Serum Biomarkers of a Pro-Neuroinflammatory State May Define the Pre-Operative Risk for Postoperative Delirium in Spine Surgery.

Advances in spine surgery enable technically safe interventions in older patients with disabling spine disease, yet postoperative delirium (POD) poses a serious risk for postoperative recovery. This study investigates biomarkers of pro-neuroinflammatory states that may help objectively define the pre-operative risk for POD. This study enrolled patients aged ≥60 scheduled for elective spine surgery under general anesthesia. Biomarkers for a pro-neuroinflammatory state included S100 calcium-binding protein ß (S100ß), brain-derived neurotrophic factor (BDNF), Gasdermin D, and the soluble ectodomain of the triggering receptor expressed on myeloid cells 2 (sTREM2). Postoperative changes of Interleukin-6 (IL-6), Interleukin-1ß (IL-1ß), and C-reactive protein (CRP) were assessed as markers of systemic inflammation preoperatively, intraoperatively, and early postoperatively (up to 48 h). Patients with POD (n = 19, 75.7 ± 5.8 years) had higher pre-operative levels of sTREM2 (128.2 ± 69.4 pg/mL vs. 97.2 ± 52.0 pg/mL, p = 0.049) and Gasdermin D (2.9 ± 1.6 pg/mL vs. 2.1 ± 1.4 pg/mL, p = 0.29) than those without POD (n = 25, 75.6 ± 5.1 years). STREM2 was additionally a predictor for POD (OR = 1.01/(pg/mL) [1.00-1.03], p = 0.05), moderated by IL-6 (Wald-χ2 = 4.06, p = 0.04). Patients with POD additionally showed a significant increase in IL-6, IL-1ß, and S100ß levels on the first postoperative day. This study identified higher levels of sTREM2 and Gasdermin D as potential markers of a pro-neuroinflammatory state that predisposes to the development of POD. Future studies should confirm these results in a larger cohort and determine their potential as an objective biomarker to inform delirium prevention strategies.

Cerebrovascular pulsatility indicates preoperative subcortical cognitive impairment and an increased risk for postoperative delirium in elderly patients undergoing elective spine surgery.

Introduction: Advances in spine surgery enable safe interventions in elderly patients, but perioperative neurocognitive disorders (pNCD), such as post-operative delirium (POD) and cognitive dysfunction (POCD), remain a serious concern. Pre-operative cognitive impairment is a major risk factor for pNCD. Comprehensive pre-operative cognitive assessments are not feasible in clinical practice, making effective screening methods desirable. This study investigates whether pre-operative cerebrovascular duplex sonography can assess subcortical (vascular) cognitive impairment and the risk for POD. Methods: This prospective single-center study recruited patients aged ≥60 years scheduled for elective spine surgery at a German university hospital. Patients underwent pre-operative assessments including cognitive abilities (CERAD test battery), structural MRI, and cerebrovascular duplex sonography. POD screening was conducted three times daily for at least 3 days. The primary hypothesis, that the mean pulsatility index (PI) of both internal carotid arteries (ICA) predicts POD risk, was tested using logistic regression. Secondary analyses examined the association between POD risk and ICA flow (time-averaged peak velocities, TAPV) and correlations with cognitive profiles and MRI characteristics. Results: POD occurred in 22% of patients (n = 22/99) within three postoperative days. Patients with POD were significantly older (75.9 ± 5.4 vs. 70.0 ± 6.9 years, p < 0.01) but did not differ by gender (p = 0.51). ICA PI significantly predicted POD risk (OR = 5.46 [95%CI: 1.81-16.49], p = 0.003), which remained significant after adjustment for age and duration of surgery (ORadj = 6.38 [95% CI: 1.77-23.03], p = 0.005). TAPV did not inform the POD risk (p = 0.68). ICA PI Pre-operative cognitive scores were significantly associated with ICA PI (mean CERAD score: r = -0.32, p < 0.001). ICA PI was also significantly associated with total white matter lesion volume (τ = 0.19, p = 0.012) and periventricular white matter lesion volume (τ = 0.21, p = 0.007). Discussion: This is the first study to demonstrate that cerebrovascular duplex sonography can assess the risk for POD in elderly spine surgery patients. Increased ICA PI may indicate subcortical impairment, larger white matter lesion load, and lower white matter volume, predisposing factors for POD. Pre-operative cerebrovascular duplex sonography of the ICA is widely available, easy-to-use, and efficient, offering a promising screening method for POD risk. Increased ICA PI could supplement established predictors like age to adjust surgical and peri-operative procedures to individual risk profiles.

Duration of Surgery and Intraoperative Blood Pressure Management Are Modifiable Risk Factors for Postoperative Neurocognitive Disorders After Spine Surgery: Results of the Prospective CONFESS Study.

STUDY DESIGN: Prospective quasi-experimental observational study. OBJECTIVE: The objective of this study was to evaluate whether duration of surgery is a modifiable risk factor for postoperative delirium (POD) after spine surgery and explore further modifiable risk factors. In addition, we sought to investigate the association between POD and postoperative cognitive dysfunction and persistent neurocognitive disorders. SUMMARY OF BACKGROUND DATA: Advances in spine surgery enable technically safe interventions in elderly patients with disabling spine disease. The occurrence of POD and delayed neurocognitive complications ( e.g. postoperative cognitive dysfunction/persistent neurocognitive disorder) remain a concern since these contribute to inferior functional outcomes and long-term care dependency after spine surgery. MATERIALS AND METHODS: This prospective single-center study recruited patients aged 60 years or above and scheduled for elective spine surgery between February 2018 and March 2020. Functional (Barthel Index, BI) and cognitive outcomes [Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test battery; telephone Montréal Cognitive Assessment] were assessed at baseline, three (V3), and 12 months postoperatively. The primary hypothesis was that the duration of surgery predicts POD. Multivariable predictive models of POD included surgical and anesthesiological parameters. RESULTS: Twenty-two percent of patients developed POD (n=22/99). In a multivariable model, duration of surgery [OR adj =1.61/h (95% CI, 1.20-2.30)], age [OR adj =1.22/yr (95% CI, 1.10-1.36)], and baseline deviations of intraoperative systolic blood pressure [25th percentile: OR adj =0.94/mm Hg (95% CI, 0.89-0.99); 90th percentile: OR adj =1.07/mm Hg (95% CI, 1.01-1.14)] were significantly associated with POD. Postoperative cognitive scores generally improved (V3, ΔCERAD total z -score: 0.22±0.63). However, this positive group effect was counteracted by POD [beta: -0.87 (95% CI, -1.31 to 0.42)], older age [beta: -0.03/yr (95% CI, -0.05 to 0.01)], and lack of functional improvement [ΔBI; beta: -0.04/point (95% CI, -0.06 to 0.02)]. Cognitive scores at twelve months remained inferior in the POD group, adjusted for baseline cognition/age. CONCLUSIONS: This study identified distinct neurocognitive effects after spine surgery, which are influenced by perioperative risk factors. Potential cognitive benefits are counteracted by POD, rendering its prevention critical in an aging population.