A retrospective analysis of ketamine administration by Critical Care Paramedics in a pre-hospital care setting

This document is the Accepted Manuscript version of the following article: Alan Cowley, Julia Williams, Pete Westhead, Nick Gray, Adam Watts, and Fionna Moore, ‘A retrospective analysis of ketamine administration by critical care paramedics in a pre-hospital care setting’, British Paramedic Journal, Vol. 2 (4): 25-31, January 2018. Under embargo until 1 January 2019. The final, definitive version is available online via: https://doi.org/10.29045/14784726.2018.03.2.4.25ABSTRACT  Objective: This project aims to describe pre-hospital use of Ketamine in trauma by South East Coast Ambulance Service Critical Care Paramedics and evaluate the occurrence of any side effects or adverse events.  Methods: A retrospective analysis of patients receiving pre-hospital ketamine for trauma between 16th March 2013 and 30th April 2017. Administrations were identified from Advanced Life Saving Intervention and Procedure reports submitted by the clinician and, later, from an electronic database. Each was scrutinised for patient demographics, indication, doses and reports of side effects or adverse events.  Results: A total of 510 administrations were identified. Thirty-four of these were excluded due to a lack of completeness, ketamine being drawn and not administered or the administering clinician not being a Critical Care Paramedic. A further twenty-seven were excluded due to being given for a non-traumatic reason. Of the remaining 449 administrations, males accounted for 302 (67.3%) compared to 147 (32.7%) females. The average age was 45.26 with women older (53.2 years vs. 41.4 years). The mean dose was 32.63mg (IQR 20; 5-180mg). Isolated lower limb trauma was the most common indication (228/449; 50.8%). Notable side effects were reported on 15 occasions with one adverse event. The mean dose for side effect was 29.3mg. Males received a higher dose when exhibiting a side effect (31.90mg vs. 26.43mg).  Conclusions: Critical Care Paramedics within a well governed system are able to safely administer ketamine within an approved dosing regimen under a Patient Group Direction. Mean doses are in keeping with nationally approved guidelines. The demographics represent the national trauma statistics. Reported side effects were within the described frequencies in the British National Formulary, and reported in other studies. Numbers Needed to Harm (NNH) also appear acceptable given that the side effects are easy to manage within a Critical Care Paramedic’s scope of practice. However, the project has significant limitations and so further, prospective research is required. Peer reviewe

National initiatives to improve outcomes from out-of-hospital cardiac arrest in England

NHS England report that the ambulance services attempt to resuscitate approximately 28 000 people from out-of-hospital cardiac arrest each year (approximately 1 per 2000 inhabitants per year).1 The rate of initial success (return of spontaneous circulation) was 25%, with less than half of those who are successfully resuscitated initially surviving to go home from hospital (survival to discharge 7%–8%, 2011–2014).1 (see figure 1). The survival rates contrast sharply with those observed in the best-performing emergency medical services systems, which have survival rates of 20%–25%.2–4 In 2013, the government's Cardiovascular Disease Outcomes Strategy for England set the ambitious, but achievable target of increasing survival from out-of-hospital cardiac arrest by 50%, leading to an additional 1000 lives saved each year

Improvement in the pre-hospital care of recreational drug users through the development of club specific ambulance referral guidelines

<p>Abstract</p> <p>Background</p> <p>Previously developed 'club guidelines' developed for club owners and promoters have tended to focus more on the legislative aspects of clubs, rather than the medical management of unwell clubbers within club environments. Despite this lack of guidance on the management of unwell clubbers, a significant proportion of clubs have 'club medic' rooms for managing these individuals. However, due to the lack of specific guidance on the training of staff working in these rooms and guidelines on when an ambulance should be called for an unwell clubber, there have been instances previously where clubbers have been inappropriately managed within the club environment, and often referred to hospital only after significant physiological derangement has occurred, thereby leading to an increased risk of morbidity and mortality.</p> <p>Methods</p> <p>We identified owners and promoters of local club venues within the catchment area of our Emergency Department and working jointly with them and other key stakeholders, in particular the London Ambulance Service and Metropolitan Police, identified strategies to improve pre-hospital care for clubbers who become unwell as a result of recreational drug use. These included developing guidelines detailing indications for ambulance transfer to hospital for clubbers with recreational drug toxicity and the training of club medic staff to use the guidelines</p> <p>Results</p> <p>Following the initial development of a pilot set of guidelines, an audit of their use identified training needed relating to the assessment of unwell clubbers with recreational drug toxicity and revisions required to the pilot version of the guidelines. After training related to the revised guidelines, all the club medic staff were confident in their ability to assess unwell clubbers with recreational drug toxicity, the use of the guidelines and also when to call an ambulance.</p> <p>Conclusion</p> <p>Working with key stakeholders in the local community, we have developed guidelines that can be used to improve the pre-hospital care of clubber unwell with recreational drug toxicity, and demonstrated that individuals with a variety of medical knowledge can be trained to use these guidelines. Wider dissemination of these guidelines, both regionally, nationally and potentially internationally, may help to reduce the pre-hospital morbidity and mortality associated with recreational drug toxicity encountered in club environments.</p

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 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.

Pre-hospital assessment of the role of adrenaline : measuring the effectiveness of drug administration in cardiac arrest (PARAMEDIC-2) : trial protocol

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)

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

Endovascular strategy or open repair for ruptured abdominal aortic aneurysm: one-year outcomes from the IMPROVE randomized trial.

AIMS: To report the longer term outcomes following either a strategy of endovascular repair first or open repair of ruptured abdominal aortic aneurysm, which are necessary for both patient and clinical decision-making. METHODS AND RESULTS: This pragmatic multicentre (29 UK and 1 Canada) trial randomized 613 patients with a clinical diagnosis of ruptured aneurysm; 316 to an endovascular first strategy (if aortic morphology is suitable, open repair if not) and 297 to open repair. The principal 1-year outcome was mortality; secondary outcomes were re-interventions, hospital discharge, health-related quality-of-life (QoL) (EQ-5D), costs, Quality-Adjusted-Life-Years (QALYs), and cost-effectiveness [incremental net benefit (INB)]. At 1 year, all-cause mortality was 41.1% for the endovascular strategy group and 45.1% for the open repair group, odds ratio 0.85 [95% confidence interval (CI) 0.62, 1.17], P = 0.325, with similar re-intervention rates in each group. The endovascular strategy group and open repair groups had average total hospital stays of 17 and 26 days, respectively, P < 0.001. Patients surviving rupture had higher average EQ-5D utility scores in the endovascular strategy vs. open repair groups, mean differences 0.087 (95% CI 0.017, 0.158), 0.068 (95% CI -0.004, 0.140) at 3 and 12 months, respectively. There were indications that QALYs were higher and costs lower for the endovascular first strategy, combining to give an INB of £3877 (95% CI £253, £7408) or €4356 (95% CI €284, €8323). CONCLUSION: An endovascular first strategy for management of ruptured aneurysms does not offer a survival benefit over 1 year but offers patients faster discharge with better QoL and is cost-effective. CLINICAL TRIAL REGISTRATION: ISRCTN 48334791