University of Groningen
Studies on delirium and associated cognitive and functional decline in older surgical patients
Beishuizen, Sara
DOI:
10.33612/diss.135861414
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Publication date: 2020
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Beishuizen, S. (2020). Studies on delirium and associated cognitive and functional decline in older surgical patients: The time is now to improve perioperative care and outcomes. University of Groningen.
https://doi.org/10.33612/diss.135861414
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Chapter 1
General introduction
General introduction
7
Delirium
Delirium is a neurocognitive disorder that is characterized by a disturbance in attention and cognition with an acute onset and fluctuating course, and has an underlying medical cause.1
Diagnosis is made by recognition of the clinical criteria as formulated by the Diagnostic Manual
of Mental Disorders.1 Delirium prevalence rises with age and is highly dependent on the setting
and population studied. The highest incidence rates are found in the intensive care unit (ICU) and in the postoperative and palliative care setting.2 The pathophysiology of delirium is not fully
elucidated. Currently it is hypothesized that the symptoms of delirium are the result of dysregulated neuronal activity, for which neuronal aging, neuroinflammation, oxidative stress, neuroendocrine dysregulation and circadian rhythm disorders can all be precursors, to a varying degree and in varies combinations.3,4 Whether or not a patient will experience delirium depends
on the interaction between predisposing factors (baseline vulnerability) and precipitating factor (noxious insults that acutely affect the patient).5 A patient with dementia (high baseline
vulnerability) will require a small insult, for example an urinary retention, to become delirious, whereas a previously healthy and active older person might experience delirium only after major surgery or during ICU admission. Prevention and treatment of delirium is most effective with non-pharmacological multicomponent interventions, including reorientation, early mobilization, promotion of sleep, adequate hydration and nutrition, and providing vision and hearing aids.2
The evidence for any effectiveness of pharmacological treatment is poor and is therefore only recommended when the interventions above fail and psychotic features and agitation predominate.6 Delirium negatively impacts important, patient relevant health outcomes, as it
results in an increased risk of institutionalisation, dementia and death.7
Perioperative delirium
Delirium is frequently encountered in the perioperative period, and its incidence depends on type of surgery. In cardiac surgery delirium incidence is generally the highest, with rates of up to 65% being reported.8 In orthopaedic surgery, incidence of delirium ranges between 4-53% in hip
fracture samples and 3-28% in elective samples.29 In vascular surgery incidence rates of 5-39%
are found, and in gastrointestinal surgery numbers range between 8-54%.9,10
When evaluating outcomes, hip fracture surgery patients who experience delirium have a higher mortality rate than patients without delirium.11 There is an increased incidence of dementia
hip fracture surgery.12-14 Delirium superimposed on dementia can further accelerate cognitive
decline in these patients.15 Perioperative delirium also results in functional decline and increased
risk of institutionalization after hip fracture.13,16,17 The same accounts for patients undergoing
cardiac surgery and experiencing delirium, as it was found they are at increased risk of premature death, and cognitive and functional decline.18
With advances in surgical techniques and postoperative care, the number of older patients that are considered suitable for surgery grows.19 This results in more patients that are at risk of
experiencing perioperative delirium and associated negative outcomes. Besides the direct impact that this has on patients and their caregivers, it will also lead to more need for nursing home placements, use of other health care services and thus expanded health care costs. Therefore, a better understanding of the underlying mechanisms that relate delirium to these negative sequelae, and of the characteristics of the patients at risk for these outcomes, is urgently needed.
