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A randomized controlled trial to compare the effect of oxycodone and sufentanil on postoperative analgesia and immune function for laparoscopic resection of colorectal cancer

BMC Anesthesiology volume 25, Article number: 58 (2025) Cite this article

Abstract

Background

The purpose of this study is to evaluate the effect of oxycodone and sufentanil on postoperative analgesia and immune function in patients with laparoscopic resection of colorectal cancer (CRC), as well as the serum level of inflammatory cytokine.

Methods

40 patients from August 2023 to August 2024 in Shenzhen Nanshan Hospital undergoing laparoscopic resection of CRC were randomly divided into Group O (n = 20) and Group S (n = 20). The visual analog scale (VAS) score and serial blood samples were assessed during perioperative period. The primary outcomes were VAS scores and immune indicators (including IL-2, C3, C4, IgG, IgA, IgE, IgM, CD3+, CD4+, CD8+ and CD4+/CD8+) at 24 h and 72 h post-surgery at 24 h and 72 h after surgery. The secondary outcomes were inflammatory markers (including IL-4, IL-6, IL-10, TNF-a and INF-y) at 24 h and 72 h after surgery.

Results

The VAS scores at cough in Group O at 24 h and 72 h postoperative were lower than those in Group S (p < 0.001). No significant difference was found in VAS scores at rest between the two groups (P > 0.05). The immune indicators did not show significant changes after using oxycodone or sufentanil for patient-controlled intravenous analgesia (PCIA), respectively. There was no significant difference in inflammatory factors at 24 h and 72 h after surgery between the Group O and Group S.

Conclusion

Oxycodone is more effective than sufentanil in alleviating visceral pain, although it does not surpass sufentanil in managing cutting pain. In addition, there is no significant superiority in the effects of oxycodone on immune function and inflammatory cytokine release compared to sufentanil.

Trial registration

Chinese Clinical Trial Registry (ChiCTR2400089072).

Peer Review reports

Background

Colorectal cancer (CRC) is one of the most common malignancies with high attack incidence and mortality [1]. In 2023, the number of people suffering from CRC will exceed 150,000 and about 50,000 will died due to the disease in USA [2]. Laparoscopic tumor resection surgery is the effective treatment for CRC [3]. Postoperative pain, the common complication of laparoscopic surgery, can lead to adverse effects. Bum and coworkers have found that visceral pain is an important component of postoperative pain during laparoscopic surgery [4]. And postoperative pain can also trigger inflammatory reactions. Serum IL-6 is the sensitive inflammatory in stress response with positive correlation with postoperative analgesia [5], while serum IL-10 is an anti-inflammatory factor that can downregulate inflammatory responses and inhabit inflammatory mediators [6]. In addition, the impact of surgery and anesthesia on immune system cannot be ignored. Cancer patients are susceptible to external stimuli during perioperative period due to the suppressed state of immune function, resulting in the increase of cancer metastasis and postoperative mortality rate [7]. The hypothalamic–pituitary–adrenal axis and sympathetic nervous system will be activated during perioperative period, which leads to the release of specific lymphocyte-stimulating factors and the decrease of immune function. Furthermore, anesthetics can also affect the immune function of patients with malignant tumors, affecting the ability of cancer cells to invade, migrate, proliferate, and metastasize [8]. All strong opioids have immunosuppressive effects, which can reduce T cells and inhibit postoperative recovery.

Oxycodone, an agonist of mu and kappa opioid receptors, has been widely used for patient-controlled intravenous analgesia (PCIA) during laparoscopic surgery due to the outstanding effect in reducing visceral pain [9]. An and coworkers have found that patients with oxycodone for postoperative analgesia had lower numerical rating scale (NRS) of visceral pain at 2 h and 4 h after laparoscopic cholecystectomy surgery compared to the sufentanil group [10]. In addition, oxycodone can alleviate perioperative inflammatory response. Research has shown that oxycodone can significantly decrease the levels of TNF-α and IL-1β by lipopolysaccharide in rat [11] A study on laparoscopic gastrectomy has demonstrated that the administration of oxycodone for pain relief led to a reduction in serum IL-6 levels and an elevation in serum IL-10 levels at 6- and 24-h post-surgery [12]. Meanwhile, compared to other opioids with a hydroxyl group on both C3 and C6 in the molecular structure, oxycodone exhibited less immunosuppressive effects due to the carbonyl substitution on C6 especially for cancer patients [13]. Gene expression profiles indicated that morphine induced more immunosuppressive as compared to oxycodone in gynecological laparotomy patients [14]. Other studies comparing oxycodone with other opioid drugs have shown that oxycodone has less immunosuppressive effects [15,16,17]. However, there is currently no research about the effects of sufentanil and oxycodone on postoperative pain, immune function and inflammatory effects in patients undergoing laparoscopic resection of CRC.

