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.

Abstract

BACKGROUND Anesthetic agents are well known for their effects on memory and pain, however, prior studies quantifying anesthetic-modulation of memory have not included experimental noxious stimulation. This study used functional magnetic resonance imaging (fMRI) to determine how low doses of propofol, dexmedetomidine, and fentanyl affect the brain systems for memory encoding and pain perception. METHODS This was a single-blind 1:1:1 randomized placebo-controlled crossover study of 92 healthy volunteers age 18-40. Effect-site concentrations were targeted for propofol (1.0 mcg/ml), dexmedetomidine (0.15 ng/ml), or fentanyl (0.9 ng/ml). Participants listened to a series of 80 words creating a mental picture. Thirty were accompanied by a 2 s painful shock. Blood oxygen-weighted images were obtained at 7 Tesla using a custom head coil. The primary outcome was next-day memory performance, measured by d´, a normalized measure of correct identifications versus false positives. Mixed models were fit to test outcome differences between drug groups. Only statistically significant (p < 0.05) changes are reported, after adjustment for multiple comparisons. RESULTS Recollection, reported as mean d´ (95% confidence interval), was 1.16 (0.97-1.34) under No Drug. This was reduced under propofol 0.51 (0.182-0.842), P=0.006, but not dexmedetomidine 1.04 (0.73-1.35), P=0.99, or fentanyl 0.98 (0.68-1.28), P=0.99. Propofol decreased memory-encoding activation of the hippocampus and amygdala. Propofol reduced pain-related activation in the insula, anterior cingulate, hippocampus, and amygdala. Dexmedetomidine showed decreased memory-related activation in the hippocampus, but did not change pain ratings nor show activation differences in pain-processing areas. Fentanyl showed decreased memory activation in the hippocampus and amygdala. During painful stimulation, fentanyl decreased activation in the primary somatosensory cortex, insula, and increased activation in the anterior cingulate, hippocampus, and amygdala. CONCLUSIONS These findings add important details to the complex framework of how these distinct anesthetics affect different aspects of cognition through diverse neuroanatomical targets in the brain.