The design of the PRINCESS 2 trial: A randomized trial to study the impact of ultrafast hypothermia on complete neurologic recovery after out-of-hospital cardiac arrest with initial shockable rhythm.

BACKGROUND: Delayed hypothermia, initiated after hospital arrival, several hours after cardiac arrest with 8-10 hours to reach the target temperature, is likely to have limited impact on overall survival. However, the effect of ultrafast hypothermia, i.e., delivered intra-arrest or immediately after return of spontaneous circulation (ROSC), on functional neurologic outcome after out-of-hospital cardiac arrest (OHCA) is unclear. In two prior trials, prehospital trans-nasal evaporative intra-arrest cooling was safe, feasible and reduced time to target temperature compared to delayed cooling. Both studies showed trends towards improved neurologic recovery in patients with shockable rhythms. The aim of the PRINCESS2-study is to assess whether cooling, initiated either intra-arrest or immediately after ROSC, followed by in-hospital hypothermia, significantly increases survival with complete neurologic recovery as compared to standard normothermia care, in OHCA patients with shockable rhythms. METHODS/DESIGN: In this investigator-initiated, randomized, controlled trial, the emergency medical services (EMS) will randomize patients at the scene of cardiac arrest to either trans-nasal cooling within 20 minutes from EMS arrival with subsequent hypothermia at 33°C for 24 hours after hospital admission (intervention), or to standard of care with no prehospital or in-hospital cooling (control). Fever (>37,7°C) will be avoided for the first 72 hours in both groups. All patients will receive post resuscitation care and withdrawal of life support procedures according to current guidelines. Primary outcome is survival with complete neurologic recovery at 90 days, defined as modified Rankin scale (mRS) 0-1. Key secondary outcomes include survival to hospital discharge, survival at 90 days and mRS 0-3 at 90 days. In total, 1022 patients are required to detect an absolute difference of 9% (from 45 to 54%) in survival with neurologic recovery (80% power and one-sided α=0,025, ß=0,2) and assuming 2,5% lost to follow-up. Recruitment starts in Q1 2024 and we expect maximum enrolment to be achieved during Q4 2024 at 20-25 European and US sites. DISCUSSION: This trial will assess the impact of ultrafast hypothermia applied on the scene of cardiac arrest, as compared to normothermia, on 90-day survival with complete neurologic recovery in OHCA patients with initial shockable rhythm. TRIAL REGISTRATION: NCT06025123.

Underlying reasons for sex difference in survival following out-of-hospital cardiac arrest: a mediation analysis.

AIMS: Previous studies have indicated a poorer survival among women following out-of-hospital cardiac arrest (OHCA), but the mechanisms explaining this difference remain largely uncertain.This study aimed to assess the survival after OHCA among women and men and explore the role of potential mediators, such as resuscitation characteristics, prior comorbidity, and socioeconomic factors. METHODS AND RESULTS: This was a population-based cohort study including emergency medical service-treated OHCA reported to the Swedish Registry for Cardiopulmonary Resuscitation in 2010-2020, linked to nationwide Swedish healthcare registries. The relative risks (RR) of 30-day survival were compared among women and men, and a mediation analysis was performed to investigate the importance of potential mediators. Total of 43 226 OHCAs were included, of which 14 249 (33.0%) were women. Women were older and had a lower proportion of shockable initial rhythm. The crude 30-day survival among women was 6.2% compared to 10.7% for men [RR 0.58, 95% confidence interval (CI) = 0.54-0.62]. Stepwise adjustment for shockable initial rhythm attenuated the association to RR 0.85 (95% CI = 0.79-0.91). Further adjustments for age and resuscitation factors attenuated the survival difference to null (RR 0.98; 95% CI = 0.92-1.05). Mediation analysis showed that shockable initial rhythm explained ∼50% of the negative association of female sex on survival. Older age and lower disposable income were the second and third most important variables, respectively. CONCLUSION: Women have a lower crude 30-day survival following OHCA compared to men. The poor prognosis is largely explained by a lower proportion of shockable initial rhythm, older age at presentation, and lower income.

The INTOXICATE study: methodology and preliminary results of a prospective observational study.

