Apr 21, 2025

Public workspaceComparison of pre-treatment with different diluted sufentanil in reducing propofol injection pain in gastrointestinal endoscopy: a randomized controlled study

DOI
dx.doi.org/10.17504/protocols.io.14egn4mwmv5d/v1
  • Qian Su1,
  • Shu He2,
  • Lu Li1,
  • Xiangqing Wei1,
  • Xin Sun1,
  • Xuefeng Yang1,
  • Boxiang Du1,
  • Lei Yao1
  • 1Department of Anesthesiology, Affiliated Hospital 2 of Nantong University;
  • 2Department of Epidemiology and Biostatistics, School of Public Health, Nantong University
Lei Yao
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DOI: dx.doi.org/10.17504/protocols.io.14egn4mwmv5d/v1
Protocol Citation: Qian Su, Shu He, Lu Li, Xiangqing Wei, Xin Sun, Xuefeng Yang, Boxiang Du, Lei Yao 2025. Comparison of pre-treatment with different diluted sufentanil in reducing propofol injection pain in gastrointestinal endoscopy: a randomized controlled study. protocols.io https://dx.doi.org/10.17504/protocols.io.14egn4mwmv5d/v1
License: This is an open access protocol distributed under the terms of the Creative Commons Attribution License,  which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Protocol status: Working
We use this protocol and it's working
Created: April 19, 2025
Last Modified: April 21, 2025
Protocol Integer ID: 131003
Keywords: Sufentanil, Propofol-induced pain, Diluted, Adverse events
Funders Acknowledgements:
The Health Commission of Nan-tong City Health and Family Planning Scientific Research Projects
Grant ID: QNZ2023026
The Health Commission of Nan-tong City Health and Family Planning Scientific Research Projects
Grant ID: MS2024033
Nantong Municipal Science and Technology Scientific Research Projects
Grant ID: MSZ2024097
Disclaimer
  1. Accuracy Limitation This protocol describes methods that worked in our specific experimental conditions. Variations in reagents, equipment, or operator techniques may affect results. Users should validate critical steps with pilot experiments.
  2. Liability Exclusion The authors disclaim responsibility for any damage to equipment, loss of biological materials, or invalid data arising from protocol implementation.
  3. Intellectual Property Commercial use requires prior written authorization. Academic users may modify the protocol but must cite the original version (DOI: ).
  4. Ethical Compliance For human subject research: This protocol was approved by The Second Affiliated Hospital of Nantong University Ethics Committee (Reference: 2023KT006).
Abstract
Background: This study aimed to investigate the efficacy of pre-treatment with different concentrations of sufentanil in mitigating propofol injection-induced pain.
Methods: In total, we randomly divided 421 patients who were scheduled for gastrointestinal endoscopy into four groups. Group A received 5 μg of sufentanil (1 ml, 5 µg/ml). Group B received 5 μg of sufentanil (5 ml, 1 µg/ml). Group C received 5 μg of sufentanil 10 ml (0.5 µg/ml). The control group received 10 ml of 0.9% normal saline.
Expected Results:  Compared to the control group, other groups showed significantly reduced pain after propofol injection ,especially the group B . Compared to the control group, group B had significantly lower rates of cough, hypotension, and dizziness.
