Effects of Sedative Doses of Propofol, Dexmedetomidine, and Fentanyl on Memory and Pain in Healthy Young Adults: A Randomized, Controlled, Single-blind Crossover Study Using Functional Magnetic Resonance Imaging at 7 Tesla.

Summary

In a 92-participant single-blind randomized crossover study with 7T fMRI and concurrent painful stimulation, propofol significantly impaired next-day recollection (reduced d') and decreased hippocampus/amygdala activation for memory encoding while attenuating pain-related activation in insula and anterior cingulate. Dexmedetomidine preserved recollection and pain ratings, with limited hippocampal effects. Fentanyl altered memory and pain network activity in a distinct pattern.

Key Findings

• Propofol reduced next-day recollection (d') versus no drug; dexmedetomidine and fentanyl did not show significant d' reductions.
• Propofol decreased memory-encoding activation in hippocampus and amygdala and reduced pain-related activation in insula and anterior cingulate.
• Fentanyl decreased primary somatosensory and insular activation during painful stimuli but increased anterior cingulate, hippocampus, and amygdala activation; dexmedetomidine had limited effects on pain processing.

Clinical Implications

When amnesia is desired, propofol’s stronger impairment of recollection and limbic memory encoding may be advantageous, but its broader impact on pain networks should be considered. Dexmedetomidine may preserve memory while providing sedation, and fentanyl modulates pain networks differently; these distinctions can guide balanced sedation-analgesia strategies.

Limitations

• Healthy young volunteers limit generalizability to surgical patients and elderly populations
• Single-blind design and surrogate outcomes (memory tests, fMRI signals) rather than clinical endpoints

Future Directions

Extend to surgical populations across age groups, integrate EEG and clinical outcomes (awareness, delirium, pain), and test dose-response relationships to refine sedative-analgesic combinations.