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Excessively deep sedation is prevalent in mechanically ventilated patients and often considered suboptimal. We hypothesized that the bispectral index (BIS), a quantified electroencephalogram instrument, would accurately detect deep levels of sedation.We prospectively enrolled 90 critically ill mechanically ventilated patients who were receiving sedation. The BIS was monitored for 24 hours and compared with the Richmond Agitation Sedation Scale (RASS) evaluated every 4 hours. Deep sedation was defined as a RASS of −3 to −5. Threshold values of baseline BIS (the lowest value before RASS assessment) and stimulated BIS (the highest value after standardized assessment) for detecting deep sedation were determined in a training set (45 patients, 262 RASS assessments). Diagnostic accuracy was then analyzed in a validation set (45 patients, 264 RASS assessments).Deep sedation was only prescribed in 6 (6.7%) patients, but 76 patients (84.4%) had at least 1 episode of deep sedation. Thresholds for detecting deep sedation of 50 for baseline and 80 for stimulated BIS were identified, with respective areas under the receiver-operating characteristic curve of 0.771 (95% confidence interval, 0.714–0.828) and 0.805 (0.752–0.857). The sensitivity and specificity of baseline BIS were 94.0% and 66.5% and of stimulated BIS were 91.0% and 66.5%. When baseline and stimulated BIS were combined, the sensitivity, specificity, and clinical utility index were 85.0% (76.1%–91.1%), 85.9% (79.5%–90.7%), and 66.9% (57.8%–76.0%), respectively.Combining baseline and stimulated BIS may help detect deep sedation in mechanically ventilated patients.