BACKGROUND: There is currently no practice-based, multicenter database of poisoned patients admitted to intensive care units (ICUs). The INTOXICATE study, endorsed by the ESICM and EAPCCT, aimed to determine the rate of eventful admissions among acutely intoxicated adult ICU patients. METHODS: Ethical approval was obtained for this multicenter, prospective observational study, and data-sharing agreements were signed with each participating center. An electronic case report form was used to collect data on patient demographics, exposure, clinical characteristics, investigations, treatment, and in-hospital mortality data. The primary outcome, 'eventful admission', was a composite outcome defined as the rate of patients who received any of the following treatments in the first 24 h after the ICU admission: oxygen supplementation with a FiO2 > 40%, mechanical ventilation, vasopressors, renal replacement therapy (RRT), cardiopulmonary resuscitation, antidotes, active cooling, fluid resuscitation (> 1.5 L of intravenous fluid of any kind), sedation, or who died in the hospital. RESULTS: Seventy-eight ICUs, mainly from Europe, but also from Australia and the Eastern Mediterranean, participated. A total of 2,273 patients were enrolled between November 2020 and June 2023. The median age of the patients was 41 years, 72% were exposed to intoxicating drugs. The observed rate of patients with an eventful ICU admission was 68% (n = 1546/2273 patients). The hospital mortality was 4.5% (n = 103/2273). CONCLUSIONS: The vast majority of patients survive, and approximately one third of patients do not receive any ICU-specific interventions after admission in an intensive care unit for acute intoxication. High-quality detailed clinical data have been collected from a large cohort of acutely intoxicated ICU patients, providing information on the pattern of severe acute poisoning requiring intensive care admission and the outcomes of these patients. TRIAL REGISTRATION: OSF registration ID: osf.io/7e5uy.

Automated external defibrillators delivered by drones to patients with suspected out-of-hospital cardiac arrest.

AIMS: Early defibrillation is critical for the chance of survival in out-of-hospital cardiac arrest (OHCA). Drones, used to deliver automated external defibrillators (AEDs), may shorten time to defibrillation, but this has never been evaluated in real-life emergencies. The aim of this study was to investigate the feasibility of AED delivery by drones in real-life cases of OHCA. METHODS AND RESULTS: In this prospective clinical trial, three AED-equipped drones were placed within controlled airspace in Sweden, covering approximately 80 000 inhabitants (125 km2). Drones were integrated in the emergency medical services for automated deployment in beyond-visual-line-of-sight flights: (i) test flights from 1 June to 30 September 2020 and (ii) consecutive real-life suspected OHCAs. Primary outcome was the proportion of successful AED deliveries when drones were dispatched in cases of suspected OHCA. Among secondary outcomes was the proportion of cases where AED drones arrived prior to ambulance and time benefit vs. ambulance. Totally, 14 cases were eligible for dispatch during the study period in which AED drones took off in 12 alerts to suspected OHCA, with a median distance to location of 3.1 km [interquartile range (IQR) 2.8-3.4). AED delivery was feasible within 9 m (IQR 7.5-10.5) from the location and successful in 11 alerts (92%). AED drones arrived prior to ambulances in 64%, with a median time benefit of 01:52 min (IQR 01:35-04:54) when drone arrived first. In an additional 61 test flights, the AED delivery success rate was 90% (55/61). CONCLUSION: In this pilot study, we have shown that AEDs can be carried by drones to real-life cases of OHCA with a successful AED delivery rate of 92%. There was a time benefit as compared to emergency medical services in cases where the drone arrived first. However, further improvements are needed to increase dispatch rate and time benefits. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT04415398.

Effect of intra-arrest trans-nasal evaporative cooling in out-of-hospital cardiac arrest: a pooled individual participant data analysis.

BACKGROUND: Randomized trials have shown that trans-nasal evaporative cooling initiated during CPR (i.e. intra-arrest) effectively lower core body temperature in out-of-hospital cardiac arrest patients. However, these trials may have been underpowered to detect significant differences in neurologic outcome, especially in patients with initial shockable rhythm. METHODS: We conducted a post hoc pooled analysis of individual data from two randomized trials including 851 patients who eventually received the allocated intervention and with available outcome ("as-treated" analysis). Primary outcome was survival with favourable neurological outcome at hospital discharge (Cerebral Performance Category [CPC] of 1-2) according to the initial rhythm (shockable vs. non-shockable). Secondary outcomes included complete neurological recovery (CPC 1) at hospital discharge. RESULTS: Among the 325 patients with initial shockable rhythms, favourable neurological outcome was observed in 54/158 (34.2%) patients in the intervention and 40/167 (24.0%) in the control group (RR 1.43 [confidence intervals, CIs 1.01-2.02]). Complete neurological recovery was observed in 40/158 (25.3%) in the intervention and 27/167 (16.2%) in the control group (RR 1.57 [CIs 1.01-2.42]). Among the 526 patients with initial non-shockable rhythms, favourable neurological outcome was in 10/259 (3.8%) in the intervention and 13/267 (4.9%) in the control group (RR 0.88 [CIs 0.52-1.29]; p = 0.67); survival and complete neurological recovery were also similar between groups. No significant benefit was observed for the intervention in the entire population. CONCLUSIONS: In this pooled analysis of individual data, intra-arrest cooling was associated with a significant increase in favourable neurological outcome in out-of-hospital cardiac arrest patients with initial shockable rhythms. Future studies are needed to confirm the potential benefits of this intervention in this subgroup of patients.

