Stimulants for disorders of consciousness in the intensive care unit: a randomized, placebo-controlled trial.

In the intensive care unit (ICU), management of unresponsive patients with brain injury focuses on preventing secondary brain damage. Therapeutic strategies that directly promote the recovery of consciousness are urgently needed. In an investigator-initiated, randomized, placebo-controlled, double-blind, cross-over trial, we studied the effects of apomorphine and methylphenidate in ICU patients with acute disorders of consciousness (DoC).

Clarithromycin Versus Azithromycin for Community-Acquired Pneumonia and the Risk of Major Adverse Cardiovascular Events: A Multicentre Cohort Study Using Data From Canada and Denmark.

Background: Studies suggest that clarithromycin is associated with an increased risk of major adverse cardiovascular events (MACE) among adults with coronary artery disease. However, data comparing clarithromycin to other macrolides, such as azithromycin, in a broader population are lacking.

Methods: A multicenter study was conducted in 33 hospitals in Ontario, Canada, and Copenhagen, Denmark, using the Target Trial framework.

Nitric oxide biomarkers and circulatory failure in critical illness: A cohort study.

Purpose: Arterial hypotension is frequently observed in critically ill patients. Nitric oxide (NO) is pivotal in vasodilation. We investigated the associations between NO-biomarkers (asymmetrical dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), arginine, and homoarginine) and treatment with norepinephrine and plasma lactate on ICU days 1-3.

INCEPT: The Intensive Care Platform Trial-Design and protocol.

Background: Adult intensive care unit (ICU) patients receive many interventions, but few are supported by high-certainty evidence. Randomised clinical trials (RCTs) are essential for trustworthy comparisons of intervention effects, but conventional RCTs are costly, cumbersome, inflexible, and often turn out inconclusive. Adaptive platform trials may mitigate these issues and have higher probabilities of obtaining conclusive results faster and at lower costs per participant.

Intraoperative opioid administrations, rescue doses in the post-anaesthesia care unit and clinician-perceived factors for dose adjustments in adults: A Danish nationwide survey.

Background: The impact of demographic- and surgical factors on individual perioperative opioid requirements is not fully understood. Anaesthesia personnel adjust opioid administrations based on their own clinical experience, expert opinions and local guidelines. This survey aimed to assess the current practice of anaesthesia personnel regarding intraoperative opioid treatment for postoperative analgesia and rescue opioid dosing strategies in the post-anaesthesia care unit in Denmark.

Changes in nitric oxide inhibitors and mortality in critically ill patients: a cohort study.

Background: Optimal balance between macro- and microcirculation in critically ill patients is crucial for ensuring optimal organ perfusion. Nitric oxide (NO) is a regulator of vascular hemostasis and tone. The availability of NO is controlled by asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and the availability of the NO substrates arginine and homoarginine.

Personalized mechanical ventilation guided by ultrasound in patients with acute respiratory distress syndrome (PEGASUS): study protocol for an international randomized clinical trial.

Background: Acute respiratory distress syndrome (ARDS) is a frequent cause of hypoxemic respiratory failure with a mortality rate of approximately 30%. Identifying ARDS subphenotypes based on "focal" or "non-focal" lung morphology has the potential to better target mechanical ventilation strategies of individual patients. However, classifying morphology through chest radiography or computed tomography is either inaccurate or impractical.

Existing Data Sources in Clinical Epidemiology: Database of Community Acquired Infections Requiring Hospital Referral in Eastern Denmark (DCAIED) 2018-2021.

Infectious diseases are major health care challenges globally and a prevalent cause of admission to emergency departments. Epidemiologic characteristics and outcomes based on population level data are limited. The Database of Community Acquired Infections in Eastern Denmark (DCAIED) 2018-2021 was established with the aim to explore and estimate the population characteristics, and outcomes of patients suffering from community acquired infections at the emergency departments in the Capital Region and the Zealand Region of Denmark using data from electronic medical records.

Bioimpedance and Duration of Organ Dysfunction in Septic Shock-A Prospective Observational Study.

Bioimpedance may be a useful tool to guide fluid treatment and avoid organ dysfunction related to fluid overload. We examined the correlation between bioimpedance and organ dysfunction in patients with septic shock. Prospective observational study of adult intensive care unit patients fulfilling the sepsis-3 criteria.

Mild induced hypothermia and coagulation and platelet function in patients with septic shock: Secondary outcome of a randomized trial.

Coagulation abnormalities and microthrombi contribute to septic shock, but the impact of body temperature regulation on coagulation in patients with sepsis is unknown. We tested the hypothesis that mild induced hypothermia reduces coagulation and platelet aggregation in patients with septic shock. Secondary analysis of randomized controlled trial.

Novel subgroups in acute respiratory failure based on the trajectories of three endotheliopathy biomarkers: A cohort study.

Baseline levels of endotheliopathy are associated with worse respiratory outcomes and mortality in undifferentiated acute respiratory failure (ARF), but knowledge is lacking on the development of endotheliopathy over time in ARF. We, therefore, aimed to evaluate the prognostic significance of trajectories of endotheliopathy during the first days of ARF. We performed a secondary, exploratory analysis of a single-center prospective cohort including 459 patients requiring mechanical ventilation.

Goal-directed fluid removal with furosemide versus placebo in intensive care patients with fluid overload: A randomised, blinded trial (GODIF trial-First version).

Background: Salt and water accumulation leading to fluid overload is associated with increased mortality in intensive care unit (ICU) patients, but diuretics' effects on patient outcomes are uncertain. In this first version of the GODIF trial, we aimed to assess the effects of goal-directed fluid removal with furosemide versus placebo in adult ICU patients with fluid overload.

