Effect of a Point-of-Care Ultrasound-Driven vs Standard Diagnostic Pathway on 24-Hour Hospital Stay in Emergency Department Patients with Dyspnea-Protocol for A Randomized Controlled Trial.

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.

Combined use of the Montreal Cognitive Assessment and Symbol Digit Modalities Test improves neurocognitive screening accuracy after cardiac arrest: A validation sub-study of the TTM2 trial.

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. CLINICALTRIALS: gov Identifier: NCT03543371.

Low-dose ketamine as an adjunct to morphine: A randomized controlled trial among patients with and without current opioid use.

BACKGROUND: Pain is a common complaint among patients presenting to the emergency department (ED), yet pain treatment is frequently suboptimal. The aim of this study was to determine the effectiveness of low-dose ketamine (LDK) as an adjunct to morphine versus morphine alone for treatment of acute pain among ED patients with and without current opioid use. METHODS: Adult patients presenting with acute pain of ≥5 on a numeric rating scale (0-10) who were deemed by their treating ED physician to require intravenous opioids were randomized to receive either 0.1 mg/kg ketamine (treatment group) or isotonic saline (placebo) as an adjunct to morphine. Patients with and without current opioid use were randomized separately. Pain was measured at baseline (T0) and 10, 20, 30, 45, 60, and 120 min after randomization. The primary outcome was pain reduction from T0 to T10. Secondary outcomes included pain intensity over 120 min, need of rescue opioids, side effects, and patient and provider satisfaction. RESULTS: A total of 116 patients were included from May 2022 to August 2023. Median (IQR) age was 51 (36.5-67) years; 58% were male and 36% had current opioid use. Pain reduction from T0 to T10 was greater in the LDK group (4 [IQR 3-6]) compared to the placebo group (1 [IQR 0-2]; p = 0.001). Pain intensity was lower in the LDK group at T10, T20, and T30, compared to the placebo group. There was a higher risk of nausea, vomiting, and dissociation in the LDK group during the first 10 min. CONCLUSIONS: LDK may be effective as an adjunct analgesic to morphine for short-term pain relief in treatment of acute pain in the ED for both patients with and without current opioid use.

Patients suffering traumatic brain injury: patient characteristics, prehospital triage, primary referral and mortality - A population-based follow-up study.

BACKGROUND: Traumatic brain injury (TBI) is a potential high-risk condition, but appropriate care pathways, including prehospital triage and primary referral to a specialised neurosurgical centre, can improve neurological outcome and survival. The care pathway starts with layman triage, wherein the patient or bystander decides whether to contact a general practitioner (GP) or emergency services (1-1-2 call) as an entryway into the health care system. The GP or 112-health care professional then decides on the level of urgency and dispatches emergency medical services (EMS) when needed. Finally, a decision is made regarding referral of the TBI patient to a specialised neurotrauma centre or a local hospital. Recent studies have shown that injuries are generally more severe in patients entering the health care system through EMS (112-calls) than through GPs; however, no information exists on whether mortality and morbidity outcomes differ depending on the referral choice. The aim of this study was to examine triage pathways, including the method of entry into the health care system, as well as patient characteristics and place of primary referral, to determine the associated 30-day and 1-year mortality rates in TBI patients with confirmed intracranial lesions. METHODS: This retrospective observational population-based follow-up study was conducted in the Central Denmark Region from 1 February 2017 to 31 January 2019. We included all adult patients who contacted hospitals and were ascribed a predefined TBI ICD-10 diagnosis code in the Danish National Patient Register. The obtained TBI cohort was merged with prehospital data from the Prehospital Emergency Medical Services, Central Denmark Region, and vital status from the Danish Civil Registration System. Binary logistic regression analysis of mortality was conducted. In all patients with TBI (including concussions), the primary outcome was primary referral to a specialised centre based on mode of entry ('GP/HCP', '112-call' or 'Unreferred') into the health care system. In the subgroup of patients with confirmed intracranial lesions, the secondary outcomes were the relative risk of death at day 30 and 1 year based on the place of primary referral. RESULTS: Of 5,257 first TBI hospital contacts of adult patients included in the cohort, 1,430 (27.2%) entered the health care system via 1-1-2 emergency medical calls. TBI patients triaged by 112-calls were more likely to receive the highest level of emergency response (15.6% vs. 50.3%; p < 0.001) and second-tier resources and were more frequently referred directly to a specialised centre than were patients entering through GPs or other health care personnel. In the subgroup of 1188/5257 (22.4%) patients with confirmed intracranial lesions, we found no difference in the risk ratio of 30 day (RR 1.04 (95%CI 0.65-1.63)) or 1 year (RR 0.96 (95%CI 0.72-1.25)) all-cause mortality between patients primarily referred to a regional hospital or to a specialised centre when adjusting for age, sex, comorbidities, antiplatelet/anticoagulant treatment and type of intracranial lesions. CONCLUSION: TBI patients mainly enter the health system by contact with GPs or other health care professionals. However, patients entering through 112-calls are more frequently triaged directly to specialised centres. We were unable to demonstrate any significant difference in the adjusted 30-day and 1-year mortality based on e primary referral to a specialised centre. The inability to demonstrate an effect on mortality based on primary referral to a specialised centre may reflect a lack of clinical data in the registries used. Considerable differences may exist in nondocumented baseline characteristics (i.e., GCS, blood pressure and injury severity) between the groups and may limit conclusions about differences in mortality. Further research providing high-quality evidence on the effect of primary referral is needed to secure early neurosurgical interventions in TBI patients.