Survival in Out-of-Hospital Cardiac Arrest After Standard Cardiopulmonary Resuscitation or Chest Compressions Only Before Arrival of Emergency Medical Services: Nationwide Study During Three Guideline Periods.

BACKGROUND: In out-of-hospital cardiac arrest, chest compression-only cardiopulmonary resuscitation (CO-CPR) has emerged as an alternative to standard CPR (S-CPR), using both chest compressions and rescue breaths. Since 2010, CPR guidelines recommend CO-CPR for both untrained bystanders and trained bystanders unwilling to perform rescue breaths. The aim of this study was to describe changes in the rate and type of CPR performed before the arrival of emergency medical services (EMS) during 3 consecutive guideline periods in correlation to 30-day survival. METHODS: All bystander-witnessed out-of-hospital cardiac arrests reported to the Swedish register for cardiopulmonary resuscitation in 2000 to 2017 were included. Nonwitnessed, EMS-witnessed, and rescue breath-only CPR cases were excluded. Patients were categorized as receivers of no CPR (NO-CPR), S-CPR, or CO-CPR before EMS arrival. Guideline periods 2000 to 2005, 2006 to 2010, and 2011 to 2017 were used for comparisons over time. The primary outcome was 30-day survival. RESULTS: A total of 30 445 patients were included. The proportions of patients receiving CPR before EMS arrival changed from 40.8% in the first time period to 58.8% in the second period, and to 68.2% in the last period. S-CPR changed from 35.4% to 44.8% to 38.1%, and CO-CPR changed from 5.4% to 14.0% to 30.1%, respectively. Thirty-day survival changed from 3.9% to 6.0% to 7.1% in the NO-CPR group, from 9.4% to 12.5% to 16.2% in the S-CPR group, and from 8.0% to 11.5% to 14.3% in the CO-CPR group. For all time periods combined, the adjusted odds ratio for 30-day survival was 2.6 (95% CI, 2.4-2.9) for S-CPR and 2.0 (95% CI, 1.8-2.3) for CO-CPR, in comparison with NO-CPR. S-CPR was superior to CO-CPR (adjusted odds ratio, 1.2; 95% CI, 1.1-1.4). CONCLUSIONS: In this nationwide study of out-of-hospital cardiac arrest during 3 periods of different CPR guidelines, there was an almost a 2-fold higher rate of CPR before EMS arrival and a concomitant 6-fold higher rate of CO-CPR over time. Any type of CPR was associated with doubled survival rates in comparison with NO-CPR. These findings support continuous endorsement of CO-CPR as an option in future CPR guidelines because it is associated with higher CPR rates and overall survival in out-of-hospital cardiac arrest.

Long-term mortality and cause of death for patients treated in Intensive Care Units due to poisoning.

BACKGROUND: Poisoned patients treated in the Intensive Care Unit are common, representing up to 6% of all ICU admissions. The in-hospital mortality is generally low but little is known about the long-term mortality in these patients. The aim of this study was to describe long-term mortality and cause of death in patients treated in the ICU for poisoning. METHOD: A national observational study based on three registers: the National Patient Register, the Swedish Intensive Care Register and the Cause of Death Register. All patients ≥19 years admitted to a Swedish Intensive Care Unit between January 1, 2010 and December 31, 2011 with an ICD-10 code for poisoning were included. RESULTS: A total of 6730 patients were included. The one-year mortality was 4.5% (n = 303), with an overweight of men among the deceased (59.1%, P = 0.002). Patients aged 19-39 years had a 48 times increased one-year mortality compared to the age-matched general population and 94% of these patients died from suicide and/or accident, of which 70% were from a new poisoning. The two-year mortality was 7.2%. Women have a slightly higher overall long-term survival over two years (P< 0.001). CONCLUSION: The risk of premature death is markedly increased in younger patients one and two years after an ICU hospitalisation for non-fatal poisoning compared to the general population. A large majority die due to a new poisoning incident despite a previously known recent severe poisoning. EDITORIAL COMMENT: Admission to ICU with poisoning, and particularly self-poisoning, may be associated with long-term mortaliity. In this study of 6730 patients admitted to a Swedish ICU for poisoning, the in-hospital mortality was low for that admission, but there is an increased risk of later mortality in young patients one and two years after hospital discharge.

Effect of Trans-Nasal Evaporative Intra-arrest Cooling on Functional Neurologic Outcome in Out-of-Hospital Cardiac Arrest: The PRINCESS Randomized Clinical Trial.

