Effect of Hypotensive Anesthesia on Cerebral Perfusion and Blood Antioxidant Levels and HIF 1a

The aim of this study to evaluate the patients who underwent controlled hypotensive anesthesia under standardized depth of anesthesia; preoperative and postoperative blood HIF 1a, TAS, TOS measurement and cerebral perfusion evaluation with NIRS and to investigate tissue hypoxia secondary to hypotensive anesthesia and the changes of the mediators at the tissue level and which blood pressure parameters are related.

Study Overview

• Status: Completed
• Conditions: Hypoxia, Brain; Hypoxemia During Surgery
• Intervention / Treatment: Procedure: systolic blood pressure (SBP); Procedure: mean blood pressure (MBP)

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18-75 years old
• ASA Physical Status Classification System 1-2
• Undergoing to Elective rhinoplasty or maxillofacial surgery

Exclusion Criteria:

• 1. Those with SVO history 2. Patients with carotid stenosis and cardiac failure 3. Chronic smoking 4. Patients with allergies to drugs to be used 5. Patients without intraoperative hypotension 6. Presence of morbid obesity (BMI> 40 kg / m2) 7. Patients who refused to participate in the study

Termination criteria

1. Development of severe hypotension and bradycardia during measurements
2. Development of severe drug allergy during follow-up
3. 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: systolic blood pressure (SBP); Systolic blood pressure (SBP) for group 1 patients 80-90 mmHg	Procedure: systolic blood pressure (SBP); Systolic blood pressure (SBP) 80-90 mmHg remifentanil infusion was applied to Group 1 patients. In addition to remifentanil infusion, 0.002 μg.kg of glycerol trinitrate (Perlinganit) was administered as an intermittent bolus in patients who needed to achieve target blood pressure. 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, SpO2 and NIRS were recorded at 5 minute intervals. At the end of the operation, 3 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
Active Comparator: mean blood pressure (MBP); Mean blood pressure (MBP) for group 2 patients 50-65 mmHg	Procedure: mean blood pressure (MBP); For group 2, remifentanil infusion was performed with a mean blood pressure (OCD) of 50-65 mmHg. In addition to remifentanil infusion, 0.002 μg.kg of glycerol trinitrate (Perlinganit) was administered as an intermittent bolus in patients who needed to achieve target blood pressure. 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, SpO2 and NIRS were recorded at 5 minute intervals. At the end of the operation, 3 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the relationship between hypotensive anesthesia technique and brain hypoxia by the rate of NIRS	The investigators used to detect brain hypoxia with Near Infrared Spectroscopy (NIRS) (INVOS 5100 Medtronic). Near Infrared measurement, primary absorbing molecules in tissue are metal complex chromophores such as hemoglobin, bilirubin and cytochrome. The absorption spectra of deoxyhemoglobin (Hb) range between 650-1000 nm, the oxyhemoglobin (Hb02) absorption spectra range between 700-1150 and the cytochrome oxidase aa3 (Caa3) absorption spectra range from 820-840 nm. NIRS measures the ratio of oxyhemoglobin to total hemoglobin at a depth of 2.5-3 cm in the area under the sensor.This ratio represents regional cerebral oxygen (RsO2) saturation. RSO2 below 40% or more than 25% decrease in baseline is associated with neurological dysfunction and side effects. A 15-20% reduction or less than 50% of the baseline is considered a critical threshold and requires action.	intraoperative 2 hours
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. 3 ml blood was taken into MiniCollect® tubes from the venous cannula placed before anesthesia induction for measure HIF 1a,TAS and TOS. At the end of the operation, 3 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 at 2 hours
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. 3 ml blood was taken into MiniCollect® tubes from the venous cannula placed before anesthesia induction for measure HIF 1a,TAS and TOS. At the end of the operation, 3 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 2 hours
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). 3 ml blood was taken into MiniCollect® tubes from the venous cannula placed before anesthesia induction for measure HIF 1a,TAS and TOS. At the end of the operation, 3 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 2 hours

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	Standard anesthesia induction and propofol and remifentanil infusion were applied to all patients with TIVA 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): November 14, 2018
• Primary Completion (Actual): May 15, 2019
• Study Completion (Actual): June 30, 2019

Study Registration Dates

• First Submitted: November 12, 2019
• First Submitted That Met QC Criteria: November 20, 2019
• First Posted (Actual): November 22, 2019

Study Record Updates

• Last Update Posted (Actual): December 3, 2019
• Last Update Submitted That Met QC Criteria: December 2, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: hypotensive anesthesia; HIF 1a; Brain Hypoxia; tissue hypoxia
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Respiratory; Hypoxia; Hypoxia, Brain
• Other Study ID Numbers: Ayse01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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