Unlike expired sevoflurane concentration, propofol lacks a biomarker for its brain effect site concentration, leading to dosing imprecision particularly in infants. Electroencephalography monitoring can serve as a biomarker for propofol effect site concentration, yet proprietary electroencephalography indices are not validated in infants. The authors evaluated spectral edge frequency (SEF95) as a propofol anesthesia biomarker in infants. It was hypothesized that the SEF95 targets will vary for different clinical stimuli and an inverse relationship existed between SEF95 and propofol plasma concentration.


This prospective study enrolled infants (3 to 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.


Of 49 enrolled infants, 44 evaluable (90%) showed distinct SEF95 for endpoints: pacifier (ED50, 21.4 Hz; ED90, 19.3 Hz), electrical stimulation (ED50, 12.6 Hz; ED90, 10.4 Hz), and laryngoscopy (ED50, 8.5 Hz; ED90, 5.2 Hz). From propofol 0.5 to 6 μg/ml, a 1-Hz SEF95 increase was linearly correlated to a 0.24 (95% CI, 0.19 to 0.29; P < 0.001) μg/ml decrease in plasma propofol concentration (marginal R2 = 0.55).


SEF95 can be a biomarker for propofol anesthesia depth in infants, potentially improving dosing accuracy and utilization of propofol anesthesia in this population.

Editor’s Perspective
What We Already Know about This Topic
  • In older children and adults, an electroencephalography (EEG) index called the spectral edge frequency 95 (SEF95), the frequency that the majority (95%) of EEG power lies under, decreases with increasing propofol concentrations.

  • Because the EEG of infants is markedly different from that of older children and adults, it is unknown whether the SEF95 can be used as a reliable indicator of propofol concentrations and depth of anesthesia in children under a year of age.

What This Article Tells Us That Is New
  • Increasing concentrations of propofol caused a linear decrease in the SEF95.

  • The propofol concentrations and SEF95 targets that were needed to prevent 50% of the infants responding to various noxious clinical stimuli were comparable to those found in adults and older children.

  • The SEF95 is a reasonable biomarker of propofol anesthesia in this age group.

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