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

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

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.

Study Overview

• Status: Completed
• Conditions: Inflammation; Colorectal Cancer; Anesthesia; Cancer Metastatic
• Intervention / Treatment: Drug: Lidocaine IV; Drug: Dexmedetomidine IV; Drug: intrathecal morphine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 114
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lidocaine group; 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; Continuous intravenous infusion of lidocaine; Other Names: Lidocaine
Active Comparator: Dexmedetomidine group; 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; Continuous intravenous infusion of dexmedetomidine; Other Names: Precedex
Active Comparator: Intrathecal Morphine group; 200~300mcg of Intrathecal morphine will be injected at the anesthesia induction for colorectal surgery.	Drug: intrathecal morphine; intrathecal morphine injection; Other Names: Morphine

What is the study measuring?

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
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
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
MMP	plasma Matrix metalloproteinase-2	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

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Collaborators: Korea Institute of Science and Technology
• Investigators: Study Director: Mihye Park, MD, PhD, Samsung Medical Center

Publications and helpful links

General Publications

• Wall TP, Buggy DJ. Perioperative Intravenous Lidocaine and Metastatic Cancer Recurrence - A Narrative Review. Front Oncol. 2021 Aug 2;11:688896. doi: 10.3389/fonc.2021.688896. eCollection 2021.
• Galos EV, Tat TF, Popa R, Efrimescu CI, Finnerty D, Buggy DJ, Ionescu DC, Mihu CM. Neutrophil extracellular trapping and angiogenesis biomarkers after intravenous or inhalation anaesthesia with or without intravenous lidocaine for breast cancer surgery: a prospective, randomised trial. Br J Anaesth. 2020 Nov;125(5):712-721. doi: 10.1016/j.bja.2020.05.003. Epub 2020 Jun 29.
• Wang K, Wu M, Xu J, Wu C, Zhang B, Wang G, Ma D. Effects of dexmedetomidine on perioperative stress, inflammation, and immune function: systematic review and meta-analysis. Br J Anaesth. 2019 Dec;123(6):777-794. doi: 10.1016/j.bja.2019.07.027. Epub 2019 Oct 24.
• Liu Y, Sun J, Wu T, Lu X, Du Y, Duan H, Yu W, Su D, Lu J, Tian J. Effects of serum from breast cancer surgery patients receiving perioperative dexmedetomidine on breast cancer cell malignancy: A prospective randomized controlled trial. Cancer Med. 2019 Dec;8(18):7603-7612. doi: 10.1002/cam4.2654. Epub 2019 Oct 30.
• Le-Wendling L, Nin O, Capdevila X. Cancer Recurrence and Regional Anesthesia: The Theories, the Data, and the Future in Outcomes. Pain Med. 2016 Apr;17(4):756-75. doi: 10.1111/pme.12893. Epub 2016 Feb 2.
• Levins KJ, Prendeville S, Conlon S, Buggy DJ. The effect of anesthetic technique on micro-opioid receptor expression and immune cell infiltration in breast cancer. J Anesth. 2018 Dec;32(6):792-796. doi: 10.1007/s00540-018-2554-0. Epub 2018 Sep 18.

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2023
• Primary Completion (Actual): July 5, 2023
• Study Completion (Actual): August 5, 2023

Study Registration Dates

• First Submitted: February 6, 2023
• First Submitted That Met QC Criteria: February 14, 2023
• First Posted (Actual): February 24, 2023

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Inflammation; Colorectal Neoplasms; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Analgesics, Opioid; Narcotics; Membrane Transport Modulators; Hypnotics and Sedatives; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Dexmedetomidine; Lidocaine; Morphine
• Other Study ID Numbers: SMC 2022-10-021-002

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
• product manufactured in and exported from the U.S.: No