In this study, 40 patients undergoing laparoscopic resection of CRC were included according to inclusion and exclusion criteria. We assessed the postoperative pain levels using VAS at 24 h and 72 h after surgery, evaluating the efficacy of oxycodone and sufentanil as patient-controlled intravenous analgesia (PCIA). The aim of this study is to provide more evidence for postoperative analgesia in clinical research.

Method

Ethical approval

This study was registered at Chinese Clinical Trial Registry (ChiCTR2400089072). The informed consents were obtained from patients before experiment. This manuscript adheres to the applicable Consolidated Standards of Reporting Trials (CONSORT) guidelines refer (Fig. 1).

Fig. 1
figure 1

CONSORT patient enrolment diagram. CONSORT, Consolidated Standards of Reporting Trials O: oxycodone; S: sufentanil

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Patient cohort

Patients were enrolled from August 2023 to August 2024 in Shenzhen Nanshan Hospital. The preoperative evaluation of participates was performed based on the preoperative assessment guidelines for adults undergoing elective noncardiac surgery from the European Society of Anaesthesiology and Intensive Care [18]. Inclusion criteria were: aged over 18 years old, American society of anesthesiologists (ASA) physical status 1 to 3, performed elective laparoscopic resection of CRC. Exclusion criteria were: non-compliant patients, patients with mental or cognitive impairments, patients with serious systemic diseases or uncontrolled chronic diseases, patients with autoimmune diseases or hematologic malignancies, patients with long-term use of sedatives or antidepressants, pregnant and lactating people.

Patient grouping and randomization

Forty patients undergoing laparoscopic resection of CRC were recruited. Participants were randomly allocated to oxycodone group (Group O) and sufentanil group (Group S) in a 1:1 ratio. Investigators (Chunmei Lin) used the computer to perform the block randomization, and then the mark was placed into sealed envelopes. Anesthesiologist (Zhiqiao Xu or Hong Wei) configured PCIA pump with oxycodone or sufentanil according to the mark in the envelope.

Procedures

After entering the operation room, all patients were under monitored, including electrocardiogram, saturation of peripheral oxygen (SpO2), invasive blood pressure, bispectral index (BIS). General anesthesia was performed for patients in both groups. Induction: 1.5 to 2.5 mg/ kg of propofol, 0.5 to 1ug/kg of sufentanil, 0.08 to 0.1 mg/kg of vecuronium. Maintenance: 1 to 2 mg/ (kg*h) of propofol, 1 to 2% of sevoflurane, 0.15 to 0.25ug/ (kg*min) of remifentanil, and 0.02 to 0.03 mg/kg of vecuronium. Mechanical ventilation was conducted after endotracheal intubation. Ventilator parameters were set as follows: tidal volume of 6 to 8 ml/kg, respiratory rate of 12 to 14 bpm, I/E ratio of 1:2, and end-tidal carbon dioxide pressure maintained at 35 to 45 mmHg. The depth of anesthesia was adjusted based on BIS and surgical stimulation during operation. Furthermore, tramadol was administered to prevent postoperative tremors, while palonosetron was used to prevent postoperative vomiting. Ropivacaine with concentration of 1% was used to local anesthesia for the incision at the end of the surgery. The PCIA pump: the group O was the combination of 1 mg/kg oxycodone and 10 mg tropisetron at the rate of 1 ml/h, while the group S was the combination of 1ug/kg sufentanil and 10 mg tropisetron at the rate of 2 ml/h. Based on expert consensus [19] and clinical experience, the continuous infusion rate of sufentanil for postoperative analgesia is 1-2ug/h. The potency of sufentanil is about 1000 times of oxycodone. In the pilot experiment, the continuous infusion rate of the PCIA pump in Group O was 2 ml/h, similar to the Group S, but the incidence of adverse reactions such as dizziness and nausea was high. Therefore, we changed the continuous infusion rate of the PCIA pump with oxycodone to 1 ml/h, which can achieve good analgesic effect and low incidence of adverse reactions.

