Protective Effect of Celecoxib on Early Postoperative Cognitive Dysfunction in Geriatric Patients

Abstract

Objective: Inflammation plays a key role in the etiology and pathology of postoperative cognitive dysfunction (POCD). Cyclooxygenase (COX)-2 inhibitor celecoxib is used for the treatment of acute pain due to its potent anti-inflammatory and analgesic effects. Herein, we evaluated the effects of celecoxib on POCD in geriatric patients.Methods: A total of 178 geriatric patients undergoing total knee arthroplasty were randomly divided into two groups and treated with celecoxib (group C) or placebo (group P). The levels of perioperative plasma COX-2, IL-1β, IL-6, TNF-α, neuron-specific enolase, and S100β were detected in all patients. The pain intensity was measured by numerical rating scale (NRS). A battery of 9 neuropsychological tests was performed pre-operatively and 1 week, and 3 months postoperatively. Patients, whose postoperative performance declined by ≧1 standard deviation as compared to each preoperative test score on ≧2 tests, were classified as POCD.Results: A significant decrease in POCD incidence was found in group C as compared to group P on postoperative day 7 (12.3% vs. 34.1%; p < 0.05). POCD incidence did not differ between the two groups at the 3-month follow-up (8.8 vs. 9.7%). NRS scores at days 3 and 4 post-surgery were significantly lower in group C (p < 0.05). Patients in group C showed lower level of plasma COX-2, IL-1β, IL-6, TNF-α, and S100β as compared to group P postoperatively (p < 0.05).Conclusion: These results demonstrated that celecoxib can decrease early POCD incidence after total knee arthroplasty in geriatric patients, which might be mediated by suppressing inflammation and acute postoperative pain caused by surgical trauma.Registration: Chinese Clinical Trial Register, ChiCTR-IOR-16008168.

Postoperative Pain Management in Total Knee Arthroplasty

“…of 165 patients after TKA suggested that preoperative administration of etoricoxib 120 mg orally was superior to postoperative administration of the same dose in terms of its morphine‐sparing effect during the first postoperative 48 h, without difference in the incidence of side effects. Apart from analgesia, celecoxib and parecoxib could also decrease early postoperative cognitive dysfunction incidence after TKA in elderly patients. At present, COX‐2 inhibitors are usually added to multimodal analgesia to reduce the consumption of opioids, without serious complications.…”

Perioperative Neurocognitive Disorder

“…89,90 Blockage of either tumor necrosis factor α or interleukin 6 using antibodies effectively reduced rodent postoperative cognitive dysfunction, but also delayed wound healing. 79,82 More conventional antiinflammatory drugs (dexamethasone and cyclooxygenase-2 inhibitors) given before, during, or after the procedure have yielded variable results, [91][92][93][94][95] a result that has shifted attention to innate processes that actively turn off or resolve inflammation. Initial studies of mice with the tibial fracture model show promising results with proresolution strategies, such as resolvin-D1 and maresin-1, 96,97 as well as bioelectronic approaches, such as electrical stimulation of the vagus nerve.…”

The Role of Neuroinflammation in Postoperative Cognitive Dysfunction: Moving From Hypothesis to Treatment

“…In a trial of 134 elderly patients, parecoxib was shown to decrease pro-inflammatory markers and POCD incidence (as assessed using a neurocognitive battery) compared to placebo at 1 week, but not 3 months following surgery (152), although this negative result was largely due to improved cognitive performance in the placebo group. Similarly, a trial of 178 elderly patients showed that celecoxib reduced pro-inflammatory markers and POCD (determined by reduction in performance of ≥2 of 5 cognitive tests) at 1 week following surgery compared to placebo (153). There are no ongoing registered clinical trials testing the use of NSAIDs or selective COX-2 inhibitors in POCD.…”

“…Indeed, rodent models have shown that the COX-2 inhibitor parecoxib is capable of downregulating IL-1 β and TNFα expression (168); furthermore, meloxicam, a non-steroidal anti-inflammatory drug (NSAID) with relative selectivity for COX-2 has been shown to decrease short-term deficits in recognition memory following surgery (169). So far, two human trials have evaluated the efficacy of COX-2 inhibition on POCD, both in geriatric patients undergoing total knee arthroplasty (152, 153). In a trial of 134 elderly patients, parecoxib was shown to decrease pro-inflammatory markers and POCD incidence (as assessed using a neurocognitive battery) compared to placebo at 1 week, but not 3 months following surgery (152), although this negative result was largely due to improved cognitive performance in the placebo group.…”