Publications

OBJECTIVES

To summarize the delirium treatment trial literature, identify the unique challenges in delirium treatment trials, and formulate recommendations to address each in older adults.

DESIGN

A 39-member interprofessional and international expert working group of clinicians (physicians, nurses, and pharmacists) and nonclinicians (biostatisticians, epidemiologists, and trial methodologists) was convened. Four expert panels were assembled to explore key subtopics (pharmacological/nonpharmacologic treatment, methodological challenges, and novel research designs).

METHODS

To provide background and context, a review of delirium treatment randomized controlled trials (RCTs) published between 2003 and 2023 was conducted and evidence gaps were identified. The four panels addressed the identified subtopics. For each subtopic, research challenges were identified and recommendations to address each were proposed through virtual discussion before a live, full-day, and in-person conference. General agreement was reached for each proposed recommendation across the entire working group via moderated conference discussion. Recommendations were synthesized across panels and iteratively discussed through rounds of virtual meetings and draft reviews.

RESULTS

We identified key evidence gaps through a systematic literature review, yielding 43 RCTs of delirium treatments. From this review, eight unique challenges for delirium treatment trials were identified, and recommendations to address each were made based on panel input. The recommendations start with design of interventions that consider the multifactorial nature of delirium, include both pharmacological and nonpharmacologic approaches, and target pathophysiologic pathways where possible. Selecting appropriate at-risk patients with moderate vulnerability to delirium may maximize effectiveness. Targeting patients with at least moderate delirium severity and duration will include those most likely to experience adverse outcomes. Delirium severity should be the primary outcome of choice; measurement of short- and long-term clinical outcomes will maximize clinical relevance. Finally, plans for handling informative censoring and missing data are key.

CONCLUSIONS

By addressing key delirium treatment challenges and research gaps, our recommendations may serve as a roadmap for advancing delirium treatment research in older adults.

BACKGROUND

Older adults often require surgical care and are at elevated risk of delirium. We explored delirium risk profiles across the population of U.S. older adults who underwent one of 10 common noncardiac surgeries.

METHODS

We analyzed Health and Retirement Study (HRS) participants linked with Medicare billing data who underwent the following 10 noncardiac surgeries from 2000 to 2018 at age 65 or more: total knee arthroplasty (TKA), total hip arthroplasty (THA), spine surgery, cholecystectomy, colorectal surgery, hernia repair (ventral, umbilical, or incisional), endarterectomy, prostatectomy, transurethral resection of the prostate (TURP), and hysterectomy. Demographic and health covariates were obtained from the HRS dataset. Latent cognitive ability was calculated from cognitive testing, proxy reports, and demographics at the preoperative HRS interview. We compared standardized differences for delirium risk factors across the 10 surgeries and qualitatively clustered them into phenotypical subgroups.

RESULTS

We analyzed 7424 older adults (mean age 76 ± 6 years, 45% male). Endarterectomy patients presented with the highest burden of nearly all health and cognitive factors, implying higher delirium risk (e.g., stroke, 22%; depressive symptoms, 30%; high school or less education, 73%; frailty, 42%; lowest latent cognitive ability). A second "general surgery" phenotype, including cholecystectomy, colorectal, and hernia surgery patients, experienced more frailty (29%-32%) and depressive symptoms (24%-26%), with moderate comorbidity burden. A third "pain" phenotype, which included TKA, THA, and spine surgery patients, commonly reported moderate or severe pain (47%-53%) and impairment in activities of daily living (ADL, 23%-30%), but fewer comorbid medical conditions. The remaining surgery types (hysterectomy, prostatectomy, TURP) were not phenotypically grouped and generally had lower risk features for delirium.

CONCLUSION

In an epidemiological cohort of US older adults, we identified clinically meaningful heterogeneity in delirium risk profiles across different surgical types, which may have implications for delirium risk stratification and delirium prevention or treatment.