Role of a selective cyclooxygenase-2 inhibitor on pain and enhanced recovery after open hepatectomy: a randomized controlled trial

Background: Although combination of opioid and selective cyclooxygenase-2 (COX) inhibitor had been widely used in postoperative pain management, but less study focused on open hepatectomy. This study investigated the efficacy of a selective COX-2 inhibitor (parecoxib) on postoperative pain management for open hepatic hemangioma resection. Methods: We enrolled patients who underwent open hepatic hemangioma resection at the Department of Liver Surgery at Peking Union Medical College Hospital from September 2014 to December 2016. Patients were divided randomly into a control group [patient-controlled analgesia (PCA) only] and an experimental group (parecoxib and PCA). We analyzed the perioperative serum biochemical profile, cytokine concentration including interleukin (IL)-1beta, IL-4, IL-6, IL-8, and transforming growth factor (TGF)-beta, as well as postsurgical analgesia, recovery, adverse effects, and hospital fee. Results: Fifty-six eligible patients were equally and randomly divided into the parecoxib or control group. Erythrocyte sedimentation rate (ESR) was significantly lower in parecoxib group than control. Pro-inflammatory cytokine levels (IL-6 and IL-8) increased after surgery while anti-inflammatory cytokine levels (TGF-beta) decreased. Patients in the parecoxib group showed a significantly lower IL-4 plasma concentration on postsurgical days 2 and 3 (P=0.036 and P=0.011, respectively). The difference between pre- and postoperative TGF-beta concentration was significantly increased in the parecoxib group (P= 0.007). The results indicated that there was higher consumption of the anti-inflammatory factors TGF-beta and IL-4 in the parecoxib group. This effect is accompanied by lower visual analogue scores, pain supplementation and postoperative vomiting. Conclusions: A selective COX-2 inhibitor relieved postoperative pain after open hepatic surgery. Parecoxib reduced systemic ESR, IL-6, IL-4, and TGF-beta concentrations 48 hours after surgery, indicating that both the COX-2 pathway and an immune cell balance effect is involved in surgery-induced inflammation.