Does analgesia and condition influence immunity after surgery? Effects of fentanyl, ketamine and clonidine on natural killer activity at different ages

A Special Authors Introduction

By Patrice Forget and Marc De Kock

Cancer incidence growing is a public health problem. It is, at least partially, due to the longer life expectancy. Tumor pathogenesis is associated with an escape from recognition and elimination of neoplasic cells. Indeed, cellular-mediated immunity is a keystone of host defenses against tumors. The tumoricidal deficiency may be worse in elderly, due to alterations in intracellular signaling. Moreover, positive or negative influence of pain, narcotics and analgesics has been suspected. In particular, Natural Killer cells activity (NK activity), has been described to be highly vulnerable during the perioperative period. Then, the place of different analgesic techniques in oncological sugery, like systemic opioids and other analgesics need to be determined. Studies should also focus on the influence of age and immunosenescence on these effects.

In the literature, opposite effects are described concerning the effects of pain and opioids on NK activity. Sometimes opioids protect against pain-induced immunosuppression, sometimes not. These discrepancies may be explained by the dynamic of immune change, and the need to explore these effects at different postoperative time points. Moreover, the mechanisms of opioid-induced immunosuppression are not well known and must be compared with other non-opioid analgesics and in different conditions.

In this article, we describe the effect of fentanyl, ketamine and clonidine, compared with a placebo, on NK activity at different ages. We confirm the immunosuppressive effects of surgery, and the contrasted effects of analgesics in the postoperative period. A contrario, we highlight the potential immunosuppressive effects of all these drugs in non-operated animals.

These results are important preclinical data that must be known to implement research toward a possible "onco-anesthesia", i.e. anesthetic protocols that may be, in the future, dedicated to special situations, like cancer, where non-anesthetic effect of drugs may influence their choice (e.g. avoiding large doses of synthetic opioids). Anesthesiologists must keep in mind that their drugs may be associated with long term consequences, sometimes opposite, that must be clarified.

Nevertheless, the results of these animal models need clinical confirmation. Ideally, different immune parameters should be combined, and associated with clinical endpoints before drawing definitive conclusions.

This article was published in European Journal of Anaesthesiology
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