Facilitators and barriers to the delivery of the PARAMEDIC2 trial.

Background: PARAMEDIC2 was a medicines trial comparing adrenaline with placebo in out-of-hospital cardiac arrest (OHCA). At the time, United Kingdom (UK) Emergency Medical Systems (EMS) were inexperienced in delivering such research. Aim: To identify barriers and facilitators to delivery of the PARAMEDIC2 (Adrenaline) trial by five UK NHS EMS. Methods: This qualitative study took a grounded theory approach to thematic analysis of workshop data. Members of the trial teams from each service attended a workshop in November 2018 and discussed their experiences in answer to two prompt questions. Data were coded and themes presented. Results: Three main themes were identified: professionalism, organisational investment and unique features of EMS. The study provided an opportunity for recruiting paramedics and research paramedics to demonstrate their professionalism. Research paramedics felt it was part of their professional duty to initiate discussions with the patient/family regarding the trial rather than leave this task to the hospital teams as would usually happen. Organisational investment was reflected by prioritising trial training and further development of research paramedics. By these means, research culture was developed. The unique features of EMS such as geographical challenges were often addressed with technological solutions and through building relationships with internal teams. Conclusion: Barriers to trial delivery included infrequent exposure to the condition of interest and lack of continuity in research paramedic roles. Facilitators identified included flexibility of the research protocol, and organisational investment in the development of research paramedics.Participating in PARAMEDIC2 was challenging for the EMS involved, but ultimately strengthened their research culture.

Systematic analysis of approaches used in cardiac arrest trials to inform relatives about trial enrolment of non-surviving patients.

BACKGROUND: The recruitment of patients to emergency research studies without the requirement for prior informed consent has furthered the conduct of randomised studies in cardiac arrest. Frameworks enabling this vary around the world depending on local legal or ethical requirements. When an enrolled patient does not survive, researchers may take one of three approaches to inform relatives of their enrolment: a direct (active) approach, providing information indirectly (passively) and inviting relatives to seek further information if they choose, or providing no information about the trial (no attempt). Previous studies have described experiences of US researchers' active approach but there is little known about approaches elsewhere.We aimed to conduct a structured investigation of methods used in cardiac arrest trials to provide information about trial enrolment to relatives of non-surviving patients. METHODS: We systematically searched trial registries to identify randomised clinical trials that recruited cardiac arrest patients. Trials were eligible for inclusion if they recruited adults during cardiac arrest (or within 1 hour of return of spontaneous circulation) between 2010 and 2022 (in the decade prior to study conception). We extracted data from trial registries and, where relevant, published papers and protocols. Investigators were contacted and asked to describe the style, rationale and timing of approach to relatives of non-surviving patients. We present descriptive statistics. RESULTS: Our trial registry search identified 710 unique trials, of which 108 were eligible for inclusion. We obtained information from investigators for 64 (62%) trials. Approximately equal numbers of trials attempted to actively inform relatives of non-survivors (n=28 (44% (95% CI; 31% to 57%))), or made no attempt (n=25 (39% (95% CI; 27% to 52%))). The remaining studies provided general information about the trial to relatives but did not actively inform them (n=11 (17% (95% CI; 8% to 29%))). CONCLUSIONS: There is wide variability in the approach taken to informing relatives of non-surviving patients enrolled in cardiac arrest randomised clinical trials.

Prehospital optimal shock energy for defibrillation (POSED): A cluster randomised controlled feasibility trial.

