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Stig Holm Ovesen,1,2 Søren Helbo Skaarup,3 Rasmus Aagaard,4 Hans Kirkegaard,1 Bo Løfgren,1,5 Michael Dan Arvig,6– 8 Bo Martin Bibby,9 Stefan Posth,10 Christian B Laursen,11,12 Jesper Weile1,2 1Research Center for Emergency Medicine, Department of Clinical Medicine, Aarhus University Hospital and Aarhus University, Aarhus, Denmark; 2Emergency Department, Horsens Regional Hospital, Horsens, Denmark; 3Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark; 4Department of Anesthesiology, Aarhus University Hospital, Aarhus, Denmark; 5Department of Internal Medicine, Randers Regional Hospital, Randers, Denmark; 6Emergency Department, Slagelse Hospital, Slagelse, Denmark; 7Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 8Department of Regional Health Research, University of Southern Denmark, Odense, Denmark; 9Department of Biostatistics, Aarhus University, Aarhus, Denmark; 10Emergency Department, Odense University Hospital, Odense, Denmark; 11Department of Respiratory Medicine, Odense University Hospital, Odense, Denmark; 12Odense Respiratory Research Unit (ODIN), Department of Clinical Research, University of Southern Denmark, Odense, DenmarkCorrespondence: Stig Holm Ovesen, Research Center for Emergency Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, J103, Aarhus, 8200, Denmark, Email stigholm@clin.au.dkPurpose: Point-of-care ultrasound (POCUS) helps emergency department (ED) physicians make prompt and appropriate decisions, but the optimal diagnostic integration and potential clinical benefits remain unclear. We describe the protocol and statistical analysis plan for a randomized controlled trial. The objective is to determine the effect of a POCUS-driven diagnostic pathway in adult dyspneic ED patients on the proportion of patients having a hospital stay of less than 24 hours when compared to the standard diagnostic pathway.Patients and Methods: This is a multicenter, random

Background This scoping review was conducted to provide an overview of the evidence of point-of-care lung ultrasound (LUS) in emergency medicine. By emphasizing clinical topics, time trends, study designs, and the scope of the primary outcomes, a map is provided for physicians and researchers to guide their future initiatives. Research Question Which study designs and primary outcomes are reported in published studies of LUS in emergency medicine? Study Design and Methods We performed a systematic search in the PubMed/MEDLINE, Embase, Web of Science, Scopus, and Cochrane Library databases for LUS studies published prior to May 13, 2023. Study characteristics were synthesized quantitatively. The primary outcomes in all papers were categorized into the hierarchical Fryback and Thornbury levels. Results A total of 4,076 papers were screened and, following selection and handsearching, 406 papers were included. The number of publications doubled from January 2020 to May 2023 (204 to 406 papers). The study designs were primarily observational (n = 375 [92%]), followed by randomized (n = 18 [4%]) and case series (n = 13 [3%]). The primary outcome measure concerned diagnostic accuracy in 319 papers (79%), diagnostic thinking in 32 (8%), therapeutic changes in 4 (1%), and patient outcomes in 14 (3%). No increase in the proportions of randomized controlled trials or the scope of primary outcome measures was observed with time. A freely available interactive database was created to enable readers to search for any given interest (https://public.tableau.com/app/profile/blinded/viz/LUSinEM_240216/INFO). Interpretation Observational diagnostic studies have been produced in abundance, leaving a paucity of research exploring clinical utility. Notably, research exploring whether LUS causes changes to clinical decisions is imperative prior to any further research being made into patient benefits. Key Words emergency, Background: This scoping review was conducted to provide an overview of the evidence of point-of-care lung ultrasound (LUS) in emergency medicine. By emphasizing clinical topics, time trends, study designs, and the scope of the primary outcomes, a map is provided for physicians and researchers to guide their future initiatives. Research Question: Which study designs and primary outcomes are reported in published studies of LUS in emergency medicine? Study Design and Methods: We performed a systematic search in the PubMed/MEDLINE, Embase, Web of Science, Scopus, and Cochrane Library databases for LUS studies published prior to May 13, 2023. Study characteristics were synthesized quantitatively. The primary outcomes in all papers were categorized into the hierarchical Fryback and Thornbury levels. Results: A total of 4,076 papers were screened and, following selection and handsearching, 406 papers were included. The number of publications doubled from January 2020 to May 2023 (204 to 406 papers). The study designs were primarily observational (n = 375 [92%]), followed by randomized (n = 18 [4%]) and case series (n = 13 [3%]). The primary outcome measure concerned diagnostic accuracy in 319 papers (79%), diagnostic thinking in 32 (8%), therapeutic changes in 4 (1%), and patient outcomes in 14 (3%). No increase in the proportions of randomized controlled trials or the scope of primary outcome measures was observed with time. A freely available interactive database was created to enable readers to search for any given interest (https://public.tableau.com/app/profile/blinded/viz/LUSinEM_240216/INFO). Interpretation: Observational diagnostic studies have been produced in abundance, leaving a paucity of research exploring clinical utility. Notably, research exploring whether LUS causes changes to clinical decisions is imperative prior to any further research being made into patient benefits.

