Trans-auricular Vagus Nerve Stimulation to Reduce Perioperative Pain and Morbidity: Protocol for a Single-Blind Analyser-Masked Randomised Controlled Trial.

Background: Activation of central autonomic pathways, including those regulating the arterial baroreflex, might reduce acute pain. We tested the hypothesis that transcutaneous auricular nerve stimulation (TAN) reduces pain after ortho-paedic trauma surgery through autonomic modulation.Methods: A total of 86 participants aged >18 yr were randomly assigned to 50 min of either sham or active bilateral TAN, undertaken before, and again 24 h after, surgery for orthopaedic trauma. The primary outcome was absolute change in pain 24 h postoperatively, comparing the 100 mm visual analogue scale (VAS) before and after TAN. Secondary outcomes included the minimal clinically important difference in pain (>10 mm increase or reduction in VAS) before/after surgery, using intention-to-treat analysis. Holter monitoring, the analysis of which was masked to allocation, quantified auto-nomic modulation of heart rate.Results: From June 22, 2021 to July 7, 2022, 79/86 participants (49 yr; 45% female) completed TAN before and after surgery. For the primary outcome, the mean reduction in VAS was 19 mm (95% confidence interval [CI]: 12-26) after active TAN (n=40), vs 10 mm (95% CI: 3-17) after sham TAN (n=39; P=0.023). A minimally clinically important reduction in post-operative pain occurred in 31/40 (78%) participants after active TAN, compared with 15/39 (38%) allocated to sham TAN (odds ratio 5.51 [95% CI: 2.06-14.73]; P=0.001). Only active TAN increased heart rate variability (log low-frequency power increased by 0.19 ms2 [0.01-0.37 ms2]). Prespecified adverse events (auricular skin irritation) occurred in six participants receiving active TAN, compared with two receiving sham TAN.Conclusion: Bilateral TAN reduces perioperative pain through autonomic modulation. These proof-of-concept data support a non-pharmacological, generalisable approach to improve perioperative analgesia.