Charles D. Deakin

Background: Early defibrillation is a key factor of survival following out-of-hospital cardiac arrest (OHCA). In the United Kingdom, initial anterior–lateral (AL) defibrillator pad placement is standard practice. However, anterior–posterior (AP) pad positioning has been proposed as a method of improving current flow through the myocardium particularly in cases of refractory ventricular fibrillation (VF). Concerns remain regarding potential delays to defibrillation associated with alternative pad placement strategies and the practical application of AP positioning. Objective: We conducted two consecutive simulation studies to explore whether there is a difference in the time taken to apply defibrillator pads, and placement accuracy, between AP and AL positions during simulated OHCA. Methods: This research study comprised of two simulation studies. First, we evaluated pad placement accuracy before and after written instruction showing optimal pad placement (RESTART-SIM accuracy). Second, we undertook a randomised crossover examining time to pad placement, timing to successful pad application was recorded for each attempt (RESTART-SIM speed). Results: RESTART-SIM (accuracy) out of 14 participants 50% correctly placed AL pads and 14% correctly placed AP pads initially. Following provision of guidance this increased to 93% for AL but remained at 14% for AP placement. 9 participants completed RESTART-SIM (speed). Mean AP pad placement time was 14.2 seconds and standard deviation of 2.64, compared with 10.6 seconds for AL placement and a standard deviation of 4.24. AP first strategy mean placement time was 15.3 seconds and mean AL placement time was 11.5 seconds. In AL first mean AP placement time was 12.8 seconds and mean AL placement time was 9.6 seconds. Conclusion: AP pad placement whilst slower than AL placement the time difference of 4 seconds is unlikely to be clinically significant. However, without guidance, both AL and AP placements were often inaccurate. After a guidance picture AL placement was increased but AP remained poorly placed.

Background: Current cardiopulmonary resuscitation (CPR) guidelines recommend a ventilation rate of 10 breaths/min in adult cardiac arrest patients with an advanced airway in place; however, this guideline is based almost exclusively on animal model studies. The objective of this study was to examine the association between mean ventilation rates during in-hospital cardiac arrest with return of spontaneous circulation (ROSC). Methods: This was a secondary analysis of a cohort undergoing CPR for in-hospital cardiac arrest with an advanced airway in place had that ventilation rate and end-tidal CO ₂ (ETCO ₂ ) continuously recorded. Subjects were enrolled at 25 tertiary care centers in the United States and United Kingdom. A subset of subjects also had intra-cardiac arrest arterial blood gases collected as part of routine clinical care. Results: Ventilation rate and ETCO ₂ measurements were collected for 222 subjects and arterial blood gas data for 127 subjects. We observed 84.7% of subjects were ventilated > 10 breaths/min. When dichotomized to subjects receiving close to current guidelines (6-12 breaths/min) and those with higher ventilation rates >12 breaths/min, subjects with higher ventilation rates had greater rate of ROSC (45% vs. 24% p = 0.009). Ventilation rate had a significant impact on ROSC even after adjusting for age, sex, shockable initial rhythm, pre-cardiac arrest severity of critical illness, and mechanical chest compression device usage, with an adjusted odds ratio of 1.15 per two breaths/min increase (95% CI 1.04-1.28; p = 0.006). Regression analysis suggested increasing ventilation rates may start to have a negative association with ROSC when beyond 26 breaths/min. Patients ventilated > 12 breaths/min demonstrated increased mean ETCO ₂ levels (median 25 mm Hg vs. 17 mm Hg for those with mean ventilation rates within 6-12 breaths/min; p < 0.001). PaO ₂ and PaCO ₂ levels did not differ between ventilation groups, suggesting that the observed effects may relate to hemodynamic rather than ventilatory effects. Conclusions: Ventilation in excess of guideline-recommended rates is common. Higher ventilation rates above 6-12 breaths and below 26 breaths/min were associated with increased odds of ROSC. This may be due to improved hemodynamics. Guidelines on ventilation during CPR may require further examination.

