Helen Pocock

Mechanical versus manual chest compression for out-of-hospital cardiac arrest (PARAMEDIC) : a pragmatic, cluster randomised controlled trial

BACKGROUND Mechanical chest compression devices have the potential to help maintain high-quality cardiopulmonary resuscitation (CPR), but despite their increasing use, little evidence exists for their effectiveness. We aimed to study whether the introduction of LUCAS-2 mechanical CPR into front-line emergency response vehicles would improve survival from out-of-hospital cardiac arrest. METHODS The pre-hospital randomised assessment of a mechanical compression device in cardiac arrest (PARAMEDIC) trial was a pragmatic, cluster-randomised open-label trial including adults with non-traumatic, out-of-hospital cardiac arrest from four UK Ambulance Services (West Midlands, North East England, Wales, South Central). 91 urban and semi-urban ambulance stations were selected for participation. Clusters were ambulance service vehicles, which were randomly assigned (1:2) to LUCAS-2 or manual CPR. Patients received LUCAS-2 mechanical chest compression or manual chest compressions according to the first trial vehicle to arrive on scene. The primary outcome was survival at 30 days following cardiac arrest and was analysed by intention to treat. Ambulance dispatch staff and those collecting the primary outcome were masked to treatment allocation. Masking of the ambulance staff who delivered the interventions and reported initial response to treatment was not possible. The study is registered with Current Controlled Trials, number ISRCTN08233942. FINDINGS We enrolled 4471 eligible patients (1652 assigned to the LUCAS-2 group, 2819 assigned to the control group) between April 15, 2010 and June 10, 2013. 985 (60%) patients in the LUCAS-2 group received mechanical chest compression, and 11 (<1%) patients in the control group received LUCAS-2. In the intention-to-treat analysis, 30 day survival was similar in the LUCAS-2 group (104 [6%] of 1652 patients) and in the manual CPR group (193 [7%] of 2819 patients; adjusted odds ratio [OR] 0·86, 95% CI 0·64-1·15). No serious adverse events were noted. Seven clinical adverse events were reported in the LUCAS-2 group (three patients with chest bruising, two with chest lacerations, and two with blood in mouth). 15 device incidents occurred during operational use. No adverse or serious adverse events were reported in the manual group. INTERPRETATION We noted no evidence of improvement in 30 day survival with LUCAS-2 compared with manual compressions. On the basis of ours and other recent randomised trials, widespread adoption of mechanical CPR devices for routine use does not improve survival. FUNDING National Institute for Health Research HTA - 07/37/69.

Prehospital randomised assessment of a mechanical compression device in out-of-hospital cardiac arrest (PARAMEDIC): a pragmatic, cluster randomised trial and economic evaluation

BACKGROUND Mechanical chest compression devices may help to maintain high-quality cardiopulmonary resuscitation (CPR), but little evidence exists for their effectiveness. We evaluated whether or not the introduction of Lund University Cardiopulmonary Assistance System-2 (LUCAS-2; Jolife AB, Lund, Sweden) mechanical CPR into front-line emergency response vehicles would improve survival from out-of-hospital cardiac arrest (OHCA). OBJECTIVE Evaluation of the LUCAS-2 device as a routine ambulance service treatment for OHCA. DESIGN Pragmatic, cluster randomised trial including adults with non-traumatic OHCA. Ambulance dispatch staff and those collecting the primary outcome were blind to treatment allocation. Blinding of the ambulance staff who delivered the interventions and reported initial response to treatment was not possible. We also conducted a health economic evaluation and a systematic review of all trials of out-of-hospital mechanical chest compression. SETTING Four UK ambulance services (West Midlands, North East England, Wales and South Central), comprising 91 urban and semiurban ambulance stations. Clusters were ambulance service vehicles, which were randomly assigned (approximately 1 : 2) to the LUCAS-2 device or manual CPR. PARTICIPANTS Patients were included if they were in cardiac arrest in the out-of-hospital environment. Exclusions were patients with cardiac arrest as a result of trauma, with known or clinically apparent pregnancy, or aged < 18 years. INTERVENTIONS Patients received LUCAS-2 mechanical chest compression or manual chest compressions according to the first trial vehicle to arrive on scene. MAIN OUTCOME MEASURES Survival at 30 days following cardiac arrest; survival without significant neurological impairment [Cerebral Performance Category (CPC) score of 1 or 2]. RESULTS We enrolled 4471 eligible patients (1652 assigned to the LUCAS-2 device and 2819 assigned to control) between 15 April 2010 and 10 June 2013. A total of 985 (60%) patients in the LUCAS-2 group received mechanical chest compression and 11 (< 1%) patients in the control group received LUCAS-2. In the intention-to-treat analysis, 30-day survival was similar in the LUCAS-2 (104/1652, 6.3%) and manual CPR groups [193/2819, 6.8%; adjusted odds ratio (OR) 0.86, 95% confidence interval (CI) 0.64 to 1.15]. Survival with a CPC score of 1 or 2 may have been worse in the LUCAS-2 group (adjusted OR 0.72, 95% CI 0.52 to 0.99). No serious adverse events were noted. The systematic review found no evidence of a survival advantage if mechanical chest compression was used. The health economic analysis showed that LUCAS-2 was dominated by manual chest compression. LIMITATIONS There was substantial non-compliance in the LUCAS-2 arm. For 272 out of 1652 patients (16.5%), mechanical chest compression was not used for reasons that would not occur in clinical practice. We addressed this issue by using complier average causal effect analyses. We attempted to measure CPR quality during the resuscitation attempts of trial participants, but were unable to do so. CONCLUSIONS There was no evidence of improvement in 30-day survival with LUCAS-2 compared with manual compressions. Our systematic review of recent randomised trials did not suggest that survival or survival without significant disability may be improved by the use of mechanical chest compression. FUTURE WORK The use of mechanical chest compression for in-hospital cardiac arrest, and in specific circumstances (e.g. transport), has not yet been evaluated. TRIAI REGISTRATION Current Controlled Trials ISRCTN08233942. 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. 21, No. 11. See the NIHR Journals Library website for further project information.

