The Effect of Propofol vs. Isoflurane Anesthesia on Postoperative Changes in Cerebrospinal Fluid Cytokine Levels: Results from a Randomized Trial

Abstract

IntroductionAside from direct effects on neurotransmission, inhaled and intravenous anesthetics have immunomodulatory properties. In vitro and mouse model studies suggest that propofol inhibits, while isoflurane increases, neuroinflammation. If these findings translate to humans, they could be clinically important since neuroinflammation has detrimental effects on neurocognitive function in numerous disease states.Materials and methodsTo examine whether propofol and isoflurane differentially modulate neuroinflammation in humans, cytokines were measured in a secondary analysis of cerebrospinal fluid (CSF) samples from patients prospectively randomized to receive anesthetic maintenance with propofol vs. isoflurane (registered with , identifier NCT01640275). We measured CSF levels of EGF, eotaxin, G-CSF, GM-CSF, IFN-α2, IL-1RA, IL-6, IL-7, IL-8, IL-10, IP-10, MCP-1, MIP-1α, MIP-1β, and TNF-α before and 24 h after intracranial surgery in these study patients.ResultsAfter Bonferroni correction for multiple comparisons, we found significant increases from before to 24 h after surgery in G-CSF, IL-10, IL-1RA, IL-6, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β, and TNF-α. However, we found no difference in cytokine levels at baseline or 24 h after surgery between propofol- (n = 19) and isoflurane-treated (n = 21) patients (p > 0.05 for all comparisons). Increases in CSF IL-6, IL-8, IP-10, and MCP-1 levels directly correlated with each other and with postoperative CSF elevations in tau, a neural injury biomarker. We observed CSF cytokine increases up to 10-fold higher after intracranial surgery than previously reported after other types of surgery.DiscussionThese data clarify the magnitude of neuroinflammation after intracranial surgery, and raise the possibility that a coordinated neuroinflammatory response may play a role in neural injury after surgery.

Impact of Total Knee Arthroplasty with General Anesthesia on Brain Networks: Cognitive Efficiency and Ventricular Volume Predict Functional Connectivity Decline in Older Adults

“…We also encourage future research on the mechanism of the functional connectivity changes after surgery. A review of effects of general anesthesia on the brain [99] raises some mechanistic possibilities, including impaired neurotrophin signaling and inflammation [100]. …”

The INTUIT Study: Investigating Neuroinflammation Underlying Postoperative Cognitive Dysfunction

“…Several studies have shown higher proinflammatory cytokine levels in serum and cerebrospinal fluid (CSF) of patients with postoperative delirium, POCD, and/or AD . CSF MCP‐1 levels and monocyte numbers increase from 1 hour before to 24 hours after surgery/anesthesia . In a pilot study, we found that CSF monocyte MCP‐1 receptor expression decreased 24 hours after surgery in patients who later developed POCD, suggesting that increased monocyte chemoattractant protein 1 (MCP‐1) levels induce monocyte influx into the central nervous system and monocyte MCP‐1 receptor downregulation…”

“…The monocyte‐to‐lymphocyte ratio is used to evaluate these two major leukocyte populations in CSF as recently described . CSF supernatant is analyzed using multiplex enzyme‐linked immunosorbent assay (ELISA) to measure levels of the cytokines MCP‐1, interleukin (IL)‐6, IL‐8, and granulocyte colony‐stimulating factor (G‐CSF) …”

“…CSF tau levels are measured before surgery and 24 hours and 6 weeks after surgery at the Alzheimer's Disease Neuroimaging Initiative biomarker core lab that has well‐validated multiplex ELISA‐based bead assays for CSF tau, phospho‐tau, and amyloid‐beta levels . To avoid measurement bias, sample measurements are performed in random order, and technicians are blinded to study subject number and time point.…”

“…Increased CSF MCP‐1 levels and monocyte brain influx have also been associated with AD progression . We recently demonstrated that neuroinflammation magnitude (as measured by CSF MCP‐1 levels) is associated with postoperative increases in the CSF AD biomarker tau after neurosurgery . CSF tau levels also increase after cardiac and orthopedic surgery.…”