University of Groningen The effects of age, delirium and frailty on outcome after vascular surgery Visser, Linda

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University of Groningen

The effects of age, delirium and frailty on outcome after vascular surgery

Visser, Linda

DOI:

10.33612/diss.167691672

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.

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Publication date: 2021

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Citation for published version (APA):

Visser, L. (2021). The effects of age, delirium and frailty on outcome after vascular surgery. University of Groningen. https://doi.org/10.33612/diss.167691672

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GENERAL INTRODUCTION AND OUTLINE OF THIS THESIS

The population in Western countries is ageing rapidly, with the percentage of the population aged over 60 increasing from 20-30% to >30% between 2015 and 2050 in Europe.1_Since

cardiovascular diseases are to a great extent age-related, the number of patients affected is increasing, and will increase even more in the future. As a result, more elderly patients will be referred for surgery, especially vascular surgery. In these patients, the burden of chronic disease increases, making them prone to more and other types of postoperative complications, including delirium.

Atherosclerosis, the basis of vascular disease, leads to a high prevalence of additional diabetes mellitus, hypertension and myocardial infarction. Elderly vascular surssgery patients therefore have a decreased tolerance for operation, leading to impaired outcome. Most classic vascular procedures are major operations, including open abdominal aortic repair and limb amputation. Historically, clinicians were used to make their decisions on whether or not to operate based on their own expertise. Therefore, in the past elderly patients were often refrained from surgery because of their age and comorbidities. But novel surgical techniques have led to less invasive treatment options, associated with lower morbidity and mortality rates, resulting in more elderly patients undergoing surgery. For instance, with the introduction of endovascular aneurysm repair (EVAR) patients confronted with abdominal aortic aneurysm (AAA) could be offered a safe, less invasive alternative to open aortic repair.

Although previous studies have shown that the elderly could be treated safely, they are more susceptible to certain types of postoperative complications compared to younger patients. One of these complications is postoperative delirium (POD), one of the most common complications after major surgery, with a prevalence up to 51%%.2-5_{The American Psychiatric Association’s}

Diagnostic and Statistical manual of Mental Disorders 5th_{Edition (DSM-V) defined delirium}

as a disturbance in attention cognition and/or awareness that develops over a short period and has a fluctuating course.6 _{Although the pathogenesis is not completely understood,}

delirium is a multifactorial syndrome, resulting from predisposing patient related risk factors and precipitating factors related to surgery, anaesthesia and hospitalization. Especially when both are present, delirium is common during hospitalization. The most important patient related risk factor is advanced age, due to an accumulation of other comorbidities, including those linked to atherosclerosis, and a reduced cognitive reserve. Surgery causes the release of psychoactive inflammatory markers that, through dopamine, GABA or cholinergic-mediated pathways, contribute to the development of POD. In addition, general anaesthesia exposes the brain to a cascade of chemical reactions resulting in an altered sleep-wake cycle.7 _Since

vascular surgery patients are often older, and frequently scheduled for major interventions, they are at increased risk for POD compared to other types of surgical patients. Symptoms of POD generally arise shortly after surgery, but can also occur after a few days, and can last up to several weeks. On the short-term, patients suffering from POD are at increased risk for

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other complications, for instance (aspiration) pneumonia or urinary tract infections, longer intensive care unit (ICU) stay, longer hospital stay, increased post discharge institutionalization, and even mortality. On the long-term, postoperative cognitive dysfunction, prolonged brain dysfunction, early dementia, and acceleration in the cognitive decline in Alzheimer’s patients are all associated with POD.8,9 _{All those factors not only have influence on the wellbeing of}

the patient, but also on the patient’s family.10_{Moreover, POD leads to increased nursing}

workload and resource use, resulting in extra healthcare costs, making it a problem for the entire community.11

One of the challenging aspects of POD, is that because of fluctuating symptoms it is unrecognized in approximately 50% of hospitalized patients. Especially in the elderly, in which hypoactive delirium is more frequent, the diagnosis is frequently missed, although it is related with a poor prognosis. Various interventions have been studied to reduce the morbidity of delirium, but primary prevention seems to be the most effective strategy. With simple non-pharmacological interventions by dedicated staff, delirium is preventable in one third of cases. When POD does occur despite these interventions, early geriatric consultation in combination with medication reduces the severity and duration of POD.12 _{Therefore, pre-operative identification of high-risk}

patients is of great value. Parameters related to POD are different in various types of patients, underlining the need for identification of these factors in all medical fields.

