Comparison of the negative effect of remimazolam and propofol on cardiac contractility: Analysis of a randomised parallel-group trial and a preclinical ex vivo study

Abstract

Remimazolam is a newly developed ultra-short-acting benzodiazepine that exerts sedative effects. This study aimed to clarify the effects of remimazolam on cardiac contractility. In a randomised-parallel group trial, haemodynamic parameters were compared between propofol (n = 11) and remimazolam (n = 12) groups during the induction of general anaesthesia in patients undergoing non-cardiac surgery. In a preclinical study, the direct effects of remimazolam on cardiac contractility were also evaluated using isolated rat hearts. RNA sequence data obtained from rat and human hearts were analysed to assess the expression patterns of the cardiac γ-aminobutyric acid type A (GABA_A) receptor subunits. In a clinical study, the proportional change of the maximum rate of arterial pressure rise was milder during the study period in the remimazolam group (propofol: −52.6 [10.2] (mean [standard deviation])% vs. remimazolam: −39.7% [10.5%], p = 0.007). In a preclinical study, remimazolam did not exert a negative effect on left ventricle developed pressure, whereas propofol did exert a negative effect after bolus administration of a high dose (propofol: −26.9% [3.5%] vs. remimazolam: −1.1 [6.9%], p < 0.001). Analysis of the RNA sequence revealed a lack of γ subunits, which are part of the major benzodiazepine binding site of the GABA_A receptor, in rat and human hearts. These results indicate that remimazolam does not have a direct negative effect on cardiac contractility, which might contribute to its milder effect on cardiac contractility during the induction of general anaesthesia. The expression patterns of cardiac GABA_A receptor subunits might be associated with the unique pharmacokinetics of benzodiazepines in the heart.