Effect of Lower vs Higher Oxygen Saturation Targets on Survival to Hospital Discharge Among Patients Resuscitated After Out-of-Hospital Cardiac Arrest: The EXACT Randomized Clinical Trial.

Importance: The administration of a high fraction of oxygen following return of spontaneous circulation in out-of-hospital cardiac arrest may increase reperfusion brain injury. Objective: To determine whether targeting a lower oxygen saturation in the early phase of postresuscitation care for out-of-hospital cardiac arrest improves survival at hospital discharge. Design, Setting, and Participants: This multicenter, parallel-group, randomized clinical trial included unconscious adults with return of spontaneous circulation and a peripheral oxygen saturation (Spo2) of at least 95% while receiving 100% oxygen. The trial was conducted in 2 emergency medical services and 15 hospitals in Victoria and South Australia, Australia, between December 11, 2017, and August 11, 2020, with data collection from ambulance and hospital medical records (final follow-up date, August 25, 2021). The trial enrolled 428 of a planned 1416 patients. Interventions: Patients were randomized by paramedics to receive oxygen titration to achieve an oxygen saturation of either 90% to 94% (intervention; n = 216) or 98% to 100% (standard care; n = 212) until arrival in the intensive care unit. Main Outcomes and Measures: The primary outcome was survival to hospital discharge. There were 9 secondary outcomes collected, including hypoxic episodes (Spo2 <90%) and prespecified serious adverse events, which included hypoxia with rearrest. Results: The trial was stopped early due to the COVID-19 pandemic. Of the 428 patients who were randomized, 425 were included in the primary analysis (median age, 65.5 years; 100 [23.5%] women) and all completed the trial. Overall, 82 of 214 patients (38.3%) in the intervention group survived to hospital discharge compared with 101 of 211 (47.9%) in the standard care group (difference, -9.6% [95% CI, -18.9% to -0.2%]; unadjusted odds ratio, 0.68 [95% CI, 0.46-1.00]; P = .05). Of the 9 prespecified secondary outcomes collected during hospital stay, 8 showed no significant difference. A hypoxic episode prior to intensive care was observed in 31.3% (n = 67) of participants in the intervention group and 16.1% (n = 34) in the standard care group (difference, 15.2% [95% CI, 7.2%-23.1%]; OR, 2.37 [95% CI, 1.49-3.79]; P < .001). Conclusions and Relevance: Among patients achieving return of spontaneous circulation after out-of-hospital cardiac arrest, targeting an oxygen saturation of 90% to 94%, compared with 98% to 100%, until admission to the intensive care unit did not significantly improve survival to hospital discharge. Although the trial is limited by early termination due to the COVID-19 pandemic, the findings do not support use of an oxygen saturation target of 90% to 94% in the out-of-hospital setting after resuscitation from cardiac arrest. Trial Registration: ClinicalTrials.gov Identifier: NCT03138005.

A comparison of LKB1/AMPK/mTOR metabolic axis response to global ischaemia in brain, heart, liver and kidney in a rat model of cardiac arrest.

BACKGROUND: Cellular energy failure in high metabolic rate organs is one of the underlying causes for many disorders such as neurodegenerative diseases, cardiomyopathies, liver and renal failures. In the past decade, numerous studies have discovered the cellular axis of LKB1/AMPK/mTOR as an essential modulator of cell homeostasis in response to energy stress. Through regulating adaptive mechanisms, this axis adjusts the energy availability to its demand by a systematized control on metabolism. Energy stress, however, could be sensed at different levels in various tissues, leading to applying different strategies in response to hypoxic insults. METHODS: Here the immediate strategies of high metabolic rate organs to time-dependent short episodes of ischaemia were studied by using a rat model (n = 6/group) of cardiac arrest (CA) (15 and 30 s, 1, 2, 4 and 8 min CA). Using western blot analysis, we examined the responses of LKB1/AMPK/mTOR pathway in brain, heart, liver and kidney from 15 s up to 8 min of global ischaemia. The ratio of ADP/ATP was assessed in all ischemic and control groups, using ApoSENSOR bioluminescent assay kit. RESULTS: Brain, followed by kidney showed the early dephosphorylation response in AMPK (Thr172) and LKB1 (Ser431); in the absence of ATP decline (ADP/ATP elevation). Dephosphorylation of AMPK was followed by rephosphorylation and hyperphosphorylation, which was associated with a significant ATP decline. While heart's activity of AMPK and LKB1 remained at the same level during short episodes of ischaemia, liver's LKB1 was dephosphorylated after 2 min. AMPK response to ischaemia in liver was mainly based on an early alternative and a late constant hyperphosphorylation. No significant changes was observed in mTOR activity in all groups. CONCLUSION: Together our results suggest that early AMPK dephosphorylation followed by late hyperphosphorylation is the strategy of brain and kidney in response to ischaemia. While the liver seemed to get benefit of its AMPK system in early ischameia, possibly to stabilize ATP, the level of LKB1/AMPK activity in heart remained unchanged in short ischaemic episodes up to 8 min. Further researches must be conducted to elucidate the molecular mechanism underlying LKB1/AMPK response to oxygen supply.

