A Combined Multi-Route Regimen of Multiple Low-Dose Intravenous and Periarticular Dexamethasone Improves Perioperative Outcomes After Total Knee Arthroplasty: A Prospective, Double-Blind, Randomized Controlled Trial.

Abstract

The objective of our study was to compare five low-dose perioperative dexamethasone (DEX) regimens on early recovery after total knee arthroplasty and identify an optimal route combination. In a prospective, double-blind, randomized controlled trial, patients were randomized to five groups. The COMB group received a combined regimen of pre- and postoperative intravenous (IV) doses with intraoperative periarticular injection, the IV2 group received pre- and postoperative IV doses, the IV1 group received a single preoperative IV dose, the PAI group received intraoperative periarticular injection, and the CON group received no DEX. Outcomes within 72 hours were visual analog scale (VAS) pain (rest, passive flexion, and ambulation); postoperative nausea and vomiting (PONV); opioid consumption; range of motion (ROM); C-reactive protein (CRP); interleukin-6 (IL-6); white blood cell (WBC) count and neutrophil percentage; Knee Society Score (KSS); knee swelling; Quality of Recovery-15 (QoR-15); lengths of stay (LOS); and complications. Versus the CON group, the COMB group showed lower rest pain on postoperative days (POD) one to three, and the PAI group showed lower pain on POD one to two. Both groups had lower passive flexion pain on POD one to two and lower ambulation pain on POD three. Compared with IV2 and IV1 groups, the COMB group yielded lower rest, passive-flexion, and ambulation pain across the same windows. The PONV rates were lower in the COMB, IV2, and IV1 groups than in CON and PAI groups; the PAI group did not differ from the CON group. Across POD one to three, ROM was higher in all intervention groups than in the CON group. Both CRP and IL-6 were lower in the COMB, IV2, and IV1 groups versus the CON group. Peripheral WBC count and neutrophil percentage increased in the COMB and PAI groups. There was one mild gastrointestinal bleed that occurred in the COMB group; no other serious adverse events were observed. In primary TKA, low-dose DEX reduced pain and PONV within 72 hours and facilitated early ROM recovery. A combined multi-route regimen balanced efficacy and safety, supporting optimized and individualized DEX pathways.