The purpose of this study is to analyze the effectiveness of apneic oxygenation and CPAP applied to the non-dependent lung during pulmonary resection surgery in reducing inflammatory response, ischemia-reperfusion injury, and postoperative complications. We will conduct a randomized, controlled, and blinded study in 177 patients with three arms:

• Control Group: Oxygen therapy according to standard clinical practice
• Apneic oxygenation group: A probe will be introduced through the lumen of the double-lumen tube (DLT) to administer a continuous source of oxygen without any mechanism that generates airway pressure.
• CPAP Group: Continuous positive airway pressure with 3-5 L/min oxygen flow and 2 cm H2O pressure delivered via a Mapleson system.

Inflammatory mediators in blood and in both lungs will be measured intraoperatively and 24 hours after surgery. Patients will be followed from hospital admission until discharge and again 30 days after surgery to evaluate the postoperative course, particularly the occurrence of complications according to the revised Clavien-Dindo classification for thoracic surgery, as well as other relevant clinical outcomes.

Surgical interventions, particularly lung resection, provoke a significant inflammatory response at both local and systemic levels, characterized by hyperemia and increased vascular permeability. Thoracic surgery requiring one-lung ventilation (OLV) leads to complications such as intraoperative hypoxemia and an exaggerated pulmonary inflammatory response, threatening patient stability. Hypoxemia-commonly defined as SpO2 < 85-90% or PaO2 < 60 mmHg-is frequent and increases the risk of complications such as arrhythmias, cognitive dysfunction, pulmonary hypertension, and renal failure, particularly in patients with comorbidities. The difficulty in defining a precise threshold for complications reflects that oxygen deprivation-related tissue hypoxia depends on the balance between oxygen supply and consumption, which is influenced by individual variables such as cardiovascular function and pre-existing conditions.

To mitigate hypoxemia during OLV, several strategies have been implemented. The most common are increasing FiO2 and applying continuous positive airway pressure (CPAP), which significantly improves arterial oxygenation. However, higher pressures may hinder surgical manipulation due to anatomical distortion. Currently, low-pressure CPAP (around 2 cmH2O) is recommended because it provides oxygenation benefits without interfering with the surgery, although clinical evidence remains limited. Apneic oxygenation has also been proposed: oxygen is administered without positive pressure, taking advantage of the fact that during apnea oxygen can diffuse into the alveoli down pressure gradients, sustaining arterial oxygenation even with collapsed lung regions. This technique can prolong safe apnea time, reduce hyperoxia risk, and maintain oxygenation while minimizing interference with surgical exposure.

Conversely, OLV triggers a strong inflammatory response caused by tissue injury, atelectrauma, volutrauma, and barotrauma in the dependent lung, along with oxidative stress damage in the non-ventilated lung. Prolonged exposure to high FiO2 contributes to lung injury through oxidative mechanisms similar to those in adult acute respiratory distress syndrome. Re-expansion of the collapsed lung after OLV also releases free radicals, exacerbating ischemia-reperfusion injury, especially in lung cancer patients who may have reduced antioxidant capacity. Activation of the NLRP3 inflammasome, stimulated by reactive oxygen species, promotes proinflammatory cytokine production, contributing to tissue damage, increased capillary permeability, and pulmonary edema, thereby raising the risk of postoperative respiratory failure.

Although advances have been made, evidence is limited regarding the impact of apneic oxygenation on reducing inflammation, oxidative stress, and postoperative complications in lung surgery. However, studies in other surgeries suggest this technique could decrease inflammatory markers and improve oxygenation without impairing surgical exposure. Therefore, this study aims to evaluate and compare the efficacy of apneic oxygenation and CPAP applied to the nondependent lung during lung resection surgery, focusing on reducing inflammatory response, ischemia-reperfusion injury, and postoperative complications, and thus providing evidence to improve perioperative strategies for these patients.

Hypothesis: Maintaining a continuous oxygen flow to the nondependent lung, with minimal pressure (CPAP) or none at all (apneic oxygenation), during OLV will reduce alveolar hypoxia in that lung, thereby attenuating ischemia-reperfusion-related lung injury and improving the postoperative course. Additionally, it will reduce the incidence of intraoperative hypoxemia and permit use of lower oxygen concentrations to the dependent lung, which may further improve prognosis.

Inclusion Criteria:

• Patients of both genders undergoing lung resection surgery in the Thoracic Surgery Department at Hospital General Universitario Gregorio Marañón
• Lung isolation using a double-lumen tube (DLT)
• Scheduled surgery
• Patients able and willing to give written informed consent
• Patients over 18 years old and legally competent

Exclusion Criteria:

• Patients with evidence of pulmonary bullae
• Pregnancy or breastfeeding
• Blood transfusion within 10 days prior to surgery
• Treatment with immunosuppressants or corticosteroids within 3 months prior to surgery
• Patient refusal to participate
• Prior contralateral thoracic surgery
• Robotic surgery
• Pneumonectomy
• Enrollment in another clinical trial

All clinical staff (thoracic surgeons, pulmonologists, ICU physicians, and any other physicians involved in assessing postoperative complications) and laboratory personnel involved in the study will be blinded to the patient's group assignment, except for the anesthesiologist responsible for the case. The sealed randomization envelope will be handed to the anesthesiologist by the operating-room nurse before the start of OLV. Likewise, those responsible for entering data into the database will be blinded to group assignment; the group will be recorded in the database only immediately prior to statistical analysis.