Discussion
In our study, we found that perioperative administration of celecoxib, a selective COX-2 inhibitor, reduced postoperative VAS pain scores at rest and decreased morphine usage while providing better ROM rehabilitation results. Perioperative administration of celecoxib did not increase perioperative bleeding or blood transfusion amounts.
Coxibs are effective analgesics for post-operative pain.[20,21,22] To the best of our knowledge, the literature lacks a review of perioperative celecoxib for pain management in TKA patients. Perioperative coxibs have been shown to reduce postoperative pain and analgesic consumption while enhancing patient satisfaction.[6] In 2000, Reuben and Connelly studied perioperative use of celecoxib (200 mg) and rofecoxib (50 mg) for spinal fusion surgery.[12] They concluded that both celecoxib and rofecoxib decrease morphine consumption, but that celecoxib's effects are limited. In their follow-up study, preoperative celecoxib 400 mg showed better morphine-sparing effects than a single 200 mg preoperative dose of celecoxib.[23] Therefore, we suggest that 400 mg of celecoxib is more optimal than 200 mg in controlling acute postoperative pain.[4,6] In our study, although VAS scores were significantly improved at 48 and 72 hrs at rest, and repeated measures ANOVA test also indicated that the celecoxib group had significantly lower pain scores at rest (p = 0.023), there was no significant difference between the two groups in pain scores at ambulation. We also demonstrate that perioperative celecoxib improves postoperative ROM results. The mean knee ROM was 92 degrees in the celecoxib group and 83.8 degrees in the control group, seven days after surgery.
NSAIDs are known to decrease opioid consumption by 30-50%.[6,7,24] In our study, perioperative celecoxib significantly lowered it by 40%. However, the effects of perioperative coxibs on opioid-related side effects are still uncertain.[6] This study also showed reduced postoperative nausea and vomiting (28% vs. 43%). However, there were no differences in PONV incidence. Further evaluation, using a larger sample, is called for.
Previous studies have shown that conventional preoperative non-selective NSAIDs increase bleeding risks.[17,25] Conventional non-selective NSAIDs reversibly inhibit COX and interfere with platelet functions, while selective COX-2 inhibitors have less antiplatelet effects than conventional non-selective NSAIDs.[26,27] In this study, perioperative administration of 400 mg of celecoxib had no significant effects on blood loss, thus confirming indirectly that celecoxib has little effect on serum thromboxane or platelet functions.[16] The analgesic effects of aspirin may confuse the benefits of celecoxib, even though both groups are allowed to have aspirin in our study, and use of aspirin does not prevent the thromboembolic adverse effects of coxibs.
Selective COX-2 inhibitors may be a better choice for multimodal analgesia than conventional non-selective NSAID. Selective COX-2 inhibitors may have better gastrointestinal tolerance and less risk for cardiovascular events. It's suggested that selective COX-2 inhibitors have less gastrointestinal toxicity than conventional non-selective NSAIDs.[28,29] It's suggested that selective COX-2 inhibitors increase the risks of cardiovascular events, myocardial infarction, stroke and heart failure,[29,30] too. White et al. also demonstrated no significant increase in CV risks with celecoxib in comparison to placebo or non-selective NSAIDs.[31] Moore et al. even demonstrated that celecoxib had less gastrointestinal and cardiovascular risk than conventional non-selective NSAIDs and all other coxibs.[32] However, there might not be any difference in the coxibs and conventional non-selective NSAIDs with respect to serious vascular events.[33] Selective COX-2 inhibitors may cause less bleeding than non-selective NSAID, because coxibs do not interfere the normal mechanisms of platelet aggregation and hemostasis, whereas non-selective NSAID produces significant reductions in platelet aggregation and serum thromboxane B2.[34] It has been shown that prior exposure of non-selective NSAID such as ibuprofen in THR surgery significant increases bleeding.[10] Therefore, we suggest that selective COX-2 is optimal for multimodal analgesia.
One limitation of this study is the lack of a true placebo group. Placebo response has been observed in up to 30% of patients that undergo surgery. However, placebo usage may present ethical concerns in the postoperative care of TKA surgery; we therefore adopted an active-control trial design that compared celebrex treatment to the standard therapy (PCA morphine) at our institute. Another limitation was the limited research period. We recorded data for only the first seven days. Although we demonstrated that celecoxib had better rehabilitative results in the first week than PCA morphine, long-term efficacy is still in question. There may be many reasons for the resting VAS scores to not have reached significance until 48 hours after surgery. One possibility is that the true difference does exist and that a larger trial size is needed to draw out the difference, despite that we had shown that the trial size in our study had adequate power.
