Relationship between fentanyl dosage and immune function in the postoperative period

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.

Opioids in the immune system: from experimental studies to clinical practice

“…8 This study found that both doses had the same effect on NKCC on the first postoperative day; however, patients exposed to the low dosage showed faster recovery of NKCC suppression, while patients given the higher doses of fentanyl still showed suppression 48 hours after surgery. 8 Similar findings were reported in a study by Yardeni et al 27 who investigated the ex vivo effects of high, intermediate, and low doses of fentanyl on immune function during the postoperative period of 60 patients. Secretion of the proinflammatory cytokines IL-1 and IL-6 were significantly diminished in patients treated with the high and intermediate doses of fentanyl when compared with the low dose.…”

“…However, similar suppression of NKCC and IL-2 secretion was observed among the three groups . 27 Yeager et al 28 administered fentanyl to seven healthy volunteers at an initial dose of 3 µg/kg followed by an infusion of 1.2 µg/kg/h for 2 hours to evaluate the effects on innate and acquired immunity in humans and on leukocyte subpopulations in peripheral blood. This short-term exposure to fentanyl produced a significant increase in circulating CD16+ and CD8+ lymphocytes.…”

Interleukin-1 signaling in the basolateral amygdala is necessary for heroin-conditioned immunosuppression

“…Non-sterile intravenous drug use, including needle sharing, is one possible mechanism for this effect; however, opiates also produce abnormalities in defensive immune parameters. Consistent with the latter, heroin users exhibit decreases in circulating lymphocytes, natural killer (NK) cell activity, cytokine production, and antibody-dependent cellular cytotoxicity (Govitrapong et al, 1998; Nair et al, 1986; Yardeni et al, 2008). Similarly, rats treated with morphine, the centrally active metabolite of heroin, exhibit lower rates of lymphocyte proliferation, splenic NK cell activity, blood lymphocyte proliferation, and proinflammatory cytokine production (Fecho et al, 1993a; Fecho et al, 1993b, 1996a,b; Lysle et al, 1993; Saurer et al, 2006a,b).…”

Do All Opioid Drugs Share the Same Immunomodulatory Properties? A Review From Animal and Human Studies

“…This study showed that both doses induced an inhibition of NK cytotoxicity on the first postoperative day; however, patients on the low dosage recovered faster, while patients on higher doses still showed reduction of immune parameters 48 h after surgery. These results were confirmed by Yardeni et al (24), who studied the effect of high (70- In a randomized controlled trial of 25 patients undergoing neck surgery, NK activity was assessed in patients treated with either fentanyl of flurbiprofen. In fentanyl treated patients NK cell cytotoxicity was suppressed more than in patients treated with flurbiprofen on day 1, but not day 2 postoperatively (25).…”

“…The immunosuppressive properties of fentanyl have been consistently observed also in the human. The drug affects cellular immune responses and cytokine production in patients and healthy volunteers in a dose related fashion (1,2,(21)(22)(23)(24).…”