| Abstract: |
Introduction: Anesthetic/sedative drugs can impair memory by a specific amnesic or a sedative effect. Dexmedetomidine (DEX) is a new sedative agent with a unique mechanism of effect and a different "quality" of sedation. (1) We used a continuous recognition word task (CRT) to assess the memory impairment of DEX in direct comparison with propofol (PRP) and thiopental (THP) to differentiate amnesic vs. sedative properties. Methods: After informed consent, 83 right-handed subjects (Ss), (32 F; median 30 yrs, 72 kg) were given PRP (n=30), THP (n=31), DEX (n=10) or placebo (n=12) at one of 3 sedative/sleep doses using Stanpump (S. Shafer; http://anesthesia.stanford.edu/pkpd). Only responsive subjects (n=54) are reported here. Ss performed a CRT 40 min before, and again during drug effect. The CRT consists of 220 words (ISI 3 sec) with a subset of words repeated once after a lag of 1 or 10 words. Reaction time (RT) was obtained when Ss pressed one of two buttons to indicate a new or old (repeated) word. Item recognition was measured approx 3-4 hours later by Ss making an old/new response upon hearing a list of previously presented words and distractors. All stimuli were presented aurally using foam earplugs, with all scores given here representing lag 10 words. Ss were classified as High or Low performers using a median split of correct old's during the drug CRT (median for PRP: 48%, THP: 42%, DEX: 45%). Data from n=9 Ss were discarded (Plac n=3, PRP n=4, THP n=2), because of poor performance in baseline (<50% correct), missing data at Recognition, interruptions in the infusion, or absence of detectable drug effect. Statistical analysis was by oneway ANOVA using SPSS v. 11.5 with a priori contrasts to the Placebo group. Results: The profile of DEX was almost identical to THP. There was no evidence of increased information loss over time, as with PRP: PRP-High (-41+-23%; n=7) vs. Placebo (-12+-8%, n=8, P=.002), THP High (-17+-19%, n=8, p<.02) and DEX-High (-23+- 8%, n=4, p<.10). Low performers (n=8 THP, n=9 PRP, n=4 DEX) had a significantly greater sedative effect by RT (increase of 97 msec or 6%, p<0.05). There were no differences between groups in the rate of guessing (false alarms) during the recognition test (18.5+-12.6 % overall). Conclusions: These preliminary findings indicate that Dexmedetomidine impairs memory similarly to thiopental, with a different profile from propofol. The amnesic effect of propofol is associated with loss of successfully acquired information over time during drug effect. Dexmedetomidine impairs initial acquisition of material, and the loss of this material over time is less than propofol, similar to thiopental. We postulate that the impairment of initial acquisition of material is related to sedation, while a specific amnesic effect is represented by loss of information over time. The optimal clinical use of dexmedetomidine may require a deep level of sedation, which its unique profile readily provides. |
