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.).

Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest.

BACKGROUND: Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. METHODS: In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33°C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, ≥37.8°C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. RESULTS: A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P = 0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score ≥4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. CONCLUSIONS: In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, NCT02908308.).

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.

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.

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.

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.

The Prehospital Stroke Score and telephone conference: A prospective validation.

OBJECTIVES: The main aim of the study is to investigate the performance of a two-part stroke scale for screening and subsequent severity assessment combined with a telephone conference (teleconference). MATERIALS AND METHODS: During a 6-month period, we prospectively tested the Prehospital Stroke Score (PreSS). PreSS part 1 is designed to identify stroke or TIA in a prehospital setting. PreSS part 2 is a stroke severity scale designed to identify large-vessel occlusion (LVO). PreSS was performed by emergency medical service (EMS) providers prior to a teleconference with a stroke neurologist. RESULTS: Combined teleconference and PreSS part 1 were performed on 79.3% of all patients diagnosed with stroke/TIA, and 99.1% of the patients with positive scores were subsequently PreSS part 2 scored. PreSS part 1 and teleconference had a sensitivity to identify stroke/TIA of 89.3% (95% CI 85.7-92.2), specificity of 64.5% (95% CI 59.3-69.5), and an area under the curve (AUC) of 0.80 (95% CI 0.77-0.83). Regarding LVO, PreSS part 1 with teleconference recognized 96.7% (95% CI 88.7-99.6) of all cases as stroke. PreSS part 2 had a sensitivity of 55.7% (95% CI 42.4-68.5), specificity of 91.5% (95% CI 89.0-93.6), and AUC of 0.86 (95% CI 0.82-0.90) for identification of LVO. CONCLUSIONS: PreSS was feasible and the sensitivity for stroke/TIA and LVO was high to moderate providing an overall high precision. Almost all LVO cases were ensured acute stroke admission. The high specificity for LVO could be useful for determining transfers strategies. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence when evaluating PreSS combined with teleconference.

Kinetics of 2 different high-sensitive troponins during targeted temperature management in out-of-hospital cardiac arrest patients with acute myocardial infarction: a post hoc sub-study of a randomised clinical trial.

INTRODUCTION: Short term hypothermia has been suggested to have cardio protective properties in acute myocardial infarction (AMI) by reducing infarct size as assessed by troponins. There are limited data on the kinetics of these biomarkers in comatose out-of-hospital cardiac arrest (OHCA) patients, with and without AMI, undergoing targeted temperature management (TTM) in the ICU. PURPOSE: The aim of this post hoc analyses was to evaluate and compare the kinetics of two high-sensitivity cardiac troponins in OHCA survivors, with and without acute myocardial infarction (AMI), during TTM of different durations [24 h (standard) vs. 48 h (prolonged)]. METHODS: In a sub-cohort (n = 114) of the international, multicentre, randomized controlled study "TTH48" we measured high-sensitive troponin T (hs-cTnT), high-sensitive troponin I (hs-cTnI) and CK-MB at the following time points: Arrival, 24 h, 48 h and 72 h from reaching the target temperature range of 33 ± 1 °C. All patients diagnosed with an AMI at the immediate coronary angiogram (CAG)-18 in the 24-h group and 25 in the 48-h group-underwent PCI with stent implantation. There were no stent thromboses. RESULTS: Both the hs-cTnT and hs-cTnI changes over time were highly influenced by the cause of OHCA (AMI vs. non-AMI). In contrast to non-AMI patients, both troponins remained elevated at 72 h in AMI patients. There was no difference between the two time-differentiated TTM groups in the kinetics for the two troponins. CONCLUSION: In comatose OHCA survivors with an aetiology of AMI levels of both hs-cTnI and hs-cTnT remained elevated for 72 h, which is in contrast to the well-described kinetic profile of troponins in normotherm AMI patients. There was no difference in kinetic profile between the two high sensitive assays. Different duration of TTM did not influence the kinetics of the troponins. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01689077, 20/09/2012.

Effect of the COVID-19 pandemic at a major Danish trauma center in 2020 compared with 2018-2019: A retrospective cohort study.