A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest

BACKGROUND Concern about the use of epinephrine as a treatment for out‐of‐hospital cardiac arrest led the International Liaison Committee on Resuscitation to call for a placebocontrolled trial to determine whether the use of epinephrine is safe and effective in such patients. METHODS In a randomized, double‐blind trial involving 8014 patients with out‐of‐hospital cardiac arrest in the United Kingdom, paramedics at five National Health Service ambulance services administered either parenteral epinephrine (4015 patients) or saline placebo (3999 patients), along with standard care. The primary outcome was the rate of survival at 30 days. Secondary outcomes included the rate of survival until hospital discharge with a favorable neurologic outcome, as indicated by a score of 3 or less on the modified Rankin scale (which ranges from 0 [no symptoms] to 6 [death]). RESULTS At 30 days, 130 patients (3.2%) in the epinephrine group and 94 (2.4%) in the placebo group were alive (unadjusted odds ratio for survival, 1.39; 95% confidence interval [CI], 1.06 to 1.82; P = 0.02). There was no evidence of a significant difference in the proportion of patients who survived until hospital discharge with a favorable neurologic outcome (87 of 4007 patients [2.2%] vs. 74 of 3994 patients [1.9%]; unadjusted odds ratio, 1.18; 95% CI, 0.86 to 1.61). At the time of hospital discharge, severe neurologic impairment (a score of 4 or 5 on the modified Rankin scale) had occurred in more of the survivors in the epinephrine group than in the placebo group (39 of 126 patients [31.0%] vs. 16 of 90 patients [17.8%]). CONCLUSIONS In adults with out‐of‐hospital cardiac arrest, the use of epinephrine resulted in a significantly higher rate of 30‐day survival than the use of placebo, but there was no significant between‐group difference in the rate of a favorable neurologic outcome because more survivors had severe neurologic impairment in the epinephrine group. (Funded by the U.K. National Institute for Health Research and others; Current Controlled Trials number, ISRCTN73485024.)

Post-admission outcomes of participants in the PARAMEDIC trial : a cluster randomised trial of mechanical or manual chest compressions

BACKGROUND The PARAMEDIC cluster randomised trial evaluated the LUCAS mechanical chest compression device, and did not find evidence that use of mechanical chest compression led to an improvement in survival at 30 days. This paper reports patient outcomes from admission to hospital to 12 months after randomisation. METHODS Information about hospital length of stay and intensive care management was obtained through linkage with Hospital Episode Statistics and the Intensive Care National Audit and Research Centre. Patients surviving to hospital discharge were approached to complete questionnaires (SF-12v2, EQ-5D, MMSE, HADS and PTSD-CL) at 90days and 12 months. The study is registered with Current Controlled Trials, number ISRCTN08233942. RESULTS 377 patients in the LUCAS arm and 658 patients in the manual chest compression were admitted to hospital. Hospital and intensive care length of stay were similar. Long term follow-up assessments were limited by poor response rates (53.7% at 3 months and 55.6% at 12 months). Follow-up rates were lower in those with worse neurological function. Among respondents, long term health related quality of life outcomes and emotional well-being was similar between groups. Cognitive function, measured by MMSE, was marginally lower in the LUCAS arm mean 26.9 (SD 3.7) compared to control mean 28.0 (SD 2.3), adjusted mean difference -1.5 (95% CI -2.6 to -0.4). CONCLUSION There were no clinically important differences identified in outcomes at long term follow-up between those allocated to the mechanical chest compression compared to those receiving manual chest compression.

