Methods
The study was approved by the Ethics Committee for Clinical Trials of
the First Hospital affiliated of China University of Science and
Technology, Hefei, China [approval no. : 2021-ky095]. The research
was signed in the Chinese Clinical Trial Registry before patients
enrollment (ChiCTR 2000040130). All participants completed written
informed consent.
Patients scheduling gynecological laparoscopic operation with American
Society of Anesthesiologists (ASA) physical status I or II were enrolled
in this research. All patients aged range is between 30 and 65, body
mass index (BMI) in between 18.5 and 29.5 kg/m2. They
were eliminated if anyone met any of the following standards: poor
compliance or non-cooperate; presence of serious disease (cardiovascular
disease, bronchial asthma, uncontrolled severe hypertension, fearful
blood system dysfunction, liver or kidney dysfunction, obvious
electrolyte abnormalities); second degree atrioventricular block,
bradycardia (HR< 50 bpm), low blood pressure (SBP<
90 mmHg); history of neurological disease, chronic pain, drug addiction
and alcoholism, long-term opioid use; history of allergy to opioids;
slow intestinal peristalsis or intestinal obstruction; participant in
clinical trials involving other drugs within four weeks; the presence of
other conditions. Patients were split into 3 groups according to the
effect-site concentration of propofol at in high concentration (3
ug/mL), middle concentration (2.5 ug/mL), low concentration (2 ug/mL)
respectively during maintenance.
All participants fasted for 8 h, intravenous access was established
after reaching the operating room, and received lactated Ringer’s or
colloid solution maintained to expand blood volume. All patients avoided
receiving any sedative or analgesic drugs before induction of
anesthesia, and measured vital parameters, including invasive arterial
blood pressure, cardiac rate, electrocardiography,
pulse oxygen saturation,
nasopharyngeal temperature and end-tidal carbon dioxide partial
pressure. For BIS and PSI monitoring, set different single-use,
disposable sensors at the forehead after the skin was cleaned with
alcohol swabs. The two sets of EEG recording electrodes were closed to
where they were used, in line with the manufacturer’s recommendations,
and there was no significant interference between the two monitoring
systems. (Fig. 1 ).
Preoxygenated with 100% oxygen before induction. General anesthesia was
induced with TCI propofol 4 µg/mL and REM 4 ng/mL[21], after PSI
dropped below 50, or the eyelash reflex disappearance, muscle relaxation
was performed with rocuronium 0.5mg/kg. Controlled breathing for 5 min,
inserted tracheal tube, meanwhile, set mechanical ventilation as target
a PETCO2 in the 35 - 45 mmHg and SpO2 > 95%. Kept the
patient’s body temperature between 36.0 °C and 37.0 °C. Anesthesia was
maintained with propofol and REM, which were adjusted to the target
concentration according to the patient’s group.
Sufentanil was administered with 0.15 - 0.7 µg/kg half an hour after the
operation began to achieve the long-term analgesia. Propofol and REM
were quit by the end of surgery. Patients were organized in a
post-anesthesia care unit (PACU), set back to the inpatient ward with a
Steward resuscitation score of above 4[22] after surgery. All
patients used patient-controlled analgesia for 48 h. The ingredient
consisted of 2.5 μg/kg sufentanil and 2 mg granisetron (total volume of
100 ml, including 0.9% normal saline).
The first patient of respective group administrated an effect-site
concentration of REM at 3.5 ng/mL, then determined by using a
modified up-and-down sequential
method[23, 24]. In other words, the reaction of each patient decided
the concentration of REM set to the succeeding patient. If the reaction
of the previous patient was positive (the PSI value increased by
>10 during 2 min after skin incision), the concentration
given to the next patient was increased by 0.4 ng/mL. Otherwise, the
concentration was decreased by 0.4 ng/mL. Adjusted the concentration of
REM according to the group to hold PSI between 25 and 50, if excceed
25% of initial concentration, the patient was eliminated during the
period of anesthesia. Infused additional fluids and an intermittent
bolus of ephedrine when observed hypotension. Equally, cardiac rate was
modulated with atropine of 0.05 mg if lower than 50 beats/min, and
esmolol of 20 mg on condition that exceeding 100 beats/min.
Recorded the PSI, BIS, HR and MAP at the following moments: before the
induction (T0), induction of anesthesia
(T1), 1 min after intubation (T2),
pre-incision (T3), 2 min after incision
(T4), discontinuation of drugs (T5) and
extubation (T6). Additionally, , Incidence of adverse
events (including PSI exceed the recommended range, hypertension,
hypotension, bradycardia), duration of operation, extubation time,
residence time in PACU, hospital day, VAS score in the first day after
operation, the occurrence of intraoperative awareness, postoperative
delirium were registered. Density spectral array (DSA) was saved at
SedLine® Root during the surgery.
According to the sequence method, when each group reached at least seven
positive points, the experiment was completed.
SPSS version 27.0 (SPSS Inc., Chicago, IL, USA) was employed for
statistical analyses. The modified up-and-down sequential method and
probit analysis were used for the EC50 of REM with different
concentration of propofol. All data were tested for normality by Shapiro
test. The PSI, BIS, HR and MAP at each time were analyzed by using
repeated measures ANOVA. Characteristics data of the patients, surgery,
anesthesia and postoperative data among groups using one-way analysis of
variance (ANOVA) for continuous variables. When a difference in
proportions was found among the groups, and a Least Significance
Difference or Tamhane T2 was made for multiple comparisons. ROC curve
was used to compare the sensitive of PSI and BIS. P < 0.05 was
regarded as a statistical difference.
Quantitative data were perfomed as
the mean (standard deviation) (SD), median [Min, Max], or number
(n).