Effects of Different Doses of Intravenous Lidocaine Infusion on Peri-operative Pain and Incidence of Postoperative Chronic Pain Within ERAS Protocols, a Dose Finding Study.

This study aimed To investigate the effects of different doses of Intraoperative intravenous lidocaine infusion on intraoperative opioid consumption, perioperative pain control and incidence of postoperative chronic pain.

Study Overview

• Status: Recruiting
• Conditions: Perioperative Pain Management
• Intervention / Treatment: Drug: Lidocaine IV

Detailed Description

Enhanced recovery after surgery (ERAS) protocols or fast track surgery are a number of interventions which are carried out in the perioperative period. They are aimed to decrease the harmful effects of surgery on the body and help the patient recover better after surgery. ERAS has been shown to reduce the length of hospital stay, overall hospital costs, opioid consumption in the perioperative period and to reduce complication rates.

One of the most important components of ERAS is adequate perioperative pain control using a multi-modal analgesic approach to help decrease dependence on opioids and provide better recovery and less postoperative hospital stay. Also, the severity and duration of acute postoperative pain is one of the predictors of chronic postsurgical pain (CPSP). Neuroplasticity (spinal sensitization) following the trauma of surgery can transform an acute pain to chronic pain if not treated effectively by aggressive management of acute pain.

Lidocaine (or 2-(diethylamino)-N-(2.6-dimethylphenyl) acetamide) is the main prototype of amino-amide local anesthetics. It has analgesic, anti-hyperalgesic and anti-inflammatory properties, which enable its use as a general anesthetic adjuvant. It can reduce nociception, cardiovascular responses to surgical stress, postoperative pain, and analgesic requirements.

Accordingly, Lidocaine infusion can have a role in enhancing postoperative quality of recovery, decreasing incidence of chronic postoperative pain and even increasing overall survival in patients undergoing major surgeries like in pancreatectomy.

The Systemic effects of intravenous Lidocaine infusion depends on its plasma level which is affected by the rate and dose of administration, drug interactions and speed of metabolism and elimination. Around 90% of lidocaine undergoes hepatic metabolism (CYP3A4), with the production of active metabolites. During lidocaine continuous infusion, the accumulation of these metabolites may inhibit its biotransformation and might be involved in some cases of intoxication. The clearance rate of lidocaine is approximately 0.85 L/kg/h. Finally, lidocaine is eliminated by the kidney (10% of lidocaine is eliminated unchanged in the urine).

The target plasma concentrations for Lidocaine for providing effective analgesia is 2.4 ± 0.6 μg/mL, while side effects as - have been reported when the plasma concentration was higher than 5-8 μg/mL. The suggested dosing regimens mentioned in literature to achieve this effective plasma level while avoiding toxicity is a bolus of 1-2 mg/kg at surgery start followed by infusion of 1-2 mg/kg/h over the duration of the surgery which is a relatively wide range, specially, considering the wide variability in type and duration of surgeries, demographics, physical and medical status of patients and type of anesthetic agents and drugs used which all can affect Lidocaine activity, elimination & toxicity.

To the best of our knowledge, no evidence exist in the literature that can point towards the ideal dosing regimen for intravenous Lidocaine infusion that can achieve the desired valuable clinical effects while decreasing the incidence of adverse side effects among the wide variety of surgeries and patients encountered within ERAS protocols.

• Study Type: Interventional
• Enrollment (Estimated): 69
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Alaa Magdy Ahmed Hassan, Master; Phone Number: 01090282616; Email: loka272@yahoo.com
• Study Contact Backup: Name: Amany Ezzat Ayad Ibrahim, Professor; Phone Number: 01223429325; Email: amanymounir@kasralainy.edu.eg

Study Locations

• Egypt
  • Cairo, Egypt, 1111
    • Recruiting
    • Cairo University
    • Contact: Omnia Y Kamel, MD; Phone Number: 01270130326; Email: omniayehiakamel90@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients age between 18 and 65.
• Patients with ASA I and II status.
• Patients undergoing open laparotomy surgeries (including open cholecystectomies).