Induction of Therapeutic Hypothermia During Out-of-Hospital Cardiac Arrest Using a Rapid Infusion of Cold Saline: The RINSE Trial (Rapid Infusion of Cold Normal Saline).

BACKGROUND: Patients successfully resuscitated by paramedics from out-of-hospital cardiac arrest often have severe neurologic injury. Laboratory and observational clinical reports have suggested that induction of therapeutic hypothermia during cardiopulmonary resuscitation (CPR) may improve neurologic outcomes. One technique for induction of mild therapeutic hypothermia during CPR is a rapid infusion of large-volume cold crystalloid fluid. METHODS: In this multicenter, randomized, controlled trial we assigned adults with out-of-hospital cardiac arrest undergoing CPR to either a rapid intravenous infusion of up to 2 L of cold saline or standard care. The primary outcome measure was survival at hospital discharge; secondary end points included return of a spontaneous circulation. The trial was closed early (at 48% recruitment target) due to changes in temperature management at major receiving hospitals. RESULTS: A total of 1198 patients were assigned to either therapeutic hypothermia during CPR (618 patients) or standard prehospital care (580 patients). Patients allocated to therapeutic hypothermia received a mean (SD) of 1193 (647) mL cold saline. For patients with an initial shockable cardiac rhythm, there was a decrease in the rate of return of a spontaneous circulation in patients who received cold saline compared with standard care (41.2% compared with 50.6%, P=0.03). Overall 10.2% of patients allocated to therapeutic hypothermia during CPR were alive at hospital discharge compared with 11.4% who received standard care (P=0.71). CONCLUSIONS: In adults with out-of-hospital cardiac arrest, induction of mild therapeutic hypothermia using a rapid infusion of large-volume, intravenous cold saline during CPR may decrease the rate of return of a spontaneous circulation in patients with an initial shockable rhythm and produced no trend toward improved outcomes at hospital discharge. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01173393.

Global review of delay time in seeking medical care for chest pain: An integrative literature review.

OBJECTIVES: The aim of this review is to summarise research from a range of countries describing the differences in time taken to seek medical care for chest pain and factors which contribute to delay times. METHODS: An integrative literature review was undertaken using the Medline, CINAHL and Scopus databases for publications between 1994 and 2014. Articles dealing with delay time, and the factors associated with delay time, were extracted from the literature. RESULTS: The search yielded 395 articles of which 205 full-text articles were assessed for eligibility. Finally, twenty-three articles met the inclusion criteria for the review. It was found that time to seeking treatment (delay times) varied between countries, ranging from 1.6 to 12.9h, with a mean of 3.4h. The mean delay times reported in all the selected studies were greater than the recommended time-frame for seeking treatment. As well, time to decision to seek treatment (decision time) was reported as a major component of delay time. Meanwhile, the utilisation rates of ambulance services ranged from 3.1% in Brazil to 61.0% in Australia. A majority of the reviewed studies reported on the factors associated with longer delay times, including old age, female gender, ethnicity, low education level, history of chronic disease, lack of knowledge of the symptoms, and underutilisation of ambulance services. Only three studies included a sub-analysis by ethnicity, reporting that ethnic groups had longer delay times than Caucasians. CONCLUSION: Variability in delay times occurred across countries and within continents. The mean time taken to seek care for chest pain in the countries reviewed did not meet the recommended times according to international guidelines. Demographic and social factors, as well as cognitive and emotional factors, influenced delay times. Further research on these influencing factors is recommended, including the impact of ethnicity on patient's care-seeking behaviours for chest pain.

