Series Study on the Application of G Protein-Biased Receptor Agonist Oliceridine in Gynecological Surgery (2)：Effects of Oliceridine Versus Sufentanil on Postoperative Nausea and Vomiting After Gynecological Laparoscopic Surgery
Phase: PHASE4
Conditions: Gynecologic Surgical Procedures, Postoperative Nausea and Vomiting (PONV), Laparoscopy
Sponsor: YanYing Xiao

The Second Xiangya Hospital of Central South University 
(Investigator-initiated) Clinical Research Protocol 
(Protocol Version Number: 3.2; Protocol Version Date: 2024.12.11) 
 
Project Title: Series Study on the Application of G Protein-Biased Receptor 
Agonist Oliceridine in Gynecological Surgery Based on ERAS Principles (2): Effects 
of Oliceridine Versus Sufentanil on Postoperative Nausea and Vomiting After 
Gynecological Laparoscopic Surgery  
Sponsor: None 
Initiating Institution: The Second Xiangya Hospital of Central South 
University 
Leading Unit Information: Single-center 
Research Nature/Type: Interventional/Randomized Controlled Clinical Trial 
Principal Investigator: Wang Yaping/Professor；Xiao Yanying/Attending 
Physician 
Application Specialty: Anesthesiology 
 
The Second Xiangya Hospital of Central South University 
 
 
 

 
1. Research Background and Rationale 
Postoperative nausea and vomiting (PONV) is a common complication following 
surgery. Reports indicate that the incidence of PONV is 30% among all postoperative 
patients and can reach up to 80% in high-risk patients. Well-established risk factors 
for increased PONV include female sex, age under 50 years, non-smoking status, and 
a history of PONV or motion sickness [1, 2]. PONV not only diminishes patients’ 
well-being, but may also result in severe consequences such as dehydration, 
electrolyte imbalance, wound dehiscence, and regurgitation with aspiration. These 
complications can lead to delayed recovery, unplanned hospital admission, and 
postponed return to work. Such outcomes are associated with prolonged recovery 
room stay, delayed discharge, and increased healthcare costs [3-5]. Procedures such as 
laparoscopy, gynecological surgery, and operations of longer duration are also 
associated with an increased incidence of PONV. Similarly, the use of general 
anesthesia and postoperative administration of opioid drugs contribute to a higher 
incidence of this complication [6, 7]. 
It is well established that conventional opioid drugs increase the risk of PONV in 
a dose-dependent manner [8]. Although the exact mechanisms by which opioid drugs 
cause nausea and vomiting are not yet fully understood, multiple mechanisms may be 
involved [9]. At the cellular level, traditional opioid agonists bind to the MOR and 
stimulate G protein signaling to produce analgesia, while activation of the β-arrestin 
pathway leads to adverse effects related to respiratory and gastrointestinal function 
[10]. In preclinical studies, β-arrestin-2 gene knockout mice treated with morphine 
exhibited enhanced analgesic effects and reduced respiratory depression and 
gastrointestinal dysfunction compared with wild-type animals treated with morphine 
[11, 12]. 
Oliceridine is a new generation intravenous opioid drug and a G protein-selective 
agonist. Oliceridine was approved for marketing in China in May 2023. In two 
randomized, double-blind, placebo- and morphine-controlled phase 3 pivotal studies, 
oliceridine provided rapid and effective analgesia with a favorable safety profile [13, 
14]. In these two studies, the incidence of nausea in the 0.1 mg (40%) and 0.35 mg 
(59%) demand dose groups was lower than that in the morphine 1 mg group (70%), 
with the relative risk in the 0.1 mg demand dose group being 43% (P<0.001). The 
incidence of vomiting for oliceridine at three different required doses—0.1 mg (20%), 

