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

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

Antiarrhythmic Drugs for Nonshockable-Turned-Shockable Out-of-Hospital Cardiac Arrest: The ALPS Study (Amiodarone, Lidocaine, or Placebo).

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) commonly presents with nonshockable rhythms (asystole and pulseless electric activity). It is unknown whether antiarrhythmic drugs are safe and effective when nonshockable rhythms evolve to shockable rhythms (ventricular fibrillation/pulseless ventricular tachycardia [VF/VT]) during resuscitation. METHODS: Adults with nontraumatic OHCA, vascular access, and VF/VT anytime after ≥1 shock(s) were prospectively randomized, double-blind, to receive amiodarone, lidocaine, or placebo by paramedics. Patients presenting with initial shock-refractory VF/VT were previously reported. The current study was a prespecified analysis in a separate cohort that initially presented with nonshockable OHCA and was randomized on subsequently developing shock-refractory VF/VT. The primary outcome was survival to hospital discharge. Secondary outcomes included discharge functional status and adverse drug-related effects. RESULTS: Of 37 889 patients with OHCA, 3026 with initial VF/VT and 1063 with initial nonshockable-turned-shockable rhythms were treatment-eligible, were randomized, and received their assigned drug. Baseline characteristics among patients with nonshockable-turned-shockable rhythms were balanced across treatment arms, except that recipients of a placebo included fewer men and were less likely to receive bystander cardiopulmonary resuscitation. Active-drug recipients in this cohort required fewer shocks, supplemental doses of their assigned drug, and ancillary antiarrhythmic drugs than recipients of a placebo (P<0.05). In all, 16 (4.1%) amiodarone, 11 (3.1%) lidocaine, and 6 (1.9%) placebo-treated patients survived to hospital discharge (P=0.24). No significant interaction between treatment assignment and discharge survival occurred with the initiating OHCA rhythm (asystole, pulseless electric activity, or VF/VT). Survival in each of these categories was consistently higher with active drugs, although the trends were not statistically significant. Adjusted absolute differences (95% confidence interval) in survival from nonshockable-turned-shockable arrhythmias with amiodarone versus placebo were 2.3% (-0.3, 4.8), P=0.08, and for lidocaine versus placebo 1.2% (-1.1, 3.6), P=0.30. More than 50% of these survivors were functionally independent or required minimal assistance. Drug-related adverse effects were infrequent. CONCLUSIONS: Outcome from nonshockable-turned-shockable OHCA is poor but not invariably fatal. Although not statistically significant, point estimates for survival were greater after amiodarone or lidocaine than placebo, without increased risk of adverse effects or disability and consistent with previously observed favorable trends from treatment of initial shock-refractory VF/VT with these drugs. Together the findings may signal a clinical benefit that invites further investigation. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01401647.

Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest.

BACKGROUND: Antiarrhythmic drugs are used commonly in out-of-hospital cardiac arrest for shock-refractory ventricular fibrillation or pulseless ventricular tachycardia, but without proven survival benefit. METHODS: In this randomized, double-blind trial, we compared parenteral amiodarone, lidocaine, and saline placebo, along with standard care, in adults who had nontraumatic out-of-hospital cardiac arrest, shock-refractory ventricular fibrillation or pulseless ventricular tachycardia after at least one shock, and vascular access. Paramedics enrolled patients at 10 North American sites. The primary outcome was survival to hospital discharge; the secondary outcome was favorable neurologic function at discharge. The per-protocol (primary analysis) population included all randomly assigned participants who met eligibility criteria and received any dose of a trial drug and whose initial cardiac-arrest rhythm of ventricular fibrillation or pulseless ventricular tachycardia was refractory to shock. RESULTS: In the per-protocol population, 3026 patients were randomly assigned to amiodarone (974), lidocaine (993), or placebo (1059); of those, 24.4%, 23.7%, and 21.0%, respectively, survived to hospital discharge. The difference in survival rate for amiodarone versus placebo was 3.2 percentage points (95% confidence interval [CI], -0.4 to 7.0; P=0.08); for lidocaine versus placebo, 2.6 percentage points (95% CI, -1.0 to 6.3; P=0.16); and for amiodarone versus lidocaine, 0.7 percentage points (95% CI, -3.2 to 4.7; P=0.70). Neurologic outcome at discharge was similar in the three groups. There was heterogeneity of treatment effect with respect to whether the arrest was witnessed (P=0.05); active drugs were associated with a survival rate that was significantly higher than the rate with placebo among patients with bystander-witnessed arrest but not among those with unwitnessed arrest. More amiodarone recipients required temporary cardiac pacing than did recipients of lidocaine or placebo. CONCLUSIONS: Overall, neither amiodarone nor lidocaine resulted in a significantly higher rate of survival or favorable neurologic outcome than the rate with placebo among patients with out-of-hospital cardiac arrest due to initial shock-refractory ventricular fibrillation or pulseless ventricular tachycardia. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT01401647.).