Early glycogen synthase kinase-3ß and protein phosphatase 2A independent tau dephosphorylation during global brain ischaemia and reperfusion following cardiac arrest and the role of the adenosine monophosphate kinase pathway.

Abnormal tau phosphorylation (p-tau) has been shown after hypoxic damage to the brain associated with traumatic brain injury and stroke. As the level of p-tau is controlled by Glycogen Synthase Kinase (GSK)-3ß, Protein Phosphatase 2A (PP2A) and Adenosine Monophosphate Kinase (AMPK), different activity levels of these enzymes could be involved in tau phosphorylation following ischaemia. This study assessed the effects of global brain ischaemia/reperfusion on the immediate status of p-tau in a rat model of cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR). We reported an early dephosphorylation of tau at its AMPK sensitive residues, Ser(396) and Ser(262) after 2 min of ischaemia, which did not recover during the first two hours of reperfusion, while the tau phosphorylation at GSK-3ß sensitive but AMPK insensitive residues, Ser(202) /Thr(205) (AT8), as well as the total amount of tau remained unchanged. Our data showed no alteration in the activities of GSK-3ß and PP2A during similar episodes of ischaemia of up to 8 min and reperfusion of up to 2 h, and 4 weeks recovery. Dephosphorylation of AMPK followed the same pattern as tau dephosphorylation during ischaemia/reperfusion. Catalase, another AMPK downstream substrate also showed a similar pattern of decline to p-AMPK, in ischaemic/reperfusion groups. This suggests the involvement of AMPK in changing the p-tau levels, indicating that tau dephosphorylation following ischaemia is not dependent on GSK-3ß or PP2A activity, but is associated with AMPK dephosphorylation. We propose that a reduction in AMPK activity is a possible early mechanism responsible for tau dephosphorylation.

Neuronal response in Alzheimer's and Parkinson's disease: the effect of toxic proteins on intracellular pathways.

Accumulation of protein aggregates is the leading cause of cellular dysfunction in neurodegenerative disorders. Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, Prion disease and motor disorders such as amyotrophic lateral sclerosis, present with a similar pattern of progressive neuronal death, nervous system deterioration and cognitive impairment. The common characteristic is an unusual misfolding of proteins which is believed to cause protein deposition and trigger degenerative signals in the neurons. A similar clinical presentation seen in many neurodegenerative disorders suggests the possibility of shared neuronal responses in different disorders. Despite the difference in core elements of deposits in each neurodegenerative disorder, the cascade of neuronal reactions such as activation of glycogen synthase kinase-3 beta, mitogen-activated protein kinases, cell cycle re-entry and oxidative stress leading to a progressive neurodegeneration are surprisingly similar. This review focuses on protein toxicity in two neurodegenerative diseases, AD and PD. We reviewed the activated mechanisms of neurotoxicity in response to misfolded beta-amyloid and α-synuclein, two major toxic proteins in AD and PD, leading to neuronal apoptosis. The interaction between the proteins in producing an overlapping pathological pattern will be also discussed.

Opinions of Nurses and Physicians on a Patient, Family, and Visitor Activated Rapid Response System in Use Across Two Hospital Settings.