Hospital at home for elderly acute patients: a study protocol for a randomised controlled trial.

INTRODUCTION: The increasing elderly population has led to a growing demand for healthcare services. A hospital at home treatment model offers an alternative to standard hospital admission, with the potential to reduce readmission and healthcare consumption while improving patients' quality of life. However, there is little evidence regarding hospital at home treatment in a Danish setting. This article describes the protocol for a randomised controlled trial (RCT) comparing standard hospital admission to hospital at home treatment. The main aim of the intervention is to reduce 30-day acute readmission after discharge and improve the quality of life of elderly acute patients. METHODS AND ANALYSIS: A total of 849 elderly acute patients will be randomised in a 1:2 ratio to either the control or intervention group in the trial. The control group will receive standard hospital treatment in a hospital emergency department while the intervention group will receive treatment at home. The primary outcomes of the trial are the rate of 30-day acute readmission and quality of life, assessed using the European Quality of Life-5 Dimensions-5-Level instrument. Primary analyses are based on the intention-to-treat principle. Secondary outcomes are basic functional mobility, resource use in healthcare, primary and secondary healthcare cost, incremental cost-effectiveness ratio, and the mortality rate 3 months after discharge. ETHICS AND DISSEMINATION: The RCT was approved by the Ethical Committee, Central Denmark Region (no. 1-10-72-67-20). Results will be presented at relevant national and international meetings and conferences and will be published in international peer-reviewed journals. Furthermore, we plan to communicate the results to relevant stakeholders in the Danish healthcare system. TRIAL REGISTRATION NUMBER: NCT05360914.

The association of recent simulation training and clinical experience of team leaders with cardiopulmonary resuscitation quality during in-hospital cardiac arrest.

OBJECTIVE: We aimed to investigate the association of recent team leader simulation training (<6 months) and years of clinical experience (≥4 years) with chest compression quality during in-hospital cardiac arrest (IHCA). METHODS: This cohort study of IHCA in four Danish hospitals included cases with data on chest compression quality and team leader characteristics. We assessed the impact of recent simulation training and experienced team leaders on longest chest compression pause duration (primary outcome), chest compression fraction (CCF), and chest compression rates within guideline recommendations using mixed effects models. RESULTS: Of 157 included resuscitation attempts, 45% had a team leader who recently participated in simulation training and 66% had an experienced team leader. The median team leader experience was 7 years [Q1; Q3: 4; 11]. The median duration of the longest chest compression pause was 16 s [10; 30]. Having a team leader with recent simulation training was associated with significantly shorter longest pause durations (difference: -7.11 s (95%-CI: -12.0; -2.2), p = 0.004), a higher CCF (difference: 3% (95%-CI: 2.0; 4.0%), p < 0.001) and with less guideline compliant chest compression rates (odds ratio: 0.4 (95%-CI: 0.19; 0.84), p = 0.02). Having an experienced team leader was not associated with longest pause duration (difference: -1.57 s (95%-CI: -5.34; 2.21), p = 0.42), CCF (difference: 0.7% (95%-CI: -0.3; 1.7), p = 0.17) or chest compression rates within guideline recommendations (odds ratio: 1.55 (95%-CI: 0.91; 2.66), p = 0.11). CONCLUSION: Recent simulation training of team leaders, but not years of team leader experience, was associated with shorter chest compression pauses during IHCA.

