Skip to main content
Log in

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

  • Original Article
  • Published:
Journal of Anesthesia Aims and scope Submit manuscript

Abstract

Purpose

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.

Methods

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.

Results

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).

Conclusion

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Reves JG, Glass P, Lubarsky D, McEvoy M, Martinez-Ruiz R. Intravenous anesthetics. In: Miller RD, editor. Miller's anesthesia. 7th ed. San Francisco: Elsevier; 2010. p. 719–768.

    Chapter  Google Scholar 

  2. Shafer SL, Stanski DR. Intravenous anesthesia: techniques and new drugs; 1991. p. 7. https://triallib.net/doc/5828823/intravenous-anesthesia-1991. Accessed Sep 26, 2018.

  3. Jacobi J, Fraser GL, Coursin DB, Riker RR, Fontaine D, Wittbrodt ET, Chalfin DB, Masica MF, Bjerke HS, Coplin WM, Crippen DW, Fuchs BD, Kelleher RM, Marik PE, Nasraway SA Jr, Murray MJ, Peruzzi WT, Lumb PD, Task Force of the American College of Critical Care Medicine (ACCM) of the Society of Critical Care Medicine (SCCM), American Society of Health-System Pharmacists (ASHP), American College of Chest Physicians. Clinical practice guidelines for the use of sedatives and analgesics in the critically ill adult. Crit Care Med. 2002;30:119–41.

    Article  Google Scholar 

  4. Propofol side effects. https://www.drugs.com/sfx/propofol-side-effects.html. Accessed Sep 26, 2018.

  5. Valente JF, Anderson GL, Branson RD, Johnson DJ, Davis K Jr, Porembka DT. Disadvantages of prolonged propofol sedation in the critical care unit. Crit Care Med. 1994;22(4):710–2.

    Article  CAS  Google Scholar 

  6. Ma Y, Shen Y, Zhang L. Comparison of midazolam and propofol as conscious sedation in oocyte retrieval of IVE-ET. J Zhejiang Univ Med Sci. 2008;37:304–7.

    Google Scholar 

  7. Magarey JM. Propofol or midazolam—which is best for the sedation of adult ventilated patients in intensive care units? A systematic review. Aust Crit Care. 2001;14(4):147–54.

    Article  CAS  Google Scholar 

  8. Barr J, Zomorodi K, Bertaccini EJ, Shafer SL, Geller E. A double-blind, randomized comparison of IV lorazepam versus midazolam for sedation of ICU patients via a pharmacologic model. Anesthesiology. 2001;95:286–98.

    Article  CAS  Google Scholar 

  9. Kusachi S, Kashimura N, Konishi T, Shimizu J, Kusunoki M, Oka M, Wakatsuki T, Kobayashi J, Sawa Y, Imoto H, Motomura N, Makuuchi H, Tanemoto K, Sumiyama Y. Length of stay and cost for surgical site infection after abdominal and cardiac surgery in Japanese hospitals: multicenter surveillance. Surg Infect (Larchmt). 2012;13(4):257–65. https://doi.org/10.1089/sur.2011.007.

    Article  PubMed  Google Scholar 

  10. Rogers WK, McDowell TS. Remimazolam, a short-acting GABA(A) receptor agonist for intravenous sedation and/or anesthesia in day-case surgical and non-surgical procedures. IDrugs. 2010;13(12):929–37.

    CAS  PubMed  Google Scholar 

  11. Brice DD, Hetherington RR, Utting JE. A simple study of awareness and dreaming during anaesthesia. Br J Anaesth. 1970;42:535–42.

    Article  CAS  Google Scholar 

  12. Doi M. Remimazolam. J Jpn Soc Clin Anesth. 2014;34(7):860–6 (in Japanese, Abstract in English).

    Article  Google Scholar 

  13. Singh H. Bispectral index (BIS) monitoring during propofol-induced sedation and anaesthesia. Eur J Anaesthesiol. 1999;16(1):31–6.

    Article  CAS  Google Scholar 

  14. Kazama T, Ikeda K, Morita K, Sanjo Y. Awakening propofolconcentration with and without blood-effect site equilibration after short-term and long-term administration of propofol and fentanyl anesthesia. Anesthesiology. 1998;88(4):928–34.

    Article  CAS  Google Scholar 

  15. Tassoudis V, Vretzakis G, Petsiti A, Stamatiou G, Bouzia K, Melekos M, Tzovaras G. Impact of intraoperative hypotension on hospital stay in major abdominal surgery. J Anesth. 2011;25(4):492–9.

    Article  Google Scholar 

  16. Rüsch D, Arndt C, Eberhart L, Tappert S. Bispectral index to guide induction of anesthesia: a randomized controlled trial. BMC Anesthesiol. 2018;18:66.

    Article  Google Scholar 

Download references

Acknowledgements

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.

Funding

This trial was supported by Ono Pharmaceutical Co.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Matsuyuki Doi.

Ethics declarations

Conflict of interests

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

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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). https://doi.org/10.1007/s00540-020-02776-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00540-020-02776-w

Keywords

Navigation