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CLINICAL PRACTICE

COX-2 inhibitors improve outcomes following TKA

The findings of a recent study can help healthcare professionals meet the challenge of controlling postoperative pain following total knee arthroplasty (TKA) while reducing opioid-induced adverse effects and improving surgical outcomes. Investigators from Rush Medical College at Rush-Presbyterian-St. Luke's Medical Center in Chicago found that perioperative use of a selective cyclooxygenase-2 (COX-2) inhibitor is an effective component of multimodal analgesia that improves outcomes following TKA.

This is the first randomized outcomes trial to demonstrate that administration of a selective COX-2 inhibitor during the pre- and postoperative period in patients undergoing TKA improves surgical outcomes, said Asokumar Buvanendran, M.D., assistant professor in the department of anesthesiology at Rush Medical College, who was the lead author of the study.

Buvanendran presented the study findings at an American Medical Association media briefing held last month in New York City. The study was supported by a medical school grant from Merck. The results were published in the Nov. 12 issue of the Journal of the American Medical Association.

Investigators enrolled 70 patients undergoing TKA. Of those, 35 received 50 mg of rofecoxib (Vioxx, Merck) at 24 hours and at one to two hours prior to surgery, 50 mg daily for five days following surgery, and 25 mg for another eight days. The other 35 received placebo at the same times. Buvanendran pointed out that no differences existed between the rofecoxib group and the placebo group in terms of weight, height, age, and duration of anesthesia.

In the 42 hours immediately following surgery, those randomized to rofecoxib required less total epidural analgesia compared with those randomized to placebo, said Buvanendran. In addition, persons in the rofecoxib group requested and received fewer doses of patient-controlled epidural analgesia (PCEA) compared with those in the placebo group.

Those in the rofecoxib group experienced fewer incidences of vomiting on the first postoperative day, compared with those in the placebo group, Buvanendran reported. Persons receiving rofecoxib also experienced less nausea than did those receiving placebo. Fewer patients in the rofecoxib group required antiemetic therapy, compared with patients in the placebo group, he said.

Patients were asked to assess their pain using a visual analog scale (VAS), with 0 corresponding to "no pain" and 10 corresponding to "the worst pain imaginable." Although both groups were instructed to use PCEA to achieve a pain rating of 4 or less during the immediate postoperative period, the mean VAS score was less for the rofecoxib group than for the placebo group during the hospital stay, Buvanendran said. Median VAS scores were less for the rofecoxib group than for the placebo group during the same time period and at one week after discharge from the hospital, he added.

Those randomized to rofecoxib had fewer incidences of sleep disturbance due to pain on the first three nights following surgery, said Buvanendran.

At the time of hospital discharge and at one-month follow-up, passive and active flexion of the operated knee was greater for those randomized to rofecoxib than for those randomized to placebo, Buvanendran said. In addition, those who received rofecoxib were able to achieve 90º flexion of the knee sooner following TKA than those who received placebo.

At discharge, patients in the rofecoxib group reported higher satisfaction with anesthesia and analgesia than did patients in the placebo group, said Buvanendran. At two weeks and at one month, the investigators followed up with patients via telephone and found that these differences in satisfaction persisted.

Buvanendran suggested that pharmacists could drive home the point to hospital administrators that selective COX-2 inhibitors can reduce costs by decreasing the need for expensive medications such as ondansetron HCl (Zofran, GlaxoSmithKline) and for physical therapy. When pharmacists note that patients are on high doses of opioids, they should consult with the physician regarding the need for COX-2 inhibitor therapy. He added that pharmacists dispensing postoperative drugs should verify that those patients who are candidates for COX-2 inhibitor therapy are receiving it.

Charlotte LoBuono

 

Charlotte LoBuono. COX-2 inhibitors improve outcomes following total knee arthroplasty. Drug Topics Dec. 8, 2003;147:HSE5.