The Anti-inflammatory Effect of Anesthetics in Abdominal Surgery

• ClinicalTrials.gov Identifier: NCT03821545
• Recruitment Status: Completed
• First Posted: January 30, 2019
• Last Update Posted: May 20, 2022
• Sponsor: University Hospital Dubrava
• Information provided by (Responsible Party): Helena Ostovic, University Hospital Dubrava

Tracking Information

• First Submitted Date: December 28, 2018
• First Posted Date: January 30, 2019
• Last Update Posted Date: May 20, 2022
• Actual Study Start Date: January 28, 2019
• Actual Primary Completion Date: June 12, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 14, 2022)

Concentration of inflammatory markers [ Time Frame: 1-2 days ]

Measuring of inflammatory markers in serum (CRP, IL-6, IL-8) before induction of anesthesia, then 12 hours and 36 hours following the completion of surgery

Original Primary Outcome Measures (submitted: January 27, 2019)

• LOS [ Time Frame: 1-5 days ]
  Length of stay in the ICU
• Length of Hospital Stay [ Time Frame: 1-30 days ]
• Cost of Hospitalisation [ Time Frame: 1-30 days ]

Current Secondary Outcome Measures (submitted: May 14, 2022)

• Opioid consumption during anesthesia [ Time Frame: 1 day ]
  Measuring of total opioid consumption during intraoperative period
• VAS- scores [ Time Frame: 2 days ]
  Measuring pain scores VAS scores 2 hours and 4 hours following surgery and every 12 hours the following 2 days.
• Analgesic consumption [ Time Frame: 2 days ]
  Measuring total analgesic consumption for 48 hours following the completion of surgery
• Recovery of bowel function [ Time Frame: 1-5 days ]
  Measuring time to firs bowel movement
• Length of hospital stay [ Time Frame: 1- 30 days ]
  Follow-up patients until hospital discharge

Original Secondary Outcome Measures (submitted: January 27, 2019)

• Change in opioid administration [ Time Frame: 1 day ]
  Measuring of total opioid consumption during postoperative period
• Concentration of proinflammatory markers [ Time Frame: 1-2 days ]
  Measuring of proinflammatory markers in serum (CRP, IL-6, IL-8) before induction of anesthesia, then 12 hours and 36 hours following the completion of surgery

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The Anti-inflammatory Effect of Anesthetics in Abdominal Surgery
• Official Title: The Immunomodulatory Effects of Ketamine and Lidocaine in Abdominal Surgery: Double-Blind, Placebo-Controlled Clinical Study

Brief Summary

Clinical studies have shown that IV administration of anesthetics, lidocaine and ketamine with their anti-inflammatory properties, modulates the acute immune response associated with surgical tissue injury, and in this manner they are able to reduce postoperative pain. Lidocaine has anti-inflammatory effects on polymorphonuclear granulocytes, IL-6 and IL-8 cytokines, complement component C3a and IL-1ra in serum. Ketamine produces its anti-inflammatory effects by reducing CRP and IL-6 in serum and by inhibiting NF-kB, which regulates gene transcription responsible for the production of proinflammatory factors.

Perioperative combinend IV administration of lidocaine and ketamine could have a more favorable anti-inflammatory effect compared to anesthetic given alone or with placebo.

To investigate the effects of lidocaine and ketamine in patients undergoing abdominal surgery on: acute immune response following the level of proinflammatory factors in serum (CRP, IL-6, IL-8); postoperative pain management; recovery of bowel function; administration of opioids; reduction of total treatment costs; length of hospital stay (LOHS)

A double-blind, placebo-controlled study will include 100 patients undergoing open colorectal surgery. Patients will be randomly assigned to one of four groups: lidocaine, ketamine, lidocaine-ketamine, and placebo. Lidocaine will be administered at a dose of 1.5 mg/kg prior to surgical incision followed by an infusion at a rate of 1.5-2 mg/kg/hr until the end of surgery. Ketamine will be administered at a dose of 0.5 mg/kg in a bolus prior to surgical incision followed by an infusion at a rate of 0.1-0.2 mg/kg/hr until the end of surgery. Bolus and continuous placebo infusion (0.9% NaCl) will be equally administered at the same dose as the aforementioned anesthetics until the end of the surgery.

Proinflammatory markers in serum (CRP, IL-6, IL-8) will be measured before induction of anesthesia, then 12 hours and 36 hours following the completion of surgery. The intensity of pain will be measured using the VAS score 2 hours and 4 hours following surgery and every 12 hours the following days. The investigators will measure also the consumption of opioids during and after surgery, the length of stay in the ICU, where pain control and analgesics use will be measured, as well as recovery of bowel function.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Other
• Condition: Colorectal Cancer

Intervention

• Other: Lidocaine
  Lidocaine will be administered at a dose of 1.5 mg/kg prior to surgical incision followed by an infusion at a rate of 1.5-2 mg/kg/hr until the end of surgery.
• Other: Ketamine
  Ketamine will be administered at a dose of 0.5 mg/kg in a bolus prior to surgical incision followed by an infusion at a rate of 0.1-0.2 mg/kg/hr until the end of surgery.
• Other: Lidocaine and Ketamine
  Lidocaine will be administered at a dose of 1.5 mg/kg prior to surgical incision followed by an infusion at a rate of 1.5-2 mg/kg/hr until the end of surgery. Ketamine will be administered at a dose of 0.5 mg/kg in a bolus prior to surgical incision followed by an infusion at a rate of 0.1-0.2 mg/kg/hr until the end of surgery.
• Other: Placebo (0.9% NaCl)
  Bolus and continuous placebo infusion (0.9% NaCl) will be equally administered at the same dose as the aforementioned anesthetics until the end of the surgery.

Study Arms

• Active Comparator: Lidocaine Group
  Intervention: Other: Lidocaine
• Active Comparator: Ketamine Group
  Intervention: Other: Ketamine
• Active Comparator: Lidocaine and Ketamine Group
  Intervention: Other: Lidocaine and Ketamine
• Placebo Comparator: Placebo (0.9% NaCl) Group
  Intervention: Other: Placebo (0.9% NaCl)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 18, 2021): 82
• Original Estimated Enrollment (submitted: January 27, 2019): 120
• Actual Study Completion Date: June 18, 2021
• Actual Primary Completion Date: June 12, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Elective Surgery
• Expected duration of the operation > 2 hours

Exclusion Criteria:

• Patients ≤ 18 years of age
• Patients with history of allergy to local anesthetics
• Chronic opioid analgesic
• Patients who are unwilling or unable to participate

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Croatia

Administrative Information

• NCT Number: NCT03821545
• Other Study ID Numbers: Ostovic
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Helena Ostovic, University Hospital Dubrava
• Original Responsible Party: Same as current
• Current Study Sponsor: University Hospital Dubrava
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: University Hospital Dubrava
• Verification Date: November 2020