A Randomized Trial of Drug Route in Out-of-Hospital Cardiac Arrest.

BACKGROUND: In patients with out-of-hospital cardiac arrest, the effectiveness of drugs such as epinephrine is highly time-dependent. An intraosseous route of drug administration may enable more rapid drug administration than an intravenous route; however, its effect on clinical outcomes is uncertain. METHODS: We conducted a multicenter, open-label, randomized trial across 11 emergency medical systems in the United Kingdom that involved adults in cardiac arrest for whom vascular access for drug administration was needed. Patients were randomly assigned to receive treatment from paramedics by means of an intraosseous-first or intravenous-first vascular access strategy. The primary outcome was survival at 30 days. Key secondary outcomes included any return of spontaneous circulation and favorable neurologic function at hospital discharge (defined by a score of 3 or less on the modified Rankin scale, on which scores range from 0 to 6, with higher scores indicating greater disability). No adjustment for multiplicity was made. RESULTS: A total of 6082 patients were assigned to a trial group: 3040 to the intraosseous group and 3042 to the intravenous group. At 30 days, 137 of 3030 patients (4.5%) in the intraosseous group and 155 of 3034 (5.1%) in the intravenous group were alive (adjusted odds ratio, 0.94; 95% confidence interval [CI], 0.68 to 1.32; P = 0.74). At the time of hospital discharge, a favorable neurologic outcome was observed in 80 of 2994 patients (2.7%) in the intraosseous group and in 85 of 2986 (2.8%) in the intravenous group (adjusted odds ratio, 0.91; 95% CI, 0.57 to 1.47); a return of spontaneous circulation at any time occurred in 1092 of 3031 patients (36.0%) and in 1186 of 3035 patients (39.1%), respectively (adjusted odds ratio, 0.86; 95% CI, 0.76 to 0.97). During the trial, one adverse event, which occurred in the intraosseous group, was reported. CONCLUSIONS: Among adults with out-of-hospital cardiac arrest requiring drug therapy, the use of an intraosseous-first vascular access strategy did not result in higher 30-day survival than an intravenous-first strategy. (Funded by the National Institute for Health and Care Research; PARAMEDIC-3 ISRCTN Registry number, ISRCTN14223494.).

Cardiac arrest and cardiopulmonary resuscitation outcome reports: 2024 update of the Utstein Out-of-Hospital Cardiac Arrest Registry template.

The Utstein Out-of-Hospital Cardiac Arrest Resuscitation Registry Template, introduced in 1991 and updated in 2004 and 2015, standardizes data collection to enable research, evaluation, and comparisons of systems of care. The impetus for the current update stemmed from significant advances in the field and insights from registry development and regional comparisons. This 2024 update involved representatives of the International Liaison Committee on Resuscitation and used a modified Delphi process. Every 2015 Utstein data element was reviewed for relevance, priority (core or supplemental), and improvement. New variables were proposed and refined. All changes were voted on for inclusion. The 2015 domains-system, dispatch, patient, process, and outcomes-were retained. Further clarity is provided for the definitions of out-of-hospital cardiac arrest attended resuscitation and attempted resuscitation. Changes reflect advancements in dispatch, early response systems, and resuscitation care, as well as the importance of prehospital outcomes. Time intervals such as emergency medical service response time now emphasize precise reporting of the times used. New flowcharts aid the reporting of system effectiveness for patients with an attempted resuscitation and system efficacy for the Utstein comparator group. Recognizing the varying capacities of emergency systems globally, the writing group provided a minimal dataset for settings with developing emergency medical systems. Supplementary variables are considered useful for research purposes. These revisions aim to elevate data collection and reporting transparency by registries and researchers and to advance international comparisons and collaborations. The overarching objective remains the improvement of outcomes for patients with out-of-hospital cardiac arrest.

Cardiac Arrest and Cardiopulmonary Resuscitation Outcome Reports: 2024 Update of the Utstein Out-of-Hospital Cardiac Arrest Registry Template.

