Co-administration of iloprost and eptifibatide in septic shock (CO-ILEPSS):A randomised, controlled, double-blind investigator-initiated trial investigating safety and efficacyA randomised, controlled, double-blind investigator-initiated trial investigating safety and efficacy

Publisher's version (útgefin grein). The CO-ILEPSS trial was approved by the ethics committee in The Capital Region of Denmark with protocol number: H-3-2014-087.Background: Part of the pathophysiology in septic shock is a progressive activation of the endothelium and platelets leading to widespread microvascular injury with capillary leakage, microthrombi and consumption coagulopathy. Modulating the inflammatory response of endothelium and thrombocytes might attenuate this vicious cycle and improve outcome. Method: The CO-ILEPSS trial was a randomised, placebo-controlled, double-blind, pilot trial. Patients admitted to the intensive care unit with septic shock were randomised and allocated in a 2:1 ratio to active treatment with dual therapy of iloprost 1 ng/kg/min and eptifibatide 0.5 μg/kg/min for 48 h or placebo. The primary outcomes were changes in biomarkers reflecting endothelial activation and disruption, platelet consumption and fibrinolysis. We compared groups with mixed models, post hoc Wilcoxon signed-rank test and Mann-Whitney U test. Results: We included 24 patients of which 18 (12 active, 6 placebo) completed the full 7-day trial period and were included in the per-protocol analyses of the primary outcomes. Direct comparison between groups showed no differences in the primary outcomes. Analyses of within-group delta values revealed that biomarkers of endothelial activation and disruption changed differently between groups with increasing levels of thrombomodulin (p = 0.03) and nucleosomes (p = 0.02) in the placebo group and decreasing levels of sE-Selectin (p = 0.007) and sVEGFR1 (p = 0.005) in the active treatment group. Platelet count decreased the first 48 h in the placebo group (p = 0.049) and increased from baseline to day 7 in the active treatment group (p = 0.023). Levels of fibrin monomers declined in the active treatment group within the first 48 h (p = 0.048) and onwards (p = 0.03). Furthermore, there was a significant reduction in SOFA score from 48 h (p = 0.024) and onwards in the active treatment group. Intention-to-treat analyses of all included patients showed no differences in serious adverse events including bleeding, use of blood products or mortality. Conclusion: Our results could indicate benefit from the experimental treatment with reduced endothelial injury, reduced platelet consumption and ensuing reduction in fibrinolytic biomarkers along with improved SOFA score. The results of the CO-ILEPSS trial are exploratory and hypothesis generating and warrant further investigation in a large-scale trial. Trial registration: Clinicaltrials.com, NCT02204852 (July 30, 2014); EudraCT no. 2014-002440-41Funding was provided by Professor Per I. Johansson, Senior Physician, DMSC, MPA, The Capital Region Blood Bank, and Rigshospitalet. We would like to acknowledge all the nurses and doctors at the intensive care unit and the nurses at the post-operative care unit at NOH for the work associated with the trial treatment including randomisation, preparation of trial medication and blood sampling.Peer Reviewe

Predicting recovery from acute kidney injury in critically ill patients: development and validation of a prediction model.

To access publisher's full text version of this article click on the hyperlink belowIntensive care unit (ICU) patients with acute kidney injury (AKI) who recover kidney function within 28 days experience less severe chronic kidney impairment and have increased long term survival. The aims of this study were to develop and validate a risk prediction model to identify these patients.Observational study with development and validation of a risk prediction model.Nine academic ICUs in Denmark.Development cohort of critically ill patients with AKI at ICU admission from the Procalcitonin and Survival Study cohort (n = 568), validation cohort of adult patients with AKI admitted to two university hospitals in Denmark in 2012-13 (n = 766).None.Recovery of kidney function was defined as living for 5 consecutive days with no renal replacement therapy and with creatinine plasma levels below 1.5-fold the levels determined before ICU admission.A total of 266 patients (46.8%) recovered prior kidney function in the development cohort, and 453 patients (59.1%) in the validation cohort. The prediction model included elevation in creatinine, urinary output, sex and age. In the validation cohort, 69 patients (9.0%) had a predicted chance of recovery 75%. The area under the receiver operations curves for predicting recovery in the validation cohort was 73.1%.We constructed and validated a simple model that can predict the chance of recovery from AKI in critically ill patients.Danish National Research Foundation Centre of Excellence for Health, Immunity and Infections (CHIP) Centre of Excellence for Personalised Medicine of Infectious Complications in Immune Deficiency (PERSIMUNE) Lundbeck Foundation Research Foundation for the Capital Region of Denmark Toyota Foundation Brahms Diagnostica Harboe Foundation AP Moller Foundation Fru Olga Brydes Nielsens Foundation Research Board at NordsjIlands Hospita

