Analgesic Efficacy of Free-opioid Anesthesia for Colorectal Surgery

Colorectal Cancer Clinical Trial

Official title:

Evaluation of the Analgesic Efficacy of Free Opioid Anesthesia for Patients Undergoing Colectomies and Rectal Resections: A Prospective, Randomized Controlled Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06042816
• Other study ID #: 01/CN-HDÐ
• Status: Completed
• Phase: N/A
• Start date: December 30, 2019
• Est. completion date: December 30, 2021

Study information

• Verified date: September 2023
• Source: Vietnam Military Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: December 30, 2021
• Est. primary completion date: December 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Procedure:
• Free-opioid anesthesia
Free opioid anesthesia (FOA) has been used in many countries around the world, making use of multimodal analgesia therapy which includes hypnotics, N-methyl-D-aspartate (NMDA) antagonists, local anesthetics and anti-inflammatory agents and sympathetic block in surgery. This method was demonstrated to contribute to enhanced recovery after surgery (ERAS). The use of long-acting local anesthetics also enhances postoperative pain relief. As a result, the concept of balanced anesthesia now has a change in three basic components: hypnotics, muscle relaxants and sympathomimetic inhibitors
• opioid anesthesia
Opioids have been used as one of three basic components of balanced anesthesia, including anesthetic drugs, pain relievers, and neuromuscular blockade agents (opioid anesthesia). Opioids not only facilitate deep anesthesia but also create the most favorable conditions for surgeries. Fentanyl is a potent opioid used to control pain, reduce the dose of sympathomimetic inhibitors and maintain hemodynamic stability. However, several common side effects of fentanyl are well known: nausea and vomiting, constipation, urinary retention, headache, pruritus, rash, histamine release, biliary spasm and respiratory depression, the most severe adverse effect

Locations

Country	Name	City	State
Vietnam	Viet-Tiep Friendship Hospital	Hai Phong	Le Chan

Sponsors (1)

Lead Sponsor	Collaborator
Vietnam Military Medical University

Country where clinical trial is conducted

Vietnam, 

References & Publications (5)

Bakan M, Umutoglu T, Topuz U, Uysal H, Bayram M, Kadioglu H, Salihoglu Z. Opioid-free total intravenous anesthesia with propofol, dexmedetomidine and lidocaine infusions for laparoscopic cholecystectomy: a prospective, randomized, double-blinded study. Br — View Citation

Chin KJ, Lewis S. Opioid-free Analgesia for Posterior Spinal Fusion Surgery Using Erector Spinae Plane (ESP) Blocks in a Multimodal Anesthetic Regimen. Spine (Phila Pa 1976). 2019 Mar 15;44(6):E379-E383. doi: 10.1097/BRS.0000000000002855. — View Citation

Choi H, Song JY, Oh EJ, Chae MS, Yu S, Moon YE. The Effect of Opioid-Free Anesthesia on the Quality of Recovery After Gynecological Laparoscopy: A Prospective Randomized Controlled Trial. J Pain Res. 2022 Aug 3;15:2197-2209. doi: 10.2147/JPR.S373412. eCol — View Citation

Hakim KYK, Wahba WZB. Opioid-Free Total Intravenous Anesthesia Improves Postoperative Quality of Recovery after Ambulatory Gynecologic Laparoscopy. Anesth Essays Res. 2019 Apr-Jun;13(2):199-203. doi: 10.4103/aer.AER_74_19. — View Citation

