All critically ill, mechanically ventilated patients in the Intensive Care Unit receive medications to relieve pain and anxiety. However, accumulation of these medications can be associated with serious complications, most notably longer time on the breathing machine and in the ICU. Two strategies have been shown to dramatically improve patient outcomes: nurse-directed protocols for giving sedation, and daily interruption of sedation. However, these strategies have not been widely adopted, because of physicians' concerns, and because it is unclear which strategy is better. Given that patient outcome is improved with either of these strategies, the fundamental question that arises is whether patients managed with a combination of two strategies which both reduce drug accumulation (protocolized sedation and daily interruption) have an even better outcome than patients managed with only one of them (protocolized sedation). We propose a multicenter study in which 700 critically ill, mechanically ventilated patients will have their sedation managed with protocolized sedation alone, or both strategies. Both groups of patients will have the following recorded: ICU and hospital lengths of stay, mortality, total sedative drug use, ICU human resources used, side effects and recall of their ICU stay. The results of this large multi-center trial will help to inform best practice with regard to sedation management of critically ill patients in Canada and elsewhere. In addition, reducing ICU stay could be economically attractive, as the cost of an ICU day in Canada is approximately $3000.

Inclusion Criteria:

1. age>18 years
2. Mechanically ventilated, with anticipated need for MV ≥ 48 hours
3. ICU team has decided to initiate continuous sedative/analgesic infusion(s)
4. informed consent.

Exclusion Criteria:

1. Admission after resuscitation from cardiac arrest
2. Traumatic brain injury
3. Currently receiving neuromuscular blocking agents
4. Allergy to any of the study medications
5. History of alcohol, sedative or analgesic abuse
6. History of psychiatric illness
7. Acute or chronic neurologic dysfunction
8. Administration of sedatives for >24 hr,
9. Lack of commitment to aggressive treatment
10. Current enrollment in a related trial
11. Previous enrollment in this trial.