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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое 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)
• Другое 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
• Другое 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 lid

Первичные конечные точки

• serum NETs biomarkers levels . [Срок оценки: Day 1 before surgery and day 1 after surgery]

Вторичные конечные точки (6)

• colorectal cancer (CRC) cells malignancy [Срок оценки: Day 1 after surgery]
• numerical rating scale (NRS) scorespain score [Срок оценки: Day 1 and day 2 after surgery]
• adverse event: postoperative nausea and vomiting [Срок оценки: Day 1 and day 2 after surgery]
• postoperative complications [Срок оценки: On the day of surgery to the day discharge from hospital]
• postoperative rcovery profiles [Срок оценки: On the day of surgery to the day discharge from hospital]
• postoperative rcovery profiles [Срок оценки: Day 1 and day 2 after surgery]

Критерии участия

Критерии включения

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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Поддерживающая терапия

Центры проведения

Китай · 1 центр

• Fudan University Shanghai Cancer Center — Шанхай

Идентификаторы

NCT: NCT07264556 · OFA in CRC patients

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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