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Materials
Selection of Patients  Inclusion criteria —   18–65 years old, —   ASA  physical status I or III, —   Body mass index (BMI) <30 kg/m2, —   Scheduled for same-visit bidirectional endoscopy.  Exclusion criteria —    Patients with severe respiratory, cardiovascular, neurological, hepatic or renal disease (ASA physical status IV and V). —    Patients who were allergic to propofol or sufentanil. —    Patients with a preoperative assessment of difficult airway or BMI ≥30kg/m2.  —    Patients who were suffering chronic pain or long-term taking analgesic drugs. —    Patients who were punctured larger antecubital vein. —    Patients who needs to undergo endoscopic polyp treatment or a diagnostic ultrasound gastroscopy. —    Patients who decline to participate[8]. —    Patients with bradycardia. Preliminary Experimental Results We recruited 80 patients and randomly allocated them in a 1:1:1:1 ratio to four groups according to a computer-generated randomization schedule. The pain relief rates (including no pain and mild pain) for the four groups were 70%, 85%, 90%, and 85%, respectively (as shown in Table 1). Table 1 Preliminary Experiment
Degree of Pain,n(%) Normal Saline Group(n=20)5 µg/mlSF Group(n=20)1 µg/mlSF Group(n=20)0.5 µg/mlSF Group(n=20)
None(0 point)*8（40%）13(65%)14(70%)12(60%)
Mild  pain(1 point)6(30%)4(20%)4(20%)5(25%)
Moderate pain(2 point)4(20%)2(10%)2(10%)2(10%)
Severe pain2(10%)1(5%)0(0%)1(5%)
(3 point)
Pain relief rate(NRS≤1)14(70%)17(85%)18(90%)17(85%)
* The degree of pain was assessed through the Numerical Rating Scale (NRS) with a 3-point system: 0 for no pain, 1 for mild pain, 2 for moderate pain, and 3 for severe pain. SF: Sufentanil Pain relief rate: This metric indicates the proportion of patients achieving an NRS score of 0 or 1, indicating those who experience significant pain alleviation. Statistical Plan Sample size The study was conducted using the Chi-Square Tests function in the PASS I5.0 software to determine the sample size.The degrees of freedom for the test were 9, with a Type I error rate of 0.05, a two-sided test, and a Type II error rate of 0.2.According to the results of preliminary experiment,the effect size (W value) was set at 0.1974, resulting in a required sample size of 402. Taking into account a dropout rate of 15%, a total of 464 participants were included, with 116 participants in each group. Statistical analysis Statistical analysis was executed using SPSS 24.0 and PASS 15.0.Measurement data that conforms to the gaussian distribution were presented as mean±SD, and categoric-al data were expressed by the number of cases or the percentage(%).Continuous data were analyzed using one-way analysis of variance.Categorical data were analyzed using the Chi-square tests or Fisher’s exact test,and Z test was used for further comparison between two groups.One-way ANOVA was used for comparison between multiple groups, and LSD-t test was used for further comparison between two groups.The numerical scoring of pain(NRS)  were compared among the four groups using Kruskal-Wallis Test.All Pairwise test was used for further comparison between two groups.All statistical tests are 2-tailed; the corrected differences were considered significant at P < 0.05.

 Randomization and blinding
The randomization schedule was generated by EpiCalc 2000 software. Patients were randomly allocated in a 1:1:1: 1 ratio to four groups according to a computer-generated randomization schedule.Each patient was given a unique ID number and their data was collected for analysis after being de-identified.
In this study, the drug preparation process was blinded by "envelope" method.Based on the randomization sequence inside the envelopes, a nurse prepared three different concentrations of sufentanil(Yichang Humanwell Pharmaceutical Co., China) by diluting it with a 0.9% saline solution for use in various groups during the trial: 5ug/ml for group A (1 ml total), 1ug/ml for group B (5 ml total), and 0.5ug/ml for group C (10 ml total).Control group received 10 ml of 0.9% normal saline.20ml of 1% propofol was available from Liaoning Haisco Pharmaceutical Co., China.Patients and researchers (gastroenterology  physicians  and anesthetists) were blinded to group allocation.
In case of an emergency (e.g., unexpected rapid deterioration in the patient’s clinical status), attending anesthesiologists or endoscopists could request unmasking of the treatment allocation, or adjust drug administration if necessary. To maintain the overall    quality, legitimacy, and integrity of the clinical trial, unblinding of the test drug may occur only in critical circumstances when severe adverse events happen and considered to be related tosufentanil administration. In this circumstance, the PI. fully documents and explains the reasons for unblinding in a report to the Institutional Review Board (IRB).
