The Anti-inflammatory Effect of Anesthetics in Abdominal Surgery

Study Overview
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Brief Summary
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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.

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

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Other: Lidocaine
* Other: Ketamine
* Other: Lidocaine and Ketamine
* Other: Placebo (0.9% NaCl)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lidocaine Group<br> | Other: Lidocaine<br>* 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.<br>|
| Active Comparator: Ketamine Group<br> | Other: Ketamine<br>* 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.<br>|
| Active Comparator: Lidocaine and Ketamine Group<br> | Other: Lidocaine and Ketamine<br>* 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.<br>|
| Placebo Comparator: Placebo (0.9% NaCl) Group<br> | Other: Placebo (0.9% NaCl)<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anti-Inflammatory Effect, Surgical Stress, Lidocaine, Ketamine, Abdominal Surgery