Background: We explored the feasibility of a large-scale UK ambulance services trial of optimal defibrillation shock energy for out-of-hospital cardiac arrest. The primary objective of this feasibility study was to establish the number of eligible patients and the number recruited. Secondary outcomes were adherence to allocated treatment and data completeness. Methods: We conducted a three-arm parallel group cluster randomised controlled feasibility study in a single ambulance service in southern England. Adult patients in out-of-hospital cardiac arrest treated for a shockable rhythm were included. Zoll X series defibrillators (clusters) were randomised to deliver 120-150-200 J, 150-200-200 J, or 200-200-200 J shock strategies. Results: Between March 2022 and February 2023, we randomised 38 eligible patients (120-150-200 J (n = 12), 150-200-200 J (n = 10), 200-200-200 J (n = 16)) to the study. The recruitment rate per cluster was 0.07 per month. The median patient age was 71 years (IQR 59-81 years); 79% were male. Twenty-eight cardiac arrests (74%) occurred in a private residence, 29 (76%) were witnessed and 32 (84%) patients received bystander CPR. Treatment adherence was 93% and completeness of clinical and electrical outcomes was 86%. At 30 days, 3/36 (8.3%) patients survived; we were unable to collect survival outcomes for two patients. Defibrillation data collection became difficult when defibrillators became separated from their allocated vehicles. Conclusion: We have demonstrated the feasibility of a cluster randomised controlled trial of optimal shock energy for defibrillation in a UK ambulance service. We have identified possible solutions to issues relating to trial design.

Route of drug administration in out-of-hospital cardiac arrest: A protocol for a randomised controlled trial (PARAMEDIC-3).

Aims: The PARAMEDIC-3 trial evaluates the clinical and cost-effectiveness of an intraosseous first strategy, compared with an intravenous first strategy, for drug administration in adults who have sustained an out-of-hospital cardiac arrest. Methods: PARAMEDIC-3 is a pragmatic, allocation concealed, open-label, multi-centre, superiority randomised controlled trial. It will recruit 15,000 patients across English and Welsh ambulance services. Adults who have sustained an out-of-hospital cardiac arrest are individually randomised to an intraosseous access first strategy or intravenous access first strategy in a 1:1 ratio through an opaque, sealed envelope system. The randomised allocation determines the route used for the first two attempts at vascular access. Participants are initially enrolled under a deferred consent model.The primary clinical-effectiveness outcome is survival at 30-days. Secondary outcomes include return of spontaneous circulation, neurological functional outcome, and health-related quality of life. Participants are followed-up to six-months following cardiac arrest. The primary health economic outcome is incremental cost per quality-adjusted life year gained. Conclusion: The PARAMEDIC-3 trial will provide key information on the clinical and cost-effectiveness of drug route in out-of-hospital cardiac arrest.Trial registration: ISRCTN14223494, registered 16/08/2021, prospectively registered.

Validation of oxygen saturations measured in the community by emergency medical services as a marker of clinical deterioration in patients with confirmed COVID-19: a retrospective cohort study.

OBJECTIVES: To evaluate oxygen saturation and vital signs measured in the community by emergency medical services (EMS) as clinical markers of COVID-19-positive patient deterioration. DESIGN: A retrospective data analysis. SETTING: Patients were conveyed by EMS to two hospitals in Hampshire, UK, between 1 March 2020 and 31 July 2020. PARTICIPANTS: A total of 1080 patients aged ≥18 years with a COVID-19 diagnosis were conveyed by EMS to the hospital. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary study outcome was admission to the intensive care unit (ICU) within 30 days of conveyance, with a secondary outcome representing mortality within 30 days of conveyance. Receiver operating characteristic (ROC) analysis was performed to evaluate, in a retrospective fashion, the efficacy of different variables in predicting patient outcomes. RESULTS: Vital signs measured by EMS staff at the first point of contact in the community correlated with patient 30-day ICU admission and mortality. Oxygen saturation was comparably predictive of 30-day ICU admission (area under ROC (AUROC) 0.753; 95% CI 0.668 to 0.826) to the National Early Warning Score 2 (AUROC 0.731; 95% CI 0.655 to 0.800), followed by temperature (AUROC 0.720; 95% CI 0.640 to 0.793) and respiration rate (AUROC 0.672; 95% CI 0.586 to 0.756). CONCLUSIONS: Initial oxygen saturation measurements (on air) for confirmed COVID-19 patients conveyed by EMS correlated with short-term patient outcomes, demonstrating an AUROC of 0.753 (95% CI 0.668 to 0.826) in predicting 30-day ICU admission. We found that the threshold of 93% oxygen saturation is prognostic of adverse events and of value for clinician decision-making with sensitivity (74.2% CI 0.642 to 0.840) and specificity (70.6% CI 0.678 to 0.734).