In ward, all patients were ordered a standardized postoperative pain regimen. Pain scores were regularly examined by ward nurses. The patients primarily received intravenous infusion of PCIA, and were additionally administered intravenous tramadol 100 mg or flurbiprofen axetil 50 mg as supplementary analgesics, upon requesting additional pain relief or reporting pain levels exceeding VAS 4.

Data collection

The blood samples were centrifuged at 3000 g for 10 min to obtain serum, which was then separated and stored at −80 °C for further testing. According to the instruction manual, the counts of CD4+, CD8+, and CD3+ cells were measured by the flow cytometry (FACSLyric; USA), and then calculate ratio of CD4+/CD8+ T cells. In addition, inflammatory markers (including IL-4, IL-6, IL-10, TNF-a and INF-y) and IL-2 were also measured by flow cytometry (FACSLyric; USA). Other immune indicators (including C3, C4, IgG, IgA, IgE and IgM) were detected based on Scattering Nephelometry by protein analyzer (BNIIsystem, Germany). Moreover, the VAS of visceral pain at 24 h and 72 h after surgery were all recorded.

Statistical analysis

The SPSS25.0 software was applied to analyze collected data. In our study, mean ± standard deviation was used to describe continuous data, while number (%) to categorical data was performed. Besides, using t-test to analyze continuous data, and p value < 0.05 was considered as statistically significant.

Result

Forty-three patients with laparoscopic resection of CRC were screened in the study. 2 patients refused to participate the study, and 1 patient with hypertension had difficulty to control the blood pressure due to nervousness after entering the operating room. In the end, only 40 patients were included in the analysis (Fig. 1). There was no statistical difference in the patient characteristics between Group O and Group S (Table 1).

Table 1 Baseline Patient Characteristics and Perioperative Variables
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As shown in Table 2, the VAS scores for cough in Group O were lower than those in Group S at 24 h and 72 h after surgery (P < 0.01). However, there was no significant difference in VAS scores at rest between the two groups (P > 0.05), as shown in Table 3.

Table 2 Comparison of visceral pain VAS between the two groups
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Table 3 Comparison of incision pain VAS between the two groups
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As shown in Table 4, the serum concentration of IL-2 in group O was higher than that in group S at T2 (P < 0.05). The serum C3 and C4 concentrations were similar at T1 and T2 in Group O, and Group S showed the same trend of change. There was no statistical difference in serum C3 and C4 concentration at T1 and T2 between Group O and Group S (P > 0.05). After using oxycodone for PCIA, there was no significant change in serum lgA, lgE and lgM concentrations at T1 and T2, and Group S showed the same trend of change (P > 0.05). There was no statistical difference in serum lgA, lgE and lgM concentrations at T1 and T2 between Group O and Group S (P > 0.05). Compared to T0, the serum lgG concentration decreased at T1 (P < 0.05), but there was no significant change at T2 in Group O. There was no significant change in serum lgG concentration for S Group. At T2, the serum lgG concentration in Group O was higher than that in Group S(P < 0.05). Compared to the baseline level, the count of immune cells suggested that CD3+, CD4+ and CD8+ did not show significant changes at T1 and T2 whether in Group O or Group S (P > 0.05). And there was no difference between groups either (P > 0.05). Besides, no differences were observed in the ratios of CD4+/CD8+ T cells between groups or within groups (P > 0.05).

Table 4 Comparison of immune indicators between the two groups
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As shown in Table 5, there was no significant difference in serum IL-4, IL-6 and TNF-a concentrations at T1 and T2 between the two groups (P > 0.05). In Group O, the serum levels of IL-6 and TNF-a at T1 were higher than the baseline level, but decreased in T2 (P > 0.05), and Group S showed the same trend of change. In Group O, the IL-10 concentrations in T1 and T2 were lower than those in T0, but the difference was not statistically significant, while the IL-10 concentration in T1 was higher than that in T0 in group S (P < 0.05). The INF-y concentration at T1 and T2 were lower than those in T0 in O Group (P > 0.05), while the S Group showed the opposite trend.