Point-of-Care Lung Ultrasound in Emergency Medicine: A Scoping Review With an Interactive Database.

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.

As-needed opioid dosing for emergency patients with a daily use of opioids.

BACKGROUND: Patients with a daily use of opioids have a higher risk of insufficient pain treatment during hospitalization than other patients. This study aimed to examine whether as-needed opioid doses (PRN) were adequately adjusted when patients were admitted to the emergency department (ED) with pain. METHODS: Patients, with a daily use of opioids, who received PRN opioid within the first 3 h after admission at the ED at Aarhus University Hospital, Denmark, were prospectively included from February 2021 to June 2021. The primary outcome was the proportion of patients receiving an inadequate initial dose of PRN opioid, here defined as <15% of daily dose of opioids (DDO) based on sparse evidence, but aligning with the prevailing clinical practice. Secondary outcomes included risk of an inadequate PRN dose in relation to DDO (patients were dichotomized into two groups (DDO <60 or ≥60 mg/day). RESULTS: Among 252 patients admitted to the ED with a daily use of opioids, 149 were admitted with pain and 82 received a PRN opioid dose within 3 h. Twenty-seven out of 82 (33%) patients received a PRN dose of <15% of DDO (95% CI: 23.7-43). When dichotomised; 10 out of 50 (20%) patients with a DDO <60 mg/day (95% CI: 10.0-33.7) versus 17 out of 32 (53.1%) patients with a DDO ≥60 mg/day (95% CI: 34.7-70.9) received an inadequate PRN dose (relative risk, RR: 2.65 [95% CI: 1.4-5.1]). CONCLUSIONS: Patients with daily use of opioids presenting in the ED with acute pain had a high risk of inadequate PRN opioid dose, especially if the DDO was high. Awareness about and education focusing on sufficient PRN doses for patients with a daily use of opioids is (still) called for.

Prostacyclin in trauma patients with hemorrhagic shock: A randomized clinical trial.

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.

Dysnatremia at ICU admission and functional outcome of cardiac arrest: insights from four randomised controlled trials.

PURPOSE: To evaluate the potential association between early dysnatremia and 6-month functional outcome after cardiac arrest. METHODS: We pooled data from four randomised clinical trials in post-cardiac-arrest patients admitted to the ICU with coma after stable return of spontaneous circulation (ROSC). Admission natremia was categorised as normal (135-145 mmol/L), low, or high. We analysed associations between natremia category and Cerebral Performance Category (CPC) 1 or 2 at 6 months, with and without adjustment on the modified Cardiac Arrest Hospital Prognosis Score (mCAHP). RESULTS: We included 1163 patients (581 from HYPERION, 352 from TTH48, 120 from COMACARE, and 110 from Xe-HYPOTHECA) with a mean age of 63 ± 13 years and a predominance of males (72.5%). A cardiac cause was identified in 63.6% of cases. Median time from collapse to ROSC was 20 [15-29] minutes. Overall, mean natremia on ICU admission was 137.5 ± 4.7 mmol/L; 211 (18.6%) and 31 (2.7%) patients had hyponatremia and hypernatremia, respectively. By univariate analysis, CPC 1 or 2 at 6 months was significantly less common in the group with hyponatremia (50/211 [24%] vs. 363/893 [41%]; P = 0.001); the mCAHP-adjusted odds ratio was 0.45 (95%CI 0.26-0.79, p = 0.005). The number of patients with hypernatremia was too small for a meaningful multivariable analysis. CONCLUSIONS: Early hyponatremia was common in patients with ROSC after cardiac arrest and was associated with a poorer 6-month functional outcome. The mechanisms underlying this association remain to be elucidated in order to determine whether interventions targeting hyponatremia are worth investigating. Registration ClinicalTrial.gov, NCT01994772, November 2013, 21.