Predicting recovery from acute kidney injury in critically ill patients: development and validation of a prediction model.

To access publisher's full text version of this article click on the hyperlink belowIntensive care unit (ICU) patients with acute kidney injury (AKI) who recover kidney function within 28 days experience less severe chronic kidney impairment and have increased long term survival. The aims of this study were to develop and validate a risk prediction model to identify these patients.Observational study with development and validation of a risk prediction model.Nine academic ICUs in Denmark.Development cohort of critically ill patients with AKI at ICU admission from the Procalcitonin and Survival Study cohort (n = 568), validation cohort of adult patients with AKI admitted to two university hospitals in Denmark in 2012-13 (n = 766).None.Recovery of kidney function was defined as living for 5 consecutive days with no renal replacement therapy and with creatinine plasma levels below 1.5-fold the levels determined before ICU admission.A total of 266 patients (46.8%) recovered prior kidney function in the development cohort, and 453 patients (59.1%) in the validation cohort. The prediction model included elevation in creatinine, urinary output, sex and age. In the validation cohort, 69 patients (9.0%) had a predicted chance of recovery 75%. The area under the receiver operations curves for predicting recovery in the validation cohort was 73.1%.We constructed and validated a simple model that can predict the chance of recovery from AKI in critically ill patients.Danish National Research Foundation Centre of Excellence for Health, Immunity and Infections (CHIP) Centre of Excellence for Personalised Medicine of Infectious Complications in Immune Deficiency (PERSIMUNE) Lundbeck Foundation Research Foundation for the Capital Region of Denmark Toyota Foundation Brahms Diagnostica Harboe Foundation AP Moller Foundation Fru Olga Brydes Nielsens Foundation Research Board at NordsjIlands Hospita

Effect of intermediate care on mortality following emergency abdominal surgery. The InCare trial: study protocol, rationale and feasibility of a randomised multicentre trial

<p>Abstract</p> <p>Background</p> <p>Emergency abdominal surgery carries a 15% to 20% short-term mortality rate. Postoperative medical complications are strongly associated with increased mortality. Recent research suggests that timely recognition and effective management of complications may reduce mortality. The aim of the present trial is to evaluate the effect of postoperative intermediate care following emergency major abdominal surgery in high-risk patients.</p> <p>Methods and design</p> <p>The InCare trial is a randomised, parallel-group, non-blinded clinical trial with 1:1 allocation. Patients undergoing emergency laparotomy or laparoscopic surgery with a perioperative Acute Physiology and Chronic Health Evaluation II score of 10 or above, who are ready to be transferred to the surgical ward within 24 h of surgery are allocated to either intermediate care for 48 h, or surgical ward care. The primary outcome measure is all-cause 30-day mortality. We aim to enrol 400 patients in seven Danish hospitals. The sample size allows us to detect or refute a 34% relative risk reduction of mortality with 80% power.</p> <p>Discussion</p> <p>This trial evaluates the benefits and possible harm of intermediate care. The results may potentially influence the survival of many high-risk surgical patients. As a pioneer trial in the area, it will provide important data on the feasibility of future large-scale randomised clinical trials evaluating different levels of postoperative care.</p> <p>Trial registration</p> <p>Clinicaltrials.gov identifier: NCT01209663</p