BACKGROUND: The COVID-19 pandemic demanded changes in societal behavior and health care worldwide. Previous studies have compared trauma patient admissions in COVID-19-related lockdowns to prior years. This study describes the COVID-19 impact on trauma patient admissions during entire 2020 at a major trauma center in Denmark. METHODS: We retrospectively analyzed trauma patients received by a trauma team and admitted at Aarhus University Hospital in 2020 compared with 2018-2019. The incidence of injuries, mechanism of injury, 30-day mortality, and Injury Severity Score (ISS) were investigated. RESULTS: The incidence of minor injuries (ISS 1-15) increased by 24% in 2020 compared with 2018-2019 (incidence rate ratio 1.24 [95% CI: 1.11-1.39]). The incidence of severe injuries (ISS >15) in 2020 did not change compared with 2018-2019 (incidence rate ratio 0.97 [95% CI: 0.80-1.17]). The 30-day mortality was similar in 2020 compared with 2018-2019. Comparing 2020 with 2018-2019, the risk ratio of traffic injuries decreased (0.90 [95% CI: 0.82-0.99]), risk ratio for fall injuries was 1.13 (95% CI: 0.97-1.30), for violence 1.13 (95% CI: 0.51-2.50), and for self-harm 1.94 (95% CI: 0.95-3.94). During the first lockdown of 2020, trauma team activations declined from 49.5 to 42 and the risk ratio for traffic injuries was 0.74 (95% CI: 0.50-1.10) compared with the same period in 2018-2019. CONCLUSION: The incidence of minor injuries increased, but the incidence of severe injuries was similar in 2020 compared with 2018-2019. Societal restrictions might alter the mechanism of injuries. The first lockdown indicated an association with reduced traffic injuries.

Ten-year trends of adult trauma patients in Central Denmark Region from 2010 to 2019: A retrospective cohort study.

BACKGROUND: Trauma causes significant economic and societal burdens, and the trauma patient population and their prognosis change over time. This study aims to analyze 10-year trends of trauma patients at a major trauma center in Central Denmark Region. METHODS: Five thousand three hundred and sixty-six patients aged ≥16 years with Injury Severity Score (ISS) > 0 admitted by trauma team activation at a major trauma center between January 1, 2010, and December 31, 2019, were included. An annual percent change with a 95% confidence interval was used to estimate trends in the mechanism of injuries. Multiple logistic regression with mortality as the outcome was adjusted for age, sex, and ISS. Admission year was used as continuous variable in logistic regressions. RESULTS: The median age increased from 37 in 2010 to 49 in 2019, and the proportion of patients aged ≥65 doubled. The annual incidence of minor injuries (ISS 1-15) decreased from 181.3/105 inhabitants in 2010 to 112.7/105 in 2019. Severe injuries (ISS > 15) increased from 10.1/105 inhabitants in 2010 to 13.6/105 in 2019. The proportion of patients with ISS > 15 increased from 18.1% in 2010 to 31.1% in 2019. Multivariable logistic regression indicates lower 30-day mortality for all trauma patients over the study period when adjusting for age, sex, and ISS (odds ratio: 0.94, 95% CI: 0.90-0.99). The 30-day mortality for severely injured patients with ISS > 15 seems to decrease during the study period when adjusting for age, sex, and ISS (Odds ratio: 0.92, 95% CI: 0.87-0.97). Fall injuries increased by 4.1% annually (95% CI: 2.3%-6.1%). CONCLUSIONS: Ten-year trends of trauma patients at a major trauma center show an increasing median age, injury severity, and number of fall injuries. The 30-day mortality of trauma patients decreased slightly for both minor injuries and severe injuries when adjusting for age, sex, and injury severity.

Quantitative pupillometry in comatose out-of-hospital cardiac arrest patients: A post-hoc analysis of the TTH48 trial.

BACKGROUND: Quantitative pupillometry is an objective method to examine pupil reaction and subsequently grade the response on a neurological pupil index (NPi) scale from 0 to 5. The aim of the present sub-study was to explore the long-term prognostic value of NPi in comatose out-of-hospital cardiac arrest patients undergoing targeted temperature management (TTM). METHODS: This planned sub-study of the "Targeted temperature management for 48 versus 24 h and neurological outcome after out-of-hospital cardiac arrest: A randomized clinical trial." NPi was assessed from admission and throughout day 3 and linked to the Cerebral Performance Categories score at 6 months. We compared the prognostic performance of NPi in 65 patients randomized to a target temperature of 33 ± 1°C for 24 or 48 h. RESULTS: The NPi values were not different between TTM groups (p > .05). When data were pooled, NPi was strongly associated with neurological outcome at day 1 with a mean NPi of 3.6 (95% CI 3.4-3.8) versus NPi 3.9 (3.6-4.1) in the poor versus good outcome group, respectively (p < .01). At day 2, NPi values were 3.6 (3.1-4.0) and 4.1 (3.9-4.2) (p = .01) and at day 3, the values were 3.3 (2.6-4.0) and 4.3 (4.1-4.6), respectively (p < .01). The prognostic ability of NPi, defined by area under the receiver operating characteristic curve was best at day three. CONCLUSION: Quantitative pupillometry measured by NPi was not different in the two TTM groups, but overall, significantly associated with good and poor neurological outcomes at 6 months. NPI has a promising diagnostic accuracy, but larger studies are warranted.

