Search

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.

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., (Copyright © 2019. Published by Elsevier B.V.)

Background: Adrenaline is the primary drug of choice for resuscitation from out-of-hospital cardiac arrest (OHCA). Although adrenaline may increase the chance of achieving return of spontaneous circulation (ROSC), there is limited evidence that repeated doses of adrenaline improves overall survival, and increasing evidence of a detrimental effect on neurological function in survivors. This paper reports the relationship between repeated doses of adrenaline and survival in a cohort of patients attended by the London Ambulance Service in the United Kingdom., Methods: A retrospective review of OHCA treated by the London Ambulance Service over a one year period. Patients aged ≥18 years who received one or more doses of adrenaline (1 mg bolus) during resuscitation were included in the analyses. Outcomes described are survival to hospital discharge and survival to one year post-arrest., Results: Over the one year study period, 3151 patients received adrenaline during OHCA. A significant inverse relationship was found between increasing cumulative doses of adrenaline and survival both to hospital discharge and one year post-arrest. No patients survived after receiving more than ten adrenaline doses., Conclusion: Our study indicates that repeated doses of adrenaline are associated with decreasing odds of survival. There were no survivors amongst patients requiring more than 10 doses of adrenaline., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

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 placebo-controlled 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 .).

Background: Epinephrine has been presumed to improve cerebral oxygen delivery during cardiopulmonary resuscitation (CPR), but animal and registry studies suggest that epinephrine-induced capillary vasoconstriction may decrease cerebral capillary blood flow and worsen neurological outcome. The effect of epinephrine on cerebral oxygenation (rSO 2 ) during CPR has not been documented in the clinical setting., Methods: rSO 2 was measured continuously using cerebral oximetry in patients with in-hospital cardiac arrest. During CPR, time event markers recorded the administration of 1mg epinephrine. rSO 2 values were analysed for a period beginning 5min before and ending 5min after the first epinephrine administration., Results: A total of 56 epinephrine doses were analysed in 36 patients during CPR. The average rSO 2 value in the 5-min following epinephrine administration was 1.40% higher (95% CI=0.41-2.40%; P=0.0059) than in the 5-min period before epinephrine administration. However, there was no difference in the overall rate of change of rSO 2 when comparing the 5-min period before, with the 5-min period immediately after a single bolus dose of epinephrine (0.88%/min vs 1.07%/min respectively; P=0.583), There was also no difference in the changes in rSO 2 at individual 1, 2, 3, or 4-min time windows before and after a bolus dose of epinephrine (P=0.5827, 0.2371, 0.2082, and 0.6707 respectively)., Conclusions: A bolus of 1mg epinephrine IV during CPR produced a small but clinically insignificant increase in rSO 2 in the five minutes after administration. This is the first clinical data to demonstrate the effects of epinephrine on cerebral rSO 2 during CPR., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Despite its use since the 1960s, the safety or effectiveness of adrenaline as a treatment for cardiac arrest has never been comprehensively evaluated in a clinical trial. Although most studies have found that adrenaline increases the chance of return of spontaneous circulation for short periods, many studies found harmful effects on the brain and raise concern that adrenaline may reduce overall survival and/or good neurological outcome. The PARAMEDIC-2 trial seeks to determine if adrenaline is safe and effective in out-of-hospital cardiac arrest. This is a pragmatic, individually randomised, double blind, controlled trial with a parallel economic evaluation. Participants will be eligible if they are in cardiac arrest in the out-of-hospital environment and advanced life support is initiated. Exclusions are cardiac arrest as a result of anaphylaxis or life threatening asthma, and patient known or appearing to be under 16 or pregnant. 8000 participants treated by 5 UK ambulance services will be randomised between December 2014 and August 2017 to adrenaline (intervention) or placebo (control) through opening pre-randomised drug packs. Clinical outcomes are survival to 30 days (primary outcome), hospital discharge, 3, 6 and 12 months, health related quality of life, and neurological and cognitive outcomes (secondary outcomes). Trial registration (ISRCTN73485024)., (Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.)