Effect-site concentration of alfentanil combined with propofol for nociceptive and hemodynamic control during skull pin fixation

Skull pin fixation during neurosurgery induces intense nociceptive and hemodynamic responses. Alfentanil, a short-acting opioid with rapid blood–brain equilibration, may provide effective attenuation of these responses during total intravenous anesthesia (TIVA); however, the effective effect-site concentration (Ce) of alfentanil during skull pin fixation remains undefined. This prospective study enrolled 27 patients undergoing elective intracranial surgery to determine the 50% and 95% effective concentration (EC 50 and EC 95 ) of alfentanil for skull pin fixation using the surgical pleth index (SPI) and hemodynamic parameters. General anesthesia was maintained with propofol-based TIVA using target-controlled infusion (TCI), and alfentanil was administered according to the Scott pharmacokinetic model. The initial alfentanil Ce was set at 100.0 ng/mL and adjusted in 25.0 ng/mL increments using Dixon’s up-and-down sequential allocation method. Analgesic success was defined as SPI < 60 with mean arterial pressure (MAP) and heart rate (HR) remaining within 20% of baseline values during skull pin fixation. Probit regression analysis revealed EC 50 and EC 95 values of alfentanil at 92.4 ng/mL and 125.7 ng/mL, respectively, for achieving adequate analgesia and hemodynamic stability during skull pin fixation. Patients in the successful analgesia group demonstrated significantly lower MAP, smaller increases in MAP and SPI, and lower intra-fixation SPI values compared with those in the failed analgesia group. Higher alfentanil Ce were significantly associated with improved suppression of nociceptive and sympathetic responses. These findings suggest a concentration-dependent association between alfentanil Ce and attenuation of nociceptive and hemodynamic responses during skull pin fixation. The estimated EC 95 of 125.7 ng/mL may inform future dose-validation studies but should not be regarded as a definitive clinical target. In addition, SPI-guided monitoring may facilitate individualized opioid titration and improve perioperative stability during neurosurgical anesthesia.