SAGES - Successful Aging after Elective Surgery

Objectives

The Successful Aging after Elective Surgery (SAGES) I study was performed to identify novel risk factors for delirium, including blood-based biomarkers and cognitive reserve markers, and to describe the long-term effects of delirium on cognitive and functional capacity in older adults following elective surgery. The study was funded by a Program Project grant (P01AG031720) from the National Institute on Aging, a component of the National Institutes of Health. The SAGES I study was completed during the first cycle of this Program Project grant.

Background

Older adults commonly develop delirium after major surgical procedures, characterized by acute confusion and reduced awareness. From the literature, delirium has been associated with many adverse short-term outcomes including increased postoperative complications, prolonged hospital stay, increased need for post-discharge skilled nursing facility care, and increased perioperative mortality. Long term, delirium is associated with cognitive and functional decline, increased costs, and possibly incident dementia. SAGES’ overall aims were to examine the long-term effects of postoperative delirium on trajectories of physical and cognitive function in older patients, controlling for detailed baseline status, and to identify novel risk factors associated with delirium, which might shed light on its pathophysiology, enabling design and testing of targeted interventions.

Study Design

SAGES I was a five-year prospective cohort study that enrolled 560 patients, who were all recruited from two large hospitals in Boston, Massachusetts from 2010 to 2013, with follow-up to 2015. Participants were age 70 years and older, scheduled to undergo major elective surgery with an expected hospital stay of at least two days, and who did not have diagnosed or recognizable dementia. Individuals were excluded from enrollment if dementia, active delirium, or other cognitive impairment were present prior to surgery; other exclusions included hospitalization within three months of study enrollment, terminal illness, or a condition that might confound recognition of delirium (e.g., schizophrenia), or that might preclude completion of follow-up interviews (e.g., cancer requiring intensive chemotherapy). Study participants underwent detailed in-home baseline assessments for physical and cognitive function prior to surgery. During their post-surgery hospital stay, patients were interviewed daily to assess for delirium using the long Confusion Assessment Method (CAM), which enables determination of delirium presence using the CAM algorithm, and measurement of delirium severity using the CAM-S long and short forms. Delirium presence was also ascertained by a validated chart review approach. After hospital discharge, participants completed telephone and in-home assessments to measure cognitive and physical function at predetermined intervals (1,2,6,12, and 18 months post-operatively) during follow-up, which ranged up to 18 months. Additionally, blood-based biomarkers were obtained from participants at four time points—baseline (preoperatively), in the post-anesthesia care unit, on the morning of postoperative day 2, and at one-month following surgery. Clinical data included health habits, hearing/vision impairment, comorbidity, and frailty at baseline. Finally, cognitive reserve markers, including personal educational history and reading level, were obtained.

Conditions

Interventions/Treatment Groups

SAGES I was an observational study; as such, no therapeutic interventions or treatment groups were used in this study.

Outcomes

The major outcomes for the SAGES I study were incidence of postoperative delirium, and serial cognitive and physical functional status after surgery, which were obtained at pre-specified follow-up periods as noted above. Additional outcomes include: 1) delirium severity (CAM-S); 2) hospital length of stay, 3) discharge to a post-acute facility.

Results/Conclusions

Among the 560 SAGES I participants, 134 (24%) developed postoperative delirium. Patients with delirium experienced prolonged hospital length of stay, higher rates of discharge to institutional settings, and worse physical functional recovery after discharge. In terms of cognitive function, patients who experienced delirium (relative to those who did not) demonstrated acute declines from baseline at one month after surgery, followed by recovery at 2 months, and then a steeper long term cognitive decline after surgery. Additional study findings include the identification of blood-based markers of delirium linked to inflammation, including C-reactive protein (CRP). Additionally, analyses of cognitive reserve/vulnerability markers demonstrated the importance of pre-surgical cognitive functioning, with the Wechsler Test of Adult Reading (WTAR), a measure of crystallized intelligence, and general cognitive performance (neuropsychological composite) among the strongest predictors of postoperative delirium. Data generated from the SAGES I study continues to serve as a foundation for further research and statistical analyses pertaining to postoperative delirium in older patients, with over 125 scientific publications to date.