A Single Preemptive Dose of Intravenous Nefopam Augmenting Multimodal Analgesia for Total Knee Arthroplasty: A Prospective, Triple-Blind, Randomized Controlled Trial
In brief
One nefopam dose shortened discharge after knee replacement by 8 hours
In a 60-patient randomized trial, a 20-mg dose before surgery lowered pain and reduced 48-hour morphine use from 7.6 to 5.8 mg; patients were discharged about 8 hours sooner. Nausea was less common, but transient rapid heart rate was more frequent, and larger trials are needed to confirm the benefits and safety.
- Journal
- The Journal of arthroplasty (Q1)
- Published
- 6 November 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Kritsada Sukha, Ratchaphon Khasemsiri, Burin Sutthapakti, Wiboon Wanitcharoenporn, Thisayapong Inta-Ngam, Artit Laoruengthana
- PMID
- 42994642
- DOI
- 10.1016/j.arth.2026.11.009
Why clinicians should know about it
- Picked for Anesthesiology and Pain Medicine (paper of the day, 8 November 2026): Randomized trial of preemptive nefopam in multimodal analgesia
Abstract
BACKGROUND: Fast-track total knee arthroplasty (TKA) requires robust multimodal analgesia (MMA) while minimizing opioid-related adverse effects. We hypothesized that a single preemptive dose of intravenous (IV) nefopam would optimize postoperative pain control, reduce opioid consumption, and accelerate functional recovery in TKA. METHODS: In this prospective, triple-blind, randomized controlled trial, 60 patients undergoing unilateral TKA were allocated to receive either a 20-mg IV nefopam or placebo infusion 30 minutes before surgical incision. All patients adhered to a standardized Enhanced Recovery After Surgery (ERAS) protocol. The primary endpoint was the Visual Analog Scale (VAS) pain score during 90 degrees of active knee flexion at 24 hours postoperatively. The secondary outcomes included cumulative IV morphine consumption, functional recovery milestones, and safety profiles. RESULTS: The nefopam group demonstrated significantly lower dynamic VAS scores at 24 hours compared to placebo (51.9 versus 64.0, P < 0.001), along with reduced pain at rest from six to 48 hours. Preemptive nefopam significantly reduced cumulative 48-hour morphine consumption (5.8 versus 7.6 mg, P = 0.005). This opioid-sparing effect translated to a significantly lower incidence of postoperative nausea and vomiting (47 versus 73%, P < 0.001). Furthermore, the nefopam cohort achieved earlier first ambulation, superior active range of motion, and an approximately 8-hour reduction in time-to-discharge (48.0 versus 56.1 hours, P < 0.001). Tachycardia occurred more frequently with nefopam (23 versus 3%, P = 0.01), but was transient, self-limiting, and did not impede rehabilitation. CONCLUSION: A single preemptive dose of IV nefopam is an effective adjunct to MMA in TKA. It significantly reduces opioid consumption and nausea while accelerating functional recovery and hospital discharge, supporting outpatient and short-stay arthroplasty pathways. LEVEL OF EVIDENCE: Level I, Therapeutic Study.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.