Cardiac Arrest Bundle of cARE Trial (CABARET) survey of current UK neuroprotective CPR practice.

Despite low out of hospital cardiac arrest (OOHCA) survival rates within the UK, animal studies hint at improved cerebral blood flow via a bundled neuroprotective CPR approach. The CABARET study introduces three key devices: the Head Up Position (HUP), Active Compression/Decompression (ACD) CPR, and the Impedance Threshold Device (ITD). A survey involving 27 UK pre-hospital critical care services indicated none are using these interventions widely, either alone or bundled. The CABARET team is now initiating a pilot study to investigate the feasibility of this CPR bundle, aiming to fill the prevailing evidence void in resuscitation research.

Protocol for a cluster randomised controlled feasibility study of Prehospital Optimal Shock Energy for Defibrillation (POSED).

Aims: The Prehospital Optimal Shock Energy for Defibrillation (POSED) study will assess the feasibility of conducting a cluster randomised controlled study of clinical effectiveness in UK ambulance services to identify the optimal shock energy for defibrillation. Methods: POSED is a pragmatic, allocation concealed, open label, cluster randomised, controlled feasibility study. Defibrillators within a single UK ambulance service will be randomised in an equal ratio to deliver one of three shock strategies 120-150-200 J, 150-200-200 J, 200-200-200 J. Consecutive adults (≥18 years) presenting with out of hospital cardiac arrest requiring defibrillation will be eligible. The study plans to enrol 90 patients (30 in each group). Patients (or their relatives for non-survivors) will be informed about trial participation after the initial emergency has resolved. Survivors will be invited to consent to participate in follow-up (i.e., at 30 days or discharge).The primary feasibility outcome is the proportion of eligible patients who receive the randomised study intervention. Secondary feasibility outcomes will include recruitment rate, adherence to allocated treatment and data completeness. Clinical outcomes will include Return of an Organised Rhythm (ROOR) at 2 minutes post-shock, refibrillation rate, Return of Spontaneous Circulation (ROSC) at hospital handover, survival and neurological outcome at 30 days. Conclusion: The POSED study will assess the feasibility of a large-scale trial and explore opportunities to optimise the trial protocol.Trial registration: ISRCTN16327029.

Effectiveness of alternative shock strategies for out-of-hospital cardiac arrest: A systematic review.

Aim: To determine the optimal first-shock energy level for biphasic defibrillation and whether fixed or escalating protocols for subsequent shocks are most effective. Methods: We searched Medline, Embase, Cochrane CENTRAL, CINAHL, the Web of Science and national and international trial registry databases for papers published from database inception to January 2022. We reviewed reference lists of key papers to identify additional references. The population included adults sustaining non traumatic out-of-hospital cardiac arrest subject to attempted defibrillation. Studies of internal or monophasic defibrillation and studies other than randomised controlled trials or prospective cohorts were excluded. Two reviewers assessed study relevance. Data extraction and risk of bias assessment, using the ROBINS-I tool, were conducted by one reviewer and checked by a second reviewer. Data underwent intention-to-treat analysis. Results: We identified no studies evaluating first shock energy. Only one study (n = 738) comparing fixed versus escalating energy met eligibility criteria: a prospective cohort analysis of a randomised controlled trial of manual versus mechanical CPR. High fixed (360 J) energy was compared with an escalating (200-200/300-360 J) strategy. Researchers found 27.5% (70/255) of patients in the escalating energy group and 27.61% (132/478) in the fixed high energy group survived to hospital discharge (unadjusted risk ratio 0.99, 95% CI 0.73, 1.23). Results were of very low certainty as the study was at serious risk of bias. Conclusion: This systematic review did not identify an optimal first-shock energy for biphasic defibrillation. We identified no survival advantage at 30 days when comparing 360 J fixed with 200 J escalating strategy.

Improving recording and reporting of dementia and frailty via electronic patient record by ambulance staff in a single service (IDEAS).

