Clinical trial NCT06042816: Analgesic Efficacy of Free-opioid Anesthesia for Colorectal Surgery
Official title: Evaluation of the Analgesic Efficacy of Free Opioid Anesthesia for Patients Undergoing Colectomies and Rectal Resections: A Prospective, Randomized Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Colorectal Cancer
Keywords: Free-opioid anesthesia
Opioid anesthesia
colorectal surgery
Lead sponsor: Vietnam Military Medical University
Sponsor class: OTHER
First posted: 2023-09-21
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients were randomized into 2 groups: Group OA - Opioid anesthesia (n = 49): Intraoperative pain control by fentanyl; FOA group - Free-opioid anesthesia (n = 49): Intraoperative pain control by continuous infusion of lidocaine, bolus doses of ketamine combined with epidural levobupivacaine.
Primary purpose: SUPPORTIVE_CARE

Brief summary: Objectives: To compare free-opioid anesthesia (the combination of epidural anesthesia, intravenous lidocaine, ketamine, propofol, and sevoflurane) and opioid anesthesia (fentanyl, propofol and sevoflurane) regarding intraoperative analgesic efficacy in colectomies and rectal resections at Viet Tiep Friendship Hospital.

Methods: A prospective, randomized controlled clinical trial was performed on 98 patients who were anesthetized for colorectal surgery from December 2019 to November 2021. Patients were randomized into 2 groups: Group OA - Opioid anesthesia (n = 49): Intraoperative pain control by fentanyl; FOA group - Free-opioid anesthesia (n = 49): Intraoperative pain control by continuous infusion of lidocaine, bolus doses of ketamine combined with epidural levobupivacaine.

Detailed description: After being placed an epidural catheter and given a bolus dose of dexamethasone 0.1 mg/kg, patients was endotracheal anesthetized with propofol 1% 2-2.5 mg/kg, rocuronium 0.6 mg/kg. Intubation was implemented when TOF (Train Of Four)=0 and RE (Response Entropy), SE (State Entropy) ≤ 60. Patients in OA group received a bolus dose of fentanyl 2 µg/kg before induction of anesthesia while those in FOA group received bolus doses of lidocaine 1 mg/kg and ketamine 0.5 mg/kg. In FOA group, lidocaine 10% was sprayed on the patients glottis to facilitate intubation.

For anesthesia maintenance, in group OA, a bolus dose of fentanyl 3 µg/kg was given 5 minutes before skin incision, and then a continuous infusion of fentanyl 2 µg/kg/h was maintained for intraoperative pain management; fentanyl 0.5 μg/kg was bolused when SPI (Surgical Pleth Index) \> 50, 40 \< SE \< 60, TOF = 0 and the patient was hemodynamically stable. Propofol and fentanyl were discontinued at the start of skin closure. In FOA group, patients received intraoperative multimodal analgesia, in which an epidural bolus of 3 - 5 ml of levobupivacaine 0.1% was followed by a continuous infusion of 3 - 5 ml/h epidurally; in addition, intravenous infusion of lidocaine 1 mg/kg/hour and ketamine 0.25 mg/kg/h were maintained until the end of surgery. Patients were given a bolus of 3-5 ml levobupivacaine 0.1% epidurally and ketamine 0.25 mg/kg intravenously if SPI \> 50, 40 \< SE \< 60, TOF = 0 and hemodynamics was stable.

For all patients, anesthesia was maintained by volatile anesthetics (Sevoflurane or Desflurane) to ensure 40 \< SE \< 60, and rocuronium 0.2 mg/kg was repeated when TOF = 2 (the last injection of neuromuscular blockade was not given when the estimated duration from the point of injection to the point of abdominal closure is shorter than 20 minutes). Mechanical ventilation was provided with a tidal volume 6-8 ml/kg in the volume-controlled mode and respiratory rate at 10-12 breath/minute, FiO2 (Fraction of inspired oxygen)=50%. Peak airway pressure was maintained within the range of 12-16 cmH2O and EtCO2 (End-tidal Carbon dioxide) was kept from 35 to 40 mmHg with a fresh gas flow of 1.2 - 2 liters/minute. At the end of surgery, reversal of neuromuscular blockade was performed with neostigmine combined with atropine, and extubation was carried out when patients met the criteria. Postoperative pain management was implemented with patient-controlled epidural levobupivacaine 0.1% for 72 hours, and pain rescue with fentanyl 0.5 μg/kg.

Eligibility criteria: Inclusion Criteria:

* Patients agreed to participate in the study.
* Patients aged ≥ 18 years old,
* Those who underwent elective colectomies or rectal resections,
* Those who were ASA (American Society of Anesthesiologists) classified as I - III,
* Those who were indicated for general endotracheal anesthesia from December 2019 to November 2021 at Viet Tiep Friendship Hospital

Exclusion Criteria:

* Patients refused to participate in the study,
* Patients had BMI (Body Mass Index) ≥ 35;
* Pregnant or lactating or menstruating women;
* Those who had liver failure, renal failure, heart failure, history of chronic pain, alcohol or drug abuse, mental illnesses, allergies or contraindications to any studied medications.
* Those who were unable to assess pain or use of patient-controlled analgesia devices (PCA).