Fluid management of emergency department patients with sepsis-A survey of fluid resuscitation practices.

BACKGROUND: Fluid administration and resuscitation of patients with sepsis admitted through emergency departments (ED) remains a challenge, and evidence is sparse especially in sepsis patients without shock. We aimed to investigate emergency medicine physicians' and nurses' perceptions, self-reported decision-making and daily behavior, and challenges in fluid administration of ED sepsis patients. METHODS: We developed and conducted a multicenter, web-based, cross-sectional survey focusing on fluid administration to ED patients with sepsis sent to all nurses and physicians from the five EDs in the Central Denmark Region. The survey consisted of three sections: (1) baseline information; (2) perceptions of fluid administration and daily practice; and (3) clinical scenarios about fluid administration. The survey was performed from February to June, 2021. RESULTS: In total, 138 of 246 physicians (56%) and 382 of 595 nurses (64%) responded to the survey. Of total, 94% of physicians and 97% of nurses regarded fluid as an important part of sepsis treatment. Of total, 80% of physicians and 61% of nurses faced challenges regarding fluid administration in the ED, and decisions were usually based on clinical judgment. The most common challenge was the lack of guidelines for fluid administration. Of total, 96% agreed that they would like to learn more about fluid administration, and 53% requested research in fluid administration of patients with sepsis. For a normotensive patient with sepsis, 46% of physicians and 44% of nurses administered 1000 ml fluid in the first hour. Of total, 95% of physicians and 89% of nurses preferred to administer ≥1000 ml within an hour if the patients' blood pressure was 95/60 at admission. There was marked variability in responses. Blood pressure was the most commonly used trigger for fluid administration. Respondents preferred to administer less fluid if the patient in the scenario had known renal impairment or heart failure. Normal saline was the preferred fluid. CONCLUSION: Fluid administration is regarded as an important but challenging aspect of sepsis management. Responses to scenarios revealed variability in fluid volumes. Blood pressure was the most used trigger. ED nurses and physicians request evidence-based guidelines to improve fluid administration.

Electrolyte profiles with induced hypothermia: A sub study of a clinical trial evaluating the duration of hypothermia after cardiac arrest.

BACKGROUND: Electrolyte disturbances can result from targeted temperature treatment (TTM) in out-of-hospital cardiac arrest (OHCA) patients. This study explores electrolyte changes in blood and urine in OHCA patients treated with TTM. METHODS: This is a sub-study of the TTH48 trial, with the inclusion of 310 unconscious OHCA patients treated with TTM at 33°C for 24 or 48 h. Over a three-day period, serum concentrations were obtained on sodium potassium, chloride, ionized calcium, magnesium and phosphate, as were results from a 24-h diuresis and urine electrolyte concentration and excretion. Changes over time were analysed with a mixed-model multivariate analysis of variance with repeated measurements. RESULTS: On admission, mean ± SD sodium concentration was 138 ± 3.5 mmol/l, which increased slightly but significantly (p < .05) during the first 24 h. Magnesium concentration stayed within the reference interval. Median ionized calcium concentration increased from 1.11 (IQR 1.1-1.2) mmol/l during the first 24 h (p < .05), whereas median phosphate concentration dropped to 1.02 (IQR 0.8-1.2) mmol/l (p < .05) and stayed low. During rewarming, potassium concentrations increased, and magnesium and ionizes calcium concentration decreased (p < .05). Median 24-h diuresis results on days one and two were 2198 and 2048 ml respectively, and the electrolyte excretion mostly stayed low in the reference interval. CONCLUSIONS: Electrolytes mostly remained within the reference interval. A temporal change occurred in potassium, magnesium and calcium concentrations with TTM's different phases. No hypothermia effect on diuresis was detected, and urine excretion of electrolytes mostly stayed low.

