Abstract
BackgroundPostoperative delirium is prevalent in older patients and associated with worse outcomes. Recent data in animal studies demonstrate increases in inflammatory markers in plasma and cerebrospinal fluid (CSF) even after aseptic surgery, suggesting that inflammation of the central nervous system may be part of the pathogenesis of postoperative cognitive changes. We investigated the hypothesis that neuroinflammation was an important cause for postoperative delirium and cognitive dysfunction after major non-cardiac surgery.MethodsAfter Institutional Review Board approval and informed consent, we recruited patients undergoing major knee surgery who received spinal anesthesia and femoral nerve block with intravenous sedation. All patients had an indwelling spinal catheter placed at the time of spinal anesthesia that was left in place for up to 24 h. Plasma and CSF samples were collected preoperatively and at 3, 6, and 18 h postoperatively. Cytokine levels were measured using ELISA and Luminex. Postoperative delirium was determined using the confusion assessment method, and cognitive dysfunction was measured using validated cognitive tests (word list, verbal fluency test, digit symbol test).ResultsTen patients with complete datasets were included. One patient developed postoperative delirium, and six patients developed postoperative cognitive dysfunction. Postoperatively, at different time points, statistically significant changes compared to baseline were present in IL-5, IL-6, I-8, IL-10, monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, IL-6/IL-10, and receptor for advanced glycation end products in plasma and in IFN-γ, IL-6, IL-8, IL-10, MCP-1, MIP-1α, MIP-1β, IL-8/IL-10, and TNF-α in CSF.ConclusionsSubstantial pro- and anti-inflammatory activity in the central neural system after surgery was found. If confirmed by larger studies, persistent changes in cytokine levels may serve as biomarkers for novel clinical trials.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0681-9) contains supplementary material, which is available to authorized users.
Highlights
Postoperative delirium is prevalent in older patients and associated with worse outcomes
cerebrospinal fluid (CSF) and plasma cytokine analysis was performed in all ten patients
The activation of CSF IL-5, IL-6, IL-8, monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, and MIP-1β indicates that chemoattraction of monocytes may play a key role similar to what had been previously observed in preclinical studies [14, 18, 41]
Summary
Postoperative delirium is prevalent in older patients and associated with worse outcomes. Cognitive impairment, including the conditions of postoperative delirium [1, 2] and postoperative cognitive dysfunction (POCD) [2, 3], is frequently observed after major surgery, in older patients [3,4,5,6,7]. POCD, which is measured by cognitive testing, has been shown to be associated with premature inability to work, dependency on social transfer payments, inability to cope independently, and long-term mortality [7, 9]. Risk factors such as advanced age and neurodegenerative processes have been identified [5], the pathophysiology for either condition is still unclear
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