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

BACKGROUND AND AIMS: Previous studies have indicated a poorer survival among women following out-of-hospital cardiac arrest (OHCA), but the mechanisms explaining this difference remains 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: 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. RESULTS: 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% 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 approximately 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. CONCLUSIONS: 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.

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.

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.

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.

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.

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 Hypothermia vs Normothermia on Societal Participation and Cognitive Function at 6 Months in Survivors After Out-of-Hospital Cardiac Arrest: A Predefined Analysis of the TTM2 Randomized Clinical Trial.

Importance: The Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial reported no difference in mortality or poor functional outcome at 6 months after out-of-hospital cardiac arrest (OHCA). This predefined exploratory analysis provides more detailed estimation of brain dysfunction for the comparison of the 2 intervention regimens. Objectives: To investigate the effects of targeted hypothermia vs targeted normothermia on functional outcome with focus on societal participation and cognitive function in survivors 6 months after OHCA. Design, Setting, and Participants: This study is a predefined analysis of an international multicenter, randomized clinical trial that took place from November 2017 to January 2020 and included participants at 61 hospitals in 14 countries. A structured follow-up for survivors performed at 6 months was by masked outcome assessors. The last follow-up took place in October 2020. Participants included 1861 adult (older than 18 years) patients with OHCA who were comatose at hospital admission. At 6 months, 939 of 1861 were alive and invited to a follow-up, of which 103 of 939 declined or were missing. Interventions: Randomization 1:1 to temperature control with targeted hypothermia at 33 °C or targeted normothermia and early treatment of fever (37.8 °C or higher). Main outcomes and measures: Functional outcome focusing on societal participation assessed by the Glasgow Outcome Scale Extended ([GOSE] 1 to 8) and cognitive function assessed by the Montreal Cognitive Assessment ([MoCA] 0 to 30) and the Symbol Digit Modalities Test ([SDMT] z scores). Higher scores represent better outcomes. Results: At 6 months, 836 of 939 survivors with a mean age of 60 (SD, 13) (range, 18 to 88) years (700 of 836 male [84%]) participated in the follow-up. There were no differences between the 2 intervention groups in functional outcome focusing on societal participation (GOSE score, odds ratio, 0.91; 95% CI, 0.71-1.17; P = .46) or in cognitive function by MoCA (mean difference, 0.36; 95% CI,-0.33 to 1.05; P = .37) and SDMT (mean difference, 0.06; 95% CI,-0.16 to 0.27; P = .62). Limitations in societal participation (GOSE score less than 7) were common regardless of intervention (hypothermia, 178 of 415 [43%]; normothermia, 168 of 419 [40%]). Cognitive impairment was identified in 353 of 599 survivors (59%). Conclusions: In this predefined analysis of comatose patients after OHCA, hypothermia did not lead to better functional outcome assessed with a focus on societal participation and cognitive function than management with normothermia. At 6 months, many survivors had not regained their pre-arrest activities and roles, and mild cognitive dysfunction was common. Trial Registration: ClinicalTrials.gov Identifier: NCT02908308.

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.

Risk factors for severe COVID-19 in the young-before and after ICU admission.