Using social media for community consultation and public disclosure in exception from informed consent trials.

BACKGROUND: The US Food and Drug Administration and the Department of Health and Human Services outline regulations allowing an exception from informed consent (EFIC) for research conducted in an emergency setting. Acute care clinical trials using EFIC must include community consultation and public disclosure (CC/PD) activities. We describe our experience using social media to facilitate the CC/PD process in two trauma resuscitation clinical trials. METHODS: We conducted local CC/PD activities for two multicenter trauma clinical trials, Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) and Prehospital Tranexamic Acid Use for Traumatic Brain Injury (ROC-TXA). As part of the CC/PD process, we developed research study advertisements using the social media Web site Facebook. The Facebook advertisements directed users to a regional study Web site that contained trial information. We targeted the advertisements to specific demographic users, in specific geographic areas. We analyzed the data using descriptive statistics. RESULTS: During the study periods, the PROPPR Facebook advertisement was displayed 5,001,520 times (12 displays per target population) with 374 individuals selecting the advertisement. The ROC-TXA Facebook advertisement was displayed 3,806,448 times (8 per target population) with 790 individuals selecting the advertisement. Respondents to both Facebook advertisements were mostly male (52.6%), with the highest proportion between the ages 15 years and 24 years (28.2%). Collectively, 26.9% of individuals that clicked on the Facebook advertisement spent more than 3 minutes on the study Web site (3-49 minutes). Commonly accessed Web pages were "contact us" (PROPPR, 5.5%; ROC-TXA, 7.7%), "study-specific FAQs" (PROPPR, 2.4%; ROC-TXA, 6.7%), and "opt out of research" (PROPPR, 2.5%; ROC-TXA, 3.8%). Of 51 total individuals viewing the opt out of research information (PROPPR, 19; ROC-TXA, 32), time spent on that specific page was modest (PROPPR, 62 seconds; ROC-TXA, 55 seconds), with no individuals requesting to opt out of either study participation. CONCLUSIONS: In clinical trauma trials using EFIC, social media may provide a viable option for facilitating the CC/PD process.

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

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

Chest compression rates and survival following out-of-hospital cardiac arrest.

OBJECTIVE: Guidelines for cardiopulmonary resuscitation recommend a chest compression rate of at least 100 compressions/min. A recent clinical study reported optimal return of spontaneous circulation with rates between 100 and 120/min during cardiopulmonary resuscitation for out-of-hospital cardiac arrest. However, the relationship between compression rate and survival is still undetermined. DESIGN: Prospective, observational study. SETTING: Data is from the Resuscitation Outcomes Consortium Prehospital Resuscitation IMpedance threshold device and Early versus Delayed analysis clinical trial. PARTICIPANTS: Adults with out-of-hospital cardiac arrest treated by emergency medical service providers. INTERVENTIONS: None. MEASUREMENTS MAIN RESULTS: Data were abstracted from monitor-defibrillator recordings for the first five minutes of emergency medical service cardiopulmonary resuscitation. Multiple logistic regression assessed odds ratio for survival by compression rate categories (<80, 80-99, 100-119, 120-139, ≥140), both unadjusted and adjusted for sex, age, witnessed status, attempted bystander cardiopulmonary resuscitation, location of arrest, chest compression fraction and depth, first rhythm, and study site. Compression rate data were available for 10,371 patients; 6,399 also had chest compression fraction and depth data. Age (mean±SD) was 67±16 years. Chest compression rate was 111±19 per minute, compression fraction was 0.70±0.17, and compression depth was 42±12 mm. Circulation was restored in 34%; 9% survived to hospital discharge. After adjustment for covariates without chest compression depth and fraction (n=10,371), a global test found no significant relationship between compression rate and survival (p=0.19). However, after adjustment for covariates including chest compression depth and fraction (n=6,399), the global test found a significant relationship between compression rate and survival (p=0.02), with the reference group (100-119 compressions/min) having the greatest likelihood for survival. CONCLUSIONS: After adjustment for chest compression fraction and depth, compression rates between 100 and 120 per minute were associated with greatest survival to hospital discharge.

Comparison of methods for the determination of cardiopulmonary resuscitation chest compression fraction.

