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To determine whether benzodiazepine and propofol doses are increased at night and whether daytime and nighttime sedative doses are associated with delirium, coma, and delayed liberation from mechanical ventilation.Single-center, prospective cohort study nested within the Awakening and Breathing Controlled randomized trial.Saint Thomas Hospital in Nashville, TN, from 2004 to 2006.Adult patients receiving mechanical ventilation for >12 hrs with continuous recording of hourly sedation dosing.We measured hourly doses of benzodiazepine and propofol exposure during the daytime (7 AM to 11 PM) and nighttime (11 PM to 7 AM) for 5 days. We quantified nighttime dose increases by subtracting the average hourly daytime dose on the preceding day from subsequent average hourly nighttime dose. We used multivariable logistic regression to determine whether daytime and nighttime dose increases were independently associated with delirium, coma, and delayed liberation from mechanical ventilation.Among 140 patients, the median Acute Physiology and Chronic Health Evaluation II score was 27 (interquartile range 22–33). Among those receiving the sedatives, benzodiazepine and propofol doses were increased at night on 40% and 41% of patient-days, respectively. Of 485 patient-days, delirium was present on 160 (33%) and coma on 206 (42%). In adjusted models, greater daytime benzodiazepine dose was independently associated with failed spontaneous breathing trial and extubation, and subsequent delirium (p < .02 for all). Nighttime increase in benzodiazepine dose was associated with failed spontaneous breathing trial (p < .01) and delirium (p = .05). Daytime propofol dose was marginally associated with subsequent delirium (p = .06).Nearly half of mechanically ventilated intensive care unit patients received greater doses of sedation at night, a practice associated with failed spontaneous breathing trials, coma, and delirium. Over the first 5 days in our study, patients spent 75% of their time in coma or delirium, outcomes that may be reduced by efforts to decrease sedative exposure during both daytime and nighttime hours in the intensive care unit.