Evaluation of the Effect of Sevoflurane and Propofol Hypotensive Anesthesia on Blood Antioxidant Levels and HIF 1 Levels

The aim of this study to evaluate the patients who underwent controlled hypotensive anesthesia under standardized depth of anesthesia with total intravenous anesthesia or inhalation anesthesia; preoperative and 30. ,60. ,120. second of intraoperative period blood HIF 1a, TAS, TOS measurement and to investigate tissue hypoxia secondary to hypotensive anesthesia and the changes of the mediators at the tissue level and which hypotensive anesthesia technique is related.

Study Overview

• Status: Suspended
• Conditions: Hypoxia; Hypoxemia During Surgery
• Intervention / Treatment: Procedure: Mean Blood Pressure (MBP); Drug: Add to 0.5 mcg / kg fentanyl.

Detailed Description

Controlled hypotension is the voluntary reversible reduction of arterial blood pressure. Hypotensive anesthesia is a method of anesthesia in which blood pressure is reduced in a controlled manner, especially in certain surgeries. İt reduces intraoperative bleeding and need for blood transfusion and provides a clean surgical vision in narrow-field surgeries or with high bleeding potential. Hypotensive anesthesia can be performed according to mean blood pressure (MBP) or systolic blood pressure (SBP).

A non-invasive cerebral oximeter is used to see the changes in the brain due to high oxygen-dependent metabolism during induction and maintenance of anesthesia.

Hypoxia inducible factor (HIF) is a transcription factor involved in cell adaptation mechanism activated in response to hypoxia.

The biological activity of HIF 1 is determined by the expression and activity of the HIF 1a subunit.

Total antioxidant status (TAS) shows the total effect of all antioxidants in the human body and total oxidant status (TOS) shows the total effect of oxidants.

Near Infrared Spectroscopy (NIRS) allows continuous and non-invasive monitoring of cerebral oxygenation. HIF 1a, TAS and TOS are laboratory markers that predict tissue oxygenation and perfusion.

Hypotensive anesthesia can be performed according to both MBP and SBP. However, in our study that follow-up MBP is more advantageous/protective, although it is not supported by very strong data. The investigators recommend hypotensive anesthesia compared to MBP; but further studies are needed

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey
  • Fatih
    • İstanbul, Fatih, Turkey, 34093
      • Bezmialem Vakif University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18-55 years old
• ASA Physical Status Classification System 1
• Undergoing to Elective rhinoplasty

Exclusion Criteria:

• Patients have any autoimmune disease
• Smoking of patients
• Development of any allergic reaction during the procedure
• Failure to collect blood to be examined at the appropriate time
• Body mass index is less than 19 or greater than 30