BACKGROUND: Dementia is common in older adults assessed by ambulance services. However, inconsistent reporting via the patient record may result in this diagnosis being overlooked by healthcare staff further down the care pathway. This can have a deleterious effect on subsequent patient care, increasing morbidity and mortality. We sought to understand how and where ambulance staff would like to record this finding on the electronic patient record (ePR). METHODS: We designed and implemented a survey of ambulance staff in a single service to understand how they identify patients with dementia, how they record dementia on the ePR and how the ePR could be improved to better capture dementia. Scoping questions on frailty were included. The survey was tested using cognitive interviewing. Analysis was conducted using descriptive statistics for closed questions and thematic analysis for open questions as appropriate. RESULTS: 131 surveys were completed; 60% of participants were paramedics and 40% were other grades of front line staff. Participants reported consulting electronic/paper sources, and individuals such as carers involved in the patients' care, to establish whether dementia had been diagnosed. Frailty assessments were prompted by social context, reduced mobility, a fall or diagnosis of dementia. Staff reported documenting dementia in 20 different areas on the ePR and 46% of participants stated a preference for a designated area to record the information. However, 15% indicated it was not necessary to record dementia or that no ePR changes were required. CONCLUSIONS: We have highlighted the variation in ambulance staff practice in recording of dementia. Alterations to the ePR are required to ensure that dementia is recorded consistently and is easily retrievable. Clearer guidance on when to assess frailty may also enhance information provision to care staff in other sectors, resulting in more appropriate clinical and social care.

Reducing ambulance conveyance for older people with and without dementia: evidence of the role of social care from a regional, year-long service evaluation using retrospective routine data.

INTRODUCTION: Older people, especially those with dementia, have a high risk of deterioration following admission to hospital. More than 60% of older people attended by South Central Ambulance Service (SCAS) clinicians are conveyed to hospital, although many conveyances may not have been due to life-threatening conditions. We aimed to understand patterns of conveyance and alternative referral pathways used following ambulance attendance to an older person. METHODS: Service evaluation, using routinely collected, anonymised electronic records. PARTICIPANTS: Electronic records of people aged ≥75 years for whom an ambulance was dispatched between April 2016 and March 2017 within the geographical boundaries of SCAS NHS Foundation Trust, who were alive on arrival of the ambulance. Conveyance rates are described according to patient and emergency-call characteristics. Logistic regression was used to produce adjusted odds ratios for conveyance. Alternative referral pathways used are described. RESULTS: Of 110,781 patients attended, 64% were conveyed to hospital. Factors associated with reduced odds of conveyance included out-of-hours calls (adjusted odds ratio (aOR) 0.82 [0.79-0.85]), living alone with a care package or with family plus care package (aOR 0.66 [0.62-0.69]; aOR 0.58 [0.54-0.62] respectively) and a record of dementia (0.91 [0.87-0.96]). Living in a nursing home was associated with an increased risk of conveyance (aOR 1.25 [1.15-1.36]). Patients with dementia with more income were significantly less likely to be conveyed than those with less income. Alternative referral services were used in 22% of non-conveyed patients, most commonly GP, out-of-hours and falls services. DISCUSSION: People aged ≥75 years have high rates of conveyance, which are influenced by factors such as out-of-hours calls, dementia and receipt of social care. Low use of alternative referral services may reflect limited availability or difficulty in access. A better understanding of how these factors influence ambulance clinician decision-making is integral to improvement of outcomes for older people.

An EXploration of the facilitators and barriers to paramedics' assessment and treatment of pain in PAediatric patients following Trauma (EX-PAT).