Purpose: Point-of-care ultrasound (POCUS) helps emergency department (ED) physicians make prompt and appropriate decisions, but the optimal diagnostic integration and potential clinical benefits remain unclear. We describe the protocol and statistical analysis plan for a randomized controlled trial. The objective is to determine the effect of a POCUS-driven diagnostic pathway in adult dyspneic ED patients on the proportion of patients having a hospital stay of less than 24 hours when compared to the standard diagnostic pathway. Patients and Methods: This is a multicenter, randomized, investigator-initiated, open-labeled, pragmatic, controlled trial. Adult ED patients with chief complaint dyspnea are eligible. Patients are randomized (1:1) to the POCUS-driven diagnostic pathway or standard diagnostic pathway, with 337 patients in each group. The primary outcome is the proportion of patients having a hospital stay (from ED arrival to hospital discharge) of less than 24 hours. Key secondary outcomes include hospital length-of-stay, 72-hour revisits, and 30-day hospital-free days. Conclusion: Sparse evidence exists for any clinical benefit from a POCUS-integrated diagnostic pathway. The results from this trial will help clarify the promising signals for POCUS to influence patient care among ED patients with dyspnea. Keywords: focused lung ultrasound, focused cardiac ultrasound, shortness-of-breath, diagnostic effectiveness, Purpose: Point-of-care ultrasound (POCUS) helps emergency department (ED) physicians make prompt and appropriate decisions, but the optimal diagnostic integration and potential clinical benefits remain unclear. We describe the protocol and statistical analysis plan for a randomized controlled trial. The objective is to determine the effect of a POCUS-driven diagnostic pathway in adult dyspneic ED patients on the proportion of patients having a hospital stay of less than 24 hours when compared to the standard diagnostic pathway. Patients and Methods: This is a multicenter, randomized, investigator-initiated, open-labeled, pragmatic, controlled trial. Adult ED patients with chief complaint dyspnea are eligible. Patients are randomized (1:1) to the POCUS-driven diagnostic pathway or standard diagnostic pathway, with 337 patients in each group. The primary outcome is the proportion of patients having a hospital stay (from ED arrival to hospital discharge) of less than 24 hours. Key secondary outcomes include hospital length-of-stay, 72-hour revisits, and 30-day hospital-free days. Conclusion: Sparse evidence exists for any clinical benefit from a POCUS-integrated diagnostic pathway. The results from this trial will help clarify the promising signals for POCUS to influence patient care among ED patients with dyspnea.

Aim To assess the merit of clinical assessment tools in a neurocognitive screening following out-of-hospital cardiac arrest (OHCA). Methods The neurocognitive screening that was evaluated included the performance-based Montreal Cognitive Assessment (MoCA) and Symbol Digit Modalities Test (SDMT), the patient-reported Two Simple Questions (TSQ) and the observer-reported Informant Questionnaire on Cognitive Decline in the Elderly-Cardiac Arrest (IQCODE-CA). These instruments were administered at 6-months in the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. We used a comprehensive neuropsychological test battery from a TTM2 trial sub-study as a gold standard to evaluate the sensitivity and specificity of the neurocognitive screening. Results In our cohort of 108 OHCA survivors (median age = 62, 88% male), the most favourable cut-off scores were: MoCA < 26; SDMT z ≤ -1; IQCODE-CA ≥ 3.04. The MoCA (sensitivity 0.64, specificity 0.85) and SDMT (sensitivity 0.59, specificity 0.83) had a higher classification accuracy than the TSQ (sensitivity 0.28, specificity 0.74) and IQCODE-CA (sensitivity 0.42, specificity 0.60). When using the cut-points for MoCA or SDMT in combination to identify neurocognitive impairment, sensitivity improved (0.81, specificity 0.74), area under the curve = 0.77, 95% CI [0.69, 0.85]. The most common unidentified impairments were within the episodic memory and executive functions domains, with fewer false negative cases on the MoCA or SDMT combined. Conclusion The MoCA and SDMT have acceptable diagnostic accuracy for screening for neurocognitive impairment in an OHCA population, and when used in combination the sensitivity improves. Patient and observer-reports correspond poorly with neurocognitive performance.

