Balanced Multi-Electrolyte Solution Versus Saline Trial for Diabetic KetoAcidosis

The goal of this blinded, cluster cross-over, randomised controlled trial is to determine whether fluid therapy with Plasma-Lyte® 148 increases the number of days alive and days out of hospital to day-28 compared to 0.9% sodium chloride ('0.9% saline') in critically ill patients presenting to the Emergency Department (ED) and deemed to require admission to a critical care area (ICU, HDU) with moderate to severe diabetic ketoacidosis (DKA).

DKA is a life-threatening complication of diabetes mellitus, described in patients with both type-1 diabetes, and type-2 diabetes(1). Data from the Australian Institute of Health and Welfare suggest that between 2009-10 to 2014-15, there has been a 21% increase in the hospitalisation amongst young people with DKA(2). An interrogation of the Australian and New Zealand Intensive Care Society (ANZICS) Centre for Outcomes Research (CORE) database revealed that the incidence of ICU admission of patients with DKA in Australia and New Zealand increased 5-fold between 2000 and 2013 (0.97/100000, 95%CI 0.84 to1.10) in 2000 to (5.3/100000, 95%CI 4.98to 5.53, (P\<0.0001)(3). Increasing incidences were observed predominantly in rural and metropolitan hospitals (Figure 1), about 88% of the admissions to the ICU were from the ED. The median (IQR) ICU and hospital length of stay were 1.8 (1-2.8) and 4 (2.6-7.4) days respectively. Recent data from the ANZICS-CORE database confirmed the persistent high admission rate of severe DKA to Australian ICUs - 2849 and 2862 admissions in 2019 and 2020. A major review of DKA management protocols in 2017 concluded that there are major deficiencies in evidence for optimal management of DKA(33). Current practice is guided by weak evidence and consensus opinion. Studies comparing Plasma-Lyte® 148 vs. 0.9% saline in DKA demonstrate a trend towards a more rapid resolution of acidosis, equivalent glucose control and stable ketones with Plasma-Lyte® 148. In addition, there are trends towards reduced length of ICU and hospital stay with the use of Plasma-Lyte® 148. Given the clinical uncertainty and substantial variability in practice. there is a scientific, clinical and health economic imperative to conduct a high-fidelity study to provide definitive evidence to inform clinicians regarding the choice of resuscitation fluids for patients with DKA. BEST-DKA will address this critical knowledge gap. BEST-DKA is a multi-centre, blinded, cluster-crossover trial conducted in 20 Australian hospitals, consisting of two 12-month intervention periods with a one-month inter-period gap. Each hospital is a single cluster, with all patients admitted with DKA to that hospital's ED during the intervention periods will potentially be eligible for inclusion in the trial. After the first 12-month intervention period during which recruited patients will receive either Plasma-Lyte® 148 or 0.9% saline, there will be a one-month inter-period gap during which patients will not be recruited into the trial. Following this each critical care area will change to using the fluid to which they were not assigned for the first period (Figure 4). All included patients will receive blinded fluids (Plasma-Lyte® 148 or 0.9% saline) as part of their DKA therapy depending on the fluid assigned to the site for the relevant intervention period. Both study fluids are manufactured by Baxter Healthcare Pty Ltd (Old Toongabbie, NSW) and will be labelled, packed and d Покажи пълното описание...

Inclusion Criteria: * Patients in the ED with a primary diagnosis of moderate to severe DKA for whom both saline and Plasma-Lyte® 148 are considered appropriate fluids * Blood glucose level \> 14mmol/L * pH \< 7.25 * Serum bicarbonate \<15 mmol/L * Elevated anion gap \> 12mEq/L * Ketones positive on finger prick measurements * In the judgement of the treating clinician critical care area admission is required Exclusion Criteria: * Age less than 18 years * Patients who have received more than 2000ml of non study fluid prior to study enrolment * Serum Na \> 155 or \<120 mmol/L * Contraindication to either study fluid e.g. previous allergic reaction to Plasma-Lyte® 148 * Patients with hyperosmotic hyperglycaemic non-ketotic syndrome * Other clinical conditions that preclude large volumes of fluid resuscitation * Previous inclusion in BEST-DKA trial