Effect of OFA, OSA Versus Opioid-based Anesthesia on NETs and Cancer Cell Malignancy After Colorectal Cancer Surgery

Effect of Opioid-Free, Opioid-sparing Versus Opioid-based Anesthesia on Perioperative NETs and Cancer Cell Malignancy in Patients Undergoing Surgery for Colorectal Cancer: A Randomized, Controlled Trial

Adult patients aged 18-80 years old, American Society of Anesthesiologists physical status I-III, who were scheduled for elective colorectal cancer surgery under general anesthesia were recruited for this study. They were randomized to receive opioid-free anesthesia (OFA), opioid-sparing anesthesia (OSA) and opioid-based anesthesia (OA) group.

Blood samples were collected pre-surgery and 24h post-surgery. As primary endpoint, serum neutrophil myeloperoxidase (MPO) and citrullinated histone3 (CitH3) was measured. The secondary endpoints included the effects of postoperative serum on colorectal cancer (CRC) cells malignancy, numerical rating scale (NRS) scores, postoperative adverse events and recovery profiles.

For OA group, intraoperative remifentanil and sufentanil were used and postoperative patient controlled intravenous analgesia (PCIA) was performed with 0.5μg/ml of sufentanil and 0.75 mg/mL flurbiprofen, and the PCIA was stopped 48 h after surgery.

For OSA group, remifentanil and sufentanil were used only for anesthetic induction and the patient received ultrasound-guided transversus abdominis plane (TAP) nerve blockwas performed. Patient controlled intravenous analgesia (PCIA) was performed with 1mg/mL of oxycodone and 0.75 mg/mL flurbiprofen after surgery, and the PCIA was stopped 48 hours after surgery.

For OFA group, intraoperative epidural anesthesia combined with general anesthesia was used, and esketamine, lidocaine and dexmedetomidine for analgesia. Patient controlled epidural analgesia (PCEA) was used and terminated 48 hours after surgery.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; NETs; Opioid-free Anesthesia
• Intervention / Treatment: Other: OA strategy; Other: OSA stategy; Other: OFA strategy

Detailed Description

Adult patients aged 18-80 years old, American Society of Anesthesiologists physical status I-III, who were scheduled for elective colorectal cancer surgery under general anesthesia with endotracheal tube were recruited for this study. Tthey were randomized to receive opioid-free anesthesia (OFA), opioid-sparing anesthesia (OSA) and opioid-based anesthesia (OA) group.Blood samples were collected pre-surgery and 24h post-surgery. As primary endpoint, serum neutrophil myeloperoxidase (MPO) was detected. The secondary endpoints included the effects of postoperative serum on colorectal cancer (CRC) cells malignancy, numerical rating scale (NRS) scores, side effects and postoperative complications.

For OA group, anesthesia induction was conducted with an intravenous targeted control infusion (TCI) of 3-4 μg/mL propofol (effect-site concentration, Marsh mode), 2-3 ng/mL remifentanil (effect-site concentration, Minto mode), 0.5 μg/kg sufentanil, and 0.6 mg/kg rocuronium. General anesthesia was maintained with a continuous TCI infusion of 3 to 4 μg/mL propofol and 1 to 2 ng/mL remifentanil, intermittently administrated sufentanil and rocuronium. Patient controlled intravenous analgesia (PCIA) was performed with 0.5μg/ml of sufentanil and 0.75 mg/mL flurbiprofen after surgery. The PCIA scheme was set with the continuous infusion rate of 4 ml/h and single bolus injection volume of 4ml. The locking time was 15 min, and the PCIA was stopped 48 h after surgery.

For OSA group, anesthesia induction was conducted with an intravenous targeted control infusion (TCI) of 3 to 4 μg/mL propofol, 2 to 3 ng/mL remifentanil, 0.3 μg/kg sufentanil, and 0.6 mg/kg rocuronium. After intubation, the patient received ultrasound-guided transversus abdominis plane (TAP) nerve block, with 0.375% ropivacaine 40mL injection. General anesthesia maintenance was consistent with OA group. Patient controlled intravenous analgesia (PCIA) was performed with 1mg/mL of oxycodone and 0.75 mg/mL flurbiprofen after surgery. The PCIA scheme was set with the continuous infusion rate was 4 ml/h and single bolus injection of 4ml. The locking time was 15 min, and the PCIA was stopped 48 hours after surgery.

For OFA group, before induction, an epidural catheter was inserted under sterile conditions using the "loss-of-resistance" technique, and the catheter was advanced 4 cm cephalad. When the aspiration test results for blood and cerebrospinal fluid were negative, a test dose of lidocaine 1% (3 ml) was injected through the catheter. Ropivacaine (0.25%) was maintained at a rate of 5 ml/h during surgery. Anesthesia induction was conducted with an intravenous targeted control infusion (TCI) of 3-4 μg/mL propofol, 0.6 mg/kg rocuronium, 0.5mg/kg esketamine, 1mg/kg lidocaine and 0.5ug/kg dexmedetomidine. General anesthesia was maintained with a continuous TCI infusion of 3 to 4 μg/mL propofol, 1.5-mg/kg/h continuous infusion of lidocaine, 0.25 mg/kg/h continuous infusion of esketamine. At the postoperative stage, the epidural administration regimen included 0.15% ropivacaine. The continuous infusion rate was 5ml/h, with an additional 5 ml upon the patient's request, and the locking time was 15 min. The epidural catheter was removed 48 hours after surgery.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lingling Gao, MD; Phone Number: 086-18818211563; Email: LinglingGao@aliyun.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Jun Zhang, PhD; Phone Number: +86-21-64175590; Email: snapzhang@aliyun.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• aged 18-80 years old,
• American Society of Anesthesiologists physical status I-III,
• elective colorectal cancer surgery under general anesthesia

