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

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.

Study Overview

• Status: Completed
• Conditions: Inflammatory Response; Anesthesia; Breast Disease
• Intervention / Treatment: Drug: Remifentanil; Drug: Fentanyl

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Indonesia
  • Bali
    • Denpasar, Bali, Indonesia, 80114
      • Sanglah General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Remifentanil; Patients assigned to this group will receive IV Remifentanil as an opioid for general anesthesia.	Drug: Remifentanil; Loading dose: 0.5 mcg/kg Maintenance dose: 1 mcg/kg/minute
PLACEBO_COMPARATOR: Fentanyl; Patients assigned to this group will receive IV Fentanyl as an opioid for general anesthesia.	Drug: Fentanyl; Loading dose: 2 mcg/kg Maintenance dose: 0.4 mcg/kg/30-minutes

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Udayana University
• Investigators: Principal Investigator: I Gusti AG Hartawan, Udayana University

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 27, 2020
• Primary Completion (ACTUAL): December 30, 2020
• Study Completion (ACTUAL): April 30, 2021

Study Registration Dates

• First Submitted: June 11, 2020
• First Submitted That Met QC Criteria: June 15, 2020
• First Posted (ACTUAL): June 17, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 2, 2021
• Last Update Submitted That Met QC Criteria: May 30, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Breast Diseases; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Remifentanil; Fentanyl
• Other Study ID Numbers: UNUD-CTR-FK110620-001

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