The primary objective of our study is to compare the effects of total intravenous anesthesia (TIVA), combined intravenous-volatile anesthesia (CIVA), and balanced anesthesia (BAL) methods on perioperative oxidative stress parameters, such as Malondialdehyde (MDA), Total Oxidant Status (TOS), Total Antioxidant Status (TAS), and Superoxide Dismutase (SOD), in patients undergoing video-assisted thoracoscopic surgery (VATS). The secondary objective is to record perioperative vital parameters, arterial blood gas values obtained at specific stages of the surgery, and the incidence of postoperative nausea and vomiting (PONV).

Scientific Rationale and Validity of the Medical Research Hypoxic pulmonary vasoconstriction (HPV) is a homeostatic mechanism unique to the pulmonary vascular system. In response to alveolar hypoxia, intrapulmonary arteries constrict and redirect blood flow toward better-oxygenated lung segments, thereby optimizing ventilation/perfusion matching and systemic oxygenation . Additionally, HPV acts as a physiological protective mechanism by reducing the shunt of deoxygenated blood and improving the degree of hypoxemia. This physiological modulation is influenced by various factors including medications, temperature, acid-base status, airway pressure, patient positioning, and cardiac output . Numerous animal and isolated lung studies have demonstrated that HPV is modulated by volatile anesthetics . However, human studies have reported inconsistent results regarding the effects of various anesthetics on systemic oxygenation during one-lung ventilation.

One-lung ventilation is frequently employed during thoracic surgical procedures such as thoracotomy and thoracoscopy to provide an adequate surgical view. Patients undergoing one-lung ventilation are at risk of hypoxemia due to impaired oxygenation, as well as postoperative lung injury attributable to oxidative damage occurring during reventilation of the non-dependent lung.

During one-lung ventilation, the non-ventilated lung becomes not only atelectatic but also hypoperfused as a result of HPV. Once two-lung ventilation is re-established, the reintroduction of oxygen into the airways triggers reactive pulmonary vasodilation and reperfusion of the lung tissue, which may result in the generation of excessive oxidative radicals. Although the lung is relatively resistant to hypoxia owing to dual blood supply and consumption of oxygen stored in alveolar spaces, re-expansion injury observed after pneumothorax treatment and reperfusion injury following lung transplantation serve as examples of potential oxidative damage .

Research Questions How do TIVA, CIVA, and BAL anesthetic techniques affect oxidative stress responses in patients undergoing one-lung ventilation? Which anesthetic management approach (CIVA, TIVA, BAL) provides better preservation of oxygenation? Will there be a significant difference in postoperative nausea and vomiting (PONV) incidence among the groups? Study Design, Methods, and Procedures Participants Written informed consent will be obtained from all participants. Sixty patients aged 18-65 years, classified as American Society of Anesthesiologists (ASA) Physical Status I-II, scheduled for elective video-assisted thoracoscopic surgery (VATS) at Atatürk University Medical Faculty Hospital between December 1, 2025 and May 1, 2026, and requiring one-lung ventilation for more than 60 minutes will be included. Patients will be informed about the study prior to enrollment. Individuals who decline participation, have known allergies to the study drugs, have a recent history of vitamin supplementation, or who have significant cardiovascular, renal, or hepatic disease will be excluded. The study will be conducted in three groups.

Randomization Patients will be randomly assigned into three equal groups (TIVA, CIVA, and BAL) using the Microsoft Excel RAND function. All other investigators and outcome assessors will remain blinded to group allocation.

Total Intravenous Anesthesia (TIVA) Group Anesthesia induction will include 2 mg midazolam, 2-2.5 mg/kg propofol, 0.6-0.9 mg/kg rocuronium, and 1 μg/kg remifentanil. Maintenance will be provided with target-controlled infusion (TCI) propofol at a Ce of 4-6 μg/mL and TCI remifentanil at a Ce of 1.5-3 ng/mL while maintaining the bispectral index (BIS) between 40-60.

Balanced Anesthesia (BAL) Group Induction will follow the same protocol as the TIVA group. During maintenance, desflurane 5-7% (MAC 1-1.3) and TCI remifentanil at a Ce of 1.5-3 ng/mL will be administered, targeting a BIS value between 40-60.

Combined Intravenous-Volatile Anesthesia (CIVA) Group Induction will follow the same protocol as other groups. Maintenance will include TCI propofol at a Ce of 2-4 μg/mL and TCI remifentanil at a Ce of 1.5-3 ng/mL along with 3% desflurane (MAC 0.5), keeping BIS values between 40-60.

Perioperative Monitoring and Sample Collection Upon arrival to the operating room, standard monitoring (ECG and SpO₂) will be applied. A 20G radial arterial catheter will be inserted under sterile conditions for continuous invasive blood pressure monitoring and blood sampling.

Following induction, patients will be intubated using an appropriately sized (35Fr, 37Fr, or 39Fr) Robertshaw double-lumen endotracheal tube. Position verification will be conducted with a fiberoptic bronchoscope before and after lateral positioning. Pressure-controlled volume-guaranteed (PCV-VG) ventilation will be used during both two-lung and one-lung ventilation with PEEP set at 5 cmH₂O. During one-lung ventilation, tidal volume will be set at 4-6 mL/kg keeping peak inspiratory pressure <30 cmH₂O, FiO₂ between 0.6-1.0 to maintain SpO₂ >90%, and respiratory rate adjusted to ensure normocapnia.

Blood samples for measurement of oxidative stress markers-Malondialdehyde (MDA), Total Oxidant Status (TOS), Total Antioxidant Status (TAS), and Superoxide Dismutase (SOD)-will be drawn from the arterial catheter at three time points:

T1: Before anesthesia induction T2: Before re-establishing two-lung ventilation T3: 30 minutes after re-establishing two-lung ventilation Samples will be centrifuged at +4°C, 4500 rpm for 7 minutes. The obtained serum will be stored at -80°C in Eppendorf tubes until analysis. Serum levels will be determined using the ELISA method. Recorded values will be transferred to Excel spreadsheets for evaluation and statistical processing.

During anesthesia, at 15, 30, 45, and 60 minutes of one-lung ventilation and 30 minutes after resuming two-lung ventilation, TCI remifentanil dose, TCI propofol dose, minimum alveolar concentration (MAC), peak inspiratory pressure (Ppeak), BIS values, heart rate, and mean arterial pressure will be recorded. Arterial blood gas samples will be routinely obtained. After extubation, patients will be transferred to the post-anesthesia care unit (PACU) and evaluated for postoperative nausea and vomiting (PONV) at the 30th minute.

Statistical Analysis Statistical analyses will be performed using SPSS Statistics Version 22 (IBM, Armonk, NY, USA). Normality will be assessed with the Kolmogorov-Smirnov test. Normally distributed variables will be analyzed using the Student's t-test, whereas non-normally distributed variables will be evaluated using the Mann-Whitney U test. A p-value < 0.05 will be considered statistically significant.

Inclusion Criteria:

• Aged between 18 and 65 years,
• American Society of Anesthesiologists (ASA) Physical Status Class I-II,
• Scheduled for elective Video-Assisted Thoracoscopic Surgery (VATS)
• Requiring one-lung ventilation for more than 60 minutes

Exclusion Criteria:

• Refusal to participate in the study
• History of allergy to the drugs to be used
• Recent history of vitamin supplementation
• History of severe cardiac, renal, or hepatic disease
• ASA III-IV

Individual participant data (IPD) will not be shared due to patient privacy concerns and institutional regulations. Data will be securely stored and used solely for the purposes of this study and related scientific publications.