Exclusion Criteria:

• previous history of colorectal surgery,
• addicted to opioids,
• serious major mental or physical illness (heart, pulmonary, hepatic, or renal diseases),
• radiotherapy or chemotherapy history within 8 weeks prior to the surgery,
• contraindications to anesthetic agents or epidural.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OA group; petients received opioid-based anesthesia	Other: OA strategy; For OA group, anesthesia induction was conducted with an intravenous targeted control infusion (TCI) of 3-4 μg/mL propofol (effect-site concentration, Marsh mode), 2-3 ng/mL remifentanil (effect-site concentration, Minto mode), 0.5 μg/kg sufentanil, and 0.6 mg/kg rocuronium. General anesthesia was maintained with a continuous TCI infusion of 3 to 4 μg/mL propofol and 1 to 2 ng/mL remifentanil, intermittently administrated sufentanil and rocuronium. Patient controlled intravenous analgesia (PCIA) was performed with 0.5μg/ml of sufentanil and 0.75 mg/mL flurbiprofen after surgery. The PCIA scheme was set with the continuous infusion rate of 4 ml/h and single bolus injection volume of 4ml. The locking time was 15 min, and the PCIA was stopped 48 h after surgery.
Experimental: OSA group; patients received opioid-sparing anesthesia	Other: OSA stategy; For OSA group, anesthesia induction was conducted with an intravenous targeted control infusion (TCI) of 3 to 4 μg/mL propofol, 2 to 3 ng/mL remifentanil, 0.3 μg/kg sufentanil, and 0.6 mg/kg rocuronium. After intubation, the patient received ultrasound-guided transversus abdominis plane (TAP) nerve block, with 0.375% ropivacaine 40mL injection. General anesthesia maintenance was consistent with OA group. Patient controlled intravenous analgesia (PCIA) was performed with 1mg/mL of oxycodone and 0.75 mg/mL flurbiprofen after surgery. The PCIA scheme was set with the continuous infusion rate was 4 ml/h and single bolus injection of 4ml. The locking time was 15 min, and the PCIA was stopped 48 hours after surgery.
Experimental: OFA group; patients received opioid-free anesthesia	Other: OFA strategy; For OFA group, before induction, an epidural catheter was inserted , and the catheter was advanced 4 cm cephalad. When the aspiration test results for blood and cerebrospinal fluid were negative, a test dose of lidocaine 1% (3 ml) was injected through the catheter. Ropivacaine (0.25%) was maintained at a rate of 5 ml/h during surgery. Anesthesia induction was conducted with an intravenous targeted control infusion (TCI) of 3-4 μg/mL propofol, 0.6 mg/kg rocuronium, 0.5mg/kg esketamine, 1mg/kg lidocaine and 0.5ug/kg dexmedetomidine. General anesthesia was maintained with a continuous TCI infusion of 3 to 4 μg/mL propofol, 1.5-mg/kg/h continuous infusion of lidocaine, 0.25 mg/kg/h continuous infusion of esketamine. At the postoperative stage, the epidural administration regimen included 0.15% ropivacaine. The continuous infusion rate was 5ml/h, with an additional 5 ml upon the patient's request, and the locking time was 15 min. The epidural catheter was removed 48 hours after surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
serum NETs biomarkers levels .	serum levels of neutrophil myeloperoxidase (MPO) and citrullinated histone3 (CitH3)	Day 1 before surgery and day 1 after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
colorectal cancer (CRC) cells malignancy	the effects of postoperative serum on CRC cells proliferation, migration and invasion	Day 1 after surgery
numerical rating scale (NRS) scorespain score	numerical rating scale (NRS) scores at rest and on cough,NRS score is a scale of 0 to 10, the higher the score, the greater the degree of pain.	Day 1 and day 2 after surgery
adverse event: postoperative nausea and vomiting	The incidence of the postoperative nausea and vomiting, ask the patient bedside if they have any complaints of nausea or vomiting postoperatively.	Day 1 and day 2 after surgery
postoperative complications	surgical complications	On the day of surgery to the day discharge from hospital
postoperative rcovery profiles	length of PACU and hospital stay	On the day of surgery to the day discharge from hospital
postoperative rcovery profiles	first postoperative flatus,was defined as the proportion of patients passage of flatus or stool within 24 and 48 hours.	Day 1 and day 2 after surgery

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2025
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): December 15, 2025

Study Registration Dates

• First Submitted: November 17, 2025
• First Submitted That Met QC Criteria: November 24, 2025
• First Posted (Estimated): December 4, 2025

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: colorectal cancer; Opioid free anesthesia; Neutrophil extracellular trapping markers
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms
• Other Study ID Numbers: OFA in CRC patients

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No