The Impact of Intravenous Anaesthesia on Angiogenesis in Patients With Breast Cancer (TIVA/TCI-BC)

NCT02839668 | Completed Phase 2

• 1 other identifier: IuliuHatieganu Cluj-Napoca
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Because neoplastic disease is one of the leading causes of death worldwide and breast cancer is one of the most frequent neoplasia among women, the possibility of influencing the evolution of patients starting from the moment of surgical intervention using a perianesthesic intervention is a scientific topic of high interest. The study will compare two anesthetic techniques and their efficiency in lowering the factors that can favorize the dissemination of neoplasia and their role in the prevention of postoperative pain. The serum level of vascular endothelial growth factor A (VEGF-A) will be determined before and after the surgical intervention after using two different types of anesthesia (inhalational and intravenous), and the immunohistochemical expression of vascular endothelial growth factor receptors (VEGFR) will be determined on the excised tissue. For the two different types of anesthesia a continuous infusion of lidocaine 1% will be associated. The study will compare the short-term and long term-outcome of the patients assigned the two different types of anesthesia and their immediate postoperative evolution .

Conditions

Breast Cancer

Keywords

breast cancer; angiogenesis; VEGF

Outcome Measures

Primary Outcomes (1)

• serum concentration of vascular endothelial growth factor A (VEGF-A)

  1 year

Secondary Outcomes (3)

• pain score

  1 year

• survival of patients

  up to 5 years

• Vascular endothelial growth factor receptor 1 and 2 (VEGFR1 and VEGFR2) density

  at the end of the study

Study Arms (4)

Sevoflurane

EXPERIMENTAL

The patients enrolled in this arm will receive general anesthesia in which the hypnosis will be maintained with Sevoflurane. Postoperative analgesia will be assured by the administration of tramadol and acetaminophen.A 0.05 mg/kg dose of neostigmine will be administered to antagonize the neuromuscular block at the end of surgery.A 0.2 mg/kg dose of atropine will be administered at the end of surgery to attenuate the parasymatomimetic effects of neostigmine.The bispectral index- BIS will be monitored throughout the anesthesia

Drug: Sevoflurane; Drug: Acetaminophen; Drug: Tramadol; Drug: Neostigmine; Drug: Atropine; Device: BIS

Sevoflurane+Lidocaine

ACTIVE COMPARATOR

The patients enrolled in this group will receive general anesthesia in which the hypnosis will be maintained with Sevoflurane. At the induction of anesthesia the patients will receive a bolus of lidocaine 1% 1.5 mg/kg. A continuous infusion of lidocaine 1% of 2 mg/kg/h will be associated throughout the surgical procedure and 1mg/kg/h until 24 h postoperative. Postoperative analgesia will be assured by the administration of tramadol and acetaminophen.A 0.05 mg/kg dose of neostigmine will be administered to antagonize the neuromuscular block at the end of surgery. A 0.2 mg/kg dose of atropine will be administered at the end of surgery to attenuate the parasymatomimetic effects of neostigmine.The bispectral index- BIS will be monitored throughout the anesthesia

Drug: Lidocaine; Drug: Sevoflurane; Drug: Acetaminophen; Drug: Tramadol; Drug: Neostigmine; Drug: Atropine; Device: BIS

TIVA-TCI

EXPERIMENTAL

The patients enrolled in this group will receive total intravenous anesthesia with propofol using a target controlled infusion technique for the maintenance of hypnosis throughout the surgery. Postoperative analgesia will be assured by the administration of tramadol and acetaminophen.A 0.05 mg/kg dose of neostigmine will be administered to antagonize the neuromuscular block at the end of surgery.A 0.2 mg/kg dose of atropine will be administered at the end of surgery to attenuate the parasymatomimetic effects of neostigmine. The bispectral index- BIS will be monitored throughout the anesthesia.

Drug: TIVA-TCI; Drug: Acetaminophen; Drug: Tramadol; Drug: Neostigmine; Drug: Atropine; Device: BIS

TIVA-TCI+lidocaine

ACTIVE COMPARATOR

The patients enrolled in this group will receive total intravenous anesthesia with propofol using a target controlled infusion technique for the maintenance of hypnosis throughout the surgery. At the induction of anesthesia the patients will receive a bolus of lidocaine 1% 1.5 mg/kg. A continuous infusion of lidocaine 1% of 2 mg/kg/h will be associated throughout the surgical procedure and 1mg/kg/h until 24 h postoperative. Postoperative analgesia will be assured by the administration of tramadol and acetaminophen.A 0.05 mg/kg dose of neostigmine will be administered to antagonize the neuromuscular block at the end of surgery. A 0.2 mg/kg dose of atropine will be administered at the end of surgery to attenuate the parasymatomimetic effects of neostigmine.The bispectral index- BIS will be monitored throughout the anesthesia.

