Effect of Oxygen Administration in the Non-dependent Lung on Postoperative Complications After Lung Surgery

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.

• Gas exchange and acid-base balance [Time frame: Intraoperative period and 24 hours]
• Degree of interference with surgical exposure (Surgeon Satisfaction Scale on Oxygen Therapy Interference, 1-5) [Time frame: Surgery duration; assessed at end of surgery]
• Incidence of postoperative pulmonary complications [Time frame: Up to 30 days after intervention]
• Special Care Units stay [Time frame: Up to 30 days after intervention]
• Readmisions to Special Care Units [Time frame: Up to 30 days after intervention]
• Hospital Stay [Time frame: Up to 30 days after intervention]
• Hospital readmission [Time frame: Up to 30 days after intervention]
• Inflammatory biomarkers in blood and bronchoalveolar lavages [Time frame: Up to 24 hours after intervention]
• New molecules involved in oxidative stress [Time frame: Up to 24 hours after intervention]