Medicine (St Vincent's) - Theses
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ItemPerioperative cardiovascular complications: incidence in patients undergoing cancer surgery and preoperative risk prediction using 18F-fluorodeoxyglucose cardiac positron emission tomography imaging( 2018)Background: Major perioperative cardiac complications affect over 10 million patients annually worldwide. Cancer is associated with multiple shared cardiovascular risk factors, but the incidence of cardiovascular complications after cancer surgery is unknown. Furthermore, cardiovascular risk prediction remains challenging. Cardiopulmonary exercise testing (CPET) objectively assesses exercise capacity and can predict overall perioperative morbidity and mortality and guide prehabilitation strategies, but cardiac imaging is required to determine the location and severity of coronary artery disease preoperatively. Currently available stress tests rely on surrogate markers for ischaemia and the evidence supporting these investigations perioperatively is weak. Cardiac positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) can image myocardial metabolism directly. Myocardial ischaemia appears as a ‘hot spot’ due to uptake of radiolabelled glucose in ischaemic myocytes undergoing anaerobic metabolism. Performing cardiac PET imaging after CPET may improve cardiac-specific perioperative risk prediction. However, accurate imaging requires preparation with a high-fat low-carbohydrate (HF-LC) diet, and the feasibility of incorporating cardiac PET imaging into existing preoperative CPET clinics is unknown. This thesis explores the incidence of cardiovascular complications in a cancer surgery population, and the feasibility of post-exercise cardiac PET imaging for preoperative risk assessment prior to major cancer surgery, within the setting of a CPET clinic. Methods: Cardiovascular complications within 30 days of cancer surgery were retrospectively investigated during a 12-month period at a single cancer institution (Peter MacCallum Cancer Centre, Melbourne, Australia). Screening identified patients via positive troponin results, ICD-10 diagnosis, and a manual search of intensive care unit discharge summaries. Standardized diagnostic criteria then identified the primary outcome—the incidence of myocardial injury after noncardiac surgery (MINS) or perioperative myocardial infarction (MI). Secondary outcomes included arrhythmias, cardiac failure, pulmonary oedema/fluid overload, pulmonary embolism, stroke, and cardiac death. A prospective pilot study investigating the feasibility of cardiac PET imaging after CPET was conducted. Feasibility endpoints included compliance with preoperative HF-LC diet and fasting; the ability to inject the FDG tracer within 15 minutes of peak exercise, the ability to complete cardiac PET imaging within 120 minutes, and the ability to suppress FDG uptake in background normal myocardium. Postoperative follow-up included cardiac complications and mortality within 30 days of surgery. Results: Over a 12-month period, 4,743 patients underwent cancer surgery. Seventy patients experienced 95 cardiovascular complications within 30 days postoperatively (overall incidence 1.5%). Amongst patients undergoing intermediate/high-risk surgery, the incidence was 8.4%. Perioperative MI/MINS occurred in 13 patients (0.27%). The 30-day all-cause mortality in those with cardiovascular complications after cancer surgery was 10% (n=7), and 42% (n=3) had a documented cardiac cause of death. Twenty-six patients undergoing intermediate to high-risk cancer surgery were enrolled in the cardiac PET pilot study over an eighteen-month period (July 2014-January 2016). Overall protocol feasibility was achieved in 81% (95% CI 62% to 91%). Of the 24 patients who completed exercise testing, FDG was injected within 15 minutes (mean 9.8 minutes) of peak exercise in all patients, and cardiac PET imaging completed within 120 minutes (mean 84.2 minutes) in 96% of patients. Twenty-one patients proceeded to surgery; three patients experienced postoperative myocardial injury or infarction, of which two had positive or equivocal cardiac PET imaging (and negative sestamibi myocardial perfusion imaging). One patient with normal CPET and cardiac PET results suffered MINS following bleeding requiring massive transfusion. Conclusions: Overall, there is a low incidence of perioperative acute myocardial infarction following cancer surgery. However, the retrospective study design and lack of routine postoperative troponin monitoring may have underestimated the true incidence. Patients undergoing intermediate/high risk cancer surgery are at greater risk, and the 30-day all-cause mortality in those with cardiovascular complications is significant.
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ItemCognitive change that matters: the impact of cognitive change as a result of anaesthesia and surgery on functional outcomes and dementia( 2013)This work was undertaken to investigate the long-term impact of anaesthesia and surgery in older and elderly individuals. Cognitive decline has been known to occur following anaesthesia and surgery for some years, however the functional impact of these changes in the short, medium and long-term has not been investigated beyond quality of life. In addition, the association of this cognitive decline with the cognitive decline associated with ageing, dementia and Alzheimer’s disease, has not been prospectively considered. Four study groups were investigated to determine preexisting cognitive impairment (PreCI) and amnestic mild cognitive impairment (aMCI) at baseline prior to healthcare intervention. Postoperative cognitive dysfunction (POCD), aMCI and dementia were then assessed in these patients following non-cardiac (total hip joint replacement [THJR]) surgery and sedation procedures at day 7, 3 months and 12 months; and also at 5 – 10 years following cardiac (coronary artery bypass graft [CABG]) surgery. Patients undergoing non-cardiac surgery (THJR) with normal baseline cognition as assessed by MMSE followed a trajectory of cognitive decline similar to that expected in the general population. For this group, 2% of those without baseline aMCI, and 9% of those with baseline aMCI progressed to dementia over 12 months. In patients undergoing coronary angiography (i.e. with likely cardiovascular disease – CVD) progression to dementia was much greater affecting 9% of those without aMCI at baseline and 30% of those with baseline aMCI by 12 months. Those with subtle impairment of cognition at baseline as evidenced by MMSE ≤ 25 were at even greater risk independent of baseline aMCI status with 43% affected by 12 months. Patients undergoing CABG surgery had a prevalence of dementia at 5 – 10 years following surgery (33%) which is much greater than population prevalence expected for the same age (9%). Patients with dementia at 12 months or 5 – 10 years had reduced quality of life and reduced independent function as measured by instrumental activities of daily living. Baseline cognitive function, measured as aMCI or PreCI, was predictive of decline following healthcare interventions. This work has established that an overlap exists between the cognitive impairment and cognitive changes measured in anaesthetic literature following surgery and anaesthesia (PreCI and POCD) and those from geriatric medicine (aMCI and dementia) in the medium-term (one-year) and long-term (five-ten years). Amnestic MCI (aMCI) and dementia are shown to occur at rates which exceed population expectations in the medium-term following sedation for coronary angiography independent of baseline cognitive status, following general anaesthesia for non-cardiac (THJR) surgery in those with subtle impairment at baseline (MMSE ≤ 25), and in the long-term following CABG surgery. This work has established that those at particular risk are those with subtle impairment of cognition at baseline (aMCI or MMSE ≤ 25), and those with cardiovascular disease (silent or overt). An association between long-term dementia and high dose opioid anaesthesia is identified. This work provides evidence for the critical need to routinely assess cognition at presentation to hospital in older individuals, especially prior to procedures. There is now sound, prospective evidence that patients who have subtle baseline cognitive impairment and cardiovascular disease are at particular risk of accelerated cognitive decline and dementia, even for those procedures requiring light sedation.