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.

Pulmonary embolism with paradoxical embolization to right coronary artery in the presence of a large patent foramen ovale: a case report.

Background: Pulmonary embolism (PE) is the leading cause of in-hospital death and the third most frequent cause of cardiovascular death. The clinical presentation of PE is variable, and choosing the appropriate treatment for individual patients can be challenging. Case summary: A 64-year-old man presented to hospital with acute chest pain, shortness of breath, and pulmonary oedema. Electrocardiogram revealed ST-elevation myocardial infarction. D-dimer was 18.8 mg/L fibrinogen equivalent units (FEU) (normal <0.64), and troponin was 25 (normal 5-14 ng/L). After systemic thrombolysis, respiratory failure persisted, and the arterial blood gas showed PaO2 of 6.0 kPa (normal 10.5-13.5 kPa), with 100% oxygen delivery via high-flow nasal cannula. A computed tomography diagnosed bilateral lobar PE, and coronary angiogram showed multiple thrombus in the right coronary artery. A bubble study with thoracic echocardiogram revealed a large right-left inter-atrial shunt. The patient denied treatment with extracorporeal membrane oxygenation and surgical thrombectomy. With no access to percutaneous catheter-directed thrombectomy, the patient received three separate thrombolysis treatments followed by a continued infusion for 22 h. After 6 weeks in hospital, the patient was discharged to rehab. Discussion: For a long time, PE has been largely seen as a medical disease. Intra-cardiac shunts such as patent foramen ovale can complicate thrombo-venous disease and introduce paradoxical shunts leading to arterial emboli and persistent hypoxaemia. Over recent years, modern percutaneous catheter-directed thrombectomy has been developed for both high-risk and intermediate to high-risk PEs. Thrombectomy might improve right ventricular function and haemodynamics, but there is lacking evidence from randomized trials on efficacy, safety, and long-term outcome.

Effects of restrictive fluid therapy on the time to resolution of hyperlactatemia in ICU patients with septic shock. A secondary post hoc analysis of the CLASSIC randomized trial.

PURPOSE: The aim of this study was to examine the effects of intravenous (IV) fluid restriction on time to resolution of hyperlactatemia in septic shock. Hyperlactatemia in sepsis is associated with worse outcome. Sepsis guidelines suggest targeting lactate clearance to guide fluid therapy despite the complexity of hyperlactatemia and the potential harm of fluid overload. METHODS: We conducted a post hoc analysis of serial plasma lactate concentrations in a sub-cohort of 777 patients from the international multicenter clinical CLASSIC trial (restriction of intravenous fluids in intensive care unit (ICU) patients with septic shock). Adult ICU patients with septic shock had been randomized to restrictive (n = 385) or standard (n = 392) intravenous fluid therapy. The primary outcome, time to resolution of hyperlactatemia, was analyzed with a competing-risks regression model. Death and discharge were competing outcomes, and administrative censoring was imposed 72 h after randomization if hyperlactatemia persisted. The regression analysis was adjusted for the same stratification variables and covariates as in the original CLASSIC trial analysis. RESULTS: The hazard ratios (HRs) for the cumulative probability of resolution of hyperlactatemia, in the restrictive vs the standard group, in the unadjusted analysis, with time split, were 0.94 (confidence interval (CI) 0.78-1.14) at day 1 and 1.21 (0.89-1.65) at day 2-3. The adjusted analyses were consistent with the unadjusted results. CONCLUSION: In this post hoc retrospective analysis of a multicenter randomized controlled trial (RCT), a restrictive intravenous fluid strategy did not seem to affect the time to resolution of hyperlactatemia in adult ICU patients with septic shock.

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.

A retrospective multicenter cohort study of the association between anti-Factor Xa values and death, thromboembolism, and bleeding in patients with critical COVID-19.

