Linking Of Physiological Models Of Iv Anaesthetic Disposition With Models Of The Cardio- And Cerebro-vascular Systems
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
On average, nearly 1 in 10 Australians are anaesthetised each year. Most cases include an injection of either thiopentone or propofol directly into a vein. These drugs quickly produce the desired loss of consciousness, but can also produce significant undesirable effects on the circulatory system. To date, anaesthetists have relied on their accumulated experience to choose doses of these drugs that achieve an appropriate balance between their desirable and undesirable effects. However, the scien ....On average, nearly 1 in 10 Australians are anaesthetised each year. Most cases include an injection of either thiopentone or propofol directly into a vein. These drugs quickly produce the desired loss of consciousness, but can also produce significant undesirable effects on the circulatory system. To date, anaesthetists have relied on their accumulated experience to choose doses of these drugs that achieve an appropriate balance between their desirable and undesirable effects. However, the scientific basis of this process was poorly understood. Consequently, we conducted experiments in sheep in which we showed that the level of unconsciousness produced by these drugs depended on their concentration in the brain. Each sheep was unharmed and could be studied repeatedly. We established the important factors that influenced this brain concentration, and developed a unique computer model of the processes governing the desirable effects of thiopentone and propofol. However, understanding of what influences the undesirable effects of these drugs is less well developed. In this project, we propose a series of experiments in which we inject the thiopentone and propofol in special sites within the sheep so that we achieve low concentrations in some parts of the body, but high concentrations in others, while also measuring their undesirable effects. This will show which sites in the body high concentrations of drug should be avoided to minimise these undesirable effects. Another series of studies will be used to extend our computer model so that it can predict these undesirable effects. This extended model will allow anaesthetists to visualise and understand the fundamental factors influencing both the desirable and undesirable effects of thiopentone and propofol. This in turn will lead to dose strategies that help the anaesthetist maximise the desirable effects, while minimising the undesirable, in individual patients.Read moreRead less
We will conduct a clinical trial of the effectiveness of a continuous auditory display of an anesthetized patient's respiratory status. Expired carbon dioxide monitoring has helped reduce respiratory incidents since its widespread introduction in the late 1980s, but a continuous auditory display of respiratory status may reduce incidents further. We will conduct a clinical trial with 10 anaesthetists of continuous auditory respiratory monitoring. Successful outcome may lead to commercial uptake.
A Double Blind Randomised Placebo Controlled Trial Of Melatonin As An Adjuvant Agent In Induction Of Labour
Funder
National Health and Medical Research Council
Funding Amount
$384,566.00
Summary
Induction of labour, a common obstetric intervention fails in almost 40% of first time mothers. There is evidence to suggest that the endogenous hormone melatonin has important roles in the progress of labour. We will undertake a double-blind randomised placebo controlled trial of melatonin supplementation to improve the success of induction of labour in first time mothers. We will also assess the economic impact of melatonin supplementation at induction of labour.
Mimetics Of Natural Triggers Of Innate Immunity As Vaccines
Funder
National Health and Medical Research Council
Funding Amount
$241,650.00
Summary
Knowledge of what properties of an antigen allow it to induce an immune response is central to our understanding of how we fight disease and how we can vaccinate effectively against disease. The fact that an antigen is foreign to the host is not in itself sufficient for it to initiate the series of events that must take place in order to activate B and T lymphocytes, the cells involved in immunity. For vaccine purposes, antigens must be delivered with substances called adjuvants to be effective. ....Knowledge of what properties of an antigen allow it to induce an immune response is central to our understanding of how we fight disease and how we can vaccinate effectively against disease. The fact that an antigen is foreign to the host is not in itself sufficient for it to initiate the series of events that must take place in order to activate B and T lymphocytes, the cells involved in immunity. For vaccine purposes, antigens must be delivered with substances called adjuvants to be effective. There is very little known about how adjuvants actually work but many of the highly effective experimental adjuvants contain an immunostimulant which is usually either whole dead bacteria or components of the cell walls of bacteria or other organisms. From evidence emerging in the literature and our own experimental observations, we have begun to understand the requirements for and the chain of events leading to