Background: Ambulance services treat over 32,000 patients sustaining an out-of-hospital cardiac arrest annually, receiving over 90,000 calls. The definitive treatment for out-of-hospital cardiac arrest is defibrillation. Prompt treatment with an automated external defibrillator can improve survival significantly. However, their location in the community limits opportunity for their use. There is a requirement to identify the optimal location for an automated external defibrillator to improve out-of-hospital cardiac arrest coverage, to improve the chances of survival. Methods: This was a secondary analysis of data collected by the Out-of-Hospital Cardiac Arrest Outcomes registry on historical out-of-hospital cardiac arrests, data held on the location of automated external defibrillators registered with ambulance services, and locations of points of interest. Walking distance was calculated between out-of-hospital cardiac arrests, registered automated external defibrillators and points of interest designated as potential sites for an automated external defibrillator. An out-of-hospital cardiac arrest was deemed to be covered if it occurred within 500 m of a registered automated external defibrillator or points of interest. For the optimisation analysis, mathematical models focused on the maximal covering location problem were adapted. A de novo decision-analytic model was developed for the cost-effectiveness analysis and used as a vehicle for assessing the costs and benefits (in terms of quality-adjusted life-years) of deployment strategies. A meeting of stakeholders was held to discuss and review the results of the study. Results: Historical out-of-hospital cardiac arrests occurred in more deprived areas and automated external defibrillators were placed in more affluent areas. The median out-of-hospital cardiac arrest – automated external defibrillator distance was 638 m and 38.9% of out-of-hospital cardiac arrests occurred within 500 m of an automated external defibrillator. If an automated external defibrillator was placed in all points of interests, the proportion of out-of-hospital cardiac arrests covered varied greatly. The greatest coverage was achieved with cash machines. Coverage loss, assuming an automated external defibrillator was not available outside working hours, varied between points of interest and was greatest for schools. Dividing the country up into 1 km² grids and placing an automated external defibrillator in the centre increased coverage significantly to 78.8%. The optimisation model showed that if automated external defibrillators were placed in each points-of-interest location out-of-hospital cardiac arrest coverage levels would improve above the current situation significantly, but it would not reach that of optimisation-based placement (based on grids). The coverage efficiency provided by the optimised grid points was unmatched by any points of interest in any region. An economic evaluation determined that all alternative placements were associated with higher quality-adjusted life-years and costs compared to current placement, resulting in incremental cost-effectiveness ratios over £30,000 per additional quality-adjusted life-year. The most appealing strategy was automated external defibrillator placement in halls and community centres, resulting in an additional 0.007 quality-adjusted life-year (non-parametric 95% confidence interval 0.004 to 0.011), an additional expected cost of £223 (non-parametric 95% confidence interval £148 to £330) and an incremental cost-effectiveness ratio of £32,418 per quality-adjusted life-year. The stakeholder meeting agreed that the current distribution of registered publicly accessible automated external defibrillators was suboptimal, and that there was a disparity in their location in respect of deprivation and other health inequalities. Conclusions: We have developed a data-driven framework to support decisions about public-access automated external defibrillator locations, using optimisation and statistical models. Optimising automated external defibrillator locations can result in substantial improvement in coverage. Comparison between placement based on points of interest and current placement showed that the former improves coverage but is associated with higher costs and incremental cost-effectiveness ratio values over £30,000 per additional quality-adjusted life-year. Study registration: This study is registered as researchregistry5121. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR127368) and is published in full in Health and Social Care Delivery Research; Vol. 13, No. 5. See the NIHR Funding and Awards website for further award information.

Background: Adrenaline has been used as a treatment for cardiac arrest for many years, despite uncertainty about its effects on long-term outcomes and concerns that it may cause worse neurological outcomes.Objectives: The objectives were to evaluate the effects of adrenaline on survival and neurological outcomes, and to assess the cost-effectiveness of adrenaline use.Design: This was a pragmatic, randomised, allocation-concealed, placebo-controlled, parallel-group superiority trial and economic evaluation. Costs are expressed in Great British pounds and reported in 2016/17 prices.Setting: This trial was set in five NHS ambulance services in England and Wales.Participants: Adults treated for an out-of-hospital cardiac arrest were included. Patients were ineligible if they were pregnant, if they were aged < 16 years, if the cardiac arrest had been caused by anaphylaxis or life-threatening asthma, or if adrenaline had already been given.Interventions: Participants were randomised to either adrenaline (1 mg) or placebo in a 1 : 1 allocation ratio by the opening of allocation-concealed treatment packs.Main outcome measures: The primary outcome was survival to 30 days. The secondary outcomes were survival to hospital admission, survival to hospital discharge, survival at 3, 6 and 12 months, neurological outcomes and health-related quality of life through to 6 months. The economic evaluation assessed the incremental cost per quality-adjusted life-year gained from the perspective of the NHS and Personal Social Services. Participants, clinical teams and those assessing patient outcomes were masked to the treatment allocation.Results: From December 2014 to October 2017, 8014 participants were assigned to the adrenaline (n = 4015) or to the placebo (n = 3999) arm. At 30 days, 130 out of 4012 participants (3.2%) in the adrenaline arm and 94 out of 3995 (2.4%) in the placebo arm were alive (adjusted odds ratio for survival 1.47, 95% confidence interval 1.09 to 1.97). For secondary outcomes, survival to hospital admission was higher for those receiving adrenaline than for those receiving placebo (23.6% vs. 8.0%; adjusted odds ratio 3.83, 95% confidence interval 3.30 to 4.43). The rate of favourable neurological outcome at hospital discharge was not significantly different between the arms (2.2% vs. 1.9%; adjusted odds ratio 1.19, 95% confidence interval 0.85 to 1.68). The pattern of improved survival but no significant improvement in neurological outcomes continued through to 6 months. By 12 months, survival in the adrenaline arm was 2.7%, compared with 2.0% in the placebo arm (adjusted odds ratio 1.38, 95% confidence interval 1.00 to 1.92). An adjusted subgroup analysis did not identify significant interactions. The incremental cost-effectiveness ratio for adrenaline was estimated at £1,693,003 per quality-adjusted life-year gained over the first 6 months after the cardiac arrest event and £81,070 per quality-adjusted life-year gained over the lifetime of survivors. Additional economic analyses estimated incremental cost-effectiveness ratios for adrenaline at £982,880 per percentage point increase in overall survival and £377,232 per percentage point increase in neurological outcomes over the first 6 months after the cardiac arrest.Limitations: The estimate for survival with a favourable neurological outcome is imprecise because of the small numbers of patients surviving with a good outcome.Conclusions: Adrenaline improved long-term survival, but there was no evidence that it significantly improved neurological outcomes. The incremental cost-effectiveness ratio per quality-adjusted life-year exceeds the threshold of £20,000–30,000 per quality-adjusted life-year usually supported by the NHS.Future work: Further research is required to better understand patients’ preferences in relation to survival and neurological outcomes after out-of-hospital cardiac arrest and to aid interpretation of the trial findings from a patient and public perspective.Trial registration: Current Controlled Trials ISRCTN73485024 and EudraCT 2014-000792-11.Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 25, No. 25. See the NIHR Journals Library website for further project information.