0.35 mg (30%), and 0.5 mg (42%)—was lower than that reported for morphine 1 mg 
(52%), with the relative risk for the 0.1 mg and 0.5 mg doses significantly reduced by 
41%–61% (P < 0.001) [15, 16]. Hammer et al. [23] performed an exploratory analysis 
of these two trial datasets, defining the absence of vomiting and the non-use of rescue 
antiemetic medications as 'complete gastrointestinal response' as a composite endpoint. 
The analysis demonstrated that, compared to morphine, oliceridine achieved a 2–3-
fold higher rate of 'complete gastrointestinal response' [16]. 
Gynecological surgical procedures predominantly involve the pelvic and 
abdominal cavities. Intraoperative mechanical traction and compression of pelvic and 
abdominal organs readily stimulate the vagus nerve and visceral afferent nerves, 
resulting in the release of central neurotransmitters that trigger PONV. It is 
noteworthy that with the widespread adoption of gynecological laparoscopic surgery, 
intraoperative pneumoperitoneum and the Trendelenburg position can increase intra-
abdominal pressure, stimulating gastrointestinal emetic receptors and inducing PONV 
[17]. 
Oliceridine demonstrates safe and effective analgesic properties, with a marked 
advantage in gastrointestinal tolerability, which may support its rational application in 
gynecological surgery. This also constitutes the rationale for our research. However, 
oliceridine has only recently been introduced to the market, and there remains a lack 
of robust clinical evidence regarding its use in general anesthesia. Therefore, this 
study is designed as a randomized controlled trial, using sufentanil—a commonly 
used opioid drug in clinical practice—as the control, to compare the incidence of 
postoperative nausea and vomiting (PONV) following gynecological laparoscopic 
surgery. 
2. Research Objectives 
To explore the effects of oliceridine versus sufentanil on postoperative nausea 
and vomiting after gynecological laparoscopic surgery. 
3. Research Protocol and Plan 
3.1 Study Design 
This study is a randomized, double-blind, parallel-controlled clinical trial to be 
conducted in the Department of Anesthesiology at the Second Xiangya Hospital of 
Central South University. Prior to initiation, the study will be approved by the 
hospital's medical ethics committee, and informed consent will be obtained from 
patients or their families. Patients will be randomized according to a computer-

generated randomization sequence into the sufentanil group and the oliceridine group. 
The sufentanil group will receive sufentanil for both anesthesia and postoperative 
analgesia, while the oliceridine group will receive oliceridine for both anesthesia and 
postoperative analgesia. Group allocation results are delivered to the anesthesia nurse 
using the sealed envelope method. Based on the study design and allocation, injection 
solutions with identical appearance and volume are prepared and provided to the 
attending anesthesiologist. The anesthesia nurse responsible for drug preparation does 
not participate in patient recruitment, randomization, data collection, or analysis. 
3.2 Study Population 
Inclusion criteria: Elective gynecological laparoscopic surgery; age 18–65 years; 
American Society of Anesthesiologists (ASA) physical status I–III; and body mass 
index (BMI) 18–30 kg/m². 
Exclusion criteria: Severe dysfunction of major organs such as the heart, lungs, 
or brain; history of allergy to opioid drugs, propofol, soybeans, or eggs; recent use of 
sedatives, analgesics, or monoamine oxidase inhibitors; history of alcohol abuse; 
obstructive sleep apnea syndrome; difficult airway; psychiatric or neurological 
disorders; communication disorders; or women who are lactating or pregnant. 
Withdrawal criteria: Subject requests withdrawal or withdraws voluntarily; 
change in surgical method requiring combined gastrointestinal surgery; occurrence of 
allergy to the investigational drug or life-threatening complications; or reoperation 
within 48 hours postoperatively due to bleeding or other factors. 
3.3 Group Allocation and Interventions 
Patients were randomly assigned to either the Sufentanil group or the Oliceridine 
group. No preoperative medications were administered. Upon entering the operating 
room, standard monitoring of ECG, SpO2, BP, and BIS was implemented, and 
intravenous access was established. Anesthesia induction: Sequential intravenous 
administration of midazolam 0.05–0.10 mg/kg, sufentanil 0.3 μg/kg (Sufentanil group) 
or oliceridine (0.06 mg/kg, based on the oliceridine injection package insert, where 1 
mg oliceridine is approximately equivalent to 5 mg morphine), and propofol.1.5~2.0 
mg/kg and cisatracurium besylate 0.2~0.3 mg/kg. Following intubation, both groups 
of patients underwent volume-controlled mechanical ventilation, with a tidal volume 
of 6~8 ml/kg, respiratory rate of 8~12 breaths/min, and an inspiratory-to-expiratory 
ratio of 1:2. Ventilation parameters were adjusted to maintain PCO2 at 35~40 mmHg 
(1 mmHg = 0.133 kPa). Prior to skin incision, patients received sufentanil 0.1–0.2 

