Hardenberg Jan-Hendrik Bernhard, Hinz Ricarda Merle, Pigorsch Mareen, Uhrig Alexander, Müller-Redetzky Holger, Nee Jens, Schroeder Tim, Witzenrath Martin, Trost Ulrike, Zickler Daniel, Hunsicker Oliver, Weiss Bjoern, Weber-Carstens Steffen, Spies Claudia, Tampe Björn, Borgstedt Rainer, Abu-Tair Mariam, Zarbock Alexander, Strauß Christian, Schenk Heiko, Hildebrand Uta, von Wedel Dario, Balzer Felix, Eckardt Kai-Uwe, Enghard Philipp
Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany
Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany.
BMJ Open. 2025 Jun 5;15(6):e097361. doi: 10.1136/bmjopen-2024-097361.
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).
高钠血症定义为血浆钠浓度>145 mmol/L，是重症监护病房（ICU）接受治疗的危重症患者常见的并发症（即ICU获得性高钠血症），报道的患病率在4%至26%之间。高钠血症对各种生理功能产生不利影响，并与谵妄、住院时间延长以及ICU死亡率和出院后死亡率增加相关。静脉药物稀释剂中的钠负荷是ICU获得性高钠血症的重要原因，药物输注量约占ICU平均患者每日液体量的30%。本研究旨在调查使用5%葡萄糖溶液而非0.9%氯化钠溶液作为默认药物稀释剂是否能降低ICU获得性高钠血症的患病率并改善患者预后。
为测试5%葡萄糖溶液作为默认药物稀释剂的有效性，我们将进行一项多中心、实用、嵌入式、开放标签、阶梯式楔形整群随机试验。该研究将纳入德国六家医院的12个整群（ICU和一个中级护理单元），预计总样本量为4485例患者。按照阶梯式楔形整群随机设计，一个ICU每4周将按照随机顺序从使用0.9%氯化钠溶液作为默认药物稀释剂转换为使用5%葡萄糖溶液。主要终点是至第28天>150 mmol/L高钠血症的患病率。至第28天存活且未入住ICU的天数将作为关键次要终点进行分层检验。其他探索性终点包括ICU死亡率、无ICU天数、无住院天数及其他临床结局。主要终点将使用逻辑混合效应模型进行分析。
该试验已获得柏林夏里特大学医学伦理委员会以及各参与医院伦理委员会的批准。研究结果将提交至同行评审期刊发表，并在一个或多个科学会议上展示。
在患者入组前，试验方案于2024年6月21日在德国临床试验注册中心注册（DRKS00033至397）。
