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.
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
Improving Long-term Weight Loss By Deactivating The Famine Reaction With Molecular Or Lifestyle Means
Funder
National Health and Medical Research Council
Funding Amount
$420,872.00
Summary
Dr Amanda Sainsbury-Salis’ research will clarify which hormones and natural brain chemicals interact in the hypothalamus of the brain to control the famine reaction, the survival mechanism that slows your weight loss when you are on a diet. By knowing precisely which natural chemicals mediate the famine reaction and how they interact, it will be possible to weaken them by pharmaceutical and - or lifestyle means, thereby enabling more people to reap the benefits of being lean and healthy.
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
A Trial Of Therapeutic Drug Monitoring In Methadone Maintenance Treatment
Funder
National Health and Medical Research Council
Funding Amount
$542,025.00
Summary
Heroin addiction is an established and increasing problem in developed countries and in many developing nations. Although there have been several new treatments for heroin addiction, methadone maintenance remains the most effective way to minimize the harms associated with heroin addiction. The current research proposal seeks to test a new approach to setting of methadone dose, using monitoring of methadone blood levels, effects and side-effects in determining when to increase doses, and when to ....Heroin addiction is an established and increasing problem in developed countries and in many developing nations. Although there have been several new treatments for heroin addiction, methadone maintenance remains the most effective way to minimize the harms associated with heroin addiction. The current research proposal seeks to test a new approach to setting of methadone dose, using monitoring of methadone blood levels, effects and side-effects in determining when to increase doses, and when to switch to alternative therapies. This provides an objective method of planning treatment that focuses on suppressing heroin use. The potential subjects of the study are the 50% of patients who continue to use heroin regularly during treatment. All will undergo assessment involving measurement of blood levels of methadone, testing of effects and side-effects of methadone, and monitoring of safety. Half will be randomly allocated to usual care, and half to therapeutic drug monitoring, with dose adjustments according to the results of testing. At 3 and 6 months all subjects will undergo repeat test sessions. It is hypothesized that those in the experimental group will be using less heroin (confirmed by hair testing). It is expected that the study will also identify a small group of subjects with genetically different opioid receptors, who will require very high doses of methadone to be stabilized. The study will allow a detailed analysis of how best to monitor dose adequacy; the relationship between withdrawal symptoms, methadone blood levels, and heroin use, and will provide the first clear investigation of the relationship between changes in methadone blood concentration and certain potentially dangerous changes in the electrical activity of the heart. The intended outcome of this research project is a model for a higher standard methadone program that is more effective in reducing the problems of heroin use in our community.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.