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Safety and efficacy of remimazolam in induction and maintenance of general anesthesia in high-risk surgical patients (ASA Class III): results of a multicenter, randomized, double-blind, parallel-group comparative trial

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Remimazolam, an ultra-short-acting benzodiazepine sedative is equally effective as propofol in induction and maintenance of general anesthesia with improved hemodynamic stability in American Society of Anesthesiologists (ASA) Class I and II patients. This trial investigated remimazolam’s efficacy and safety in vulnerable patients (ASA Class III) undergoing elective general surgery.


A multicenter, randomized, double-blind, parallel-group trial in 67 adult surgical patients undergoing general anesthesia with two remimazolam induction doses (6 mg kg−1 h−1—group A and 12 mg kg−1 h−1—group B) has been conducted in 6 trials sites in Japan. Remimazolam was infused up to 2 mg kg−1 h−1 for maintenance of anesthesia in both groups.


The functional anesthetic capability of the investigated drug was 100% in both arms. The mean time to loss of consciousness (LoC) was significantly shorter in group B (81.7 s) compared to group A (97.2 s), p = 0.0139. The mean bispectral index (BIS) value during maintenance of anesthesia ranged from 46.0 to 68.0 and from 44.7 to 67.5 in group A and B, respectively. There was no statistically significant difference between the remimazolam arms concerning the incidence of blood pressure (BP) decrease (67.7% in group B vs. 54.8% in group A), recovery profile or the incidence or severity of adverse events (AEs) or adverse drug reactions (ADRs).


Both induction regimens (6 and 12 mg kg−1 h−1) were equally efficacious and safe in surgical patients ASA Class III. A significantly shorter time to LoC was observed with the higher remimazolam dosage.

Clinical trial registration

This trial is registered with the Japan Pharmaceutical Information Center—Clinical Trials Information (JapicCTI). JapicCTI number: 121977.

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Shigehito Sato, who served as the Lead Investigator of this clinical trial of remimazolam at the Hamamatsu University Hospital in Japan. Maki Kondo, who was responsible for planning of the trial and the preparation of the trial protocol and trial report at Ono Pharmaceutical Co., Ltd. Nagashige Omawari, who was responsible for collecting and evaluating safety information and for reporting to regulatory authorities at Ono Pharmaceutical Co., Ltd. Shuya Kiyama, Professor of Anesthesiology at the Jikei University Hospital in Tokyo, Japan, who served as the Medical Officer for this trial. Satoru Fukinbara, who served as Senior Director Data Science at Ono Pharmaceutical Co., Ltd and provided the statistical analysis plan as well as the statistical analyses. Olga Rassokhina, who provided medical writing support on behalf of CCR Creative Clinical Research GmbH, Berlin, Germany. This trial was conducted at 6 trial sites in Japan.


This trial was supported by Ono Pharmaceutical Co.

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Correspondence to Matsuyuki Doi.

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M. Doi is a consultant of PAION UK and Mundipharma. All other authors have no interests to declare.

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Doi, M., Hirata, N., Suzuki, T. et al. Safety and efficacy of remimazolam in induction and maintenance of general anesthesia in high-risk surgical patients (ASA Class III): results of a multicenter, randomized, double-blind, parallel-group comparative trial. J Anesth 34, 491–501 (2020).

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