Abstract
BACKGROUND: Dexmedetomidine (DEX) is an α(2)-adrenergic agonist widely used for intravenous sedation. Its pharmacological properties suggest autonomic modulatory effects; however, these remain insufficiently characterized during operative procedures. This pilot study compared autonomic responses to surgical stress of DEX and propofol (PPF) during third molar extraction using the Analgesia Nociception Index (ANI), a heart rate variability-derived marker of autonomic balance. METHODS: Adults aged ≥18 years undergoing extraction of mandibular third molars under intravenous sedation were prospectively enrolled. Sedation was maintained with either DEX or PPF infusion following a small pre-induction dose of midazolam. ANI was continuously recorded using a High-Frequency Variability Index module, with a 240-s moving average considered equivalent to ANI. The primary outcome was the minimum ANI value within each predefined 5-min intraoperative interval; percent change from baseline (%Δx) was also calculated to account for interindividual variability. Hemodynamic and respiratory variables were evaluated as secondary outcomes. Protocol deviations or incomplete ANI data prompted exclusion. Between-group comparisons were performed using the Wilcoxon rank-sum test, and p-values were interpreted descriptively given the exploratory study design. RESULTS: Thirty patients were enrolled, 24 (n = 12 per group) of whom were included in the final analysis. The baseline demographics, sedation depth (Ramsay Sedation Scale 3-4), and procedural characteristics were comparable. The minimum intraoperative ANI values were consistently higher with DEX; between-group differences were observed at 5-10, 10-15, 15-20, and 25-30 min after surgery onset (all unadjusted P < 0.05). The %Δx values were positive or near zero with DEX, whereas PPF showed progressively negative values with wider dispersion; ANI values intermittently fell below 50 only in the PPF group. Blood pressure was lower with DEX, whereas cardiorespiratory parameters remained similar. Patient State Index (PSI) during sedation was higher with DEX, but intraoperative PSI values were comparable. CONCLUSION: DEX was associated with greater intraoperative autonomic stability than PPF during intravenous sedation despite similar clinical sedation depths. These findings reflect the distinct pharmacological profiles of both agents. ANI monitoring provides objective insights into autonomic modulatory responses during sedation. Larger randomized trials are required to confirm these preliminary findings.