The Utstein Out-of-Hospital Cardiac Arrest Resuscitation Registry Template, introduced in 1991 and updated in 2004 and 2015, standardizes data collection to enable research, evaluation, and comparisons of systems of care. The impetus for the current update stemmed from significant advances in the field and insights from registry development and regional comparisons. This 2024 update involved representatives of the International Liaison Committee on Resuscitation and used a modified Delphi process. Every 2015 Utstein data element was reviewed for relevance, priority (core or supplemental), and improvement. New variables were proposed and refined. All changes were voted on for inclusion. The 2015 domains-system, dispatch, patient, process, and outcomes-were retained. Further clarity is provided for the definitions of out-of-hospital cardiac arrest attended resuscitation and attempted resuscitation. Changes reflect advancements in dispatch, early response systems, and resuscitation care, as well as the importance of prehospital outcomes. Time intervals such as emergency medical service response time now emphasize precise reporting of the times used. New flowcharts aid the reporting of system effectiveness for patients with an attempted resuscitation and system efficacy for the Utstein comparator group. Recognizing the varying capacities of emergency systems globally, the writing group provided a minimal dataset for settings with developing emergency medical systems. Supplementary variables are considered useful for research purposes. These revisions aim to elevate data collection and reporting transparency by registries and researchers and to advance international comparisons and collaborations. The overarching objective remains the improvement of outcomes for patients with out-of-hospital cardiac arrest.

Improving Outcomes After Post-Cardiac Arrest Brain Injury: A Scientific Statement From the International Liaison Committee on Resuscitation.

This scientific statement presents a conceptual framework for the pathophysiology of post-cardiac arrest brain injury, explores reasons for previous failure to translate preclinical data to clinical practice, and outlines potential paths forward. Post-cardiac arrest brain injury is characterized by 4 distinct but overlapping phases: ischemic depolarization, reperfusion repolarization, dysregulation, and recovery and repair. Previous research has been challenging because of the limitations of laboratory models; heterogeneity in the patient populations enrolled; overoptimistic estimation of treatment effects leading to suboptimal sample sizes; timing and route of intervention delivery; limited or absent evidence that the intervention has engaged the mechanistic target; and heterogeneity in postresuscitation care, prognostication, and withdrawal of life-sustaining treatments. Future trials must tailor their interventions to the subset of patients most likely to benefit and deliver this intervention at the appropriate time, through the appropriate route, and at the appropriate dose. The complexity of post-cardiac arrest brain injury suggests that monotherapies are unlikely to be as successful as multimodal neuroprotective therapies. Biomarkers should be developed to identify patients with the targeted mechanism of injury, to quantify its severity, and to measure the response to therapy. Studies need to be adequately powered to detect effect sizes that are realistic and meaningful to patients, their families, and clinicians. Study designs should be optimized to accelerate the evaluation of the most promising interventions. Multidisciplinary and international collaboration will be essential to realize the goal of developing effective therapies for post-cardiac arrest brain injury.

Improving Outcomes After Post-Cardiac Arrest Brain Injury: A Scientific Statement From the International Liaison Committee on Resuscitation.

This scientific statement presents a conceptual framework for the pathophysiology of post-cardiac arrest brain injury, explores reasons for previous failure to translate preclinical data to clinical practice, and outlines potential paths forward. Post-cardiac arrest brain injury is characterized by 4 distinct but overlapping phases: ischemic depolarization, reperfusion repolarization, dysregulation, and recovery and repair. Previous research has been challenging because of the limitations of laboratory models; heterogeneity in the patient populations enrolled; overoptimistic estimation of treatment effects leading to suboptimal sample sizes; timing and route of intervention delivery; limited or absent evidence that the intervention has engaged the mechanistic target; and heterogeneity in postresuscitation care, prognostication, and withdrawal of life-sustaining treatments. Future trials must tailor their interventions to the subset of patients most likely to benefit and deliver this intervention at the appropriate time, through the appropriate route, and at the appropriate dose. The complexity of post-cardiac arrest brain injury suggests that monotherapies are unlikely to be as successful as multimodal neuroprotective therapies. Biomarkers should be developed to identify patients with the targeted mechanism of injury, to quantify its severity, and to measure the response to therapy. Studies need to be adequately powered to detect effect sizes that are realistic and meaningful to patients, their families, and clinicians. Study designs should be optimized to accelerate the evaluation of the most promising interventions. Multidisciplinary and international collaboration will be essential to realize the goal of developing effective therapies for post-cardiac arrest brain injury.

