The George Institute’s Critical Care team have secured funding to address gaps in evidence that have led to uncertainties around the best choice of treatment in the intensive care setting with great potential to reduce hospital costs as well as deaths and disability. 

The grants are part of the Australian Government’s Medical Research Future Fund Clinical Trials Activity grants round, designed to evaluate effective health interventions that address unmet needs.

Defining the best choice of fluid therapy in severe diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes in which the body produces excess blood acids known as ketones. It occurs when there isn't enough insulin in the body and can be triggered by infection or other illness.

The incidence is rising in Australia, particularly in metropolitan and rural or regional hospitals - approximately 3,000 people with the condition are admitted to Australian ICUs each year, according to data stored at the Australia New Zealand Intensive Care Society registries.

Fluid therapy is a vital component of the treatment of DKA, but which fluid provides the best outcomes is unknown. Saline is widely recommended in national and international guidelines despite a lack of high-quality evidence to support its use. It can lead to complications associated with worse outcomes in critically ill patients.

An alternative fluid, Plasma-Lyte 148 – a balanced salt solution which more closely matches the biochemistry of human blood - has theoretical advantages over saline and is recommended in some DKA guidelines.

Dr Mahesh Ramanan, Intensive Care Specialist at Caboolture Hospital and The Prince Charles Hospital, Queensland, and PhD student at The George Institute, will work with the Critical Care Division at The George Institute and other clinician-researchers around Australia to conduct a clinical trial evaluating whether Plasma-Lyte compared with normal saline increases days alive and out of hospital in patients with DKA.

It is hoped that the results will provide definitive guidance on the best choice of fluid therapy in DKA and reduce healthcare costs by reducing the time patients need to spend in ICU and hospital.

Improving outcomes for younger people with a debilitating form of stroke

A subarachnoid haemorrhage is a devastating type of stroke affecting around 2000 Australians a year, a third of whom will die from the condition with the remainder at risk of permanent disability. Up to 40% of this often young and previously fit population are unable to return to their previous occupation. Despite the impact of this condition, there has been no new treatment shown to improve outcomes for these patients over the last 15 years.

A common complication in this type of stroke is low blood levels of sodium (or hyponatremia) which occurs in up to two thirds of hospitalised patients. Hyponatremia is associated with a twofold increase in duration of hospital and ICU stay in these patients.

Previous work by Dr Jeremy Cohen, Director of the Wesley Hospital Intensive Care Unit and Honorary Professorial Fellow at The George Institute, confirmed that hyponatraemia during ICU admission is also significantly associated with worse levels of disability six months later.

This study will investigate if fludrocortisone, a low cost and well-established corticosteroid that regulates salt and water balance in the body, can prevent this fall in sodium and therefore improve outcomes in these patients. 

It will be the only multi-centre, randomised, double blinded trial involving enough patients with this condition to be able to detect clinically meaningful functional outcomes and is therefore likely to have a substantial impact upon clinical practice.

Three research programs have received Round 4 funding for projects in key priority areas for the Institute: cardiovascular, nephrology, neurology and food policy.

Identifying the most effective integrated method to reduce CVD & CKD risk in diabetes

Receiving an Early-Mid Career Researcher Grant is Dr Min Jun, Renal and Metabolic Program Lead at The George Institute and Scientia Associate Professor at the Faculty of Medicine, UNSW Sydney. The funding will support execution of the REVERSE study - REducing cardioVascular and kidnEy RiSk in people with diabEtes.

For Australians living with diabetes, cardiovascular disease (CVD) and chronic kidney disease (CKD) are the leading causes of disability and death. Integrated care approaches that bring together a multidisciplinary team to improve coordination have been proposed as optimal models to overcome barriers such as lack of care coordination or poor communication between primary and secondary services, but wide variation makes it difficult to determine the most effective strategies, particularly across differing health service areas with varying needs and resources. Previous work has shown guideline-recommended glycaemic and blood pressure targets are not met in 32% and 39% of patients with diabetes respectively, despite the availability of strategies proven to delay and prevent the effects of CVD and CKD in high-risk patients with diabetes.

REVERSE is a large-scale, multicentre, randomised study that aims to fill this evidence gap by designing and assessing the key elements for successful integrated care with a focus on socioeconomically disadvantaged communities and individuals from culturally and linguistically diverse backgrounds. The study will co-create and test a comprehensive suite of interventions managed by an embedded cardiovascular nurse coordinator across health service regions that have a high prevalence of at-risk patients, e.g. Western and South Western Sydney region in NSW. The role will support patient management planning, improve support to general practice, promote lifestyle changes and self-management, and facilitate communication between primary and secondary health services. Ultimately the research aims to determine how effective this multi-faceted approach is in reducing CVD and CKD risk in people living with diabetes.

Using artificial intelligence to support treatment decisions in acute stroke

Senior Research Fellow Dr Xia Wang has secured an Early-Mid Career Researcher Grant for a project examining the potential for artificial intelligence (AI) to provide enhanced treatment recommendations and predictions for outcomes in patients with acute ischaemic stroke (AIS) and intracerebral haemorrhage (ICH).

The treatment of patients with stroke is increasingly complex, as new relationships are continually being discovered between features of the disease and emerging treatment options. Clinicians must constantly strive to keep up to date with advances and apply them to practice. AI could reduce variations in routine clinical practice and extract vital information that could improve the prediction of treatment responses and patient outcomes, including adverse events. This would then support healthcare professionals with the information they need to weigh up the probability of good and poor outcomes for an individual and to discuss treatment options with the patient and their family.

Dr Wang and her team will seek to answer whether a machine learning model that integrates routinely recorded clinical, laboratory and brain imaging data is able to reliably predict key clinical outcomes at a personalised level in patients, and whether the model is practical, acceptable to clinicians, nursing staff and family carers, as well as widely applicable.

Switching salts to make Australians healthier

Professor Bruce Neal, Executive Director of The George Institute Australia, has secured a Senior Researcher Grant for his work on ‘Switching the Salt Supply’.

High blood pressure remains a leading cause of premature death and disability in Australia and worldwide. Guidelines recommend people with hypertension (which includes six million Australians) eat a diet low in sodium to help manage their blood pressure and prevent cardiovascular diseases. The behavioural changes required, however, are too difficult for most people, who are unable to easily identify low-sodium foods and unwilling to reduce salt levels in cooking and seasoning because of the changes in taste. 

Professor Neal’s team has shown that switching from regular salt (100% sodium chloride) to potassium-enriched salt (25% potassium chloride, 75% sodium chloride) can safely reduce blood pressure and prevent disease. Modelling studies show that millions of strokes and heart attacks could be prevented worldwide every year through making this switch, but potassium-enriched salt, while available in some Australian supermarkets and in 40 other countries around the world, is rarely recommended by doctors and is purchased by very few people. 

The research aims to identify the best way to scale up appropriate use of potassium-enriched salt in people with hypertension. This will be achieved by building a NSW-based, but globally collaborative, multidisciplinary research translation platform that uses mixed methods research to define and test the optimal pathways to market. While the work will deliver a solution for Australia, the platform will also support countries all around the world to implement similar programs.