Importance: Therapeutic hypothermia may increase survival with good neurologic outcome after cardiac arrest. Trans-nasal evaporative cooling is a method used to induce cooling, primarily of the brain, during cardiopulmonary resuscitation (ie, intra-arrest). Objective: To determine whether prehospital trans-nasal evaporative intra-arrest cooling improves survival with good neurologic outcome compared with cooling initiated after hospital arrival. Design, Setting, and Participants: The PRINCESS trial was an investigator-initiated, randomized, clinical, international multicenter study with blinded assessment of the outcome, performed by emergency medical services in 7 European countries from July 2010 to January 2018, with final follow-up on April 29, 2018. In total, 677 patients with bystander-witnessed out-of-hospital cardiac arrest were enrolled. Interventions: Patients were randomly assigned to receive trans-nasal evaporative intra-arrest cooling (n = 343) or standard care (n = 334). Patients admitted to the hospital in both groups received systemic therapeutic hypothermia at 32°C to 34°C for 24 hours. Main Outcomes and Measures: The primary outcome was survival with good neurologic outcome, defined as Cerebral Performance Category (CPC) 1-2, at 90 days. Secondary outcomes were survival at 90 days and time to reach core body temperature less than 34°C. Results: Among the 677 randomized patients (median age, 65 years; 172 [25%] women), 671 completed the trial. Median time to core temperature less than 34°C was 105 minutes in the intervention group vs 182 minutes in the control group (P < .001). The number of patients with CPC 1-2 at 90 days was 56 of 337 (16.6%) in the intervention cooling group vs 45 of 334 (13.5%) in the control group (difference, 3.1% [95% CI, -2.3% to 8.5%]; relative risk [RR], 1.23 [95% CI, 0.86-1.72]; P = .25). In the intervention group, 60 of 337 patients (17.8%) were alive at 90 days vs 52 of 334 (15.6%) in the control group (difference, 2.2% [95% CI, -3.4% to 7.9%]; RR, 1.14 [95% CI, 0.81-1.57]; P = .44). Minor nosebleed was the most common device-related adverse event, reported in 45 of 337 patients (13%) in the intervention group. The adverse event rate within 7 days was similar between groups. Conclusions and Relevance: Among patients with out-of-hospital cardiac arrest, trans-nasal evaporative intra-arrest cooling compared with usual care did not result in a statistically significant improvement in survival with good neurologic outcome at 90 days. Trial Registration: ClinicalTrials.gov Identifier: NCT01400373.

Drones for Provision of Flotation Support in Simulated Drowning.

OBJECTIVE: The feasibility and potential of using drones for providing flotation devices in cases of drowning have not yet been assessed. We hypothesize that a drone carrying an inflatable life buoy is a faster way to provide flotation compared with traditional methods. The purpose of this study is to explore the feasibility and efficiency of using a drone for delivering and providing flotation support to conscious simulated drowning victims. METHODS: A simulation study was performed with a simulated drowning victim 100 m from the shore. A drone (DJI Phantom 4; dji, Shenzhen, China) equipped with an inflatable life buoy of 60 N was compared with traditional surf rescue swimming for providing flotation. The primary outcome was delay (minutes:seconds). RESULTS: A total number of 30 rescues were performed with a median time to delivery of the floating device of 30 seconds (interquartile range [IQR] = 24-32 seconds) for the drone compared with 65 seconds (IQR = 60-77 seconds) with traditional rescue swimming (P < .001). The drone had an accuracy of 100% in dropping the inflatable life buoy < 5 m from the victim, with a median of 1 m (IQR = 1-2 m). CONCLUSION: Using drones to deliver inflatable life buoys is safe and may be a faster method to provide early flotation devices to conscious drowning victims compared with rescue swimming.

Surviving two hours of ventricular fibrillation in accidental hypothermia.

BACKGROUND: Cardiac arrest as a consequence of deep accidental hypothermia is associated with high mortality. Standardized prehospital management as well as rewarming with extracorporeal circulation (ECC) are important factors to improve survival. The objective of this case report is to illustrate the importance of effective cardiopulmonary resuscitation (CPR) and ECC in a cardiac arrest following deep accidental hypothermia. CASE REPORT: A 42-year-old man was found unresponsive to external stimuli and pulseless at an outdoor temperature of 1°C. CPR was started at the scene by laypersons, and the emergency medical services (EMS) arrived 5 minutes after the emergency call. Resuscitation according to International Liaison Committee on Resuscitation (ILCOR) guidelines was initiated by EMS. The first recorded rhythm was ventricular fibrillation (VF), which persisted, despite repeated defibrillation. The patient showed signs of severe hypothermia and, during ongoing CPR, was transported to hospital where on arrival the patient's rectal temperature was measured at 22°C. Resuscitation measures were continued and warming was started at the emergency room. Due to persistent VF and deep hypothermia, the patient was transferred to a cardiothoracic surgical unit for rewarming with ECC. At commencement of ECC, CPR had been going for approximately 130 minutes and a total of 38 defibrillations had been made. During this time interval the patients was pulseless. At a core temperature of 30°C, one defibrillation restored sinus rhythm and subsequently stable circulation was achieved. The patient received a further 24 hours of hypothermia treatment at 32-34°C. He was discharged to rehabilitation facilities after 3 weeks of hospital care. Three months after the cardiac arrest the patient was fully recovered, was back to work, and had resumed normal activities. CONCLUSIONS: We demonstrate a case of cardiac arrest due to deep accidental hypothermia that stresses the importance of effective CPR and early-stage consideration of the use of ECC for safe and effective rewarming.