Advanced life support interventions during intra-operative cardiac arrest among adults as reported to the 7th National Audit Project of the Royal College of Anaesthetists.

BACKGROUND: Few existing resuscitation guidelines include specific reference to intra-operative cardiac arrest, but its optimal treatment is likely to require some adaptation of standard protocols. METHODS: We analysed data from the 7th National Audit Project of the Royal College of Anaesthetists to determine the incidence and outcome from intra-operative cardiac arrest and to summarise the advanced life support interventions reported as being used by anaesthetists. RESULTS: In the baseline survey, > 50% of anaesthetists responded that they would start chest compressions when the non-invasive systolic pressure was < 40-50 mmHg. Of the 881 registry patients, 548 were adult patients (aged > 18 years) having non-obstetric procedures under the care of an anaesthetist, and who had arrested during anaesthesia (from induction to emergence). Sustained return of spontaneous circulation was achieved in 425 (78%) patients and 338 (62%) were alive at the time of reporting. In the 365 patients with pulseless electrical activity or bradycardia, adrenaline was given as a 1 mg bolus in 237 (65%). A precordial thump was used in 14 (3%) patients, and although this was associated with return of spontaneous circulation at the next rhythm check in almost three-quarters of patients, in only one of these was the initial rhythm shockable. Calcium (gluconate or chloride) and 8.4% sodium bicarbonate were given to 51 (9%) and 25 (5%) patients, but there were specific indications for these treatments in less than half of the patients. A thrombolytic drug was given to 5 (1%) patients, and extracorporeal cardiopulmonary resuscitation was used in 9 (2%) of which eight occurred during cardiac procedures. CONCLUSIONS: The specific characteristics of intra-operative cardiac arrest imply that its optimal treatment requires modifications to standard advanced life support guidelines.

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.

Critical Care Management of Patients After Cardiac Arrest: A Scientific Statement From the American Heart Association and Neurocritical Care Society.

The critical care management of patients after cardiac arrest is burdened by a lack of high-quality clinical studies and the resultant lack of high-certainty evidence. This results in limited practice guideline recommendations, which may lead to uncertainty and variability in management. Critical care management is crucial in patients after cardiac arrest and affects outcome. Although guidelines address some relevant topics (including temperature control and neurological prognostication of comatose survivors, 2 topics for which there are more robust clinical studies), many important subject areas have limited or nonexistent clinical studies, leading to the absence of guidelines or low-certainty evidence. The American Heart Association Emergency Cardiovascular Care Committee and the Neurocritical Care Society collaborated to address this gap by organizing an expert consensus panel and conference. Twenty-four experienced practitioners (including physicians, nurses, pharmacists, and a respiratory therapist) from multiple medical specialties, levels, institutions, and countries made up the panel. Topics were identified and prioritized by the panel and arranged by organ system to facilitate discussion, debate, and consensus building. Statements related to postarrest management were generated, and 80% agreement was required to approve a statement. Voting was anonymous and web based. Topics addressed include neurological, cardiac, pulmonary, hematological, infectious, gastrointestinal, endocrine, and general critical care management. Areas of uncertainty, areas for which no consensus was reached, and future research directions are also included. Until high-quality studies that inform practice guidelines in these areas are available, the expert panel consensus statements that are provided can advise clinicians on the critical care management of patients after cardiac arrest.

