Transcutaneous auricular vagus nerve stimulation reduces cytokine production in sepsis: An open double-blind, sham-controlled, pilot study

BACKGROUND: Studies have shown that vagus nerve-mediated inflammatory reflex could inhibit cytokine production and inflammation in sepsis animals. OBJECTIVES: This study aimed to explore the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) on inflammation and disease severity of sepsis patients. METHODS: A randomized, double-blind, sham-controlled pilot study was performed. Twenty sepsis patients were randomly assigned to receive taVNS or sham stimulation for five consecutive days. Stimulation effect was assessed with serum cytokine levels, Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score, and Sequential Organ Failure Assessment (SOFA) score at baseline and on Day 3, Day 5, and Day 7. RESULTS: TaVNS was well tolerated in the study population. Patients receiving taVNS experienced significant reductions in serum TNF-α and IL-1β levels and increases in IL-4 and IL-10 levels. SOFA scores decreased on Day 5 and Day 7 compared with baseline in the taVNS group. However, no changes were found in sham stimulation group. The changes of cytokine from Day 7 to Day 1 were greater with taVNS than sham stimulation. No differences in the APACHE Ⅱ score and SOFA score were observed between the two groups. CONCLUSIONS: TaVNS resulted in significantly lower serum pro-inflammatory cytokines and higher serum anti-inflammatory cytokines in sepsis patients.