Episode #176 Keeping Patients Safe with Remimazolam Administration, PART 2

Hello and welcome back to the Anesthesia Patient Safety Podcast.  My name is Alli Bechtel, and I am your host. Thank you for joining us for another show. We are back for Part 2 of our two-part series on Remimazolam. This is a novel, possibly practice-changing medication. But before you start using Remimazolam in your practice, it is so important to understand how to use this mediation while keeping patients safe.

Before we dive into the episode today, we’d like to recognize Medtronic, a major corporate supporter of APSF. Medtronic has generously provided unrestricted support to further our vision that “no one shall be harmed by anesthesia care”. Thank you, Medtronic – we wouldn’t be able to do all that we do without you!”

Our featured article is once again “Remimazolam: Patient Safety Considerations of a Novel, Practice-Changing Drug in Perioperative Medicine” by Arnoley Abcejo and Miguel Teixeira. To follow along with us, head over to APSF.org and click on the Newsletter headings. First one down is the Current Issue. Then, scroll down until you get to our featured article today. We hope that you listened to episode #175 last week when we started the conversation on Remimazolam. We are so excited to continue the conversation today.

Before we dive back into the article, let’s review Figure 2 from the article, Practical Clinical Considerations.

• Following administration of a 0.1mg/kg bolus of remimazolam, onset of sedation is within 60 seconds, maximum plasma concentration occurs within 1-2 minutes, and peak sedation lasts for 1-4 minutes with the patient being fully alert in 1.5 minutes.
• There is rapid systemic clearance that is three times faster than midazolam. For bonus points, remember that remimazolam is hydrolyzed by CES-1 into inactive metabolites, and severe hepatic dysfunction will reduce clearance by almost 40%. There is a low volume of distribution and a short terminal elimination half-life.
• Here’s a quick review of route and dosage.
  • Intravenous is clear and painless, but it is incompatible with lactated ringers and safe to y-site with other anesthetics.
  • Intranasal is painful and has a bioavailability of only 50%.
  • Oral route has very low bioavailability at 1-2%.
  • For sedation, fixed boluses may be administered in 1-5mg IV every 2 minutes as needed for desired effect.
  • For general anesthesia, induction doses range from 6-12 mg/kg/hr with maintenance rates of 1-2 mg/kg/hr.

This week, we are going to hear from the other author of the article. Here he is now.

[Abcejo] “Hello, my name is Arnie Abcejo. I am an anesthesiologist at Mayo Clinic, Rochester, the division chair of neuro-anesthesiology and radiology and the APSF website medical director.”

[Bechtel] To kick off the show today, I asked Abcejo, why he wrote this article. Let’s take a listen to what he had to say.

[Abcejo] “We wrote this article for a couple reasons. First, anecdotally, our group has been asked by many other large and small private and academic practices across the country on our use, why we use it, how we use it, and how it’s made an impact on our large practice.

We wanted to share that information more broadly with a venue like the APSF. Secondly, there are patient safety considerations that we need to be aware of in this drug, and because so, it behaves so much unlike midazolam. Thirdly, a lot of information in GI and pulmonology, and not necessarily from anesthesia.

I think as the experts in perioperative patient safety, we should have a leadership role in what makes this drug safe and how we should use it. I think what, uh, I’m really astounded with remimazolam is its impact on our practice, um, here at Mayo Clinic.

Since we first launched this trial use of this drug in 2021, we’ve administered the drug safely and successfully in thousands of patients. And in many ways, it’s become the standard of care for some specific procedures for sedation. To have an impact on a large quaternary system like ours, I’ve never really seen a drug like that before.

Uh, before, and I’m absolutely sure this drug will have an impact on not only perioperative medicine, but also health care as a whole.”

[Bechtel] Thank you so much to Abcejo for contributing to the show today. We are so excited to learn more about remimazolam and see what kind of impact this medication will have in the future.

And now it’s time to jump back into the article. We left off last week by discussing important patient safety considerations associated with remimazolam use that we need to evaluate going forward. We are going to pick up right there.

We still need to figure out the administration and practice guided by non-anesthesia professionals. Administration of midazolam by periprocedural nursing staff is very common. At this time, there are gastrointestinal endoscopic studies that report the safe use of remimazolam by non-anesthesia professionals. The authors’ experience at the Mayo clinic has been that changing from a midazolam sedative nursing practice to a remimazolam sedative nursing practice takes time, training, and cultural shifts and this is especially important to help ensure patient safety.

Another consideration is the cost and access. Remimazolam is more expensive than other common sedative medications including midazolam and propofol. This increased cost may be balanced by the faster recovery times that may facilitate increased procedural efficiency.

