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 24 hours. After 24 hours, 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 48 hours 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 48 hours 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 48 hours 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.

Opioid free anesthesia: evidence for short and long-term outcome - Minerva Anestesiologica 2021 February;87(2):230-7 - Minerva Medica - Journals

Systemic inflammatory response (SIR) has actually been shown as an important prognostic factor associated with lower postoperative survival in several types of cancer. Thus, the challenge for physicians is to find specific, low-cost, and highlyreliable inflammatory markers, clearly correlated with prognosis and able to preoperatively stratify patient’s risk. Inflammation is a promising target to improve perioperative outcome, and data show that anti-inflammation techniques have a great potential in the perioperative period of cancer surgery. Inflammation scores could be useful to stratify patients with a potential better response to anti-inflammation strategies. Furthermore, inflammation scores could prevent failure of clinical trials by a better definition of patients to be included in such trials; inflammation scoring could clarify the real role of different drugs and techniques on outcome after cancer surgery, defining if different therapies are required for different patients. The role of this review is to focus on the currently available scores, in order to clarify their rationale and to analyze the actual evidence and limits, providing physicians with an updated overview of the possible inflammation-based prognostic scores for cancer patients undergoing surgery.

Opioids are extensively used in patients with cancer pain; despite their efficacy, several patients can experience ineffective analgesia and/or side effects. Pharmacogenetics is a new approach to drug prescription based on the “personalized-medicine” concept, i.e., the ability of tailoring treatments to each individual’s genetic/genomic profile. Pharmacogenetics aims to identify specific genetic variants that influence pharmacokinetics and pharmacodynamics of drugs, better determining their effectiveness/safety profile. Opioid response is a complex scenario, but some gene variants have shown a correlation with pain sensitivity, as well as with opioid metabolism and clinical efficacy/adverse events. Although questions remain unanswered, some of these gene variants may already be used to identify specific patients’ phenotypes that are more prone to experience better clinical response (i.e., better analgesia and/or less adverse events). Once adopted, this approach to opioid prescription may improve a patient’s outcome. This review summarizes the available data on genetic variants and opioid response: we will focus on basic pharmacogenetic and its impact in the clinical scenario discussing how they may lead to more appropriate opioid prescription in cancer patients.