Lidocaine Infusion With ERAS Protocol 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 , 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.

• Lidocaine IV (Drug): lidocaine infusion as bolus 1.5mg/kg then 2mg/kg/hr
• saline IV (Other): saline infusion same volume as lidocaine

Primary outcomes

• Post-operative nociceptive pain assessment. [24 hours postoperative]: 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.

Secondary outcomes

• Effect on immune response [pre-operative and 5 days postoperative]: Natural killer cell isolation will be done preoperatively and 5 days postoperative
• Effect on i tumor recurrence [pre-operative and 5 days postoperative]: cytotoxic lymphocytes assay will be measured preoperatively and 5 days postoperative
• Total intra-operative fluid requirements. [intra-operative every 10 minutes]: Total intraoperative fluid requirements in liters and fluid responsiveness assessed by pleth variability index (PVI) every 10 minutes to keep value < 13 %.
• Gastro-intestinal recovery. [up to 5 days postoperative]: 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.
• Time to first ambulation [up to 5 days post-operative]: effect of lidocaine and epidural analgesia on pain
• Total analgesic consumption [up to 5 days post-operative]: effect of lidocaine on analgesic requirements
• Length of hospital stay in days [up to 5 days postoperative]: 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
• Effect on haemodynamics [intraoperative and 5 days post-operative]: effect of lidocaine on heart rate in beats per minute
• Effect on haemodynamics [intraoperative and 5 days post-operative]: effect of lidocaine on blood pressure in mmHg
• Perioperative complications [intraoperative and up to 5 days postoperative]: 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.

Sex: All, ages: 30 Years to 70 Years

Inclusion Criteria:

1. Age 30-70 years
2. Both sex.
3. American society of anesthesiology (ASA) physical status class II;III.
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.