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 distributed by the company directly to the study sites in
periodic shipments. Study fluid will be coded and labelled in compliance with applicable
regulations, and in a manner that protects the blinding.
All clinicians involved in the prescription of blinded study treatment must read Product
Information for both Plasma-Lyte® 148 and 0.9% saline which provide detailed information
about the composition, indications, side effects, suggested dosage and contraindications of
the study treatments.
The volume and rate of blinded study fluid administered will be guided by the standard
clinical endpoints determined by the treating clinician. Study treatments will be started
following study enrolment and continue until discharge from a critical care area or for a
maximum of 72 hrs, whichever is earlier. If patients are re-admitted to the critical care
area within 72 hours with a relapse of ketoacidosis, the clinician may use open label fluids
for the managements of ketoacidosis. within 72 hours they will continue to receive blinded
treatment fluid. Glucose containing solutions can be added in as required for blood glucose
or ketosis management. The use of bicarbonate therapy and the need for potassium, phosphate
and magnesium supplementation will be at the discretion of the treating clinician and data on
its use will be collected.
The primary outcome will be evaluated at day-28 and patients contacted via telephone.
End-user/consumer representatives have been involved in all components of the research
program including protocol development, choice of primary outcome, funding applications, and
membership of the management committee. End-user/consumer representatives will continue to be
involved in the conduct of the study and play a key role in the dissemination of results.
Currently, membership of the study management committee includes the President of the
advocacy group, Diabetes Australia; Director of Australian Centre for Accelerating Diabetes
Innovations (ACADI); and a consumer who lives with diabetes.
This study aligns with the Medical Research Future Fund (Australia Government grant) funded
ACADI objective to address the acute complications of diabetes including management of DKA.
The study has been endorsed by the Australasian College for Emergency Medicine (ACEM) and a
letter of support from for the study from Diabetes Australia.