BACKGROUND: Patients with critical COVID-19 have a high risk of thromboembolism, but intensified thromboprophylaxis has not been proven beneficial. The activity of low-molecular-weight heparins can be monitored by measuring anti-Factor Xa. We aimed to study the association between anti-Factor Xa values and death, thromboembolism, and bleeding in patients with critical COVID-19. METHOD: This retrospective cohort study included adult patients with critical COVID-19 admitted to an intensive care unit at three Swedish hospitals between March 2020 and May 2021 with at least one valid peak and/or trough anti-Factor Xa value. Within the peak and trough categories, patients' minimum, median, and maximum values were determined. Logistic regressions with splines were used to assess associations. RESULTS: In total, 408 patients had at least one valid peak and/or trough anti-Factor Xa measurement, resulting in 153 patients with peak values and 300 patients with trough values. Lower peak values were associated with thromboembolism for patients' minimum (p = 0.01), median (p = 0.005) and maximum (p = 0.001) values. No association was seen between peak values and death or bleeding. Higher trough values were associated with death for median (p = 0.03) and maximum (p = 0.002) values and with both bleeding (p = 0.01) and major bleeding (p = 0.02) for maximum values, but there were no associations with thromboembolism. CONCLUSIONS: Measuring anti-Factor Xa activity may be relevant for administrating low-molecular-weight heparin to patients with critical COVID-19. Lower peak values were associated with an increased risk of thromboembolism, and higher trough values were associated with an increased risk of death and bleeding. Prospective studies are needed to confirm the results. TRIAL REGISTRATION: The study was retrospectively registered at Clinicaltrials.gov, NCT05256524, February 24, 2022.

Short-Term Ambient Air Pollution Exposure and Risk of Out-of-Hospital Cardiac Arrest in Sweden: A Nationwide Case-Crossover Study.

Background Air pollution is one of the main risk factors for cardiovascular disease globally, but its association with out-of-hospital cardiac arrest at low air pollution levels is unclear. This nationwide study in Sweden aims to investigate if air pollution is associated with a higher risk of out-of-hospital cardiac arrest in an area with relatively low air pollution levels. Methods and Results This study was a nationwide time-stratified case-crossover study investigating the association between short-term air pollution exposures and out-of-hospital cardiac arrest using data from the SRCR (Swedish Registry for Cardiopulmonary Resuscitation) between 2009 and 2019. Daily air pollution levels were estimated in 1×1-km grids for all of Sweden using a satellite-based machine learning model. The association between daily air pollutant levels and out-of-hospital cardiac arrest was quantified using conditional logistic regression adjusted for daily air temperature. Particulate matter <2.5 µm exposure was associated with a higher risk of out-of-hospital cardiac arrest among a total of 29 604 cases. In a multipollutant model, the association was most pronounced for intermediate daily lags, with an increased relative risk of 6.2% (95% CI, 1.0-11.8) per 10 µg/m3 increase of particulate matter <2.5 µm 4 days before the event. A similar pattern of association was observed for particulate matter <10 µm. No clear association was observed for O3 and NO2. Conclusions Short-term exposure to air pollution was associated with higher risk of out-of-hospital cardiac arrest. The findings add to the evidence of an adverse effect of particulate matter on out-of-hospital cardiac arrest, even at very low levels below current regulatory standards.

A survey of preferences for respiratory support in the intensive care unit for patients with acute hypoxaemic respiratory failure.

BACKGROUND: When caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes allowing for spontaneous breaths or ventilation fully controlled by the ventilator. The preferences of clinicians managing such patients, and what motivates their choice of ventilator mode, are largely unknown. To better understand how clinicians' preferences may impact the choice of ventilatory support for patients with AHRF, we issued a survey to an international network of intensive care unit (ICU) researchers. METHODS: We distributed an online survey with 32 broadly similar and interlinked questions on how clinicians prioritise spontaneous or controlled ventilation in invasively ventilated patients with AHRF of different severity, and which factors determine their choice. RESULTS: The survey was distributed to 1337 recipients in 12 countries. Of these, 415 (31%) completed the survey either fully (52%) or partially (48%). Most respondents were identified as medical specialists (87%) or physicians in training (11%). Modes allowing for spontaneous ventilation were considered preferable in mild AHRF, with controlled ventilation considered as progressively more important in moderate and severe AHRF. Among respondents there was strong support (90%) for a randomised clinical trial comparing spontaneous with controlled ventilation in patients with moderate AHRF. CONCLUSIONS: The responses from this international survey suggest that there is clinical equipoise for the preferred ventilator mode in patients with AHRF of moderate severity. We found strong support for a randomised trial comparing modes of ventilation in patients with moderate AHRF.

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.

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.

Dispatch of Volunteer Responders to Out-of-Hospital Cardiac Arrests.

