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We sought to evaluate the utility and validity of ICU-free days and ventilator-free days as candidate outcomes for OHCA trials.We conducted a secondary analysis of the Pragmatic Airway Resuscitation Trial. We determined ICU-free (days alive and out of ICU during the first 30 days) and ventilator-free days (days alive and without mechanical ventilation). We determined ICU-free and ventilator-free day distributions and correlations with Modified Rankin Scale (MRS). We tested associations with trial interventions (laryngeal tube (LT), endotracheal intubation (ETI)) using continuous (t-test), non-parametric (Wilcoxon Rank-Sum test - WRS), count (negative binomial - NB) and survival models (Cox proportional hazards (CPH) and competing risks regression (CRR)). We conducted bootstrapped simulations to estimate statistical power.ICU-free days was skewed; median 0 days (IQR 0, 0), survivors only 24 (18, 27). Ventilator-free days was skewed; median 0 (IQR 0, 0) days, survivors only 27 (IQR 23, 28). ICU-free and ventilator-free days correlated with MRS (Spearman's ρ = -0.95 and -0.97). LT was associated with higher ICU-free days using t-test (p = 0.001), WRS (p = 0.003), CPH (p = 0.02) and CRR (p = 0.04), but not NB (p = 0.13). LT was associated with higher ventilator-free days using t-test (p = 0.001), WRS (p = 0.001) and CRR (p = 0.03), but not NB (p = 0.13) or CPH (p = 0.13). Simulations suggested that t-test and WRS would have had the greatest power to detect the observed ICU- and ventilator-free days differences.ICU-free and ventilator-free days correlated with MRS and differentiated trial interventions. ICU-free and ventilator-free days may have utility in the design of OHCA trials.

Ventilation control is important during resuscitation from out-of-hospital cardiac arrest (OHCA). We compared different methods for calculating ventilation rates (VR) during OHCA.We analyzed data from the Pragmatic Airway Resuscitation Trial, identifying ventilations through capnogram recordings. We determined VR by: 1) counting the number of breaths within a time epoch ("counted" VR), and 2) calculating the mean of the inverse of measured time between breaths within a time epoch ("measured" VR). We repeated the VR estimates using different time epochs (10, 20, 30, 60 seconds). We defined hypo- and hyperventilation as VR6 and12 breaths/min, respectively. We assessed differences in estimated hypo- and hyperventilation with each VR measurement technique.Of 3,004 patients, data were available for 1,010. With the counted method, total hypoventilation increased with longer time epochs ([10-second epoch: 75 seconds hypoventilation] to [60-second epoch: 97 seconds hypoventilation]). However, with the measured method, total hypoventilation decreased with longer time epochs ([10-second epoch: 223 seconds hypoventilation] to [60-second epoch: 150 seconds hypoventilation]). With the counted method, the total duration of hyperventilation decreased with longer time epochs ([10-second epochs: 35 seconds hyperventilation] to [60-second epoch: 0 seconds hyperventilation]). With the measured method, total hyperventilation decreased with longer time epochs ([10-second epoch: 78 seconds hyperventilation] to [60-second epoch: 0 seconds hyperventilation]). Differences between the measured and counted estimates were smallest with a 60-second time epoch.Quantifications of hypo- and hyperventilation vary with the applied measurement methods. Measurement methods are important when characterizing ventilation rates in OHCA.

