Plasma concentration of dexmedetomidine combined with fixed remifentanil for nociceptive and hemodynamic control during skull pin fixation.

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.