We thank Drs. Jäntti and Alahuhta for reading carefully our manuscript and appreciate their comments. Drs. Jäntti and Ala-huhta focus on the phrase “we observed an unexplained increase in the BIS value during increasing blood concentrations” in the Results section of our manuscript. 1We did not intend to explain how either electroencephalographic amplitude or Bispectral Index (BIS) are derived from the analog electroencephalogram, but to determine the reproducibility of the pharmacodynamic relationship between blood concentrations of propofol and electroencephalographic amplitude and BIS during sequential propofol infusions. The propriety BIS algorithm was developed to show a unidirectional decrease of its value upon decreasing levels of consciousness. 2We did not observe burst suppression, spindles, spike activity, or electromyographic or other artifacts in the analog electroencephalogram during this episode in these two patients. Other derived parameters, like spectral edge 95% and median frequency, did not show an increase. Therefore, we could not explain the increase of the BIS value during the increasing concentration of propofol. More recent software versions of the BIS algorithm might not have shown such an increase.

Jäntti and Alahuhta also state that the physiology of the brain during rapidly increasing concentrations is different from that during steady state situations. This statement is concordant with our explanation for the poor prediction of electroencephalographic effect during the sequential infusions, that as a result of the complexity of the brain the electroencephalographic signal is not necessarily a simple function of the blood concentration, especially during changing blood concentrations.

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