Lower Oxygen Concentration for Preventing Collapsed Lung

(RESPIRA-EIT Trial)

Overseen By Maximilian S Schaefer, M.D., PhD.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Beth Israel Deaconess Medical Center

Disqualifiers: Morbid obesity, Coronary artery disease, Sleep apnea, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

48 Participants Needed

Trial Summary

What is the purpose of this trial?

Patients undergoing general anesthesia require mechanical ventilation (artificial delivery of air and oxygen to their lungs). It is well known that during mechanical ventilation, so-called atelectasis formation occurs. This is a condition characterized by partial or complete collapse of lung tissue that can result in a reduction in oxygen uptake through the lung. A known risk factor for atelectasis formation during mechanical ventilation is the utilization of high oxygen concentration, as the oxygen molecules are absorbed in the lung, which then can lead to collapse of the tissue. Despite the proven association, standard operating procedure at the end of anesthesia still requires utilization of 100% oxygen. Its justification is the goal to ensure sufficient oxygenation throughout the extubation phase. However, clinical observation doesn't show a lack of oxygenation in this phase, but the patient is still exposed to the risk of atelectasis formation. This study aims to investigate the hypothesis of whether the utilization of reduced inspiratory oxygen concentration before extubation (70% or 40% compared to 100%) reduces atelectasis formation. The study was originally planned to randomize 24 patients to either 70% or 100% inspiratory oxygen concentration at the end of anaesthesia. After completion of this first phase, the study was amended to enroll another 24 patients randomized to 40% or 100% inspiratory oxygen concentration at the end of anaesthesia. Of note, both concentrations are still higher than when breathing room air in, which has of 21% oxygen. During the intervention, parameters such as the oxygen content in the blood (oxygen saturation, SpO₂), heart rate, and blood pressure are recorded, and atelectasis formation is measured using a technique called electrical impedance tomography (EIT). EIT measurements are performed at designated time points during the procedure. Anesthesia care providers are asked to document procedural, patient, and ventilator data in a questionnaire. Secondary outcomes are the homogeneity and distribution of air measured with EIT, as well as some clinical outcomes including post-extubation desaturation (\<90% SpO₂), incidence of re-intubation or non-invasive ventilation, and the Post-anesthesia Care Unit (PACU) length of stay.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment involving mechanical ventilation with reduced oxygen concentration for preventing collapsed lung?

Research suggests that while high oxygen levels can be harmful in some conditions, using a lower oxygen concentration during mechanical ventilation may help avoid potential lung damage. This approach aligns with findings that conservative oxygen therapy can be beneficial in managing severe respiratory conditions. ^{1 2 3 4 5}

Is it safe to use lower oxygen concentrations in clinical trials for preventing collapsed lung?

Using high oxygen concentrations can have harmful effects, especially in certain conditions like chronic obstructive pulmonary disease (COPD) and heart issues. However, short-term use of high oxygen levels in controlled settings, like mechanical ventilation, has not shown injury in some studies. It's important to follow guidelines to avoid excessive oxygen use. ^{1 2 3 6 7}

How does the treatment of ventilating with 70% oxygen concentration differ from other treatments for preventing collapsed lung?

This treatment is unique because it uses a lower oxygen concentration (70%) compared to the more common practice of using higher concentrations, like 100%, in mechanical ventilation. This approach aims to prevent lung injury that can occur with high oxygen levels while still providing sufficient oxygen to the patient. ^{1 8 9 10 11}

Eligibility Criteria

This trial is for adults over 18 who are having elective surgery with general anesthesia and endotracheal intubation, lasting between 1-5 hours. They must consent to participate in the study.

Inclusion Criteria

I have given my consent to participate.

I am scheduled for a surgery that requires being put to sleep and a breathing tube.

My surgery is expected to last between 1 to 5 hours.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Intervention

Participants are randomly assigned to receive either 70% or 100% oxygen concentration during the washout phase before extubation. EIT measurements and other parameters are recorded.

1 day

1 visit (in-person)

Postoperative Monitoring

Participants are monitored in the PACU for 60 minutes post-extubation, with EIT measurements and SpO2 levels recorded.

1-2 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including re-intubation or non-invasive ventilation needs within 7 days.

7 days

Treatment Details

Interventions

• Ventilating the patient with 70% oxygen concentration

Trial Overview The study tests if using a lower oxygen concentration (70%) before removing a patient's breathing tube reduces lung collapse compared to the standard high oxygen level (100%). Patients are randomly assigned to one of these two approaches.

Participant Groups

Group I: Intervention group Active Control 1 Intervention

Ventilating the patient with lower (40 or 70%) oxygen concentration during the wash out phase, before extubation

Group II: Control group Active Control 1 Intervention

Ventilating the patient with 100% oxygen concentration during the wash out phase, before extubation

Who Is Running the Clinical Trial?