Supraglottic Airway Versus Tracheal Intubation for Airway Management in Out-of-Hospital Cardiac Arrest: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis of Randomized Controlled Trials.

OBJECTIVES: Given the uncertainty regarding the optimal approach for airway management for adult patients with out-of-hospital cardiac arrest (OHCA), we conducted a systematic review and meta-analysis to compare the use of supraglottic airways (SGAs) with tracheal intubation for initial airway management in OHCA. DATA SOURCES: We searched MEDLINE, PubMed, Embase, Cochrane Library, as well as unpublished sources, from inception to February 7, 2023. STUDY SELECTION: We included randomized controlled trials (RCTs) of adult OHCA patients randomized to SGA compared with tracheal intubation for initial prehospital airway management. DATA EXTRACTION: Reviewers screened abstracts, full texts, and extracted data independently and in duplicate. We pooled data using a random-effects model. We used the modified Cochrane risk of bias 2 tool and assessed certainty of evidence using the Grading Recommendations Assessment, Development, and Evaluation approach. We preregistered the protocol on PROSPERO (CRD42022342935). DATA SYNTHESIS: We included four RCTs ( n = 13,412 patients). Compared with tracheal intubation , SGA use probably increases return of spontaneous circulation (ROSC) (relative risk [RR] 1.09; 95% CI, 1.02-1.15; moderate certainty) and leads to a faster time to airway placement (mean difference 2.5 min less; 95% CI, 1.6-3.4 min less; high certainty). SGA use may have no effect on survival at longest follow-up (RR 1.06; 95% CI, 0.84-1.34; low certainty), has an uncertain effect on survival with good functional outcome (RR 1.11; 95% CI, 0.82-1.50; very low certainty), and may have no effect on risk of aspiration (RR 1.04; 95% CI, 0.94 to 1.16; low certainty). CONCLUSIONS: In adult patients with OHCA, compared with tracheal intubation, the use of SGA for initial airway management probably leads to more ROSC, and faster time to airway placement, but may have no effect on longer-term survival outcomes or aspiration events.

Critical Care Management of Patients After Cardiac Arrest: A Scientific Statement from the American Heart Association and Neurocritical Care Society.

The critical care management of patients after cardiac arrest is burdened by a lack of high-quality clinical studies and the resultant lack of high-certainty evidence. This results in limited practice guideline recommendations, which may lead to uncertainty and variability in management. Critical care management is crucial in patients after cardiac arrest and affects outcome. Although guidelines address some relevant topics (including temperature control and neurological prognostication of comatose survivors, 2 topics for which there are more robust clinical studies), many important subject areas have limited or nonexistent clinical studies, leading to the absence of guidelines or low-certainty evidence. The American Heart Association Emergency Cardiovascular Care Committee and the Neurocritical Care Society collaborated to address this gap by organizing an expert consensus panel and conference. Twenty-four experienced practitioners (including physicians, nurses, pharmacists, and a respiratory therapist) from multiple medical specialties, levels, institutions, and countries made up the panel. Topics were identified and prioritized by the panel and arranged by organ system to facilitate discussion, debate, and consensus building. Statements related to postarrest management were generated, and 80% agreement was required to approve a statement. Voting was anonymous and web based. Topics addressed include neurological, cardiac, pulmonary, hematological, infectious, gastrointestinal, endocrine, and general critical care management. Areas of uncertainty, areas for which no consensus was reached, and future research directions are also included. Until high-quality studies that inform practice guidelines in these areas are available, the expert panel consensus statements that are provided can advise clinicians on the critical care management of patients after cardiac arrest.

