A comparison of the effects of propofol and midazolam on memory during twolevels of sedation by using target-controlled infusion

We examined memory during sedation with target-controlled infusions of prop ofol and midazolam in a double-blinded five-way, cross-over study in 10 vol unteers. Each active drug infusion was targeted to sedation level 1 (asleep ) and level 4 (lethargic) as determined with the Observer Assessment of Ale rtness/ Sedation scale. At the target level of sedation, drug concentration was clamped for 30 min, during which time neutral words were presented. Af ter 2 h, explicit memory was assessed by recall, and implicit memory by usi ng a wordstem completion test. Venous drug concentrations (mean +/- SD) wer e 1350 ng/mL (+/-332 ng/ mL) for propofol and 208 ng/mL (+/-112 ng/mL) for midazolam during Observer Assessment of Alertness/ Sedation scale level 4; and 1620 ng/mL (+/-357 ng/mL) and 249 ng/mL (+/-82 ng/mL) respectively duri ng level 1. The wordstem completion test frequencies at low level sedation were significantly higher than spontaneous frequencies (8.7% + 2.4%; P < 0. 05 in all cases), and lower than during placebo (33.6% + 23%) (P < 0.05 in all cases, except P = 0.076 for propofol at level 4). Clinically distinct l evels of sedation were accompanied by small differences in venous propofol or midazolam concentrations. This indicates steep concentration-effect rela tionships. Neutral information is still memorized during low-lever sedation with both drugs. The memory effect of propofol and midazolam did not diffe r significantly.