January 2023

[A Schutter]

This month's journal club article comes to you from Samantha Simmons. She chose an article titled:  Remimazolam: the pharmacological characteristics and clinical applications in anesthesiology.

Here is the link to the article

Questions for discussion:

Have you had the opportunity to work with remimazolam in this institution or others?

Discuss the pharmacokinetics of remimazolam and the patient population in which it would be most beneficial? And In which type of cases would remimazolam be most useful?

[janeporter]

Hi Sam! I enjoyed reading this article. I went to the MANA conference last year and was able to learn about Remimazolam, briefly.

I have not had the opportunity to work with remimazolam yet. Do we know if this will be added to our formulary in the future?\

The pharmacokinetic profile of remimazolam are different from traditional benzodiazepines. It is shown that remimazolam has a high clearance, small steady-state volume of distribution, a short elimination half-life, a short context-sensitive half-life, and it follows first and linear pharmacokinetics. It is rapidly metabolized by tissue esterase into inactive carboxy acid metabolites (CNS 7054). Even when administered as an infusion, remimazolam provides stable metabolism. Also, flumazenil is effective as a reversal agent.

Remimazolam would seem to be beneficial in procedures that require a fast onset of sedation and fast recovery with minimal residual effects. Patients receiving a colonoscopy may benefit from the use of remimazolam.

[Anne McNulty CRNA]

(1) I have not had the opportunity to use this drug. It will be at least a decade before JHU allows the use of this new drug. (2) This is a new ultra short acting benzo. Remimazolam has an ester linkage that permits rapid hydrolysis to inactive metabolites by non-specific tissue esterase . Remimazolam has rapid onset, predictable duration of action and rapid elimination. There is no injection pain and less cardio -respiratory depression. It has high protein binding. It is not eliminated well in patients with renal and hepatic failure. The article states that this drug has a higher safety profile than propofol. It is reversible with flumazenil. It could be used in endoscopy procedures, sedation in critically ill ICu patients, Tiva adjunct in GA and other procedural tiva procedures. Propofol offers better PONV protection than remimazolam, It will be interesting to see how this plays out in the future.

[Amy Swank CRNA]

1. I have not seen remimazolam in use in the clinical setting. I see that one of the lead authors of research article is "L. Antonik" is this our Dr. Antonik, by chance?
2. Remimazolam would be a terrific option for procedures like endoscopies and colonoscopies, being careful with patients with renal or liver disease due to its clearance. Also, the fact that it has a reversal agent of flumazenil and cardiac stability makes it appealing as an option.

[aileenm4]

I have not had the opportunity to use Remimazolam
The quick on/off titration, reversible with flumazanil if needed, mostly organ independant metabolism makes it attrative for broncoscopy, colonoscopy or endoscopy, maybe TEE or cardioversion as well.

[kels]

I have not had the opportunity to work with remimazolam. Remimazoam is a ultra-short-acting benzodiazepine. Due to the rapid onset and elimination it seems like a good medication to use in locations such as endo and out pt where cases are not long in duration

-esterase linkage in remimazolam permits rapid hydrolysis to inactivate metabolites by non-specific tissue esterase resulting in rapid onset and offset of sedation leading to predictable duration
of action
-reversal agent : flumazenil
-relatively high clearance
-small steady-state volume of distribution
-short context-sensitive half-life
- minimal tissue accumulation
- low cardiorespiratory depression