A Single Preemptive Dose of Intravenous Nefopam Augmenting Multimodal Analgesia for Total Knee Arthroplasty: A Prospective, Triple-Blind, Randomized Controlled Trial.

J Arthroplasty · Nov 06 2026 · Recent

Sukha K, Khasemsiri R, Sutthapakti B, Wanitcharoenporn W, Inta-Ngam T, Laoruengthana A

Department of Orthopaedics, Buddhachinaraj Hospital, Phitsanulok, Thailand

Adult Reconstruction

SUMMARY — THE REDUCTIONIn this randomized trial of 60 TKA patients, one preemptive 20-mg IV nefopam dose lowered 24-hour dynamic pain, morphine use, and nausea, and shortened discharge by about 8 hours, with transient tachycardia.
Abstract, as published

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.

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