Vaswani JP, Debata D, Vyas V, Pattil S. Comparative Study of the Effect of Dexmedetomidine Vs. Fentanyl on Haemodynamic Response in Patients Undergoing Elective Laparoscopic Surgery. J Clin Diagn Res. 2017 Sep;11(9):UC04-UC08. doi: 10.7860/JCDR/2017/27020 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	analgesic efficacy of free-opioid anesthesia	intraoperative alteration of Surgical Pleth Index (SPI). The Surgical Pleth Index (SPI) is an objective tool that can reflect nociception-antinociception balance and guide the use of intraoperative analgesics. The values of the SPI range from 0 to 100. During general anaesthesia, maintaining a value between 20 and 50 is generally recommended. When the SPI value is greater than 50 and exceeds 3-5 min, it routinely indicates that the noxious stimulation is too strong and that additional analgesic drugs are needed.	before induction of anesthesia
Primary	analgesic efficacy of free-opioid anesthesia	intraoperative alteration of Surgical Pleth Index (SPI)	After intubation
Primary	analgesic efficacy of free-opioid anesthesia	intraoperative alteration of Surgical Pleth Index (SPI)	After skin incision
Primary	analgesic efficacy of free-opioid anesthesia	intraoperative alteration of Surgical Pleth Index (SPI)	when the restoration of eyelids reflex emerged
Primary	analgesic efficacy of free-opioid anesthesia	The number of times of intraoperative analgesics adjustment	Intraoperatively (From the induction of anesthesia to the emergence)
Primary	analgesic efficacy of free-opioid anesthesia	the proportion of patients requiring postoperative pain rescue	postoperatively (upto 3 days after surgery)
Secondary	Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure	Non-invasive blood pressure was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The mean arterial blood pressure at each time point was compared between the two groups.	T0 (right after entering the operating theatre)
Secondary	Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure	Non-invasive blood pressure was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The mean arterial blood pressure at each time point was compared between the two groups.	T1 (before induction of anesthesia)
Secondary	Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure	Non-invasive blood pressure was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The mean arterial blood pressure at each time point was compared between the two groups.	T2 (patients lost eyelid reflex and response to verbal command)
Secondary	Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure	Non-invasive blood pressure was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The mean arterial blood pressure at each time point was compared between the two groups.	T3 (before intubation)
Secondary	Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure	Non-invasive blood pressure was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The mean arterial blood pressure at each time point was compared between the two groups.	T4 (after intubation)
Secondary	Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure	Non-invasive blood pressure was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The mean arterial blood pressure at each time point was compared between the two groups.	T5 (before skin incision)
Secondary	Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure	Non-invasive blood pressure was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The mean arterial blood pressure at each time point was compared between the two groups.	T6 (after skin incision)
Secondary	Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure	Non-invasive blood pressure was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The mean arterial blood pressure at each time point was compared between the two groups.	T7 (colon release)
Secondary	Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure	Non-invasive blood pressure was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The mean arterial blood pressure at each time point was compared between the two groups.	T8 (dissection of colorectal mesentery)
Secondary	Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure	Non-invasive blood pressure was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The mean arterial blood pressure at each time point was compared between the two groups.	T9 (colon resection)
Secondary	Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure	Non-invasive blood pressure was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The mean arterial blood pressure at each time point was compared between the two groups.	T10 (restore gastrointestinal flow)
Secondary	Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure	Non-invasive blood pressure was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The mean arterial blood pressure at each time point was compared between the two groups.	T11 (drainage placement)
Secondary	Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure	Non-invasive blood pressure was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The mean arterial blood pressure at each time point was compared between the two groups.	T12 (before skin closure)
Secondary	Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure	Non-invasive blood pressure was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The mean arterial blood pressure at each time point was compared between the two groups.	T13 (immediately after skin closure)
Secondary	Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure	Non-invasive blood pressure was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The mean arterial blood pressure at each time point was compared between the two groups.	T14 (eyelids reflex restored and patients eyes could open on command)
Secondary	Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure	Non-invasive blood pressure was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The mean arterial blood pressure at each time point was compared between the two groups.	T15 (before extubation)
