R Alagesan

Propofol versus midazolam for monitored sedation: a comparison of intraoperative and recovery parameters

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.

THE EEG AS A MONITOR OF MIDAZOLAM AMNESIA : CHANGES IN POWER AND TOPOGRAPHY AS A FUNCTION OF AMNESIC STATE

In order to identify EEG parameters that might be specific for identifying amnesia during midazolam infusion, we examined changes in the EEG power spectrum associated with a period of amnesia, determined by inability to recall a sequence of numbers and objects presented verbally, after intravenous midazolam 0.07 mg/kg in ten normal volunteers. Measurements were taken at baseline, during infusion immediately before and after the onset of amnesia, immediately at end of infusion, and 0.5 and 1.5 h after infusion. All subjects had onset of amnesia during infusion, were completely amnesic by the end of infusion, partially amnesic 0.5 h after infusion, and had complete recall by 1.5 h after infusion. The EEG beta power increased and alpha power decreased during amnesic periods. The beta 1/alpha power ratio was the parameter most specific for amnesia. From a baseline value of 0.20 +/- 0.05 (standard error of the mean [SEM]), it increased to 0.96 +/- 0.26 at the end of infusion and decreased to 0.61 +/- 0.15 0.5 h after infusion. By 1.5 h after infusion, all EEG parameters had returned to baseline values. Beta power changes associated with midazolam amnesia were most pronounced in the Fz and Cz lead positions, and alpha power changes were most pronounced in the Oz position. We conclude that 1) EEG power values, particularly the beta 1/alpha ratio, can identify periods of amnesia after midazolam infusion; 2) specific EEG changes and the presence of amnesia vary with the probable serum concentration of midazolam; and 3) the characteristic EEG pattern during partial or complete amnesia varies as one moves across the cerebral cortex.

Effect of midazolam on the auditory event-related potential : measures of selective attention

To elucidate the delayed effects of midazolam, we assessed electrophysiologic and motor responses by measuring auditory event-related potentials and a button-press reaction time response in 10 normal volunteers (aged 25–36 yr). Fifty minutes after intravenous infusion of 0.07 mg/kg of midazolam, subjects were mildly sedated, oriented, and readily responsive to verbal commands. To obtain ERPs, frequent tones (85%: 1000 Hz) and rare tones (15%: 2500 Hz) were presented at intervals of 1.5 s. Electroencephalographic signals were collected from FZ, CZ, and Pz, for 1000 ms after stimulus presentation until 40 artifact-free rare-tone responses were obtained (average time, 6 min). Peak-to-peak amplitudes and latencies for N2, P3, and the subsequent negative slow wave (N3) were averaged within condition and were analyzed by repeated measures analysis of variance. After midazolam infusion, there was a 50% decrease in amplitude of P3 in response to target tones (P < 0.006), whereas N3 latency increased by 40 ms (P < 0.05). Event-related potential amplitudes were still significantly larger to rare (target) stimuli (P < 0.003) after midazolam infusion. Although reaction time increased by 70 ms (P = 0.031), performance accuracy remained unchanged. Self-ratings of sleepiness and concentration show that a significant sedation effect was still present 50 min after infusion. Although routine clinical examination may be normal, full recovery from the effects of a typical intravenous dose of midazolam requires more than 50 min. The potential for adverse drug interaction, particularly with narcotics, is still present at this time.