Bispectral index during remimazolam versus propofol sedation at matched depths: a randomized, double-blind crossover trial in healthy volunteers

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Abstract

BACKGROUND: The bispectral index (BIS) was derived primarily from propofol data, and whether its thresholds apply to remimazolam is uncertain. We compared BIS between the two agents at matched sedation depths and examined early cognitive recovery. METHODS: In this prospective, randomized, double-blind, two-period crossover trial, 16 healthy volunteers (American Society of Anesthesiologists physical status I) received remimazolam and propofol in random order, ≥ 7 days apart. Each agent was titrated to moderate (Modified Observer's Assessment of Alertness/Sedation [MOAA/S] 3) and deep (MOAA/S 1) sedation. The confirmatory outcome was mean BIS at deep sedation. All other outcomes were exploratory: BIS at moderate sedation and at loss of the eyelash reflex, emergence time, and cognitive recovery at 30 and 120 min. RESULTS: At deep sedation, mean BIS was higher with remimazolam (57.6 ± 7.5) than with propofol (46.5 ± 7.9; adjusted difference 11.1 units; 95% CI, 7.3 to 14.8; p < 0.001). In exploratory analyses, BIS was also higher at moderate sedation and at loss of the eyelash reflex (both p < 0.001), and emergence time did not differ (p = 0.606). At 30 min, processing speedand  executive function recovered faster after remimazolam (p = 0.012 and p < 0.001), whereas verbal memory did not differ between agents. All domains converged by 120 min. Adverse events were uncommon, and the trial was not powered to compare them. CONCLUSION: At clinically matched sedation depths, remimazolam produced higher BIS values than propofol. Spectral data were not recorded, so the basis of this offset is undetermined, and the cognitive findings were exploratory. Whether this offset warrants agent-specific reference values requires validation in clinical populations.

Abstract as published, via PubMed.