Compression-Only or Standard Cardiopulmonary Resuscitation for Trained Laypersons in Out-of-Hospital Cardiac Arrest: A Nationwide Randomized Trial in Sweden.

BACKGROUND: The ongoing TANGO2 (Telephone Assisted CPR. AN evaluation of efficacy amonGst cOmpression only and standard CPR) trial is designed to evaluate whether compression-only cardiopulmonary resuscitation (CPR) by trained laypersons is noninferior to standard CPR in adult out-of-hospital cardiac arrest. This pilot study assesses feasibility, safety, and intermediate clinical outcomes as part of the larger TANGO2 survival trial. METHODS: Emergency medical dispatch calls of suspected out-of-hospital cardiac arrest were screened for inclusion at 18 dispatch centers in Sweden between January 1, 2017, and March 12, 2020. Inclusion criteria were witnessed event, bystander on the scene with previous CPR training, age above 18 years of age, and no signs of trauma, pregnancy, or intoxication. Cases were randomized 1:1 at the dispatch center to either instructions to perform compression-only CPR (intervention) or instructions to perform standard CPR (control). Feasibility included evaluation of inclusion, randomization, and adherence to protocol. Safety measures were time to emergency medical service dispatch CPR instructions, and to start of CPR, intermediate clinical outcome was defined as 1-day survival. RESULTS: Of 11 838 calls of suspected out-of-hospital cardiac arrest screened for inclusion, 2168 were randomized and 1250 (57.7%) were out-of-hospital cardiac arrests treated by the emergency medical service. Of these, 640 were assigned to intervention and 610 to control. Crossover from intervention to control occurred in 16.3% and from control to intervention in 18.5%. The median time from emergency call to ambulance dispatch was 1 minute and 36 s (interquartile range, 1.1-2.2) in the intervention group and 1 minute and 30 s (interquartile range, 1.1-2.2) in the control group. Survival to 1 day was 28.6% versus 28.4% (P=0.984) for intervention and control, respectively. CONCLUSIONS: In this national randomized pilot trial, compression-only CPR versus standard CPR by trained laypersons was feasible. No differences in safety measures or short-term survival were found between the 2 strategies. Efforts to reduce crossover are important and may strengthen the ongoing main trial that will assess differences in long-term survival. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02401633.

Hospitalized patients' attitudes towards participating in a randomized control trial in case of a cardiac arrest.

Background: No previous study has evaluated patients attitudes towards inclusion in an ongoing cardiac arrest clinical trial. The aim of this study was to assess patients willingness and motives to participate in the ongoing randomized controlled drug trial "Vasopressin and Steroids in addition to Adrenaline in cardiac arrest" (VAST-A trial) in case of an in-hospital cardiac arrest (IHCA). Objectives: Hospitalized patients, men ≥ 18 and women ≥ 50 years, were asked for informed consent for inclusion in the VAST-A trial in case of an IHCA, the reason for approving or declining inclusion in the trial and baseline characteristics. Methods: Patients admitted to hospital were asked to give informed consent of inclusion in VAST-A in case of an IHCA during their hospital stay. Patients were also asked why they approved or declined inclusion as well as baseline characteristics questions. Results: 1,064 patients were asked about willingness to participate in the VAST-A trial, of these 902 (84.8%) patients approved inclusion. A subgroup of 411 patients were, except willingness, also asked about motives to participate or not and basic characteristics. The main reason for approving inclusion was to contribute to research (n = 328, 83.9%). The main reason for declining inclusion was concerns regarding testing the drug treatment (n = 6, 30%). Conclusion: Among hospitalized patients the vast majority gave informed consent to inclusion in an ongoing randomized cardiac arrest drug trial. The main reason for approving inclusion was to contribute to research.

Outline and validation of a new dispatcher-assisted cardiopulmonary resuscitation educational bundle using the Delphi method.

