Effect of TIVA Propofol vs Sevoflurane Anaesthetic on Serum Biomarkers and on PBMCs in Breast Cancer Surgery

Not Applicable

Withdrawn

• Conditions: Female Breast Cancer
• Interventions: Drug: Fluoromethyl hexafluoroisopropyl ether; Drug: 2,6-Diisopropylphenol; Drug: Fentanyl Citrate; Drug: Atracurium Besylate

• Registration Number: NCT03005860
• Lead Sponsor: Tata Memorial Centre

Brief Summary

Surgery, perioperative stress, anaesthetics and analgesics may modulate the immunosurveillance mechanisms and overwhelm host defences that normally maintain a balance between immunity \& carcinogenesis. This may lead to escape of cancer cells and tilt the scales toward a more protumorigenic microenvironment. Volatile agents, in particular, have been shown to exhibit profound immunosuppressive effects. In comparison, propofol has a favorable profile and inhibits cancer cell activity. Determining "cancer-protective" role of TIVA with propofol presents an exciting window of opportunity that has potential to improve outcomes in cancer patients undergoing resection surgery

Detailed Description

For the current study, consenting patients planned for upfront surgery, will be randomly allocated to 2 groups- 20 patients each group: Propofol TCI-based Total Intravenous Anesthesia group (Propofol group) and Sevoflurane group (Sevoflurane group), according to computer generated randomization number.

Patients will be monitored routinely with ECG, non invasive blood pressure, and a pulse- oximetery (SPO2), every 5 min. An intravenous access will be established with 20- 22 G cannula. A perioperative antibiotic prophylaxis will be given to all patients. None of the patients will receive any premedication.

After preoxygenation with 100% O2 for 3 min: group specific separate interventions will be performed.

Patient will be ventilated with TV of 6-8ml/kg,respiratory rate will be adjusted to maintain end-tidal CO2 value between 40 - 45 mmHg. Crystalloids will be used for hydration (4-6 ml/kg/h), and intraoperative volume deficits will be replaced by additional administration of a solution according to clinical needs. For TIVA group, the depth of anaesthesia will be monitored using Bispectral Index, with target BIS value between 40 and 60. For Sevoflurane group, the depth of anaesthesia will be monitored using MAC, with target MAC value between 0.8 and 1. Half hour before conclusion of surgery, all patients will receive 0.1mg/kg of ondansetron as prophylaxis for PONV. At the end of surgery, muscle relaxation will be reversed by glycopyrrolate (10mcg/kg) and neostigmine (50mcg/kg).

Patients in both groups will receive intra-venous non-steroidal anti-inflammatory drug 1-1.5mg/kg diclofenac + Paracetamol 1gm just before conclusion of surgery for postoperative analgesia. Postoperative pain \& PONV will be managed as per institutional protocols.

ASSAY Peripheral blood (5ml) will be collected from patients in EDTA vaccutainer and (5ml) in another vaccutainer containing clot activator. The sample will be collected at following time points.

1. before anaesthesia (Tpre)

2. after removal of tumor intraoperative (Ti)

3. 2 h after surgery (T2h) , and

4. (T24h) 24 hours after surgery

Estimation of serum cytokines : by sandwich ELISA and by cytokine bead array (CBA) method.

Expression of various lymphocyte subsets (CD3+ T cells, CD4+ helper T cells, CD8+ cytotoxic T cells, γδT cells, NK cells and B cells) by flow cytometry

Study Timeline

• Study First Submitted: 2016-12-20
• Study First Submitted QC: 2016-12-26
• Study First Posted: 2016-12-29
• Study Start: 2017-01-01
• Status Verified: 2020-03
• Primary Completion: 2020-10
• Study Completion: 2020-12
• Last Update Submitted: 2023-12-15
• Last Update Posted: 2023-12-21

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Female
• Target Recruitment: Not specified

Inclusion Criteria

1. Women with histopathologically (biopsy/FNAC) proven breast carcinoma with Resectable disease (T 1-4, N 0-1, M 0) [Stage I-III].
2. Willing for upfront modified radical mastectomy.
3. ASA Physical Status 1-2

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Exclusion Criteria

1. use of morphine or on steroid therapy upto 3 months before surgery;
2. history of substance abuse or cognitive dysfunction;
3. endocrine disorders- diabetes, hypothyroid;
4. history of HIV, Hep-B or Hep-C infections;
5. Contraindication to analgesics or anaesthetic drugs;
6. Pregnant & lactating women

