Relationship between fentanyl dosage and immune function in the postoperative period

Authors

  • Israel Z. Yardeni, MD
  • Benzion Beilin, MD
  • Eduard Mayburd, MD
  • Yifat Alcalay, MSc
  • Hanna Bessler, PhD

DOI:

https://doi.org/10.5055/jom.2008.0005

Keywords:

fentanyl, surgery, cytokines, NK cell cytotoxicity

Abstract

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 μg/kg), intermediate (IDFA, 23-30 μg/kg) and small (SDFA, 2-4 μg/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-1β, 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-1β 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.

Author Biographies

Israel Z. Yardeni, MD

Department of Anesthesiology, Rabin Medical Center, Hasharon Hospital, Petah Tiqva, Israel; Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.

Benzion Beilin, MD

Department of Anesthesiology, Rabin Medical Center, Hasharon Hospital, Petah Tiqva, Israel; Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.

Eduard Mayburd, MD

Department of Anesthesiology, Rabin Medical Center, Hasharon Hospital, Petah Tiqva, Israel; Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.

Yifat Alcalay, MSc

Immunology and Hematology Research Laboratory, Rabin Medical Center, Hasharon Hospital, Petah Tiqva, Israel; Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.

Hanna Bessler, PhD

Immunology and Hematology Research Laboratory, Rabin Medical Center, Hasharon Hospital, Petah Tiqva, Israel; Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.

References

Lennard TW, Shenton BK, Borzotta A, et al.: The influence of surgical operation on components of the human immune system. Br J Surg. 1985; 72: 771-776.

Salo M: Effects of anaesthesia and surgery on the immune response. Acta Anaesthesiol Scand. 1992; 36(3): 201-220.

Vallejo R, Le Leon-Casasola O, Benyamin R: Opiod therapy and immunosuppression: A review. Am J Ther. 2004; 11(5): 354-365.

Beilin B, Martin FC, Shavit Y, et al.: Suppression of natural killer cell activity by high-dose narcotic anesthesia in rats. Brain Behav Immunol. 1989; 3(2): 129-137.

Beilin B, Shavit Y, Cohn S, et al.: Narcotic-induced suppression of natural killer cell activity in ventilated rats. Clin Immunol Immunpathol. 1992; 64(2): 173-176.

Beilin B, Shavit Y, Hart J, et al.: Effects of anesthesia based on large versus small doses of fentanyl on natural killer cell cytotoxicity in the perioperative period. Anesth Analg. 1996; 82(3): 492-497.

Hall GM, Young C, Holderoft A, et al.: Substrate mobilization during surgery. A comparison between halothane and fentanyl anaesthesia. Anaesthesia. 1978; 33: 924-930.

Tonnesen E, Brinklov MM, Christensen NJ, et al.: Natural killer cell activity and lymphocyte function during and after coronary artery bypass grafting in relation to the endocrine stress response. Anesthesiology. 1987; 67(4): 526-533.

Stenseth R, Bjella L, Berg EM, et al.: Thoracic epidural analgesia in aortocoronary bypass surgery. II. Effects of endocrine metabolic response. Acta Anaesthesiol Scand. 1994; 38(8): 834-839.

Chia YY, Liu K, Wang JJ, et al.: Intraoperative high dose fentanyl induces postoperative fentanyl tolerance. Can J Anaesth. 1999; 46(9): 872-877.

Duncan HP, Cloote A, Weir PM, et al.: Reducing stress response in the pre-bypass phase of open surgery in infants and young children: A comparison of different fentanyl doses. Brit J Anaesth. 2000; 84(5): 556-564.

Brand JM, Kirchner H, Poppe C, et al.: The effects of general anesthesia on human peripheral immune cell distribution and cytokine production. Clin Immunol Immunopathol. 1997; 83(2): 190-194.

Costa A, Benedetto V, Ricci C, et al.: Endocrine, hematological and immunological changes in surgical patients undergoing general anesthesia. Ital J Surg Sci. 1989; 19(1): 41-49.

Delvin EG, Clarke RSJ, Mirakhur RK, et al.: Effect of four i.v. induction agents on T-lymphocyte proliferations PHA in vitro. Br J Anaesth 1994; 73(3): 315-317.

Crozier TA, Muller JE, Quittkatt D, et al.: The effect of laparotomy on plasma concentrations of interleukin (IL)-1β and IL-6. Are there interactions with neuroendocrine secretion or postoperative temperature regulation? Anaesthesist. 1993; 42(6): 343-349.

Hellstrand K, Hermodsson S: Interleukin-2 can induce suppression of human natural killer cell cytotoxicity. Clin Exp Immunol. 1989; 77(3): 410-416.

