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
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
ANTIPODES The Australian National Trial Investigating Post-Operative Deficit, Early Extubation And Survival
Funder
National Health and Medical Research Council
Funding Amount
$370,509.00
Summary
Brain damage following cardiac surgery is an unfortunate but common complication occuring variously in 30-80% of patients. Although severe strokes are uncommon (<1%), more subtle effects such as forgetfulness or behaviour changes may persist and make daily living difficult. Many attempts have been made to identify the exact cause of the brain damage, but no answer has been forthcoming. Recently, the introduction of modern anaesthetic techniques, which allow patients to wake up quickly after t ....Brain damage following cardiac surgery is an unfortunate but common complication occuring variously in 30-80% of patients. Although severe strokes are uncommon (<1%), more subtle effects such as forgetfulness or behaviour changes may persist and make daily living difficult. Many attempts have been made to identify the exact cause of the brain damage, but no answer has been forthcoming. Recently, the introduction of modern anaesthetic techniques, which allow patients to wake up quickly after the operation, have given strong indications that they may also cause less brain damage. We plan to test this aspect of modern anaesthesia, by comparing the results of tests for brain damage after anaesthesia that has been given by traditional methods and the recent method which allows patients to wake up quickly.Read moreRead less
Nitrous Oxide Anaesthesia And Cardiac Morbidity In Major Surgery
Funder
National Health and Medical Research Council
Funding Amount
$2,952,623.00
Summary
Nitrrous oxide is an anaesthtic gas that has been in use for more than 160 years. It has been considered a safe and cheap drug, but newer anaesthetic drugs and improvements in technology provide alternatives that might be safer. Our recent research has found some potentialy serious (but rare) complications associated with nitrous oxide. These are more likely to occur in people with existing heart disease. The purpose of this study is to investigate the safety of nitrous oxide in such people. Whe ....Nitrrous oxide is an anaesthtic gas that has been in use for more than 160 years. It has been considered a safe and cheap drug, but newer anaesthetic drugs and improvements in technology provide alternatives that might be safer. Our recent research has found some potentialy serious (but rare) complications associated with nitrous oxide. These are more likely to occur in people with existing heart disease. The purpose of this study is to investigate the safety of nitrous oxide in such people. When considering its widespread use in about 90% of all surgery in Australia (and around the world), small differences in outcome would have major implications for healthcare delivery. A large well-designed study is necessary to answer this question. We plan to study 7,000 patients having major surgery from around the world.Read moreRead less
PREOPERATIVE RISK FACTORS, ADVERSE OUTCOMES AND EFFECTS OF EPIDURAL AND SPINAL ANAESTHESIA
Funder
National Health and Medical Research Council
Funding Amount
$66,110.00
Summary
Anaesthesia and major surgery in patients with coexisting important medical problems present a major challenge to health professionals to avoid and minimise life threatening complications of such surgery. Accurate prediction of which patients are likely to fare badly, and therefore need more intensive peri-operative care and supervision, and knowing definitively whether epidural techniques really do improve the outcome of surgery are issues of central importance in the practice of anaesthesia. P ....Anaesthesia and major surgery in patients with coexisting important medical problems present a major challenge to health professionals to avoid and minimise life threatening complications of such surgery. Accurate prediction of which patients are likely to fare badly, and therefore need more intensive peri-operative care and supervision, and knowing definitively whether epidural techniques really do improve the outcome of surgery are issues of central importance in the practice of anaesthesia. Providing clear answers to both questions requires careful analysis of large amounts of data in which systematic and random errors have been minimised. Databases from well-designed and supervised clinical trials represent an invaluable resource in this regard because they have been compiled through the rigorous application of unambiguous definitions and protocols during the process of recording, coding and entering the information. By bringing together the resources and expertise of the MASTER Trial group and the Collaborative Overview of Randomised of Trials of Regional Anaesthesia (CORTRA), both of which are major international projects led from the Australasian region, we have a unique opportunity to provide exceptionally robust answers to some of the most challenging issues in anaesthesia. The combined study of two large international databases will provide a more precise quantitative analysis of the components of preoperative risk and their relationship to life threatening post operative complications, and the possible role of epidural and spinal anaesthesia in minimising risk by reducing the frequency of these complications.Read moreRead less