Aim: Dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) is time-dependent. To date, evidence-based training programmes for dispatchers are lacking. This study aimed to reach expert consensus on an educational bundle content for dispatchers to provide DA-CPR using the Delphi method. Method: An educational bundle was created by the Swedish Resuscitation Council consisting of three parts: e-learning on DA-CPR, basic life support training and audit of emergency out-of-hospital cardiac arrest calls. Thereafter, a two-round modified Delphi study was conducted between November 2022 and March 2023; 37 experts with broad clinical and/or scientific knowledge of DA-CPR were invited. In the first round, the experts participated in the e-learning module and answered a questionnaire with 13 closed and open questions, whereafter the e-learning part of the bundle was revised. In the second round, the revised e-learning part was evaluated using Likert scores (20 items). The predefined consensus level was set at 80%. Results: Delphi rounds one and two were assessed by 20 and 18 of the invited experts, respectively. In round one, 18 experts (18 of 20, 90%) stated that they did not miss any content in the programme. In round two, the scale-level content validity index based on the average method (S-CVI/AVE, 0.99) and scale-level content validity index based on universal agreement (S-CVI/UA, 0.85) exceeded the threshold level of 80%. Conclusion: Expert consensus on the educational bundle content was reached using the Delphi method. Further work is required to evaluate its effect in real-world out-of-hospital cardiac arrest calls.

Implementation of an extracorporeal resuscitation (ECPR) program for out-of-hospital cardiac arrest in Stockholm, Sweden: Feasibility, safety, and outcome.

Background: The aim of this study was to evaluate the implementation of a novel extra corporeal cardiopulmonary (ECPR) program in the greater Stockholm area with focus on feasibility, safety aspects and clinical outcomes. Methods: Prospective observational study of ECPR program including patients with OHCA from January 2020 to December 2022, fulfilling ECPR criteria: age 18-65 years, initial shockable rhythm or pulseless electrical activity, witnessed arrest, bystander cardiopulmonary resuscitation and refractory arrest after three cycles of advance cardiac life support. The predefined time threshold from collapse to extracorporeal membrane oxygenation (ECMO) initiation was set at 60 min. Results: We included 95 patients. Of these, 22/95 (23%) had return of spontaneous circulation before ECMO initiation, 39/95 (41%) were excluded for ECMO and 34/95 (36%) had ECMO initiated out of which 23 patients were admitted alive to the ICU. ECMO-initiation within 60 min was met in 9%. In 6 patients vascular access was complicated, 2 patients had severe bleeding at access site requiring intervention. Survival to discharge among all cases was 25% (24/95). Among patients admitted to ICU on ECMO 39% (9/23) survived to discharge, of these 78% had cerebral performance category scale score 1-2 within 12 months. 8 out of 9 survivors had time from OHCA to ECMO-initiation >60 min. Conclusion: The implementation of an ECPR protocol was feasible without any major, unexpected safety aspects but did not meet the intended target time intervals. Despite this, survival rates were similar to previous studies although most survivors had >60 min to ECMO-initiation.

Design of the PRINCESS trial: pre-hospital resuscitation intra-nasal cooling effectiveness survival study (PRINCESS).

BACKGROUND: Therapeutic hypothermia (TH, 32-34°C) has been shown to improve neurological outcome in comatose survivors of out-of-hospital cardiac arrest (OHCA) with ventricular tachycardia or fibrillation. Earlier initiation of TH may increase the beneficial effects. Experimental studies have suggested that starting TH during cardiopulmonary resuscitation (CPR) may further enhance its neuroprotective effects. The aim of this study was to evaluate whether intra-arrest TH (IATH), initiated in the field with trans nasal evaporative cooling (TNEC), would provide outcome benefits when compared to standard of care in patients being resuscitated from OHCA. METHODS/DESIGN: We describe the methodology of a multi-centre, randomized, controlled trial comparing IATH delivered through TNEC device (Rhinochill, Benechill Inc., San Diego, CA, USA) during CPR to standard treatment, including TH initiated after hospital admission. The primary outcome is neurological intact survival defined as cerebral performance category 1-2 at 90 days among those patients who are admitted to the hospital. Secondary outcomes include survival at 90 days, proportion of patients achieving a return to spontaneous circulation (ROSC), the proportion of patients admitted alive to the hospital and the proportion of patients achieving target temperature (<34°C) within the first 4 hours since CA. DISCUSSION: This ongoing trial will assess the impact of IATH with TNEC, which may be able to rapidly induce brain cooling and have fewer side effects than other methods, such as cold fluid infusion. If this intervention is found to improve neurological outcome, its early use in the pre-hospital setting will be considered as an early neuro-protective strategy in OHCA. TRIAL REGISTRATION: NCT01400373.

Aetiology and outcome in hospitalized cardiac arrest patients.

