C‐reactive protein for risk prediction of post‐operative delirium and post‐operative neurocognitive disorder

Abstract

Background: Post-operative delirium (POD) and post-operative neurocognitive disorder (NCD) are frequently seen in the elderly. Development of biomarkers for pre-operative risk prediction is of major relevance. As inflammation present before surgery might predispose to POD and post-operative NCD development, we aim to determine associations between pre-operative C-reactive protein (CRP) and the incidence of POD and post-operative NCD. Methods:In this observational study, we analyzed 314 patients enrolled in the SuDoCo trial, who had a pre-operative CRP measurement the day before surgery.Primary outcomes were POD assessed according DSM-4 from day 1 until day 7 after surgery and post-operative NCD assessed 3 months after surgery. We conducted multivariable logistic regression analysis adjusted for age, sex, randomization, body mass index, MMSE, ASA status, infection/autoimmune disease/malignoma and types of surgery to determine associations between CRP with POD and post-operative NCD, respectively. Results: Pre-operative CRP was independently associated with POD [OR 1.158 (95% CI 1.040, 1.291); P = .008]. Patients with CRP values ≥5 mg/dL had a 4.8-fold increased POD risk [OR 4.771 (95% CI 1.765, 12.899; P = .002)] compared to patients with lower CRP values. However, no association was seen between pre-operative CRP and post-operative NCD [OR 0.552 (95% CI 0.193, 1.581); P = .269].Conclusions: Pre-operative CRP levels were independently associated with POD but not post-operative NCD after three months. Moreover, higher pre-operative CRP levels showed higher risk for POD. This strengthens the role of inflammation in the development of POD. Assessment of CRP before surgery might allow risk stratification of POD.

Delirium due to hip fracture is associated with activated immune-inflammatory pathways and a reduction in negative immunoregulatory mechanisms

“…Here we report that the NLR is a highly significant biomarker of delirium which strongly reflects IRS, M1, Th2, Th17, and IRS/CIRS activation and Tcell growth as well. As such, the present study extends previous research that high serum and CSF CRP and an increased NLR in peripheral blood are consistently reported as biomarkers or predictive risk factors of post-operative delirium [17] [19,[57][58][59][60]. Nevertheless, the immune profiles assayed here better predict delirium symptoms than NLR.…”

“…It is important to note that the above inflammatory markers are all consistently associated with delirium [53,54]. [39,[59][60][61].…”

Delirium due to hip fracture is associated with activated immune-inflammatory pathways and a reduction in negative immunoregulatory mechanisms

“…, Th17, and IRS/CIRS activation and Tcell growth as well. As such, the present study extends previous research that high serum and CSF CRP and an increased NLR in peripheral blood are consistently reported as biomarkers or predictive risk factors of post-operative delirium[17][19,[57][58][59][60]. Nevertheless, the immune pro les assayed here better predict delirium…”

“…It is important to note that the above in ammatory markers are all consistently associated with delirium [53,54]. [39,[59][60][61]. Unsurprisingly, our study also observed signi cantly increased levels the Th1 (combination of IL-2, IFN-γ and IL-12) and T cell growth and activation factors (a combination of IL-4, IL-IL-9, IL-12, IL-15, GM-CSF) in the delirious hip fracture patients compared to the non-delirious group.…”

Interleukin 8 in postoperative delirium – Preliminary findings from two studies

“…Beyond neuronal damage, disoriented inflammatory responses could mediate susceptibility to delirium in patients with neuropsychiatric diseases. ( Dasgupta and Dumbrell, 2006 ; Knaak et al., 2019 ). Increased IL-8 has been associated with poorer cognitive function in healthy elderly ( Baune et al., 2008 ).…”