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

Sponsor

Udayana University (Other)

Overall Status

Completed

CT.gov ID

NCT04435925

Collaborator

(none)

Enrollment

Location

Arms

9.1

Actual Duration (Months)

5.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Disease Anesthesia Inflammatory Response	Drug: Remifentanil Drug: Fentanyl	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

48 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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 (Participant)

Masking Description:

The opioid selection disguised to the patient. Eligible subjects will be randomized so that each research subject has the same opportunity to be included in both groups.

Primary Purpose:

Supportive Care

Official Title:

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

Actual Study Start Date :

Jul 27, 2020

Actual Primary Completion Date :

Dec 30, 2020

Actual Study Completion Date :

Apr 30, 2021

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Epinephrine [1-hour (postoperative)]
Serum epinephrine level
Epinephrine [24-hours (postoperative)]
Serum epinephrine level
Norepinephrine [1-hour (postoperative)]
Serum norepinephrine level
Norepinephrine [24-hours (postoperative)]
Serum norepinephrine level
PLR [1-hour (postoperative)]
platelet-to-lymphocyte ratio
PLR [24-hours (postoperative)]
platelet-to-lymphocyte ratio
LMR [1-hour (postoperative)]
lymphocyte-to-monocyte ratio
LMR [24-hours (postoperative)]
lymphocyte-to-monocyte ratio
Glucose [1-hour (postoperative)]
serum glucose level
Glucose [24-hours (postoperative)]
serum glucose level

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years to 65 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sanglah General Hospital	Denpasar	Bali	Indonesia	80114

Sponsors and Collaborators

Udayana University

Investigators

Principal Investigator: I Gusti AG Hartawan, Udayana University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Christopher Ryalino, Principal Investigator, Udayana University

ClinicalTrials.gov Identifier:

NCT04435925

Other Study ID Numbers:

UNUD-CTR-FK110620-001

First Posted:

Jun 17, 2020

Last Update Posted:

Jun 2, 2021

Last Verified:

May 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Breast Diseases

Fentanyl

Remifentanil

Study Results

No Results Posted as of Jun 2, 2021