The Effect of Blood Carboxyhemoglobin Levels on NF-kB, NRF2 and PGC-1α During Low-flow and Normal-flow Anesthesia

January 13, 2026 updated by: Veysel Koksal, MD, Ataturk Training and Research Hospital
Carbon monoxide (CO) is a colorless, odorless, and tasteless gas that exerts diverse biological effects across tissues and organs. At high concentrations, it is recognized as toxic because of harmful effects such as tissue hypoxia, oxidative stress, peroxynitrite formation, inflammation, apoptosis, and immune damage. However, the endogenous production of CO suggests that it may confer protective mechanisms to the host. These protective effects include inhibition of platelet activation, smooth muscle relaxation, vasoactive properties, anti-inflammatory and anti-apoptotic actions, and beneficial influences on neurotransmission. Despite its toxic potential, low-concentration endogenous CO may provide protection linked to the body's defense mechanisms. In this study, we aimed to investigate the anti-apoptotic effects of carbon monoxide at low concentrations. To this end, the relationships between COHb levels and plasma levels of NF-κB, NRF2, and PGC-1α were analyzed statistically.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

A total of 120 patients aged 18-70 years, classified as ASA I and scheduled for inhalational anesthesia lasting ≥2 hours, will be included. Patients with cardiovascular disease, respiratory system disease, hepatic or renal disease; pregnant or breastfeeding women; trauma patients; those undergoing emergency surgery; procedures lasting <2 hours; those receiving intraoperative blood transfusion; smokers; and individuals who decline participation will be excluded.

All participants who agree to join the study will read and sign an informed consent form describing the study. Preoperative evaluations will be performed 1 day before surgery. Thirty minutes before surgery, a 22G intravenous cannula will be inserted, and 8 mL of blood will be drawn into a yellow-cap gel biochemistry tube and 1.5 mL into a blood gas syringe containing 60 IU of dry heparin. Biochemistry samples will be centrifuged at 4000 rpm for 10 minutes in the medical biochemistry laboratory. The separated sera will be transferred to Eppendorf tubes and stored at -80 °C until the day of analysis. Blood gas samples will be analyzed on a blood gas analyzer (Radiometer ABL 520, Copenhagen, Denmark). After blood sampling, an infusion of 0.9% sodium chloride (NaCl) at 10 mL/kg/h will be initiated. Patients will receive IV premedication with 1.5 mg midazolam; on the operating table, ECG, noninvasive blood pressure, and peripheral oxygen saturation (SpO₂) will be monitored. Before induction, all patients will undergo preoxygenation with O₂ at 6 L/min via face mask for 3 minutes.

For induction of anesthesia, fentanyl 1 µg/kg (Fentanyl Citrate, Abbott Laboratories, North Chicago, USA) and propofol 2 mg/kg IV (Propofol, Fresenius Kabi, Sweden) will be administered over 20-30 seconds. After loss of the eyelash reflex, rocuronium bromide 0.6 mg/kg (Esmeron, Organon, Netherlands) will be given IV for neuromuscular blockade, and endotracheal intubation will be performed with a cuffed tube of appropriate size for the patient's age and body habitus. Following propofol administration and until intubation, all patients will be manually ventilated with 100% O₂. After intubation, mechanical ventilation will be provided with an anesthesia machine (Datex-Ohmeda Aisys CS2, Madison, USA) in volume-controlled mode with a tidal volume of 6-8 mL/kg, respiratory rate of 12-14/min, and PEEP of 5 cmH₂O. Soda lime will be used as the CO₂ absorbent (Sorbolime, Berkim, Türkiye), and replacement of the absorbent will be verified before induction for each patient.

Patients will be randomly assigned to one of two groups: Group LF (low-flow, n=60) and Group NF (normal-flow, n=60). In both groups, fresh gas flow (FGF) will be set at 4 L/min (O₂ 50%, air 50%) until the minimum alveolar concentration (MAC) reaches 1. In Group LF, FGF will then be maintained at 0.6 L/min (O₂ 50%, air 50%), with desflurane adjusted to maintain MAC = 1. In Group NF, FGF will be maintained at 2 L/min (O₂ 50%, air 50%), with desflurane adjusted to maintain MAC = 1. In both groups, blood sampling will be repeated at the 2nd hour of surgery.