μg/kg (Sufentanil group) or oliceridine 0.02–0.04 mg/kg (Oliceridine group). Total 
intravenous anesthesia was maintained intraoperatively with continuous infusion of 
propofol at 4–10 mg/kg/h and remifentanil at 0.1–0.2 μg/kg/min, along with 
intermittent intravenous injections of cisatracurium besylate 4 mg. Approximately 30 
minutes before the end of surgery, sufentanil 0.1 μg/kg (Sufentanil group) or 
oliceridine 0.02 mg/kg (Oliceridine group) was administered. 
Postoperative analgesia protocol: The Sufentanil group received 2 μg/kg 
sufentanil, and the Oliceridine group received 0.4 mg/kg oliceridine. Ondansetron 8 
mg and dexamethasone 10 mg were added to normal saline to a total volume of 100 
ml. The initial loading dose was 2 ml, with no background infusion. Each bolus dose 
was 2 ml, the lockout interval was 10 minutes, and the maximum dose was 10 ml/h. 
All enrolled patients were connected to the electronic analgesia pump immediately 
after surgery, and patients and their families received preoperative instruction on the 
use of the electronic analgesia pump. If postoperative pain could not be alleviated by 
the analgesia pump, the anesthesiologist administered rescue sufentanil 5 μg or 
oliceridine 0.2 mg as needed. If rescue therapy is ineffective, the anesthesiologist will 
determine alternative remedial measures and document the medications and dosages 
administered. If the patient develops PONV of grade 2 or above, a combination of 
ondansetron 4 mg and dexamethasone 5 mg will be administered intravenously. If 
symptoms are not alleviated after one hour, haloperidol 1 mg will be administered in 
combination. 
3.4 Outcome Measures and Follow-up Plan 
Primary outcome measure: Incidence of PONV within 48 hours postoperatively. 
PONV will be assessed within 48 hours postoperatively in the ward by a blinded 
investigator. Subjects are required to use the simplified PONV impact scale to report 
whether any PONV events occurred in the past 48 hours and to provide a rating. 
(Consisting of two questions: Q1. Have you experienced vomiting or symptoms 
of vomiting? If yes, how many episodes in total? Under what circumstances did it 
occur? Was any medication administered for treatment? Q2. Have you experienced 
nausea? If yes, did the sensation of nausea affect your daily activities? Was any 
medication administered for treatment?) Based on the number, frequency, and triggers 
of nausea and vomiting, the incidents are classified into four grades: absence of 
vomiting or nausea not requiring rescue treatment after onset is defined as complete 
remission; Mild PONV is defined as mild nausea or a single episode of vomiting 

induced by drinking water or physical activity. Moderate PONV is defined as two 
episodes of vomiting or significant nausea requiring rescue therapy. Severe PONV is 
defined as more than two episodes of vomiting or the need for more than one dose of 
rescue therapy. 
General patient data: including age, height, weight, BMI, ASA classification, 
smoking history, previous history of PONV, history of motion sickness, surgical 
history, history of hypertension, history of diabetes, among others. 
Intraoperative indicators: surgical method, surgical site, blood loss, operative 
duration, anesthesia duration, anesthetic dosage, infusion volume, and incidence of 
hypotension. 
Secondary outcome measures: 
1) Record the occurrence of PONV separately for four time periods (T1: PACU 
stay; T2: from departure from PACU to 12 hours postoperatively; T3: 12 to 24 hours 
postoperatively; T4: 24 to 48 hours postoperatively). Incidence of postoperative 
vomiting (POV) and POV scores during the four time periods (T1–T4) within 48 
hours after surgery. Record the use of rescue antiemetic medications. 
Postoperative analgesia assessment: Resting visual analog scale (VAS) pain 
scores at four time points (T1–T4) within 48 hours after surgery, measured using a 10 
cm movable ruler with a numerical scale of 0–10 on the reverse side. The left end (“0”) 
indicates no pain, while the right end (“10”) represents unbearable severe pain. 
Record the number of PCA presses, total analgesic consumption, and the use of rescue 
analgesics within 48 hours after surgery. 
Ramsay sedation score at 2 hours postoperatively: a score of 1 indicates agitation, 
3 or 4 indicates somnolence, and 5 or 6 indicates excessive sedation. 
Sleep quality score on the night after surgery: Patient sleep quality will be 
assessed using a numerical rating scale based on an 11-point Likert scale, ranging 
from 0 to 10. A score of 0 indicates complete insomnia and extremely poor sleep 
quality, while a score of 10 represents excellent sleep quality. Severe insomnia is 
defined as a score of 0–3, moderate insomnia as 4–6, and good sleep quality as 7–10.  
QOR-15 score: A score of 0 indicates extremely poor quality of recovery, while a 
score of 150 indicates excellent quality of recovery. Assessments will be conducted 
preoperatively, on postoperative day 1, and on postoperative day 3. 
Length of stay in the recovery room, time to first postoperative bowel movement, 
time to resumption of oral intake, time to first postoperative feeding, time to first 