Table 5 Comparison of inflammatory markers between the two groups
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Discussion

In the study, the results were found as follows: 1) The VAS scores of visceral pains for Group O at 24 h and 72 h after surgery were lower than those for Group S; 2) The serum lgG concentration at T1 was lower than that at T0 in Group O, and the serum lgG concentration in Group O was higher than that in Group S at 72 h after the surgery. Additionally, Group O exhibited a higher serum concentration of IL-2 at T2 compared to Group S. Other immune indicators including C3, C4, IgA, IgE, IgM, CD3+, CD4+, CD8+ and CD4+/CD8+did not show significant changes after using oxycodone or sufentanil for PCIA. 3) The IL-10 concentration in T1 was higher than that in T0 in group S. Other inflammatory factors including IL-4, IL-6, TNF-a and INF-y did not show significant changes after using oxycodone or sufentanil for PCIA.

Postoperative pain is a common perioperative complication that can have adverse effects on the patients, including atelectasis, pulmonary embolism, and sleep disorders [20]. It is important to choose appropriate analgesics for different types of pain [21]. For example, NSAID drugs can be used for inflammatory pain, opioids can be used for incision pain and visceral pain can be treated with oxycodone, while neuropathic pain can be treated with gabapentin or pregabalin. Oxycodone, a unique dual receptor agonist, has outstanding effects in reducing visceral pain on different types of surgeries, including laparoscopic surgery[22], laparotomy[23], thoracic surgery [24],and painless endoscopy operation[25]. Recent research has found that patients with oxycodone for postoperative analgesia had lower numerical rating scale (NRS) of visceral pain at 2 h and 4 h after laparoscopic cholecystectomy surgery compared to the sufentanil group [10]. In our study, we have found that oxycodone can significantly reduce pain, particularly in cancer patients, where it has been shown to improve pain management outcomes. visceral pains in patients at 24 h and 72 h after elective laparoscopic resection of CRC compared to sufentanil, which was consistent with the results of the previous study [10]. Peripheral κ-opioid receptors are considered as a potential target for reducing visceral pain [26]. Compared to sufentanil, oxycodone has a stronger affinity for peripheral κ-opioid receptors, so its inhibitory effect on visceral pain is significant. Oxycodone increases the threshold of visceral pain stimulation [27], thereby blocking peripheral pain signals and weakening the input of the central nervous system [26]. Numerous studies have shown that oxycodone can alleviate inflammatory reactions after surgery such as IL-6, TNF-α and IL-1β, which may be related to reducing visceral pain [11, 12]. Inflammatory mediators such as cytokines and prostaglandins can cause pain by stimulating visceral sensory nerves. In addition, inflammation can cause swelling, congestion, and spasms in internal organs, which can stimulate nerves, and then leading to pain [10].