Soluble Urokinase-Type Plasminogen Activator Receptor in Comatose Survivors After Out-of-Hospital Cardiac Arrest Treated with Targeted Temperature Management.

Exposure to whole-body ischemia/reperfusion after out-of-hospital cardiac arrest (OHCA) triggers a systemic inflammatory response where soluble urokinase plasminogen activator receptor (suPAR) is released. This study investigated serial levels of suPAR in differentiated target temperature management and the associations with mortality and 6-month neurological outcome. This is a single-center substudy of the randomized Targeted Temperature Management (TTM) for 24-hour versus 48-hour trial. In this analysis, we included 82 patients and measured serial levels of suPAR at 24, 48, and 72 hours after achievement of target temperature (32-34°C). We assessed all-cause mortality and neurological function evaluated by the Cerebral Performance Categories (CPC) at 6 months after OHCA. Levels of suPAR between TTH groups were evaluated in repeated measures mixed models. Mortality was assessed by the Kaplan-Meier method and serial measurements of suPAR (log2 transformed) were investigated by Cox proportional-hazards models. Good neurological outcome at 6 months was assessed by logistic regression analyses. Levels of suPAR were significantly different between TTH groups (pinteraction = 0.04) with the highest difference at 48 hours, 4.7 ng/mL (95% CI: 4.1-5.4 ng/mL) in the TTH24 group compared to 2.8 ng/mL (95% CI: 2.2-3.5 ng/mL) in the TTH48 group, p < 0.0001. Levels of suPAR above the median value were significantly associated with increased all-cause mortality at any time point (plog-rank<0.05). The interaction of suPAR levels and TTH group was not significant (pinteraction = NS). A twofold increase in levels of suPAR was significantly associated with a decreased odds ratio of a good neurological outcome in both unadjusted and adjusted analyses without interaction of TTH group (pinteraction = NS). Prolonged TTM of 48 hours versus 24 hours was associated with lower levels of suPAR. High levels of suPAR were associated with increased mortality and lower odds for good neurological outcome at 6 months with no significant interaction of TTH group.

Remote Ischemic Conditioning for Acute Stroke: The RESIST Randomized Clinical Trial.

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 outcome at 90 days (odds ratio [OR], 0.95; 95% CI, 0.75 to 1.20, P = .67; absolute difference in median mRS score, -1; -1.7 to -0.25). In all randomized patients, there were no significant differences in the number of serious adverse events: 169 patients (23.7%) in the RIC group with 1 or more serious adverse events vs 175 patients (24.3%) in the sham group (OR, 0.97; 95% CI, 0.85 to 1.11; P = .68). Upper extremity pain during treatment and/or skin petechia occurred in 54 (7.2%) in the RIC group and 11 (1.5%) in the sham group. Conclusions and Relevance: RIC initiated in the prehospital setting and continued in the hospital did not significantly improve functional outcome at 90 days in patients with acute stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT03481777.

Neurofilament Light Chain and Glial Fibrillary Acidic Protein as early prognostic biomarkers after out-of-hospital cardiac arrest.

