Predisposing and Precipitating Factors Associated With Delirium

Abstract

ImportanceDespite discrete etiologies leading to delirium, it is treated as a common end point in hospital and in clinical trials, and delirium research may be hampered by the attempt to treat all instances of delirium similarly, leaving delirium management as an unmet need. An individualized approach based on unique patterns of delirium pathophysiology, as reflected in predisposing factors and precipitants, may be necessary, but there exists no accepted method of grouping delirium into distinct etiologic subgroups.ObjectiveTo conduct a systematic review to identify potential predisposing and precipitating factors associated with delirium in adult patients agnostic to setting.Evidence ReviewA literature search was performed of PubMed, Embase, Web of Science, and PsycINFO from database inception to December 2021 using search Medical Subject Headings (MeSH) terms consciousness disorders, confusion, causality, and disease susceptibility, with constraints of cohort or case-control studies. Two reviewers selected studies that met the following criteria for inclusion: published in English, prospective cohort or case-control study, at least 50 participants, delirium assessment in person by a physician or trained research personnel using a reference standard, and results including a multivariable model to identify independent factors associated with delirium.FindingsA total of 315 studies were included with a mean (SD) Newcastle-Ottawa Scale score of 8.3 (0.8) out of 9. Across 101 144 patients (50 006 [50.0%] male and 49 766 [49.1%] female patients) represented (24 015 with delirium), studies reported 33 predisposing and 112 precipitating factors associated with delirium. There was a diversity of factors associated with delirium, with substantial physiological heterogeneity.Conclusions and RelevanceIn this systematic review, a comprehensive list of potential predisposing and precipitating factors associated with delirium was found across all clinical settings. These findings may be used to inform more precise study of delirium’s heterogeneous pathophysiology and treatment.

Multivariable model of postoperative delirium in cardiac surgery patients: proteomic and demographic contributions

“…From the demographic perspective, we found that age is associated with increased risk of delirium, as previously shown 27 . However, even though males represent the larger portion of patients undergoing cardiac surgery, our data indicate that females are more likely to experience delirium, differing from the current literature reporting male sex as an inconsistent risk factor for delirium in both cardiac and noncardiac surgeries [28][29][30] .…”

Sex-specific clinical characteristics and treatment responses in delirium management: findings from a prospective cohort study in elderly patients

“…Subtype assignment was based on DOS items 10, 11, and 13, an acknowledged procedure (Scheffer et al, 2011). Most previous studies reported similar findings using different assessment tools (Ormseth et al, 2023). From those reports neglecting sex differences, one recent study analyzed the Delirium Motor Subtype Scale (DMSS) and the Delirium Rating Scale R98 (DRS-R98) in a pooled cohort of medical and surgical in-and outpatients (Trzepacz et al, 2018).…”

“…The investigation of sex differences in neuropsychiatric diseases is clinically relevant to tailor individualized patient care but remains, so far, under-recognized (Tierney et al ., 2017). A recently published comprehensive systematic review consisting of 315 studies and data from more than 100 000 patients indicated that the data remain unclear as to whether sex is a predisposing factor regarding the development of delirium and distinct subtypes (Ormseth et al ., 2023). Sex differences in the incidence of delirium have been reported in surgical patients often observing a higher incidence in men (Aldemir et al ., 2001; Shiiba et al ., 2009; Vasilevskis et al ., 2012; Oh et al ., 2016; Wittmann et al ., 2022), although other studies do not support this notion (Oe et al ., 2019).…”

Reexamining cholinesterase inhibitors for the prevention and treatment of delirium in high-risk populations

“…Several randomized controlled trials have evaluated the ability of AChEi to prevent or treat delirium [8][9][10][11][12][13]; however, none has tested these medicines in a critically ill population enriched for preexisting central cholinergic deficits, such as those with dementia. Early studies that focused on prevention of delirium prior to an elective operation showed minimal benefit, although these were of varying methodological rigor [8,9,13,14]. Unfortunately, a large trial comparing behavioral management with haloperidol and placebo versus haloperidol and rivastigmine in a general population of critically ill adults was stopped early due to a signal suggesting increased mortality in the rivastigmine group; however, differences in baseline characteristics between the groups call into question whether this would have been borne out in a fully powered trial [11].…”

“…1). Given the broad range of predisposing factors and precipitants for delirium among critically ill patients [14], careful study population selection, including those with preexisting cognitive impairment or biomarkers of reduced cholinergic signaling, may maximize the potential for detecting a clinically relevant benefit. Designing such a clinical trial would necessitate identifying a population at high risk for developing delirium.…”