BACKGROUND: Pain is a common symptom among patients presenting to ambulance services and is often associated with traumatic injury. Assessment and management of pain in children in the pre-hospital setting is suboptimal. This study aimed to understand the facilitators and barriers experienced by paramedics in their assessment and management of pain in children who have sustained traumatic injuries. METHODS: Face-to-face, audio-recorded semi-structured interviews using a piloted topic guide were conducted with paramedics employed by South Central Ambulance Service NHS Foundation Trust. Interviews were professionally transcribed, coded manually and analysed using thematic analysis. RESULTS: Eleven interviews were conducted; three themes related to assessment and three related to management were identified. Previous positive experiences of utilising pain scoring tools were identified as a facilitator to pain assessment, whereas a lack of confidence in using pain scoring tools was a barrier. Patients' understanding of and compliance with the tools were both a facilitator and a barrier to assessment. Facilitators to management included personal sub-themes of colleagues/others, exposure, being a parent, technology, severity of the injury and subjective pain scoring. Organisational facilitators included medicines, routes, and alternative methods. Situational facilitators included patient-specific solutions and parents. Five personal barriers to management included medicines, skill, consequences to self or patient, negative interactions, and limited exposure. Three organisational barriers included medicines and routes, equipment issues and choices, and training and culture. Within the theme of situation, two sub-themes emerged: patient-specific issues and environment-specific issues. Novel facilitators to emerge were those of alternative methods and being a parent. CONCLUSION: A multitude of factors incorporating situational, organisational, and personal all combine to determine how paramedics treat paediatric trauma patients. A multi-stakeholder approach to providing clearer assessment tools, improved education, equipment, and pharmacy options may improve assessment and management compliance for the benefit of the patient.

Adrenaline to improve survival in out-of-hospital cardiac arrest: the PARAMEDIC2 RCT.

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 in Health Technology Assessment; Vol. 25, No. 25. See the NIHR Journals Library website for further project information.

Cardiac arrest is a medical emergency that happens when the heart suddenly stops pumping effectively. When cardiac arrest happens, awareness is lost within seconds. If emergency treatment is not started quickly, the person will die. The first treatments of cardiac arrest involve pressing on the chest, giving rescue breaths and defibrillation (electric shocks applied to the heart). If these treatments do not work, ambulance paramedics use a drug called adrenaline to try to restart the heart. Although this treatment has been used for many years, some recent research suggests that it may cause more harm than good. In this research study, we compared the effects of giving adrenaline with the effects of not giving adrenaline to people who had a cardiac arrest in the community. The research showed that adrenaline was effective at restarting the heart, so more people survived long enough to be admitted to hospital. Thirty days later, 130 out of 4012 patients (3.2%) who received adrenaline and 94 out of 3995 (2.4%) who did not receive adrenaline were alive. However, adrenaline did not improve the number of patients who went home from hospital having made a good recovery and were able to care for themselves. The evidence suggests that adrenaline represents a poor use of NHS funds on cost-effectiveness grounds. In a community survey, 95% of people who responded thought that long-term survival with good brain function was more important than just being alive. Further research exploring the opinions of patients and the public will help to understand the results of this research for the NHS.

Long term outcomes of participants in the PARAMEDIC2 randomised trial of adrenaline in out-of-hospital cardiac arrest.

AIMS: We recently reported early outcomes in patients enrolled in a randomised trial of adrenaline in out-of-hospital cardiac arrest: the PARAMEDIC2 (Prehospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug Administration in Cardiac Arrest) trial. The purpose of the present paper is to report long-term survival, quality of life, functional and cognitive outcomes at 3, 6 and 12-months. METHODS: PARAMEDIC2 was a pragmatic, individually randomised, double blind, controlled trial with an economic evaluation. Patients were randomised to either adrenaline or placebo. This paper reports results on the modified Rankin Scale scores at 6-months, survival at 6 and 12-months, as well as other cognitive, functional and quality of life outcomes collected at 3 and 6 months (Two Simple Questions, the Mini Mental State Examination, the Informant Questionnaire on Cognitive Decline Evaluation for Cardiac Arrest, Hospital Anxiety and Depression Scale, the Post Traumatic Stress Disorder Checklist - Civilian Version, Short-Form 12-item Health Survey and the EuroQoL EQ-5D-5L). RESULTS: 8014 patients were randomised with confirmed trial drug administration. At 6-months, 78 (2.0%) of the patients in the adrenaline group and 58 (1.5%) of patients in the placebo group had a favourable neurological outcome (adjusted odds ratio 1.35 [95% confidence interval: 0.93, 1.97]). 117 (2.9%) patients were alive at 6-months in the adrenaline group compared with 86 (2.2%) in the placebo group (1.43 [1.05, 1.96], reducing to 107 (2.7%) and 80 (2.0%) respectively at 12-months (1.38 [1.00, 1.92]). Measures of 3 and 6-month cognitive, functional and quality of life outcomes were reduced, but there was no strong evidence of differences between groups. CONCLUSION: Adrenaline improved survival through to 12-months follow-up. The study did not find evidence of improvements in favourable neurological outcomes. (ISCRTN 73485024).

