• Gordana Kristek, Ivan Radoš, Dalibor Kristek, Leonardo Kapural, Nenad Nešković, Sonja Škiljić, Vesna Horvat, Sanja Mandić, and Ivana Haršanji-Drenjančević.
• Department of Anaesthesiology, Josip Juraj Strossmayer University of Osijek, University Hospital Osijek, Reanimatology and Intensive Care, Osijek, Croatia.
• Reg Anesth Pain Med. 2019 Jan 1; 44 (1): 59-68.

Background And ObjectivesTo investigate the possible effect of postoperatively applied analgesics-epidurally applied levobupivacaine or intravenously applied morphine-on systemic inflammatory response and plasma concentration of interleukin (IL)-6 and to determine whether the intensity of inflammatory response is related to postoperative cognitive dysfunction (POCD).MethodsThis is a randomized, prospective, controlled study in an academic hospital. Patients were 65 years and older scheduled for femoral fracture fixation from July 2016 to September 2017. Inflammatory response was assessed by leukocytes, neutrophils, C reactive protein (CRP) and fibrinogen levels in four blood samples (before anesthesia, 24 hours, 72 hours and 120 hours postoperatively) and IL-6 concentration from three blood samples (before anesthesia, 24 hours and 72 hours postoperatively). Cognitive function was assessed using the Mini-Mental State Examination preoperatively, from the first to the fifth postoperative day and on the day of discharge.ResultsThe study population included 70 patients, 35 in each group. The incidence of POCD was significantly lower in the levobupivacaine group (9%) than in the morphine group (31%) (p=0.03). CRP was significantly lower in the levobupivacaine group 72 hours (p=0.03) and 120 hours (p=0.04) after surgery. IL-6 values were significantly lower in the levobupivacaine group 72 hours after surgery (p=0.02). The only predictor of POCD in all patients was the level of IL-6 72 hours after surgery (p=0.03).ConclusionsThere is a statistically significant association between use of epidural levobupivacaine and a reduction in some inflammatory markers. Postoperative patient-controlled epidural analgesia reduces the incidence of POCD compared with intravenous morphine analgesia in the studied population.Trial Registration NumberNCT02848599.© American Society of Regional Anesthesia & Pain Medicine 2019. No commercial re-use. See rights and permissions. Published by BMJ.

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