
Dr Stephen Macdonald
Effect of intravenous fluid volume on the pathobiology of sepsis
Raine Priming Grant
$150,000
2019 - 2022
Royal Perth Hospital
Dr Stephen Macdonald is a clinician researcher, holding dual appointments as an Emergency Physician at Royal Perth Hospital and as a Research Fellow at the University of Western Australia. Dr Macdonald’s research seeks to identify better treatments for sepsis in hopes of improving outcomes for patients.
Sepsis has recently been estimated to cause 8700 deaths each year in Australia. The hallmark of sepsis, and the principal driver of morbidity and mortality, is organ failure. Septic shock is a severe subset of sepsis where the body’s immune response to an infection results in insufficient blood pressure to supply oxygen to its tissues. If not corrected quickly, septic shock can be fatal.
The optimal means of resuscitating patients with septic shock has been the subject of active investigation. Traditionally, doctors infuse fluids into a patient’s vein to help restore their blood pressure, however there is increasing uncertainty about the safety and effectiveness of this. Indeed, data are emerging that liberal use of fluids may be associated with increased organ failure, ICU length of stay and mortality. Some doctors have suggested giving a smaller amount of fluid and giving medications to raise the blood pressure, however it remains unknown which of these methods is best for the patient.
In the current ‘REFRESH’ trial, Dr Macdonald sought to collect pilot data investigating these two treatment approaches in a small number (100) of patients who were being treated for septic shock. To try and better understand the way in which fluids and medications affected the patient, the researchers collected blood samples and measured a range of different chemical markers of inflammation in the blood.
This pivotal trial, endorsed by the Australasian College for Emergency Medicine (ACEM) Clinical Trials Group, is the first step towards resolving a critical research question of global importance: in sepsis with hypotension, does resuscitation with a smaller volume of intravenous fluid, along with earlier institution of key medications, improve outcomes? Their preliminary findings support the hypothesis that intravenous fluids may exacerbate inflammation in the setting of septic shock. The clinical implications of these results need to be tested further, whereby the results of this pilot trial will be used to inform the design of larger clinical trials designed to find out the best way for doctors to treat patients with septic shock in the future.
Following the conclusion of the Raine Priming Grant, Dr Macdonald has been successful in obtaining additional funding to continue this promising work, including the Department of Health (DoH) Near Miss funding program (2022-2023) for being the top-ranked unsuccessful NHMRC Investigator Grant EL2 applicant in the state, as well as a DoH/Raine Clinician Research Fellowship (2021-2024). Furthermore, across the course of this project Dr Macdonald has developed collaborations with several national and international leaders in the field of sepsis research, including a paper currently underway with a world-leading research team at Harvard University.