Effect of Remimazolam Induction on the Recovery Quality After Day Surgery in Elderly Patients: a Comparison Study With Etomidate
Phase: NA
Conditions: Elderly Patients, Ambulatory Surgery
Sponsor: Xijing Hospital

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Effect of Remazolam benzene-induced laryngeal mask
general anesthesia on the quality of recovery after day
surgery in elderly patients: a comparative study with
etomidate induction
Version number: V 2.0
Version date: November 3,2022

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1. Research Background
Elderly patients have reduced organ function, often with
comorbidity, and the incidence of complications and mortality are
significantly higher after undergoing anesthesia and surgical trauma
than those in other adult patients.[1-3] At the same time, elderly
patients often have problems with hemodynamic instability such as
hypotension during the induction of anesthesia.[4]
Eomidate, a widely used general anesthetic, is often used for
induction of general anesthesia in elderly or hemodynamically
unstable patients because of its small effects on blood pressure and
heart rate. However, etomidate has an inhibitory effect on adrenal
function and can cause muscle tremor and stiffness. Moreover,
some studies have shown that etomidate anesthesia increases
postoperative nausea and vomiting (PONV), which may not be
conducive to patient prognosis and reduce satisfaction.[5]
Remazolam (RT) is a new ultra-short-acting benzodiazepine
drug that has been approved for clinical use since 2019. It is
characterized
by
rapid
hydrolysis
into
inactive
carboxylate
metabolites by ubiquitous tissue esterases. Compared to the classic
benzodiazepine
midazolam.[6-8]
Also,
like
the
other
benzodiazepines, remazolam can be antagonized by the flumazenil
injection. A recent study showed that remazolam is more stable
hemodynamic than propofol during anesthesia.[9]
With
significant
advances
in
surgical
techniques,
the
proportion of patients undergoing day surgery with postoperative

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complications has gradually decreased. Current perioperative care
that improves the recovery of surgical patients focuses more on the
time to restore normal function and the subjective postoperative
experience, rather than just the incidence of complications. The
Quality of Recovery (QOR) score, as an objective measure of
patient-centered surgery and post-anesthesia general health, is often
used to assess the quality of postoperative recovery, where QoR-15
is a reliable tool for assessing early postoperative recovery [10] and
has been validated for [12] in patients undergoing various surgical
procedures.
If hemodynamic stabilization during the etomidate induction
phase can be achieved with another anesthetic without the above
associated side effects, and the quality of postoperative recovery is
no worse than that in elderly patients receiving etomidate, this
would provide a new option for the induction of anesthesia during
daytime surgery in elderly patients. In this study, we aimed to
evaluate the quality of recovery following general anesthesia with
remazolam-induced laryngeal mask in elderly day surgery patients,
comparing that of remazolam versus etomidate, to better guide
anesthesiologists in the choice of intraoperative induced medication
in elderly patients.

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Effect of general anesthesia on the quality of recovery after
day surgery in elderly patients: a comparative study with
etomidate induction
1. Purpose Of
Research
To compare the quality of postoperative recovery
induced by general anesthesia with Remimazolam and
etomidate in elderly patients undergoing day surgery.
2. Study Design And Methods
1. Research Design
1.1 Study Objectives
The study plans to use the Chinese version of QoR-15
score to evaluate the quality of postoperative recovery after
general anesthesia in elderly day surgery patients receiving
remazolam or etomidate, while observing hemodynamic
changes and other adverse effects.
1.2 Study Content
This study is a randomized, double-blind
parallel-controlled non-inferiority trial to enroll 112 elderly
day surgery patients randomized at 1:1 to receive
Remazolam or etomidate-induced general anesthesia after
inclusion 1, along with three QoR-15 assessments to assess
the quality of their recovery after surgery.
1.3 Primary outcome measures: quality of recovery at 24h
after surgery (QoR-15 score)

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Secondary
study
index:
time
of
eyelash
reflex
disappearance after induction; SpO2, HR, MBP, and frequency
of use of vasoactive drugs during anesthesia; incidence of
adverse events in PACU.
1.4 Subject selection
Selection criteria:
1)Age:> 65 years old and above;
2)The American Association of Anesthesiologists (ASA) is
grades I-III;
3)The body mass index (body mass index) was 18-30 kg/m2；
4)Voluntary provide written informed consent;
5) The patient underwent day surgery under general anesthesia
with a laryngeal mask.
Exclusion criteria:
1)Cognitive dysfunction and neuropsychiatric disorders;
2)Use of benzodiazepines or opioids within 1 month;
3)
Patients
with
contraindications
or
allergies
to
benzodiazepines, opioids, etomidates and their components;
4)Patients estimated to have a difficult airway;
5)Have
adrenocortical
insufficiency,
porphyria,
or
have
received chronic corticoid therapy.
2. Research methods
2.1
Study
design:
Randomized,
controlled,
parallel
non-inferiority trial