AIMS: Neurofilament Light Chain (NfL) and Glial Fibrillary Acidic Protein (GFAP) are proteins released into the bloodstream upon hypoxic brain injury. We evaluated the biokinetics and examined the prognostic performance of serum NfL and GFAP in comatose out-of-hospital cardiac arrest (OHCA) patients. Furthermore, we compared the prognostic performance to that of serum Neuron Specific Enolase (NSE). METHODS: This is a sub-study of the "Targeted temperature management for 48 vs 24 hours" (NCT01689077) trial. NfL and GFAP serum values from 82 patients were examined in blood samples collected at 24, 48 and 72 hours (h) after reaching target temperature of 33 ± 1 °C. This temperature was reached within a median of 281-320 minutes after intensive care unit admission. GFAP was analysed at 48 and 72 h. The neuroprognostic performance of NfL and GFAP was evaluated after 6 months follow-up. RESULTS: NfL and GFAP values were significantly higher in patients with a poor outcome (Cerebral Performance Category (CPC) score 3-5) vs. good outcome (CPC 1-2). NfL 24 h: 1371.5 (462.0; 2125.1) vs. 24.8 (14.0; 61.6). GFAP 48 h: 1285.3 (843.9; 2236.7) vs. 361.2 (200.4; 665.6) (both p < 0.001). Both biomarkers were promising markers of poor functional outcome at 24 and 48 h respectively: NfL 24 h: AUROC 0.95 (95% CI: 0.91-1.00). GFAP 48 h: AUROC 0.88 (95% CI: 0.81-0.96). NfL and GFAP both predicted outcome better than NSE at 48 h (both p < 0.01). At 72 h NfL but not GFAP outperformed NSE (p = 0.01). CONCLUSION: Serum NfL and GFAP may be strong biomarkers of poor functional outcome after OHCA from an early timepoint.

Inter-Rater Agreement on Cincinnati Prehospital Stroke Scale (CPSS) and Prehospital Acute Stroke Severity Scale (PASS) Between EMS Providers, Neurology Residents and Neurology Consultants.

Objective: 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 neurology residents and 240 by neurology consultants. The overall relative and absolute IRA for all items combined from the CPSS and PASS score was 0.84 (95% CI 0.80; 0.87) and 0.81 (95% CI 0.77; 0.85), respectively. Using the CPSS, the agreement on a group-level resulted in AUCs of 0.83 (95% CI 0.78; 0.88) for the EMS providers and 0.86 (95% CI 0.82; 0.90) for the neurology residents when compared with the gold standard. Using the PASS, the AUC was 0.82 (95% CI 0.77; 0.87) for the EMS providers and 0.88 (95% CI 0.84; 0.93) for the neurology residents. Conclusion: The high relative and absolute inter-rater agreement underpins a high robustness/generalisability of the two scales. A high agreement exists across individual raters and different groups of healthcare professionals supporting widespread applicability of the stroke scales.

Neuropsychological outcome after cardiac arrest: results from a sub-study of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial.

BACKGROUND: Cognitive impairment is common following out-of-hospital cardiac arrest (OHCA), but the nature of the impairment is poorly understood. Our objective was to describe cognitive impairment in OHCA survivors, with the hypothesis that OHCA survivors would perform significantly worse on neuropsychological tests of cognition than controls with acute myocardial infarction (MI). Another aim was to investigate the relationship between cognitive performance and the associated factors of emotional problems, fatigue, insomnia, and cardiovascular risk factors following OHCA. METHODS: This was a prospective case-control sub-study of The Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Eight of 61 TTM2-sites in Sweden, Denmark, and the United Kingdom included adults with OHCA of presumed cardiac or unknown cause. A matched non-arrest control group with acute MI was recruited. At approximately 7 months post-event, we administered an extensive neuropsychological test battery and questionnaires on anxiety, depression, fatigue, and insomnia, and collected information on the cardiovascular risk factors hypertension and diabetes. RESULTS: Of 184 eligible OHCA survivors, 108 were included, with 92 MI controls enrolled. Amongst OHCA survivors, 29% performed z-score ≤ - 1 (at least borderline-mild impairment) in ≥ 2 cognitive domains, 14% performed z-score ≤ - 2 (major impairment) in ≥ 1 cognitive domain while 54% performed without impairment in any domain. Impairment was most pronounced in episodic memory, executive functions, and processing speed. OHCA survivors performed significantly worse than MI controls in episodic memory (mean difference, MD = - 0.37, 95% confidence intervals [- 0.61, - 0.12]), verbal (MD = - 0.34 [- 0.62, - 0.07]), and visual/constructive functions (MD = - 0.26 [- 0.47, - 0.04]) on linear regressions adjusted for educational attainment and sex. When additionally adjusting for anxiety, depression, fatigue, insomnia, hypertension, and diabetes, executive functions (MD = - 0.44 [- 0.82, - 0.06]) were also worse following OHCA. Diabetes, symptoms of anxiety, depression, and fatigue were significantly associated with worse cognitive performance. CONCLUSIONS: In our study population, cognitive impairment was generally mild following OHCA. OHCA survivors performed worse than MI controls in 3 of 6 domains. These results support current guidelines that a post-OHCA follow-up service should screen for cognitive impairment, emotional problems, and fatigue. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03543371. Registered 1 June 2018.

