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STUDY OBJECTIVE: To compare intraoperative and recovery parameters in patients who received either propofol infusion (PI), propofol bolus (PB), or midazolam bolus (MZ) for sedation. DESIGN: Randomized clinical study. SETTING: Medical/surgical patients in a specialized hospital. PATIENTS: Ninety patients, aged 18 to 85 years, scheduled for central venous access for chemotherapy and/or total parenteral nutrition. INTERVENTIONS: In 30 patients, sedation was induced with MZ 0.02 mg/kg intravenously (i.v.), repeated every 2 to 3 minutes to achieve a sedation level of 3 (eyes closed, responds to verbal stimulus) (SL3). Maintenance was with MZ 0.005 mg/kg i.v. repeated as necessary to maintain SL3. In both propofol groups (30 patients each), induction of sedation was with a bolus of propofol 0.75 to 1.0 mg/kg i.v. Maintenance in the PB group was with propofol 0.25 mg/kg IV, repeated as necessary to maintain SL3. Maintenance in the PI group was with propofol 2 to 4 mg/kg/hr or 33 to 66 micrograms/kg/min to maintain SL3. MEASUREMENTS AND MAIN RESULTS: Blood pressure, heart rate, respiratory rate, oxygen saturation, and sedation level were monitored each minute for 5 minutes and then at 5-minute intervals during the procedure. A right atrial blood sample was taken for pH and partial pressure of carbon dioxide at maximum sedation. Adequate sedation was achieved in all three groups. The time to reach SL3 was significantly shorter in the PB group than in the PI and MZ groups (p < 0.05 and p < 0.01, respectively). Cardiovascular and respiratory parameters were remarkably stable. Immediate recovery, as judged by spontaneous eye opening, response to commands, and ability to state date of birth, was significantly shorter in both the PB and PI groups than in the MZ group (p < 0.0001). Intermediate recovery, as measured by sedation score at recovery entry, Aldrete score, and time to standing, was slower in the MZ group (p < 0.05 for the MZ group vs. the PB and PI groups for sedation score and Aldrete score; p < 0.05 for the MZ group vs. the PI group in time to standing). Psychomotor recovery, judged by digit symbol substitution tests, was significantly faster in the PB and PI groups (p < 0.05 vs. the MZ group). Amnesia, measured by picture recall, was significantly greater in the MZ group than in the PI and PB groups (p < 0.05). Mood changes were measured on a visual analog scale. All groups showed improvement. Nausea, headache, dizziness, blurred vision, appetite, tension, pain, depression, drowsiness, and ability to concentrate were evaluated in the preoperative and postoperative periods. The frequency did not differ significantly between groups due to confounding factors such as postoperative chemotherapy and premedicant drugs. CONCLUSION: The PI, PB, and MZ groups all gave excellent sedation for patients undergoing surgical procedures with local anesthesia. Amnesia was greatest with midazolam, and recovery was more rapid with propofol.