Death and dying in prehospital care: what are the experiences and issues for prehospital practitioners, families and bystanders? A scoping review.

OBJECTIVE: To identify the factors that shape and characterise experiences of prehospital practitioners (PHPs), families and bystanders in the context of death and dying outside of the hospital environment where PHPs respond. DESIGN: A scoping review using Arksey and O'Malley's five-stage framework. Papers were analysed using thematic analysis. DATA SOURCES: MEDLINE; Embase; CINAHL; Scopus; Social Sciences Citation Index (Web of Science), ProQuest Dissertations & Theses A&I (Proquest), Health Technology Assessment database; PsycINFO; Grey Literature Report and PapersFirst were searched from January 2000 to May 2019. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Qualitative and mixed methods studies reporting the experiences of PHPs, families and bystanders of death and dying in prehospital settings as a result of natural causes, trauma, suicide and homicide, >18 years of age, in Europe, USA, Canada, Australia and New Zealand. RESULTS: Searches identified 15 352 papers of which 51 met the inclusion criteria. The review found substantial evidence of PHP experiences, except call handlers, and papers reporting family and bystander experiences were limited. PHP work was varied and complex, while confident in clinical work, they felt less equipped to deal with the emotion work, especially with an increasing role in palliative and end-of-life care. Families and bystanders reported generally positive experiences but their support needs were rarely explored. CONCLUSIONS: To the best of our knowledge this is the first review that explores the experiences of PHPs, families and bystanders. An important outcome is identifying current gaps in knowledge where further empirical research is needed. The paucity of evidence suggested by this review on call handlers, families and bystanders presents opportunities to investigate their experiences in greater depth. Further research to address the current knowledge gaps will be important to inform future policy and practice.

Cost-effectiveness of adrenaline for out-of-hospital cardiac arrest.

BACKGROUND: The 'Prehospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug Administration In Cardiac Arrest' (PARAMEDIC2) trial showed that adrenaline improves overall survival, but not neurological outcomes. We sought to determine the within-trial and lifetime health and social care costs and benefits associated with adrenaline, including secondary benefits from organ donation. METHODS: We estimated the costs, benefits (quality-adjusted life years (QALYs)) and incremental cost-effectiveness ratios (ICERs) associated with adrenaline during the 6-month trial follow-up. Model-based analyses explored how results altered when the time horizon was extended beyond 6 months and the scope extended to include recipients of donated organs. RESULTS: The within-trial (6 months) and lifetime horizon economic evaluations focussed on the trial population produced ICERs of £1,693,003 (€1,946,953) and £81,070 (€93,231) per QALY gained in 2017 prices, respectively, reflecting significantly higher mean costs and only marginally higher mean QALYs in the adrenaline group. The probability that adrenaline is cost-effective was less than 1% across a range of cost-effectiveness thresholds. Combined direct economic effects over the lifetimes of survivors and indirect economic effects in organ recipients produced an ICER of £16,086 (€18,499) per QALY gained for adrenaline with the probability that adrenaline is cost-effective increasing to 90% at a £30,000 (€34,500) per QALY cost-effectiveness threshold. CONCLUSIONS: Adrenaline was not cost-effective when only directly related costs and consequences are considered. However, incorporating the indirect economic effects associated with transplanted organs substantially alters cost-effectiveness, suggesting decision-makers should consider the complexity of direct and indirect economic impacts of adrenaline. TRIAL REGISTRATION: ISRCTN73485024 . Registered on 13 March 2014.

Patient safety incidents and medication errors during a clinical trial: experience from a pre-hospital randomized controlled trial of emergency medication administration.

