We appreciate the comments of Drs. Litvan and Paniagua regarding our article 1and accompanying editorial. 2We realize that it is impossible to validate whatever monitor of “anesthetic depth” is used within one study due to the complexity of the phenomenon itself. The hypothesis of our study was based on the concept of anesthetic depth as described by Dr. Glass in a recent editorial in this Journal. 3He concluded that what is called “general anesthesia” is a process requiring a state of unconsciousness of the brain (produced primarily by the volatile anesthetic or propofol). If only unconsciousness is achieved, a noxious stimulus needs to be inhibited from reaching higher centers (called an arousal reaction). This is achieved by the action of the opiate at opiate receptors within the spinal cord (or, local anesthetics on peripheral nerves, or volatile anesthetics on the spinal cord when administered at concentrations equal to the minimum alveolar concentration (MAC). Previously, I. Kissin 4already stated that the diversity of pharmacological actions that in combination provide anesthesia make it almost impossible to determine the potency of different actions with one measurement. It has not been our intention to investigate the complete “spectrum of anesthetic depth.” Therefore, we only have concluded in our article that both BIS®, AAI and propofol effect-site concentration were accurate indicators for the level of sedation and loss of consciousness (LOC) but poor indicators for predicting response to noxious stimulus. As propofol was given without opiates, a poststimulus arousal reaction was detected at these hypnotic levels too low to block these reactions. Both BIS® and AAI were able to detect these arousal reactions as plotted in figure 9 of our article.
We disagree with Drs. Litvan and Paniagua when they state that the measures of anesthetic depth could have been influenced by the assessments of the OAA/S scale (Observer's Assessment of Alertness/Sedation) and might explain the overlapping values seen in figure 3 of our study. As described in our methodology and validated by others before, 5all “electronic” measures were and have to be recorded before the assessment of the clinical scores and could not cause bias in the data. Of course, these clinical assessments were responsible for the poststimulus arousal phenomenon.
Regarding the so-called “overlapping values,” Drs Litvan and Paniagua might have been misled by the authors of the editorial. 2Based on figures 3A and B of our original article, 1the editorial focuses on an overlap between OAA/S level 3 and 0. Although present, this doesn't explain an overlap between consciousness and unconsciousness, because level 0 of the OAA/S scale measures “no reaction to a trapezius squeeze,” being a painful stimulus. We are aware of the potential limits of the OAA/S scale. Below level 2, this scale is only based on reaction to painful stimulus. To avoid bias in our methodology, we have defined LOC as the transition between OAA/S levels 3 and 2. It might have been more correct that the authors of the editorial would have compared OAA/S levels 3 and 2 where nearly no overlap is seen. One has also to realize that the box and whisker plots are not showing Gaussian distributions (!). Because of the asymmetry in the data, some overlap in the figures doesn't have to result in an equal amount of overlap in the population. In their editorial, the authors conclude, “many patients with BIS scores between 50 and 60 must have been responsive to voice command or to minimal prodding or shaking.” They have not followed our interpretation of LOC because “minimal prodding or shaking” is defined as OAA/S level 2 (being “nonresponsive” or “unconscious”). They also have not interpreted figure 7 of our article, otherwise they should have observed that only two patients had a conscious level at BIS® levels lower than 60 (also observable in table 5). One lost consciousness at a BIS® level of 55 and the last one at 53. As also seen in figure 7, the overlap in values originates more in the unconscious than in the conscious data. This means that these monitors of anesthetic depth lose power in the indication of a too excessive level of hypnosis, making the complete reasoning of this editorial questionable.