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.
Rapidly giving intravenous fluid to prevent or treat shock (fluid resuscitation) is one of the commonest treatments given to critically ill patients. Current guidelines recommend crystalloid solutions but it is unknown whether any particular crystalloid is better than others. This trial will determine whether the use of one of two crystalloid fluids, saline or PlasmaLyte, reduces the risk of organ injuries, such as kidney failure, and improves patients chances of surviving critically 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.
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.
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.
Randomised Comparison Of Fluid Resuscitation With Human Albumin Solution Or Normal Saline Among Critically Ill Patients
Funder
National Health and Medical Research Council
Funding Amount
$611,728.00
Summary
Human albumin solution is widely used for the emergency treatment of severely ill patients requiring fluid replacement, both in Australia and worldwide. However, a recent report suggests that compared to the other standard treatment (salt solution), the use of human albumin solution may be associated with a higher death rate (about six additional deaths among every one hundred patients treated). But, this report was based on data from a relatively small number of patients among whom there was a ....Human albumin solution is widely used for the emergency treatment of severely ill patients requiring fluid replacement, both in Australia and worldwide. However, a recent report suggests that compared to the other standard treatment (salt solution), the use of human albumin solution may be associated with a higher death rate (about six additional deaths among every one hundred patients treated). But, this report was based on data from a relatively small number of patients among whom there was a relatively small number of deaths, and there is widespread uncertainty among doctors about the reliability of the evidence and the implications for patient care. This is reflected in the large difference between intensive care units in the use of human albumin solution (in Australia, its use ranges from 10-90% of all patients needing fluid). Human albumin solution costs, about thirty times more than salt solution, and during 1998 more than 200,000 bottles of human albumin solution were administered to patients in Australia, at a cost of about A$35 million. In an effort to provide definitive evidence about the effects (and cost-effectiveness) of fluid replacement with human albumin solution, the Australia and New Zealand Intensive Care Society, in collaboration with the Australian Red Cross Blood Services and the Institute for International Health, has proposed the conduct of new large-scale study (SAFE - Saline vs Albumin Fluid Evaluation). This study will involve 7,000 patients from 15 intensive care units in Australia and New Zealand. These patients (all of whom require fluid replacement) will be randomly assigned to receive either human albumin solution or salt solution and outcome in terms of deaths and other serious events will be monitored over 28 days. Results will be available within 2 years of starting the study, and these are likely to influence the care of the majority of seriously ill patients admitted to intensive care units worldwide.Read moreRead less
My program of research will focus on one of the most common interventions in medicine _ determining the best resuscitation fluid for resuscitation of critically ill patients. The program includes completion of a major clinical trial in intensive care followed by a series of comparative studies of past and current studies in Australia and internationally. These results will produce clear evidence that will be incorporated in practice guidelines to inform clinicians about optimal practice.
Management Of Burn Injury: Fluid Dynamics And Antibiotic Pharmacokinetics
Funder
National Health and Medical Research Council
Funding Amount
$342,375.00
Summary
It is well known that major burns, as well as being relatively common injuries, are notoriously difficult to manage. Patients exhibit significant variability due to a combination of anatomic, physiologic, hormonal and immunologic alterations occurring both at the wound site and, more importantly, in other body compartments and vital organ systems. Skin burn injury results in the release of multiple inflammatory mediators in addition to significant fluid loss. The distribution of inflammatory med ....It is well known that major burns, as well as being relatively common injuries, are notoriously difficult to manage. Patients exhibit significant variability due to a combination of anatomic, physiologic, hormonal and immunologic alterations occurring both at the wound site and, more importantly, in other body compartments and vital organ systems. Skin burn injury results in the release of multiple inflammatory mediators in addition to significant fluid loss. The distribution of inflammatory mediators and wound bacteria to central organs can cause complex physiological changes that may lead to multiple organ failure, with serious infections occurring in around 50% of patients with serious burns. Antibiotic distribution kinetics, such as bioavailability, clearance, volume of distribution, elimination half-life and unbound fraction in plasma can be significantly altered in burn patients. Without detailed knowledge of changes and relationships between factors such as wound pH, tissue oxygenation, protein concentrations of fluid leaked from the local wound microvasculature, tissue binding, oedema and changes in burned and non-burned tissue induced by resuscitation therapies, the optimisation of both local and systemic infection contriol therapies can hardly be expected to advance. This project aims to determine how changes the physiology of burn patients, in particular in the burn wound environment, affect antibiotic penetration and distribution into tissues. We also believe that these changes will vary between patients and are aiming to determine whether certain parameters can be used to give an indication of the best antibiotic dosing regimens for individual patients.Read moreRead less
Hormonal Resuscitation And P38 MAP Kinase Inhibition To Enhance Quality Of Cadaveric Donor Organs For Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$469,500.00
Summary
The transplantation of organs such as the heart, lung, liver, kidney and pancreas from brain-dead donors is limited primarily by the shortage of donor organs. It is now recognised that as many as 25% (one in four) potentially usuable donor organs are lost after brain death due to the rapid deterioration that occurs in organs after brain death. There is evidence that this deterioration is due to loss of the normal hormones that are essential to the normal functioning of these organs. In this proj ....The transplantation of organs such as the heart, lung, liver, kidney and pancreas from brain-dead donors is limited primarily by the shortage of donor organs. It is now recognised that as many as 25% (one in four) potentially usuable donor organs are lost after brain death due to the rapid deterioration that occurs in organs after brain death. There is evidence that this deterioration is due to loss of the normal hormones that are essential to the normal functioning of these organs. In this project, we will use a pig model of brain death that we have extablished in our laboratory to examine the effects of hormone replacement on the function of organs that are used for transplantation. We will also test a novel drug aimed at protecting donor organs during the period between removal of the organ and transplantation. If successful, these treatments have the potential to markedly increase the numbers of organ transplants and to improve the outcomes for recipients of these transplants. In the Australian and New Zealand setting, a 25% increase in the number of donor organs would results in approximately 220 more people per year receiving these life-saving operations.Read moreRead less