Lidocaine Infusion With ERAS Protocol for Pancreatic Cancer Surgery: Effect on Pain and Patient Immunity. (ERAS)

Lidocaine Infusion With Enhanced Recovery Program for Pancreatic Cancer Surgery: Effect on Pain and Patient Immunity

The whole world now is directed to implement strategies that enhance the patient's quality of life and prevent tumor relapse.

Enhanced recovery after pancreatic surgery (ERAPS) program was found to improve the quality of life as it is an evidence-based protocol designed to standardize and optimize perioperative medical care in order to reduce surgical trauma, perioperative physiological stress, organ dysfunction, reduction of clinical complications, length of hospital stay and the health costs together with increase of patient satisfaction.

lidocaine; it is an amide local anaesthetic Recently its use as intravenous perioperative infusion for abdominal cancer surgeries is encouraging, as it significantly reduces postoperative pain, opioid consumption and nausea and vomiting. it also promotes gastrointestinal function recovery, and shortens the postoperative hospital stay. In addition, lidocaine in particular can act directly and indirectly on pancreatic cancer cells and the tumor microenvironment.

The investigators suggest that IV lidocaine infusion in combination with ERAPS protocol may achieve better postoperative outcomes after pancreatic surgery for cancer.

Study Overview

• Status: Recruiting
• Conditions: Lidocaine; ERAS
• Intervention / Treatment: Drug: Lidocaine IV; Other: saline IV

Detailed Description

The whole world now is directed to implement strategies that enhance the patient's quality of life and prevent tumor relapse , so the Enhanced recovery after pancreatic surgery (ERAPS) program was found to improve the quality of life as it is an evidence-based protocol designed to standardize and optimize perioperative medical care in order to reduce surgical trauma, perioperative physiological stress, organ dysfunction, reduction of clinical complications, length of hospital stay and the health costs together with increase of patient satisfaction.

ERAPS was applied for pancreatic surgery in 2012, since that time 27 developed ERAPS items were evaluated, 5 of them got the highest level of evidence those include (avoiding hypothermia, use of wound catheters for continuous analgesia, antimicrobial, thromboprophylaxis protocols and preoperative nutritional interventions for patients with severe weight loss (15%). ERAS society encourages further researches to improve compliance and outcome and to confirm the benefit of current updated recommendations.

Many drugs had been used in the anaesthetic management of major abdominal surgeries and of which is lidocaine; it is an amide local anaesthetic commonly used for regional and neuraxial blocks. Recently its use as intravenous perioperative infusion for abdominal cancer surgeries is encouraging, as it significantly reduces postoperative pain, opioid consumption and nausea and vomiting. it also promotes gastrointestinal function recovery, and shortens the postoperative hospital stay.

In addition, lidocaine in particular can act directly and indirectly on pancreatic cancer cells and the tumor microenvironment. At the tumor level, lidocaine can induce apoptosis in cancer cells by inhibiting Src phosphorylation and reducing the expression of adhesion molecules. In the tumor microenvironment, lidocaine can enhance the activity of immune cells such as natural killer cells, which are responsible for directly attacking cancer cells. Furthermore the impact of lidocaine on post-operative opioid consumption could be another factor that reduces the opioid associated cancer progression.

Natural killer (NK) cells are cluster of differentiation 3 (CD3-) -cluster of differentiation 56 (CD56+) lymphocytes playing a pivotal role in the innate immune response against cancer. Their main purpose is identification and eradication of virus infected cells and metastatic cells. Diminished activity of NK cells is a predisposing factor for cancer recurrence. Preservation of innate immune function and the direct anti-inflammatory effects may be the cause of the protective effects of local anaesthetics and regional techniques.

