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

Impact of Continuous Oxygen Flow With or Without Airway Pressure in the Non-dependent Lung During One-lung Ventilation on Postoperative Complications in Lung Resection Surgery: A Randomized Controlled Clinical Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Anesthesia General; Lung Resection Surgery
• Intervention / Treatment: Procedure: Oxygen therapy according to standard clinical practice; Device: CPAP; Drug: Medicinal gas - oxygen (Nippon Gases 200 bar)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 177
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Francisco de la Gala, MD, PhD; Phone Number: +34915868367; Email: francisco.gala@salud.madrid.org
• Study Contact Backup: Name: Ignacio Garutti, MD; Phone Number: +34915868367; Email: ignacio.garutti@salud.madrid.org

Study Locations

• Spain
  • Madrid, Spain, 28007
    • Recruiting
    • Hospital General Universitario Gregorio Marañón
    • Contact: Francisco de la Gala, MD, PhD; Phone Number: +34915868367; Email: francisco.gala@salud.madrid.org
    • Contact: Ignacio Garutti, MD; Phone Number: +34915868367; Email: ignacio.garutti@salud.madrid.org
    • Sub-Investigator: David Martínez, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group; Oxygen therapy according to standard clinical practice. The nondependent lung (surgical) will be connected to ambient air by opening the lumen of the double-lumen tube (DLT) directed towards that lung	Procedure: Oxygen therapy according to standard clinical practice; Ambient air connection
Experimental: CPAP Group; Continuous positive airway pressure with 3-5 L/min oxygen and 2 cmH2O pressure delivered via a Mapleson system	Device: CPAP; Continuous positive pressure
Experimental: APNEIC OXYGENATION group; A probe will be introduced through the lumen of the DLT to deliver a continuous flow of oxygen without any mechanism that generates airway pressure	Drug: Medicinal gas - oxygen (Nippon Gases 200 bar); Medicinal gas, compressed. Oxygen 99.5% v/v

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative complications	To compare the proportion of patients in each grade of the revised Clavien-Dindo classification for thoracic surgery across the three study groups	Up to 30 days after intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gas exchange and acid-base balance	To compare gas exchange and acid-base balance during the intraoperative period and during the first 24 hours postoperatively	Intraoperative period and 24 hours
Degree of interference with surgical exposure (Surgeon Satisfaction Scale on Oxygen Therapy Interference, 1-5)	Assessed by the surgeon at the end of the procedure using the Surgeon Satisfaction Scale on Oxygen Therapy Interference, an ordinal 5-point scale: 1 = Surgery impossible (change O2 administration method required); 2 = Very difficult technique (no change in O2 administration required); 3 = Considerably more difficult than usual; 4 = Somewhat more difficult than usual; 5 = Similar to usual.	Surgery duration; assessed at end of surgery
Incidence of postoperative pulmonary complications	To compare de incidence of postoperative pulmonary complications among the three study groups	Up to 30 days after intervention
Special Care Units stay	To compare the length of stay in Special Care Units among the three study groups	Up to 30 days after intervention
Readmisions to Special Care Units	To compare the number of readmissions to Special Care Units among the three study groups	Up to 30 days after intervention
Hospital Stay	To compare the average hospital stay (measure in days) among the three study groups	Up to 30 days after intervention
Hospital readmission	To compare hospital readmissions among the three study groups	Up to 30 days after intervention
Inflammatory biomarkers in blood and bronchoalveolar lavages	To evaluate the inflammatory response measured in blood and bronchoalveolar lavages during the first 24 hours postoperatively in the three patient groups. Blood samples and bronchoalveolar lavages will be taken at the beginning of surgery, at the end of one-lung ventilation, and at 24 hours postoperatively	Up to 24 hours after intervention
New molecules involved in oxidative stress	Identification of new molecules involved in oxidative stress: Plasma concentrations of oxidative stress markers (SOD, MDA, MPO, CP, ROS index, plasma thiols). All biochemical determinations will be performed by spectrophotometry using validated specific kits. Samples collected pre-intervention and at 2, 6 and 24 hours post-intervention.	Up to 24 hours after intervention

Collaborators and Investigators

• Sponsor: Francisco Andres de la Gala
• Collaborators: Instituto de Salud Carlos III
• Investigators: Principal Investigator: Francisco de la Gala, MD, PhD, Hospital General Universitario Gregorio Marañón

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2025
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): March 30, 2027

Study Registration Dates

• First Submitted: November 24, 2025
• First Submitted That Met QC Criteria: March 6, 2026
• First Posted (Actual): March 10, 2026

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Postoperative complications; Thoracic surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Signs and Symptoms; Postoperative Complications
• Other Study ID Numbers: ECAOI-22

Drug and device information, study documents

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