardiovascular medication use and AMSA were tested in a multivariate linear regression model, adjusting for CVD, CVD risk factors, and OHCA characteristics. Model performance was shown using R-square and R-change. We also calculated whether medication use was associated with faster dissolution of AMSA to lower values with increasing time delay. RESULTS: In the multivariate analysis, when corrected for CVD, CVD risk factors and OHCA characteristics, only potassium-sparing agents were associated with a lower AMSA when compared to patients using other cardiovascular medications (OR 0.46 [95% CI 0.10-0.81]; P < 0.012). The decrease in AMSA with increasing EMS-call-to-ECG delay was the same for patients with and without cardiovascular medication use (all P > 0.05). Only a small part of the variance in AMSA could be explained by medication use (R-square 0.003- 0.026). Adding OHCA characteristics to the model resulted in the largest R square change (0.09-0.15). CONCLUSIONS: It is unlikely that there is a strong and clinically relevant independent pharmacologic effect of cardiovascular medication use on AMSA. In OHCA, AMSA might be used as patient management tool without considering cardiovascular medication use.

Survival After Intravenous Versus Intraosseous Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Shock-Refractory Cardiac Arrest.

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.