BACKGROUND: Early detection of deterioration of hospitalized patients with timely intervention improves outcomes in the hospital. Patients, family members, and visitors (consumers) at the patient's bedside who are familiar with the patient's condition may play a critical role in detecting early patient deterioration. The authors sought to understand clinicians' views on consumer reporting of patient deterioration through an established hospital consumer-initiated escalation-of-care system. METHODS: A convenience sample of new graduate-level to senior-level nurses and physicians from two hospitals in South Australia was administered a paper survey containing six open-ended questions. Data were analyzed with a matrix-style framework and six steps of thematic analysis. RESULTS: A total of 244 clinicians-198 nurses and 46 physicians-provided their views on the consumer-initiated escalation-of-care system. Six major themes and subthemes emerged from the responses indicating that (1) clinicians were supportive of consumer reporting and felt that consumers were ideally positioned to recognize deterioration early and raise concerns about it; (2) management support was required for consumer escalation processes to be effective; (3) clinicians' workload could possibly increase or decrease from consumer escalation; (4) education of consumers and staff on escalation protocol is a requirement for success; (5) there is need to build consumer confidence to speak up; and (6) there is a need to address barriers to consumer escalation. CONCLUSION: Clinicians were supportive of consumers acting as first reporters of patient deterioration. Use of interactive, encouraging communication skills with consumers was recognized as critical. Annual updating of clinicians on consumer reporting of deterioration was also recommended.

Hospital Testing of the Effectiveness of Co-Designed Educational Materials to Improve Patient and Visitor Knowledge and Confidence in Reporting Patient Deterioration.

BACKGROUND: Co-designed educational materials could significantly improve the likelihood of patients and visitors (consumers) escalating care through hospital systems. The objective was to investigate patients' and visitors' knowledge and confidence in recognizing and reporting patient deterioration in hospitals before and after exposure to educational materials. METHODS: A multimethod design involved a convenience sample of patients and visitors at a South Australian hospital. Knowledge and confidence of participants to report patient deterioration was assessed using a validated questionnaire. Baseline group was surveyed, and a second group was surveyed after exposure to a poster and on-hold message relating to consumer-initiated escalation-of-care. Nominal data were examined using chi-square analysis, and ordinal data using the Mann-Whitney U test. Open-ended questions were examined using thematic analysis. RESULTS: A total of 407 participants completed the study, 203 undertook the baseline survey, and 204 the postintervention survey. Respondents exposed to the educational materials reported significantly higher recognition of responsibility to report concerns about patient deterioration compared to controls (86.3% vs. 73.1%; p = 0.007). Respondents exposed to the educational materials also had better ability to identify signs that a patient was becoming sicker compared to controls (77.5% vs. 71.3%, p = 0.012). Four overarching themes emerged from the questions: patient/visitor understanding of key messages, patient/visitor recognition of deterioration, patient/visitor response to deterioration and patient/visitor recommendations. CONCLUSION: Following educational interventions, patients and visitors report improved awareness of their role in recognizing and responding to clinical deterioration. They advise additional active interventions and caution that the materials should accommodate language, cultural, and disability needs.

Basic and advanced cardiac life support--what's new?

BACKGROUND: Australian Resuscitation Council guidelines on basic and advanced life support are amended periodically. These changes are informed by recent evidence on best practice in resuscitation medicine. In December 2010, the latest guidelines were released for implementation in 2011. OBJECTIVE: This article outlines the key messages from the latest Australian Resuscitation Council guidelines on basic and advanced life support. DISCUSSION: The latest Australian Resuscitation Council guidelines on basic and advanced life support emphasise the importance of early recognition of deterioration before cardiac arrest. Once resuscitation commences, there is a focus on early defibrillation and early chest compressions with a simplification of drug treatment. Postresuscitation phase changes emphasise early intervention to re-establish coronary artery patency and therapeutic hypothermia.

Review article: Roles of activities of daily living and frailty assessments for residents of residential aged care services in emergency department transfers: A scoping review.

Residents from residential aged care services (RACS) (i.e. nursing homes) many of whom are frail or disabled, are frequently transferred to ED for treatment of acute episodes of illness or injury. This review scoped the research related to the ways in which frailty or activities of daily living (ADL) measures are used for clinical purposes, either prior to the transfer of patients to ED or in ED themselves. A search for original studies up to June 2021 that included participants aged 65 years or over was conducted across four databases. Abstracts were first reviewed, leading to full text screening and article selection. Thirty-four studies were included in the scoping review. Most of the ADL and frailty assessments were conducted in residential aged care settings. In seven studies, ADL or frailty assessments in the aged care setting contributed to reduced transfer rates to ED. No results were found that associated the assessment of ADL or frailty with decisions related to treatment in the ED. A single ED study involved specialist emergency nursing in an ED as an intervention which included frailty assessment and led to decreased hospitalisation. This scoping review confirms an opportunity for further research into the ways frailty and ADL assessments are used for decision making in relation to the transfer of frail older people to ED, including how these assessments influence their treatment.