OBJECTIVE: While cardiopulmonary resuscitation (CPR) chest compression fraction (CCF) is associated with out-of-hospital cardiac arrest (OHCA) outcomes, there is no standard method for the determination of CCF. We compared nine methods for calculating CCF. METHODS: We studied consecutive adult OHCA patients treated by Alabama Emergency Medical Services (EMS) agencies of the Resuscitation Outcomes Consortium (ROC) during January 1, 2010 to October 28, 2010. Paramedics used portable cardiac monitors with real-time chest compression detection technology (LifePak 12, Physio-Control, Redmond, WA). We performed both automated CCF calculation for the entire care episode as well as manual review of CPR data in 1-min epochs, defining CCF as the proportion of each treatment interval with active chest compressions. We compared the CCF values resulting from 9 calculation methods: (1) mean CCF for the entire patient care episode (automated calculation by manufacturer software), (2) mean CCF for first 3 min of patient care, (3) mean CCF for first 5 min, (4) mean CCF for first 10 min, (5) mean CCF for the entire episode except first 5 min, (6) mean CCF for last 5 min, (7) mean CCF from start to first shock, (8) mean CCF for the first half of resuscitation, and (9) mean CCF for the second half of resuscitation. We compared CCF for Methods 2-9 with Method 1 using paired t-tests with a Bonferroni-adjusted p-value of 0.006 (99.5% confidence intervals). RESULTS: Among 102 adult OHCA, patient demographics were: mean age 60.3 years (SD 20.8 years), African American 56.9%, male 63.7%, and shockable ECG rhythm 23.5%. Mean CPR duration was 728 s (95% CI: 647-809 s). Mean CCF for the 9 CCF calculation methods were: (1) 0.587%; (2) 0.526%; (3) 0.541%; (4) 0.566%; (5) 0.562%; (6) 0.597%; (7) 0.530%; (8) 0.550%; and (9) 0.590%. Compared with Method 1, Method 7 CCF (start to first shock) was slightly lower (-0.057; 99.5% CI: -0.100 to -0.014). There were no other statistically significant CCF differences (range: -0.054 to 0.013). Correlation between CCF 2-9 and CCF varied (ρ=0.48-0.85). CONCLUSION: CCF varies minimally with different calculation methods. Automated CCF determination may prove sufficient for evaluating CPR quality.

Ventricular tachyarrhythmias after cardiac arrest in public versus at home.

BACKGROUND: The incidence of ventricular fibrillation or pulseless ventricular tachycardia as the first recorded rhythm after out-of-hospital cardiac arrest has unexpectedly declined. The success of bystander-deployed automated external defibrillators (AEDs) in public settings suggests that this may be the more common initial rhythm when out-of-hospital cardiac arrest occurs in public. We conducted a study to determine whether the location of the arrest, the type of arrhythmia, and the probability of survival are associated. METHODS: Between 2005 and 2007, we conducted a prospective cohort study of out-of-hospital cardiac arrest in adults in 10 North American communities. We assessed the frequencies of ventricular fibrillation or pulseless ventricular tachycardia and of survival to hospital discharge for arrests at home as compared with arrests in public. RESULTS: Of 12,930 evaluated out-of-hospital cardiac arrests, 2042 occurred in public and 9564 at home. For cardiac arrests at home, the incidence of ventricular fibrillation or pulseless ventricular tachycardia was 25% when the arrest was witnessed by emergency-medical-services (EMS) personnel, 35% when it was witnessed by a bystander, and 36% when a bystander applied an AED. For cardiac arrests in public, the corresponding rates were 38%, 60%, and 79%. The adjusted odds ratio for initial ventricular fibrillation or pulseless ventricular tachycardia in public versus at home was 2.28 (95% confidence interval [CI], 1.96 to 2.66; P < 0.001) for bystander-witnessed arrests and 4.48 (95% CI, 2.23 to 8.97; P<0.001) for arrests in which bystanders applied AEDs. The rate of survival to hospital discharge was 34% for arrests in public settings with AEDs applied by bystanders versus 12% for arrests at home (adjusted odds ratio, 2.49; 95% CI, 1.03 to 5.99; P = 0.04). CONCLUSIONS: Regardless of whether out-of-hospital cardiac arrests are witnessed by EMS personnel or bystanders and whether AEDs are applied by bystanders, the proportion of arrests with initial ventricular fibrillation or pulseless ventricular tachycardia is much greater in public settings than at home. The incremental value of resuscitation strategies, such as the ready availability of an AED, may be related to the place where the arrest occurs.