Aims: To describe the level of physical activity 6 months after an out-of-hospital cardiac arrest (OHCA) and to explore potential risk factors of a low level of physical activity. Methods: Post-hoc analyses of the international multicentre Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac arrest (TTM2) trial. At 6 months, survivors at 61 sites in Europe, Australia and New Zeeland were invited to a follow-up. The participants answered two questions on self-reported physical activity. Answers were categorized as a low, moderate, or high level of physical activity and further dichotomized into a low versus moderate/high level of physical activity. Potential risk factors for a low level of physical activity were collected and investigated by univariable and multivariable logistic regression. Results: At 6 months, 807 of 939 (86%) OHCA survivors answered the two questions of physical activity; 34% reported a low, 44% moderate and 22% high level of physical activity. Obesity (OR = 1.75, 95% CI 1.10-2.77, p = 0.018), mobility problems by EuroQol 5 dimensions 5 levels (OR = 1.73, 95% CI 1.06-2.84, p = 0.029), and cognitive impairment by Symbol Digit Modalities Test (OR = 1.78, 95% CI 1.13-2.82, p = 0.013) were significantly associated with a low level of physical activity in the multivariable analysis. Conclusion: One third of the OHCA survivors reported a low level of physical activity. Obesity, mobility problems, and cognitive impairment were associated with a low level of physical activity.

Background Neuroimaging with magnetic resonance imaging (MRI) may assist clinicians in evaluating brain injury and optimising care in comatose adults resuscitated after out-of-hospital cardiac arrest (OHCA). However, contemporary international data on its use are lacking. Aim The primary aim was to compare the patient characteristics, early postresuscitation care, and neurological outcomes of patients according to MRI use. Methods We performed a posthoc analysis of the Targeted Therapeutic Mild Hypercapnia after Resuscitated Cardiac Arrest (TAME) trial, a multinational randomised trial comparing targeted mild hypercapnia or normocapnia in comatose adults after OHCA. Results After exclusions, 1639 patients enrolled in the TAME trial were analysed. Of these, 149 (9%) had an MRI. Compared to non-MRI patients, MRI patients were younger (58.9 versus 61.7 years, p: 0.02), had a longer median time from OHCA to return of spontaneous circulation (30 versus 25 min, p < 0.0001), and had a higher average arterial lactate level (8.78 versus 6.74 mmol/L, p < 0.0001) on admission to hospital. MRI patients were more likely to receive additional advanced diagnostic assessments during intensive care unit admission (p < 0.0001). At 6 months, 23 of 140 patients (16.4%) in the MRI group had a favourable neurological outcome, compared with 659 of 1399 patients (47.1%) in the no-MRI group (p < 0.001). On multivariable modelling, country of enrolment was the dominating predictor in the likelihood of an MRI being performed. Conclusions In the TAME trial, 9% of patients had an MRI during their intensive care unit admission. Among these patients, only 16% had a favourable neurological outcome at 6 months.

BACKGROUND A main cause of trauma morbidity and mortality is multiple-organ failure, and endotheliopathy has been implicated. Pilot studies indicate that low-dose prostacyclin improves endothelial functionality in critically ill patients, suggesting that this intervention may improve trauma patient outcome. METHODS We conducted a multicenter, randomized, blinded, clinical investigator-initiated trial in 229 trauma patients with hemorrhagic shock who were randomized 1:1 to 72 hours infusion of the prostacyclin analog iloprost (1 ng/kg/min) or placebo. The primary outcome was the number of intensive care unit (ICU)-free days alive within 28 days of admission. Secondary outcomes included 28-day all-cause mortality and hospital length of stay. RESULTS The mean number of ICU-free days alive within 28 days was 15.64 days in the iloprost group versus 13.99 days in the placebo group (adjusted mean difference, -1.63 days [95% confidence interval (CI), -4.64 to 1.38 days]; p = 0.28). The 28-day mortality was 18.8% in the iloprost group versus 19.6% in the placebo group (odds ratio, 1.01 [95% CI, 0.51-2.0]; p = 0.97). The mean hospital length of stay was 19.96 days in the iloprost group versus 27.32 days in the placebo group (adjusted mean difference, 7.84 days [95% CI, 1.66-14.02 days], p = 0.01). CONCLUSION Iloprost did not result in a statistically significant increase in the number of ICU-free days alive within 28 days of admission, whereas it was safe and a statistically significant reduction in hospital length of stay was observed. Further research on prostacyclin in shocked trauma patients is warranted. LEVEL OF EVIDENCE Therapeutic/Care Management; Level II.

