aprepitant and Osteoarthritis

Postoperative opioid analgesia increases the incidence of postoperative nausea and vomiting (PONV). We investigated whether a combination of the neurokinin-1 antagonist aprepitant and dexamethasone decreases PONV incidence compared with dexamethasone alone in high-risk patients receiving continuous epidural fentanyl.. Sixty nonsmoking female patients scheduled for elective knee osteoarthritis surgery were randomly allocated to receive oral aprepitant 80 mg (aprepitant+dexamethasone group, N.=30) 2 h before anesthesia induction or no oral aprepitant (dexamethasone group, N.=30). All patients received intravenous dexamethasone 8 mg immediately before anesthesia induction. Anesthesia was maintained with remifentanil and sevoflurane. Continuous infusion of epidural analgesia, including fentanyl, was provided during and after surgery. We assessed complete response (no PONV and no rescue antiemetic use), incidence of nausea and vomiting, nausea severity scale, vomiting frequency, rescue antiemetic use, and postoperative pain at 2 and 24 h after surgery.. The cumulative incidence of vomiting at 24 h was 3% in the aprepitant+dexamethasone group and 27% in the dexamethasone group (P=0.011). The incidence and frequency of vomiting in the late postoperative period was also significantly lower in the aprepitant+dexamethasone group than in the dexamethasone group. However, there were no significant group differences in the proportion of patients who experienced a complete response, the incidence and severity of nausea, and rescue antiemetic use at 24 h.. The combination of aprepitant and dexamethasone was more effective in preventing postoperative vomiting compared with dexamethasone alone in patients at high-risk of PONV from continuous epidural fentanyl analgesia.

Topics: Aged; Analgesia, Epidural; Analgesics, Opioid; Antiemetics; Aprepitant; Dexamethasone; Female; Fentanyl; Humans; Knee; Middle Aged; Morpholines; Osteoarthritis; Postoperative Nausea and Vomiting

Substance P (SP) modulates NK1 and has various functions such as regulation of pain response, bone metabolism, and angiogenesis, which are recognized as important factors in osteoarthritis (OA). We aimed to evaluate the therapeutic effect of targeting SP on OA progression.. SP expression patterns were analysed histologically in articular cartilage and subchondral bone of human knees from OA patients and autopsy donors as non-OA samples and in mouse articular cartilage. Moreover, to examine the effect of SP on the progression of OA, we administered drugs to mice following the surgical destabilization of the medial meniscus: Phosphate-buffered saline (PBS), septide (NK1 receptor agonist), or aprepitant (NK1 receptor antagonist). Histological analysis and bone morphologic analysis using micro-computed tomography were performed.. In human analysis, the expression of SP in mild OA samples was significantly higher than that in severe OA, and that in healthy cartilage was significantly higher than that in OA. In mouse analysis, Osteoarthritis Research Society International scores in the septide group were significantly lower than those in the control group. Computed tomography analysis showed that the subchondral bone's epiphysis in the control group had sclerotic change, not observed in the septide group.. The administration of septide ameliorates OA progression through preventing subchondral bone sclerosis.

Topics: Animals; Aprepitant; Cartilage, Articular; Disease Models, Animal; Humans; Mice; Osteoarthritis; Phosphates; Substance P; X-Ray Microtomography