Methods: We conducted a multicentre, randomised, stratified, parallel-group, blinded, placebo-controlled trial in clinically stable, adult ICU patients with at least 5% fluid overload.

Bioimpedance as a measure of fluids in patients with septic shock. A prospective observational study.

Background: Septic shock is often treated with aggressive fluid resuscitation leading to profound fluid overload. The assessment of fluid status relies on suboptimal measures making treatment difficult. Bioelectrical impedance analysis is an alternative but the validity is unclear.

Early Biomarker-Guided Prediction of Bloodstream Infection in Critically Ill Patients: C-Reactive Protein, Procalcitonin, and Leukocytes.

Background: Bloodstream infections (BSIs) often lead to critical illness and death. The primary aim of this study was to determine the diagnostic accuracy of the biomarkers C-reactive protein (CRP), procalcitonin (PCT), and leukocyte count for the diagnosis of BSI in critically ill patients.

Methods: This was a nested case-control study based on the Procalcitonin And Survival Study (PASS) trial (n = 1200).

Goal directed fluid removal with furosemide versus placebo in intensive care patients with fluid overload: A trial protocol for a randomised, blinded trial (GODIF trial).

Background: Fluid overload is a risk factor for mortality in intensive care unit (ICU) patients. Administration of loop diuretics is the predominant treatment of fluid overload, but evidence for its benefit is very uncertain when assessed in a systematic review of randomised clinical trials. The GODIF trial will assess the benefits and harms of goal directed fluid removal with furosemide versus placebo in ICU patients with fluid overload.

Loop diuretics in adult intensive care patients with fluid overload: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis.

Background: Fluid overload is a risk factor for organ dysfunction and death in intensive care unit (ICU) patients, but no guidelines exist for its management. We systematically reviewed benefits and harms of a single loop diuretic, the predominant treatment used for fluid overload in these patients.

Methods: We conducted a systematic review with meta-analysis and Trial Sequential Analysis (TSA) of a single loop diuretic vs.

Endotheliopathy is associated with slower liberation from mechanical ventilation: a cohort study.

Background: Endotheliopathy is suggested as pivotal pathophysiology of sepsis and trauma-associated organ failure, but its role in acute respiratory failure is not yet determined. We investigated if endotheliopathy biomarkers at ICU admission are associated with illness severity and clinical outcomes in patients with acute respiratory failure requiring mechanical ventilation.

Methods: We conducted a prospective single-center cohort study including 459 mechanically ventilated adults at ICU admission.

Bioimpedance as a measure of fluid status in critically ill patients: A systematic review.

Objective: Precise measurements of fluid status lack valid methods. Bioimpedance is an attractive diagnostic tool because it is noninvasive, quick, and relatively cheap. This systematic review aims to assess the existing evidence of bioimpedance as an accurate measure of fluid status in critically ill patients.

ABO blood types and sepsis mortality.

Background: We aimed to determine if the ABO blood types carry different risks of 30-day mortality, acute kidney injury (AKI), and endothelial damage in critically ill patients with sepsis. This was a retrospective cohort study of three independent cohorts of critically ill patients from the United States and Scandinavia consisting of adults with septic shock. We compared the 30-day mortality across the blood types within each cohort and pooled the results in a meta-analysis.

Biomarkers of Acute Lung Injury The Individualized Approach: for Phenotyping, Risk Stratification and Treatment Surveillance.

Do we need biomarkers of lung damage and infection: For what purpose and how should they be used properly? Biomarkers of lung damage can be used for diagnosis, risk stratification/prediction, treatment surveillance and adjustment of targeted therapy. Additionally, novel "omics" methods may offer a completely different and effective way of improving the understanding of pathogenesis of lung damage and a way to develop new candidate lung damage biomarkers. In the current review, we give an overview within the field of acute lung damage of (i) disease mechanism biomarkers, (ii) of "ready to use" evidence-based biomarker-guided lung infection management, (iii) of novel strategies of inflammatory phenotyping and how this can be used to tailor corticosteroid treatment, (iv) a future perspective of where "omics" technologies and mindsets may become increasingly important in developing new strategies for treatment and for understanding the development of acute lung damage.

Biomarker-assisted identification of sepsis-related acute liver impairment: a frequent and deadly condition in critically ill patients.

Background The prognostic impact of mild/moderate liver impairment among critically ill patients is not known. We aimed to determine whether acute liver impairment, as measured by several biomarkers, (i) is frequent, (ii) influences prognosis and (iii) to determine whether such an effect is specific for infected critically ill patients. Methods A biomarker and clinical cohort study based on a randomized controlled trial.

Mortality in critical illness: The impact of asymmetric dimethylarginine on survival-A systematic review and meta-analysis.

Introduction: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of the nitric oxide system, may be associated with an adverse outcome in critically ill patients. The aim of the present review was to clarify if plasma ADMA and the arginine-to-ADMA ratio (arginine/ADMA) are associated with mortality in critically ill patients.

Methods: We searched PubMed, EMBASE and Web of Science/BIOSIS Previews on 31 July 2017 for studies published after 2000 including critically ill paediatric or adult patients and evaluating any association between all-cause mortality and admission ADMA and/or arginine/ADMA ratio.

Acute Lung Injury in Critically Ill Patients: Actin-Scavenger Gelsolin Signals Prolonged Respiratory Failure.

Background: Gelsolin is an actin-scavenger controlling the tissue damage from actin in the blood. Gelsolin levels in circulation drops when tissue damage and corresponding actin release is pronounced due to catabolic conditions. The purpose of this study was to determine if low plasma gelsolin independently predicts a reduced chance of weaning from ventilator-demanding respiratory failure in critically ill patients within 28 days from admission.