Patient will be selected from the ICU, based on the defined inclusion and exclusion criteria. Potential study subjects will be screened by the research fellow or the on-site study co-investigator. Eligible patients will be allocated to receive propofol sedation titrated to 3 different BIS levels in a random order. BIS XP monitors (Aspect Medical Systems, Norwood, MA, USA) will be used which are relatively resistant to EMG artifact; a BIS sensor will be position on forehead of the patient after the skin is degreased and gently abraded. Esophageal pressure monitoring will be performed by a catheter inserted from the nose to the esophagus and left there trough the study period.
If patients are on sedation they will be placed on propofol sedation for a washout period. Each patient will receive propofol sedation by continuous infusion titrated to a different levels of BIS in a randomized fashion according to a computer-generated random-number sequence;
1. BIS levels of 70, will be targeted (Anxiolysis/high-frequency EEG activity, beta-augmentation);
2. BIS levels of 50 will be targeted, (Low frequency EEG activity, theta-delta activity);
3. BIS levels of 35 will be targeted (low frequency EEG activity). A propofol infusion will be titrated by the investigators to the designated BIS target according to randomization. Clinical personnel will not be blinded to the study, and if patient has clinically significant change in hemodynamic parameters study will be interrupted. Each BIS target level will be kept as constant as possible for at least one hour; thereafter, lower esophageal pressures will be recorded for 15 minutes using high resolution esophageal manometry. Studies will be done in supine position \[Most ICU patients are now kept head-up.\], and the manometric assembly will be positioned to record from the hypopharynx to the stomach with 4-6 of the sensors positioned in the stomach.
All patients will otherwise receive routine ICU care and medications without interruption of standard clinical care.