BACKGROUND: Factors associated with severe COVID-19 and death among young adults are not fully understood, including differences between the sexes. The aim of this study was to identify factors associated with severe COVID-19 requiring intensive care and 90-day mortality among women and men below 50 years of age. METHODS: A register-based study using data from mandatory national registers, where patients with severe COVID-19 admitted to the ICU with need for mechanical ventilation (cases) between March 2020 and June 2021 were matched regarding age, sex, and district of residence with 10 population-based controls. Both the study population and the controls were divided into groups based on age (< 50 years, 50-64, and ≥ 65 years) and sex. Multivariate logistic regression models including socioeconomic factors were used to calculate odds ratios (OR) with 95% confidence intervals (CIs) for associations between severe COVID-19 in the population to compare the magnitude of the risk associations for co-morbidities in the different age categories, and subsequently factors associated with 90-day mortality among patients admitted to ICU. RESULTS: In total, 4921 cases and 49,210 controls (median age 63 years, 71% men) were included. The co-morbidities with the strongest associations with severe COVID-19 for the young population compared to older patients were chronic kidney disease (OR 6.80 [3.61-12.83]), type 2 diabetes (OR 6.31 [4.48-8.88]), hypertension (OR 5.09 [3.79-6.84]), rheumatoid arthritis (OR 4.76 [2.29-9.89]), obesity (OR 3.76 [2.88-4.92]), heart failure (OR 3.06 [1.36-6.89]), and asthma (OR 3.04 [2.22-4.16]). When comparing women vs. men < 50 years of age, stronger associations were seen for women regarding type 2 diabetes (OR 11.25 [6.00-21.08] vs OR 4.97 [3.25-7.60]) and hypertension (OR 8.76 [5.10-15.01] vs OR 4.09 [2.86-5.86]). The factors associated with 90-day mortality in the young were previous venous thromboembolism (OR 5.50 [2.13-14.22]), chronic kidney disease (OR 4.40 [1.64-11.78]) and type 2 diabetes (OR 2.71 [1.39-5.29]). These associations with 90-day mortality were foremost driven by the female population. CONCLUSION: Chronic kidney failure, type 2 diabetes, hypertension, rheumatoid arthritis, obesity, heart failure, and asthma were the strongest risk factors associated with severe COVID-19 requiring ICU-care in individuals < 50 years compared to the older population. However, after ICU admission, previous thromboembolism, chronic kidney failure, and type 2 diabetes were associated with increased 90-day mortality. The risk associations for co-morbidities were generally stronger among younger individuals compared to older and in women compared to men.

Hyperoxemia after reperfusion in cardiac arrest patients: a potential dose-response association with 30-day survival.

BACKGROUND: Hyperoxemia may aggravate reperfusion brain injury after cardiac arrest. The aim of this study was to study the associations between different levels of hyperoxemia in the reperfusion period after cardiac arrest and 30-day survival. METHODS: Nationwide observational study using data from four compulsory Swedish registries. Adult in- and out-of-hospital cardiac arrest patients admitted to an ICU, requiring mechanical ventilation, between January 2010 and March 2021, were included. The partial oxygen pressure (PaO2) was collected in a standardized way at ICU admission (± one hour) according to the simplified acute physiology score 3 reflecting the time interval with oxygen treatment from return of spontaneous circulation to ICU admission. Subsequently, patients were divided into groups based on the registered PaO2 at ICU admission. Hyperoxemia was categorized into mild (13.4-20 kPa), moderate (20.1-30 kPa) severe (30.1-40 kPa) and extreme (> 40 kPa), and normoxemia as PaO2 8-13.3 kPa. Hypoxemia was defined as PaO2 < 8 kPa. Primary outcome was 30-day survival and relative risks (RR) were estimated by multivariable modified Poisson regression. RESULTS: In total, 9735 patients were included of which 4344 (44.6%) were hyperoxemic at ICU admission. Among these, 2217 were classified as mild, 1091 as moderate, 507 as severe, and 529 as extreme hyperoxemia. Normoxemia was present in 4366 (44.8%) patients and 1025 (10.5%) had hypoxemia. Compared to the normoxemia group, the adjusted RR for 30-day survival in the whole hyperoxemia group was 0.87 (95% CI 0.82-0.91). The corresponding results for the different hyperoxemia subgroups were; mild 0.91 (95% CI 0.85-0.97), moderate 0.88 (95% CI 0.82-0.95), severe 0.79 (95% CI 0.7-0.89), and extreme 0.68 (95% CI 0.58-0.79). Adjusted 30-day survival for the hypoxemia compared to normoxemia group was 0.83 (95% CI 0.74-0.92). Similar associations were seen in both out-of-hospital and in-hospital cardiac arrests. CONCLUSION: In this nationwide observational study comprising both in- and out-of-hospital cardiac arrest patients, hyperoxemia at ICU admission was associated with lower 30-day survival.