Prognostic factors associated with favourable functional outcome among adult patients requiring extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: A systematic review and meta-analysis.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR), has demonstrated promise in the management of refractory out-of-hospital cardiac arrest (OHCA). However, evidence from observational studies and clinical trials are conflicting and the factors influencing outcome have not been well established. METHODS: We conducted a systematic review and meta-analysis summarizing the association between pre-ECPR prognostic factors and likelihood of good functional outcome among adult patients requiring ECPR for OHCA. We searched Medline and Embase databases from inception to February 28, 2023 and screened studies with two independent reviewers. We performed meta-analyses of unadjusted and adjusted odds ratios, adjusted hazard ratios and mean differences separately. We assessed risk of bias using the QUIPS tool and certainty of evidence using the GRADE approach. FINDINGS: We included 29 observational and randomized studies involving 7,397 patients. Factors with moderate or high certainty of association with increased survival with favourable functional outcome include pre-arrest patient factors, such as younger age (odds ratio (OR) 2.13, 95% CI 1.52 to 2.99) and female sex (OR 1.37, 95% CI 1.11 to 1.70), as well as intra-arrest factors, such as shockable rhythm (OR 2.79, 95% CI 2.04 to 3.80), witnessed arrest (OR 1.68 (95% CI 1.16 to 2.42), bystander CPR (OR 1.55, 95% CI 1.19 to 2.01), return of spontaneous circulation (OR 2.81, 95% CI 2.19 to 3.61) and shorter time to cannulation (OR 1.14, 95% CI 1.17 to 1.69 per 10 minutes). INTERPRETATION: The findings of this review confirm several clinical concepts wellestablished in the cardiac arrest literature and their applicability to the patient for whom ECPR is considered - that is, the impact of pre-existing patient factors, the benefit of timely and effective CPR, as well as the prognostic importance of minimizing low-flow time. We advocate for the thoughtful consideration of these prognostic factors as part of a risk stratification framework when evaluating a patient's potential candidacy for ECPR.

Expedited transfer to a cardiac arrest centre for non-ST-elevation out-of-hospital cardiac arrest (ARREST): a UK prospective, multicentre, parallel, randomised clinical trial.

BACKGROUND: The International Liaison Committee on Resuscitation has called for a randomised trial of delivery to a cardiac arrest centre. We aimed to assess whether expedited delivery to a cardiac arrest centre compared with current standard of care following resuscitated cardiac arrest reduces deaths. METHODS: ARREST is a prospective, parallel, multicentre, open-label, randomised superiority trial. Patients (aged ≥18 years) with return of spontaneous circulation following out-of-hospital cardiac arrest without ST elevation were randomly assigned (1:1) at the scene of their cardiac arrest by London Ambulance Service staff using a secure online randomisation system to expedited delivery to the cardiac catheter laboratory at one of seven cardiac arrest centres or standard of care with delivery to the geographically closest emergency department at one of 32 hospitals in London, UK. Masking of the ambulance staff who delivered the interventions and those reporting treatment outcomes in hospital was not possible. The primary outcome was all-cause mortality at 30 days, analysed in the intention-to-treat (ITT) population excluding those with unknown mortality status. Safety outcomes were analysed in the ITT population. The trial was prospectively registered with the International Standard Randomised Controlled Trials Registry, 96585404. FINDINGS: Between Jan 15, 2018, and Dec 1, 2022, 862 patients were enrolled, of whom 431 (50%) were randomly assigned to a cardiac arrest centre and 431 (50%) to standard care. 20 participants withdrew from the cardiac arrest centre group and 19 from the standard care group, due to lack of consent or unknown mortality status, leaving 411 participants in the cardiac arrest centre group and 412 in the standard care group for the primary analysis. Of 822 participants for whom data were available, 560 (68%) were male and 262 (32%) were female. The primary endpoint of 30-day mortality occurred in 258 (63%) of 411 participants in the cardiac arrest centre group and in 258 (63%) of 412 in the standard care group (unadjusted risk ratio for survival 1·00, 95% CI 0·90-1·11; p=0·96). Eight (2%) of 414 patients in the cardiac arrest centre group and three (1%) of 413 in the standard care group had serious adverse events, none of which were deemed related to the trial intervention. INTERPRETATION: In adult patients without ST elevation, transfer to a cardiac arrest centre following resuscitated cardiac arrest in the community did not reduce deaths. FUNDING: British Heart Foundation.

