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.

Prediction of survival in out-of-hospital cardiac arrest: the updated Swedish cardiac arrest risk score (SCARS) model.

Aims: Out-of-hospital cardiac arrest (OHCA) is a major health concern worldwide. Although one-third of all patients achieve a return of spontaneous circulation and may undergo a difficult period in the intensive care unit, only 1 in 10 survive. This study aims to improve our previously developed machine learning model for early prognostication of survival in OHCA. Methods and results: We studied all cases registered in the Swedish Cardiopulmonary Resuscitation Registry during 2010 and 2020 (n = 55 615). We compared the predictive performance of extreme gradient boosting (XGB), light gradient boosting machine (LightGBM), logistic regression, CatBoost, random forest, and TabNet. For each framework, we developed models that optimized (i) a weighted F1 score to penalize models that yielded more false negatives and (ii) a precision-recall area under the curve (PR AUC). LightGBM assigned higher importance values to a larger set of variables, while XGB made predictions using fewer predictors. The area under the curve receiver operating characteristic (AUC ROC) scores for LightGBM were 0.958 (optimized for weighted F1) and 0.961 (optimized for a PR AUC), while for XGB, the scores were 0.958 and 0.960, respectively. The calibration plots showed a subtle underestimation of survival for LightGBM, contrasting with a mild overestimation for XGB models. In the crucial range of 0-10% likelihood of survival, the XGB model, optimized with the PR AUC, emerged as a clinically safe model. Conclusion: We improved our previous prediction model by creating a parsimonious model with an AUC ROC at 0.96, with excellent calibration and no apparent risk of underestimating survival in the critical probability range (0-10%). The model is available at www.gocares.se.

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.

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.

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.

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.

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.

Hypothermic versus Normothermic Temperature Control after Cardiac Arrest.

BACKGROUND: The evidence for temperature control for comatose survivors of cardiac arrest is inconclusive. Controversy exists as to whether the effects of hypothermia differ per the circumstances of the cardiac arrest or patient characteristics. METHODS: An individual patient data meta-analysis of the Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest (TTM) and Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trials was conducted. The intervention was hypothermia at 33°C and the comparator was normothermia. The primary outcome was all-cause mortality at 6 months. Secondary outcomes included poor functional outcome (modified Rankin scale score of 4 to 6) at 6 months. Predefined subgroups based on the design variables in the original trials were tested for interaction with the intervention as follows: age (older or younger than the median), sex (female or male), initial cardiac rhythm (shockable or nonshockable), time to return of spontaneous circulation (above or below the median), and circulatory shock on admission (presence or absence). RESULTS: The primary analyses included 2800 patients, with 1403 assigned to hypothermia and 1397 to normothermia. Death occurred for 691 of 1398 participants (49.4%) in the hypothermia group and 666 of 1391 participants (47.9%) in the normothermia group (relative risk with hypothermia, 1.03; 95% confidence interval [CI], 0.96 to 1.11; P=0.41). A poor functional outcome occurred for 733 of 1350 participants (54.3%) in the hypothermia group and 718 of 1330 participants (54.0%) in the normothermia group (relative risk with hypothermia, 1.01; 95% CI, 0.94 to 1.08; P=0.88). Outcomes were consistent in the predefined subgroups. CONCLUSIONS: Hypothermia at 33°C did not decrease 6-month mortality compared with normothermia after out-of-hospital cardiac arrest. (Funded by Vetenskapsrådet; ClinicalTrials.gov numbers NCT02908308 and NCT01020916.)