We are going to shift gears to talk about the adverse reactions and contraindications for remimazolam use. Remimazolam appears to be a safe medication with mild and short-lived adverse reactions that are reversed by a single dose of flumazenil. Remember, remimazolam has a short context-sensitive half-life, but you still need to be careful to ensure adequate reversal in patients receiving a prolonged infusion, with significant liver disease, and with co-administration with opioids. Even though re-sedation from remimazolam after reversal is unlikely, this has been reported in the literature.

Let’s review the common adverse reactions following remimazolam administration.

• Heart rate and blood pressure changes
• Body movement
• Nausea
• Dizziness
• Headaches

Keep in mind that adverse reactions are less likely to occur than following propofol administration and at a similar rate to midazolam. Co-administration of remimazolam with other central nervous system depressants including opioids may lead to significant respiratory depression. Remain vigilant for anaphylaxis which has been reported in the literature. Contraindications to remimazolam administration includes patients with a known severe hypersensitivity reaction to Dextran 40. More studies are needed to evaluate the risk of postoperative nausea and vomiting and remimazolam administration. There is likely a decreased risk compared to volatile anesthetics, but not when compared to propofol.

Now is the moment you have all been waiting for, a deep dive into the clinical practice implications. The authors report that since its introduction at their institution, remimazolam was quickly adopted in almost every area of practice especially in clinical areas with complex patients and procedures. Let’s take a look at the specific clinical areas.

First up, for patients with complex cardiovascular or hemodynamically unstable patients remimazolam has limited impact on respiratory depression, systemic vascular tone, and inotropic, dromotropic, and chronotropic function. Thus, remimazolam may be used for patients undergoing cardiac catheterization, especially cardioversions, and during cardiac surgery and trauma cases in patients with limited cardiopulmonary reserve.

Second, remimazolam may be used for non-operating room anesthesia or NORA procedures. Remimazolam may be used for patients undergoing GI and Pulmonary Endoscopic Procedures. Studies have revealed a comparable efficacy for procedural sedation with less hemodynamic variability, painless IV injection, decreased postoperative nausea and vomiting, and a rapid return to baseline neurological function. Wow, that all sounds great! For patients undergoing interventional radiology procedures, remimazolam may be used to provide sedation, amnesia, and anxiolysis. The new medication may have a big impact in this space since these patients may be sicker with multiple comorbidities, require deeper levels of sedation, and are too unstable to open surgical procedures and these procedures often have limited, intermittent periods of stimulation. Patients, such as those with claustrophobia, musculoskeletal discomfort, and tremors, who need sedation when undergoing magnetic resonance imaging may benefit from remimazolam administration. Remimazolam may also be used with dexmedetomidine to provide monitored anesthesia care for MRI. Here are some good examples, patients with central spinal cord stenosis may be safely sedated with intermittent remimazolam boluses to obtain the imaging with intermittent neurological exams to monitor for permanent spinal cord ischemia. Small doses may be given to patients for anxiolysis while maintaining a patent airway to complete a brain MRI. The authors point out that the Mayo Clinic does not formally have nurses performing sedation with remimazolam.

Finally, there appears to be a role during neurosurgical procedures since it provides rapid amnestic sedation and anxiolysis which may be quickly followed by a meaningful neurologic exam. The authors report using this medication for awake craniotomies during pin placement, local anesthetic administration, urethral catheter placement, and surgical incision.

The authors’ experience with remimazolam is that it will likely have a big impact on a variety of clinical situations given the attractive pharmacokinetics, relative respiratory and hemodynamic safety profile, and rapid reversal with likely expansion into nurse sedation practice as well as outpatient and ambulatory settings going forward. The authors leave us with this call to action:

“Anesthesia professionals have a unique opportunity to identify patient safety practice guidelines, clinical guardrails, and safety algorithms for remimazolam. More large patient cohort safety data are forthcoming to truly delineate its safety profile compared to the other commonly used sedatives in the anesthesia professionals’ arsenal.”

We are looking forward to learning more about remimazolam going forward and it will be exciting to see if this is the next practice-changing medication. If you are using remimazolam at your institution and in your clinical practice, let us know by tagging us on twitter @APSF.org. We want to hear from you and your experience.

If you have any questions or comments from today’s show, please email us at [email protected]. Please keep in mind that the information in this show is provided for informational purposes only and does not constitute medical or legal advice. We hope that you will visit APSF.org for detailed information and check out the show notes for links to all the topics we discussed today. We’ll be back next week to talk about an all-new article from the October 2023 APSF Newsletter.

Until next time, stay vigilant so that no one shall be harmed by anesthesia care.

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