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

Breast Cancer Clinical Trial

— TIVA/TCI-BC  

Official title:

The Impact of Intravenous Anaesthesia on Angiogenesis in Patients With Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02839668
• Other study ID #: IuliuHatieganu Cluj-Napoca
• Status: Completed
• Phase: Phase 2
• Start date: August 2016
• Est. completion date: September 2019

Study information

• Verified date: October 2019
• Source: Iuliu Hatieganu University of Medicine and Pharmacy
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 .

Description:

The study will enroll patients with ages between 18 and 80 years old, diagnosed with breast cancer but without proof of disease dissemination on medical imaging. After obtaining an informed consent the patients will be computer randomized to 4 groups. Each group will benefit from a certain type of anesthesia. The first group will be assigned general anesthesia using Sevoflurane for maintenance of hypnosis, the second group will be assigned general anesthesia with Sevoflurane and a continuous infusion of lidocaine 1%. The thrid group will be assigned total intravenous anesthesia using propofol for maintenance of hypnosis and the fourth group will be assigned to total intravenous anesthesia with propofol and a continuous infusion of lidocaine 1%. Before the surgical procedure a blood sample will be drawn from each patient for the measurement of serum vascular endothelial growth factor A ( VEGF-A). All the patients will receive pre-medication a night before the intervention with low molecular weight heparin (LMWH) and midazolam 5mg the morning of the intervention. For the first two groups the anesthetic induction will be conducted using propofol 1,5-2 mg/kg, fentanyl 1-3 microg/kg, atracurium 0,5 mg/kg.For the maintenance of anesthesia Sevoflurane will be used at a alveolar concentration of 1-1,5 MAC, as to maintain a BIS between 45-55. Intraoperative anesthesia will be ensured by using fentanyl boluses of 100 microg and the muscular relaxation needed for mechanical ventilation will be maintained using boluses of 10 mg of atracurium. At the end of the surgery the neuromuscular blockade will be antagonized with neostigmine 0.05 mg/kg and atropine 0.2 mg/kg. For the second group at the induction of anesthesia the patient will be administered a bolus of lidocaine 1% of 1.5 mg/kg and a continuous infusion of lidocaine 1% 2 mg/kg/h will be associated throughout the procedure and 1mg/kg/h,24 h postoperative. The postoperative analgesia will be assured by administering acetaminophen 1 g each 8 h and tramadol 25-50 mg each 4-6 h as needed. For the third and fourth groups the induction of aneshesia will be made using propofol administered by target controlled infusion (TCI) technique with a target plasma concentration of 4 microg/ml . Throughout the intervention the plasma concentration of propofol will be adjusted with increments of 0.2 microg/ml as to maintain a BIS between 45-55. To attenuate the response to laryngoscopy the patient will receive a bolus of fentanyl 1-3 microg/ml. During the intervention fentanyl will be administered in boluses of 100microg as needed. Muscular relaxation necessary for intubation will be provided using atracurium 0.5 mg/kg at induction of anesthesia and 10 mg boluses during the surgery as needed. At the end of the surgery the neuromuscular blockade will be antagonized with neostigmine 0.05 mg/kg and atropine 0.2 mg/kg. For the fourth group at the induction of anesthesia the patient will be administered a bolus of lidocaine 1% of 1.5 mg/kg and a continuous infusion of lidocaine 1% 2 mg/kg/h will be associated throughout the procedure and 1mg/kg/h, 24 h postoperative.Postoperative analgesia will be assured by administering acetaminophen 1 g each 8 h and tramadol 25-50 mg each 4-6 h as needed. Throughout the surgical intervention the patients will be monitored accordingly to the American Society of Anesthesiologists (ASA) standards (electrocardiogram-ECG, heart rate- HR, peripheral capillary oxygen saturation- SpO2, non-invasive blood pressure- NIBP, capnography and for the 3rd and 4th groups the bispectral index - BIS will be monitored). In the postoperative period non-invasive blood pressure -NIBP, heart rate- HR,peripheral capillary oxygen saturation SpO2, intensity of pain at 24 and 48 h will be monitored.Vascular endothelial growth factor- VEGF levels will be monitored at 24 h postoperative using ELISA technique. Vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2) will be determined using immunohistochemical staining.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: September 2019
• Est. primary completion date: September 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• diagnosis of breast cancer

• ASA risk class I-III

• no metastatic disease

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Lidocaine
Continuous infusion of lidocaine
• Sevoflurane
maintenance of hypnosis during anaesthesia with sevoflurane
• TIVA-TCI
maintenance of hypnosis during anaesthesia with sevoflurane
• Acetaminophen
administration of 1 g acetaminophen for postoperative analgesia
• Tramadol
administration of tramadol for postoperative analgesia
• Neostigmine
A 0.05 mg/kg dose of neostigmine will be administered to antagonize the neuromuscular block at the end of surgery.
• Atropine
A 0.2 mg/kg dose of atropine will be administered at the end of surgery to attenuate the parasymatomimetic effects of neostigmine

Device:
• BIS
For the groups receveing TIVA-TCI anesthesia the bispectral index will be monitored

Locations

Country	Name	City	State
Romania	IOCN Prof Dr I chiricuta	Cluj-Napoca

Sponsors (2)

Lead Sponsor	Collaborator
Iuliu Hatieganu University of Medicine and Pharmacy	Prof. Dr. I. Chiricuta Institute of Oncology

Country where clinical trial is conducted

Romania, 

References & Publications (4)

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. Review. — View Citation

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. — View Citation

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. — View Citation

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- — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	serum concentration of vascular endothelial growth factor A (VEGF-A)		1 year
Secondary	pain score	assesed using visual-analogue scale	1 year
Secondary	survival of patients		up to 5 years
Secondary	Vascular endothelial growth factor receptor 1 and 2 (VEGFR1 and VEGFR2) density		at the end of the study