Effects of Dexmedetomidine/Lidocaine/Intrathecal Morphine on Cancer Metastasis Biomarker After Colorectal Surgery

Study Overview
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Brief Summary
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This is a prospective randomized controlled trial. Investigators aimed to compare the effect of three different anesthetic adjuvants (continuous infusion of lidocaine or dexmedetomidine, intrathecal morphine injection) on the biomarker for cancer recurrence and metastasis. Patients undergoing elective colorectal cancer surgery will be randomly allocated to three parallel arms and the biomarkers for cancer recurrence and metastasis, inflammation, and immune response will be compared. And we will compare the clinical outcomes in the three method.

Detailed Description
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Perioperative period is critical in determining the risk of postoperative metastatic disease. Surgical damage and related stress response could suppress cell-mediated immunity and facilitate malignant cell survival, motility, invasion and proliferation. Increasing evidence supported that the continuous infusion of lidocaine or dexmedetomidine, or intrathecal morphine were associated with the reduction of postoperative pain and opioid consumption and improved the quality of recovery. Also, they were reported to decrease perioperative inflammatory responses and preserve immune response which is known to be critical in anti-metastatic process during perioperative period. However, no comparison was conducted among these anesthetic adjuvants. Thus, Investigators try to evaluate the effect on the biomarkers and clinical outcomes in the three methods.

Official Title
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Effect of Dexmedetomidine Infusion, Lidocaine Infusion, and Intrathecal Morphine Injection on Biomarker for Perioperative Stress and Immune Response, and Cancer Progression and Metastasis in Colorectal Cancer Surgery

Conditions
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Colorectal Cancer, Anesthesia, Cancer Metastatic, Inflammation

Intervention / Treatment
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* Drug: Lidocaine IV
* Drug: Dexmedetomidine IV
* Drug: intrathecal morphine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who were scheduled for elective colorectal cancer surgery American Society of Anesthesiologists physical status of I-III Exclusion Criteria: Atrioventricular conduction disorder Having Bradycardia (<50 bpm) Severe pulmonary dysfunction in pulmonary function test High risk for cardiovascular complications(expected postoperative event >5%) Allergy or hypersensitivity reaction to each adjuvant. History or risk factors for Malignant hyperthermia Body mass index >40 kg/m2

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lidocaine group<br>A loading dose of 1.5mg/kg lidocaine will be infused for 10 minutes during anesthesia induction. During the surgery and post-anaesthesia care unit (PACU) stay, 1.5 mg/kg/h of lidocaine were continuously infused until the patient was transferred to the general ward. | Drug: Lidocaine IV<br>* Continuous intravenous infusion of lidocaine<br>* Other names: Lidocaine;|
| Active Comparator: Dexmedetomidine group<br>A loading dose of 0.3mcg/kg dexmedetomidine will be infused for 10 minutes during anesthesia induction. During the surgery and PACU stay, 0.3 mcg/kg/h of dexmedetomidine were continuously infused until the patient was transferred to the general ward. | Drug: Dexmedetomidine IV<br>* Continuous intravenous infusion of dexmedetomidine<br>* Other names: Precedex;|
| Active Comparator: Intrathecal Morphine group<br>200 300mcg of Intrathecal morphine will be injected at the anesthesia induction for colorectal surgery. | Drug: intrathecal morphine<br>* intrathecal morphine injection<br>* Other names: Morphine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MMP | plasma Matrix metalloproteinase-9 | 1 day after surgery | 
| MMP | plasma Matrix metalloproteinase-9 | before surgery | 
| MMP | plasma Matrix metalloproteinase-9 | 1 hour after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MMP | plasma Matrix metalloproteinase-2 | before surgery, 1 hour after surgery, 1 day after surgery | 
| IL-6 | Interleukin-6 | before surgery, 1 hour after surgery, 1 day after surgery | 
| VEGF | vascular endothelial growth factor | before surgery, 1 hour after surgery, 1 day after surgery | 
| lymphocyte subset | CD3+CD4+ (inducer and helper T cells), CD3+CD8+ (suppressor and cytotoxic T cells), CD3-CD16+CD56+ (Natural killer cells), CD39+CD73+ (circulating regulatory T cells), CD73+CD8+ T cells, CD73+CD4+ T cells | before surgery, 1 hour after surgery, 1 day after surgery | 
| numeric rating scale | Pain severity with numeric rating scale for postoperative pain, the value range (0 10), a higher score means more painful | within 3 days after the surgery (0, 1, 6, 24, 48, 72 hour) | 
| postoperative nausea/vomiting | the requirement of rescue antiemetic | within 3 days after the surgery (0, 1, 6, 24, 48, 72 hour) | 
| Opioid consumption | morphine equivalent unit of opioid consumption | within 3 days after the surgery | 
| Time to flatus | from the end of surgery to the time of first flatus | within 7 days after the surgery | 
| Hospital stay | from the end of surgery to patient discharge | Until the discharge (up to postoperative day 30) | 
| Postoperative pulmonary complications | according to the predetermined definition for postoperative pulmonary complications (atelectasis diagnosed by radiographic findings, diagnosed pneumonia) | within 7 days after the surgery | 
| postoperative complications | need for in-and-out catheterization or reinsertion of an indwelling urinary catheter during the hospital stay after the original urinary catheter was removed, and re-operation | within 1 year after the surgery | 
| cancer recurrence | local recurrence or distant metastasis | within 1 year after the surgery | 
| Mortality | patient survival | within 1 year after the surgery |