Bacteremia Prediction With Prognostic Scores and a Causal Probabilistic Network - A Cohort Study of Emergency Department Patients.

BACKGROUND: Physicians tend to overestimate patients' pretest probability of having bacteremia. The low yield of blood cultures and contaminants is associated with significant financial cost, as well as increased length of stay and unnecessary antibiotic treatment. OBJECTIVE: This study examined the abilities of the National Early Warning Score (NEWS), the Quick Sequential Organ Failure Assessment (qSOFA), the Modified Sequential Organ Failure Assessment (mSOFA), and two versions of the causal probabilistic network, SepsisFinder™ (SF) to predict bacteremia in adult emergency department (ED) patients. METHODS: This cohort study included adult ED patients from a large urban, academic tertiary hospital, with blood cultures obtained within 24 h of admission between 2016 and 2017. The outcome measure was true bacteremia. NEWS, qSOFA, mSOFA, and the two versions of SF score were calculated for all patients based on the first available full set of vital signs within 2 h and laboratory values within 6 h after drawing the blood cultures. Area under the receiver operating characteristic curve (AUROC) was calculated for each scoring system. RESULTS: The study included 3106 ED patients, of which 199 (6.4%) patients had true bacteremia. The AUROCs for prediction of bacteremia were: NEWS = 0.65, qSOFA = 0.60, SF I = 0.65, mSOFA = 0.71, and SF II = 0.80. CONCLUSIONS: Scoring systems using only vital signs, NEWS, and SF I showed moderate abilities in predicting bacteremia, whereas qSOFA performed poorly. Scoring systems using both vital signs and laboratory values, mSOFA and especially SF II, showed good abilities in predicting bacteremia.

Consensus on predictors of clinical deterioration in emergency departments: A Delphi process study.

AIM: The study aim was to determine relevance and applicability of generic predictors of clinical deterioration in emergency departments based on consensus among clinicians. METHODS: Thirty-three predictors of clinical deterioration identified from literature were assessed in a modified two-stage Delphi-process. Sixty-eight clinicians (physicians and nurses) participated in the first round and 48 in the second round; all treating hospitalized patients in Danish emergency departments, some with pre-hospital experience. The panel rated the predictors for relevance (relevant marker of clinical deterioration) and applicability (change in clinical presentation over time, generic in nature and possible to detect bedside). They rated their level of agreement on a 9-point Likert scale and were also invited to propose additional generic predictors between the rounds. New predictors suggested by more than one clinician were included in the second round along with non-consensus predictors from the first round. Final decisions of non-consensus predictors after second round were made by a research group and an impartial physician. RESULTS: The Delphi-process resulted in 19 clinically relevant and applicable predictors based on vital signs and parameters (respiratory rate, saturation, dyspnoea, systolic blood pressure, pulse rate, abnormal electrocardiogram, altered mental state and temperature), biochemical tests (serum c-reactive protein, serum bicarbonate, serum lactate, serum pH, serum potassium, glucose, leucocyte counts and serum haemoglobin), objective clinical observations (skin conditions) and subjective clinical observations (pain reported as new or escalating, and relatives' concerns). CONCLUSION: The Delphi-process led to consensus of 19 potential predictors of clinical deterioration widely accepted as relevant and applicable in emergency departments.

A new situation awareness model decreases clinical deterioration in the emergency departments-A controlled intervention study.

BACKGROUND: Studies have suggested that adding subjective parameters to early warning score (EWS) systems might prompt more proactive treatment and positively affect clinical outcomes. Hence, the study aimed to investigate effect of a situation awareness model consisting of objective and subjective parameters on clinical deterioration in adult emergency department (ED) patients. METHODS: This controlled pre-and-post interventional study was carried out in July-December 2016 and November 2017-April 2018. In ED patients ≥ 18 years, we examined if a situation awareness model compared with a conventional EWS system could reduce clinical deterioration. The new model consisted of a regional EWS, combined with skin observation, clinical concern and patients' and relatives' concerns, pain, dyspnea, and team risk assessment. Clinical deterioration was defined as change in vital signs requiring increased observation or physician assessment, that is, increase in early warning score from either 0 or 1 to score ≥2 or an increase from score ≥2 and above. Secondary outcomes were mortality, intensive care unit (ICU) admissions, and readmissions. RESULTS: We included 34 556 patients. Patients with two or more registered EWS were included in the primary analysis (N = 21 839). Using difference-in-difference regression, we found a reduced odds of clinical deterioration of 21% (OR 0.79 95% CI [0.69; 0.90]) in the intervention groups compared with controls. No impact on mortality, ICU, or readmissions was found. CONCLUSION: The situation awareness model reduces odds of clinical deterioration, defined as a clinically relevant increase in EWS, in an unselected adult population of ED patients. However, there was no effect on secondary outcomes.

