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
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
Molecular Mechanisms Underlying Recovery From General Anaesthesia
Funder
National Health and Medical Research Council
Funding Amount
$335,983.00
Summary
Even though general anaesthesia is an extremely common and safe procedure, doctors do not really know how it works. We have found that general anaesthetics might work in two steps, by first promoting natural sleep, and then by impairing communication between all nerve cells in the brain. It is this second step that makes surgery possible, but also makes recovery difficult – especially among patients with brain disorders. Understanding these mechanisms will promote better anaesthesia procedures.
Commercial Testing Of A Physiologically Based Theory Of Oscillatory Brain Electrical Activity In Anaesthesia Monitoring
Funder
National Health and Medical Research Council
Funding Amount
$191,165.00
Summary
While the mechanisms of local anaesthesia are comparatively well known, the mechanisms whereby anaesthetics impair consciousness remain unresolved. This lack of understanding has implications in our ability to monitor the level of anaesthesia while anaesthetic consumption and side effects are minimized. Despite this a number of devices have been developed that attempt to monitor the depth of anaesthesia by quantifying the brains electrical activity. All monitors analyse the activity using a set ....While the mechanisms of local anaesthesia are comparatively well known, the mechanisms whereby anaesthetics impair consciousness remain unresolved. This lack of understanding has implications in our ability to monitor the level of anaesthesia while anaesthetic consumption and side effects are minimized. Despite this a number of devices have been developed that attempt to monitor the depth of anaesthesia by quantifying the brains electrical activity. All monitors analyse the activity using a set of criteria that have been developed by trial and error. The research of Dr David Liley and his team, at Swinburne University of Technology, has resulted in a detailed understanding of the physiological mechanisms that generate brain electrical activity. The outcome is a practical means to carry out a System Based Analysis of Brain Electrical Response (SABER). In 2004, Dr Liley began working with Cortical Dynamics, a company involved in the commercialisation of medical devices. This collaboration incorporated the SABER system into a new prototype device called the Brain Anaesthesia Response (BAR) monitor. In 2004 Dr Liley and Associate Professor Kate Leslie collaborated in a trial, at the Royal Melbourne Hospital to test the sensitivity of the SABER system in quantifying the effect that various levels of nitrous oxide have on measures of anaesthetic depth. The Australian and New Zealand College of Anaesthetists supported this study. Initial results obtained with sevoflurane and 3 levels of nitrous oxide showed the ability to differentiate between conscious and unconscious states of patients based on two physiological characterizations of higher brain dynamic state. The next step requires commercial product validation (ie scale up) and further clinical efficacy in testing beta stage depth of anaesthesia BAR units. Completion of this will help the technology move away from a low volume prototype system into a commercially applicable device.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 Randomized Controlled Trial Of Effects Of Early Life Exposure To General Anaesthesia On Neurobehavioural Outcomes In Children With Cystic Fibrosis (CF)
Funder
National Health and Medical Research Council
Funding Amount
$587,240.00
Summary
Anaesthesia permits surgeries and other interventional procedures that benefit the health of children to be performed painlessly and non-traumatically. This study will provide critical information about whether the drugs used commonly for general anaesthesia represents a risk to very young children in terms of their neurobehavioural development.
IV Iron For Treatment Of Anaemia Before Cardiac Surgery (ITACS Trial)
Funder
National Health and Medical Research Council
Funding Amount
$2,285,290.00
Summary
Our aim is to evaluate intravenous iron to treat anaemia in 1000 patients waiting for their cardiac surgery. This could reduce the risks of the operation and enable patients to recover faster and can go home earlier.