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)

BACKGROUNDFluid 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.METHODSAn investigator-initiated, international, randomised, stratified, blinded, parallel-group trial allocating 1000 adult ICU patients with fluid overload to infusion of furosemide versus placebo. The goal is to achieve a neutral fluid balance. The primary outcome is days alive and out of hospital 90 days after randomisation. Secondary outcomes are all-cause mortality at day 90 and 1-year after randomisation; days alive at day 90 without life support; number of participants with one or more serious adverse events or reactions; health-related quality of life; and cognitive function at 1-year follow-up. A sample size of 1000 participants is required to detect an improvement of 8% in days alive and out of hospital 90 days after randomisation with a power of 90% and a risk of type 1 error of 5%. The conclusion of the trial will be based on the point estimate and 95% confidence interval; dichotomisation will not be used.\ngov identifier: NCT04180397.PERSPECTIVEThe GODIF trial will provide important evidence of possible benefits and harms of fluid removal with furosemide in adult ICU patients with fluid overload. This article is protected by copyright. All rights reserved.</p

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

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

Jon Gitz Holler,1 Jens Ulrik Stæhr Jensen,2– 4 Frederik Neess Engsig,5 Morten H Bestle,3,6 Birgitte Lindegaard,1,3,7 Jens Henning Rasmussen,8 Henning Bundgaard,3,9 Finn Erland Nielsen,8 Kasper Karmark Iversen,3,10 Jesper Juul Larsen,11 Barbara Juliane Holzknecht,3,12 Jonas Boel,12,13 Pradeesh Sivapalan,2,3 Theis Skovsgaard Itenov3,14 1Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital - North Zealand, Hilleroed, Denmark; 2Department of Medicine, Section of Respiratory Medicine, Copenhagen University Hospital - Herlev and Gentofte Hospital, Copenhagen, Denmark; 3Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 4PERSIMUNE & CHIP: Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; 5Department of Emergency Medicine, Copenhagen University Hospital – Amager and Hvidovre, Copenhagen, Denmark; 6Department of Anesthesia and Intensive Care Medicine, Copenhagen University Hospital – North Zealand, Hilleroed, Denmark; 7Centre for Physical Activity, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; 8Department of Emergency Medicine, Copenhagen University Hospital – Bispebjerg and Frederiksberg, Copenhagen, Denmark; 9Department of Cardiology, The Capital Region’s Unit of Inherited Cardiac Diseases, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; 10Department of Emergency Medicine, Copenhagen University Hospital – Herlev and Gentofte, Copenhagen, Denmark; 11Department of Emergency Medicine, Copenhagen University Hospital - North Zealand, Hilleroed, Denmark; 12Department of Clinical Microbiology, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark; 13Copenhagen University Hospital - Capital Region Pharmacy, Copenhagen, Denmark; 14Department of Anesthesiology and Intensive Care Medicine, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, DenmarkCorrespondence: Jon Gitz Holler, Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital - North Zealand, Copenhagen, Denmark, Tel +45-48292578, Fax +45-48293935, Email [email protected]: 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. Adult patients (≥ 18 years) presenting to the emergency department with suspected or confirmed infection are included in the cohort. Presence of sepsis and organ failure are assessed using modified criteria from the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). During the inclusion period from January 2018 to January 2022, 2,241,652 adult emergency department visits have been registered. Of these, 451,825 were unique encounters of which 60,316 fulfilled criteria of suspected infection and 28,472 fulfilled sepsis criteria and 8,027 were defined as septic shock. The database covers the entire Capital and Zealand Region of Denmark with an uptake area of 2.6 million inhabitants and includes demographic, laboratory and outcome indicators, with complete follow-up. The database is well-suited for epidemiological research for future national and international collaborations.Keywords: emergency department, infectious diseases, sepsis, shock, database, epidemiology, community acquire

The effect of saponins from <it>Ampelozizyphus amazonicus</it> Ducke on the renal Na⁺ pumps’ activities and urinary excretion of natriuretic peptides

<p>Abstract</p> <p>Background</p> <p>In a previous study, we showed that a saponin mixture isolated from the roots of <it>Ampelozizyphus amazonicus</it> Ducke (SAP<it>Aa</it>D) reduces urine excretion in rats that were given an oral loading of 0.9 % NaCl (4 ml/100 g body weight). In the present study, we investigated whether atrial natriuretic peptides (ANP) and renal ATPases play a role in the SAP<it>Aa</it>D- induced antidiuresis in rats.</p> <p>Methods</p> <p>To evaluate the effect of SAP<it>Aa</it>D on furosemide-induced diuresis, Wistar rats (250-300 g) were given an oral loading of physiological solution (0.9 % NaCl, 4 ml/100 g body weight) to impose a uniform water and salt state. The solution containing furosemide (Furo, 13 mg/kg) was given 30 min after rats were orally treated with 50 mg/kg SAP<it>Aa</it>D (<it>SAPAaD + Furo</it>) or 0.5 ml of 0.9 % NaCl (<it>NaCl + Furo</it>). In the <it>SAPAaD + NaCl</it> group, rats were pretreated with SAP<it>Aa</it>D and 30 min later they received the oral loading of physiological solution. Animals were individually housed in metabolic cages, and urine volume was measured every 30 min throughout the experiment (3 h). To investigate the role of ANP and renal Na⁺ pumps on antidiuretic effects promoted by SAP<it>Aa</it>D, rats were given the physiological solution (as above) containing SAP<it>Aa</it>D (50 mg/kg). After 90 min, samples of urine and blood from the last 30 min were collected. Kidneys and atria were also removed after previous anesthesia. ANP was measured by radioimmunoassay (RIA) and renal cortical activities of Na⁺- and (Na⁺,K⁺)-ATPases were calculated from the difference between the [³²P] Pi released in the absence and presence of 1 mM furosemide/2 mM ouabain and in the absence and presence of 1 mM ouabain, respectively.</p> <p>Results</p> <p>It was observed that SAP<it>Aa</it>D inhibited furosemide-induced diuresis (at 90 min: from 10.0 ± 1.0 mL, <it>NaCl + Furo</it> group, n = 5, to 5.9 ± 1.0 mL, <it>SAPAaD + Furo</it> group n = 5, p < 0.05), increased both Na⁺-ATPase (from 25.0 ± 5.9 nmol Pi.mg^-1.min^-1, control, to 52.7 ± 8.9 nmol Pi.mg^-1.min^-1, p < 0.05) and (Na⁺,K⁺)-ATPase (from 47.8 ± 13.3 nmol Pi.mg^-1.min^-1, control, to 79.8 ± 6.9 nmol Pi .mg^-1.min^-1, p < 0.05) activities in the renal cortex. SAP<it>Aa</it>D also lowered urine ANP (from 792 ± 132 pg/mL, control, to 299 ± 88 pg/mL, p < 0.01) and had no effect on plasma or atrial ANP.</p> <p>Conclusion</p> <p>We concluded that the SAP<it>Aa</it>D antidiuretic effect may be due to an increase in the renal activities of Na⁺- and (Na⁺,K⁺)-ATPases and/or a decrease in the renal ANP.</p