T cells mainly mediate cellular immunity, while B cells mainly mediate humoral immunity. According to the different differentiation antigens on the cell surface, T cells can be divided into two subgroups: CD4+and CD8+ [15]. And B cells produce antibodies after receiving antigen stimulation. Both B cells and T cells express opioid receptors on their surfaces, and opioid drugs can bind to these receptors, affecting T cell differentiation and inhibiting B cell function. Many studies have revealed that opioid drugs have inhibitory effects on immune function [28] such as fentanyl, sufentanil, and morphine. On one hand, due to the impact of surgery and anesthesia on immune function, the use of opioid drugs during the perioperative period will further increase the risk of immune suppression [29]. On the other hand, opioid-induced immunosuppression has negative impact on the development of tumor [30]. Due to the specific molecular structure, the immunosuppressive function of oxycodone is limited [13]. Wan et al. revealed that administering oxycodone combined with flurbiprofen axetil as postoperative analgesia for CRC patients can reverse the status of immunosuppression [16]. Compared to pre injection, NK cells showed a decreasing trend at 0.5-, 6-, 12-, and 24-h after using oxycodone, but the rate of decrease was slower than that of the morphine group [15]. Wodehouse et al. evaluated the effects of morphine and oxycodone on the immune function of patients undergoing gynecological laparotomy, and proved that the activity of NK cells was suppressed by morphine, but maintained by oxycodone [14]. Recently, Chen et al. demonstrated that repeated intraperitoneal injections of oxycodone exceeding 20 mg/kg lead to a dose-dependent decrease in the count of CD4+ T cells, with little effect on CD8+ T cells [31]. In our study, we found that the serum lgG concentration at T1 was lower than that at T0 in Group O, and the serum lgG concentration in Group O was higher than that in Group S at 72 h after the surgery. Besides, the serum concentration of IL-2 in group O was higher than that in group S at T2. Other immune indicators including C3, C4, IgA, IgE, IgM, CD3+, CD4+, CD8+ and CD4+/CD8+ did not show significant changes after using oxycodone or sufentanil for PCIA. Undoubtedly, the immunosuppression may result in the enhancement of differentiation, metastasis and proliferation for tumor cells. This is very detrimental to cancer patients. Besides, cellular immune activity will be inhibited by all anesthesia methods. Hence, taking appropriate measures to develop individualized anesthesia and analgesia schemes is of great significance for protecting the perioperative immune function of cancer patients and improving their prognosis. IgG is the main component of immunoglobulin in serum, accounting for approximately 75% of immunoglobulin in serum. IgG is the most important antibody with functions of antiviral, neutralizing viruses, antibacterial, and immune regulation. The present results suggested that the serum lgG concentration in Group O was higher than that in Group S at 72 h after the surgery, which means that oxycodone may help to decrease the degree of immunosuppression compared to sufentanil. Moreover, IL-2 is an immunomodulator, which has antiviral, antitumor and immune enhancement effects. It can enhance the proliferation and killing activity of Cytotoxic T cells, natural killer cell and lymphokine activated killer cells, and can also promote the secretion of antibodies and interferon by lymphocytes. The results that oxycodone can promote the serum concentration of IL-2 at 72 h after the surgery but not sufentanil suggested it has a weakened immunosuppressive effect. However, we found that after using oxycodone for 24 h, the serum concentration of IgG decreased, which may be related to detection errors. In future clinical practice, using oxycodone as a postoperative intravenous analgesic can alleviate immune suppression, reduce the recurrence of disease and mortality rates, and shorten hospitalization time.

Currently, many articles have confirmed that oxycodone can alleviate inflammatory reactions [10, 12, 16, 32]. An and coworkers found that pre administration of oxycodone can alleviate inflammatory markers for forty patients undergoing laparoscopic cholecystectomy in 2019 [10]. Oxycodone combined with flurbiprofen axetil can reduce the serum level of TNF-α and IL-6 at 12-, 24-, 48-, and 72-h post-surgery in 2021 by wan and coworkers [16]. For patients undergoing laparoscopic resection surgery, oxycodone also has the effect of reducing inflammatory response [12]. In addition, oxycodone induced less inflammatory responses in patients undergoing laparoscopic gallbladder-preserving cholecystolithotomy compared with sufentanil [32]. However, Wang and coworkers found oral oxycodone can upregulate the levels of IL-2, IL-4, IL-6, IL-10, TNF-a, and IFN-y in patients with moderate to severe cancer pain [33]. In our study, we found that the IL-10 concentration in T1 was higher than that in T0 in group S. Other inflammatory factors including IL-4, IL-6, TNF-a and INF-y did not show significant changes after using oxycodone or sufentanil for PCIA. IL-10, an anti-inflammatory cytokine, can downregulate T lymphocyte activity and inhibit the activation, migration and adhesion of inflammatory cells. At the same time, IL-10 can also inhibit the synthesis and release of inflammatory factors. Our experimental results showed that the serum concentration of IL-10 increased with the use of sufentanil as PCIA for 24 h, which demonstrated that sufentanil has anti-inflammatory effects compared to oxycodone. The result was contrary to many current studies [10, 12, 16, 32]. More data is needed to prove this conclusion due to the small sample.

