Effectiveness and safety of sedation in gastrointestinal endoscopy:
An opinion review
Ryoji Ichijima, Mitsuru Esaki, Sho Suzuki, Chika Kusano, Hisatomo Ikehara, Takuji Gotoda
www.wjgnet.com/2308-3840/full/v8/i2/48.htm
CURRENT STATUS IN THE USAGE OF SEDATIVES
MIDAZOLAM’S CHARACTERISTICS AND CLINICAL TRIALS
PROPOFOL CHARACTERISTICS AND CLINICAL TRIALS
WHICH DRUG IS MORE EFFECTIVE FOR SADATION
MIDAZOLAM OR PROPOFOL?
REMIMAZOLAM: A NEW SEDATIVE
Remimazolam is an ultra-short-acting intravenous novel benzodiazepine sedative,
with a shorter half-life (approximately 40 min) compared with other conventional
benzodiazepines. It can rapidly pass through the blood-brain barrier and provide a
rapid effect because it is a fat-soluble drug. Remimazolam is rapidly metabolized by
carboxylic acid elastase, which does not involve the liver enzyme CYP3A4, and shows
organ-independent metabolism. Its organ-independent metabolism makes it less
likely to impair liver and kidney function. Remimazolam’s metabolites are
pharmacologically inactive. Therefore, the adjustability of remimazolam seems to be
superior to Midazolam.
Remimazolam is safer than propofol because it can be reversed with flumazenil to
rapidly terminate sedation, similar to other benzodiazepines if necessary.
Furthermore, remimazolam’s half-life is as short as flumazenil’s and therefore, there is
low risk of re-sedation unlike other benzodiazepines.
In a phase IIa study conducted in the United States, the induction times from drug
administration to sedation was 1.5-2.5 min in remimazolam (0.10-0.20 mg/kg) and 5
min in midazolam (0.075 mg/kg) in upper gastrointestinal endoscopies[36]
.The time to recover from sedation (3 consecutive Modified Observer’s Assessment of Alertness
and Sedation scores of 5) was significantly shorter in remimazolam than that in
midazolam (6.8-9.9 min vs 11.5 min, respectively). These results suggest that
remimazolam had a faster onset of action and a faster recovery time after endoscopic
examination/treatment compared with midazolam.
In a phase IIb study conducted in the United States, remimazolam (5.0 mg, 7.0 mg,
and 8.0 mg) achieved a lower rate of additional administrations compared with
Midazolam (2.5 mg) during colonoscopies[37]
.
Similarly in a phase III study conducted in the United States, remimazolam (5 mg)
achieved a higher procedural completion rate without the requirement for additional
fixed doses (5 doses in any 15-min interval), compared with placebo (5 doses in any
15-min interval) and midazolam (3 doses in any 12-min interval; aged < 60 years, 1.75
mg; aged ≥ 60 years, 1.0 mg) in outpatient colonoscopies[38]
.
All studies have suggested that remimazolam was as safe as Midazolam as a
sedative for gastrointestinal endoscopy. Remimazolam, has the combined advantage
of a short half-life, similar to propofol and an antagonist like midazolam.
Furthermore, it can be managed by non-anesthesiologists. Therefore, remimazolam
may increasingly be used as a sedative for gastrointestinal endoscopies.
The use of Remimazolam in clinical practice remains insufficient. New issues might
arise after clinical administration. To the best of our knowledge, there are no studies
comparing the clinical outcomes of remimazolam with propofol. There is a lack of
clinical data on Remimazolam. Various additional clinical studies to improve the
efficacy and safety of remimazolam as a sedative for endoscopic procedures is desired
in the future. Preparation for clinical trial for insurance coverage are currently in
progress in Japan
CONCLUSION
Conscious sedation, without tracheal intubation, during endoscopy differs greatly
depending on the country and region. Endoscopic examination using sedation should
be safely completed without pain. Currently, benzodiazepine sedatives and propofol
are the predominant drugs administered during endoscopic examinations. Propofol
might be useful for patients in countries or regions with sufficient anesthesiologists.
While a novel benzodiazepine sedative, remimazolam, could be a desired option in
countries or regions without adequate numbers of anesthesiologists to attend endoscopic procedures.
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