Association Between CKD, Obesity, Cardiometabolic Risk Factors, and Severe COVID-19 Outcomes.

Introduction: Chronic kidney disease (CKD) is a risk factor for acquiring severe COVID-19, but underlying mechanisms are unknown. We aimed to study the risk associated with CKD for severe COVID-19 outcomes in relation to body mass index (BMI) and diabetes because they are common risk factors for both CKD and severe COVID-19. Methods: This nationwide case-control study with data from mandatory national registries included 4684 patients (cases) admitted to the intensive care units (ICUs) requiring mechanical ventilation and 46,840 population-based controls matched by age, sex, and district of residency. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for associations between severe COVID-19 and exposures with adjustment for confounders, in subgroups by BMI, and matched by type 2 diabetes. Results: The median age was 64 years, and 27.7% were female. CKD was observed in 5.4% of the cases and 1.5% of the controls, whereas 1.9% and 0.3% had end-stage CKD, respectively. CKD was associated with severe COVID-19 (OR, 2.20 [95% CI, 1.85-2.62]), continuous renal replacement therapy (CRRT) in ICU (OR, 7.36 [95% CI, 5.39-10.05]), and death any time after ICU admission (OR, 2.51 [95% CI, 1.96-3.22]). The risk associated with CKD for severe COVID-19 did not differ significantly by weight but was higher in those without diabetes (OR, 2.76 [95% CI, 2.15-3.55]) than in those with diabetes (OR, 1.88 [95% CI, 1.37-2.59]). Conclusion: CKD, especially end-stage CKD, is an important risk factor for severe COVID-19 and death after ICU admission also in patients with normal BMI and without type 2 diabetes.

Effect of Smartphone Dispatch of Volunteer Responders on Automated External Defibrillators and Out-of-Hospital Cardiac Arrests: The SAMBA Randomized Clinical Trial.

Importance: Smartphone dispatch of volunteer responders to nearby out-of-hospital cardiac arrests (OHCAs) has emerged in several emergency medical services, but no randomized clinical trials have evaluated the effect on bystander use of automated external defibrillators (AEDs). Objective: To evaluate if bystander AED use could be increased by smartphone-aided dispatch of lay volunteer responders with instructions to collect nearby AEDs compared with instructions to go directly to patients with OHCAs to start cardiopulmonary resuscitation (CPR). Design, Setting, and Participants: This randomized clinical trial assessed a system for smartphone dispatch of volunteer responders to individuals experiencing OHCAs that was triggered at emergency dispatch centers in response to suspected OHCAs and randomized 1:1. The study was conducted in 2 main Swedish regions: Stockholm and Västra Götaland between December 2018 and January 2020. At study start, there were 3123 AEDs in Stockholm and 3195 in Västra Götaland and 24 493 volunteer responders in Stockholm and 19 117 in Västra Götaland. All OHCAs in which the volunteer responder system was activated by dispatchers were included. Excluded were patients with no OHCAs, those with OHCAs not treated by the emergency medical services, and those with OHCAs witnessed by the emergency medical services. Interventions: Volunteer responders were alerted through the volunteer responder system smartphone application and received map-aided instructions to retrieve nearest available public AEDs on their way to the OHCAs. The control arm included volunteer responders who were instructed to go directly to the OHCAs to perform CPR. Main Outcomes and Measures: Overall bystander AED attachment, including those attached by volunteer responders and lay volunteers who did not use the smartphone application. Results: Volunteer responders were activated for 947 patients with OHCAs. Of those, 461 were randomized to the intervention group (median [IQR] age of patients, 73 [61-81] years; 295 male patients [65.3%]) and 486 were randomized to the control group (median [IQR] age of patients, 73 [63-82] years; 312 male patients [65.3%]). Primary outcome of AED attachment occurred in 61 patients (13.2%) in the intervention arm vs 46 patients (9.5%) in the control arm (difference, 3.8% [95% CI, -0.3% to 7.9%]; P = .08). The majority of AEDs were attached by lay volunteers who were not using the smartphone application (37 in intervention arm, 28 in control). There were no significant differences in secondary outcomes. Among the volunteer responders using the application, crossover was 11% and compliance to instructions was 31%. Volunteer responders attached 38% (41 of 107) of all AEDs and provided 45% (16 of 36) of all defibrillations and 43% (293 of 666) of all CPR. Conclusions and Relevance: In this study, smartphone dispatch of volunteer responders to OHCAs to retrieve nearby AEDs vs instructions to directly perform CPR did not significantly increase volunteer AED use. High baseline AED attachement rate and crossover may explain why the difference was not significant. Trial Registration: ClinicalTrials.gov Identifier: NCT02992873.