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.

Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest.

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 [Paco2], 50 to 55 mm Hg) or 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 patients 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. (Funded by the National Health and Medical Research Council of Australia and others; TAME ClinicalTrials.gov number, NCT03114033.).

Associations between emergency call stroke triage and pre-hospital delay, primary hospital admission, and acute reperfusion treatment among early comers with acute ischemic stroke.

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.

Effect of Out-Of-Hour Admission on Fluid Treatment of Emergency Department Patients with Suspected Infection; a Multicenter Post-Hoc Analysis.

Introduction: Sepsis is a life-threatening and common cause of Emergency department (ED) referrals. Out-of-hour staffing is limited in ED, which may potentially affect fluid administration. This study aimed to investigate fluid volume variation in out-of-hour vs. routine-hour admissions. Methods: The present study is a post-hoc analysis of a multicentre, prospective, observational study investigating fluid administration in ED patients with suspected infection, from Jan 20th - March 2nd, 2020. Patient groups were "routine-hours" (RH): weekdays 07:00-18:59 or "out-of-hours" (OOH): weekdays 19:00-06:59 or Friday 19:00-Monday 06:59. Primary outcome was 24-hour total fluid volumes (oral + intravenous (IV)). Secondary outcomes were total fluids 0-6 hours, oral fluids 0-6 and 0-24 hours, and IV fluids 0-6 and 0-24 hours. Linear regression adjusted for site and illness severity was used. Results: 734 patients had suspected infection; 449 were admitted during RH and 287 during OOH. Mean (95% CI) total 24-hour fluid volumes were equal in simple infection and sepsis regardless of admission time: Simple infection RH: 3640 (3410 - 3871) ml and OOH: 3681 (3451 - 3913) ml. Sepsis RH: 3671 (3443;3898) ml and OOH: 3896 (3542;4250) ml. Oral fluids 0-6h were reduced in simple infection and sepsis among OOH vs. RH. Sepsis patients received more 0-6-hour IV fluid when admitted OOH vs. RH. There were no associations between admission time and 0-24-hour oral or IV volumes in simple infection or sepsis. Conclusion: Admission time did not have an association with 24-hour total fluid volumes. Sepsis patients admitted during OOH received more 0-6-hour IV fluids than RH patients, and simple infection and sepsis patients received less oral fluid in 0-6 hours if admitted during OOH vs. RH.

Acute pain treatment of children in the Danish emergency departments.

INTRODUCTION: Preconditions for good pain treatment in children include education and guidelines. This study investigated whether the guidelines on acute pain treatment of children in Danish emergency departments reflected the national guideline, examined the knowledge and use of guidelines, and explored the approach adopted to treating pain in children. METHODS: This cross-sectional study consisted of two parts. Part I compared the guidelines in each emergency department with a national guideline; Part II was a structured interview with the emergency department doctors regarding their approach to treating pain in children. RESULTS: Several guidelines did not include pain assessment, dose schedules and non-pharmacological methods as recommended in the national guideline. The doctors knew where to find the guidelines, but a considerable share of them did not use the guidelines. Most doctors felt competent in treating children, but reported a reluctance to using opioids and reported using pain assessment irregularly. CONCLUSION: The Danish guidelines on acute pain treatment of children in many emergency departments vary compared with the national guideline. We found that several doctors do not use the guidelines, are reluctant to use opioids and do not use pain assessment. We suggest a thorough implementation of a national guideline in emergency departments to standardise pain treatment. FUNDING: none. TRIAL REGISTRATION: not relevant.