postoperative ambulation, and any other adverse events. 
3.5 Statistical Analysis Plan 
Sample size calculation: The primary outcome is the incidence of PONV within 
48 hours postoperatively, and the sample size will be calculated based on this primary 
endpoint. According to the study by Zhao et al., the incidence of PONV within 48 
hours after gynecological laparoscopic surgery is 71.7%. It is expected that the 
incidence of PONV will be reduced by at least 40%. Assuming α = 0.05 and a power 
of 80%, PASS 15 software was used to calculate a sample size of N = 45 per group. 
Considering a 5% dropout rate, a total of 48 patients per group will be enrolled, 
requiring 96 subjects in total. 
Statistical analysis was conducted using SPSS 26.0. Normally distributed 
continuous data were expressed as mean ± standard deviation (mean ± SD), and 
between-group comparisons were performed using the independent samples t-test. 
Non-normally distributed continuous data were expressed as median (M) and 
interquartile range (IQR), and between-group comparisons were performed using the 
Wilcoxon rank-sum test. Repeated measures data were analyzed using repeated 
measures analysis of variance or the generalized estimating equation model, 
according to the distribution characteristics of the data. Categorical data were 
expressed as rates or percentages, and comparisons were performed using the χ2 test 
or Fisher's exact test. Ordinal data were analyzed using the rank-sum test. Subgroup 
analyses will be performed based on operative duration (≤2h or >2h), smoking status 
(non-smoker or history of smoking within the past six months), history of 
chemotherapy, age (≤50 or >50), and BMI (18-25 or 25-30), using logistic regression 
analysis. A P value <0.05 will be considered statistically significant. 
4. Data Management and Quality Control 
All drugs and materials used in the clinical research must be subjected to quality 
control. Researchers or relevant medical management authorities are entitled to audit 
the clinical research to ensure the authenticity of recorded data and compliance with 
the clinical research protocol. 
This study is an investigator-initiated clinical trial and will adhere to the 
standards and requirements of the Good Clinical Practice (GCP) guidelines and ICH-
GCP regulations. At the project initiation stage, the principal investigator is 
responsible for designing and developing the study protocol, case report forms, and 
other relevant documents, and will submit the necessary application materials for 

project approval in accordance with the requirements of the hospital's administrative 
office. After obtaining the project number from the institutional office, the project 
materials will be submitted to the Ethics Office for ethical review. Upon completion 
of the ethical review, the project will be registered with the administrative office in 
preparation for implementation. 
During the implementation of the project, all researchers participating in the trial 
will obtain GCP qualification certificates. Researchers shall conduct the clinical trial 
in accordance with relevant Chinese GCP, ICH-GCP, and related SOPs. During 
project quality management, the principal investigator authorizes the quality control 
officer to conduct monthly project quality control, completing the 'Clinical Trial 
Quality Control Checklist for Project Teams' to ensure that the clinical trial is 
conducted in accordance with GCP and protocol requirements. Upon completion of 
the project, the principal investigator shall issue a formal 'Project Closure Letter' to 
the Ethics Office and the institutional office. At project conclusion, the principal 
investigator is responsible for organizing and preserving the research data. A hard 
copy of the 'Study Completion Report' shall be submitted to the Ethics Office, and the 
principal investigator shall be responsible for the authenticity of the report. 
5. Risks and Benefits 
The oliceridine package insert clearly indicates that it is approved for the 
treatment of acute pain in adult patients severe enough to require intravenous opioid 
drugs. As intraoperative pain in adult gynecological surgery necessitates the use of 
opioid drugs for management, the application of oliceridine injection for acute pain in 
gynecological surgery is consistent with the approved indications. Oliceridine not 
only provides safe and effective analgesia, but also offers significant advantages in 
gastrointestinal tolerability. Currently, this drug has been successfully tendered and 
stocked in our hospital pharmacy, enabling its rational application in gynecological 
surgery and thereby improving perioperative comfort for gynecological patients. 
The social benefits and subject gains from this study are reflected in the 
following aspects: 
Social benefits: 
(1) Improvement of patients' postoperative experience: By effectively controlling 
postoperative pain and reducing severe vomiting, this approach can significantly 
enhance overall patient satisfaction, shorten hospital stays caused by pain and 
vomiting, and reduce the consumption of medical resources. 

