Bispectral EEG Index Monitoring of High-Dose Nitrous Oxide: DISCUSSION

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2 Dec 2009

Bispectral EEG Index Monitoring of High-Dose Nitrous Oxide


This study confirms the sensitivity of BIS monitoring for sevoflurane at the highest concentration studied, 0.8% inspired sevoflurane with average BIS depression from the 90s into the 80s. Overall, BIS functioned without any noticeable problems in a dental setting without a procedure being performed. At light levels of sedation, EMG activity, including eye motion, did not interfere with BIS readings.

The results of this study confirmed the findings of Rampil et al and Barr et al demonstrating no correlation between N20 dose and BIS. Study results also extended the near linear sevoflurane/BIS dose-response curve reported by Katoh et al downward to include a lower dose threshold of 0.8% inspired sevoflurane.
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Previous investigators have attempted to use EMG data as a measure of sedation levels with variable results. Ironically, the BIS monitor measures frontotemporal EMG so that it can be filtered out as potential interference during EEG preprocessing, the first of 3 major steps of BIS analysis. EMG values are, however, factored back into the BIS algorithm at higher BIS ranges to account for expected facial muscle activity in relatively awake patients. The results of this study included reductions in EMG readings only at the highest dose (0.7% ET) of sevoflurane. Movement artifact and procedural interferences might further limit EMG monitoring of dental patients on whom a procedure is performed. The use of relatively low dosages of sevoflurane (0.2-0.8%) in ASA 1 subjects for short times (1 hour or less) in this study did not result in hypotension, nausea, and/or respiratory depression as has been previously reported with higher concentrations.

Amnesia results showing 10-20% lower memory scores in male versus female subjects are also consistent with numerous behavioral science studies, where males typically exhibit less detail memory in a wide variety of situations. A group of control subjects who did not participate in this study were also tested for memory with the same pictures, sounds, and overall protocols later used in this study. Their scores demonstrated a strong positive correlation to study controls, including higher memory scores for female subjects.
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The paradoxic minor BIS depression observed by Rampil et al during what should have been N20 recovery (100% 02) periods was occasionally seen in this study but did not approach statistical significance. Although the unusually sensitive subject (114) was not available for a follow-up verification session due to his graduation, he later had his third molars removed by a faculty oral surgeon and experienced an exaggerated response to and a prolonged recovery from intravenous general anesthesia. His response to low-dose sevcompared with control (P < .01) oflurane was also somewhat exaggerated, but overall impairment as indicated by OAA/S readings and clinical observation was less than with N20.

The highest dose of N20 used in this study was selected because most dental sedation machines are flow-safe limited to 70% N20 and because it was hoped that BIS might be affected by a concentration greater than 50%. The 0.8% maximum inspired dose of sevoflurane was selected because it was expected to result in an ET concentration of approximately 0.7%, which is close to the MAC-awake (0.65%) of sevoflurane. Most subjects (70%) did tolerate an inhaled concentration of 70% N20 for a full 15-minute period, but this corresponded to registered ET N20 concentrations greater than 50% in only 27% (6/22). The highest ET N20 concentration attained by any subject was 58%. Although no participants received emergency 100% 02 for oversedation, 30% (6/22) had maximal N20 inspired dosage reduced because they became uncomfortable and/or exhibited signs of overdosage. Four of these subjects reached 60% N20 and 2 stopped at 50%. All subjects tolerated the maximal inspired dose of 0.8% sevoflurane, with almost all reaching an ET maximum of 0.7%. These results seem to be consistent with the MAC values of N20 (105%) and sevoflurane (1.7-2%), current pharmacokinetic models and data, and the inherent inefficiency of nasal hoods. A relatively larger maximum two-thirds MAC 70% N20 dose was used compared with the maximum one-third MAC 0.8% sevoflurane dose, but there was a larger discrepancy between high-dose inspired and ET N20 concentrations compared with maximal-dose sevoflurane inspired and ET values. Sevoflurane mirrored anticipated end tidal pharmacokinetics more closely than nitrous oxide and oxygen. One previous uncontrolled study by Haraguchi et al compared equi-MAC doses of N20 and sevoflurane up to a maximum of 30% N20 = 0.5% sevoflurane given to healthy volunteers via a full facemask. Even though Haraguchi’s subjects showed a marked preference for sevoflurane, all but 1 found both gases acceptable.
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The results of this study support that a desired acceptable level of sedation, relaxation, and partial amnesia can be produced with inspired concentrations of either 40-70% N20 or 0.6-0.8% sevoflurane. It would appear that BIS is of little value in assessing sedative level of low-dose sevoflurane but may be of benefit in evaluating deeper levels of conscious sedation with high subgeneral anesthetic doses of sevoflurane. BIS correlated well with changes in OAA/S and the occurrence of partial anterograde amnesia at end tidal concentrations of 0.4-0.7% sevoflurane. BIS did not correlate with changes in N20 sedation levels except in 1 unusually susceptible subject, who became unresponsive and presumably deeply sedated. OAA/S is a more sensitive measure of the level of sedation for all concentrations of N20 up to 70% and sevoflurane end tidal concentrations below 0.7%.

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