immune response induction. The interaction of certain lipid-containing groups, present on antigens from pathogenic organisms, with a specialised type of cell, the dendritic cell, is a key event in this process. We have designed synthetic mimics of lipid-containing moieties from bacteria and coupled them to unrelated parts of viral proteins. We showed that these lipopeptides can elicit potent anti-viral immune responses and long lived memory responses. The experiments outlined in this proposal will examine the interaction of these and other second generation lipopeptides with dendritic cells. We will determine whether these can bind to particular molecules on the dendritic cell surface to initiate a specific series of signals leading to immune induction and if so we will seek to use different lipid groups to trigger the immune response in different and predictable ways. The outcomes of this work may have a major impact on the design of new vaccines as well as increase our understanding of how the immune system is triggered to respond to invading organisms.Read moreRead less
Development And Clinical Evaluation Of A Depth Of Anaesthesia Monitor
Funder
National Health and Medical Research Council
Funding Amount
$424,785.00
Summary
Waking up during surgery (awareness under anaesthesia) is a frightening reality for some patients. Although uncommon (occurring in about 1 in 1000 operations), it remains one of the main concerns of patients before their surgery. Recent studies (including our own) have demonstrated that processed EEG monitoring using bispectral index (BIS) can markedly reduce the risk of awareness. Other EEG monitors are being developed, but each have weaknesses. As approximately two million Australians have a g ....Waking up during surgery (awareness under anaesthesia) is a frightening reality for some patients. Although uncommon (occurring in about 1 in 1000 operations), it remains one of the main concerns of patients before their surgery. Recent studies (including our own) have demonstrated that processed EEG monitoring using bispectral index (BIS) can markedly reduce the risk of awareness. Other EEG monitors are being developed, but each have weaknesses. As approximately two million Australians have a general anaesthetic each year, about 2000 will suffer an episode of awareness. More than 60 million people around the world have an anaesthetic, and so the problem is substantial. This suggests the potential benefits (health outcomes, commercial gains) are very great. In 2000 less than 5% of US hospitals used BIS monitoring; the current figure in the US is about 69% of the best-rated hospitals (US News and World Report) and 78% of teaching hospitals. A similar rapid growth is occurring in Australia and Europe. We are working with a successful Australian Company (Compumedics Ltd) to develop a better awareness monitor. We plan studies in groups of patients have surgery.Read moreRead less
The MASTER Anaesthesia Trial (or Mulcentre Australian Study of Epidural Anaesthesia) is a large clinical experiment designed to determine whether using epidural techniques to control pain during and after surgery results in fewer complications after major surgery. The Trial involves a comparison of epidural methods, in which some of the anaesthetic and pain-killing drugs are injected into the space in the spinal column surrounding the sac that encloses the spinal cord, with conventional methods, ....The MASTER Anaesthesia Trial (or Mulcentre Australian Study of Epidural Anaesthesia) is a large clinical experiment designed to determine whether using epidural techniques to control pain during and after surgery results in fewer complications after major surgery. The Trial involves a comparison of epidural methods, in which some of the anaesthetic and pain-killing drugs are injected into the space in the spinal column surrounding the sac that encloses the spinal cord, with conventional methods, where the drugs are injected into a vein or muscle. Both approaches are well accepted in clinical practice, but it remains uncertain whether one is superior to the other. At present, nineteen hospitals in Australia, Hong Kong and Malaysia are contributing patients to the project, with others in New Zealand and Asia expected to join soon. If one method of anaesthesia and pain control is found to be significantly better than the other, in terms of avoiding complications, this would have obvious benefits to patients, but would also reduce lengths of stay in hospital and improve efficiency within the health system.Read moreRead less
Evaluation Of Nitrous Oxide In The Gas Mixture For Anaesthesia: A Randomised Controlled Trial (The ENIGMA Trial)
Funder
National Health and Medical Research Council
Funding Amount
$490,125.00
Summary