Efficacy and safety of iloprost in trauma patients with haemorrhagic shock-induced endotheliopathy-Protocol for the multicentre randomized, placebo-controlled, blinded, investigator-initiated shine-trauma trial.

BACKGROUND: Traumatic injury accounts for 800 000 deaths in the European Union annually. The main causes of deaths in trauma patients are exsanguination and multiple organ failure (MOF). We have studied >1000 trauma patients and identified shock-induced endotheliopathy (SHINE), the pathophysiological mechanism responsible for MOF and high mortality. Pilot studies indicate that low-dose iloprost (1 ng/kg/min) improves endothelial functionality in critically ill patients suggesting this intervention may improve patient outcome in traumatic SHINE. MATERIAL AND METHODS: This is a multicentre, randomized, blinded clinical investigator-initiated phase 2B trial in trauma patients with haemorrhagic shock-induced endotheliopathy. Patients are randomized 1:1 to 72 hours infusion of iloprost 1 ng/kg/min or Placebo (equal volume of saline). A total of 220 trauma patients will be included. The primary endpoint is the number of intensive care unit (ICU)-free days, within 28 days of admission. Secondary endpoints include 28- and 90-day all-cause mortality, hospital length of stay, vasopressor-free days in the intensive care unit (ICU) within 28 days, ventilator-free days in the ICU within 28 days, renal replacement-free days in the ICU within 28 days, number of serious adverse reactions and serious adverse events within the first 4 days of admission. DISCUSSION: This trial will test the safety and efficacy of administration of iloprost vs placebo for 72 hours in trauma patients with haemorrhagic shock-induced endotheliopathy. Trial endpoints focus on the potential effect of iloprost to reduce the need for ICU stay secondary to mitigation of organ failure. TRIAL REGISTRATION: SHINE-TRAUMA trial-EudraCT no. 2019-000936-24-Clinicaltrials.gov: NCT03903939 Ethics Committee no. H-19014482.

Twenty-four-hour fluid administration in emergency department patients with suspected infection: A multicenter, prospective, observational study.

BACKGROUND: To describe 24-hour fluid administration in emergency department (ED) patients with suspected infection. METHODS: A prospective, multicenter, observational study conducted in three Danish hospitals, January 20 to March 2, 2020. We included consecutive adult ED patients with suspected infection (drawing of blood culture and/or intravenous antibiotic administration within 6 hours of admission). Oral and intravenous fluids were registered for 24 hours. PRIMARY OUTCOME: 24-hour total fluid volume. We used linear regression to investigate patient and disease characteristics' effect on 24-hour fluids and to estimate the proportion of the variance in fluid administration explained by potential predictors. RESULTS: 734 patients had 24-hour fluids available: 387 patients had simple infection, 339 sepsis, eight septic shock. Mean total 24-hour fluid volumes were 3656 mL (standard deviation [SD]:1675), 3762 mL (SD: 1839), and 6080 mL (SD: 3978) for the groups, respectively. Fluid volumes varied markedly. Increasing age (mean difference [MD]: 60-79 years: -470 mL [95% CI: -789, -150], +80 years; -974 mL [95% CI: -1307, -640]), do-not-resuscitate orders (MD: -466 mL [95% CI: -797, -135]), and preexisting atrial fibrillation (MD: -367 mL [95% CI: -661, -72) were associated with less fluid. Systolic blood pressure < 100 mmHg (MD: 1182 mL [95% CI: 820, 1543]), mean arterial pressure < 65 mmHg (MD: 1317 mL [95% CI: 770, 1864]), lactate ≥ 2 mmol/L (MD: 655 mL [95% CI: 306, 1005]), heart rate > 120 min (MD: 566 [95% CI: 169, 962]), low (MD: 1963 mL [95% CI: 813, 3112]) and high temperature (MD: 489 mL [95% CI: 234, 742]), SOFA score > 5 (MD: 1005 mL [95% CI: 501, 510]), and new-onset atrial fibrillation (MD: 498 mL [95% CI: 30, 965]) were associated with more fluid. Clinical variables explained 37% of fluid variation among patients. CONCLUSIONS: Patients with simple infection and sepsis received equal fluid volumes. Fluid volumes varied markedly, a variation that was partly explained by clinical characteristics.