Different routes of administration of opioid drugs can have an impact on immune function. Beilin and coworkers revealed that immune suppression still existed in the PCIA group with morphine at 72 h after surgery, but the immune function of the PCEA group with morphine had recovered to preoperative levels [34]. Besides, Chen and coworkers found that oxycodone can inhibit immune function by intraperitoneal injection in mice [31]. In our experiment, we used sufentanil for anesthesia induction in Group O, which may increase the possibility of immune suppression. Due to the binding of opioid receptors on immune cells, sufentanil inhibits T cell differentiation and B cell function, thereby suppressing immune function. The operative method, such as the extent of lesion resection, the location of the lesion, and the method of residual treatment, also have an impact on immune function.

According to our experimental results, oxycodone has a good analgesic effect on postoperative visceral pain in patients undergoing laparoscopic resection of CRC. Oxycodone has no significant effect on inflammation and immune function. Therefore, the use of oxycodone as postoperative analgesia can achieve more satisfactory results for surgeries with significant visceral pain, such as gastrointestinal surgery, gynecological surgery, and urological surgery. Combining with nonsteroidal anti-inflammatory drugs will achieve more satisfactory analgesic effects [16]. In this study, we found that the incidence of side effects (nausea and vomiting) was higher when oxycodone was at the same potency as sufentanil. Therefore, in this study, the postoperative analgesia rate of oxycodone was 1 mg/h, which achieved good analgesic effect and the lowest incidence of complications. In conclusions, we provide more evidence about the application of oxycodone in laparoscopic resection of CRC for the Chinese population to perform postoperative analgesia.

The limitations of our study are as follow. Firstly, the data of our study is relatively small, and the variability of the data may be significant, making it impossible to statistically evaluate the significance of the experimental results. Secondly, complete blinding should be implemented between data analysts and anesthesiologists to ensure that the data is more objective and reliable. Thirdly, the observation cut-off point for this study is 72 h after surgery, and postoperative follow-up should continue to record the patient's discharge time and postoperative tumor recurrence rate. Besides, in addition to recording the patient's immune and inflammatory indicators, postoperative sleep status and the occurrence of adverse reactions can also be recorded.

Conclusion

This study suggested that using oxycodone as PCIA for patients undergoing laparoscopic resection of CRC can alleviate visceral pain in patients, but has no effect on cutting pain compared to sufentanil. In addition, oxycodone did not exhibit inhibition of inflammatory response and less immunosuppressive effects.

Data availability

No datasets were generated or analysed during the current study.

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Acknowledgements

We would like to express our thanks to all participants in this study.

CONSORT guidelines

The study adheres to CONSORT guidelines, and the completed CONSORT checklist was shown as an additional file.

Funding

None.

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Author notes

  1. Chunmei Lin and Zhiqiao Xu contributed equally to this work.

Authors and Affiliations

  1. The First Clinical Medical School, Jinan University, Guangzhou, 510632, People’s Republic of China

    Chunmei Lin

  2. Department of Anaesthesiology, Shenzhen Nanshan Hospital, Shenzhen, 518000, People’s Republic of China

    Chunmei Lin, Zhiqiao Xu,  XinLiang & Hong Wei

  3. Department of Pain Management, the First Affiliated Hospital of Jinan University, Guangzhou, 510632, People’s Republic of China

    Xiaoping Wang

Authors
  1. Chunmei Lin
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  2. Zhiqiao Xu
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  3. XinLiang
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  4. Hong Wei
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  5. Xiaoping Wang
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Contributions

Study design: Chunmei Lin, Hong Wei and Xiaoping Wang; information collection: Chunmei Lin, Zhiqiao Xu and Xin Liang; Analysis of data: Chunmei Lin and Zhiqiao Xu; manuscript drafting: Chunmei Lin; manuscript revision, editing, and approval: all authors.

Corresponding author

Correspondence to Hong Wei.

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Ethics approval and consent to participate

The project was performed by the Declaration of Helsinki and was approved by the review committee of the Shenzhen Nanshan Hospital (Shenzhen, China). Informed consent was acquired from the subjects after understanding the process and possible consequences of the study.

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Not applicable.

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The authors declare no competing interests.

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Lin, C., Xu, Z., XinLiang et al. A randomized controlled trial to compare the effect of oxycodone and sufentanil on postoperative analgesia and immune function for laparoscopic resection of colorectal cancer. BMC Anesthesiol 25, 58 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12871-025-02922-5

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  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12871-025-02922-5

Keywords

BMC Anesthesiology

ISSN: 1471-2253

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