Hypothesis on association between delirium in the perioperative period and its negative sequelae
There are several possible explanations for the link that is observed between delirium in the perioperative period and subsequent cognitive and functional decline.20 The first is that of shared
risk factors. Many risk factors for delirium, for example older age, multimorbidity and previous cerebrovascular events, are also risk factors for dementia and functional dependence. Delirium can thus be seen as a marker of general vulnerability. Another possible underlying mechanism might be that delirium unmasks previously unnoticed or undiagnosed cognitive impairment. In many cases, the need for surgery is urgent and unplanned, and testing of functional and cognitive status has not performed prior to surgery. After surgery, it is often difficult to establish if there had been any problems in retrospect, especially in the case of more subtle cognitive impairment or when there is no social support system. Lastly, there is the possibility that acute brain damage concurs with delirium, as a result of its severe precipitating factors and/or of its immediate consequences (like apathy, use of sedative medication, complicating infections). Following this hypothesis, damage to neuronal cells during delirium could contribute to the acute symptoms, and cause long term functional and cognitive problems. This brain damage can result from neurotoxicity due to drugs or anaesthesia, or neuronal damage due to ischemia, hypoglycaemia or shock, amongst others, and/or the additional effect that these processes might have on underlying Alzheimer pathology.20 To further explore this hypothesis, a biomarker of brain
General introduction
9
damage would be useful. Several biomarkers have been studied in patients with delirium. These studies have shown elevated levels of inflammatory markers (CRP, IL-6, IL-8) and neuronal cell death in populations of ICU and orthopaedic surgery patients with delirium, and elevated levels of cortisol in cardiac surgery patients with delirium as compared to controls without delirium, although findings are not consistent across all studies.21,22 From these studies, the biomarker
S100 calcium-binding protein B (S100B) emerges as a candidate to study the possible occurrence of brain damage during delirium.
To benefit or not to benefit: how to improve patient outcomes in the older surgery population
When compared to their younger counterparts, older surgery patients are at increased risk of experiencing postoperative morbidity and mortality.23 Previous research has shown that
maintaining functional independence is often valued higher by older patients than survival per se, when ranking treatment goals.24,25 Incorporating these patient-centred outcomes into medical
decision making (alongside the medical indication that is established by the physician) is increasingly being recognized as important in clinical care, especially in older patients.26 Shared
decision making refers to the process in which both the physician and the patient contribute to making a medical decision. It has been shown to improve patient risk perception and satisfaction, and reduce undesired care and costs.27 In order to make shared decision making successful, the
patient needs to be informed about the particular risks, benefits and possible outcomes of a procedure, tailored to their health status and personal circumstances.28 Carefully describing
outcomes of surgery in older patients on measures that are related to their treatment goals, could improve this process. As delirium in surgical patients seems to have an important influence on cognitive and functional performance, it might also be a factor to consider in the shared decision making process.
The aim of this thesis is therefore to study perioperative delirium and its effect on functional and cognitive outcome, in order to improve clinical care and outcomes for these patients.
Outline of the thesis
In the first part of this thesis, we will explore factors that show a temporal relation with the development of delirium in the perioperative period.
In chapter 2 and 3 we investigate the hypothesis of brain damage occurring during delirium as the cause of both the acute symptoms and the subsequent cognitive decline. In chapter 2 we measure the biomarker S100B in cerebrospinal fluid of patients with and without perioperative delirium. In chapter 3 we elaborate on these findings by also measuring S100B in repeated serum samples of patients with and without delirium, and assess if there is a relation with cognitive outcome and mortality one year after hip fracture.
Next, we tackle a clinical dilemma that is often encountered in post-operative hip fracture patients at risk of delirium: should a blood transfusion be performed in patients with a mild anaemia for which current guidelines do not clearly state that a transfusion is required? Will this precipitate a delirious episode or will it prevent one? Firstly, we provide an overview of the available evidence in chapter 4. Next in chapter 5 we return to our own hip fracture cohort to gain further knowledge on this matter.
In the second part of this thesis we investigate the effect of delirium on cognitive and functional performance in the first year after an acute or elective surgical procedure (a subject that was also touched upon in chapter 3).
In chapter 6 we describe the different trajectories of cognitive recovery and decline that are observed in an unselected cohort of hip fracture patients. Lastly, in chapter 7, we investigate the potential association between delirium and functional decline in patients undergoing transcatheter aortic valve implantation, and how this impacts quality of life.
The summary and general discussion on the main findings and recommendations for future research are presented in chapter 8 and 9.
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General introduction
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