Understanding How Sepsis Causes Kidney Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$471,770.00
Summary
Acute renal failure is a serious condition that affects up to 20% of patients in Intensive Care Units. Sepsis and septic shock remain the most important causes of acute renal failure in critically ill patients. Despite our ability to support vital organs and resuscitate patients, the incidence and mortality of septic acute renal failure remain unacceptably high at up to 55%. There have been no major advances in our understanding of its pathogenesis and in its prevention or treatment over the las ....Acute renal failure is a serious condition that affects up to 20% of patients in Intensive Care Units. Sepsis and septic shock remain the most important causes of acute renal failure in critically ill patients. Despite our ability to support vital organs and resuscitate patients, the incidence and mortality of septic acute renal failure remain unacceptably high at up to 55%. There have been no major advances in our understanding of its pathogenesis and in its prevention or treatment over the last 50 years. The traditional view is that sepsis-induced renal failure results from reduced perfusion of the kidney secondary to the low blood pressure. In a model of sepsis in sheep with renal failure, we demonstrated, however, that renal blood vessels dilated and blood flow increased. Furthermore, renal function improved following treatment with vasoconstrictor drugs that raised blood pressure and renal blood flow. These findings indicate that renal ischaemia is not the cause of the renal dysfunction in sepsis. We hypothesise that sepsis causes renal vasodilatation, which reduces glomerular filtration rate and renal function, and induces a delayed development of apopotosis. We will study in sepsis 1) the effects of a treatment to increase glomerular filtration rate 2) the development of apoptosis and the effect of an anti-apoptotic drug, and 3) whether there is bioenergetic failure in the kidney in sepsis and the effects of treatments on this. Finally, in septic patients we will measure renal blood flow and determine the effects of our novel treatment on this and renal function. These studies will significantly increase our understanding of the factors causing acute renal failure in sepsis. They are likely to lead to the development of new therapies to improve renal function in sepsis and their effectiveness will be examined in septic animals and patients.Read moreRead less
I will determine the efficacy and safety of crystalloid resuscitation fluids in conventional models of care. This is a fundamental and unresolved question in Intensive Care Medicine and will have an impact on clinical practice worldwide. I will also consolidate and enhance a series of projects to provide the next generation of clinician-researchers with high-quality research opportunities. These include projects in sepsis, traumatic brain injury, and endocrine function in critical illness.
Improving The Outcome Of Critically Ill Patients Through The Generation Of Evidence And Its Translation Into Practice
Funder
National Health and Medical Research Council
Funding Amount
$329,822.00
Summary
This research program will test new approaches to sepsis, traumatic brain injury, kidney protection, nutrition, post-operative care, sedation, cardiac arrest, and mobilisation of acutely ill patients to deliver better outcomes. Experimental research will help understand kidney injury during severe infection and develop new ways of protecting the brain during cardiac arrest. Database investigations will identify successful patterns of treatment and potential new fields of investigations.
How Does Activated Protein C Create Intact, Non-leaky, Stable Blood Vessels?
Funder
National Health and Medical Research Council
Funding Amount
$564,644.00
Summary
Vascular dysfunction is a common feature of many diseases, including sepsis, diabetes, atherosclerosis, tumours and asthma. These vessels have compromised structural and functional integrity, leading to leakage of blood components and causing inflammation in tissues. Based on our recent findings, this project aims to discover how activated protein C creates normal, healthy non-leaky blood vessels and prevents vascular dysfunction in disease.
Understanding Tissue Responses To Fluid Resuscitation And Blood Transfusion During Ovine Sepsis To Improve Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$980,810.00
Summary
Annually, sepsis affects up to 30 million patients, killing more patients than the combined totals of breast, prostate and lung cancer. Fluid resuscitation is a cornerstone of sepsis therapy, aimed at improving oxygen delivery to key organs. Data now indicates that blood and non-blood fluids may worsen mortality. This study will investigate the mechanism of sepsis and the effect of blood and non-blood fluids, to provide data to clinicians which may reduce the vast global burden of this disease.
I am an intensive care clinician who performs clinical trials and experimental large animal research in multiple aspects of acute and intensive care medicine
BLING III: A Phase III Randomised Controlled Trial Of Continuous Beta-lactam Infusion Compared With Intermittent Beta-lactam Dosing In Critically Ill Patients
Funder
National Health and Medical Research Council
Funding Amount
$3,269,943.00
Summary
This Australian-led trial of global significance will provide definitive clinical evidence of the optimal method for treating patients with severe sepsis using beta-lactam antibiotics. The trial will compare whether continuous infusion of beta-lactam antibiotics improves outcomes for patients compared with standard intermittent dosing. The potential significance of this trial is that it may lead to a simple and cost-effective intervention to improve survival for patients with severe infections.
Saving Money And Saving Lives: Integrating Comparative Effectiveness Trials And Translational Research In Critically Ill Patients
Funder
National Health and Medical Research Council
Funding Amount
$338,938.00
Summary
I am a full-time Intensive Care Specialist in Sydney who combines clinician duties with research. My research is the design and conduct of large trials that have changed and will continue to change the management of critically ill patients around the world. I led two of the largest trials ever conducted in critically ill patients and have recently been funded to lead a further even larger trial. The Practitioner Fellowship will allow me to continue and expand this essential research.
Therapeutic Thermal Regulation In Critical Illness
Funder
National Health and Medical Research Council
Funding Amount
$189,384.00
Summary
Patients who are admitted to intensive care units often develop abnormalities of their body temperature as part of their illness. Common illnesses include infections and injuries to the brain from trauma or strokes. Clinicians are unsure of how to react to these changes in temperature. My research is designed to provide high quality evidence on body temperature and the use of treatments, so that clinicians can improve patient outcomes.