(2) Promotion of clinical drug innovation: This study will provide scientific 
evidence for the clinical application of oliceridine, facilitate the broader adoption of 
new-generation opioid drugs in the field of gynecology, and offer patients safer and 
more effective analgesic regimens. 
(3) Promotion of medical research and development: This study will facilitate 
further exploration of opioid drugs in various types of surgical procedures, 
enhance understanding of the safety and efficacy of anesthetic agents, and 
promote advances in anesthesiology and related fields. 
Benefits to Subjects 
(1) Economic benefit: Subjects will be exempted from perioperative 
anesthesiology pain assessment fees (clinical scale), valued at 36 yuan. 
Effective analgesia management: Subjects participating in this study will receive 
oliceridine, which may provide superior analgesic effects, improve postoperative 
recovery quality, and reduce postoperative discomfort. 
(2) Reduction of severe vomiting: This study aims to evaluate the efficacy of 
oliceridine in reducing postoperative severe vomiting, which is critical for 
postoperative recovery and can enhance patients' quality of life. 
(3) Participation in cutting-edge research: Subjects will have the opportunity to 
take part in advanced medical research, providing real-world clinical data for the 
application of new medications and contributing to future medical progress. 
6. Safety Assessment and Risk Management Measures 
According to the procedures for handling emergency medical adverse events 
during the subject’s hospitalization (including the ICU period): 
(1) When a subject experiences harm or an unexpected event, medical staff 
should immediately report to the resident physician or on-duty physician. The resident 
physician or on-duty physician should implement appropriate emergency measures 
based on the patient's condition and immediately notify the discipline lead and 
principal investigator (the discipline lead and principal investigator may be the same 
individual), as well as the assistant researcher (authorized by the principal investigator 
and holding the title of attending physician or above). Upon receiving the report, the 
discipline lead, principal investigator, and assistant researcher should personally 
participate or assign a senior physician to assist in managing the situation in the ward 
within 15 minutes. If the situation is extremely critical, it may be necessary to 
coordinate with anesthesiologists and ICU physicians for resuscitation. 

(2) While managing the event, the resident physician or on-duty physician must 
ensure that the clinical trial investigator records the subject's symptoms, severity, time 
of onset, duration, interventions, and clinical course in the medical record and 
observation form within 12 hours. (3) The principal investigator or assistant 
researcher must report the emergency medical adverse event to the secretary of the 
drug clinical trial institution office within 12 hours, and, if necessary, may report 
directly to the institution director or office director. 
(4) The investigator may decide to terminate trial observation based on the 
subject's condition, or adjust the trial medication dosage only/ temporarily suspend 
the study. In the event of a serious adverse event or important adverse event requiring 
emergency unblinding, the investigator shall immediately notify the sponsor and the 
institutional quality control officer, perform unblinding in accordance with the 
protocol requirements and unblinding SOP, and document the unblinding process in 
detail. 
Subjects who experience a serious adverse event shall be observed and followed 
until symptoms, signs, and relevant laboratory tests return to normal, and the relevant 
departments shall be notified within 24 hours in accordance with GCP and protocol 
requirements. In the event of a medical dispute or related tendency, refer to the 
Emergency Plan for Hazards to Hospital Public Order of The Second Xiangya 
Hospital of Central South University. 
 
References: 
[1] Fourth Consensus Guidelines for the Management of Postoperative Nausea 
and Vomiting: Erratum [J]. Anesth Analg, 2020, 131(5): e241. 
10.1213/ane.0000000000005245  
[2] Habib AS, Chen YT, Taguchi A, et al. Postoperative nausea and vomiting 
following inpatient surgeries in a teaching hospital: a retrospective database analysis 
[J]. Curr Med Res Opin, 2006, 22(6): 1093-1099. 10.1185/030079906x104830 
[3] Andrew BY, Holmes R, Taicher BM, et al. The Association of Guideline-
Directed Prophylaxis With Postoperative Nausea and Vomiting in Adult Patients: A 
Single-Center, Retrospective Cohort Study [J]. Anesth Analg, 2024. 
10.1213/ane.0000000000006855  
[4] Apfel CC, Korttila K, Abdalla M, et al. A factorial trial of six interventions 
for the prevention of postoperative nausea and vomiting [J]. N Engl J Med, 2004, 