Design of the RINSE trial: the rapid infusion of cold normal saline by paramedics during CPR.

BACKGROUND: The International Liaison Committee on Resuscitation (ILCOR) now recommends therapeutic hypothermia (TH) (33 °C for 12-24 hours) as soon as possible for patients who remain comatose after resuscitation from shockable rhythm in out-of-hospital cardiac arrest and that it be considered for non shockable rhythms. The optimal timing of TH is still uncertain. Laboratory data have suggested that there is significantly decreased neurological injury if cooling is initiated during CPR. In addition, peri-arrest cooling may increase the rate of successful defibrillation. This study aims to determine whether paramedic cooling during CPR improves outcome compared standard treatment in patients who are being resuscitated from out-of-hospital cardiac arrest. METHODS/DESIGN: This paper describes the methodology for a definitive multi-centre, randomised, controlled trial of paramedic cooling during CPR compared with standard treatment. Paramedic cooling during CPR will be achieved using a rapid infusion of large volume (20-40 mL/kg to a maximum of 2 litres) ice-cold (4 °C) normal saline.The primary outcome measure is survival at hospital discharge. Secondary outcome measures are rates of return of spontaneous circulation, rate of survival to hospital admission, temperature on arrival at hospital, and 12 month quality of life of survivors. DISCUSSION: This trial will test the effect of the administration of ice cold saline during CPR on survival outcomes. If this simple treatment is found to improve outcomes, it will have generalisability to prehospital services globally. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01172678.

You're Worried, We're Listening: Online Testing of the Effectiveness of Education Materials to Improve Consumer Knowledge and Confidence in Reporting Patient Deterioration.

OBJECTIVES: Early identification of patient deterioration in hospital is important to reduce mortality, avoidable morbidity, length of stay, and associated healthcare costs. By closely observing physical and behavioral changes, deteriorating patients are more likely to be identified. Patients and family at the bedside can play an important role in reporting deterioration if made aware of how to do so. Therefore, the objective of this study was to undertake an online evaluation of educational materials designed to improve consumers' knowledge and confidence to report patient deterioration. METHODS: A convenience sample was used to recruit community-based participants for an online survey. A self-designed validated instrument was used to undertake a preintervention and postintervention test involving 3 types of educational materials. Quantitative data were analyzed with Wilcoxon signed rank test to compare participants' knowledge and confidence before and after exposure to the intervention. Conventional content analyses examined responses on key messages and recommendations to improve the educational materials. RESULTS: A total of 84 respondents completed both prequestionnaires and postquestionnaires. After exposure to the education materials, analyses confirmed that knowledge and confidence scores were significantly higher than baseline measures. Content analyses indicated a clear understanding of the key messages presented in the materials. Four main recommendations were made regarding the education materials. CONCLUSIONS: Participants readily identified the key messages in the educational materials and demonstrated increased knowledge and confidence to report concerns about deterioration. Further research is required to determine the efficacy of the educational materials in relation to consumer behavior.

Development and Validation of an Evaluation Tool of Consumers' Knowledge and Confidence to Report Patient Deterioration in Hospitals.

OBJECTIVES: Studies have shown that many preventable hospital deaths may be reduced through early reporting of deterioration by patients and their visitors to health professionals. Engagement of patients and families for safer health care was recommended by the World Health Organization. As no validated tool was identified, the objective of the study was to develop and validate a tool to measure the impact of messages contained in self-developed educational materials on consumers' knowledge and confidence to report patient deterioration. METHODS: A tool was created using consumer-based input. A test-retest methodology was used 2 weeks apart, using 37 participants sourced from consumer groups. Fourteen 5-point Likert scale questionnaire items were categorized into knowledge and confidence components to identify the impact of the materials in both of these areas. RESULTS: Test-retest reliability confirmed 10 of the 14 proposed questionnaire items (4 knowledge items and 6 confidence) had at least moderate κ agreement ranging from 0.42 to 0.69 and an intraclass correlation coefficient of 0.66. An exploratory factor analysis of the 10 remaining items indicated a 2-factor solution had the best interpretability accounting for 96.9% of variability. The Cronbach α and factor loadings for the factors, knowledge, and confidence suggested an acceptable level of reliability and validity. CONCLUSIONS: The study confirms our tool for assessment of educational materials to be a reliable, context-specific, and validated instrument. The tool is an appropriate instrument to assess the effectiveness of educational materials in public awareness campaigns that focus on consumer reporting of patient deterioration within hospitals.

