This study aimed to evaluate the efficacy of different dexamethasone doses in the perioperative period of total hip arthroplasty (THA). We randomly divided 180 patients into three groups: three perioperative saline injections (Group A, placebo); two perioperative doses of 15 mg dexamethasone plus a postoperative saline injection at 48 h (Group B); and three perioperative doses of dexamethasone (10 mg) (Group C). Primary outcomes were postoperative pain at rest and while walking. We also recorded consumption of analgesics and antiemetics, incidence of postoperative nausea and vomiting (PONV), C-reactive protein (CRP) and interleukin-6 (IL-6) levels, postoperative length of stay (p-LOS), range of motion (ROM), nausea, Identity-Consequence-Fatigue-Scale (ICFS), and severe complications (e.g., incidence of surgical site infection, SSI and gastrointestinal bleeding, GIB). Group B and C had significantly lower pain scores at rest than Group A on postoperative day 1. Group B and C also had significantly lower dynamic pain score, CRP, and IL-6 than Group A on postoperative day 1, 2, and 3. Patients in Group B and C had lower PONV incidence, reduced use of analgesics and antiemetics, improved ROM, shorter p-LOS, lower VAS nausea score, and lower ICFS than Group A patients. On postoperative day 3, patients in Group C had significantly lower dynamic pain and ICFS scores, IL-6, and CRP than Group B patients, as well as higher ROM. None of the groups exhibited SSI or GIB. Dexamethasone provides short-term advantages in reducing pain, PONV, inflammation, and ICFS, and increasing ROM in the early postoperative period after THA. Dexamethasone efficacy in reducing post-THA pain, inflammation, and PONV at 10 mg and 15 mg is similar during the first 48 h. Dexamethasone (30 mg) divided into three 10 mg doses was superior to two doses (15 mg) in reducing pain, inflammation, and ICFS, as well as in increasing ROM on postoperative day 3.
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