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2,6 diisopropylphenol	Fentanyl Citrate	In Propofol group, anesthesia will be will be induced with Propofol TCI \[target controlled infusion pump - Injectomat® TIVA Agilia (Fresenius Kabi)\] using Schneider model to achieve target site concentration of 4-6mcg/ml, fentanyl citrate 2mcg/kg and atracurium besylate 0.5mg /kg to facilitate LMA placement. Anaesthesia will be maintained with TCI propofol at 3 - 6 mcg/ml as effect site concentration to maintain BIS 40-60.
Fluoromethyl hexafluoroisopropyl ether	Fluoromethyl hexafluoroisopropyl ether	In Sevoflurane group, anaesthesia will be induced with Thiopental 5 - 7mg/kg, fentanyl citrate 2mcg/kg and atracurium besylate 0.5mg /kg to facilitate LMA placement. Anaesthesia will be maintained with sevoflurane 2-2.2 % to maintain a target MAC value between 0.8 \& 1.0.
Fluoromethyl hexafluoroisopropyl ether	Fentanyl Citrate	In Sevoflurane group, anaesthesia will be induced with Thiopental 5 - 7mg/kg, fentanyl citrate 2mcg/kg and atracurium besylate 0.5mg /kg to facilitate LMA placement. Anaesthesia will be maintained with sevoflurane 2-2.2 % to maintain a target MAC value between 0.8 \& 1.0.
Fluoromethyl hexafluoroisopropyl ether	Atracurium Besylate	In Sevoflurane group, anaesthesia will be induced with Thiopental 5 - 7mg/kg, fentanyl citrate 2mcg/kg and atracurium besylate 0.5mg /kg to facilitate LMA placement. Anaesthesia will be maintained with sevoflurane 2-2.2 % to maintain a target MAC value between 0.8 \& 1.0.
2,6 diisopropylphenol	2,6-Diisopropylphenol	In Propofol group, anesthesia will be will be induced with Propofol TCI \[target controlled infusion pump - Injectomat® TIVA Agilia (Fresenius Kabi)\] using Schneider model to achieve target site concentration of 4-6mcg/ml, fentanyl citrate 2mcg/kg and atracurium besylate 0.5mg /kg to facilitate LMA placement. Anaesthesia will be maintained with TCI propofol at 3 - 6 mcg/ml as effect site concentration to maintain BIS 40-60.
2,6 diisopropylphenol	Atracurium Besylate	In Propofol group, anesthesia will be will be induced with Propofol TCI \[target controlled infusion pump - Injectomat® TIVA Agilia (Fresenius Kabi)\] using Schneider model to achieve target site concentration of 4-6mcg/ml, fentanyl citrate 2mcg/kg and atracurium besylate 0.5mg /kg to facilitate LMA placement. Anaesthesia will be maintained with TCI propofol at 3 - 6 mcg/ml as effect site concentration to maintain BIS 40-60.

Primary Outcome Measures

Name	Time	Method
Change in baseline levels versus 24 hour postoperative levels (Tpre vs T24h ) of serum HIF-1a and VEGF-C in both groups.	Baseline levels versus 24 hour postoperative levels (Tpre vs T24h )	The primary objective of this study is to compare the potential effects of inhalation anesthetic (Sevoflurane) with intravenous anesthetic agent (Propofol) on preoperative levels versus 24hour postoperative levels (Tpre vs T24h ) of serum Hypoxia Inducible Factor-1 alpha (HIF-1a) and Vascular Endothelial Growth Factor -C (VEGF-C) in patients with breast cancer undergoing resection surgery.

Secondary Outcome Measures

Name	Time	Method
Change in levels of serum biomarkers HIF-1a & VEGF-C in patients with breast cancer undergoing resection surgery at other time points - intraoperative, at 2hr postoperative. Ti, T2h in both groups.	after removal of tumor intraoperative (Ti) and 24 hours after surgery (T24h)	Change in levels of serum biomarkers HIF-1a \& VEGF-C in patients with breast cancer undergoing resection surgery at other time points - intraoperative, at 2hr postoperative. Ti, T2h in both groups
Change in levels of serum biomarkers TGF-β, IL-17 IFN-g, TNF-a, IL-6 and MMP-2 at the four time points in both groups.	preoperative, intraoperative, at 2hr postoperative and at 24hr postoperative.	Transforming Growth Factor -beta (TGF-β), Interleukin - 17 (IL-17), Inferferon - gamma (IFN-g), Tumor Necrosis Factor - alpha (TNF-a), Interleukin - 6 (IL-6), Matrix Metalloproteinase - 2 (MMP-2)
Measure expression of various lymphocyte subsets (CD3+ T cells, CD4+ helper T cells, CD8+ cytotoxic T cells, γδT cells, NK cells and B cells peripheral blood lymphocytes at four time points	preoperative, intraoperative, at 2hr postoperative and at 24hr postoperative.	Measure expression of various lymphocyte

Trial Locations

Locations (1)

Tata Memorial Centre; 🇮🇳 Mumbai, Maharashtra, India