Out-of-hospital cardiac arrest-review of demographics in South Australia to inform decisions about the provision of automatic external defibrillators within the community.

INTRODUCTION: Sudden, out-of-hospital cardiac arrest (OHCA) has an annual incidence of approximately 50 per 100,000 population. Public access defibrillation is seen as one of the key strategies in the chain-of-survival for OHCA. Positioning of these devices is important for the maximization of public health outcomes. The literature strongly advocates widespread public access to automated external defibrillatiors (AEDs). The most efficient placement of AEDs within individual communities remains unclear. METHODS: A retrospective case review of OHCAs attended by the South Australia Ambulance Service in metropolitan and rural South Australia over a 30-month period was performed. Data were analyzed using Utstein-type indicators. Detailed demographics, summative data, and clinical data were recorded. RESULTS: A total of 1,305 cases of cardiac arrest were reviewed. The annual rate of OHCA was 35 per 100,000 population. Of the cases, the mean value for the ages was 66.3 years, 517 (39.6%) were transported to hospital, 761 (58.3%) were judged by the paramedic to be cardiac, and 838 (64.2%) were witnessed. Bystander cardiopulmonary resuscitation (CPR) was performed in 495 (37.9%) of cases. The rhythm on arrival was ventricular fibrillation (VF) or ventricular tachycardia (VT) in 419 (32.1%) cases, and 315 (24.1%) of all arrests had return of spontaneous circulation (ROSC) before or on arrival at the hospital. For cardiac arrest cases that were witnessed by the ambulance service (n=121), the incidence of ROSC was 47.1%. During the 30-month period, there only was one location that recorded more than one cardiac arrest. No other location recorded recurrent episodes. CONCLUSIONS: This study did not identify any specific location that would justify defibrillator placement over any other location without an existing defibrillator. The impact of bystander CPR and the relatively low rate of bystander CPR in this study points to an area of need. The relative potential impact of increasing bystander CPR rates versus investing in defibrillators in the community is worthy of further consideration.

Care of the patient with invasive meningococcal disease by prehospital emergency medical service clinicians: a scoping review.

OBJECTIVE: The objective of this scoping review is to systematically map the literature to identify the scope, depth, key concepts and gaps in the evidence regarding care of the patient with invasive meningococcal disease by emergency medical service (EMS) clinicians. DESIGN: Scoping review. This review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews reporting guideline. ELIGIBILITY CRITERIA: Sources which focused on patients with invasive meningococcal disease (population), where the care of EMS clinicians was the focus (concept), in EMS systems worldwide (context) were eligible for inclusion. SEARCH STRATEGY: This review utilised a comprehensive search strategy including MEDLINE, Embase, Emcare, CINAHL, Scopus, Web of Science, Google Scholar and 'grey' literature databases from 1992 to January 2019. The search also included a Google search, a hand-search of relevant journals, screening of reference lists, contact with authors of included sources and use of social media in an attempt to locate all sources of evidence which fit the inclusion criteria of the review. Two reviewers independently screened sources for inclusion. RESULTS: The search yielded 1803 unique records, of which 10 were included in the synthesis. No original research papers were identified, with all sources classed as either clinical audit or text and opinion literature. The dominant concept throughout the literature is that early antibiotic therapy is critical in the treatment of invasive meningococcal disease. CONCLUSIONS: Overall, there is a very narrow scope and shallow depth of literature on the topic of interest. There are gaps in the evidence regarding the care of the patient with invasive meningococcal disease by EMS clinicians. Despite these shortfalls, current consensus-based guidelines should direct clinical practice. Further research is planned to bridge the gaps in knowledge to support best practice.

Variations in the care of agitated patients in Australia and New Zealand ambulance services.