Drug: Lidocaine; Drug: TIVA-TCI; Drug: Acetaminophen; Drug: Tramadol; Drug: Neostigmine; Drug: Atropine; Device: BIS

Interventions

Lidocaine DRUG

Continuous infusion of lidocaine

Also known as: lidocaine 1%, lignocaine

Sevoflurane+Lidocaine; TIVA-TCI+lidocaine

Sevoflurane DRUG

maintenance of hypnosis during anaesthesia with sevoflurane

Sevoflurane; Sevoflurane+Lidocaine

TIVA-TCI DRUG

maintenance of hypnosis during anaesthesia with sevoflurane

Also known as: Diprivan

TIVA-TCI; TIVA-TCI+lidocaine

Acetaminophen DRUG

administration of 1 g acetaminophen for postoperative analgesia

Also known as: paracetamol

Sevoflurane; Sevoflurane+Lidocaine; TIVA-TCI; TIVA-TCI+lidocaine

Tramadol DRUG

administration of tramadol for postoperative analgesia

Also known as: Tramal

Sevoflurane; Sevoflurane+Lidocaine; TIVA-TCI; TIVA-TCI+lidocaine

Neostigmine DRUG

A 0.05 mg/kg dose of neostigmine will be administered to antagonize the neuromuscular block at the end of surgery.

Also known as: Prostigmin, vagostigmin

Sevoflurane; Sevoflurane+Lidocaine; TIVA-TCI; TIVA-TCI+lidocaine

Atropine DRUG

A 0.2 mg/kg dose of atropine will be administered at the end of surgery to attenuate the parasymatomimetic effects of neostigmine

Also known as: atropine sulfate

Sevoflurane; Sevoflurane+Lidocaine; TIVA-TCI; TIVA-TCI+lidocaine

BIS DEVICE

For the groups receveing TIVA-TCI anesthesia the bispectral index will be monitored

Also known as: bispectral index monitor

Sevoflurane; Sevoflurane+Lidocaine; TIVA-TCI; TIVA-TCI+lidocaine

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• diagnosis of breast cancer
• ASA risk class I-III
• no metastatic disease

You may not qualify if:

• hepatic, pulmonary metastasis
• type I and II diabetes
• rheumatoid arthritis
• osteoarthritis
• ischemic cardiovascular disease (history of myocardial infarction, angina)
• peripheral vascular disease
• endometriosis
• allergies to lidocaine, fentanyl, propofol, sevoflurane, atracurium, midazolam, acetaminophen, tramadol
• neuropsychiatric disorders
• incapacity of understanding the study
• refusal of participation

Sponsors & Collaborators

• Iuliu Hatieganu University of Medicine and Pharmacy: lead
• Prof. Dr. I. Chiricuta Institute of Oncology: collaborator

Study Sites (1)

IOCN Prof Dr I chiricuta

Cluj-Napoca, 400015, Romania

Location

Related Publications (5)

• Mao L, Lin S, Lin J. The effects of anesthetics on tumor progression. Int J Physiol Pathophysiol Pharmacol. 2013;5(1):1-10. Epub 2013 Mar 8.

  PMID: 23525301 BACKGROUND

• Byrne K, Levins KJ, Buggy DJ. Can anesthetic-analgesic technique during primary cancer surgery affect recurrence or metastasis? Can J Anaesth. 2016 Feb;63(2):184-92. doi: 10.1007/s12630-015-0523-8.

  PMID: 26497721 BACKGROUND

• Chang YC, Liu CL, Chen MJ, Hsu YW, Chen SN, Lin CH, Chen CM, Yang FM, Hu MC. Local anesthetics induce apoptosis in human breast tumor cells. Anesth Analg. 2014 Jan;118(1):116-24. doi: 10.1213/ANE.0b013e3182a94479.

  PMID: 24247230 RESULT

• Terkawi AS, Sharma S, Durieux ME, Thammishetti S, Brenin D, Tiouririne M. Perioperative lidocaine infusion reduces the incidence of post-mastectomy chronic pain: a double-blind, placebo-controlled randomized trial. Pain Physician. 2015 Mar-Apr;18(2):E139-46.

  PMID: 25794212 RESULT

• 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.

  PMID: 32616309 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Lidocaine; Sevoflurane; Propofol; Acetaminophen; Tramadol; Neostigmine; Atropine; Consciousness Monitors

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Methyl Ethers; Ethers; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Dimethylamines; Methylamines; Lipids; Phenylammonium Compounds; Quaternary Ammonium Compounds; Onium Compounds; Atropine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Surgical Equipment; Equipment and Supplies

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Universitary Assistant

Study Record Dates

• First Submitted: June 18, 2016
• First Posted: July 21, 2016
• Study Start: August 1, 2016
• Primary Completion: September 1, 2019
• Study Completion: September 1, 2019
• Last Updated: October 29, 2019

Record last verified: 2019-10

Locations

RO (1)