BACKGROUND: Systems for dispatch of volunteer responders to collect automated external defibrillators and/or to provide cardiopulmonary resuscitation (CPR) in cases of nearby out-of-hospital cardiac arrest (OHCA) are widely implemented. OBJECTIVES: This study aimed to investigate whether the activation of a volunteer responder system to OHCAs was associated with higher rates of bystander CPR, bystander defibrillation, and 30-day survival vs no system activation. METHODS: This was a retrospective observational analysis within the ESCAPE-NET (European Sudden Cardiac Arrest network: Towards Prevention, Education, New Effective Treatment) collaborative research network. Included were cases of OHCA between 2015 and 2019 from 5 European sites with volunteer responder systems. At all sites, systems were activated by dispatchers at the emergency medical communication center in response to suspected OHCA. Exposed cases (system activation) were compared with nonexposed cases (no system activation). Risk ratios (RRs) were calculated for the outcomes of bystander CPR, bystander defibrillation, and 30-day survival after inverse probability treatment weighting. Missing data were handled using multiple imputation. RESULTS: In total, 9,553 cases were included. In 4,696 cases, the volunteer responder system was activated, and in 4,857 it was not. The pooled RRs were 1.30 (95% CI: 1.15-1.47) for bystander CPR, 1.89 (95% CI: 1.36-2.63) for bystander defibrillation, and 1.22 (95% CI: 1.07-1.39) for 30-day survival. CONCLUSIONS: Activation of a volunteer response system in cases of OHCA was associated with a higher chance of bystander CPR, bystander defibrillation, and 30-day survival vs no system activation. A randomized controlled trial is necessary to determine fully the causal effect of volunteer responder systems.

Long-term effects of restriction of intravenous fluid in adult ICU patients with septic shock.

PURPOSE: To assess long-term outcomes of restrictive versus standard intravenous (IV) fluid therapy in adult intensive care unit (ICU) patients with septic shock included in the European Conservative versus Liberal Approach to Fluid Therapy in Septic Shock in Intensive Care (CLASSIC) trial. METHODS: We conducted the pre-planned analyses of mortality, health-related quality of life (HRQoL) using EuroQol (EQ)-5D-5L index values and EQ visual analogue scale (VAS), and cognitive function using Mini Montreal Cognitive Assessment (Mini MoCA) test at 1 year. Deceased patients were assigned numerical zero for HRQoL as a state equal to death and zero for cognitive function outcomes as worst possible score, and we used multiple imputation for missing data on HRQoL and cognitive function. RESULTS: Among 1554 randomized patients, we obtained 1-year data on mortality in 97.9% of patients, HRQoL in 91.3%, and cognitive function in 86.3%. One-year mortality was 385/746 (51.3%) in the restrictive-fluid group versus 383/767 (49.9%) in the standard-fluid group, absolute risk difference 1.5%-points [99% confidence interval (CI) - 4.8 to 7.8]. Mean differences were 0.00 (99% CI - 0.06 to 0.05) for EQ-5D-5L index values, - 0.65 for EQ VAS (- 5.40 to 4.08), and - 0.14 for Mini MoCA (- 1.59 to 1.14) for the restrictive-fluid group versus the standard-fluid group. The results for survivors only were similar in both groups. CONCLUSIONS: Among adult ICU patients with septic shock, restrictive versus standard IV fluid therapy resulted in similar survival, HRQoL, and cognitive function at 1 year, but clinically important differences could not be ruled out.

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.

Effects of 12 mg vs. 6 mg dexamethasone on thromboembolism and bleeding in patients with critical COVID-19 - a post hoc analysis of the randomized, blinded COVID STEROID 2 trial.

BACKGROUND: Thromboembolism is more common in patients with critical COVID-19 than in other critically ill patients, and inflammation has been proposed as a possible mechanism. The aim of this study was to investigate if 12 mg vs. 6 mg dexamethasone daily reduced the composite outcome of death or thromboembolism in patients with critical COVID-19. METHODS: Using additional data on thromboembolism and bleeding we did a post hoc analysis of Swedish and Danish intensive care unit patients enrolled in the blinded randomized COVID STEROID 2 trial comparing 12 mg vs. 6 mg dexamethasone daily for up to 10 days. The primary outcome was a composite outcome of death or thromboembolism during intensive care. Secondary outcomes were thromboembolism, major bleeding, and any bleeding during intensive care. RESULTS: We included 357 patients. Whilst in intensive care, 53 patients (29%) in the 12 mg group and 53 patients (30%) in the 6 mg group met the primary outcome with an unadjusted absolute risk difference of - 0.5% (95% CI - 10 to 9.5%, p = 1.00) and an adjusted OR of 0.93 (CI 95% 0.58 to 1.49, p = 0.77). We found no firm evidence of differences in any of the secondary outcomes. CONCLUSIONS: Among patients with critical COVID-19, 12 mg vs. 6 mg dexamethasone daily did not result in a statistically significant difference in the composite outcome of death or thromboembolism. However, uncertainty remains due to the limited number of patients.