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

Miles Berger,Daniel T Laskowitz,David S Warner,Michael L James,Nathaniel Greene,Mary Cooter,Leslie M Shaw,Jacob W Nadler,David L Mcdonagh,Vikram Ponnusamy,Allan Friedman,Mark F Newman,Joseph P Mathew

doi:10.3389/fimmu.2017.01528

Abstract

Aside 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. To 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 http://www.clinicaltrials.gov, 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. After 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. These 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.

Highlights

Many intravenous and inhaled anesthetics modulate immunologic and inflammatory function by acting at multiple receptors and ion channels on leukocytes [1,2,3]
We report that anesthetic type had no significant effect upon cerebrospinal fluid (CSF) cytokine levels after intracranial surgery, yet multiple CSF cytokine levels increased significantly after surgery, and many of these CSF cytokine increases correlated with one another and with CSF tau increases
Our comparison of propofol- and isoflurane-treated patients was limited by slight differences in age, hydromorphone dose, and bispectral index (BIS) index (Table 1), though we believe that these slight differences between groups are unlikely to have obscured a biologically significant difference in cytokines levels

Summary

Introduction

Many intravenous and inhaled anesthetics modulate immunologic and inflammatory function by acting at multiple receptors and ion channels on leukocytes [1,2,3]. If anesthetics have inflammatory-modulating properties in humans, this could be clinically significant because many human neurologic and neurocognitive disorders are thought to involve brain inflammation [e.g., multiple sclerosis (MS) [15], traumatic brain injury (TBI) [16], Alzheimer’s disease (AD) [17], human immunodeficiency virus (HIV)-associated neurocognitive dysfunction [18], and postoperative delirium and cognitive dysfunction [19]]. Many patients with these disorders undergo anesthesia and surgery each year. Understanding the effects of different anesthetics on human postoperative neuroinflammation is an important goal in perioperative medicine

Objectives

Results

Conclusion