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 =

Martin Gude,1 Hans Kirkegaard,1,2 Rolf Blauenfeldt,3 Anne Behrndtz,3 Jeppe Mainz,3 Ingunn Riddervold,4 Claus Z Simonsen,2,3 Niels Hjort,2,3 Søren P Johnsen,5 Grethe Andersen,2,3 Jan Brink Valentin5 1Department of Research and Development, Prehospital Emergency Medical Services, Central Denmark Region; and Aarhus University Hospital, Aarhus, Denmark; 2Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 3Danish Stroke Center, Department of Neurology, Aarhus University Hospital, Aarhus, Denmark; 4Norwegian Air Ambulance Foundation, Oslo, Norway; 5Danish Center for Clinical Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, DenmarkCorrespondence: Martin Gude, Prehospital Emergency Medical Services, Central Denmark Region and Aarhus University Hospital, Aarhus, Denmark, Email gude@dadlnet.dkObjective: To examine the agreement between emergency medical service (EMS) providers, neurology residents and neurology consultants, using the Cincinnati Prehospital Stroke Scale (CPSS) and the Prehospital Acute Stroke Severity Scale (PASS).Methods: Patients with stroke, transient ischemic attack (TIA) and stroke mimic were included upon primary stroke admission or during rehabilitation. Patients were included from June 2018 to September 2019. Video recordings were made of patients being assessed with CPSS and PASS. The recordings were later presented to the healthcare professionals. To determine relative and absolute interrater reliability in terms of inter-rater agreement (IRA), we used generalisability theory. Group-level agreement was determined against a gold standard and presented as an area under the curve (AUC). The gold standard was a consensus agreement between two neurology consultants.Results: A total of 120 patient recordings were assessed by 30 EMS providers, two neurology residents and two neurology consultants. Using the CPSS and the PASS, a total of 1,800 assessments were completed by EMS providers, 240 by neurol

To investigate the association between the Emergency Medical Service dispatcher’s initial stroke triage and prehospital stroke management, primary admission to hospitals offering revascularization treatment, prehospital time delay, and rate of acute revascularization. In an observational cohort study, patients with acute ischemic stroke (AIS) in Denmark (2017–2018) were included if the emergency call to the Emergency Medical Dispatch Center (EMDC) was made within three hours after symptom onset. Among 3546 included AIS patients, the EMS dispatcher identified 74.6% (95% confidence interval (CI) 73.1–76.0) correctly as stroke. EMS dispatcher stroke recognition was associated with a higher rate of primary admission to a hospital offering revascularization treatment (85.8 versus 74.5%); producing an adjusted risk difference (RD) of 11.1% (95% CI 7.8; 14.3) and a higher rate of revascularization treatment (49.6 versus 41.6%) with an adjusted RD of 8.4% (95% CI 4.6; 12.2). We adjusted for sex, age, previous stroke or transient ischemic attack, and stroke severity. EMDC stroke recognition was associated with shorter prehospital delay. For all AIS patients, the adjusted difference was − 33.2 min (95% CI − 44.4; − 22.0). Among patients receiving acute revascularization treatment (n = 1687), the adjusted difference was -12.6 min (95% CI − 18.9; − 6.3). Stroke recognition by the EMS dispatcher was associated with a higher probability of primary admission to a hospital offering acute stroke treatment, and subsequently with a higher rate of acute revascularization treatment, and with an overall reduction in prehospital delay.

BACKGROUND Guidelines recommend normocapnia for adults with coma who are resuscitated after out-of-hospital cardiac arrest. However, mild hypercapnia increases cerebral blood flow and may improve neurologic outcomes. METHODS We randomly assigned adults with coma who had been resuscitated after out-of-hospital cardiac arrest of presumed cardiac or unknown cause and admitted to the intensive care unit (ICU) in a 1:1 ratio to either 24 hours of mild hypercapnia (target partial pressure of arterial carbon dioxide [Paco ], 50 to 55 mm Hg) or 2 normocapnia (target Paco2, 35 to 45 mm Hg). The primary outcome was a favorable neurologic outcome, defined as a score of 5 indicating lower moderate disability) or higher, as assessed with the use of the Glasgow Outcome Scale–Extended (range, 1 death] to 8, with higher scores indicating better neurologic outcome) at 6 months. Secondary outcomes included death within 6 months. RESULTS A total of 1700 patients from 63 ICUs in 17 countries were recruited, with 847 pa- tients assigned to targeted mild hypercapnia and 853 to targeted normocapnia. A favorable neurologic outcome at 6 months occurred in 332 of 764 patients (43.5%) in the mild hypercapnia group and in 350 of 784 (44.6%) in the normocapnia group (relative risk, 0.98; 95% confidence interval [CI], 0.87 to 1.11; P=0.76). Death within 6 months after randomization occurred in 393 of 816 patients (48.2%) in the mild hypercapnia group and in 382 of 832 (45.9%) in the normocapnia group (relative risk, 1.05; 95% CI, 0.94 to 1.16). The incidence of adverse events did not differ significantly between groups. CONCLUSIONS In patients with coma who were resuscitated after out-of-hospital cardiac arrest, targeted mild hypercapnia did not lead to better neurologic outcomes at 6 months than targeted normocapnia.