350(24): 2441-2451. 10.1056/NEJMoa032196  
[5] Zhu H, Wang S, Wang R, et al. Effect of dexmedetomidine on postoperative 
nausea and vomiting in female patients undergoing radical thoracoscopic lung cancer 
resection [J]. Front Pharmacol, 2024, 15: 1353620. 10.3389/fphar.2024.1353620  
[6] Gan TJ, Belani KG, Bergese S, et al. Fourth Consensus Guidelines for the 
Management of Postoperative Nausea and Vomiting [J]. Anesth Analg, 2020, 131(2): 
411-448. 10.1213/ane.0000000000004833  
[7] Xue FS, Su K, Cheng Y. Opioid-free anaesthesia reduces postoperative 
nausea and vomiting after thoracoscopic lung resection. Comment on Br J Anaesth; 
132: 267-76 [J]. Br J Anaesth, 2024, 132(4): 827-828. 10.1016/j.bja.2024.01.022  
[8] Roberts GW, Bekker TB, Carlsen HH, et al. Postoperative nausea and 
vomiting are strongly influenced by postoperative opioid use in a dose-related manner 
[J]. Anesth Analg, 2005, 101(5): 1343-1348. 10.1213/01.ane.0000180204.64588.ec
 
 
[9] Smith HS, Smith JM, Seidner P. Opioid-induced nausea and vomiting [J]. 
Ann Palliat Med, 2012, 1(2): 121-129. 10.3978/j.issn.2224-5820.2012.07.08  
[10] Rankovic Z, Brust TF, Bohn LM. Biased agonism: An emerging paradigm 
in GPCR drug discovery [J]. Bioorg Med Chem Lett, 2016, 26(2): 241-250. 
10.1016/j.bmcl.2015.12.024  
[11] Raehal KM, Walker JK, Bohn LM. Morphine side effects in beta-arrestin 2 
knockout mice [J]. J Pharmacol Exp Ther, 2005, 314(3): 1195-1201. 
10.1124/jpet.105.087254  
[12] Bohn LM, Lefkowitz RJ, Gainetdinov RR, et al. Enhanced morphine 
analgesia in mice lacking beta-arrestin 2 [J]. Science, 1999, 286(5449): 2495-2498. 
10.1126/science.286.5449.2495 
 
[13] Viscusi ER, Skobieranda F, Soergel DG, et al. APOLLO-1: a randomized 
placebo and active-controlled phase III study investigating oliceridine (TRV130), a G 
protein-biased ligand at the µ-opioid receptor, for management of moderate-to-severe 
acute pain following bunionectomy [J]. J Pain Res, 2019, 12: 927-943. 
10.2147/jpr.s171013  
[14] Singla NK, Skobieranda F, Soergel DG, et al. APOLLO-2: A Randomized, 
Placebo and Active-Controlled Phase III Study Investigating Oliceridine (TRV130), a 
G Protein-Biased Ligand at the μ-Opioid Receptor, for Management of Moderate to 
Severe Acute Pain Following Abdominoplasty [J]. Pain Pract, 2019, 19(7): 715-731. 

10.1111/papr.12801  
[15] Beard TL, Michalsky C, Candiotti KA, et al. Oliceridine is Associated with 
Reduced Risk of Vomiting and Need for Rescue Antiemetics Compared to Morphine: 
Exploratory Analysis from Two Phase 3 Randomized Placebo and Active Controlled 
Trials [J]. Pain Ther, 2021, 10(1): 401-413. 10.1007/s40122-020-00216-x  
[16] Hammer GB, Khanna AK, Michalsky C, et al. Oliceridine Exhibits 
Improved Tolerability Compared to Morphine at Equianalgesic Conditions: 
Exploratory Analysis from Two Phase 3 Randomized Placebo and Active Controlled 
Trials [J]. Pain Ther, 2021, 10(2): 1343-1353. 10.1007/s40122-021-00299-0 
 
[17] Zhao K, Gao Y, Zhang J, et al. Penehyclidine for Prevention of 
Postoperative Nausea and Vomiting in Patients Undergoing Gynecological 
Laparoscopic Surgery Under Combined Intravenous and Inhalation Anesthesia: A 
Randomized, Double-Blind, Placebo-Controlled Trial [J]. Drug Des Devel Ther, 2024, 
18: 685-697. 10.2147/dddt.s453327