Effects of Anesthesia Based on Large Versus Small Doses of Fentanyl on Natural Killer Cell Cytotoxicity in the Perioperative Period

Abstract

Surgical stress and general anesthesia suppress immune functions, including natural killer cell cytotoxicity (NKCC). This suppression could be attributable, at least in part, to opiates. We have previously shown that large-dose fentanyl administration suppressed NKCC in rats. The present study sought to compare the effects of two anesthetic protocols, based on large- (LDFA) versus small (SDFA)-dose fentanyl anesthesia on NKCC in the perioperative period. Forty patients were included in this study; half were assigned to each protocol of anesthesia. In each anesthetic group, half the patients were undergoing surgery for malignant diseases, and half for benign conditions. Blood samples were collected during the perioperative period. NKCC was assessed using the chromium release assay. Initially, both types of anesthesia similarly suppressed NKCC, with a peak effect 24 h after surgery. The two types of anesthesia, however, differed in the rate of recovery of NKCC suppression. By the second postoperative day, NKCC returned to control values in the SDFA patients, whereas NKCC was still significantly suppressed after LDFA. These results indicate that LDFA causes prolonged suppression of NK cell function. Whether this suppression might have a long-term impact on the overall outcome, especially in cancer patients, remains to be determined.

Morphine and tumor growth and metastasis

“…Acute and chronic administration of exogenous opioids including the one most commonly used-morphine -inhibits components of the cellular and humoral immune function such as antibody production, NK cell activity, cytokine expression, blood lymphocyte proliferative responses to mitogen, and phagocytic activity [32][33][34][35]. While many studies have tested the immunosuppressive effects of morphine in vitro and in vivo in rodents and humans [32,33,35,36], other opioids have been shown to also possess immunosuppressive effects, e.g., therapeutic agents such as fentanyl [37][38][39], or pharmacological tools such as subtype-specific opioid receptor agonists U50 488H, deltorphin II, or DPDPE [40].…”

The Role of the Perioperative Period in Recurrence After Cancer Surgery

“…Unfortunately, it also has been established that opioids (morphine in particular) inhibit cellular and humoral immune function in humans. [35][36][37] There are no data directly implicating opioids in cancer genesis in humans, but animal data strongly suggest that they may contribute to cancer recurrence in the clinical setting. For example, in rodent studies, it was demonstrated that morphine is proangiogenic and promotes breast tumor growth.…”

“…Opioids inhibit cellular and humoral immune function in humans 36 Morphine inhibits spontaneous and cytokine-enhanced NK cell cytotoxicity [35][36][37] In contrast, IV fentanyl increases NK cell cytotoxicity and circulating CD16(ϩ) lymphocytes in humans 41 Opioid-induced promotion and stimulation of angiogenesis 39 ␤-adrenergic blockade ␤-blocker (nadolol) and a prostaglandin synthesis inhibitor (indomethacin) attenuated the metastasis-promoting effects of surgery when used alone or in combination 11 …”

Sedation Options for Intubated Intensive Care Unit Patients

“…1 Pain also suppresses natural killer cell activity by decreasing cytotoxic T cells and reduction of neutrophil phagocytic activity, resulting in critical impairment of the immune system. 1,7,8 All of these physiologic factors can lead to worsening of patient condition, increase in complications, and prolonged length of stay for the patient.…”