ImportanceThe 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.ObjectivesTo 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 ParticipantsThis 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.InterventionsRandomization 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 measuresFunctional 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.ResultsAt 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 cogni

Importance Despite some promising preclinical and clinical data, it remains uncertain whether remote ischemic conditioning (RIC) with transient cycles of limb ischemia and reperfusion is an effective treatment for acute stroke. Objective To evaluate the effect of RIC when initiated in the prehospital setting and continued in the hospital on functional outcome in patients with acute stroke. Design, Setting, and Participants This was a randomized clinical trial conducted at 4 stroke centers in Denmark that included 1500 patients with prehospital stroke symptoms for less than 4 hours (enrolled March 16, 2018, to November 11, 2022; final follow-up, February 3, 2023). Intervention The intervention was delivered using an inflatable cuff on 1 upper extremity (RIC cuff pressure, ≤200 mm Hg [n = 749] and sham cuff pressure, 20 mm Hg [n = 751]). Each treatment application consisted of 5 cycles of 5 minutes of cuff inflation followed by 5 minutes of cuff deflation. Treatment was started in the ambulance and repeated at least once in the hospital and then twice daily for 7 days among a subset of participants. Main Outcomes and Measures The primary end point was improvement in functional outcome measured as a shift across the modified Rankin Scale (mRS) score (range, 0 [no symptoms] to 6 [death]) at 90 days in the target population with a final diagnosis of ischemic or hemorrhagic stroke. Results Among 1500 patients who were randomized (median age, 71 years; 591 women [41%]), 1433 (96%) completed the trial. Of these, 149 patients (10%) were diagnosed with transient ischemic attack and 382 (27%) with a stroke mimic. In the remaining 902 patients with a target diagnosis of stroke (737 [82%] with ischemic stroke and 165 [18%] with intracerebral hemorrhage), 436 underwent RIC and 466 sham treatment. The median mRS score at 90 days was 2 (IQR, 1-3) in the RIC group and 1 (IQR, 1-3) in the sham group. RIC treatment was not significantly ass, Importance: Despite some promising preclinical and clinical data, it remains uncertain whether remote ischemic conditioning (RIC) with transient cycles of limb ischemia and reperfusion is an effective treatment for acute stroke. Objective: To evaluate the effect of RIC when initiated in the prehospital setting and continued in the hospital on functional outcome in patients with acute stroke. Design, Setting, and Participants: This was a randomized clinical trial conducted at 4 stroke centers in Denmark that included 1500 patients with prehospital stroke symptoms for less than 4 hours (enrolled March 16, 2018, to November 11, 2022; final follow-up, February 3, 2023). Intervention: The intervention was delivered using an inflatable cuff on 1 upper extremity (RIC cuff pressure, ≤200 mm Hg [n = 749] and sham cuff pressure, 20 mm Hg [n = 751]). Each treatment application consisted of 5 cycles of 5 minutes of cuff inflation followed by 5 minutes of cuff deflation. Treatment was started in the ambulance and repeated at least once in the hospital and then twice daily for 7 days among a subset of participants. Main Outcomes and Measures: The primary end point was improvement in functional outcome measured as a shift across the modified Rankin Scale (mRS) score (range, 0 [no symptoms] to 6 [death]) at 90 days in the target population with a final diagnosis of ischemic or hemorrhagic stroke. Results: Among 1500 patients who were randomized (median age, 71 years; 591 women [41%]), 1433 (96%) completed the trial. Of these, 149 patients (10%) were diagnosed with transient ischemic attack and 382 (27%) with a stroke mimic. In the remaining 902 patients with a target diagnosis of stroke (737 [82%] with ischemic stroke and 165 [18%] with intracerebral hemorrhage), 436 underwent RIC and 466 sham treatment. The median mRS score at 90 days was 2 (IQR, 1-3) in the RIC group and 1 (IQR, 1-3) in the sham group. RIC treatment was not significantly associated with improved functional out