Elevated Monocyte Chemoattractant Protein-1 as the Independent Risk Factor of Delirium after Cardiac Surgery. A Prospective Cohort Study

Abstract

Background: The pathogenesis of postoperative delirium is largely unknown. The primary objective of this study is to assess whether increased levels of monocyte chemoattractant protein-1 (MCP-1) and high-sensitivity C-reactive protein (hsCRP) are associated with postoperative delirium in patients who have undergone cardiac surgery. The secondary objective is to investigate whether any association between raised inflammatory biomarkers levels and delirium is related to surgical and anesthetic procedures or mediated by pre-existing psychiatric conditions associated with raised pro-inflammatory markers levels. Methods: The patients were screened for cognitive impairment one day preoperatively with the use of the Mini-Mental State Examination Test and the Clock Drawing Test. A diagnosis of major depressive disorder (MDD) and anxiety disorders was established on the basis of Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. Blood samples were collected pre- and postoperatively for hsCRP and chemokine levels. Results: Postoperative delirium developed in 34% (61 of 177) of patients. Both pre- and postoperative hsCRP, and preoperative MCP-1 levels were associated with postoperative delirium in univariate comparisons; p = 0.001; p < 0.001; p < 0.001, respectively. However, according to a multivariable logistic regression analysis, only a raised MCP-1 concentration before surgery was independently associated with postoperative delirium, and related to advancing age, preoperative anxiety disorders and prolonged intubation. Conclusions: The present study suggests that an elevated preoperative MCP-1 concentration is associated with delirium after cardiac surgery. Monitoring of this inflammatory marker may reveal the cardiovascular disease (CVD) patients who are at risk of neuropsychiatric syndromes development.

Outcomes of postoperative delirium in patients undergoing cardiac surgery: A systematic review and meta-analysis

“…We propose the following explanations to comprehend the results. First, higher levels of postoperative pro-inflammatory cytokines (e.g., IL-2, IL-6, TNF-α, MCP-1) were associated with a higher risk to develop POD in cardiac surgery patients ( 59 , 60 ). Elevated levels of pro-inflammatory cytokines reflect an active inflammatory response in the body, which may cause systemic inflammatory response syndrome.…”

Chemokines in ICU Delirium: An Exploratory Study

“…CCL2, also referred to as monocyte chemoattractant protein 1 (MCP1), is a proinflammatory chemokine that has been implicated in the pathophysiology of various brain diseases with an inflammatory component, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, neurodegeneration secondary to status epilepticus, and stroke ( 25 , 26 ). Elevated serum and cerebrospinal fluid levels of CCL2 have been previously associated with delirium ( 8 ). The exact mechanism by which elevated CCL2 contributes to, or results from, the cerebral dysfunction manifested as delirium has yet to be elucidated.…”

“…Regardless, repeating the chemokine multivariate analysis excluding CCL3, CXCL1, and both CCL3 and CXCL1 did not alter our findings regarding the relationship between CCL2 and delirium. Finally, our study included patients admitted to the ICU for observation after planned major cardiac surgeries; we decided to include these patients because cardiac surgery has been associated with the development of delirium ( 8 ). Future studies with larger cohorts may be best conducted in more homogeneous populations.…”

Persistent Depletion of Neuroprotective Factors Accompanies Neuroinflammatory, Neurodegenerative, and Vascular Remodeling Spectra in Serum Three Months after Non-Emergent Cardiac Surgery

“…Concomitantly, peri-operative delirium, vascular dementia, Parkinson’s-like disease, and other representations of central nervous system (CNS) dysfunction are increasingly recognized as cardiac surgery complications [ 9 , 16 , 17 , 18 , 23 , 24 ]. Delirium and atypical dementia may present a different clinical spectrum from classical AD-like dementia, yet their debilitating effect on long-term recovery is profound [ 13 , 32 , 34 ]. While the role of “classical” markers in POCD has been studied, the knowledge of the peri-operative dynamics of “non-classical” markers is lacking.…”

“…The progression of postoperative neurodegeneration depends on various processes, including the migration of peripheral leukocytes into brain parenchyma. This is driven by chemokine ligand 28 (CCL28) or monocyte chemoattractant protein-1 (MCP-1), especially if hypoxemia is present [ 16 , 34 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 ]. Perioperative damage of the blood–brain barrier and subsequent vasculitis and vascular remodeling further facilitate leukocyte infiltration into the CNS [ 59 , 60 ].…”