OBJECTIVE: The objective of the present study is to examine variations in paramedic care of the agitated patient, including verbal de-escalation, physical restraint and sedation, provided by ambulance services in Australia and New Zealand. METHODS: To examine the care of agitated patients, we first identified and reviewed all clinical practice guidelines for the management of agitated patients in Australian and New Zealand ambulance services between September and November 2018. We then conducted a structured questionnaire to obtain further information on the training, assessment and care of agitated patients by the ambulance services. Two authors extracted the data independently, and all interpretations and results were reviewed and confirmed by relevant ambulance services. RESULTS: There were 10 independent clinical practice guidelines for the care of agitated patients in the 10 ambulance services. All services reported training in the management of agitated patients, and two services used a validated tool to assess the level of agitation. All services used physical restraint, although six services required police presence to restrain the patient. All ambulance services used some form of sedation, typically divided into the management of mild to moderate, and severe agitation. The most common agent for sedation was midazolam, while ketamine was the most common agent for sedating severely agitated patients. The maximum dose was varied, and contraindications for sedating agents varied between services. CONCLUSIONS: There were wide variations across the ambulance services in terms of the assessment of agitation, as well as the use of physical restraint and sedation.

Do User-Applied Safety Labels on Medication Syringes Reduce the Incidence of Medication Errors During Rapid Medical Response Intervention for Deteriorating Patients in Wards? A Systematic Search and Review.

INTRODUCTION: Intravenous medication errors (MEs) occur during medical emergency situations. An initiative, not yet in common practice, that could address these errors is safety labeling. The aim of this review was to identify and appraise research evidence related to the impact of user-applied medication safety labeling on reducing the incidence of MEs during rapid medical response intervention for patient deterioration in the ward setting. METHODS: A systematic search and review framework was used to conduct the review. A comprehensive database search was conducted of BioMed Central, Clinical Trials, Cumulative Index to Nursing and Allied Health Literature, Expanded Academic ASAP, Joanna Briggs Institute, MEDLINE, OVID, ProQuest Central, PubMed, Wiley Online Library, and World Health Organization Library. The Young and Solomon (2009) critical appraisal tool was used to critically appraise the identified research articles. Each article was then analyzed using a thematic network strategy to identify commonality. RESULTS: Four primary themes were identified; they were as follows: MEs occur during medical emergency responses (MERs); MEs occur throughout the medication administration process; MERs are stressful and are associated with MEs; and role of medication labeling in reducing MEs during MERs. DISCUSSION: Greater vigilance is required by health professionals during the medication administration process. The implementation of specific medication safety labeling into the MER could be beneficial in reducing the overall incidence of MEs. Further research is required to validate the merits of a MER medication safety labeling system.

The EXACT protocol: A multi-centre, single-blind, randomised, parallel-group, controlled trial to determine whether early oxygen titration improves survival to hospital discharge in adult OHCA patients.

BACKGROUND: Experimental and observational research suggests hyperoxia following resuscitation from cardiac arrest is associated with neurological injury and worse clinical outcomes. This paper describes the rationale and design of the EXACT trial. EXACT aims to determine whether reducing oxygen in the acute phase of post-resuscitation care for out-of-hospital cardiac arrest (OHCA) improves survival. METHODS: EXACT is a multi-centre, randomised (1:1), single-blind, parallel trial. Presumed cardiac OHCA cases who achieve a return of spontaneous circulation will be eligible if they are comatose, with an advanced airway and have an oxygen saturation (SpO2) ≥95% on >10 L/min (or 100% oxygen). Paramedics will randomise 1416 eligible cases to receive oxygen therapy targeting an SpO2 of 90-94% (intervention) or 98-100% (control). Study treatment will continue until admission to an intensive care unit or hospital ward. The primary outcome is survival to hospital discharge. Secondary outcomes include 12-month survival and quality of life. RESULTS: The study has commenced in the Australian states of Victoria and South Australia, and has enrolled 167 eligible cases to date (80 intervention and 87 control). Further sites are due to commence in 2019, recruitment is expected to take three years. CONCLUSION: This study will determine if early reduction of oxygen leads to improved outcomes in OHCA. Such a finding may potentially change clinical practice with implications on future OHCA survival outcomes. TRIAL REGISTRATION NUMBER: NCT03138005.

