Electroencephalographic indices for clinical endpoints during propofol anesthesia in infants-an early phase propofol biomarker-finding study.

BACKGROUND:Unlike expired sevoflurane concentration, propofol lacks a biomarker for its brain effect site concentration (Ce), leading to dosing imprecision particularly in infants. Electroencephalography (EEG) monitoring can serve as a biomarker for propofol Ce, yet proprietary EEG indices are not validated in infants. We evaluated spectral edge frequency (SEF95) as a propofol anesthesia biomarker in infants. We hypothesized that the SEF95 targets will vary for different clinical stimuli and an inverse relationship existed between SEF95 and propofol plasma concentration. METHODS:This prospective study enrolled infants (3-12 months) to determine the SEF95 ranges for three clinical endpoints of anesthesia (consciousness-pacifier placement, pain-electrical nerve stimulation, and intubation-laryngoscopy) and correlation between SEF95 and propofol plasma concentration at steady state. Dixon's Up-Down method was used to determine target SEF95 for each clinical endpoint. Centered isotonic regression determined the dose-response function of SEF95 where 50% and 90% of infants (ED50 and ED90) did not respond to the clinical endpoint. Linear mixed-effect model determined the association of propofol plasma concentration and SEF95. RESULTS:Of 49 enrolled infants, 44 evaluable (90%) showed distinct SEF95 for endpoints: pacifier (ED50 21.4Hz, ED90 19.3Hz), electrical stimulation (ED50 12.6Hz, ED90 10.4Hz), and laryngoscopy (ED50 8.5Hz, ED90 5.2Hz). From propofol 0.5-6 μg/ml, a 1 Hz SEF95 increase was linearly correlated to a 0.24 (95% CI: 0.19 - 0.29, p<0.001) μg/mL decrease in plasma propofol concentration (marginal R 2 = 0.55). CONCLUSIONS:SEF95 can be a biomarker for propofol anesthesia depth in infants, potentially improving dosing accuracy and utilization of propofol anesthesia in this population.