We sought to describe ventilation rates during out-of-hospital cardiac arrest (OHCA) resuscitation and their associations with airway management strategy and outcomes.We analyzed continuous end-tidal carbon dioxide capnography data from adult OHCA enrolled in the Pragmatic Airway Resuscitation Trial (PART). Using automated signal processing techniques, we determined continuous ventilation rates for consecutive 10-second epochs after airway insertion. We defined hypoventilation as a ventilation rate 6 breaths/min. We defined hyperventilation as a ventilation rate 12 breaths/min. We compared differences in total and percentage post-airway hyper- and hypoventilation between airway interventions (laryngeal tube (LT) vs. endotracheal intubation (ETI)). We also determined associations between hypo-/hyperventilation and OHCA outcomes (ROSC, 72-hour survival, hospital survival, hospital survival with favorable neurologic status).Adequate post-airway capnography were available for 1,010 (LT n = 714, ETI n = 296) of 3,004 patients. Median ventilation rates were: LT 8.0 (IQR 6.5-9.6) breaths/min, ETI 7.9 (6.5-9.7) breaths/min. Total duration and percentage of post-airway time with hypoventilation were similar between LT and ETI: median 1.8 vs. 1.7 minutes, p = 0.94; median 10.5% vs. 11.5%, p = 0.60. Total duration and percentage of post-airway time with hyperventilation were similar between LT and ETI: median 0.4 vs. 0.4 minutes, p = 0.91; median 2.1% vs. 1.9%, p = 0.99. Hypo- and hyperventilation exhibited limited associations with OHCA outcomes.In the PART Trial, EMS personnel delivered post-airway ventilations at rates satisfying international guidelines, with only limited hypo- or hyperventilation. Hypo- and hyperventilation durations did not differ between airway management strategy and exhibited uncertain associations with OCHA outcomes.

Summary Background Benzodiazepine-refractory, or established, status epilepticus is thought to be of similar pathophysiology in children and adults, but differences in underlying aetiology and pharmacodynamics might differentially affect response to therapy. In the Established Status Epilepticus Treatment Trial (ESETT) we compared the efficacy and safety of levetiracetam, fosphenytoin, and valproate in established status epilepticus, and here we describe our results after extending enrolment in children to compare outcomes in three age groups. Methods In this multicentre, double-blind, response-adaptive, randomised controlled trial, we recruited patients from 58 hospital emergency departments across the USA. Patients were eligible for inclusion if they were aged 2 years or older, had been treated for a generalised convulsive seizure of longer than 5 min duration with adequate doses of benzodiazepines, and continued to have persistent or recurrent convulsions in the emergency department for at least 5 min and no more than 30 min after the last dose of benzodiazepine. Patients were randomly assigned in a response-adaptive manner, using Bayesian methods and stratified by age group ( 65 years), to levetiracetam, fosphenytoin, or valproate. All patients, investigators, study staff, and pharmacists were masked to treatment allocation. The primary outcome was absence of clinically apparent seizures with improved consciousness and without additional antiseizure medication at 1 h from start of drug infusion. The primary safety outcome was life-threatening hypotension or cardiac arrhythmia. The efficacy and safety outcomes were analysed by intention to treat. This study is registered in ClinicalTrials.gov , NCT01960075 . Findings Between Nov 3, 2015, and Dec 29, 2018, we enrolled 478 patients and 462 unique patients were included: 225 children (aged 65 years). 175 (38%) patients were randomly assigned to levetiracetam, 142 (31%) to fosphenyltoin, and 145 (31%) were to valproate. Baseline characteristics were balanced across treatments within age groups. The primary efficacy outcome was met in those treated with levetiracetam for 52% (95% credible interval 41–62) of children, 44% (33–55) of adults, and 37% (19–59) of older adults; with fosphenytoin in 49% (38–61) of children, 46% (34–59) of adults, and 35% (17–59) of older adults; and with valproate in 52% (41–63) of children, 46% (34–58) of adults, and 47% (25–70) of older adults. No differences were detected in efficacy or primary safety outcome by drug within each age group. With the exception of endotracheal intubation in children, secondary safety outcomes did not significantly differ by drug within each age group. Interpretation Children, adults, and older adults with established status epilepticus respond similarly to levetiracetam, fosphenytoin, and valproate, with treatment success in approximately half of patients. Any of the three drugs can be considered as a potential first-choice, second-line drug for benzodiazepine-refractory status epilepticus. Funding National Institute of Neurological Disorders and Stroke, National Institutes of Health.

