Context:Objective assessment of sedation depth is a valuable target. Spectral entropy is an anesthetic depth monitor based on the analysis of the electroencephalogram signal.Aims:To evaluate the performance of spectral entropy as an objective measure of sedation state in midazolam-premedicated patients and to correlate it with a clinically assessed sedation score.Settings and Design:This prospective double-blind placebo-controlled study was performed in King Fahd Hospital of the university.Methods:Eighty adult ASA I–II patients were randomly assigned into 4 groups. Patients were premedicated using 0.02, 0.04, or 0.06 mg/kg midazolam or saline intramuscularly. The effect of these doses on the Observer's Assessment of Alertness and Sedation (OAA/S) scale, hemodynamic variables, response entropy (RE), and state entropy (SE), was evaluated at 10, 20, and 30 min after premedication.Statistical analysis:Spearman Rank-order correlation analysis to examine the relation between OAA/S and entropy. The ability of spectral entropy to predict the depth of sedation was evaluated using Smith prediction probability.Results:Midazolam doses ≥0.04 mg/kg produced significant decreases in RE, SE, and OAA/S scores. There was a strong correlation between midazolam dose and OAA/S scale, RE, and SE since Spearman Rank R values were 0.792, 0.822, and 0.745, respectively (P<0.001). In addition, RE and SE were strong predictors of OAA/S level during midazolam sedation with no significant difference in prediction between the 2 entropy components.Conclusions:Spectral entropy is a reliable measure for the sedative premedication. It may be used to objectively assess the adequacy of midazolam premedication and to determine the dose requirement.