Relationship between fentanyl dosage and immune function in the postoperative period

J Opioid Manag. Jan-Feb 2008;4(1):27-33. doi: 10.5055/jom.2008.0005.


Background: Anesthesia and surgery are associated with impairment of the immune system expressed as an excessive proinflammatory immune response and suppression of cell mediated immunity. Opioids, an integral part of anesthetic technique, possess an inhibitory effect on both humoral and cellular immune responses. It was the aim of the present study to examine the effect of various doses of fentanyl on cytokine production during the perioperative period.

Intervention: The effect of large (LDFA, 70-100 microg/kg), intermediate (IDFA, 23-30 microg/kg) and small (SDFA, 2-4 microg/kg) doses of fentanyl on the immune function in the postoperative period was investigated.

Participants: Sixty patients, randomly assigned to one of the three groups according to the dose of fentanyl were included in the study.

Methods: The ex vivo secretion of IL-1beta, IL-2, IL-6, and IL-10 and NK cell cytotoxicity (NKCC) of peripheral blood mononuclear cells (PBMC) was tested before, and at 24, 48, and 72 hours following surgery.

Results: The pattern of postoperative secretion of the proinflammatory cytokines IL-1beta and IL-6 and that of the anti-inflammatory cytokine IL-10 differed significantly between patients receiving SDFA and those receiving IDFA and LDFA, but was similar between the last two groups. A similar suppression of NKCC and IL-2 secretion was observed in the three groups.

Conclusions: The diminished proinflammatory cytokine response observed in patients treated by LDFA and IDFA suggests that although more stable immune function can be achieved by those methods in comparison with SDFA, it is recommendable to apply IDFA to avoid the side effects that might be observed using LDFA method.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Analgesics, Opioid / adverse effects*
  • Cytotoxicity, Immunologic / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Fentanyl / administration & dosage
  • Fentanyl / adverse effects*
  • Humans
  • Immunity / drug effects*
  • Interleukin-10 / biosynthesis
  • Interleukin-1beta / biosynthesis
  • Interleukin-2 / biosynthesis
  • Interleukin-6 / biosynthesis
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Male
  • Middle Aged
  • Postoperative Period


  • Analgesics, Opioid
  • Interleukin-1beta
  • Interleukin-2
  • Interleukin-6
  • Interleukin-10
  • Fentanyl