• Different Mechanism of Action: Most general anesthetics (like propofol, sevoflurane, midazolam) primarily work by enhancing GABAergic activity, which typically leads to an increase in slow-wave EEG activity and a decrease in BIS values, reflecting a deeper hypnotic state. Ketamine, however, is an N-methyl-D-aspartate (NMDA) receptor antagonist. Its mechanism of action results in a different EEG pattern.
• Paradoxical Increase in BIS: Despite producing a "dissociative" or hypnotic state, ketamine can cause a rise in BIS values, or at least prevent them from decreasing as expected for a deeply sedated patient. This is because ketamine can lead to increased activity in certain higher-frequency bands (such as gamma activity) and a more uniform distribution of higher frequencies in the EEG, which the BIS algorithm may interpret as a lighter level of anaesthesia.
• Dose-Dependent Effects: The degree of BIS elevation can be dose-dependent. Higher bolus doses (e.g., 0.5 mg/kg) are more likely to cause a significant increase in BIS compared to lower doses (e.g., 0.2 mg/kg) or continuous infusions.
• Confounding Factor: This paradoxical effect means that BIS values may not accurately reflect the true depth of hypnosis or anesthetic state when ketamine is used, especially as a sole anesthetic or in higher doses. This can potentially mislead the anesthesiologist into administering more hypnotic agents than necessary.
• Adjunctive Use: Due to this unreliability, BIS cannot be used as the sole monitor of anaesthesia, particularly when ketamine is part of the anaesthetic regimen. It's an adjunct, and clinical assessment remains crucial.

In summary, when ketamine is administered, especially in boluses, BIS values may increase or stay higher than expected for the patient's actual level of sedation. This makes BIS monitoring less reliable for guiding hypnotic drug administration in these specific scenarios, and anesthesiologists need to be aware of this limitation.

reference

https://pubmed.ncbi.nlm.nih.gov/15591328/