Interleukin 8 in postoperative delirium – Preliminary findings from two studies

Abstract

Objective Studies have suggested that inflammation contributes to the pathogenesis of postoperative delirium, but previous results on the proinflammatory cytokine IL-8 in plasma are contradictory. Additionally, a significant fraction of IL-8 is bound to erythrocytes, but the relevance of whole blood IL-8 in delirium has not been studied. In this work, we analyzed the association of postoperative delirium with levels of unbound IL-8 in plasma and levels of IL-8 in whole blood in patients from two studies which were conducted in our department and have not been presented previously. We assessed the prognostic value of whole blood IL-8. Methods Plasma/whole blood IL-8 was measured at least once in N ​= ​504 patients preoperatively, on day one (d1) and/or three months after surgery in the BioCog observational study. Whole blood IL-8 was measured in N ​= ​64 patients from the PHYDELIO trial preoperatively, on d1 and d7 after surgery. For the determination of whole blood IL-8, EDTA-preserved blood samples underwent lysis by adding Triton-X100 surfactant. Plasma and whole blood IL-8 levels were assessed with two different immunoassay kits. Delirium was appraised systematically for seven postoperative days according to DSM criteria using two comparable protocols consisting of validated screening tools. Results Delirium occurred in 25% of BioCog and 14% of PHYDELIO patients. In BioCog, IL-8 was elevated on d1 and in delirious patients. A steeper postoperative increase in delirium was confounded by surgery-related factors. A crescendo-decrescendo pattern of whole blood IL-8 levels was observed in non-delirious patients with a peak on d1. This pattern was more distinct in delirious BioCog patients, but inverted in delirious PHYDELIO patients. Preoperative whole blood IL-8>318.4 ​pg/mL (reference <150 ​pg/mL) had adequate sensitivity (0.79/0.78) and specificity (0.53/0.67) for delirium in both samples. Conclusion Our results contribute to an inflammatory hypothesis of postoperative delirium.

An exploratory research report on brain mineralization in postoperative delirium and cognitive decline

“…Sixty‐five patients with preoperative SWI data were included in the analysis; 14/65 (22%) of the patients experienced POD and 40/65 (62%) returned for neuropsychological testing after 3 months. Overall POD rates were comparable with other analyses that used data from the BioCog cohort (i.e., 20% [Heinrich et al, 2021] and 25% [Lammers‐Lietz et al, 2022]) as well as other studies conducted in our centre (i.e., 16% [Spies et al, 2021] and 31% [van Norden et al, 2021]).…”

“…As part of the subproject, an additional SWI sequence was added to the MRI protocol to study the association of microbleeds with POD and POCD. Methods and procedures have already been described extensively in previous publications ( Heinrich et al, 2020 ; Lachmann et al, 2019 ; Lammers-Lietz et al, 2022 ; Lammers et al, 2018 ; Winterer et al, 2018 ).…”

Brain mineralization in postoperative delirium and cognitive decline

“…14/65 (22%) of the patients experienced POD and 40/65 (62%) returned for neuropsychological testing after three months. Overall POD rates were comparable to other analyses which used data from the BioCog cohort (i.e., 20% (Heinrich et al, 2021) and 25% (Lammers-Lietz et al, 2022)) as well as other studies conducted in our center (i.e., 16% (Spies et al, 2021) and 31% (van Norden et al, 2021)).…”

Multivariable model of postoperative delirium in cardiac surgery patients: proteomic and demographic contributions

“…Tau protein, NfL and more frequently IL-6 have been proposed as strong biomarker candidates due to their well-known association with cognitive decline and the shared characteristics between perioperative disorders, neurodegenerative diseases, and neuronal injury 26 . The stress-immune hypothesis for delirium has also been supported by evidence showing increased levels of cortisol, CRP, TNF-α, IL-2, IL-6, and IL-8 in delirious surgical patients 32,34,[37][38][39][40][41][42] .…”