Over the years, it has become more evident that age alone might not be the best predictor for outcome after surgery, and that frailty is a better predictor.13-15_{Frailty could be characterized}

either as a state or as a syndrome. The latter, which is widely used, defines frailty as a multifactorial syndrome, a state of increased vulnerability due to a decline in reserve and function, resulting in a decreased ability to cope with physiological stressors.16_{Recent studies}

have shown that endothelial dysfunction, an early stage of vascular disease, is associated with frailty, and that therefore vascular surgery patients are at increased risk compared to other surgical patients. Over recent years a lot of attention and research has been put in determining the influence of frailty.17-19_{Because of the underlying cause of the disease, risk factors may}

differ between different populations. It is still unclear which of the elements of frailty have the greatest impact on outcome after (vascular) surgery and which elements therefore justify a targeted intervention.

Aims and outline of this thesis

Age, delirium and frailty all have great impact on outcome after surgery. Although they are all related to each other and have similar characteristics or risk factors, they are not exchangeable. The question which patients would benefit from surgery and which will not, remains one of the most challenging aspects surgeons face in the 21st_{century. Pre-operative risk assessment gives}

us the ability to screen for possible risk factors for impaired outcome. Ideally, patients could be optimised preoperatively, so they are in the best possible condition before surgery. Also, when high risk patients are identified, this may rise vigilance to recognition of complications,

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CHAPTER 1

resulting in earlier treatment and thereby less severe manifestation of disease. The aim of this thesis was to investigate which factors contribute to impaired outcome after vascular surgery with emphasis on age, delirium and frailty.

If complications in the elderly differ from complications in younger patients, and we should approach them differently, then should follow-up also be adjusted with increasing age? With a limited life expectancy, octogenarians are more likely to die from other diseases than aneurysm related causes. Frequent follow-up may be experienced as very stressful by older patients, and also in the context of cost reduction, follow-up should be restricted to those indispensable. This is especially important in patients following EVAR, since currently life-long follow-up is standard procedure. In chapter 2 a study was performed to determine whether long-term

follow-up is mandatory after EVAR in octogenarians, or that older age could be a reason for an adjusted scheme, in which the aneurysm related death is still low.

Systemic atherosclerosis contributes to diabetes mellitus, hypertension, myocardial infarction and cerebrovascular disease, which are highly prevalent in vascular surgery patients, and appear to be nonspecific risk factors for POD. Although POD occurs in patients of all ages, old age has been proven to be a major predisposing factor. Structural brain disease, vision and hearing impairments, reduced capacity for homeostasis and changes in pharmacokinetics make the brain of the elderly more prone to POD. Although recent years there has been a lot of attention for this postoperative complication, it is still unclear which factors are the strongest predictors. Identifying those patients at risk is of great value, since frailty is potentially reversible, and improving risk factors not only lessens the incidence of delirium, but also lessens the length of hospital stay and increases the amount of patients being able to return to their own homes. In chapter 3 we present a systematic review and meta-analysis on specific risk factors for

POD in vascular surgery patients. In chapter 4 we evaluated the incidence of POD in an own

cohort of vascular surgery patients, and we provided a model which could predict the risk for POD in the individual patient.

In chapter 5 we focus not only on POD, but on postoperative complications in general,

re-admission to the hospital and type of care facility after discharge. The aim of this study was to determine whether frailty is associated with adverse outcomes. Frailty is a state of increased vulnerability due to physiological changes in the brain, endocrine system, immune system and the muscles. As a result, relatively minor illnesses have greater impact. In most screening tools, frailty is classified into different groups, consistent with the domains of function. However, they differ in the type of domains they cover, and there is no single universally accepted method to measure frailty. Also, some of the domains of frailty have more impact on outcome than others. In this study we determine whether frailty has an impact on outcome, and which domains have the most important impact.

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Other than frailty, there are several risk factors related to cardiovascular disease with influence on postoperative outcome. In chapter 6 we evaluate the incidence of the metabolic syndrome

(MetS) in patients undergoing carotid endarterectomy (CEA) and whether this syndrome leads to impaired outcome after surgery. In chapter 7, all these chapters will be summarized and

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