Effects of a selective cyclooxygenase-2 inhibitor on postoperative inflammatory reaction and pain after total knee replacement

The goal of this study was to evaluate the systemic and peripheral effects of preoperative administration of cyclooxygenase-2 inhibitor on pain and inflammation occurring with total knee replacement (TKR). Patients undergoing elective TKR were prospectively and randomly given oral rofecoxib (25 mg) or placebo (control group) 1 hour before surgery. All patients received an epidural combined with isoflurane anesthesia during the operation and patient-controlled epidural analgesia postoperatively. The outcome measures included pain scores during rest and movement of knee joints and cumulative morphine consumption. Femoral blood and knee joint drainage fluids were examined for leucocyte numbers and concentrations of cytokines (including IL-6, IL-8, IL-10, and TNF-alpha). Periarticular circumferential increments at 48 hours served as an indication of inflammatory edema. Pain scores during rest and knee joint movement on postoperative days 1 and 2 were better in those given rofecoxib than in control subjects, and cumulative morphine consumption for the first 24 hours was significantly reduced. Both groups had higher concentrations of IL-6 and IL-8 in knee drainage fluid compared with serum levels. Rofecoxib significantly decreased regional IL-6 and TNF-a level after surgery. Moreover, the incidence of febris and degree of local edema were lower in the rofecoxib group (P <.05), and peripheral IL-6 level significantly correlated with pain score at 48 hours. Preoperative administration of rofecoxib increases patient satisfaction with analgesia, reduces opioid requirement, and decreases both systemic and local anti-inflammation after TKR. Perspective: This randomized, double-blinded trial shows that preoperative administration of rofecoxib can greatly ameliorate the pain occurring with total knee joint replacement surgery and its accompanying reduction of general and local inflammatory reactions. (c) 2008 by the American Pain Society.