Aims: To study aetiologies of in-hospital cardiac arrests (IHCAs) and their association with 30-day survival. Methods and results: Observational study with data from national registries. Specific aetiologies (n = 22) of IHCA patients between April 2018 and December 2020 were categorized into cardiac vs. non-cardiac and six main aetiology categories: myocardial ischemia, other cardiac causes, pulmonary causes, infection, haemorrhage, and other non-cardiac causes. Main endpoints were proportions in each aetiology, 30-day survival, and favourable neurological outcome (Cerebral Performance Category scale 1-2) at discharge. Among, 4320 included IHCA patients (median age 74 years, 63.1% were men), approximate 50% had cardiac causes with a 30-day survival of 48.4% compared to 18.7% among non-cardiac causes (P < 0.001). The proportion in each category were: myocardial ischemia 29.9%, pulmonary 21.4%, other cardiac causes 19.6%, other non-cardiac causes 11.6%, infection 9%, and haemorrhage 8.5%. The odds ratio (OR) for 30-day survival compared to myocardial ischemia for each category were: other cardiac causes OR 1.48 (CI 1.24-1.76); pulmonary causes OR 0.36 (CI 0.3-0.44); infection OR 0.25 (CI 0.18-0.33); haemorrhage OR 0.22 (CI 0.16-0.3); and other non-cardiac causes OR 0.56 (CI 0.45-0.69). IHCA caused by myocardial ischemia had the best favourable neurological outcome while those caused by infection had the lowest OR 0.06 (CI 0.03-0.13). Conclusion: In this nationwide observational study, aetiologies with cardiac and non-cardiac causes of IHCA were evenly distributed. IHCA caused by myocardial ischemia and other cardiac causes had the strongest associations with 30-day survival and neurological outcome.

Effects of a volunteer responder system for out-of-hospital cardiac arrest in areas of different population density - A retrospective cohort study.

BACKGROUND: Volunteer responder dispatch to nearby out-of-hospital cardiac arrests using a smartphone application can increase the proportion of patients receiving cardiopulmonary resuscitation. It is unknown how population density is related to the efficacy of a volunteer responder system. This study aimed to compare the response time of volunteer responders and EMS dispatched to suspected OHCAs in areas of different population density. METHODS: A total of 2630 suspected OHCAs in Stockholm County during 2018-2020 where at least one dispatched volunteer responder reached the patient were identified through the HeartRunner™ application database. Study outcome was the proportion of cases where volunteer responders arrived at the scene before EMS, as well as the difference in time between the arrival of volunteer responders and EMS. RESULTS: Volunteer responders arrived before EMS in 68% of examined cases (n = 1613). Higher population density was associated with a lower proportion of cases where volunteer responders arrived at the scene before EMS. Time on scene before arrival of EMS was highest in areas of low population density and averaged 4:07 (mm:ss). Response time was significantly shorter for volunteer responders compared to EMS across all population density groups at 4:47 vs 8:11 (mm:ss) (p < 0.001); the largest difference in response time was found in low population density areas. CONCLUSION: Volunteer responders have significantly shorter response time than EMS regardless of population density, with the greatest difference in low population density areas. Although their impact on clinical outcome remains unknown, the benefits of dispatching volunteer responders to OHCAs may be greatest in rural areas.

Transnasal Evaporative Cooling in Out-of-Hospital Cardiac Arrest Patients to Initiate Hypothermia-A Substudy of the Target Temperature Management 2 (TTM2) Randomized Trial.

Background: In animal models, early initiation of therapeutic cooling, intra-arrest, or restored circulation has been shown to be neuroprotective shortly after cardiac arrest. We aimed to assess the feasibility and cooling efficacy of transnasal evaporative cooling, initiated as early as possible after hospital arrival in patients randomized to cooling in the TTM2 trial. Methods: This study took the form of a single-center (Södersjukhuset, Stockholm) substudy of the TTM2 trial (NCT02908308) comparing target temperature management (TTM) to 33 °C versus normothermia in OHCA. In patients randomized to TTM33 °C, transnasal evaporative cooling was applied as fast as possible. The primary objectives were the feasibility aspects of initiating cooling in different hospital locations (i.e., in the emergency department, coronary cathlab, intensive care unit (ICU), and during intrahospital transport) and its effectiveness (i.e., time to reach target temperature). Transnasal cooling was continued for two hours or until patients reached a core temperature of <34 °C. Cooling intervals were compared to participants at the same site who were randomized to hypothermia and treated at 33 °C but who for different reasons did not receive transnasal evaporative cooling. Results: From October 2018 to January 2020, 32 patients were recruited, of which 17 were randomized to the TTM33. Among them, 10 patients (8 men, median age 69 years) received transnasal evaporative cooling prior to surface systemic cooling in the ICU. In three patients, cooling was started in the emergency department; in two patients, it was started in the coronary cathlab, and in five patients, it was started in the ICU, of which three patients were subsequently transported to the coronary cathlab or to perform a CT scan. The median time to initiate transnasal cooling from randomization was 9 min (range: 5 to 39 min). The median time from randomization to a core body temperature of 34 °C was 120 min (range 60 to 334) compared to 178 min among those in the TTM33 group that did not receive TNEC and to 33 °C 230 min (range: 152 to 351) vs. 276 min (range: 150 to 546). No feasibility or technical issues were reported. No adverse events occurred besides minor nosebleeds. Conclusions: The early induction of transnasal cooling in out-of-hospital cardiac arrest patients was feasible to initiate in the emergency department, coronary cathlab, ICU, and during intrahospital transport. Time to target temperature was shortened compared to standard cooling.

