The probabilities of LOC and no response to tetanic stimulus versus predicted effect-site propofol and remifentanil concentrations are shown in Figures 1 and 2, respectively. The effect-site propofol concentrations associated with 5% and 95% probability of LOC were 1.3 (1.2–1.4) and 3.2 (3.1–3.3) μg/mL, respectively (Table 4, Fig. 1). The effect-site remifentanil concentrations associated with 5%, 50%, and 95% probability of nonresponse to tetanic stimulus were 1.5 (1.4–1.6) and 5.1 (5.0–5.2) ng/mL, respectively (Table 5, Fig. 2). The probabilities of LOC and no response to the tetanic stimulus versus BIS are shown in Figure 3. Five percent and 95% of patients lost consciousness at BIS values of 77 (76–78) and 39 (39–40), respectively. BIS values associated with 5% and 95% probability of nonresponse to tetanus stimulus were 82 (81–83) and 49 (48–50), respectively. Interestingly, the BIS values associated with nonresponse to painful stimulus were higher than that at LOC (P < 0.05).
We investigated whether predicted blood and effect-site propofol and remifentanil concentrations and values of BIS, all based on Caucasian data, are useful for predicting whether a Chinese patient is unconscious and unresponsive to painful stimulus. We found that the effect-site concentrations of propofol and the BIS values at LOC were lower in Chinese than patients that reported in Caucasians.1
Ninety percent of patients will lose consciousness at predicted effect-site propofol concentrations between the C05 and the C95. For LOC, the range of effect-site concentrations to include 90% of patients was 1.3–3.2 μg/mL. A comparison of the results of our study performed on a Chinese population with the results of a study performed on Caucasian patients administered propofol in the same manner revealed differences in the predicted effect-site concentrations.1 The C50 for effect-site propofol concentration at LOC was 2.2 μg/mL in the Chinese population and 2.8 μg/mL in the Caucasian. The C95 was 3.2 μg/mL in the Chinese compared with 4.1 μg/mL in Caucasians. There was also a large difference in the predicted blood and effect-site concentrations, the concentration in the Chinese population was consistently lower. It is impossible to know if the differences observed were due to pharmacokinetic or pharmacodynamic factors because blood concentrations of the drugs were not measured in either study. Li et al.13 measured propofol blood levels in Chinese patients and compared them to those predicted by the Diprifusor TCI system. They found the relationship acceptable for clinical use. This suggests that a pharmacokinetic difference between Caucasians and Chinese may not explain our findings. Comparison of the results is further hampered by the fact that the studies were done at different times in different countries.
Several investigations have evaluated the use of TCI propofol for total IV anesthesia, and the pharmacodynamic interactions between propofol and different opioids14,15 However, little information is available on the effect-site concentration of remifentanil required to blunt body movement responses to skin incision. The lack of direct determination of remifentanil plasma concentrations is a shortcoming of our study. However, the pharmacokinetic model we used has been demonstrated as adequately accurate in predicting plasma and effect-site concentrations of remifentanil.7,8 Data from two published studies16,17 suggested, but did not clearly demonstrate, that the concentrations of remifentanil in the Chinese were lower than that in Caucasians. There is no direct evidence of this because of the differences in methods between the two previous studies and ours.
Tetanic stimulation of the ulnar nerve has the advantage of ease of performance, repeatability, reproducibility and is frequently used in lieu of skin incision.4,18–20 One study has shown no significant difference in somatic response between C50 tetanic stimulus and C50 skin incision, but there was a significant difference in hemodynamic response.21 Tetanic stimulus was therefore suitable for our study as we used patient movement, and not hemodynamics, in response to the stimulus as an outcome variable at different remifentanil concentrations.
Several investigators have studied the sensitivity of BIS as a measure of sedation22,23 and anesthesia24 in patients receiving propofol infusions. It has been shown to be a useful monitor of propofol sedation and anesthesia. Two previous studies1,9 have evaluated the BIS values at LOC when TCI propofol is used. The C50 and C95 of BIS were 71 and 53 respectively in Caucasians,1 whereas the values were 65 and 45, respectively, in Chinese,9 which is similar to our results. We noted that the C95 of BIS was 39 at LOC in our study, which is lower than the values appropriate for “surgical” anesthesia, 40–60, in Caucasians.25 Notably, the predicted blood and effect-site propofol concentrations in our Chinese population were lower than that in Caucasians at this point. Our results therefore suggest that the correlation between the predicted blood or effect-site propofol concentrations and BIS in Chinese patients differ from that in Caucasians23,26 and that the standard BIS values25 to predict the depth of hypnosis may not be suitable for Chinese patients. A different range of BIS values and propofol TCI concentrations should be used in clinical practice in Chinese patients.
In conclusion, the blood and effect-site concentrations of propofol and the BIS values at LOC in Chinese patients were lower than that in a previously published study of Caucasians.1 This may be due to pharmacodynamic differences between races and merits future study.
The authors thank Professor Adrian W. Gelb, Department of Anesthesia, University of California San Francisco, for help with the preparation of the manuscript.
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