Remimazolam is primarily metabolized via CES1, and other drugs that are commonly metabolized by CES1 are known to have their pharmacokinetics and clinical effects affected by genetic polymorphisms in CES1. The goal of this observational study is to investigate the impact of the CES1 genotype on the pharmacokinetics, safety, and efficacy of remimazolam in patients undergoing elective surgery.
Study Type
OBSERVATIONAL
Enrollment
120
This is an observational study, meaning that no interventions are actually administered to the participants. However, blood and urine samples will be collected for research purposes. Participants will receive remimazolam besylate for at least 2 hours during anesthesia and surgery. Blood will be drawn to determine the concentration of remimazolam in the blood at the following time points: (1) before remimazolam administration, (2) after remimazolam administration has lasted at least 2 hours without a change in concentration, (3) immediately before discontinuation of remimazolam if there has been a change in concentration since the second blood draw, (4) within 5 minutes of discontinuation, (5) within 15-60 minutes of discontinuation, and (6) 90 minutes after discontinuation. Urine will also be collected after the end of anesthesia to check for metabolites of remimazolam.
Korea University Guro Hospital
Seoul, South Korea
RECRUITINGDose-adjusted steady-state concentration of remimazolam
Determine the dose-adjusted steady-state concentration of remimazolam using Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS)
Time frame: Immediately before the initiation of remimazolam administration ~ 120 minutes after the cessation of remimazolam
Maintenance dose of remimazolam for maintaining general anesthesia
Hourly maintenance dose of remimazolam for maintaining general anesthesia
Time frame: Immediately before the initiation of remimazolam administration ~ 120 minutes after the cessation of remimazolam
Total dose of remimazolam used to induce general anesthesia
Determine the total dose of remimazolam to achieve loss of consciousness (LOC). Modified Observer's Alertness/Sedation Scale (MOAA/S) \<2 indicates LOC. The MOAA/S scale assesses a patient's level of alertness and response to stimulation, and is scored on a 6-point scale (6: awake and alert, 1: deeply asleep and unresponsive to any stimulus).
Time frame: Initiation of remimazolam administration ~ 5 minutes after start of remimazolam
Time to LOC after remimazolam administration during anesthesia induction
Determine the time to achieve LOC after remimazolam dosing.
Time frame: Initiation of remimazolam administration ~ 5 minutes after start of remimazolam
Time to bispectral index(BIS) < 60 after remimazolam administration during anesthesia induction
Determine the time to achieve BIS \<60 after remimazolam dosing
Time frame: Initiation of remimazolam administration ~ 10 minutes after start of remimazolam
Changes in BIS during induction and maintenance of anesthesia
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Measure BIS during anesthesia
Time frame: Initiation of remimazolam administration ~ 30 minutes after cessation of remimazolam
Percentage maintained BIS >60 during general anesthesia
Calculate "Time maintained BIS \>60 / Time remimazolam administered"
Time frame: Initiation of remimazolam administration ~ Cessation of remimazolam(up to 10 hours after start of remimazolam administration)
Changes in BIS during anesthesia induction and maintenance
Assess BIS values during general anesthesia
Time frame: Initiation of remimazolam administration ~ 30 minutes after cessation of remimazolam
Postanesthesia care unit (PACU) length of stay
Determine how long participants stay in the PACU before being transferred to a general ward
Time frame: PACU admission ~ PACU discharge (within 3 hours after PACU admission)
Emergence delirium
Richmond Agitation Sedation Scale (RASS) ≥1 indicates emergence delirium (RASS score ranges from -5 to +4, with negative numbers indicating varying degrees of sedation or lethargy, and positive numbers indicating varying degrees of agitation or restlessness)
Time frame: Immediately after extubation ~ 3 hours after PACU admission
Resedation
Richmond Agitation Sedation Scale (RASS) ≤-2 indicates resedation
Time frame: Immediately after extubation ~ 3 hours after PACU admission
Precipitation
Visually determine whether remimazolam administration causes precipitation in the fluid line through which the agent is administered
Time frame: Initiation of remimazolam administration ~ 10 minutes after start of remimazolam
Injection pain caused by remimazolam administration
Question the patient to determine if pain occurs at the intravenous site where remimazolam is administered (check only if it occurs)
Time frame: Initiation of remimazolam administration ~ 3 minutes after start of remimazolam
Adverse events up to 48 hours after surgery
All adverse events including nausea/vomiting, hypertension/hypotension(30% or more change in preoperative blood pressure), bradycardia (heart rate \<50 beats per minute\[bpm\]), tachycardia (heart rate \>100 bpm)
Time frame: Initiation of remimazolam administration ~ 48 hours after surgery
Endogenous metabolites that occur as remimazolam is metabolized in the body (This is an exploratory check, meaning we do not know in advance what substances will be found)
Analyze collected blood and urine to determine the metabolites of remimazolam (Therefore, various laboratory methods can be used to detect endogenous metabolites, but it is not known in advance exactly how)
Time frame: Immediately before the start of remimazolam ~ 120 minutes after remimazolam cessation
Total dose of remimazolam during general anesthesia
Determine the total dose of remimazolam during general anesthesia
Time frame: Initiation of remimazolam administration ~ Cessation of remimazolam(up to 10 hours after start of remimazolam administration)
Total dose of remifentanil during general anesthesia
Determine the total dose of remifentanil during general anesthesia
Time frame: Initiation of remifentanil administration ~ Cessation of remifentanil(up to 10 hours after start of remifentanil administration)
Operation time
Determine how long the surgery was performed
Time frame: Start of surgery ~ End of surgery(up to 10 hours after start of surgery)
Anesthesia time
Determine how long the general anesthesia was performed
Time frame: Initiation of remimazolam administration ~ Exit to the PACU (within 30 minutes after remimazolam cessation)
Flumazenil dosage
If the participants are not awake within 10 minutes after discontinuation of remimazolam, administer flumazenil and verify the total dosage (max: 1 mg).
Time frame: Cessation of remimazolam ~ 30 minutes after remimazolam cessation
Pain score in PACU
If the participants are able to verbalize their pain, use a Numerical Rating Scale (NRS), otherwise use a Visual Analog Scale (VAS). Both scales are used to measure pain intensity on a scale of 0 to 10, with 0 being no pain and 10 being the worst pain imaginable.
Time frame: PACU admission ~ PACU discharge (within 3 hours after PACU admission)
Analgesic usage in PACU
Identify the type and dose of opioid or non-opioid pain medication used to control the participants' pain.
Time frame: PACU admission ~ PACU discharge (within 3 hours after PACU admission)
Delirium
Determine delirium during post-operative hospitalization through electronic medical records
Time frame: After surgery ~ Hospital discharge (within 1 month after surgery)
Postoperative complications
Identify any complications during post-operative hospitalization through electronic medical records
Time frame: After surgery ~ Hospital discharge (within 1 month after surgery)
Hospital stay after surgery
Identify the hospital length of stay after surgery
Time frame: The day of surgery ~ Hospital discharge (within 1 month after surgery)