Abstract
Skull pin fixation during neurosurgery induces intense nociceptive and hemodynamic responses. Dexmedetomidine is commonly used in anesthesia to enhance perioperative stability; however, its optimal plasma concentration (Cp) when combined with remifentanil at a fixed effect-site concentration (Ce) remains undefined. This prospective study enrolled 24 patients undergoing intracranial surgery to determine the 95% effective concentration (EC95) of dexmedetomidine for skull pin fixation using the analgesia nociception index (ANI) and hemodynamic parameters. Anesthesia was maintained with propofol and remifentanil (Ce: 2.0 ng/mL), with dexmedetomidine administered via target-controlled infusion (TCI). The initial Cp of dexmedetomidine was set at 0.4 ng/mL and adjusted in 0.05 ng/mL increments using a modified up-and-down method. Analgesia was deemed successful if ANI ≥ 30 with mean arterial pressure (MAP) and heart rate (HR) within ± 20% of baseline values. Probit regression analysis revealed EC50 and EC95 of dexmedetomidine at 0.325 ng/mL and 0.395 ng/mL, respectively, for maintaining nociceptive and hemodynamic stability. Dexmedetomidine Cp below 0.3 ng/mL were associated with greater fluctuations in ANI, MAP, and HR. ANI < 30 demonstrated a sensitivity of 81.8% and a specificity of 100% for detecting analgesic failure. These findings suggest that when remifentanil is maintained at a Ce of 2.0 ng/mL, a dexmedetomidine Cp of 0.395 ng/mL provides optimal nociceptive and hemodynamic control during skull pin fixation, supporting the use of individualized dexmedetomidine titration and ANI-guided multimodal monitoring in neurosurgical anesthesia.
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This study was conducted after receiving approval from the Institutional Review Board of Kaohsiung Medical University Hospital (KMUHIRB-F(I)-20250016; approved on January 10, 2025) and registration in the ClinicalTrials.gov database (NCT06837818; registered on February 20, 2025).
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Tseng, WC., Lieu, A., Tu, YC. et al. Plasma concentration of dexmedetomidine combined with fixed remifentanil for nociceptive and hemodynamic control during skull pin fixation. Sci Rep (2026). https://doi.org/10.1038/s41598-026-50692-y
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DOI: https://doi.org/10.1038/s41598-026-50692-y
