Perioperative celecoxib administration for total knee arthroplasty

AORN Journal, July, 2008 by George Allen

Anesthesia & Analgesia

April 2008

Total knee arthroplasty (TKA) is associated with considerable postoperative pain, which if unrelieved, may extend length of hospital stay, affect the patient's ability to participate in rehabilitation programs, delay recovery, and result in poor outcomes. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for patients with painful osteoarthritis, but because of the increased risk of perioperative bleeding, they are frequently discontinued seven to 10 days before elective surgery. Discontinuing NSAIDs before surgery can result in an arthritic flare that leads to increased preoperative and postoperative pain.

Recently some studies have demonstrated that the use of cyclooxygenase-2 (COX-2) NSAIDs offers a therapeutic advantage over standard NSAIDs for the management of perioperative pain for patients undergoing TKA and does not increase the risk of bleeding. The objective of this prospective, randomized, double-blind, placebo-controlled study was to determine whether preoperative use of celecoxib reduces postoperative opioid consumption and improves clinical outcomes after TKA.

Two hundred patients scheduled to undergo elective, unilateral TKA for osteoarthritis from March 2006 through February 2007 were enrolled in the study. Patients were excluded if they

* were younger than 40 years of age or older than 80 years of age;

* had an American Society of Anesthesiologist status of IV;

* had a diagnosis of rheumatoid arthritis;

* were depressed;

* were undergoing concurrent treatment with an antidepressant or anxiolytic agent;

* had a concurrent musculoskeletal diagnosis that would affect the interpretation of pain (eg, fibromyalgia, spinal stenosis);

* were allergic to sulfa or celecoxib;

* had a creatinine level higher than 1.5 mg/dL;

* had a blood urea nitrogen level higher than 22 mg/dL, or

* had a known coagulation disorder.

All NSAIDs were discontinued seven days before surgery. Patients were randomly assigned to one of two groups. Patients in the celecoxib group received celecoxib 100 mg orally twice daily seven days before surgery, and on the day of surgery, celecoxib 400 mg was administered one to two hours before surgery, and 200 mg was administered every 12 hours after surgery. The control group received matching placebo capsules at the same times pre- and postoperatively. For the first seven days before surgery, patients in both groups were asked to rate their pain using a numeric rating scale (NRS) in which zero equaled no pain and 10 equaled the worst pain imaginable and to record their preoperative use of acetaminophen/hydrocodone tablets.

All the patients underwent a similar perioperative anesthetic/analgesic protocol using a combined spinal-epidural technique. After completion of the surgery, patients were started on an epidural infusion of fentanyl and bupivicaine as a continuous basal infusion superimposed with a patient-controlled epidural analgesia (PCEA) of 1 mL every 12 minutes with a four hour lockout of 40 mL.

Patients were instructed to keep their NRS score at less than or equal to 3. Morphine 1 mg to 2 mg was administered intravenously as rescue medication for pain that was not relieved by the epidural analgesia. Thirty-six hours after surgery, patients were given oxycodone 5 mg to 10 mg every four hours as needed for an NRS score greater than 3. Patients were discharged by the third postoperative day, barring any complications.

Postoperatively, NRS pain scores were recorded both at rest and with knee flexion every eight hours in the hospital and then once daily at home. Range of motion was measured, and patients rated any sleep disturbance. Clinical outcomes including intraoperative and postoperative blood loss, postoperative nausea and vomiting, and the presence of postoperative pruritus were recorded. Common statistical techniques including the t test and chi-square test were used to analyze the data.

FINDINGS. Of the 200 patients enrolled in the study, 15 patients (ie, six in the placebo group and nine in the celecoxib group) dropped out because of protocol failure. There were no significant differences in demographics, duration of surgery, and blood loss between the two groups. The celecoxib group required less epidural solution at all time points. The total cumulative PCEA consumption was significantly lower in the celecoxib group compared to the placebo group (209.1 mL [ or -] 1.8 mL versus 232.8 mL [ or -] 2.0 mL, P < .001). At home after surgery, the celecoxib group experienced reduced pain intensity with movement at all time points (F = 109.7, P < .001) and consumed significantly less oxycodone than the placebo group (F = 417.8, P < .001). Additionally, the celecoxib group achieved earlier 90-degree knee flexion compared to the placebo group (P < .001), and the incidence of postoperative side effects (ie, nausea, vomiting, pruritus) in the immediate postoperative period was lower in the celecoxib group.

CLINICAL IMPLICATIONS. The results of this study demonstrated that the use of celecoxib reduces postoperative pain, opioid consumption, and opioid-related adverse effects and is associated with long-term benefits including improved knee function and less time to achieve effective knee range of movement after TKA. Perioperative nurses should understand that this study validates the efficacy of perioperative use of celecoxib to reduce postoperative pain and opioid consumption after major orthopedic surgery.