To the Editor:—

In their recent article, Kuizenga et al.  1studied pharmacodynamics of propofol using a processed electroencephalogram. In the results, they state, “… we observed an unexplained increase in the BIS value during increasing blood concentrations.” The question remains: unexplained by whom?

The Bispectral Index (BIS) is good in assessing depth of hypnosis. It is, however, unrealistic to expect BIS to yield a meaningful value when the electroencephalogram is pathologic or changes rapidly. It suffers also from the “inverse problem” of all single electroencephalogram descriptors: a certain BIS value may be produced by many different electroencephalogram samples with different patterns of different physiologic meaning. Samples with propofol could, for instance, have spindles or short suppressions, 2or epileptic activity with sevoflurane mask induction, 3,4and yield the same BIS values as electroencephalogram samples without these patterns. All of these are readily seen and counted visually but not with analyses like BIS or aperiodic analysis. Epileptiform patterns in sevoflurane anesthesia, for instance, result in unpredictable BIS values (V. Jäntti, Tampere, 2001, unpublished observation).

In this kind of study, both electroencephalogram patterns and artifacts should first be analyzed by an experienced electroencephalogram reader. Then, methods which can track fast changes like filter banks, including wavelets, should be applied, and only after that should aperiodic analysis and BIS be used. Only after that we could call fluctuation of the BIS value “unexplained.”

Apart from signal analysis, the physiology of brain is also different during rapidly increasing concentrations of anesthetic than during steady state: consider, again, the epileptogenic effect of sevoflurane during rapid mask induction. 3,4 

In summary, in this kind of study, careful inspection and analysis of electroencephalographic patterns from raw and filtered time domain electroencephalogram might explain the “unexplained.” What did the raw electroencephalogram look like during those intervals of “unexplained” increase?

Kuizenga K, Proost JH, Wierda JM, Kalkman CJ: Predictability of processed electroencephalography effects on the basis of pharmacokinetic-pharmacodynamic modeling during repeated propofol infusions in patients with extradural analgesia. A nesthesiology 2001; 95: 607–15
Jäntti V, Yli-Hankala A: Neurophysiology of anaesthesia, Clinical Neurophysiology at the Beginning of 21st Century. Edited by Ambler Z, Nevsímalová S, Kadanka Z, Rossini PM. Supplements to Clinical Neurophysiology, vol 53, Elsevier, 2000, pp 84–88
Yli-Hankala A, Vakkuri A, Särkelä M, Lindgren L, Korttila K, Jäntti V: Epileptiform electroencephalogram during mask induction of anesthesia with sevoflurane. A nesthesiology 1999; 91: 1596–603
Vakkuri A, Yli-Hankala A, Särkelä M, Lindgren L, Mennander S, Korttila K, Saarnivaara L, Jäntti V: Sevoflurane mask induction of anaesthesia is associated with epileptiform EEG in children. Acta Anaesthesiol Scand 2001; 45: 805–11