Immune function after major surgical interventions: the effect of postoperative pain treatment

Giada Amodeo,1 Dario Bugada,2–4 Silvia Franchi,1 Giorgia Moschetti,1 Stefania Grimaldi,5 Alberto Panerai,1 Massimo Allegri,2 Paola Sacerdote1 1Department of Pharmacological and Biomolecular Sciences, University of Milano, Milano, Italy; 2Study In Multidisciplinary Pain Research Group, 3Department of Anesthesia and ICU, ASST Papa Giovanni XXIII, Bergamo, Italy; 4Department of Anesthesia and ICU, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 5Department of Anesthesia, IRCCS Humanitas Research Center, Rozzano, Italy Introduction: Impaired immune function during the perioperative period may be associated with worse short- and long-term outcomes. Morphine is considered a major contributor to immune modulation. Patients and methods: We performed a pilot study to investigate postoperative immune function by analyzing peripheral blood mononuclear cells’ functionality and cytokine production in 16 patients undergoing major abdominal surgery. All patients were treated with intravenous (i.v.) patient-controlled analgesia with morphine and continuous wound infusion with ropivacaine+methylprednisolone for 24hours. After 24hours, patients were randomized into two groups, one continuing intrawound infusion and the other receiving only i.v. analgesia. We evaluated lymphoproliferation and cytokine production by peripheral blood mononuclear cells at the end of surgery and at 24 and 48hours postoperatively. Results: A significant reduction in TNF-α, IL-2, IFN-γ and lymphoproliferation was observed immediately after surgery, indicating impaired cell-mediated immunity. TNF-α and IFN-γ remained suppressed up to 48hours after surgery, while a trend to normalization was observed for IL-2 and lymphoproliferation, irrespective of the treatment group. A significant inverse correlation was present between age and morphine and between age and lymphoproliferation. No negative correlation was present between morphine and cytokine production. We did not find any differences within the two groups between 24 and 48hours in terms of morphine consumption and immune responses. Conclusion: A relevant depression of cell-mediated immunity is associated with major surgery and persists despite optimal analgesia. Even though morphine may participate in immunosuppression, we did not retrieve any dose-related effect. Keywords: opioids, postoperative pain, cytokines, immunomodulation, lymphoproliferation, surgery&nbsp