In October 2020 the FDA approved remimazolam (Byfavo, Acacia Pharmaceuticals) for the induction and maintenance of procedural sedation in adults undergoing procedures lasting 30 minutes or less. Although it has not been approved for children (and it won’t be for years), once it is marketed for adults, there is no legal reason why we cannot use it in children. It will take time, cautious optimism, and adherence to safety principles as its use bleeds out to different pediatric populations. (For those who haven’t figured it out yet, the prefix “remi”, as is also used in remifentanil, stands for rapid esterase metabolism.) Of course, the true test of its worth will come from user experience and published postmarketing trials, nearly all of which will not be sponsor-initiated.
Sneyd and Rigby-Jones have provided us a very nice summary of its pharmacology and clinical use. They use the phrase ‘Soft pharmacology’ to refer to the “precise control of drug effect by titration of boluses and infusion rate with rapid recovery when administration ceases.” The authors make the following key points about the use of remimazolam:
· It is hydrolyzed into an inactive metabolite by carboxylesterase-1, mainly located in the liver;
· It has a quicker onset and offset of hypnotic effect than midazolam;
· Preliminary reports of clinical use from Japan and South Korea suggest remimazolam may be used as the hypnotic opponent of a total intravenous anesthesia (TIVA) technique;
· It has similar cardiorespiratory stability as midazolam, but these can be overridden by concomitant use of opioids;
· It can be fully reversed by flumazenil;
· Its pharmacokinetics and pharmacodynamics can be described using standard 3-compartment effect site models and therefore, the drug may be suitable for target-controlled infusion (TCI).
More important is what the article doesn’t say, mainly because there is a dearth of clinical studies published to date. We don’t yet know how to use it effectively because we don’t yet know its onset and offset in a variety of different conditions. For example, what doses do we use? Over what time period? With what combination of other drugs, such as propofol, dexmedetomidine, or opioids? To me, this is exciting because it’s the newest, greatest addition to the anesthesia provider’s arsenal and, on the surface, it seems to be safe. Imagine a TIVA technique where we start the remimazolam along with remifentanil, and maybe low-dose propofol, and then at the end of the case, even if it lasts more than 30 minutes, even if the medical student is learning how to suture, we turn it off and the patient awakens by the time they arrive in the PACU. What will MHAUS do? Will inhalational anesthetics and MH exist only in the anesthesia history books? My med school pharmacology professor drilled into us: “Be not the first to use a drug, but be not the last”. But I can’t wait to use remimazolam.
If you have used remimazolam in your practice, tell us your experience…