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Randomization: The randomization result was generated by
the investigator using R software, sealed to the envelope and
handed over by the patient to the anesthesia nurse before
surgery, who was responsible for unpacking the randomized
envelope.
Blinding: The anesthesia nurse was responsible for unpacking
the randomized envelope and preparing drugs to cover the
syringes (with the same appearance and volume), and blinded
the anesthesiologist, postoperative visitors and patients.
2.2 Sample size estimation:
The primary outcome measure was the quality of
postoperative patient recovery (QoR-15 score). According to
previous studies, the minimal clinically important difference
was 8. The non-inferiority bound for the mean difference
between groups was set to-8. Referring to previous studies,
the standard deviation (SD) of the QoR-15 scale is 14, and
accounting for a 10% shedding rate, 112 achieves 90% of
efficacy with a type 1 error of 0.05. We chose to include 112
subjects in this study for the analysis, with 56 subjects in each
group.
3. Observation Items And Monitoring Time Point
1.1.Baseline metrics

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The following data were collected during the patient
screening period
Demographic data: age (yr), gender, education level, ASA
grade,
body
mass
index,
diagnosis
and
preoperative
comorbidities, and history of smoking and alcohol abuse.
Preoperative clinical data: pulse oxygen saturation (SpO2),
Non-invasive blood pressure (NIBP), heart rate and other vital
signs, and electrocardiogram.
The following data will be collected during the surgical
treatment period:
SpO2, HR, systolic blood pressure, diastolic blood pressure,
MBP, test time points including 5 minutes before induction of
anesthesia, 1 minute after induction, 1 minute after laryngeal mask
placement, and start of surgery. Where, data recorded 5 min before
induction of anesthesia served as baseline.
The following data were collected during the PACU
recovery period:
SpO2, HR, systolic BP, diastolic BP, and MBP
2.2.Primary outcome measures:
Quality of patient recovery at 24h after surgery
(QoR-15 score)
Patients were assessed using the Chinese version of the
Recovery Quality-15 (QoR-15) scale. This is a comprehensive
measure of postoperative recovery, assessing the five
dimensions of recovery: physical comfort (5), physical
independence (2), emotional status (4), psychological support

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(2), and pain (2). Each item was rated as 11 points based on its
frequency in the questionnaire (higher positive items scores,
lower negative items scores). The total score ranged from 0
(worst recovery quality) to 150 (best recovery quality);
order
number
contents of a project
grade
1
Smooth breathing
0~10
2
Good appetite
0~10
3
Have a good rest
0~10
4
sleep quality
0~10
5
Self-care personal hygiene
0~10
6
Talk to your family and friends
normally
0~10
7
Feel the medical staff medical
support
0~10
8
Participate in work or daily
family activities
0~10
9
Feel comfortable and can manage
your emotions by yourself
0~10
10
Overall, feeling healthy
0~10
11
Moderate pain
0~10
12
acute pain
0~10
13
N and V
0~10
14
Nervous anxiety
0~10
15
Sad depression
0~10
2.3. Secondary outcome measures:
SpO2, HR, MBP, and frequency of vasoactive medication
use during anesthesia, and incidence of adverse events in
the PACU. Time to the disappearance of the lash reflex
after induction.
4.Efficacy Evaluation Criteria
1. Main outcome measures:

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The
primary
outcome
measure
was
the
quality
of
recovery at 24h after surgery (QoR-15 score), recording
the QoR-15 score 1 day before surgery, 1 day after surgery
(POD 1) and 2 days after surgery (POD 2). The POD 1 score
was the primary study outcome.
2. Secondary outcome measures:
SpO2, HR, MBP, and frequency of vasoactive medication
use during anesthesia, and incidence of adverse events in
the PACU. Time to the disappearance of the lash reflex
after induction.
5. Statistical treatment
1. Analyze the crowd
1) Full analysis set (FAS): Subject set following the principle of
intentional treatment (Intention To Treat, ITT): the data set
consisting of all subjects participating in treatment and with
baseline efficacy evaluation.
2) Compliance with the protocol set (PPS): refers to the
completed trial and excluded the treatment population group
with serious protocol violations (refers to which the study
subjects violated the inclusion criteria or exclusion criteria).
3) Safety analysis set (SS): means the set of all subjects enrolled,
with a study intervention, and with at least one baseline level
safety evaluation.
4) Efficacy analysis will be conducted on the basis of the full
analysis set and the compliant protocol set. All baseline
demographic data analyses will be conducted based on the full

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analysis set, and safety evaluations will be conducted on the
safety set.
2. Statistical analysis method
Data
management
was
performed
by
EpiData
software;
SPSS26.0
software
was
used
for
statistical
analysis.
Quantitative variables were tested for normality by using the
Shapiro –
Wilk test. Comparison of quantitative variables
with normal distribution between groups were performed by the
t-test, and quantitative data with asymmetric distribution were
analyzed by the Mann Whitney U-test. Qualitative variables
were compared between groups with the chi-square test or
Fisher's exact test as needed. Data for the QoR-15 score are also
expressed as the median difference and their 95% confidence
interval (CI). Median difference is the median of all pairwise
differences between the two sets of observed values, with the
95% CI estimated by Hodges-Lehmann. Data on the frequency
of adverse events were reported by the proportion difference
and their 95% CI. The 95% CI of proportional differences was
calculated using the Wilson program. Among other parameters,
such as patient demographic parameters, SpO2, HR, MBP, and
vasoactive drug application frequency, median or proportional
differences and their 95% CI were calculated as described above.
All analyses were assessed using two-sided tests and a P-value
less than 0.05 was considered statistically significant.

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