Effect of IV Infusion of Lidocaine Compared to IV Infusion of Dexmedetomidine on Proinflammatory Cytokines

Effect of Intravenous Infusion of Lidocaine in Comparison to Intravenous Infusion of Dexmedetomidine on Proinflammatory Cytokines and Stress Response in Pelviabdominal Cancer Surgeries

This study is designed to compare between intravenous infusion of dexmedetomidine and intravenous infusion of lidocaine in reduction of proinflammatory cytokines as IL-6 and TNF-α, some stress reactions (serum insulin and serum lactate),and postoperative analgesic requirements in patients undergoing surgery for pelviabdominal cancers.

Study Overview

• Status: Completed
• Conditions: Inflammatory Response
• Intervention / Treatment: Drug: dexmedetomidine infusion; Drug: lidocaine infusion; Drug: Placebos

Detailed Description

Cancer patients who undergo surgery face many sources of stress. Surgery causes major cytokine and neuroendocrinal changes like increased levels of catecholamine and steroid hormones and other metabolic consequences .This stress response is considered a defense mechanism important for developing resistance to noxious insults.

The cytokine cascade caused by surgical stimulation is complex with various effects on the injured host. Increased production of proinflammatory cytokines from the site of injury causes many systemic changes such as metabolic derangements and hemodynamic instability. Some released cytokines like tumor necrosis factor alpha (TNF-α) and Interleukin 6(IL-6) can cause long lasting hyperalgesia. These proinflammatory cytokines change pain signal transmission through cytokine induced release of some neuroactive substances like nitric oxide, oxygen free radicals and excitatory amino acids. On the other hand anti-inflammatory cytokines are also released during inflammation to counteract these effects and keep balance.

Dexmedetomidine is a highly selective alpha-2 adrenergic receptor agonist that has sedative, analgesic, anesthetic-sparing properties with no respiratory depression. Its anti-inflammatory effects are being studied.

Intravenous lidocaine can be used in management of chronic pain. Lidocaine has anti-inflammatory properties and is capable of reducing postoperative analgesic requirements and the length of hospitalization.

The effect of both drugs on proinflammatory cytokines and stress response will be assessed

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11769
    • National Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• American society of anesthesia (ASA) Physical Status classification:

ASA II physical status.

• Age between 18 to 60 years old.
• Patients who will undergo major pelviabdominal surgery.

Exclusion Criteria:

• Patient refusal.
• Allergy to local anesthetics.
• Cognitive disorders.
• uncontrolled diabetes or hypertension.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: dexmedetomidine; dexmedetomidine ( precedex) infusion will be administered preoperatively and continued intraoperatively	Drug: dexmedetomidine infusion; a loading dose of 1µg/kg of dexmedetomidine (precedex) made to 50 ml using normal saline will be given over 10 minutes followed by infusion of dexmedetomidine with a dose of 0.5µg/kg/hour till the end of surgery.
Active Comparator: lidocaine; Lidocaine (Xylocaine) infusion will be administered preoperatively and continued intraoperatively	Drug: lidocaine infusion; a loading dose of 1.5 mg/kg of lidocaine made to 50 ml using normal saline and given over 10 minutes followed by infusion of lidocaine with a dose of 1.5 mg/kg/hour till the end of surgery.
Placebo Comparator: placebo; saline infusion will be administered preoperatively and continued intraoperatively	Drug: Placebos; 50 ml of normal saline given over 10 minutes followed by saline infusion intraoperatively at a rate of 10 ml/hour till the end of surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in inflammatory mediators	change in plasma levels of IL-6 (pg/ml), TNF-α (pg/ml)	preoperative (baseline), immediately postoperative and 24 hours postoperative
change in serum level of insulin and lactate	change in serum levels of insulin (ng/ml) and lactate (ng/ml)	preoperative (baseline), immediately postoperative and 24 hours postoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rescue analgesia	time of first rescue analgesia	1st 24 hours
Visual analogue scale (VAS) score for pain	assessment of postoperative pain using the visual analogue scale score. the scale is a straight horizontal line (100 mm). The ends are defined as the extreme limits of pain orientated from the left (no pain) to the right (worst pain).The patient marks on the line the point that they feel represents their perception of their current state. The VAS score is determined by measuring in millimetres from the left hand end of the line to the point that the patient marks.higher VAS score means worse pain	at 0 hour, 2 hour,6 hour, 12 hour and 24 hour
postoperative morphine requirements	total morphine consumption (mg)	1st 24 hours

Collaborators and Investigators

• Sponsor: Norma Osama Abdalla Zayed
• Collaborators: Abdelhamid, Bassant Mohamed, M.D.
• Investigators: Study Director: Emad Gerges, MD, National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2018
• Primary Completion (Actual): June 10, 2020
• Study Completion (Actual): June 13, 2020

Study Registration Dates

• First Submitted: September 24, 2019
• First Submitted That Met QC Criteria: October 30, 2019
• First Posted (Actual): November 1, 2019

Study Record Updates

• Last Update Posted (Actual): August 3, 2020
• Last Update Submitted That Met QC Criteria: July 30, 2020
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Membrane Transport Modulators; Hypnotics and Sedatives; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Dexmedetomidine; Lidocaine
• Other Study ID Numbers: 201617050.3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No