The Impact of Intravenous Anaesthesia on Angiogenesis in Patients With Breast Cancer (TIVA/TCI-BC)
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 2

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 .
    

Detailed 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.
    

Intervention name(s): Lidocaine; Sevoflurane; TIVA-TCI; Acetaminophen; Tramadol; Neostigmine; Atropine; BIS
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Device
Intervention description(s): Continuous infusion of lidocaine; maintenance of hypnosis during anaesthesia with sevoflurane; maintenance of hypnosis during anaesthesia with sevoflurane; administration of 1 g acetaminophen for postoperative analgesia; administration of tramadol for postoperative analgesia; 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; For the groups receveing TIVA-TCI anesthesia the bispectral index will be monitored
Other intervention name(s): lidocaine 1%, lignocaine; Diprivan; paracetamol; Tramal; Prostigmin, vagostigmin; atropine sulfate; bispectral index monitor
Intervention MeSH terms: Acetaminophen; Lidocaine; Atropine; Tramadol; Sevoflurane; Neostigmine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: breast cancer; angiogenesis; VEGF