Termination criteria

• Development of severe hypotension and bradycardia during measurements
• Development of severe drug allergy during follow-up
• In the event of any complications related to the surgical procedure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Total intravenous anesthesia technique for group 1 patients; Procedure/Surgery:Mean Blood Pressure (MBP) Mean blood pressure (MBP) 50-65 mmHg was applied with 6-10 mg / kg / h propofol and 0.0,4mcg / kg remifentanyl infusion / min. When BIS values are between 40-60 and muscle relaxation was sufficient (TOF 0), a 20% increase in the initial blood pressure and heart rate values of patients were added to 0.5 mcg / kg fentanyl. All patients received 5-8 ml / kg / h IV infusion of balanced electrolyte solution (Isolyte-S) during the operation. Hemodynamic parameters (HR, SBP, OCD), BIS,TOF and SpO2 were recorded at 5 minute intervals. Blood samples were taken from patients during preop preparation (t0), 30th minute (t1), 1st hour (t2) and 2nd hour (t3) of the operation. 5 ml of blood was taken from the untreated arm of all patients to the HIF1a, TAS and TOS values and sent to the biochemistry laboratory	Procedure: Mean Blood Pressure (MBP); Mean blood pressure (MBP) for patients 50-65 mmHg; Drug: Add to 0.5 mcg / kg fentanyl.; When BIS values are between 40-60 and muscle relaxation was sufficient (TOF 0), a 20% increase in the initial blood pressure and heart rate values of patients were added to 0.5 mcg / kg fentanyl.
Active Comparator: Inhalation anesthesia technique for group 2 patients; Procedure/Surgery:Mean Blood Pressure (MBP) Mean blood pressure (MBP) 50-65 mmHg was applied with 40% Oxygen 60% N2O2 and Sevoflurane at a concentration of 1.5-3.5% with 2 L / minTGA to provide a value of BIS between 40-60. When BIS values are between 40-60 and muscle relaxation was sufficient (TOF 0), a 20% increase in the initial blood pressure and heart rate values of patients were added to 0.5 mcg / kg fentanyl. All patients received 5-8 ml / kg / h IV infusion of balanced electrolyte solution (Isolyte-S) during the operation. Hemodynamic parameters (HR, SBP, OCD), BIS,TOF and SpO2 were recorded at 5 minute intervals. Blood samples were taken from patients during preop preparation (t0), 30th minute (t1), 1st hour (t2) and 2nd hour (t3) of the operation. 5 ml of blood was taken from the untreated arm of all patients to the HIF1a, TAS and TOS values and sent to the biochemistry laboratory	Procedure: Mean Blood Pressure (MBP); Mean blood pressure (MBP) for patients 50-65 mmHg; Drug: Add to 0.5 mcg / kg fentanyl.; When BIS values are between 40-60 and muscle relaxation was sufficient (TOF 0), a 20% increase in the initial blood pressure and heart rate values of patients were added to 0.5 mcg / kg fentanyl.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the relationship between hypotensive anesthesia technique and tissue hypoxia by HIF1a	Under normoxic conditions, HIF 1a protein can hardly be detected, but when hypoxia starts, its expression starts within 2 minutes and peaks at 4-8 hours of hypoxia. 5 ml blood was taken into MiniCollect® tubes from the venous cannula placed before anesthesia (t0) induction for measure HIF 1a,TAS and TOS. 30th minute (t1), 1st hour (t2) and 2nd hour (t3) of the operation 5 ml of blood was taken again from the untreated arm of all patients to the HIF1a, TAS and TOS values and sent to the biochemistry laboratory. The collected blood was centrifuged at 2000 x g for 10 minutes and the separated sera were sent to the biochemical laboratory to be stored at -80 ° C until the study was performed.	Change from Baseline HIF 1a 30th minute (t1), 1st hour (t2) and 2st hour (t3)
Evaluation of the relationship between hypotensive anesthesia technique and tissue hypoxia by the concentration of TAS	Plasma TAS and TOS levels are measured with a commercial kit developed by Erel. Values for plasma TAS are expressed in millimeters by the Trolox value per liter. 5 ml blood was taken into MiniCollect® tubes from the venous cannula placed before anesthesia (t0) induction for measure HIF 1a,TAS and TOS. 30th minute (t1), 1st hour (t2) and 2nd hour (t3) of the operation 5 ml of blood was taken again from the untreated arm of all patients to the HIF1a, TAS and TOS values and sent to the biochemistry laboratory. The collected blood was centrifuged at 2000 x g for 10 minutes and the separated sera were sent to the biochemical laboratory to be stored at -80 ° C until the study was performed.	Change from Baseline TAS levels at 30th minute (t1), 1st hour (t2) and 2st hour (t3)
Evaluation of the relationship between hypotensive anesthesia technique and tissue hypoxia by the concentration of TOS	Measurement for TOS is calibrated with hydrogen peroxide and the results are expressed in micromolar by the hydrogen peroxide value per liter (mmol H2O2 equiv / L).5 ml blood was taken into MiniCollect® tubes from the venous cannula placed before anesthesia (t0) induction for measure HIF 1a,TAS and TOS. 30th minute (t1), 1st hour (t2) and 2nd hour (t3) of the operation 5 ml of blood was taken again from the untreated arm of all patients to the HIF1a, TAS and TOS values and sent to the biochemistry laboratory. The collected blood was centrifuged at 2000 x g for 10 minutes and the separated sera were sent to the biochemical laboratory to be stored at -80 ° C until the study was performed.	Change from Baseline TOS levels at 30th minute (t1), 1st hour (t2) and 2st hour (t3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
surgical satisfaction	At the end of the surgery surgeons evaluated surgical satisfaction. the investigators used surgeon satisfaction score which one is performing like that 1- bad 2-moderate 3-good 4-excellent	postoperative 1 minute
bleeding scores	At the end of the surgery surgeons evaluated bleeding scores. the investigators used bleeding score which one is performing like that 0-No bleeding 1-minor bleeding no aspiration required 2- Minor bleeding, aspiration required 3-minor bleeding, frequent aspiration required, 4-Moderate bleeding, visible only with aspiration 5- Severe bleeding, frequent aspiration required and very hard to perform surgery	postoperative 1 minute
anesthetic consumption for group 1 propofol consumption (mg) and remifentanyl consumption(microgram)	Standard anesthesia induction and propofol and remifentanil infusion were applied to group 1 patients with TIVA technique. Standard anesthesia induction and 40% Oxygen 60% N2O2 and Sevoflurane at a concentration of 1.5-3.5% with 2 L / minTGA were applied to group 2 patients with inhalation anesthesia technique	postoperative 1 minute
anesthetic consumption for group 2 N2O2 consumption (ml) and sevoflurane consumption (ml)	Standard anesthesia induction and 40% Oxygen 60% N2O2 and Sevoflurane at a concentration of 1.5-3.5% with 2 L / minTGA were applied to group 2 patients with inhalation anesthesia technique	postoperative 1 minute

Collaborators and Investigators

• Sponsor: Bezmialem Vakif University
• Investigators: Study Director: Hayrettin Daşkaya, MD, Bezmialem Vakif University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Actual): September 1, 2019
• Study Completion (Anticipated): January 1, 2021

Study Registration Dates

• First Submitted: January 22, 2020
• First Submitted That Met QC Criteria: January 28, 2020
• First Posted (Actual): January 29, 2020

Study Record Updates

• Last Update Posted (Actual): May 11, 2020
• Last Update Submitted That Met QC Criteria: May 7, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: hypotensive anesthesia; HIF 1a; total intravenous anesthesia; inhalation anesthesia
• Additional Relevant MeSH Terms: Signs and Symptoms, Respiratory; Hypoxia; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Fentanyl
• Other Study ID Numbers: Ayse02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No