Pre-Operative, High-IL-6 Blood Level is a Risk Factor of Post-Operative Delirium Onset in Old Patients

Abstract

Background: Post-operative delirium (POD) is a common complication in elderly patients undergoing surgery, but the underpinning causes are not clear. We hypothesized that inflammaging, the subclinical low and chronic grade inflammation characteristic of old people, can contribute to POD onset. Accordingly, we investigated the association of pre-operative and circulating cytokines in elderly patients (>65 years), admitted for elective and emergency surgery.

Methods: This is a secondary analysis of a sub-cohort of patients belonging to a previous large case-control study, where 351 patients were clinically and cognitively thoroughly characterized, together with the assessment of POD (47 patients) by confusion assessment method and delirium rating scale. Seventy-four pre-operative plasma samples were selected from a larger bio-bank and they included 37 subjects with POD and 37 without POD. Inflammaging related cytokines, i.e., IL-1β, IL-2, IL-6, IL-8, IL-10, and TNF-α, were assayed by ELISA in pre-operative blood samples; univariate and multivariable analyses have been applied to identify cytokines independently associated to POD. Associations of cytokine levels with functional status, cognitive decline, intra-hospital mortality, and comorbidity were also analyzed independently of POD onset.

Results: High IL-6 and low-IL-2 levels were significantly associated with POD. After adjustment for potential confounders in multivariate analysis, high level of pre-operative IL-6 was confirmed to be significantly associated with risk of POD onset. High level of IL-6 was also associated with several baseline features (including poor functional status, cognitive impairment, emergency admission, and higher comorbidity burden) and intra-hospital mortality.

Conclusion: Pre-operative, high-plasma level of IL-6 (≥9 pg/mL) was significantly associated with POD onset. We propose IL-6 as an additional risk factor of POD onset together with the previously identified factors. Discovery of all risk factors contributing to POD onset will permit to improve hospitalized patient management and the decrease of healthcare cost.

Keywords: IL-6; aging; inflammaging; inflammatory cytokines; post-operative delirium.

Figure 1

Pre-, intra-, and post-operative risk factors were evaluated in univariate and multivariate analyses, depicted as a funnel; the numbers reported in the figure are referred to the previous work (14). In this paper, by means of a sub-cohort of 74 patients (37 controls and 37 with POD), pre-operative IL-6 plasma level (≥9 pg/mL) and age were found to be independent risk factors together with other pre-operative parameters, i.e., CIRS (cumulative illness rating scale), SPMSQ (short-portable mental status questionnaire), HADS (hospital anxiety and depression scale) showing that pre-operative variables are the most significant to predict POD onset.