Different concentrations of local anaesthetics appear to have different effects on NK cytotoxicity. High concentrations of lidocaine suppress NK cell cytotoxicity; yet clinically relevant concentrations enhance the in vitro function of NK cells via the release of lytic granules. Hence, lidocaine appears to have predominantly anticancer effects So the investigators suggest that IV lidocaine infusion in combination with ERAPS protocol may achieve better postoperative outcomes after pancreatic surgery for cancer.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alaa ghoneim, master; Phone Number: 01207305773; Email: alaa.aghoneim@gmail.com

Study Locations

• Egypt
  • Alexandria, Egypt
    • Recruiting
    • Alexandria University
    • Contact: sahar elkaradawy, professor; Phone Number: 01067940614; Email: saharelkaradawy@yahoo.com
    • Contact: emad eldin arida, professor; Phone Number: 01223129135; Email: aridae@yahoo.com
    • Sub-Investigator: ashraf arafart, professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 30-70 years
2. Both sex.
3. American society of anesthesiology (ASA) physical status class II.
4. Resectable pancreatic tumors.

Exclusion Criteria:

1. Patients with history of sensitivity to lidocaine,
2. Diabetic patients.
3. Body weight loss > 15%.
4. Opioid tolerant patient or patient receiving nonsteroidal anti-inflammatory drugs within 1 week of surgery or antiarrythmic drugs.
5. Cognitive dysfunction.
6. Any history of antitumor treatments or chemotherapy before surgery
7. Any contraindication for neuraxial anaesthesia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: infusion of intraoperative lidocaine to patients undergoing whipple surgery; lidocaine 1.5mg/kg infused as bolus, then 2mg/kg/hr through the operation	Drug: Lidocaine IV; lidocaine infusion as bolus 1.5mg/kg then 2mg/kg/hr
Experimental: saline infusion of same volume of lidocaine; same amount of normal saline infused as bolus and infusion	Other: saline IV; saline infusion same volume as lidocaine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-operative nociceptive pain assessment.	post operative pain assessment using visual analogue scale (VAS), The VAS consists of a 10cm line, with two end points representing 0 ('no pain') and 10 ('pain as bad as it could possibly be.	24 hours postoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect on immune response	Natural killer cell isolation will be done preoperatively and 5 days postoperative	pre-operative and 5 days postoperative
Effect on i tumor recurrence	cytotoxic lymphocytes assay will be measured preoperatively and 5 days postoperative	pre-operative and 5 days postoperative
Total intra-operative fluid requirements.	Total intraoperative fluid requirements in liters and fluid responsiveness assessed by pleth variability index (PVI) every 10 minutes to keep value < 13 %.	intra-operative every 10 minutes
Gastro-intestinal recovery.	effect of lidocaine on enhancing gastrointestinal motility,Time to return of bowel sounds in hours, first time to pass flatus and time to first defecation in hours will be recorded.	up to 5 days postoperative
Time to first ambulation	effect of lidocaine and epidural analgesia on pain	up to 5 days post-operative
Total analgesic consumption	effect of lidocaine on analgesic requirements	up to 5 days post-operative
Length of hospital stay in days	effect of lidocaine on ERAS and Duration of hospital stay in days will be recorded in both groups including the start of the hospitalization time	up to 5 days postoperative
Effect on haemodynamics	effect of lidocaine on heart rate in beats per minute	intraoperative and 5 days post-operative
Effect on haemodynamics	effect of lidocaine on blood pressure in mmHg	intraoperative and 5 days post-operative
Perioperative complications	recording of any complications perioperatively and postoperatively Nausea and vomiting, wound infection, urinary tract infection, deep vein thrombosis and hematoma will be recorded in both groups.	intraoperative and up to 5 days postoperative

Collaborators and Investigators

• Sponsor: Alexandria University
• Collaborators: University of Alexandria

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2022
• Primary Completion (Anticipated): May 20, 2023
• Study Completion (Anticipated): July 1, 2023

Study Registration Dates

• First Submitted: June 2, 2022
• First Submitted That Met QC Criteria: July 21, 2022
• First Posted (Actual): July 22, 2022

Study Record Updates

• Last Update Posted (Actual): July 22, 2022
• Last Update Submitted That Met QC Criteria: July 21, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: 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: lidocaine ERAS whipple

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: through clinical trials
• IPD Sharing Time Frame: 6 months up to 1 year
• IPD Sharing Access Criteria: Lidocaine ERAS whipple surgery patient immunity
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

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