Defibrillation or cardiopulmonary resuscitation first for patients with out-of-hospital cardiac arrests found by paramedics to be in ventricular fibrillation? A randomised control trial.

AIM: To determine whether in patients with an ambulance response time of >5min who were in VF cardiac arrest, 3min of CPR before the first defibrillation was more effective than immediate defibrillation in improving survival to hospital discharge. METHODS: This randomised control trial was run by the South Australian Ambulance Service between 1 July, 2005, and 31 July, 2007. Patients in VF arrest were eligible for randomisation. Exclusion criteria were: (i) <18 years of age, (ii) traumatic arrest, (iii) paramedic witnessed arrest, (iv) advanced life support performed before arrival of paramedics and (v) not for resuscitation order or similar directive. The primary outcome was survival to hospital discharge with secondary outcomes being neurological status at discharge, the rate of return of spontaneous circulation (ROSC) and the time from first defibrillation to ROSC. RESULTS: For all response times, no differences were observed between the immediate defibrillation group and the CPR first group in survival to hospital discharge (17.1% [18/105] vs. 10.3% [10/97]; P=0.16), the rate of ROSC (53.3% [56/105] vs. 50.5% [49/97]; P=0.69) or the time from the first defibrillation to ROSC (12:37 vs. 11:19; P=0.49). There were also no differences between the immediate defibrillation group and the CPR first group, for response times of < or = or > 5min: survival to hospital discharge (50.0% [7/14] vs. 25.0% [4/16]; P=0.16 or 12.1% [11/91] vs.7.4% [6/81]; P=0.31, respectively) and the rate of ROSC (71.4% [10/14] vs. 75.0% [12/16]; P=0.83 or 50.5% [46/91] vs. 45.7% [37/81]; P=0.54, respectively). No differences were observed in the neurological status of those surviving to hospital discharge. CONCLUSION: For patient in out-of-hospital VF cardiac arrest we found no evidence to support the use of 3min of CPR before the first defibrillation over the accepted practice of immediate defibrillation.

Oxygen titration after resuscitation from out-of-hospital cardiac arrest: A multi-centre, randomised controlled pilot study (the EXACT pilot trial).

INTRODUCTION: Recent studies suggest the administration of 100% oxygen to hyperoxic levels following return-of-spontaneous-circulation (ROSC) post-cardiac arrest may be harmful. However, the feasibility and safety of oxygen titration in the prehospital setting is unknown. We conducted a multi-centre, phase-2 study testing whether prehospital titration of oxygen results in an equivalent number of patients arriving at hospital with oxygen saturations SpO2 ≥ 94%. METHODS: We enrolled unconscious adults with: sustained ROSC; initial shockable rhythm; an advanced airway; and an SpO2 ≥ 95%. Initially (Sept 2015-March 2016) patients were randomised 1:1 to either 2 L/minute (L/min) oxygen (titrated) or >10 L/min oxygen (control) via a bag-valve reservoir. However, one site experienced a high number of desaturations (SpO2 < 94%) in the titrated arm and this arm was changed (April 2016) to an initial reduction of oxygen to 4 L/min then, if tolerated, to 2 L/min, and the desaturation limit was decreased to <90%. RESULTS: We randomised 61 patients to titrated (n = 37: 2L/min = 20 and 2-4 L/min = 17) oxygen or control (n = 24). Patients allocated to titrated oxygen were more likely to desaturate compared to controls ((SpO2 < 94%: 43% vs. 4%, p = 0.001; SpO2 < 90%: 19% vs. 4%, p = 0.09). The majority of desaturations (81%) occurred at 2L/min. On arrival at hospital the majority of patients had a SpO2 ≥ 94% (titrated: 90% vs. control: 100%) and all patients had a SpO2 ≥ 90%. One patient (control) re-arrested. Survival to hospital discharge was similar. CONCLUSION: Oxygen titration post-ROSC is feasible in the prehospital environment, but incremental titration commencing at 4L/min oxygen flow may be needed to maintain an oxygen saturation >90% (NCT02499042).