During the final 30 minutes of surgery, patients will receive postoperative analgesia consisting of tramadol HCl (Contramal, Türkiye) 100 mg IV, paracetamol (Partemol, Türkiye) 1 g IV, and dexketoprofen (Ketavel, Türkiye) 50 mg IV. In the normal-flow group, after placement of the final skin suture, the inhalational agent will be discontinued and the carrier gas switched to 100% O₂; FGF will be increased to 8 L/min. In the low-flow group, the inhalational agent will be discontinued 20 minutes before the anticipated end of surgery; FGF will be maintained at 0.6 L/min until the final skin suture and then increased to 8 L/min. After the return of spontaneous breathing, neostigmine 0.03 mg/kg (Plantigmin, Türkiye) and atropine 0.01 mg/kg (Turktıpsan, Türkiye) will be administered in both groups to achieve extubation.

Postoperatively, patients will be transferred to the post-anesthesia care unit, where respiratory and hemodynamic parameters will be monitored for 30 minutes before transfer to the ward. In both groups, blood sampling will be repeated at postoperative hour 24 using the same method. The following variables will be recorded: duration of anesthesia, SpO₂, venous blood gas results, hemodynamic parameters, postoperative recovery time and quality, and postoperative complications (e.g., nausea and vomiting). Blood samples obtained in the preoperative, intraoperative, and postoperative periods will be centrifuged and stored at -80 °C. Following biochemical analysis, COHb, NF-κB, NRF2, and PGC-1α levels will be subjected to statistical analysis.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
120

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

aged 18-70 years

classified as ASA I

scheduled for inhalational anesthesia lasting ≥2 hours

Exclusion Criteria:

Patients with cardiovascular disease, respiratory system disease, hepatic or renal disease

pregnant or breastfeeding women

trauma patients

those undergoing emergency surgery

procedures lasting <2 hours

those receiving intraoperative blood transfusion

smokers

individuals who decline participation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: COHb
Behavioral: low-flow anasthesia
In Group LF, FGF will then be maintained at 0.6 L/min (O₂ 50%, air 50%), with desflurane adjusted to maintain MAC = 1
Behavioral: Normal akımlı anestezi
In Group NF, FGF will be maintained at 2 L/min (O₂ 50%, air 50%) with desflurane adjusted to maintain MAC = 1..
Experimental: TAS
Behavioral: low-flow anasthesia
In Group LF, FGF will then be maintained at 0.6 L/min (O₂ 50%, air 50%), with desflurane adjusted to maintain MAC = 1
Behavioral: Normal akımlı anestezi
In Group NF, FGF will be maintained at 2 L/min (O₂ 50%, air 50%) with desflurane adjusted to maintain MAC = 1..
Experimental: TOS
Behavioral: low-flow anasthesia
In Group LF, FGF will then be maintained at 0.6 L/min (O₂ 50%, air 50%), with desflurane adjusted to maintain MAC = 1
Behavioral: Normal akımlı anestezi
In Group NF, FGF will be maintained at 2 L/min (O₂ 50%, air 50%) with desflurane adjusted to maintain MAC = 1..
Experimental: HIF 1a
Behavioral: low-flow anasthesia
In Group LF, FGF will then be maintained at 0.6 L/min (O₂ 50%, air 50%), with desflurane adjusted to maintain MAC = 1
Behavioral: Normal akımlı anestezi
In Group NF, FGF will be maintained at 2 L/min (O₂ 50%, air 50%) with desflurane adjusted to maintain MAC = 1..

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Blood COHb, NF-kB, NRF2, and PGC-1α levels during Low-Flow and Normal-Flow Anesthesia
Time Frame: 24 HOUR
COHb concentrations
24 HOUR
Blood COHb, NF-kB, NRF2, and PGC-1α levels during Low-Flow and Normal-Flow Anesthesia
Time Frame: 24 HOUR
NF-kB concentrations
24 HOUR
Blood COHb, NF-kB, NRF2, and PGC-1α levels during Low-Flow and Normal-Flow Anesthesi
Time Frame: 24 HOUR
NRF2 concentrations
24 HOUR
Blood COHb, NF-kB, NRF2, and PGC-1α levels during Low-Flow and Normal-Flow Anesthesi
Time Frame: 24 HOUR
PGC-1α concentrations
24 HOUR

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ataturk Training and Research Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 20, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 31, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 31, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 15, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 13, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 20, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 20, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 13, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • B.30.2.YYU.0.01.00.00/91

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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