AIM: To assess and evaluate patient safety incidents and in particular, medication errors, during a large multi-center pre-hospital trial of emergency therapy (PARAMEDIC2), in order to inform and improve future pre-hospital medicines trials. METHODS: The PARAMEDIC2 trial was undertaken across five NHS Ambulance Services in England and Wales with randomisation between December 2014 and October 2017. Patients with an out -of-hospital cardiac arrest unresponsive to initial resuscitation were randomly assigned to 1 mg intravenous adrenaline or matching placebo. Records were reviewed to identify trial medication errors involving documentation and/or clinical protocol errors occurring in trial participants. Causes of medication errors, including root cause analysis where available, were reviewed to identify patterns and themes contributing to these errors. RESULTS: Eight thousand sixteen patients were enrolled, of whom 4902 received trial medication. A total of 331 patient safety incidents was reported, involving 295 patients, representing an overall rate of 3.6% of these, 166 (50.2%) were documentation errors while 165 (49.8%) were clinical protocol/medication errors. An overall rate of 0-4.5% was reported across all five ambulance services, with a mean of 2.0%. These errors had no impact on patient care or the trial and were all resolved CONCLUSION: The overall medication error rate of 1.8% primarily consisted of administration of open-label adrenaline and confusion with trial medication packs. A similar number of patients had documentation errors. This study is the first to provide data on patient safety incidents relating to medication errors encountered during a pre-hospital trial of emergency medication administration and will provide supporting data for planning future trials in this area.

The influence of time to adrenaline administration in the Paramedic 2 randomised controlled trial.

PURPOSE: To examine the time to drug administration in patients with a witnessed cardiac arrest enrolled in the Pre-Hospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug Administration in Cardiac Arrest (PARAMEDIC2) randomised controlled trial. METHODS: The PARAMEDIC2 trial was undertaken across 5 NHS ambulance services in England and Wales with randomisation between December 2014 and October 2017. Patients with an out-of-hospital cardiac arrest who were unresponsive to initial resuscitation attempts were randomly assigned to 1 mg intravenous adrenaline or matching placebo according to treatment packs that were identical apart from treatment number. Participants and study staff were masked to treatment allocation. RESULTS: 8016 patients were enrolled, 4902 sustained a witnessed cardiac arrest of whom 2437 received placebo and 2465 received adrenaline. The odds of return of spontaneous circulation decreased in both groups over time but at a greater rate in the placebo arm odds ratio (OR) 0.93 (95% CI 0.92-0.95) compared with the adrenaline arm OR 0.96 (95% CI 0.95-0.97); interaction OR: 1.03, 95% CI 1.01-1.05, p = 0.005. By contrast, although the rate of survival and favourable neurological outcome decreased as time to treatment increased, the rates did not differ between the adrenaline and placebo groups. CONCLUSION: The rate of return of spontaneous circulation, survival and favourable neurological outcomes decrease over time. As time to drug treatment increases, adrenaline increases the chances of return of spontaneous circulation. Longer term outcomes were not affected by the time to adrenaline administration. (ISRCTN73485024).

The effects of adrenaline in out of hospital cardiac arrest with shockable and non-shockable rhythms: Findings from the PACA and PARAMEDIC-2 randomised controlled trials.

INTRODUCTION: Previous research suggests there may be differences in the effects of adrenaline related to the initial cardiac arrest rhythm. The aim of this study was to assess the effect of adrenaline compared with placebo according to whether the initial cardiac arrest rhythm was shockable or non-shockable. METHODS: Return of spontaneous circulation (ROSC), survival and neurological outcomes according to the initial arrest rhythm were compared amongst patients enrolled in the PARAMEDIC-2 randomised, placebo controlled trial. The results of the PARAMEDIC-2 and PACA out of hospital cardiac arrest trials were combined and meta-analysed. RESULTS: The initial rhythm was known for 3929 (98.2%) in the placebo arm and 3919 (97.6%) in the adrenaline arm. The effect on the rate of ROSC of adrenaline relative to placebo was greater in patients with non-shockable cardiac rhythms (1002/3003 (33.4%) versus 222/3005 (7.4%), adjusted OR: 6.5, (95% CI 5.6-7.6)) compared with shockable rhythms 349/716 (48.7%) versus (208/702 (29.6%), adjusted OR: 2.3, 95%CI: 1.9-2.9)). The adjusted odds ratio for survival at discharge for non-shockable rhythms was 2.5 (1.3, 4.8) and 1.3 (0.9, 1.8) for shockable rhythms (P value for interaction 0.065) and 1.8 (0.8-4.1) and 1.1 (0.8-1.6) respectively for neurological outcome at discharge (P value for interaction 0.295). Meta-analysis found similar results. CONCLUSION: Relative to placebo, the effects of adrenaline ROSC are greater for patients with an initially non-shockable rhythm than those with a shockable rhythms. Similar patterns are observed for longer term survival outcomes and favourable neurological outcomes, although the differences in effects are less pronounced. ISRCTN73485024.