Human factors in prehospital research: lessons from the PARAMEDIC trial

Background There is an urgent need to develop prehospital research capability in order to improve the care of patients presenting to emergency medical services (EMS). The Prehospital Randomised Assessment of a Mechanical compression Device In Cardiac arrest trial, a pragmatic cluster randomised trial evaluating the LUCAS-2 device, represents the largest randomised controlled trial conducted by UK ambulance services to date. The aim of this study was to identify and analyse factors that may influence paramedic attitudes to, and participation in, clinical trials. Methods Personal and organisational experience from this trial was assessed by feedback from a workshop attended by collaborators from participating EMS and a survey of EMS personnel participating in the trial. A work systems model was used to explain the impact of five interwoven themes—person, organisation, tasks, tools & technology and environment—on trial conduct including gathering of high-quality data. Results The challenge of training a geographically diverse EMS workforce required development of multiple educational solutions. In order to operationalise the trial protocol, internal organisational relationships were perceived as essential. Staff perceptions of the normalisation of participation and ownership of the trial influenced protocol compliance rates. Undertaking research was considered less burdensome when additional tasks were minimised and more difficult when equipment was unavailable. The prehospital environment presents practical challenges for undertaking clinical trials, but our experience suggests these are not insurmountable and should not preclude conducting high-quality research in this setting. Conclusions Application of a human factors model to the implementation of a clinical trial protocol has improved understanding of the work system, which can inform the future conduct of clinical trials and foster a research culture within UK ambulance services. Trial registration number ISRCTN08233942.

Feasibility of data linkage in the PARAMEDIC trial : a cluster randomised trial of mechanical chest compression in out of hospital cardiac arrest

Objectives There is considerable interest in reducing the cost of clinical trials. Linkage of trial data to administrative datasets and disease-specific registries may improve trial efficiency, but it has not been reported in resuscitation trials conducted in the UK. To assess the feasibility of using national administrative and clinical datasets to follow up patients transported to hospital following attempted resuscitation in a cluster randomised trial of a mechanical chest compression device in out-of-hospital cardiac arrest. Methods Hospital data on trial participants were requested from Hospital Episode Statistics (HES), the Intensive Care National Audit and Research Centre, and Myocardial Ischaemia National Audit Project and National Audit of Percutaneous Coronary Interventions, using unique patient identifiers. Linked data were received between June 2014 and June 2015. Results Of 4471 patients randomised in the pre-hospital randomised assessment of a mechanical compression device in cardiac arrest (PARAMEDIC) trial, 2398 (53.6%) were not known to be deceased at emergency department arrival and were eligible for linkage. We achieved an overall match rate of 86.7% in the combined HES accident and emergency, inpatient and critical care dataset, with variable match rates (4.2%–80.4%) in individual datasets. Patient demographics, cardiac arrest-related characteristics and major outcomes were predominantly similar between HES matched and unmatched groups, in the linkage apart from location, response time and return of spontaneous circulation (ROSC) at handover. Conclusions This study shows that it is feasible to track patients from the prehospital setting through to hospital admission using routinely available administrative datasets with a moderate to high degree of success. This approach has the potential to complement the trial data with the demographic and clinical management information about the studied cohort, as well as to improve the efficiency and reduce the costs of follow-up in cardiac arrest trials. Clinical trial registration ISRCTN08233942; Post-results.

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 18years 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 64years (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.

PP29 Exploring factors increasing paramedics’ likelihood of administering analgesia in pre-hospital pain: cross sectional study (explain)

Background Paramedics play an important role in reducing pain in patients calling an ambulance. We aimed to identify how patient factors (age, sex), clinical condition and paramedic factors (sex, role seniority) affected pain treatment and outcomes. Methods We used a cross sectional design using routine retrospective data a one-week sample of all 999 ambulance attendances in two large regional UK ambulance services for all patients aged 18 years or over where pain was identified in people requiring primary transport to hospital. Exclusion criteria patients with a Glasgow Coma Scale score below 13, or patients not attended by a paramedic. We used a multilevel design, using a regression model to investigate which factors were independently associated with administration of analgesia and reduction in pain, taking into account confounders including patient demographics and other variables. Analysis was performed with Stata. Results We collected data on 9574 patients (service 1, 2; n=3344, 6230 respectively) including 4911 (51.3%) male and 4524 (47.3%) females (1.5% missing). Initial pain score was not recorded in 42.4% (4063/9574). The multilevel model suggested that the factors associated with use of strong opiates (morphine intravenously or orally) was a pain score of 7 or above, patient age 50–64 years and suspected fractured neck of femur. Reduction in pain score of 2 or more points was significant whatever the initial pain score and associated with age 50–84 years. There was no association between use of strong opiate analgesic or reduction in pain score and sex of patient and/or sex of paramedic or crew member. Conclusion Our initial analysis showed a high level of non-recording of pain scores. There was no association between use of strong opiate analgesics or reduction in pain score of 2 points or more with patient sex or crew sex or paramedic skill level.