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Bispectral index (BIS) is a widely used quantitative parameter for evaluating anesthesia and sedation levels. Dexmedetomidine is a novel sedative, providing sedation while patients remain cooperative and can be easily aroused; as a consequence, BIS used with dexmedetomidine may poorly characterize sedation. Thus, we tested the hypothesis that BIS values are lower with dexmedetomidine than with propofol at comparable Observer’s Assessment of Alertness and Sedation (OAA/S) scores.This was a randomized, 2-day, crossover study. On the first study day, healthy volunteers were randomly allocated to either propofol or dexmedetomidine sedation. Drugs were administered using computer-controlled infusions targeting an effect-site concentration of 1, 2, and 4 μg/mL for propofol or a plasma concentration of 0.6, 1.2, and 2.4 ng/mL for dexmedetomidine. The relationship between BIS and OAA/S score was obtained 20 and 40 min after changing each drug concentration. BIS values at each OAA/S score were compared between drugs. The cutoff values of BIS for OAA/S score of ≤2 were obtained by analysis of receiver operating characteristic curves.Nine volunteers were included in our analysis. Heart rates decreased significantly with dexmedetomidine sedation. ETco2 was significantly increased with high doses of propofol but did not increase with high doses of dexmedetomidine. BIS values at OAA/S scores of 1, 2, 3, 4, and 5 during propofol sedation were 95.5 (90-97), 78 (71-84.5), 67 (64-70), 57 (51.5-60), and 34 (30-37), respectively. BIS values at OAA/S scores of 1, 2, 3, 4, and 5 during dexmedetomidine sedation were 95 (79-98), 62 (53.5-68.5), 45.5 (45.3-52), 39.5 (34.3-41.8), and 24.5 (22.5-30.5), respectively. BIS values were significantly less with dexmedetomidine than propofol at OAA/S responsiveness scores of 2, 3, and 4. The calculated cutoff BIS values for OAA/S scores of ≤2 were 67 (sensitivity of 86%, specificity of 97%, and area under the curve of 0.98) for propofol and 46 (sensitivity of 84%, specificity of 91%, and area under the curve of 0.96) for dexmedetomidine.The combination of both BIS and sedative scales could provide different and complementary data to the clinician evaluating the patient’s response to sedation than would either tool alone, especially when dexmedetomidine is used.