Background
Delirium, derived from the Latin
deliriare “go off the furrow”, describes a disturbance, or clouding, of consciousness and is diagnosed by fulfilling diagnostic criteria such as those proposed in the Diagnostic and Statistical Manual of Mental Disorders (DSM) [
1,
2]. Additional features include agitation, hallucinations and disturbance in the sleep–wake cycle. Delirium is a multifactorial syndrome, associated with significant morbidity and mortality. A previous meta-analysis of hospitalised patients reported that a single episode of delirium was associated with a doubling of mortality rate [
3,
4]. Although traditionally considered a transient phenomenon, increasing research shows that delirium can become persistent and is a risk factor for incident dementia [
5].
Delirium can be described as prevalent, i.e. found on admission, or incident, when it develops during the hospital admission. Incident delirium is a serious concern in surgical disciplines; delirium rates of over 50% have been reported in older adults undergoing major non-cardiac surgery [
4]. Previous research into post-operative delirium (POD) has focused on major orthopaedic or cardiac surgery, with urological patients under-represented [
6,
7].
There are reasons to believe that delirium may be a particular issue in Urology. Common urological diseases, including cancers and benign prostatic hyperplasia (BPH), are strongly associated with increasing age which is a generally accepted risk factor for delirium [
8,
9]. Urological interventions can be associated with infection, electrolyte disturbance or prescription of anticholinergic drugs—all of which can be triggers to a delirium episode. With changing population demographics and changing expectations of surgery, the urological surgeon is increasingly managing older adults living with frailty and comorbidity, which may further increase the risk of delirium.
A better understanding of urological POD epidemiology and risk factors could inform decisions about treatment. Multicomponent interventions may prevent delirium and if high risk patients could be identified these resources could be applied appropriately [
10].
The aim of this study was to identify risk factors for delirium in patients undergoing urological surgery. Systematic reviews of POD in other surgical areas reported small sample sizes and uncertainty in conclusions [
6,
11‐
16]. In this context a comprehensive evidence synthesis can offer the clarity needed to inform practice, research and policy.
Discussion
Seven studies [
26‐
30] were identified for inclusion in this systematic review assessing risk factors associated with POD in urological surgical patients. The included studies had a predominantly elderly male patient population and analysed a variety of risk factors for their association with delirium post operatively. The 16 broad risk factors were reported using 26 different methods and studies included patients undergoing very different operations, allowing only nine risk factors to undergo meta-analysis; the majority only containing data from 2 studies. Of the risk factors included in meta-analysis, the clock drawing test and age were the only two that reached statistical significance.
Although the other risk factors were not found to be significantly associated with delirium, it is important to interpret these with caution as four of the included studies were deemed to be at a high risk of bias. In addition, the majority of risk factors assessed within the meta-analysis contained data from two studies. Meta-analysis was limited by the heterogeneity of the data and the types of operations included, with a number of risk factors unable to be pooled or limited studies for the meta-analysis. These included co-morbidities and IADLs, both found within the individual studies to be associated with the development of post-operative delirium.
With regard to co-morbidity, this was higher within the delirium group in four of the studies [
27,
28,
30,
31] with one study finding a significant association [
31]. Pooling was only possible for two studies (two or more co-morbidities). The result suggests that having two or co-morbidities is associated with POD, although it did not achieve our cut off for statistical significance (p = 0.056) and included one study at high risk of bias. This could be either to true lack of association or due to lack of statistical power. Therefore, research with a larger cohort of patients, using the same assessment method and possibly looking at specific co-morbidities such as dementia, depression and visual/hearing impairment would be of use. A shorter duration of education also appears to be associated with an increased risk of POD despite again not achieving significance within the meta-analysis (p = 0.051) possibly for the same reasons as co-morbidity.
The two significant results in the meta-analysis were a lower mean CDT score and higher mean age in those who developed POD. These results should be interpreted with caution as both analyses included studies at high risk of bias. The sensitivity analysis conducted, based on study risk of bias, also suggests the result for the association between older age and POD is not very robust and limits its interpretation. Despite this, advancing age is a well-recognised risk factor for delirium and similar associations have been demonstrated within the literature [
12‐
15,
39]. CDT is a screening tool for cognitive impairment and dementia [
36], and the association with delirium may justify its use to establish underlying cognitive impairment preoperatively and delirium risk postoperatively [
20]. Finally, ADL was not initially found to be associated with POD, but after excluding studies at high risk of bias, there appeared to be an association. However, its interpretation is limited due to small study sample sizes.
Numerous systematic reviews have been undertaken in both surgical and non-surgical patient populations. Reviews in post-operative surgical patients have mainly focused on Vascular [
12], Gastrointestinal [
11], Cardiac [
13,
14] and Orthopaedic [
6,
15,
16] specialties, with incidence ranges (4%-55%) aligning with the results from this systematic review. Incidence ranges are also similar in the medical inpatient setting [
17,
40], but significantly higher within intensive care [
39,
41]. A multitude of risk factors have been analysed via meta-analyses or multivariable analyses for an association with incident delirium. Most commonly, increasing age [
12‐
15,
39], cognitive impairment [
6,
13,
14,
16] and alcohol excess [
11,
39] have been identified to increase the risk of developing delirium. Other factors were more mixed, similar to results observed within this review, such as BMI and sex [
12,
15‐
17,
39].
These previous systematic reviews on incident delirium have also highlighted the heterogeneity in the risk factors analysed within the included studies and difficulties pooling results in a similar manner to this review. As discussed above, a low mean CDT score was identified within this review to be associated with POD, a result not replicated within the current body of systematic reviews. Although not technically a risk factor, it does present a potential screening tool to identify those at risk of delirium who could then be targeted for interventions to reduce the risk of POD occurring. Although promising, these results do have limitations and therefore the CDT would need extensive further evaluation before use as a screening tool within clinical practice. A recently published prospective study of over 1000 patients identified a different cognitive screening tool for dementia was associated with development of POD [
42]. The authors found that a Hasegawa Dementia Scale-Revised (HDS-R) score of less than 20 was an independent risk factors for POD in elderly urological patients [
42]. However, they also identified that its use for all urological patients would be limited as only 3% of patients with this as their only risk factor developed POD [
42]. These considerations would need to be taken into account for CDT also.
This review does have a number of limitations. The main one being that there are relatively few studies on this subject within the literature and the numbers of patients within those studies are relatively small. Therefore, the lack of association found may be a result of a lack of statistical power rather than there being no true association. The largest study was not well detailed [
26] and the majority of studies are at a high risk of bias. The heterogeneity of the risk factors studied and inconsistency between the studies in how the data were recorded makes it difficult to fully assess the various risk factors. In terms of limitations of the studies themselves, the major issue was with assessment of delirium. This occurred once per day in the majority of the studies which, in view of the fact delirium has a fluctuating course, may mean some cases were missed and thus the true incidence of post-operative delirium is likely to have been under reported. A final limitation is that two of the studies excluded patients with Alzheimer's and dementia without adequate explanation. This is especially important, as dementia is known to be a risk factor for the development of delirium [
14].
This review has highlighted that there is a lack of research in post-operative delirium in urological patients and within the relevant studies there is heterogeneity between the risk factors assessed, often with small numbers of patients. Importantly, this review has identified a number of potential areas for future research. A number of statistically significant risk factors in individual studies, including MMSE, CDT, depression, IADL functions, previous delirium, severity of urological disease, duration of surgery and intra-operative hypotension, were reported as being associated with the development of post-operative delirium. To improve our understanding of delirium in this group of patients, future studies should focus on comparable risk factors and methods of data collection as well as possible collaborative work.
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