Exclusion Criteria:

• Patients unable to comprehend the informed consent.
• Patients on long term pre-operative opioid regimens.
• Patients with impairment in hepatic or renal functions.
• Patients who are planned to receive any form of regional block for the surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A; Group A: Bolus 10 ml Syringe with Lidocaine 0.5% (2.5 ml lidocaine 2% + 7.5 ml N.S), and infusion 50 ml Syringe with Lidocaine 0.5% (12.5 ml Lidocaine 2% + 37.5 ml N.S).	Drug: Lidocaine IV; After confirming patient history, type of operation and patient group allocation, standard ASA monitoring will be attached to the patient then the I.V induction of anesthesia will be commenced using standard doses of Propofol &Tracrium in addition to 1 μg/kg Fentanyl and 1 ml/10 kg from the bolus Lidocaine syringe followed after 3 minutes by endotracheal intubation, then the Lidocaine infusion Syringe will be attached to a separate I.V line at an infusion rate of 1 ml/10 kg/h. The patient will receive 1 gm of I.V paracetamol and the surgery will be allowed to proceed.
Active Comparator: Group B; Group B: Bolus 10 ml Syringe with Lidocaine 1% (5 ml lidocaine 2% + 5 ml N.S), and infusion 50 ml Syringe with Lidocaine 1% (25 ml Lidocaine 2% + 25 ml N.S).	Drug: Lidocaine IV; After confirming patient history, type of operation and patient group allocation, standard ASA monitoring will be attached to the patient then the I.V induction of anesthesia will be commenced using standard doses of Propofol &Tracrium in addition to 1 μg/kg Fentanyl and 1 ml/10 kg from the bolus Lidocaine syringe followed after 3 minutes by endotracheal intubation, then the Lidocaine infusion Syringe will be attached to a separate I.V line at an infusion rate of 1 ml/10 kg/h. The patient will receive 1 gm of I.V paracetamol and the surgery will be allowed to proceed.
Active Comparator: Group C; Group C: Bolus 10 ml Syringe with plain Lidocaine 2%, and infusion 50 ml Syringe with plain Lidocaine 2%.	Drug: Lidocaine IV; After confirming patient history, type of operation and patient group allocation, standard ASA monitoring will be attached to the patient then the I.V induction of anesthesia will be commenced using standard doses of Propofol &Tracrium in addition to 1 μg/kg Fentanyl and 1 ml/10 kg from the bolus Lidocaine syringe followed after 3 minutes by endotracheal intubation, then the Lidocaine infusion Syringe will be attached to a separate I.V line at an infusion rate of 1 ml/10 kg/h. The patient will receive 1 gm of I.V paracetamol and the surgery will be allowed to proceed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Intraoperative opioid consumption (Fentanyl)	Fentanyl doses of 0.5 mic/kg will be given when there is increase in hemodynamics by 20% of baseline and this will be reported	Every five minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total opioid consumption (Morphine) in the first 24 hours postoperative.		Every one hour postoperative for 24 hours
Time of first rescue analgesia used in the first 24 hours postoperative	Time between end of surgery and the first dose of rescue analgesia administered to the patient	Every one hour postoperative for 24 hours
Incidence of side effects related to Lidocaine infusion during the first 24 hours postoperative.		Every one hour postoperative for 24 hours
Incidence of chronic postoperative pain 2 months after the surgery.		Every week for 2 months postoperative.

Collaborators and Investigators

• Sponsor: Cairo University
• Investigators: Study Director: Mohammed Ahmed Mansour, Assistant professor, Cairo University; Study Director: Islam Ayman Mohammed Shawky, MD, Cairo University; Study Director: Nora Amr Agiza, MD, Cairo University; Study Director: Omnia Y Kamel, MD, Cairo University

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2024
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: May 21, 2024
• First Submitted That Met QC Criteria: May 25, 2024
• First Posted (Actual): May 28, 2024

Study Record Updates

• Last Update Posted (Actual): May 28, 2024
• Last Update Submitted That Met QC Criteria: May 25, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chronic Pain; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lidocaine
• Other Study ID Numbers: Pain management

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