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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 (EC\n                    <jats:sub>95<\/jats:sub>\n                    ) 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\u2009\u2265\u200930 with mean arterial pressure (MAP) and heart rate (HR) within \u00b1\u200920% of baseline values.  Probit regression analysis revealed EC\n                    <jats:sub>50<\/jats:sub>\n                    and EC\n                    <jats:sub>95<\/jats:sub>\n                    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\u2009&lt;\u200930 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.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-50692-y","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T15:07:04Z","timestamp":1777302424000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma concentration of dexmedetomidine combined with fixed remifentanil for nociceptive and hemodynamic control during skull pin fixation"],"prefix":"10.1038","volume":"16","author":[{"given":"Wei-Cheng","family":"Tseng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann\u2011Shung","family":"Lieu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chi","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Feng","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsai-Shan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Wei","family":"Kuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Fu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"issue":"4","key":"50692_CR1","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1097\/00000542-197510000-00010","volume":"43","author":"HM Shapiro","year":"1975","unstructured":"Shapiro, H. 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