Secondary	Effects of free-opioid anesthesia on intraoperative mean arterial blood pressure	Non-invasive blood pressure was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The mean arterial blood pressure at each time point was compared between the two groups.	T16 (15 minutes after extubation)
Secondary	Effects of free-opioid anesthesia on intraoperative heart rate	Heart rate was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The heart rate at each time point was compared between the two groups.	T0 (right after entering the operating theatre)
Secondary	Effects of free-opioid anesthesia on intraoperative heart rate	Heart rate was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The heart rate at each time point was compared between the two groups.	T1 (before induction of anesthesia)
Secondary	Effects of free-opioid anesthesia on intraoperative heart rate	Heart rate was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The heart rate at each time point was compared between the two groups.	T2 (patients lost eyelid reflex and response to verbal command)
Secondary	Effects of free-opioid anesthesia on intraoperative heart rate	Heart rate was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The heart rate at each time point was compared between the two groups.	T3 (before intubation)
Secondary	Effects of free-opioid anesthesia on intraoperative heart rate	Heart rate was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The heart rate at each time point was compared between the two groups.	T4 (after intubation)
Secondary	Effects of free-opioid anesthesia on intraoperative heart rate	Heart rate was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The heart rate at each time point was compared between the two groups.	T5 (before skin incision)
Secondary	Effects of free-opioid anesthesia on intraoperative heart rate	Heart rate was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The heart rate at each time point was compared between the two groups.	T6 (after skin incision)
Secondary	Effects of free-opioid anesthesia on intraoperative heart rate	Heart rate was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The heart rate at each time point was compared between the two groups.	T7 (colon release)
Secondary	Effects of free-opioid anesthesia on intraoperative heart rate	Heart rate was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The heart rate at each time point was compared between the two groups.	T8 (dissection of colorectal mesentery)
Secondary	Effects of free-opioid anesthesia on intraoperative heart rate	Heart rate was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The heart rate at each time point was compared between the two groups.	T9 (colon resection)
Secondary	Effects of free-opioid anesthesia on intraoperative heart rate	Heart rate was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The heart rate at each time point was compared between the two groups.	T10 (restore gastrointestinal flow)
Secondary	Effects of free-opioid anesthesia on intraoperative heart rate	Heart rate was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The heart rate at each time point was compared between the two groups.	T11 (drainage placement)
Secondary	Effects of free-opioid anesthesia on intraoperative heart rate	Heart rate was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The heart rate at each time point was compared between the two groups.	T12 (before skin closure)
Secondary	Effects of free-opioid anesthesia on intraoperative heart rate	Heart rate was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The heart rate at each time point was compared between the two groups.	T13 (immediately after skin closure)
Secondary	Effects of free-opioid anesthesia on intraoperative heart rate	Heart rate was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The heart rate at each time point was compared between the two groups.	T14 (eyelids reflex restored and patients eyes could open on command)
Secondary	Effects of free-opioid anesthesia on intraoperative heart rate	Heart rate was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The heart rate at each time point was compared between the two groups.	T15 (before extubation)
Secondary	Effects of free-opioid anesthesia on intraoperative heart rate	Heart rate was assessed every 5 minutes intraoperatively and recorded at some investigated time points. The heart rate at each time point was compared between the two groups.	T16 (15 minutes after extubation)
Secondary	changes in the concentration of IL (Interleukin)-6	Blood samples were collected in a heparin tube immediately before surgery (T0) and 1 hour after extubation. They were centrifuged, and then plasma was separated and stored at -70°C until being analyzed. IL-6 levels were analyzed using enzyme-linked immunosorbent assay (ELISA). Changes in IL-6 were recorded and compared between the two groups	Before surgery
Secondary	changes in the concentration of IL (Interleukin)-6	Blood samples were collected in a heparin tube immediately before surgery (T0) and 1 hour after extubation. They were centrifuged, and then plasma was separated and stored at -70°C until being analyzed. IL-6 levels were analyzed using enzyme-linked immunosorbent assay (ELISA). Changes in IL-6 were recorded and compared between the two groups	1 hour after surgery
Secondary	changes in the concentration of IL-10	Blood samples were collected in a heparin tube immediately before surgery (T0) and 1 hour after extubation. They were centrifuged, and then plasma was separated and stored at -70°C until being analyzed. IL-10 levels were analyzed using enzyme-linked immunosorbent assay (ELISA). Changes in IL-10 were recorded and compared between the two groups	Before surgery
Secondary	changes in the concentration of IL-10	Blood samples were collected in a heparin tube immediately before surgery (T0) and 1 hour after extubation. They were centrifuged, and then plasma was separated and stored at -70°C until being analyzed. IL-10 levels were analyzed using enzyme-linked immunosorbent assay (ELISA). Changes in IL-10 were recorded and compared between the two groups	1 hour after surgery
Secondary	Adverse effects of free-opioid anesthesia	the rate of patients suffering nausea and vomiting	up to 3 days postoperatively