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

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-?2, IL-1RA, IL-6, IL-7, IL-8, IL-10, IP-10, MCP-1, MIP-1?, MIP-1?, and TNF-? 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-1?, MIP-1?, and TNF-?. 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.

SUBMITTER: Berger M

PROVIDER: S-EPMC5694037 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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

Berger Miles M Ponnusamy Vikram V Greene Nathaniel N Cooter Mary M Nadler Jacob W JW Friedman Allan A McDonagh David L DL Laskowitz Daniel T DT Newman Mark F MF Shaw Leslie M LM Warner David S DS Mathew Joseph P JP James Michael L ML

Frontiers in immunology 20171113

<h4>Introduction</h4>Aside from direct effects on neurotransmission, inhaled and intravenous anesthetics have immunomodulatory properties. <i>In vitro</i> 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.<h4>Materials and methods</h4>To examine whether propofol and isof ...[more]

PMID: 29181002

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Project description:BackgroundCerebral aneurysm surgery has significant mortality and morbidity rate. Inflammation plays a key role in the pathogenesis of intracranial aneurysms, their rupture, subarachnoid hemorrhage and neurologic complications. Proinflammatory cytokine level in blood and cerebrospinal fluid (CSF) is an indicator of inflammatory response. Cytokines contribute to secondary brain injury and can worsen the outcome of the treatment. Lidocaine is local anesthetic that can be applied in neurosurgery as regional anesthesia of the scalp and as topical anesthesia of the throat before direct laryngoscopy and endotracheal intubation. Besides analgesic, lidocaine has systemic anti-inflammatory and neuroprotective effect.Primary aim of this trial is to determine the influence of local anesthesia with lidocaine on the perioperative levels of pro-inflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α in plasma and CSF in cerebral aneurysm patients.MethodsWe will conduct prospective randomized clinical trial among patients undergoing craniotomy and cerebral aneurysm clipping surgery in general anesthesia. Patients included in the trial will be randomly assigned to the lidocaine group (Group L) or to the control group (Group C). Patients in Group L, following general anesthesia induction, will receive topical anesthesia of the throat before endotracheal intubation and also regional anesthesia of the scalp before Mayfield frame placement, both done with lidocaine. Patients in Group C will have general anesthesia only without any lidocaine administration. The primary outcomes are concentrations of cytokines interleukin-1β, interleukin-6 and tumor necrosis factor-α in plasma and CSF, measured at specific timepoints perioperatively. Secondary outcome is incidence of major neurological and infectious complications, as well as treatment outcome in both groups.DiscussionResults of the trial could provide insight into influence of lidocaine on local and systemic inflammatory response in cerebrovascular surgery, and might improve future anesthesia practice and treatment outcome. TRIAL IS REGISTERED AT CLINICALTRIALS.GOV:: NCT03823482.

Dataset Information

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

Publications

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

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