Background: Bystander cardiopulmonary resuscitation (B-CPR) delivery and survival from sudden cardiac arrest (SCA) varies at the neighborhood-level with poorer outcomes seen in predominantly black neighborhoods. Despite Latinos being the fastest growing minority population in the US, few studies have assessed whether the proportion of Latinos in a neighborhood is associated with B-CPR delivery and survival from SCA. Objective: We sought to assess whether there is variation in B-CPR rates and survival by neighborhood-level ethnicity. We hypothesized that neighborhoods with a higher proportion of Latinos are associated with lower B-CPR rates and lower survival. Methods: We conducted a retrospective cohort study, using data from the Resuscitation Outcomes Consortium (ROC) Epistry Registry US sites. Neighborhoods were classified by census tract, based on percentage of Latino residents: < 25%, 25%-50%, 51%-75%, or > 75%. We independently modelled the likelihood of receipt of layperson B-CPR and survival by neighborhood-level ethnicity controlling for site and patient-level confounding characteristics. Results: From 2011-2015, ROC collected 27,481 US arrest events; after excluding pediatric arrests, those witnessed by EMS, or occurred in a healthcare or institutional facility, 18,544 were included. B-CPR was administered in 37% events. Among neighborhoods with 75% Latino residents. B-CPR delivery varied by patient ethnicity with Latinos being less likely to receive B-CPR compared to Whites (OR: 0.73 (CI: 0.62-0.88), p75% Latino: OR: 0.75 (CI: 0.62-0.90), p75% Latino: OR: 0.62 (CI: 0.47-0.81), p Conclusion: Individuals in predominantly Latino neighborhoods were less likely to receive B-CPR and had lower likelihood of survival. These findings could inform future messaging around B-CPR educational initiatives targeting largely Latino neighborhoods.

Hospital management of out-of-hospital cardiac arrest (OHCA) patients after return of spontaneous circulation (ROSC) can influence patient survival via interventions such as hypothermia and cardiac catheterization (CATH). This study tested the hypothesis that survival differed between different types of hospitals for subjects with ROSC after OHCA. Methods: Adult (≥ 18 years) subjects with paramedic-documented ROSC or who lived >1 day after OHCA were identified with their receiving hospital in a prospective database from 9 regions in the US and Canada. Hospitals were characterized using the American Hospital Directory or the Guide to Canadian Healthcare Facilities. Hospitals were categorized by bed number (large >400; medium 250 – 400; small Results: Between December 2005 and July 2007, 3644 OHCA subjects were treated in 254 hospitals, with similar numbers in large (1026), medium (1094) and small (1276) hospitals. CATH hospitals treated 2123 (58%) subjects, and patient features (63% male, 42% VF/VT, 67% witnessed collapse, and mean call-arrival interval of 5.7 (SD 2.8) minutes) did not differ between hospital categories. CATH hospitals had higher survival than non-CATH hospitals in large (35.1% vs. 27.7%), medium (34.4% vs. 30.7%) and small (38.6% vs. 26.5%) categories (F=19.55; p Conclusions: Transport to a CATH hospital is associated with increased probability of survival to discharge after OHCA. These data cannot determine whether cardiac catheterization was performed or if CATH hospital is a surrogate for more comprehensive cardiac care. Therefore, further work should examine what aspects of in-hospital care affected outcome.