 Study interventions
On arrival at the examination room, a 07-model intravenous infusion needle (specification parameter 0.7mm×25mm)was inserted into a vein on the dorsum of the patient’s right hand.All patients will receive supplemental oxygen at a flow of 3 L/min through a nasal cannula.Monitoring included pulse oximetry, ECG (lead II), and noninvasive blood pressure.The intravenous medication process is completed by two individuals.After one anesthesiologist (who was blinded to group allocation) administered the pretreatment drug 30 seconds later, the other anesthesiologist subsequently administered intravenous 1% propofol ( initial dose of 2.5 mg/kg) to the patients at a rate of 0.5ml/sec.A supplement dose of propofol was carried out at a dose of 0.5 mg/kg[20] if patients involuntarily moved during the examination.The administration of pharmaceutical agents to patients with over weigh(defined as BMI≥ 25kg/m2 )was  according to lean body weight(LBM)[21-22].The anesthesiologist was required to inquire the patients about the degree of pain every 5 seconds,using a Numerical Rating Scale (NRS) with a 3-point system: 0 for no pain, 1 for mild pain, 2 for moderate pain, and 3 for severe pain[23].In the case of desaturation or unplanned low blood pressure,physicians could elevate the man-dible or use ephedrine (6mg iv.) as rescue therapy.During the gastrointestinal endoscopy, any adverse events were recorded (e.g. hypoxia,cough,hypotension, bradycardia, dizziness nausea and vomiting).
Adverse events were defined in a procedures manual. These events were chosen because they required skilled intervention and/or had significant patient or health service implications:
1.Hypoxia:oxygen saturation <90% and requiring sustained jaw thrust and/or increased oxygen flow[24].
2.Cough was defined as a sudden enhancement of expiratory airflow accompanied by typical cough sound during endoscopy examination,instead of drug-induced cough[25].
3.Hypotension was defined as systolic blood pressure (SBP) < 90 mmHg, a mean arterial pressure < 65 mmHg, or an SBP decrease > 40 mmHg from baseline during the painless  gastrointestinal endoscopy[26].
4.Bradycardia was defined as a heart rate less than 60 beats per minute during continuous heart monitoring[27].
5.Dizziness was defined as an unpleasant disturbance of spatial orientation or to the erroneous perception of movement [28].
6.Nausea and vomiting were defined as patients experiencing nausea or vomiting within 24 hours after painless  gastrointestinal endoscopy[29].
Expected results
Objective(s)Endpoint(s)
Primary Objective(s)The primary objective of this study aims at evaluating the effects of pretreatment of multiple diluted sufentanil on the severity of POPI.Endpoint(s) for primary objective(s)After administered the pretreatment drugs and propofol,the anesthesiologist was required to inquire the patients about the degree of pain every 5 seconds,using a Numerical Rating Scale (NRS) with a 3-point system: 0 for no pain, 1 for mild pain, 2 for moderate pain, and 3 for severe pain.
Secondary Objective(s)Endpoint(s) for secondary objective(s)
Secondary objectives are to compare the recovery time , total propofol consumption and adverse events among groups.     The recovery time is defined as:After the endoscopy, the researcher observe and recorde the time for patients from consciousness to self-opening eyes.Total propofol consumption is defined as After the examination, the researcher records the total amount of propofol used.The adverse events includes hypoxia,cough,hypotension, bradycardia, dizziness nausea and vomiting.
Ethics declarations 
The Ethics Committee of  The Affiliated Hospital 2 of  Nantong University will assess the  protocol and the written and dated approval signed by the Ethics Committee chairman will
be obtained. The study will be registered at the Chinese Clinical Trial Registry
(www.chictr.org.cn). This study will be conducted in accordance with the principles laid
down by the World Medical Assembly and all applicable amendments (Helsinki, 1964) and
the ICH guidelines for Good Clinical Practice. This clinical trial will be conducted in
compliance with international laws and regulations, and laws and regulations of China, as
well as any applicable guidelines.
Supporting information
Due to privacy protections, the raw data contains sensitive information, including the patient's hospitalization number, name, surgery date, and other details. Interested authors can apply to our hospital's ethics committee to obtain the original data.The contact person is Dr. Hongqing Xu , who can be reached at xuhongqing000@126.com and +86 159 5131 2678.
Comparison of pre-treatment with different diluted sufentanil in reducing propofol injection pain in gastrointestinal endoscopy: a randomized controlled study
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Acknowledgements
The authors express profound gratitude to Dr. Ge Zhenming, Chief Physician and Deputy Director of the Department of Gastroenterology, for personally conducting gastrointestinal endoscopies for every enrolled patient with meticulous technique and unwavering dedication. We also extend our heartfelt thanks to Nurses Gu Yongping and Zhang Chunhua for their exceptional clinical support. Their expertise in performing peripheral intravenous catheterization for enrolled patients and their dedicated monitoring during the post-anesthesia recovery period were instrumental in facilitating efficient study procedures and ensuring patient safety throughout the trial.