Speed of cooling after cardiac arrest in relation to the intervention effect: a sub-study from the TTM2-trial.

BACKGROUND: Targeted temperature management (TTM) is recommended following cardiac arrest; however, time to target temperature varies in clinical practice. We hypothesised the effects of a target temperature of 33 °C when compared to normothermia would differ based on average time to hypothermia and those patients achieving hypothermia fastest would have more favorable outcomes. METHODS: In this post-hoc analysis of the TTM-2 trial, patients after out of hospital cardiac arrest were randomized to targeted hypothermia (33 °C), followed by controlled re-warming, or normothermia with early treatment of fever (body temperature, ≥ 37.8 °C). The average temperature at 4 h (240 min) after return of spontaneous circulation (ROSC) was calculated for participating sites. Primary outcome was death from any cause at 6 months. Secondary outcome was poor functional outcome at 6 months (score of 4-6 on modified Rankin scale). RESULTS: A total of 1592 participants were evaluated for the primary outcome. We found no evidence of heterogeneity of intervention effect based on the average time to target temperature on mortality (p = 0.17). Of patients allocated to hypothermia at the fastest sites, 71 of 145 (49%) had died compared to 68 of 148 (46%) of the normothermia group (relative risk with hypothermia, 1.07; 95% confidence interval 0.84-1.36). Poor functional outcome was reported in 74/144 (51%) patients in the hypothermia group, and 75/147 (51%) patients in the normothermia group (relative risk with hypothermia 1.01 (95% CI 0.80-1.26). CONCLUSIONS: Using a hospital's average time to hypothermia did not significantly alter the effect of TTM of 33 °C compared to normothermia and early treatment of fever.

Strategies of Advanced Airway Management in Out-of-Hospital Cardiac Arrest during Intra-Arrest Hypothermia: Insights from the PRINCESS Trial.

BACKGROUND: Trans-nasal evaporative cooling is an effective method to induce intra-arrest therapeutic hypothermia in out-of-hospital cardiac arrest (OHCA). The use of supraglottic airway devices (SGA) instead of endotracheal intubation may enable shorter time intervals to induce cooling. We aimed to study the outcomes in OHCA patients receiving endotracheal intubation (ETI) or a SGA during intra-arrest trans-nasal evaporative cooling. METHODS: This is a pre-specified sub-study of the PRINCESS trial (NCT01400373) that included witnessed OHCA patients randomized during resuscitation to trans-nasal intra-arrest cooling vs. standard care followed by temperature control at 33 °C for 24 h. For this study, patients randomized to intra-arrest cooling were stratified according to the use of ETI vs. SGA prior to the induction of cooling. SGA was placed by paramedics in the first-tier ambulance or by physicians or anesthetic nurses in the second tier while ETI was performed only after the arrival of the second tier. Propensity score matching was used to adjust for differences at the baseline between the two groups. The primary outcome was survival with good neurological outcome, defined as cerebral performance category (CPC) 1-2 at 90 days. Secondary outcomes included time to place airway, overall survival at 90 days, survival with complete neurologic recovery (CPC 1) at 90 days and sustained return of spontaneous circulation (ROSC). RESULTS: Of the 343 patients randomized to the intervention arm (median age 64 years, 24% were women), 328 received intra-arrest cooling and had data on the airway method (n = 259 with ETI vs. n = 69 with SGA). Median time from the arrival of the first-tier ambulance to successful airway management was 8 min for ETI performed by second tier and 4 min for SGA performed by the first or second tier (p = 0.001). No significant differences in the probability of good neurological outcome (OR 1.43, 95% CI 0.64-3.01), overall survival (OR 1.26, 95% CI 0.57-2.55), full neurological recovery (OR 1.17, 95% CI 0.52-2.73) or sustained ROSC (OR 0.88, 95% CI 0.50-1.52) were observed between ETI and SGA. CONCLUSIONS: Among the OHCA patients treated with trans-nasal evaporative intra-arrest cooling, the use of SGA was associated with a significantly shorter time to airway management and with similar outcomes compared to ETI.