Functional decline in emergency department patients with dyspnea: a register-based cohort.

BACKGROUND: Functional decline is associated with frequent hospital admissions and elevated risk of death. Presumably, patients acutely admitted to hospital with dyspnea have a high risk of functional decline. OBJECTIVE: The aim of this study was to describe patient characteristics, hospital trajectory and use of physiotherapy services by dyspneic patients in an emergency department. The study also wanted to compare readmission and death among patients with and without a functional decline and to identify predictors of functional decline. METHODS: Data originated from a historic cohort of patients admitted to a Danish Emergency Department using prospectively collected electronic patient record data from a Business Intelligence Registry of the Central Denmark Region. The study included adult patients who were treated at the emergency department (ED) for dyspnea in 2015. The main outcome measures were readmission, death and functional decline. RESULTS: In total, 2048 dyspneic emergency treatments were registered. Within 30 days after discharge, 20% was readmitted and 3.9% had died. Patients with functional decline had a higher rate of 30-day readmission (31.2% vs. 19.1%, P < 0.001) and mortality (9.3% vs. 3.6%, P = 0.009) as well as mortality within 1 year (36.1% vs. 13.4%, P < 0.001). Predictors of functional decline were age ≥60 years and hospital stay ≥6 days. CONCLUSION: Patients suffering from acute dyspnea are seen at the ED at all hours. In total, one in five patients were readmitted and 3.9% died within 30 days. Patients with a functional decline at discharge seem to be particularly vulnerable.

Effect of Intravenous or Intraosseous Calcium vs Saline on Return of Spontaneous Circulation in Adults With Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial.

Importance: It is unclear whether administration of calcium has a beneficial effect in patients with cardiac arrest. Objective: To determine whether administration of calcium during out-of-hospital cardiac arrest improves return of spontaneous circulation in adults. Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial included 397 adult patients with out-of-hospital cardiac arrest and was conducted in the Central Denmark Region between January 20, 2020, and April 15, 2021. The last 90-day follow-up was on July 15, 2021. Interventions: The intervention consisted of up to 2 intravenous or intraosseous doses with 5 mmol of calcium chloride (n = 197) or saline (n = 200). The first dose was administered immediately after the first dose of epinephrine. Main Outcomes and Measures: The primary outcome was sustained return of spontaneous circulation. The secondary outcomes included survival and a favorable neurological outcome (modified Rankin Scale score of 0-3) at 30 days and 90 days. Results: Based on a planned interim analysis of 383 patients, the steering committee stopped the trial early due to concerns about harm in the calcium group. Of 397 adult patients randomized, 391 were included in the analyses (193 in the calcium group and 198 in the saline group; mean age, 68 [SD, 14] years; 114 [29%] were female). There was no loss to follow-up. There were 37 patients (19%) in the calcium group who had sustained return of spontaneous circulation compared with 53 patients (27%) in the saline group (risk ratio, 0.72 [95% CI, 0.49 to 1.03]; risk difference, -7.6% [95% CI, -16% to 0.8%]; P = .09). At 30 days, 10 patients (5.2%) in the calcium group and 18 patients (9.1%) in the saline group were alive (risk ratio, 0.57 [95% CI, 0.27 to 1.18]; risk difference, -3.9% [95% CI, -9.4% to 1.3%]; P = .17). A favorable neurological outcome at 30 days was observed in 7 patients (3.6%) in the calcium group and in 15 patients (7.6%) in the saline group (risk ratio, 0.48 [95% CI, 0.20 to 1.12]; risk difference, -4.0% [95% CI, -8.9% to 0.7%]; P = .12). Among the patients with calcium values measured who had return of spontaneous circulation, 26 (74%) in the calcium group and 1 (2%) in the saline group had hypercalcemia. Conclusions and Relevance: Among adults with out-of-hospital cardiac arrest, treatment with intravenous or intraosseous calcium compared with saline did not significantly improve sustained return of spontaneous circulation. These results do not support the administration of calcium during out-of-hospital cardiac arrest in adults. Trial Registration: ClinicalTrials.gov Identifier: NCT04153435.