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AMBULATORY ANESTHESIA

A Comparison of the Effects of Propofol and Midazolam on Memory During Two Levels of Sedation by Using Target-Controlled Infusion

Annemiek de Roode, MD, PhD^*, Joop M. A. van Gerven, MD, PhD, Rik C. Schoemaker, BSc, PhD, Frank H. M. Engbers, MD^*, Wim Olieman, BSc^*, J. Ria Kroon, BSc, Adam F. Cohen, MD, PhD, FFPM, and James G. Bovill, MD, PhD, FFARCSI^*

*Department of Anesthesiology and Centre for Human Drug Research, Leiden University Medical Centre, Leiden, The Netherlands

Address correspondence and reprint requests to Annemiek de Roode, MD, PhD, Department of Anesthesiology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands. Address e-mail to A.de_Roode{at}lumc.nl

We examined memory during sedation with target-controlled infusions of propofol and midazolam in a double-blinded five-way, cross-over study in 10 volunteers. Each active drug infusion was targeted to sedation level 1 (asleep) and level 4 (lethargic) as determined with the Observer Assessment of Alertness/Sedation scale. At the target level of sedation, drug concentration was clamped for 30 min, during which time neutral words were presented. After 2 h, explicit memory was assessed by recall, and implicit memory by using a wordstem completion test. Venous drug concentrations (mean ± SD) were 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 during 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 levels of sedation were accompanied by small differences in venous propofol or midazolam concentrations. This indicates steep concentration-effect relationships. Neutral information is still memorized during low-level sedation with both drugs. The memory effect of propofol and midazolam did not differ significantly.

Implications: Implicit memory can occur during different states of consciousness and might lead to psychological damage. In 10 volunteers, implicit memory was investigated during sedation with propofol and midazolam in a double-blinded, placebo-controlled study. To compare the effects of both drugs, they were titrated using a computer-controlled infusion system to produce similar high and low levels of sedation.

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