The effect of Propofol vs. isoflurane anesthesia on postoperative changes in cerebrospinal fluid cytokine levels

Results from a randomized trial

For the MAD-PIA Investigators

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Introduction: 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. Materials and methods: 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. Results: 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-1a, 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. Discussion: 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.

Original languageEnglish (US)
Article number1528
JournalFrontiers in Immunology
Volume8
Issue numberNOV
DOIs
StatePublished - Nov 13 2017

Fingerprint

Isoflurane
Propofol
Cerebrospinal Fluid
Anesthesia
Cytokines
Interleukin-8
Interleukin-6
Interleukin-10
Intravenous Anesthetics
Interleukin-7
Wounds and Injuries
Epidermal Growth Factor
Synaptic Transmission
Interleukin-2
Anesthetics
Biomarkers
Maintenance

Keywords

  • Anesthesia
  • Cerebrospinal fluid
  • Cytokine
  • Inflammation
  • Isoflurane
  • Neuroinflammation
  • Propofol
  • Surgery

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

The effect of Propofol vs. isoflurane anesthesia on postoperative changes in cerebrospinal fluid cytokine levels : Results from a randomized trial. / For the MAD-PIA Investigators.

In: Frontiers in Immunology, Vol. 8, No. NOV, 1528, 13.11.2017.

Research output: Contribution to journalArticle

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abstract = "Introduction: 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. Materials and methods: 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. Results: 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-1a, 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. Discussion: 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.",
keywords = "Anesthesia, Cerebrospinal fluid, Cytokine, Inflammation, Isoflurane, Neuroinflammation, Propofol, Surgery",
author = "{For the MAD-PIA Investigators} and Miles Berger and Vikram Ponnusamy and Nathaniel Greene and Mary Cooter and Nadler, {Jacob W.} and Allan Friedman and McDonagh, {David L.} and Laskowitz, {Daniel T.} and Newman, {Mark F.} and Shaw, {Leslie M.} and Warner, {David S.} and Mathew, {Joseph P.} and James, {Michael L.} and Carter, {James H.} and Shivanandan Lad and Ali Zomorodi and John Sampson and Takanori Fukushima and Owoicho Adogwa and Karen Clemmons and Carlos Conde and Omowunmi Olaleye and Naraida Balajonda and Jhoanna Aquino and Bonita Funk and Li, {Yi Ju} and White, {William D.}",
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T2 - Results from a randomized trial

AU - For the MAD-PIA Investigators

AU - Berger, Miles

AU - Ponnusamy, Vikram

AU - Greene, Nathaniel

AU - Cooter, Mary

AU - Nadler, Jacob W.

AU - Friedman, Allan

AU - McDonagh, David L.

AU - Laskowitz, Daniel T.

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AU - Shaw, Leslie M.

AU - Warner, David S.

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AU - James, Michael L.

AU - Carter, James H.

AU - Lad, Shivanandan

AU - Zomorodi, Ali

AU - Sampson, John

AU - Fukushima, Takanori

AU - Adogwa, Owoicho

AU - Clemmons, Karen

AU - Conde, Carlos

AU - Olaleye, Omowunmi

AU - Balajonda, Naraida

AU - Aquino, Jhoanna

AU - Funk, Bonita

AU - Li, Yi Ju

AU - White, William D.

PY - 2017/11/13

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N2 - Introduction: 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. Materials and methods: 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. Results: 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-1a, 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. Discussion: 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.

AB - Introduction: 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. Materials and methods: 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. Results: 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-1a, 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. Discussion: 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.

KW - Anesthesia

KW - Cerebrospinal fluid

KW - Cytokine

KW - Inflammation

KW - Isoflurane

KW - Neuroinflammation

KW - Propofol

KW - Surgery

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