Drone delivery of automated external defibrillators compared with ambulance arrival in real-life suspected out-of-hospital cardiac arrests: a prospective observational study in Sweden.

BACKGROUND: A novel approach to improve bystander defibrillation for out-of-hospital cardiac arrests is to dispatch and deliver an automated external defibrillator (AED) directly to the suspected cardiac arrest location by drone. The aim of this study was to investigate how often a drone could deliver an AED before ambulance arrival and to measure the median time benefit achieved by drone deliveries. METHODS: In this prospective observational study, five AED-equipped drones were placed within two separate controlled airspaces in Sweden, covering approximately 200 000 inhabitants. Drones were dispatched in addition to standard emergency medical services for suspected out-of-hospital cardiac arrests and flight was autonomous. Alerts concerning children younger than 8 years, trauma, and emergency medical services-witnessed cases were not included. Exclusion criteria were air traffic control non-approval of flight, unfavourable weather conditions, no-delivery zones, and darkness. Data were collected from the dispatch centres, ambulance organisations, Swedish Registry for Cardiopulmonary Resuscitation, and the drone operator. Core outcomes were the percentage of cases for which an AED was delivered by a drone before ambulance arrival, and the median time difference (minutes and seconds) between AED delivery by drone and ambulance arrival. Explorative outcomes were percentage of attached drone-delivered AEDs before ambulance arrival and the percentage of cases defibrillated by a drone-delivered AED when it was used before ambulance arrival. FINDINGS: During the study period (from April 21, 2021 to May 31, 2022), 211 suspected out-of-hospital cardiac arrest alerts occurred, and in 72 (34%) of those a drone was deployed. Among those, an AED was successfully delivered in 58 (81%) cases, and the major reason for non-delivery was cancellation by dispatch centre because the case was not an out-of-hospital cardiac arrest. In cases for which arrival times for both drone and ambulance were available (n=55), AED delivery by drone occurred before ambulance arrival in 37 cases (67%), with a median time benefit of 3 min and 14 s. Among these cases, 18 (49%) were true out-of-hospital cardiac arrests and a drone-delivered AED was attached in six cases (33%). Two (33%) had a shockable first rhythm and were defibrillated by a drone-delivered AED before ambulance arrival, with one person achieving 30-day survival. No adverse events occurred. AED delivery (not landing) was made within 15 m from the patient or building in 91% of the cases. INTERPRETATION: AED-equipped drones dispatched in cases of suspected out-of-hospital cardiac arrests delivered AEDs before ambulance arrival in two thirds of cases, with a clinically relevant median time benefit of more than 3 min. This intervention could potentially decrease time to attachment of an AED, before ambulance arrival. FUNDING: Swedish Heart Lung Foundation.

Swedish emergency medical dispatch centres' ability to answer emergency medical calls and dispatch an ambulance in response to out-of-hospital cardiac arrest calls in accordance with the American Heart Association performance goals: An observational study.

AIM: To investigate the ability of Swedish Emergency Medical Dispatch Centres (EMDCs) to answer medical emergency calls and dispatch an ambulance for out-of-hospital cardiac arrest (OHCA) in accordance with the American Heart Association (AHA) performance goals in a 1-step (call connected directly to the EMDC) and a 2-step (call transferred to regional EMDC) procedure over 10 years, and to assess whether delays may be associated with 30-day survival. METHOD: Observational data from the Swedish Registry for Cardiopulmonary Resuscitation and EMDC. RESULTS: A total of 9,174,940 medical calls were answered (1-step). The median answer delay was 7.3 s (interquartile range [IQR], 3.6-14.5 s). Furthermore, 594,008 calls (6.1%) were transferred in a 2-step procedure, with a median answer delay of 39 s (IQR, 30-53 s). A total of 45,367 cases (0.5%, 1-step) were registered as OHCA, with a median answer delay of 7.2 s (IQR, 3.6-14.1 s) (AHA high-performance goal, 10 s). For 1-step procedure, no difference in 30-day survival was found regarding answer delay. For OHCA (1-step), an ambulance was dispatched after a median of 111.9 s (IQR, 81.7-159.9 s). Thirty-day survival was 10.8% (n = 664) when an ambulance was dispatched within 70 s (AHA high-performance) versus 9.3% (n = 2174) > 100 s (AHA acceptable) (p = 0.0013). Outcome data in the 2-step procedure was unobtainable. CONCLUSION: The majority of calls were answered within the AHA performance goals. When an ambulance was dispatched within the AHA high-performance standard in response to OHCA calls, survival was higher compared with calls when dispatch was delayed.