Prevention of Cardiovascular and Renal Outcomes in Patients undergoing Non Cardiac Surgery

Abstract

Background- Surgery is an essential component of heath care worldwide, however is increasingly associated with significant rates of adverse peri-operative myocardial infarction (PMI) and acute kidney injury (AKI), which are both potent post-operative complications associated with major morbidity and mortality. These events can be clinically silent and their diagnosis missed, yet whether clinically symptomatic or not they are strongly associated with worse post-operative outcomes. The goal of this work is to examine the opportunities to prevent PMI and AKI. Starting in the pre-operative setting, evaluation, management and implementation of current perioperative guidelines prior to surgery is likely to be key to this. In addition, understanding the application of risk prediction and the accuracy, role and contribution of biomarkers to predicting risk of perioperative adverse events is important. Here we focus on the more sensitive and novel biomarkers of renal function including the role of estimated Glomerular Filtration Rate (eGFR), cystatin c, urinary albumin: creatinine ratio (ACR) and Neutrophil Gelatinase Associated lipocalin (NGAL) and their association with adverse post-operative cardiac events, AKI and mortality. Thesis outline- The chapters and their objectives are detailed below: Chapter 2: Describes the methodology used. This incorporated a prospective cohort study of patients > 45 years old undergoing non cardiac surgery with at least one night in hospital and at least regional anaesthesia. Patients were recruited from Westmead hospital, a tertiary hospital in Western Sydney, NSW Australia. Data were collected on pre-, intra- and post-operative clinical factors as well as follow up at 30 days after surgery. Chapter 3: This chapter examines the pre-operative evaluation in terms of cardiovascular investigations and management of patients prior to surgery. It compares this to existing guidelines identifying a number of inconsistencies. It identifies both under and over utilisation of cardiac testing in disparate groups. It identifies in particular that those with known cardiovascular disease were undertreated with respect to preventative medications. Chapter 4: This was an analysis of the international VISION cohort recruited up till June 2011 and includes both patients recruited from Westmead hospital and participants from other sites. The aim of these analyses were to examine the prevalence of cardiovascular disease in this international cohort, the use of preventative medications and thus to document opportunities for prevention. From this it used modelling to determine predicted 5-year risk of cardio-vascular events with current medication adherence and compared this with optimization of adherence. Despite a history of either coronary, cerebro or peripheral vascular disease, only 1 in four patients were on optimal prevention, and one in 10 were on no secondary prevention. Chapter 5: In focussing on the role of renal biomarkers in predicting perioperative MI and AKI, this chapter describes a systematic review and meta-analysis of the literature, examining the strength of association between eGFR and post-operative events. The eGFR was strongly associated with post-operative outcomes, with a three-fold increase in risk of death within 30 days of surgery for patients with a pre-operative eGFR < 60 ml/min/1.73m2. Chapter 6: In the Westmead cohort, among those that provided urinary samples prior to surgery, these analyses examined the association of urinary ACR with PMI and AKI. It found that pre-operative urinary ACR was not predictive of cardiac or renal events, or mortality within 30 days after surgery. Chapter 7: In this chapter, the role of pre-operative cystatin c and creatinine based eGFR on mortality at long term follow up was examined. A separate cohort of patients undergoing cardiac surgery in Aberdeen, Scotland, was analysed. Cystatin c was found to be strongly associated with all-cause mortality at long term follow up. Its predictive utility did not improve on the EUROSCORE. Chapter 8: This chapter looks at association between post-operative NGAL levels and outcomes. It was based on the non-cardiac surgical cohort recruited at Westmead hospital who supplied post-operative urine samples. From this NGAL levels were analysed for association with post-operative AKI, and predictive utility. Elevated NGAL after surgery was not associated with cardiac or renal events, or all-cause mortality within 30 days of surgery. Conclusion- Despite improvements in surgical safety, a large number of patients are at risk of post-operative medical complications leading to organ injury and death. Pre-operative risk assessment is integral to prevention, though this is haphazard with implications for cost and delay to surgery. Furthermore, many patients presenting for surgery have cardiovascular disease, but lack adequate treatment and are at higher risk of future cardiovascular events. Finally, some alternative markers of renal function have stronger association with post-operative outcomes and have potential to improve risk stratification. Within this thesis it is suggested that outcomes can be improved by: Adherence to pre-operative assessment guidelines; optimizing vascular risk management for patients with cardio-vascular disease; and use of more sensitive renal biomarkers in risk predictive algorithms.