Hypernatraemia, defined as a plasma sodium concentration >145 mmol/L, is a frequent complication in critically ill patients treated in the intensive care unit (ICU) (= ICU-acquired hypernatraemia), with reported prevalence ranging from 4% to 26%. Hypernatraemia adversely affects various physiological functions and is associated with delirium, prolonged length of stay and increased ICU and post-discharge mortality. The sodium load from intravenous drug diluents significantly contributes to ICU-acquired hypernatraemia, with drug infusions comprising about 30% of the daily fluid volume of an average ICU patient. This study aims to investigate if using glucose 5% solution as the default drug diluent, instead of sodium chloride 0.9%, can reduce the prevalence of ICU-acquired hypernatraemia and improve patient outcomes.

To test the effectiveness of glucose 5% solution as the default drug diluent, we will conduct a multicentre, pragmatic, embedded, open-label, stepped-wedge, cluster-randomised trial. The study will include twelve clusters (ICUs and one intermediate care unit) across six hospitals in Germany, with a projected total sample size of 4485 patients. In line with the stepped-wedge cluster-randomised design, one ICU will transition every 4 weeks, in a randomised sequence, from using sodium chloride 0.9% as the default drug diluent to glucose 5%.

The primary endpoint is the prevalence of hypernatraemia >150 mmol/L through day 28. The number of days alive and free of the ICU through day 28 will be tested hierarchically as a key secondary endpoint. Other exploratory endpoints include ICU mortality, ICU-free days, hospital-free days and other clinical outcomes. The primary endpoint will be analysed using a logistic mixed-effects model.

The trial was approved by the Charité—Universitätsmedizin Berlin Ethics Board and by the ethics board of each enrolled hospital. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences.

The trial protocol was registered with the German Clinical Trials Register on 21 June 2024 prior to initiation of patient enrolment (DRKS00033397).

The coronary artery calcium (CAC) scan serves as a crucial tool in assessing the risk of coronary atherosclerosis in patients with hyperlipidaemia, particularly when there is ambiguity surrounding pharmacotherapy decisions. In addition to CAC, advanced glycation end products (AGEs), glycated proteins and lipids involved in ageing are emerging as markers for atherosclerosis. However, the relationship between AGEs score and CAC scores has not been evaluated to date. Our primary objective is to evaluate abnormal CAC scores in patients with low and borderline ASCVD risk and normal low-density lipoprotein cholesterol (LDL-C) levels ≤100 mg/dL. The secondary objective is to explore potential associations between CAC and AGEs scores.

We will retrospectively review health records of adult patients seen at the General Internal Medicine Executive Health Program (Mayo Clinic; Rochester, Minnesota) between 1 September 2023 and 31 March 2024, where all patients were offered the option of a baseline CAC scan. For our primary aim, we will determine the percentage of patients with low and borderline 10-year Atherosclerotic Cardiovascular Disease (ASCVD) risk, not receiving pharmacotherapy for hyperlipidaemia, who have LDL-C levels ≤100 mg/dL and have an abnormal CAC score. For our secondary aim, we will examine potential associations between CAC and AGEs scores.

This study was determined to be exempt from institutional review board approval (ID 24–0 03 921; 45 CFR 46.104d, category/subcategory 4(iii)) at the Mayo Clinic, Rochester. The findings of this study will be published in a peer-reviewed journal.