Patients eligibility
The patients who received painless gastroscopy in the Endoscopic Center of Yangzhou University Affiliated Hospital were included for the present study in January 2021. These patients were approved by the Ethics Committee of Yangzhou University Affiliated Hospital(2020-YKL10-25), and provided a written informed-consent. The trial was registered at ClinicalTrials.gov with registration number ChiCTR2100041759(01/04/2021). This was a double-blind, randomized, parallel-group study. A total of 400 patients, 18-65 years old and scheduled to undergo diagnostic gastroscopy, were eligible for the present study. In addition, these patients with ASA physical status score of I or II had a body mass index (BMI) of 18-30 kg/m2. Patients were excluded if they were pregnant or lactating, had obvious cardiopulmonary liver and kidney dysfunction before the operation, had severe neuropsychiatric diseases, or Benzodiazepine and opioids treatment history.
Procedures
These patients were randomly divided into five groups: ideal body weight of 0.2 mg/kg remimazolam group (W1 group), ideal body weight of 0.3 mg/kg remimazolam group (W2 group), fixed dose of 10 mg remimazolam group (F1 group), fixed dose of 12 mg remimazolam group (F2 group), and 1.5 mg/kg propofol control group (C group). Male: IBW (kg) = [height (cm) - 100]. Female: IBW (kg) = [height (cm) - 105]. All patients were given 0.25 ug/kg of remifentanil before receiving the study medication.
Patients received routine fasting and drinking in that morning, and the nurse opened the venous vessels for them. Then, they orally received 10 ml of dyclonine glue before the examination for surface anesthesia. Their heart rate (HR), blood pressure (BP), and blood oxygen saturation (SpO2) were continuously monitored. Before the operation, these patients were given oxygen by nasal catheter (4L/min). All patients were intravenously given low-dose remifentanil for analgesic pretreatment. Then, according to the random arrangement, different doses of remimazolam benzenesulfonic acid were intravenously administered (Hengrui Pharmaceutical Co., Ltd., batch number: 2019S00728). Patients in the propofol group were given a 1.5mg/kg propofol injection (AstraZeneca Pharmaceutical Co., Ltd., batch number: X19134A). The gastroscopy operation began when the MOAA/S score was ≤3. When the MOAA/S score was ≥4 at three minutes after the administration, sedation failure was recorded, and propofol was used to complete the examination. The sedation was maintained by giving 1/4 of the initial dose each time when patients made any body movement, and it was ensured that the MOAA/S score was ≤3. Within 15 minutes, no more than three additions were given. If these three additional doses within the 15-minute time window were not sufficient to maintain the sedation, sedation failure was recorded. When the heart rate was less than 50 bpm, 0.5 mg of atropine was given, and when the blood pressure decreased by more than 30% of the baseline, vasoactive drugs were given. If the SpO2 was less than 90%, oxygen was given under pressure by mandible treatment or mask. The MOAA/S scores were recorded before the examination (T0), after the first administration (T1) per two minutes (T2, T3 and T4), until the check was finished (T5), and when the patient was awake. Then, recording was performed every five minutes, until the patient matched the standard for discharge. Vital signs, including HR, systolic (SBP)/diastolic (DBP), SpO2, MOAA/S score, recovery time (from the time of last dose to recovery time), time to release from hospital, and adverse reactions, were all recorded from pre-administration to post-administration.
Scoring criteria
Sedation Assessment Scores[20] in Table 1 :
Table 1. Sedation Assessment Scores
Modified Observer’s Assessment of Alertness/Sedation
|
Response
|
Score level
|
Responds readily to name spoken in normal tone
|
5(alert)
|
Lethargic response to name spoken in normal tone
|
4
|
Responds only after name is called loudly or repeatedly
|
3
|
Responds only after mild prodding or shaking
|
2
|
Does not respond to mild prodding or shaking
|
1
|
Does not respond to noxious stimulation
|
0
|
Separation criteria[ 21]:10 minutes after the end of the operation for the first time to determination of eligibility for separation, and subsequently every five minutes, until the subjects met the following conditions before leaving the hospital accompanied by their relatives; the range for blood pressure and heart rate fluctuation was within ±20% of the preoperative basic value, and stable for more than 10 minutes; no or only mild pain; no or only slight nausea and vomiting; no dizziness in the sitting position and during movement; stable gait.
Statistical methods
The SPSS 25.0 statistical software was used for data processing. The measurement data were expressed as (x̄ ± SD). Continuous variables should be normality checked first, expressed as (x̄ ± SD) if the normal distribution is met. The between-group comparisons of were analyzed by ANOVA test. And each group within the comparison was analyzed by paired sample test. The counting data was expressed in rate, and χ2 test was used. P<0.05 was considered statistically significant.