The Anti-inflammatory Effect of Anesthetics in Abdominal Surgery

The Immunomodulatory Effects of Ketamine and Lidocaine in Abdominal Surgery: Double-Blind, Placebo-Controlled Clinical Study

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Other: Lidocaine; Other: Ketamine; Other: Lidocaine and Ketamine; Other: Placebo (0.9% NaCl)

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Croatia
  • Zagreb, Croatia, 10000
    • The Anti-inflammatory Effect of Anesthetics in Abdominal Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lidocaine Group	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.
Active Comparator: Ketamine Group	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.
Active Comparator: Lidocaine and Ketamine Group	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.
Placebo Comparator: Placebo (0.9% NaCl) Group	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of inflammatory markers	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	1-2 days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University Hospital Dubrava

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2019
• Primary Completion (Actual): June 12, 2021
• Study Completion (Actual): June 18, 2021

Study Registration Dates

• First Submitted: December 28, 2018
• First Submitted That Met QC Criteria: January 27, 2019
• First Posted (Actual): January 30, 2019

Study Record Updates

• Last Update Posted (Actual): May 20, 2022
• Last Update Submitted That Met QC Criteria: May 14, 2022
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Ketamine; Lidocaine; Surgical Stress; Abdominal Surgery; Anti-Inflammatory Effect
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Ketamine; Lidocaine
• Other Study ID Numbers: Ostovic

Drug and device information, study documents

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