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Influence of postoperative analgesia on systemic inflammatory response and postoperative cognitive dysfunction after femoral fractures surgery: a randomized controlled trial
  1. Gordana Kristek1,
  2. Ivan Radoš1,
  3. Dalibor Kristek2,
  4. Leonardo Kapural3,
  5. Nenad Nešković1,
  6. Sonja Škiljić1,
  7. Vesna Horvat3,
  8. Sanja Mandić4 and
  9. Ivana Haršanji-Drenjančević1
  1. 1 Department of Anaesthesiology, Josip Juraj Strossmayer University of Osijek, University Hospital Osijek, Reanimatology and Intensive Care, Osijek, Croatia
  2. 2 Department of Surgery, Josip Juraj Strossmayer University of Osijek, University Hospital Osijek, Osijek, Croatia
  3. 3 Carolinas Pain Institute, Winston-Salem, North Carolina, USA
  4. 4 Department of Clinical Laboratory Diagnostics, Josip Juraj Strossmayer University of Osijek, University Hospital Osijek, Osijek, Croatia
  1. Correspondence to Leonardo Kapural, Carolinas Pain Institute, Winston-Salem, NC 27103, USA; lkapuralmd{at}


Background and objectives To 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).

Methods This 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.

Results The 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).

Conclusions There 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 number NCT02848599.

  • postoperative analgesia
  • systemic inflammatory response
  • pocd
  • elderly
  • femoral fractures

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  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Approval was obtained from the University Hospital Osijek Ethics Committee (approval number 25-1:6563-3/2014, 19.5.2014).