Intra-Arrest Therapeutic Hypothermia and Neurologic Outcome in Patients Admitted after Out-of-Hospital Cardiac Arrest: A Post Hoc Analysis of the Princess Trial.

Background: Despite promising results, the role of intra-arrest hypothermia in out-of-hospital cardiac arrest (OHCA) remains controversial. The aim of this study was to assess the effects of trans-nasal evaporative cooling (TNEC) during resuscitation on neurological recovery in OHCA patients admitted alive to the hospital. Methods: A post hoc analysis of the PRINCESS trial, including only patients admitted alive to the hospital, either assigned to TNEC or standard of care during resuscitation. The primary endpoint was favorable neurological outcome (FO) defined as a Cerebral Performance Category (CPC) of 1-2 at 90 days. The secondary outcomes were overall survival at 90 days and CPC 1 at 90 days. Subgroup analyses were performed according to the initial cardiac rhythm. Results: A total of 149 patients in the TNEC and 142 in the control group were included. The number of patients with CPC 1-2 at 90 days was 56/149 (37.6%) in the intervention group and 45/142 (31.7%) in the control group (p = 0.29). Survival and CPC 1 at 90 days was observed in 60/149 patients (40.3%) vs. 52/142 (36.6%; p = 0.09) and 50/149 (33.6%) vs. 35/142 (24.6%; p = 0.11) in the two groups. In the subgroup of patients with an initial shockable rhythm, the number of patients with CPC 1 at 90 days was 45/83 (54.2%) in the intervention group and 27/78 (34.6%) in the control group (p = 0.01). Conclusions: In this post hoc analysis of admitted OHCA patients, no statistically significant benefits of TNEC on neurological outcome at 90 days was found. In patients with initial shockable rhythm, TNEC was associated with increased full neurological recovery.

The association between signs of medical distress preceding in-hospital cardiac arrest and 30-day survival - A register-based cohort study.

Background: Identifying signs of medical distress prior to in-hospital cardiac arrest (IHCA) is important to prevent IHCA and improve survival. The primary objective of this study was to investigate the association between signs of medical distress present within 60 minutes prior to cardiac arrest and survival after cardiac arrest. Methods: The register-based cohort study included adult patients (≥18 years) with IHCA in the Swedish Registry of Cardiopulmonary Resuscitation (SRCR) from 2017-01-01 to 2020-07-15. Signs of distress prior to IHCA were defined as the medical signs arrhythmia, pulmonary oedema, hypotension, hypoxia or seizures present within 60 minutes prior to cardiac arrest (pre-arrest signs). Using multivariable logistic regression, the association between these pre-arrest signs and 30-day survival was analysed in both unadjusted and adjusted models. The covariates used were demographics, comorbidities, characteristics and treatment of cardiac arrest. Results: In total, 8525 patients were included. After adjusting for covariates, patients with arrhythmia had a 58% higher probability of 30-day survival. The adjusted probability of 30-day survival was 41% and 52% lower for patients with hypotension and hypoxia prior to IHCA, respectively. Pulmonary oedema and seizures were not associated with any change in 30-day survival. Conclusions: Among signs of medical distress prior to in-hospital cardiac arrest, arrhythmia was associated with a higher 30-day survival. Hypotension and hypoxia were associated with lower survival after IHCA. These findings indicate that future research on survival after cardiac arrest should take pre-arrest signs into account as it impacts the prerequisites for survival.