Pechnick RN: Effect of opioids on the hypothalamo-pituitary-adrenal axis. Annu Rev Pharmacol Toxicol. 1993; 32: 353-382.

Homo-Delarch F, Dardenne M: The neuroendocrineimmune axis. Springer Semin Immunopathol. 1993; 14(3): 221-238.

Carr DJ, Gerbhardt BM, Paul D: Alpha adrenergic and mu-2 opioid receptors are involved in morphine-induced suppression of splenocyte natural killer activity. J Pharmacol Exp Ther. 1993; 264(3): 1179-1186.

Peterson PK, Molitor TW, Chao CC: Mechanisms of morphine induced immunomodulation. Biochem Pharmacol. 1993; 46(3): 343-348.

Yeager MP, Yu CT, Campbell AS, et al.: Effect of morphine and β-endorphine on human Fc receptor-dependent and natural killer cell functions. Clin Immunol Immunopathol. 1992; 62(3): 336-343.

Sibinga NE, Goldstein A: Opioid peptides and opioid receptors in cells of the immune system. Annu Rev Immunol. 1988; 6: 219-249.

Brune IB, Wilke W, Hensler T, et al.: Downregulation of T helper type 1 immune response and altered pro-inflammatory and ant-inflammatory T cell cytokine balance following conventional but not laparoscopic surgery. Am J Surg. 1999; 177(1): 55-60.

Hensler T, Hecker H, Heeg K, et al.: Distinct mechanisms of immunosuppression as a consequence of major surgery. Infect Immun. 1997; 65(6): 2283-2289.

Faist E, Mewes A, Baker CC, et al.: Prostaglandin E2 (PGE2)-dependent suppression of interleukin-2 (IL-2) production in patients with major trauma. J Trauma. 1987; 27(8): 837-848.

Beilin B, Shavit Y, Trabekin E, et al.: The effect of postoperative pain management on immune response to surgery. Anesth Analg. 2003; 97(3): 822-827.

Berguer R, Bravo N, Bowyer M, et al.: Major surgery suppresses maximal production of helper T-cell type 1 cytokines without potentiating the release of helper T-cell type 2 cytokines. Arch Surg. 1999; 134(5): 540-544.

Decker D, Schondorf M, Bidlingmaier F, et al.: Surgical stress induces a shift in the type-1/type-2 helper t-cell balance, suggesting down-regulation of cell mediated and up-regulation of antibody mediated immunity commensurate to the trauma. Surgery. 1996; 119(3): 316-325.

Volk T, Dopfmer UR, Schmutzler M, et al.: Stress induced IL-10 does not seem to be essential for early monocyte deactivation following cardiac surgery. Cytokine. 2003; 24(6): 237-243.

Volk T, Schmutzler M, Engelhardt L, et al.: Influence of aminosteroid and glucocorticoid treatment on inflammation and immune function during cardiopulmonary bypass. Crit Care Med. 2001; 29: 2137-2142.

Rumalla V, Calvano SE, Spotnitz AJ, et al.: The effect of glucocorticoid therapy on inflammatory responses to coronary artery bypass graft surgery. Arch Surg. 2001; 136: 1039-1044.

Naito Y, Tamai S, Shingu K, et al.: Response of plasma adrenocorticotropic hormone, cortisol, and cytokines during and after upper abdominal surgery. Anesthesiology. 1992; 77(3): 426-431.

Tsukada K, Katoh H, Shiojima M, et al.: Concentration of cytokines in peritoneal fluid after abdominal surgery. Eur J Surg. 1993; 159: 475-479.

Moore CM, Desborough JP, Powell H, et al.: Effects of extradural anesthesia on interleukin-6 and acute phase response to surgery. Br J Aneasth. 1994; 72(3): 272-279.

Stefano GB, Kushnerik V, Rodriquez M, et al.: Inhibitory effect of morphine on granulocyte stimulation by tumor necrosis factor and substance P. Int J Immunopharmacol 1994; 16(4): 329-334.

Stefano GB, Leung MK, Bilfinger TV, et al.: Effect of prolonged exposure to morphine on responsiveness of human and invertebrate immunocytes to stimulatory molecules. J Neuroimmunol. 1995; 63 (2): 175-181.

Published

01/30/2018

How to Cite

Yardeni, MD, I. Z., B. Beilin, MD, E. Mayburd, MD, Y. Alcalay, MSc, and H. Bessler, PhD. “Relationship Between Fentanyl Dosage and Immune Function in the Postoperative Period”. Journal of Opioid Management, vol. 4, no. 1, Jan. 2018, pp. 27-33, doi:10.5055/jom.2008.0005.