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
Improved Patient Outcomes By Early Intervention With Therapeutic Cooling For Patients With Severe Traumatic Brain Injury, And By Optimising Patient Blood Transfusion Practice In Critically Ill Patients.
Funder
National Health and Medical Research Council
Funding Amount
$380,450.00
Summary
First, a large multicentre trial (POLAR) will complement my previous successful trials in traumatic brain injury (TBI) patients and will establish whether active therapeutic cooling, commenced early after brain injury and continued in intensive care units, will achieve its promise of improving patient outcomes. Second, a national multicentre trial (TRANSFUSE) will establish whether transfusing blood units with a shorter than usual storage time will improve patient outcomes.
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.
The appropriate dosing of antibiotics for patient admitted to ICU after a traumatic injury is poorly defined and based on intuition rather than evidence. Doctors need to predict which patients may develop very high antibiotic clearances and dose accordingly so that potentially life-threatening infections do not occur. Given these patients are unknown, this research seeks to identify such patients and recommend which antibiotic and which dose is appropriate to ensure adequate treatment.
I am an intensive care physician, clinician and researcher, interested in studying new therapies to improve outcomes in patienst with acute trauma, sepsis and lung injury. A main focus is independent phase 111 clinical trials in critically ill patients
Does Increased Non-Linear Behavior Caused By Dynamic Variables Increase Ventilatory-Induced Lung Injury (VILI)?
Funder
National Health and Medical Research Council
Funding Amount
$109,625.00
Summary
Acute lung injury (ALI) is precipitated by a variety of different insults, either directly to the lung or elsewhere to the body. Approximately 50% of the patients die. ALI is characterized by an increase in the leakiness of the barrier that normally separates the blood from the airspaces. The fluid which consequently floods the airspaces not only makes it difficult for patients to adequately obtain oxygen, but also dramatically increases the work of breathing by changing the surface forces withi ....Acute lung injury (ALI) is precipitated by a variety of different insults, either directly to the lung or elsewhere to the body. Approximately 50% of the patients die. ALI is characterized by an increase in the leakiness of the barrier that normally separates the blood from the airspaces. The fluid which consequently floods the airspaces not only makes it difficult for patients to adequately obtain oxygen, but also dramatically increases the work of breathing by changing the surface forces within the lungs. As a result, the patients must be mechanically ventilated. However, the very act of using a positive pressure to inflate the lungs often creates further damage, either through repeated opening and closing of collapse tissue or through its over distension. Ventilatory-induced lung injury (VILI), in itself is estimated to contribute to ~30% of the mortality. The best way shown to minimize VILI is through the use of small programmed breaths so as not to overinflate the lungs while still allowing adequate gas exchanges, superimposed upon a background pressure, in order to pre-inflate the lungs and prevent them from repeatedly collapsing. A remaining problem is that just as a rubber band changes its elasticity as it is stretched, so too the lung changes its mechanical properties during distension. Moreover, the lung is considerably more complex since different regions have different elasticities, which change differentially as air flows in and out of them. Airflow in turn depends on regional differences in the location, size, and number of conducting airways. Indeed, we have recently shown for the first time that dynamic changes in lung mechanics may contribute to VILI in patients, despite the use of safe ventilation modalities. This application proposes to examine the extent to which dynamic changes in lung mechanic contribute to VILI in an animal model, as a prelude to more costly, large scale clinical trials aimed at improving mortality.Read moreRead less
A Randomised Controlled Trial Of Prophylactic Hypothermia In Severe Traumatic Brain Injury.
Funder
National Health and Medical Research Council
Funding Amount
$2,061,506.00
Summary
Patients who suffer from a severe head injury (traumatic brain injury) have a 50% chance of having severe long term neurological disability or death. Some of this damage occurs after the initial injury and may be reduced by artificially lowering the body termperature for up to 7 days to protect the brain from further damage. This project will determine if early, sustained cooling is safe and if it can improve the long term neurological outcomes of patients with traumatic brain injury.
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
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.