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A-1605
2004 |
| The Hypnotic Requirement for Propofol in Women with Red Hair. Preliminary Results |
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Anthony G. Doufas, M.D., Ph.D., Yunus M. Shah, M.D., Ryu Komatsu, M.D., Papiya Sengupta, M.D., Daniel I. Sessler, M.D. Outcomes Research Institute and Department of Anesthesiology, University of Louisville, Louisville, Kentucky. |
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Backgound: It has been recently shown that the red hair phenotype in women is associated with a 19% increase in anesthetic requirement for desflurane compared to women with dark hair.1 In addition, redheads have demonstrated a significant resistance to sedation and cognitive impairment produced by midazolam.2 The human red hair phenotype can be traced to distinct mutations in the melanocortin-1 receptor gene. Thus, the melanocortin system seems to be involved in the mechanism of different anesthesia components. We tested the hypothesis that women with red hair have increased hypnotic requirement for propofol compared to those with dark hair. Methods: With IRB approval and informed consent, we studied 40 healthy female volunteers; 20 with natural red and 20 with natural dark hair. An effect-site target controlled infusion system was used to administer propofol for sedation. The protocol consisted of sequential 15-minute concentration cycles. In order to blind the study, the initial target effect-site concentration was randomly chosen among three different values (0.75, 1.00 and 1.25 µg/ml) using randomization software. At the end of each concentration cycle, the volunteers were evaluated using the observer’s assessment alertness/sedation (OAA/S) score and the target concentration was increased by 0.25 µg/ml until loss of responsiveness to mild shaking (OAA/S ≤ 1). At that time an arterial blood sample was obtained for propofol determination. We considered the period from 10 to 15 elapsed minutes within each concentration cycle to represent a pseudo-steady state. Bispectral index of the EEG was used to confirm the pseudo-steady state assumption. Our preliminary analysis was based on predicted effect-site propofol concentrations. A non-parametric (Mann-Whitney U) test for independent samples was used to compare effect-site concentrations at OAA/S ≤ 1 in red and dark haired volunteers. Results: Our preliminary results, which are based on predicted effect-site propofol concentrations, showed that there was no difference in the propofol hypnotic requirement between women with red (2.19 ± 0.60 µg/ml) and dark (1.95 ± 0.43 µg/ml, P=0.194) hair. However, the power of our preliminary analysis to demonstrate a negative result was only 50% at an alpha level of 0.05. Conclusion: Preliminary analysis suggested that the red hair phenotype does not affect the hypnotic requirement for propofol in female volunteers. Further study is needed to establish this outcome. References 1. Liem EB, Lin C-M, Suleman M-I, Doufas AG, Gregg RG, Veauthier JM, Loyd G, Sessler DI: Anesthetic requirement is increased in redheads. Anesthesiology 2004; in press 2. Chua MV, Tsueda K, Doufas AG: Midazolam causes less sedation in volunteers with red hair. Can J Anaesth 2004; 51: 25-30 Anesthesiology 2004; 101: A1605 |
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