Introduction: Take Heart America (THA) is a community-based initiative intended to improve survival from sudden, out-of-hospital cardiac arrest (OHCA) in four US communities: St. Cloud (MN), Anoka County (MN), Columbus (OH) and Austin (TX). Hypothesis: Implementing a continuum of resuscitation care that includes the most highly recommended 2005 AHA resuscitation guidelines will improve survival from OHCA. Methods: In Phase I, the two MN sites (population: greater St. Cloud: ~160K; Anoka Co: ~320K) implemented: a) widespread CPR training in schools and businesses; b) retraining of all EMS personnel in methods to enhance circulation including minimizing CPR interruptions, performing CPR prior to and after single shock defibrillation, and use of an impedance threshold device; c) more widespread deployment of AEDs in schools and public places; and d) transport to and treatment by Level One Cardiac Arrest Centers that provide: therapeutic hypothermia (applied to all comatose patients regardless of initial arrest rhythm), coronary artery evaluation and treatment, and widespread electrophysiological evaluation. During Phase II, Austin and Columbus will implement these same steps. A Standard Chi-Square analysis was performed. Results: From 2006 –2007 in the two MN sites, >12,000 people were trained in CPR, bystander CPR rates increased by ~5%, three Level One Cardiac Arrest Centers were established, and interventions a–d above were fully implemented. Survival in all patients following OCHA improved from 9.3% (14/151) in 2005 (historical control) to 17% (31/181) (P=0.0373) in 2007 in these two sites. Conclusions: In conclusion, when OHCA patients were treated with a continuum of prehospital and inhospital interventions intended to optimize defibrillation and circulation during CPR, and preserve heart and brain function following cardiac arrest, survival rates nearly doubled when compared to historical controls. The THA initiative is effective in mid-size communities, but regular retraining of EMS personnel is needed to assure full implementation of the key aspects of the program. Phase II is underway to determine if the program can be successfully implemented with similar positive results in communities with populations of 500 –1000K.

Background: During cardiac arrest use of an impedance threshold device (ITD) increases circulation and the chances for survival. The ITD has not been systematically evaluated during conventional CPR in a pediatric animal model. We hypothesized that the ITD increases blood flow to the brain by lowering intrathoracic pressure during the CPR decompression phase thus enhancing venous return to the right heart and forward flow with the subsequent compression and maintaining or lowering diastolic intracranial pressure (ICP) thus reducing resistance to forward flow. In this manner ITD use was hypothesized to mimic the ‘gasping reflex’ during CPR. Methods: In the first study 9 female propofol anesthetized piglets (10–12 kg) were subjected to 6 min of untreated ventricular fibrillation, 6 min of conventional CPR (ventilation rate 10 bpm), then 6 min of CPR with an active ITD (resistance of −10 cm H20). A second study was similar except that a sham ITD was used in 8 piglets. Results: After 2 min of active ITD treatment, decompression phase airway pressures (surrogate for intrathoracic pressure) (mmHg) decreased from −0.5 ± 0.2 to −2.6 ± 0.5 (mean ± SEM, p < 0.001) and common carotid blood flow (mL/min) increased by 65% (59.2 ± 16.7 to 91.1± 27.9, p = 0.02). In the sham group, airway pressures were unchanged and carotid blood flow decreased from 39 ± 2.5 to 38.8 ± 4.3 (p = 0.47). ICP decreased more rapidly in time and to a greater degree in 6/9 piglets when comparing ITD use to measurements preceding its application, contributing to an increase in cerebral perfusion (CePP) (mmHg) in 5/9 active ITD piglets, while in the sham group, CePPs remained the same or decreased in 8/8 piglets (p = 0.03). Coronary perfusion pressures (CPP) (mmHg) increased in 5/9 piglets after 2 min of the active ITD and remained the same or decreased in 8/8 piglets treated with the sham device (p = 0.03). Return of spontaneous circulation was achieved with a single shock in 4/9 active ITD piglets and 1/8 sham ITD piglets (p = 0.29). Conclusions: Use of an active ITD during CPR in piglets significantly increased carotid blood flow and CPPs. The ITD also lowered ICP during the decompression phase, similar to the mechanism of the ‘last gasp’, thereby reducing resistance to forward blood flow to the brain.

Inspiration through -7cm H2O resistance results in an increase in venous blood flow back to the heart and a subsequent increase in cardiac output and blood pressure in hypotensive animals and patients. Breathing through the impedance threshold device with 7cm H2O resistance (ITD-7) also reduces intracranial pressure with each inspiration, thereby providing greater blood flow to the brain. A new device called an ITD-7 was developed to exploit these physiological mechanisms to buy time in hypotensive War Fighters when other therapies are not readily available. Animal and clinical data with the ITD-7 demonstrate the potential value and limitations of this new non-invasive approach to enhancing circulation.

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