Parecoxib prevents early postoperative cognitive dysfunction in elderly patients undergoing total knee arthroplasty

Abstract

Background:Trial design neuroinflammation and postoperative pain after surgery are increasingly reported in association with postoperative cognitive dysfunction (POCD). Parecoxib, a selective cyclooxygenase (COX)-2 inhibitor, is used for postoperative analgesia for its potent anti-inflammatory and analgesic effects. This study aimed to evaluate parecoxib's effects on POCD in elderly patients undergoing total knee arthroplasty.Methods:Around 134 elderly patients undergoing total knee arthroplasty were randomly divided into parecoxib (group P) and control (group C) groups, and treated with parecoxib sodium and saline, respectively, shortly after induction of general anesthesia and 12-h postsurgery, respectively. Perioperative plasma IL-1β, IL-6, TNF-α, and C-reactive protein (CRP) 1evels were measured. Postoperative pain was assessed following surgery. Neuropsychological tests were performed before surgery, and 1 week and 3 months postoperation.Results:POCD incidence in group P was significantly lower compared with that of group C at 1 week after surgery (16.7% vs 33.9%; P < 0.05); no significant difference was found between groups C and P at 3-month follow-up (9.7% vs 6.7%). Compared with group C values, visual analog pain scale (VAS) scores at 3, 6, and 12 hours after surgery were significantly lower in group P(P < 0.05). Plasma IL-1β, IL-6, and TNF-α levels were lower in group P than in group C after the operation (P < 0.05). No significant difference in the plasma CRP level was found between groups P and C.Conclusions:Parecoxib sodium decreases POCD incidence after total knee arthroplasty in elderly patients and may explain how this drug suppresses inflammation and acute postoperative pain caused by surgical trauma.

PGE2‐EP3 signaling exacerbates hippocampus‐dependent cognitive impairment after laparotomy by reducing expression levels of hippocampal synaptic plasticity‐related proteins in aged mice

“…Preclinical studies have indicated that an increased level of PGE2 in rodent hippocampus after surgery and those selective COX‐2 inhibitors, such as meloxicam and parecoxib, ameliorate postoperative cognitive decline . This is in concordance with clinical data that advocate that surgical trauma could upregulate PGE2 in the central nervous system and parecoxib decreases POCD incidence . However, in the central nervous system, there exist 4 distinct PGE2 receptors (EP1‐4), and the exact mechanism of PGE2 meditated development of PCOD need further exploration.…”

“…Both preclinical and clinical studies suggest that selective COX‐2 inhibitors such as meloxicam and parecoxib, ameliorate postoperative cognitive decline . Moreover, selective COX‐2 inhibitor has been shown to improve memory function by downregulation of PGE2 levels in Alzheimer's diseases (AD) which have similar clinical symptoms of POCD, and these beneficial effects on memory do not depend on lowered levels of cytokines such as IL‐1 and TNF‐α .…”

“…21,22 This is in concordance with clinical data that advocate that surgical trauma could upregulate PGE2 in the central nervous system and parecoxib decreases POCD incidence. 23,24 However, in the central nervous system, there exist 4 distinct PGE2 receptors (EP1-4), 25 and the exact mechanism of PGE2 meditated development of PCOD need further exploration.…”

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.…”

Anesthetic neurotoxicity: an emerging role for glia in neuroprotection

“…For example, ketamine, a phencyclidine derivative that not only antagonizes glutamate receptors but also has a profound anti-inflammatory effect, attenuates cognitive dysfunction following cardiac surgery [6,7]. Likewise, parecoxib, a cyclooxygenase-2 inhibitor with marked anti-inflammatory effects, also prevented cognitive decline following orthopedic surgery in an elderly cohort [8]. Recently, it was further described that dexamethasone, well known for reducing neuroinflammation in traumatic brain injury and those with cerebral edema, also improved cognitive outcome following surgery [9].…”