Remimazolam: Promising sedative for upper gastrointestinal endoscopy

The demand for sedation during endoscopy has been obviously increasing, as it allows endoscopists to perform endoscopic examinations safely while providing patients with a greater sense of relief and satisfaction.¹

Sedatives commonly used during endoscopy include midazolam, diazepam, flunitrazepam, dexmedetomidine, and propofol, each with its advantages and disadvantages. The choice of sedatives depends upon the specific needs of each facility.² In Japan, midazolam is the most frequently used sedative during endoscopy. However, patients sedated with midazolam require extended recovery time due to its long half-life and prolonged sedative effects after the procedure.^{2, 3} The need for a recovery room thus limits the use of sedatives in clinical practice.

Remimazolam is a newly developed ultra-short-acting benzodiazepine. It has been approved by the U.S. Food and Drug Administration (FDA) and is used as a sedative during gastrointestinal endoscopy, while it is not yet covered by the Japanese insurance system. A recent meta-analysis comparing remimazolam with midazolam for sedative gastrointestinal endoscopy showed a higher procedural success, lower need for rescue medication, shorter total recall and delayed recall, and reduced adverse events.⁴ Since remimazolam has pharmacokinetically a shorter half-life than midazolam, it can be expected to reduce both the time to alertness and the time spent in the recovery room.^{3, 4}

Propofol, another commonly used sedative for endoscopy, has the advantage of a narrower range of sedation and anesthesia than midazolam and results in a better awakening quality. However, its primary side-effects, including respiratory and circulatory depression, are often problematic. The Japan Gastroenterological Endoscopy Society's guidelines for sedation (second edition) state that propofol may be used by nonanesthesiologists if they have undergone sedation training and only for patients with American Society of Anesthesiologists-Physical Status (ASA-PS) classification I or II.²

The study by Lee et al.⁵ was a randomized controlled trial (RCT) that compared the effects of remimazolam and propofol on oxygen reserve during upper gastrointestinal endoscopy. For this purpose, the study used the oxygen reserve index (ORi) to investigate whether a sedative dose of remimazolam maintains better oxygenation than propofol in a state of mild hyperoxia, as experienced by patients during upper gastrointestinal endoscopy. The ORi is a respiratory parameter that reflects venous blood oxygen saturation and is useful for evaluating oxygenation status in a mild hyperoxic state with a PaO₂ of 100–200 mmHg, which cannot be adequately evaluated using conventional pulse oximetry.⁵ This study found a significantly higher incidence of decreased oxygen reserves in the propofol group compared with the remimazolam group (65.7% vs. 38.2%, P = 0.022). Hypoxia was more frequent with propofol (11.4% vs. 0%, P = 0.042), as was tachycardia (22.9% vs. 5.9%, P = 0.045).

This study also showed that remimazolam and propofol showed equivalent efficacy in the completion and procedure time of sedative endoscopy, and satisfaction of endoscopists. In contrast, the incidence of postendoscopy adverse events was significantly lower in the remimazolam group than in the propofol group, primarily due to the lower incidence of nausea, while no other adverse events such as hypertension, hypotension, or bradycardia were different between the two groups. In addition, while patients receiving remimazolam took 5 min longer than those receiving propofol to become fully alert during recovery, no difference was found in the length of stay in the recovery room or overall procedure time between the two groups. Furthermore, remimazolam was administered less frequently than propofol to maintain sedation in endoscopy (32.4% vs. 65.7%, P = 0.006), resulting in no use of flumazenil during or after sedative endoscopy by remimazolam. Considering these results, remimazolam seems at present to be the most suitable sedative for short-duration upper gastrointestinal endoscopy procedures.

As has been conducted in the present study,⁵ propofol has been generally recommended to be administered by experienced anesthesiologists. Therefore, the use of propofol by nonanesthetists for sedation during upper gastrointestinal endoscopy poses safety concerns. A meta-analysis comparing propofol administration by endoscopists and anesthetists in low-risk patients (ASA-PS class I or II) found a higher incidence of bradycardia in the endoscopist-administered group, but no increase in hypotension or the need for airway management procedures. It was also reported that endoscopists use significantly less propofol than anesthetists, leading to a higher rate of patient awareness during the procedure with recall.⁶ Another meta-analysis of RCTs comparing nonanesthesiologist administration of propofol (NAAP) with anesthesia provider-administered propofol (AAP) in highly invasive endoscopic procedures found similar rates of hypoxemia, but higher rates of airway management interventions in the AAP group than in the NAAP group. This meta-analysis again found that a greater amount of propofol was used in the AAP group, and that patient and endoscopist satisfaction was higher in the AAP group.⁷ Current Japanese guidelines recommend that propofol sedation should be used for patients with an ASA-PS classification III or higher only when supervised by an anesthesiologist.² In contrast, Western guidelines permit NAAP for sedative endoscopy when they received appropriate education and training for its use or being certified as having advanced life support skills (such as airway management, defibrillation, and the use of resuscitation medications), or when one member could be dedicated to the role.⁸ Since Japan has no educational system or guidelines for the use of propofol by nonanesthetists, remimazolam can be a good choice for sedative upper gastrointestinal endoscopy.^{9, 10} The minimal respiratory side-effects of the medication further support the choice.

Because sedative endoscopy reduces patient pain and improves the satisfaction of endoscopists, the demand for sedation during gastrointestinal endoscopy continues to rise, while it requires further recovery space and staff for monitoring. However, the use of ultra-short-acting benzodiazepine with a favorable safety profile could be expected to reduce such a hospital load. Considering these factors, it is expected that remimazolam will become more widely used for sedative endoscopy, even in outpatient care. Future research should focus on evaluating potential adverse events with remimazolam, affirming its safety and efficacy in high-risk and older patients, and further exploring its use in therapeutic endoscopy. It also seems necessary to compare the cost-effectiveness of remimazolam with other sedatives for its approval in Japan.

This article, reported by Lee et al., is a meaningful RCT that highlights the suitability of remimazolam as a sedative for upper gastrointestinal endoscopy.

Authors declare no conflict of interest for this article.

None.