Patient and clinician factors associated with prehospital pain treatment and outcomes: cross sectional study.

OBJECTIVE: We aimed to identify how patient (age, sex, condition) and paramedic factors (sex, role) affected prehospital analgesic administration and pain alleviation. METHODS: We used a cross-sectional design with a 7-day retrospective sample of adults aged 18 years or over requiring primary emergency transport to hospital, excluding patients with Glasgow Coma Scale below 13, in two UK ambulance services. Multivariate multilevel regression using Stata 14 analysed factors independently associated with analgesic administration and a clinically meaningful reduction in pain (≥2 points on 0-10 numerical verbal pain score [NVPS]). RESULTS: We included data on 9574 patients. At least two pain scores were recorded in 4773 (49.9%) patients. For all models fitted there was no significant relationship between analgesic administration or pain reduction and sex of the patient or ambulance staff. Reduction in pain (NVPS ≥2) was associated with ambulance crews including at least one paramedic (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.14 to 2.04, p < 0.01), with any recorded pain score and suspected cardiac pain (OR 2.2, 95% CI 1.02 to 4.75). Intravenous morphine administration was also more likely where crews included a paramedic (OR 2.82, 95% CI 1.93 to 4.13, P < 0.01), attending patients aged 51 to 64 years (OR 2.04, 95% CI 1.21 to 3.45, p = 0.01), in moderate to severe (NVPS 4-10) compared with lower levels of pain for any clinical condition group compared with the reference condition. CONCLUSION: There was no association between patient sex or ambulance staff sex or grade and analgesic administration or pain reduction.

Optimising ambulance service contribution to clinical trials: a phenomenological exploration using focus groups.

INTRODUCTION: Out-of-hospital cardiac arrest trials can prove challenging and there is a need to share learning from those that have recruited successfully. We have just completed three years of recruitment to PARAMEDIC2, a placebo-controlled trial of adrenaline in out-of-hospital cardiac arrest. This study was designed to describe the experience of operational ambulance staff involved in recruiting patients into PARAMEDIC2. METHODS: Four focus groups involving trial paramedics and supporting members of the emergency care team were conducted across different geographical regions of a single UK ambulance service participating in the PARAMEDIC2 study. Data analysis was supported by NVivo 12 and themes were identified using a thematic analysis approach. RESULTS: Forty-four participants contributed to the focus groups. Four overarching themes were identified: context for the research, ethical concerns, concerns at the patient's side and ongoing trial support. Participants felt that research such as PARAMEDIC2 is important and necessary to drive medical progress. They valued the opportunity to be part of a large project. Due to the deferred consent model employed, public awareness of the trial was felt to be important. Most expressed equipoise regarding adrenaline, but some felt concerned about enrolling younger patients and there was discussion around what constitutes a successful outcome. Struggles with ethical concerns were overcome through training and one-to-one discussion with research paramedics. Participants valued feedback on their performance of trial tasks, but also wanted feedback on their resuscitation skills. Cardiac arrest places a high cognitive demand on paramedics; simplicity and reinforcement of trial processes were key to facilitating recruitment. Caring for relatives was a high priority for paramedics and some felt conflicted about not discussing the trial with them. CONCLUSIONS: This study has provided insights into paramedic experience of a large-scale pre-hospital trial. Investment in time and resource to provide face-to-face training and personalised feedback to paramedics can foster engagement and optimise performance.