There are about 2 million anaesthetics given each year in Australia (1:10 Australians), with more than 1 million Australians being exposed to nitrous oxide (laughing gas). Despite being around for more than 150 years, there has yet to be a large trial of the safety and benefits of nitrous oxide, particularly when compared with newer (safer?) anaesthetic drugs. Nitrous oxide is not a particularly strong anaesthetic and so it must be mixed with other drugs. Current practice in Australia and around ....There are about 2 million anaesthetics given each year in Australia (1:10 Australians), with more than 1 million Australians being exposed to nitrous oxide (laughing gas). Despite being around for more than 150 years, there has yet to be a large trial of the safety and benefits of nitrous oxide, particularly when compared with newer (safer?) anaesthetic drugs. Nitrous oxide is not a particularly strong anaesthetic and so it must be mixed with other drugs. Current practice in Australia and around the world is to give 70% nitrous oxide in oxygen along with another anaesthetic gas in order to produce a depth of anaesthesia sufficient for surgery. This is despite knowledge that nitrous oxide interferes with the production of DNA. DNA is used to programme cell division and function - it is the building block of cell and tisue growth. It is known that nitrous oxide can impair some tissue functions, such that anaemia and, possibly birth defects can occur. Such effects are rare, but recent evidence suggests that milder abnormalities may occur more commonly than previously thought. There is also good evidence that nitrous oxide increases the risk of severe nausea and vomiting after surgery. The adverse effects on DNA production raises the possibility of nitrous oxide causing immune deficiency, heart ischaemia, (angina), nerve and spinal cord damage, and increased cancer risk in hospital staff chronically exposed to low levels of nitrous oxide. The prevailing view is that nitrous oxide is a cheap, relatively safe drug that can reduce the exposure to other anaesthetic drugs. However, the development of many new anaesthetic drugs demands a re-evaluation of the role of nitrous oxide in current anaesthetic practice.Read moreRead less
The Influence Of Anaesthetic Depth On Patient Outcome After Major Surgery
Funder
National Health and Medical Research Council
Funding Amount
$2,893,795.00
Summary
Millions of high-risk patients have general anaesthesia for major surgery worldwide every year, but the optimal depth of anaesthesia for these patients is not known. The aim of this large randomised trial is to determine the impact of light versus deep general anaesthesia on survival at one year postoperatively in 6,500 older patients. If light anaesthesia is associated with better survival, this result will be immediately implementable, will save lives and will reduce the costs of care.
It is known that about 10% of patients over the age of 55 have difficulty with cognition and thinking 3 months after surgery and anaesthesia. Over 2 million operations involving anaesthesia are administered in Australia every year and increasingly the patients are elderly and thus exposed to the risk of cognitive decline after surgery. We have preliminary data showing that people who have mild changes in cognitive function before the surgery (known as mild cognitive impairment) are susceptible t ....It is known that about 10% of patients over the age of 55 have difficulty with cognition and thinking 3 months after surgery and anaesthesia. Over 2 million operations involving anaesthesia are administered in Australia every year and increasingly the patients are elderly and thus exposed to the risk of cognitive decline after surgery. We have preliminary data showing that people who have mild changes in cognitive function before the surgery (known as mild cognitive impairment) are susceptible to further cognitive decline after anaesthesia and surgery. In order to explore the relationship between preoperative cognitive function and postoperative cognitive decline we plan to measure cognition in patients scheduled for elective hip replacement surgery. This is done by asking patients to complete a standard battery of cognitive tests. We will be then able to identify those patients who already have mild cognitive impairment before surgery and by repeated testing after the operation will be able to demonstrate if preoperative cognitive status is a determinant of postoperative cognitive dysfunction. The primary aim of the research is to test whether cognitive impairment before surgery leads to cognitive deficit after surgery in patients over the age of 65 undergoing total hip replacement surgery. The study will also establish the prevalence of pre-operative mild cognitive impairment and the magnitude of postoperative cognitive dysfunction after surgery in this patient group. The study will explore the relationship between preoperative cognitive status and postoperative cognitive deficit , providing information about the incidence, natural history and risk factors of postoperative cognitive deficit. This work will enable further research to isolate specific causative factors and identify therapeutic and prophylactic strategies.Read moreRead less
A Randomised Controlled Trial Of Outpatient Cervical Priming For Induction Of Labour
Funder
National Health and Medical Research Council
Funding Amount
$611,611.00
Summary
This study aims to compare two approaches that prepare pregnant women before they are induced to give birth. Eligible women who agree to be in the study will be allocated to receive (a) the usual, standard care already used in SA hospitals or, (b) a new method. In the new approach, women will have their labour primed by a midwife and will be discharged and further monitored by the midwife from hospital. This approach might give women a more satisfying experience with less medical intervention.