Delirium is an acute confusional state and a common postoperative morbidity. Prevalent in older adults, delirium occurs at other ages but it is unclear whether the pathophysiology and biomarkers for the condition are independent of age. We quantified expression of 273 plasma proteins involved in inflammation and cardiovascular or neurologic conditions in 34 middle-aged and 42 older patients before and one day after elective spine surgery. Delirium was identified by the 3D-CAM and comprehensive chart review. Protein expression was measure by Proximity Extension Assay and results were analyzed by logistic regression, gene set enrichment, and protein–protein interactions. Twenty-two patients developed delirium postoperatively (14 older; 8 middle-aged) and 89 proteins in pre- or 1-day postoperative plasma were associated with delirium. A few proteins (IL-8, LTBR, TNF-R2 postoperatively; IL-8, IL-6, LIF, ASGR1 by pre- to postoperative change) and 12 networks were common to delirium in both age groups. However, there were marked differences in the delirium proteome by age; older patients had many more delirium-associated proteins and pathways than middle-aged subjects even though both had the same clinical syndrome. Therefore, there are age-dependent similarities and differences in the plasma proteomic signature of postoperative delirium, which may signify age differences in pathogenesis of the syndrome.
Purpose To examine the relationship between postoperative pain and opioid use and the development of postoperative delirium (POD), with attention to the preoperative opioid use status of patients. Methods This was a secondary analysis of data from a prospective observational study of patients (N = 219; ≥70 years old) scheduled to undergo elective spine surgery. Maximal daily pain scores (0–10) and postoperative morphine milligram equivalents per hour (MME/hr) were determined for postoperative days 1–3 (D1-3). POD was assessed by daily in-person interviews using the Confusion Assessment Method and chart review. Results Patients who reported regular preoperative opioid use (n = 58, 27%) reported significantly greater maximal daily pain scores, despite also requiring greater daily opioids (MME/hr) in the first 3 days after surgery. These patients were also more likely to develop POD. Interestingly, while postoperative pain scores were significantly higher in patients who developed POD, postoperative opioid consumption was not significantly higher in this group. Conclusion POD was associated with greater postoperative pain, but not with postoperative opioid consumption. While postoperative opioid consumption is often blamed for delirium, these findings suggest that uncontrolled pain may actually be a more important factor, particularly among patients who are opioid tolerant. These findings underscore the importance of employing multimodal perioperative analgesic management, especially among older patients who have a predilection to developing POD and baseline tolerance to opioids.
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