The Anti-inflammatory Effect of Anesthetics in Abdominal Surgery

NCT ID: NCT03821545

Last Updated: 2022-05-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-28
• Study Completion Date: 2021-06-18

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.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

Lidocaine Group

Group Type: ACTIVE_COMPARATOR

Lidocaine

Intervention Type: OTHER

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 Group

Group Type: ACTIVE_COMPARATOR

Ketamine

Intervention Type: OTHER

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.

Lidocaine and Ketamine Group

Group Type: ACTIVE_COMPARATOR

Lidocaine and Ketamine

Intervention Type: OTHER

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 (0.9% NaCl) Group

Group Type: PLACEBO_COMPARATOR

Placebo (0.9% NaCl)

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Dubrava

OTHER

Sponsor Role: lead

Responsible Party

Helena Ostovic

Helena Ostovic MD, Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The Anti-inflammatory Effect of Anesthetics in Abdominal Surgery

Zagreb, , Croatia

Countries

Croatia

References

Ostovic H, Simac B, Prazetina M, Bradic N, Persec J. The Effect of Intravenous Lidocaine, Ketamine, and Lidocaine-Ketamine Combination in Colorectal Cancer Surgery: A Randomized Controlled Trial. Anesth Analg. 2025 Jan 1;140(1):67-76. doi: 10.1213/ANE.0000000000006555. Epub 2023 May 24.

Reference Type: DERIVED

PMID: 37224065 (View on PubMed)

Other Identifiers

Ostovic

Identifier Type: -

Identifier Source: org_study_id