Inflammatory Effect Comparison Between Fentanyl and Remifentanil in Mastectomy Under General Anesthesia

Study Overview
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Brief Summary
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Mastectomy triggers stress and inflammation responses due to tissue trauma. Surgical stress will increase levels of hormones (adrenocorticotropic hormone, cortisol, antidiuretic hormone, epinephrine, norepinephrine, and dopamine) and inflammatory cytokines (Tumor Necrotic Factor-α, interleukin-1, interleukin-2, and interleukin-6) in the body. This causes insulin resistance, gluconeogenesis, and glycolysis, and impaired insulin secretion, which results in hyperglycemia due to intraoperative stress. Intraoperative hyperglycemia increases postoperative complications and mortality. Inhibition of hyperglycemia due to operative stress and stress hormones with good anesthetic management in improving patient outcomes. The choice of opioid type plays an important role in suppressing the perioperative stress and inflammatory response. Opioids are an alternative, besides the use of regional anesthetic techniques which have been proven to suppress the perioperative stress response. Fentanyl is one of the phenylpiperidine synthetic opioids. Large doses of fentanyl can reduce stress responses but also increase side effects, such as hemodynamic instability and decrease T-cell function. Remifentanil provides unique pharmacokinetic benefits through nonspecific esterase enzyme metabolism, so it has a very fast onset and half-life. In addition, remifentanil also provides benefits in reducing the production of interleukin 6 cytokines (IL-6) and tumor necrosis factor α (TNF-α) and inhibits neutrophil migration through the endothelial layer. The stress response to stress and inflammation is directly proportional to the dose of remifentanil given. It is reported that remifentanil can suppress cortisol response according to increasing dose. Winterhalter et al. and Lee et al. reported that remifentanil is better at suppressing the stress response than fentanyl. On the other hand, Bell et al. showed no difference in cortisol and hemodynamic levels between the two groups. The goal of this study is to see if remifentanil provides less increase in serum epinephrine level, norepinephrine level, platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), and blood glucose level at one-hour and 24-hours postoperative in patients undergoing mastectomy surgery under general anesthesia.

Official Title
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Inflammatory Effect Comparison Between Fentanyl and Remifentanil in Mastectomy Under General Anesthesia

Conditions
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Breast Disease, Anesthesia, Inflammatory Response

Intervention / Treatment
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* Drug: Remifentanil
* Drug: Fentanyl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients scheduled for a mastectomy under general anesthesia Patients aged 30-65 years old ASA physical status: I-II Exclusion Criteria: Refusal to be included in the study History of opioid allergies Long-term use of steroids Patients on β blockers medication History of diabetes, autoimmune disease, or heart disease

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a single-blind, randomized control trial. It provides a controlled treatment of general anesthesia with an opioid regimen between remifentanil and fentanyl.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Remifentanil<br>Patients assigned to this group will receive IV Remifentanil as an opioid for general anesthesia. | Drug: Remifentanil<br>* Loading dose: 0.5 mcg/kg Maintenance dose: 1 mcg/kg/minute<br>|
| Placebo Comparator: Fentanyl<br>Patients assigned to this group will receive IV Fentanyl as an opioid for general anesthesia. | Drug: Fentanyl<br>* Loading dose: 2 mcg/kg Maintenance dose: 0.4 mcg/kg/30-minutes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Epinephrine | Serum epinephrine level | 1-hour (postoperative) | 
| Epinephrine | Serum epinephrine level | 24-hours (postoperative) | 
| Norepinephrine | Serum norepinephrine level | 1-hour (postoperative) | 
| Norepinephrine | Serum norepinephrine level | 24-hours (postoperative) | 
| PLR | platelet-to-lymphocyte ratio | 1-hour (postoperative) | 
| PLR | platelet-to-lymphocyte ratio | 24-hours (postoperative) | 
| LMR | lymphocyte-to-monocyte ratio | 1-hour (postoperative) | 
| LMR | lymphocyte-to-monocyte ratio | 24-hours (postoperative) | 
| Glucose | serum glucose level | 1-hour (postoperative) | 
| Glucose | serum glucose level | 24-hours (postoperative) |