Trends in use of intraosseous and intravenous access in out-of-hospital cardiac arrest across English ambulance services: A registry-based, cohort study.

INTRODUCTION: The optimum route for drug administration in cardiac arrest is unclear. Recent data suggest that use of the intraosseous route may be increasing. This study aimed to explore changes over time in use of the intraosseous and intravenous drug routes in out-of-hospital cardiac arrest in England. METHODS: We extracted data from the UK Out-of-Hospital Cardiac Arrest Outcomes registry. We included adult out-of-hospital cardiac arrest patients between 2015-2020 who were treated by an English Emergency Medical Service that submitted vascular access route data to the registry. The primary outcome was any use of the intraosseous route during cardiac arrest. We used logistic regression models to describe the association between time (calendar month) and intraosseous use. RESULTS: We identified 75,343 adults in cardiac arrest treated by seven Emergency Medical Service systems between January 2015 and December 2020. The median age was 72 years, 64% were male and 23% presented in a shockable rhythm. Over the study period, the percentage of patients receiving intraosseous access increased from 22.8% in 2015 to 42.5% in 2020. For each study-month, the odds of receiving any intraosseous access increased by 1.019 (95% confidence interval 1.019 to 1.020, p < 0.001). This observed effect was consistent across sensitivity analyses. We observed a corresponding decrease in use of intravenous access. CONCLUSION: In England, the use of intraosseous access in out-of-hospital cardiac arrest has progressively increased over time. There is an urgent need for randomised controlled trials to evaluate the clinical effectiveness of the different vascular access routes in cardiac arrest.

Temperature control after adult cardiac arrest: An updated systematic review and meta-analysis.

AIM: To perform an updated systematic review and meta-analysis on temperature control in adult patients with cardiac arrest. METHODS: The review is an update of a previous systematic review published in 2021. An updated search including PubMed, Embase, and the Cochrane Central Register of Controlled Trials was performed on May 31, 2023. Controlled trials in humans were included. The population included adult patients with cardiac arrest. The review included all aspects of temperature control including timing, temperature, duration, method of induction and maintenance, and rewarming. Two investigators reviewed trials for relevance, extracted data, and assessed risk of bias. Data were pooled using random-effects models. Certainty of evidence was evaluated using GRADE. RESULTS: The updated systematic search identified six new trials. Risk of bias in the trials was assessed as intermediate for most of the outcomes. For temperature control with a target of 32-34 °C vs. normothermia or 36 °C, two new trials were identified, with seven trials included in an updated meta-analysis. Temperature control with a target of 32-34 °C did not result in an improvement in survival (risk ratio: 1.06 [95%CI: 0.91, 1.23]) or favorable neurological outcome (risk ratio: 1.27 [95%CI: 0.89, 1.81]) at 90-180 days after the cardiac arrest (low certainty evidence). Subgroup analysis according to location of cardiac arrest (in-hospital vs. out-of-hospital) found similar results. A sensitivity analysis of nine trials comparing temperature control at 32-34 °C to normothermia or 36 °C for favorable neurological outcome at any time point also did not show an improvement in outcomes (risk ratio: 1.14 [95%CI 0.98, 1.34]). New individual trials comparing a target of 31-34 °C, temperature control for 12-24 hours to 36 hours, a rewarming rate of 0.25-0.5 °C/hour, and the effect of temperature control with fever prevention found no differences in outcomes. CONCLUSIONS: This updated systematic review showed no benefit of temperature control at 32-34 °C compared to normothermia or 36 °C, although the 95% confidence intervals cannot rule out a potential beneficial effect. Important knowledge gaps exist for topics such as hypothermic temperature targets, rewarming rate, and fever control.