Primary outcomes:
measure: analgesic efficacy of free-opioid anesthesia
timeFrame: before induction of anesthesia
measure: analgesic efficacy of free-opioid anesthesia
timeFrame: After intubation
measure: analgesic efficacy of free-opioid anesthesia
timeFrame: After skin incision
measure: analgesic efficacy of free-opioid anesthesia
timeFrame: when the restoration of eyelids reflex emerged
measure: analgesic efficacy of free-opioid anesthesia
timeFrame: Intraoperatively (From the induction of anesthesia to the emergence)
measure: analgesic efficacy of free-opioid anesthesia
timeFrame: postoperatively (upto 3 days after surgery)
Secondary outcomes:
measure: Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure
timeFrame: T0 (right after entering the operating theatre)
measure: Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure
timeFrame: T1 (before induction of anesthesia)
measure: Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure
timeFrame: T2 (patients lost eyelid reflex and response to verbal command)
measure: Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure
timeFrame: T3 (before intubation)
measure: Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure
timeFrame: T4 (after intubation)
measure: Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure
timeFrame: T5 (before skin incision)
measure: Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure
timeFrame: T6 (after skin incision)
measure: Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure
timeFrame: T7 (colon release)
measure: Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure
timeFrame: T8 (dissection of colorectal mesentery)
measure: Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure
timeFrame: T9 (colon resection)
measure: Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure
timeFrame: T10 (restore gastrointestinal flow)
measure: Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure
timeFrame: T11 (drainage placement)
measure: Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure
timeFrame: T12 (before skin closure)
measure: Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure
timeFrame: T13 (immediately after skin closure)
measure: Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure
timeFrame: T14 (eyelids reflex restored and patients eyes could open on command)
measure: Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure
timeFrame: T15 (before extubation)
measure: Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure
timeFrame: T16 (15 minutes after extubation)
measure: Effects of free-opioid anesthesia on intraoperative heart rate
timeFrame: T0 (right after entering the operating theatre)
measure: Effects of free-opioid anesthesia on intraoperative heart rate
timeFrame: T1 (before induction of anesthesia)
measure: Effects of free-opioid anesthesia on intraoperative heart rate
timeFrame: T2 (patients lost eyelid reflex and response to verbal command)
measure: Effects of free-opioid anesthesia on intraoperative heart rate
timeFrame: T3 (before intubation)
measure: Effects of free-opioid anesthesia on intraoperative heart rate
timeFrame: T4 (after intubation)
measure: Effects of free-opioid anesthesia on intraoperative heart rate
timeFrame: T5 (before skin incision)
measure: Effects of free-opioid anesthesia on intraoperative heart rate
timeFrame: T6 (after skin incision)
measure: Effects of free-opioid anesthesia on intraoperative heart rate
timeFrame: T7 (colon release)
measure: Effects of free-opioid anesthesia on intraoperative heart rate
timeFrame: T8 (dissection of colorectal mesentery)
measure: Effects of free-opioid anesthesia on intraoperative heart rate
timeFrame: T9 (colon resection)
measure: Effects of free-opioid anesthesia on intraoperative heart rate
timeFrame: T10 (restore gastrointestinal flow)
measure: Effects of free-opioid anesthesia on intraoperative heart rate
timeFrame: T11 (drainage placement)
measure: Effects of free-opioid anesthesia on intraoperative heart rate
timeFrame: T12 (before skin closure)
measure: Effects of free-opioid anesthesia on intraoperative heart rate
timeFrame: T13 (immediately after skin closure)
measure: Effects of free-opioid anesthesia on intraoperative heart rate
timeFrame: T14 (eyelids reflex restored and patients eyes could open on command)
measure: Effects of free-opioid anesthesia on intraoperative heart rate
timeFrame: T15 (before extubation)
measure: Effects of free-opioid anesthesia on intraoperative heart rate
timeFrame: T16 (15 minutes after extubation)
measure: changes in the concentration of IL (Interleukin)-6
timeFrame: Before surgery
measure: changes in the concentration of IL (Interleukin)-6
timeFrame: 1 hour after surgery
measure: changes in the concentration of IL-10
timeFrame: Before surgery
measure: changes in the concentration of IL-10
timeFrame: 1 hour after surgery
measure: Adverse effects of free-opioid anesthesia
timeFrame: up to 3 days postoperatively
Other outcomes:
Locations:
city: Hai Phong
country: Vietnam
facility: Viet-Tiep Friendship Hospital
state: Le Chan
Study officials:
affiliation: Center of Emergency, Critical Care Medicine and Clinical Toxicology, Military Hospital 103, Vietnam
name: Kien T Nguyen, Ph.D
role: STUDY_DIRECTOR
References:
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