THE IMPACT OF CONTINOUS EPIDURAL AND MULTIMODAL SYSTEMIC ANALGESIA AND PERIPHERAL NERVE BLOCKS ON THE CELLULAR IMMUNITY IN PATIENTS AFTER TOTAL KNEE ARTHROPLASTY

Cilj istraživanja: Kirurška tkivna ozljeda nakon ugradnje endoproteze koljena (TKR) uzrokuje snažnu bol i stres koji induciraju snažni proupalni odgovor sa posljedičnom nishodnom regulacijom imunološkog odgovora. Uspostavljanje učinkovite poslijeoperacijske analgezije koja adekvatno obezboljuje i održava imunološku ravnotežu od krucijalne je važnosti. Cilj rada je istražiti utjecaj analgezije: na promjene udjela limfocita i perforinsku ekspresiju u pojedinim limfocitnim subpopulacijama te na upalni i stresni odgovor u bolesnika nakon TKR u ranom poslijeoperacijskom razdoblju. Ispitanici, materijali i metode: Istraživanje je obuhvatilo 90 bolesnika u kojih je bol liječena epiduralnom analgezijom (Grupa 1), ishijadičnim i femoralnim živčanim blokom (Grupa 2) i sustavnom analgezijom (Grupa 3). Bol se bilježila u mirovanju i u pokretu putem VAS ljestvice te su uzorci periferne venske krvi prije (T1), nakon operacije (T2), 24 (T3) i 72 (T4) sata nakon operacije. Detektirali smo udjele limfocita T, stanica NK, stanice NKT i njihovih subpopulacija te je analiziran udio perforina u navedenim stanicama. Koncentracije IL-1β, IL-6 i TNF-α u plazmi te katekolamina i kortizola analizirali smo u istim vremenima. Rezultati: Bolesnici u Grupi 1 i Grupi 2 osjećali su značajno manju bol usporedbom s Grupom 3 te je također uočeno smanjenje učestalosti limfocita T, njihovih subpopulacija, stanica NKT, perforin pozitivnih CD3+CD8+CD56- limfocita u Grupi 3 u usporedbi s Grupom 1 i 2. Uočen je pad koncentracije IL-1β i IL-6 te kortizola i noradrenalina u Grupi 1 i 2 u usporedbi s Grupom 3. Zaključak: Regionalna analgezija učinkovitije održava staničnu imunost, perforinsku ekspresiju u limfocitima te neuroendokrini i upalni odgovor u ranom poslijeoperacijskom razdoblju nakon TKR.Objectives: Pain and surgical stress after total knee replacement (TKR) cause profound pro-inflammatory response followed by down-regulation of immune response. It is mandatory to perform the most effective analgesia in order to maintain immune and stress balance. The aim of this study was to analyze the impact of analgesia on frequency of lymphocytes and perforin expression in peripheral blood lymphocytes as well as on inflammatory and stress response in patients after TKR. Patients and Methods: Ninety patients undergoing TKR were allocated into Groups 1, 2, and 3 and received epidural analgesia, sciatic and femoral nerve blocks, and systemic analgesia, respectively. Postoperative pain was assessed at rest and on movement before surgery, after surgery, after 24 and 72 hours. Blood samples were collected at the same time points. The frequencies of T lymphocytes, NK and NKT cells and their subsets as well as their perforin expression were analyzed. Serum levels of TNF-α, IL-6 and IL- β as well as concentrations of urine catecholamines and serum cortisol were measured and analyzed. Results: Patients in Group 1 and 2 experienced less severe pain than in Group 3. There was a significant decrease in the frequency of T lymphocyte, their subsets and NKT as well as lower levels of perforin and perforin+ CD3+CD8+CD56- lymphocytes were observed in Group 3 than in Groups 1 and 2. We observed lower concentrations of IL-1β and IL-6 as well as concentrations of cortisol and norepinephrine in Groups 1 and 2 than in Group 3 in early postoperative period. Conclusion: Regional analgesia is more effective in maintaining cell mediated immunity and perforin expression in lymphocytes as well as in reducing the neuroendocrine and inflammatory response compared to systemic analesia