Effect of Perioperative Lidocaine or High-Dose Dexamethasone on Immune Response in Colon Cancer Surgery (PILDI Study)

This study is a prospective, randomized, double-blind, controlled phase II interventional clinical trial conducted at the Institute of Oncology Ljubljana. The trial investigates the effects of two perioperative pharmacological interventions-intravenous lidocaine infusion and high-dose dexamethasone-on postoperative immune response and clinical outcomes in patients undergoing surgical treatment for colon cancer.

Patients undergoing major oncologic surgery may develop significant perioperative immune suppression and inflammatory responses, which can influence postoperative recovery, complication rates, and overall outcomes. Lidocaine is known to have potential anti-inflammatory and immunomodulatory effects, while dexamethasone is widely used perioperatively for its anti-inflammatory properties. However, comparative evidence regarding their impact on postoperative immune response in colorectal cancer surgery is limited.

Eligible participants are adult patients with histologically confirmed colon cancer who are scheduled for surgical resection. After providing written informed consent, participants will be randomized in a double-blind manner to one of two study groups:

Perioperative intravenous lidocaine infusion group

High-dose perioperative dexamethasone group

Both interventions are administered according to the study protocol during the perioperative period. Randomization and masking ensure that participants, investigators, and clinical staff remain blinded to treatment allocation.

The primary objective of the study is to evaluate differences in postoperative immune response between the two intervention arms, assessed through laboratory immune and inflammatory markers. Secondary objectives include evaluation of postoperative clinical outcomes, such as postoperative recovery parameters and complications.

Participants are followed during the perioperative period and after surgery, and study assessments are performed according to the predefined schedule. This study will provide evidence regarding whether perioperative lidocaine infusion may offer beneficial immunological or clinical effects compared with high-dose dexamethasone in patients undergoing surgery for colon cancer. The results may support improved perioperative supportive care strategies and optimization of postoperative recovery in oncologic surgical patients.

• Lidocaine (Drug): Perioperative intravenous lidocaine infusion administered during colorectal cancer surgery according to the study protocol, in addition to standard perioperative care.
• Dexamethasone (Drug): High-dose perioperative intravenous dexamethasone administered according to the study protocol, in addition to standard perioperative care during colorectal cancer surgery.
• Placebo (Drug): Perioperative intravenous placebo administered according to the study protocol, in addition to standard perioperative care during colorectal cancer surgery.

Primary outcomes

• Change in Serum Cytokine Concentrations (IL-6, IL-8, IL-10, TNF-alpha) [Baseline (before anesthesia induction), 2 hours after surgery, postoperative day 1, and postoperative day 2.]: Perioperative immune response is assessed by measuring serum inflammatory cytokine concentrations (IL-6, IL-8, IL-10, and TNF-alpha). Cytokine concentrations are compared between the lidocaine infusion group, the high-dose dexamethasone group, and the placebo group to evaluate differences in inflammatory response following colon cancer surgery.

Secondary outcomes

• Total Opioid Consumption Within 24 Hours After Surgery [First 24 hours after surgery.]: Total postoperative opioid consumption is assessed as the cumulative dose of opioid analgesics administered within the first 24 hours after surgery and compared between study groups.
• Postoperative Pain Intensity Measured by the Visual Analogue Scale [2 hours after surgery and postoperative days 1 and 2.]: Postoperative pain intensity is assessed using the Visual Analogue Scale (VAS) ranging from 0 to 10, where 0 indicates no pain and 10 indicates the worst imaginable pain. Pain scores are compared between study groups.
• Time to First Postoperative Bowel Movement [From end of surgery until first postoperative bowel movement (up to postoperative day 7).]: Time to first postoperative bowel movement is recorded as an indicator of gastrointestinal recovery and compared between study groups.
• Incidence of Postoperative Complications [From surgery through postoperative day 30.]: Incidence of postoperative complications is assessed and compared between study groups, including surgical complications and adverse events potentially related to study medications.

Other outcomes

• Length of Hospital Stay [From surgery until hospital discharge (up to postoperative day 30).]: Length of hospital stay is assessed as the number of days from surgery until hospital discharge and compared between study groups.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Adult patients aged 18 years or older
* Histologically confirmed colon cancer
* Scheduled for elective surgical resection of colon cancer
* Eligible for perioperative treatment with study medication (lidocaine, dexamethasone, or placebo) according to the protocol
* Ability to understand the study procedures and provide written informed consent

Exclusion Criteria:

* Known allergy or hypersensitivity to lidocaine, dexamethasone, or any excipients
* Severe hepatic impairment
* Severe renal impairment
* Severe cardiac conduction disorders or clinically significant arrhythmias
* Pregnancy or breastfeeding
* Severe uncontrolled comorbidities that could interfere with study participation
* Participation in another interventional clinical trial that could influence study outcomes
* Any other condition which, in the opinion of the investigator, makes the patient unsuitable for participation

NIH grants: 2025