Beth Israel Deaconess Medical Center

Lead Sponsor

Trials

872

Recruited

12,930,000+

Findings from Research

In a study involving 40 sets of isolated rabbit lungs, high inspiratory pressure during mechanical ventilation was linked to increased lung injury, as indicated by greater weight gain and higher rates of vascular failure.

Short-term exposure to high oxygen concentrations (100% O2) did not significantly worsen lung injury markers, suggesting that hyperoxia alone is not a major contributor to ventilator-induced lung injury in this model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term administration of a high oxygen concentration is not injurious in an ex-vivo rabbit model of ventilator-induced lung injury. Kopterides, P., Kapetanakis, T., Siempos, II., et al.[2014]

Oxygen therapy is crucial in emergency medicine and intensive care, but excessive use can lead to increased risks, such as the formation of harmful reactive-oxygen species, which may worsen patient outcomes.

While oxygen is essential to prevent hypoxemia, particularly in conditions like cardiac arrest and carbon monoxide poisoning, a normoxic oxygenation strategy is recommended to avoid the dangers of hyperoxia, especially in patients with chronic obstructive lung disease and myocardial infarction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oxygen therapy in emergency and intensive care medicine]. Grensemann, J., Wachs, C., Kluge, S.[2021]

In a study of 106 patients with acute exacerbations of hypercapnic COPD, over-oxygenation was found in 62% of admissions, indicating that oxygen prescription practices may need improvement.

While there was weak evidence suggesting that over-oxygenation could increase the risk of adverse events (with a hazard ratio of 2.5), the study's low statistical power highlights the need for larger studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of inpatient oxygen therapy in hypercapnic chronic obstructive pulmonary disease. Anderson, J., Hoang, T., Hay, K., et al.[2021]

In a systematic review of eight trials involving 4,415 mechanically ventilated patients, there was no significant difference in mortality between higher and lower oxygen targets, suggesting that oxygen therapy strategies may not impact survival rates.

However, targeting normoxemia (normal oxygen levels) compared to hyperoxemia (high oxygen levels) may reduce mortality, although this finding has low certainty and highlights the need for further research to clarify optimal oxygen therapy targets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxygen Targets During Mechanical Ventilation in the ICU: A Systematic Review and Meta-Analysis. Cumpstey, AF., Oldman, AH., Martin, DS., et al.[2022]

In a study of 110 patients with severe pneumonia requiring mechanical ventilation, conservative oxygen therapy significantly reduced ICU mortality and the incidence of complications like shock and liver insufficiency compared to conventional oxygen therapy.

While conservative oxygen therapy led to longer mechanical ventilation times, it resulted in a higher cumulative survival rate (72.7% vs. 54.9%) for patients, indicating its potential benefits in improving outcomes for severe pneumonia cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Observation of the curative effect of conservative oxygen therapy in mechanical ventilation of patients with severe pneumonia]. Yang, W., Zhang, L.[2021]

Oxygen therapy is crucial in treating hypoxemia in acute care, but excessive oxygen supplementation can lead to harmful effects, known as hyperoxemia.

The article emphasizes the importance of following current recommendations for safe oxygen supplementation to avoid the negative consequences associated with too much oxygen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oxygen toxicity in acute care settings]. Lévy, C., Schmit, A., Younossian, AB., et al.[2019]

In a study involving 45 episodes of moderate to severe asthma, administering 35% oxygen was found to be safe and likely sufficient for oxygenation before measuring arterial blood gases.

Using a lower concentration of oxygen could increase the risk of significant hypoxemia in asthma patients, highlighting the importance of starting with 35% oxygen in acute cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

'Safe oxygen' in acute asthma: prospective trial using 35% Ventimask prior to admission. Ford, DJ., Rothwell, RP.[2019]

A controlled oxygen delivery system using a 300 ml mask with a flow rate of 30 liters per minute can effectively provide the necessary inspired oxygen concentration of about 60% for patients with severe pulmonary function disturbances.

This system ensures that the oxygen concentration remains stable and does not fluctuate with the patient's breathing patterns, which is crucial for managing arterial hypoxaemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlled oxygen therapy at 60% concentration. Why and how. Campbell, EJ., Minty, KB.[2019]

In a study of 106 patients with severe asthma exacerbations, high concentration oxygen therapy significantly increased the levels of carbon dioxide (Ptco2) in the blood, with 44% of patients experiencing a rise of 4 mm Hg or more after 60 minutes.

The results suggest that titrated oxygen therapy, which adjusts oxygen levels to maintain appropriate saturation without causing excess carbon dioxide buildup, is safer and more effective for treating severe asthma exacerbations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised controlled trial of high concentration versus titrated oxygen therapy in severe exacerbations of asthma. Perrin, K., Wijesinghe, M., Healy, B., et al.[2013]

The study evaluated the use of an O2 concentrator (De VO2 955) in patients with chronic bronchopneumopathy, respiratory insufficiency, and pulmonary hypertension, focusing on the effectiveness of different gas supply methods, particularly Venturi masks.

It was found that Venturi masks providing 24% and 28% FiO2 were effective for patients with normal or low ventilation, but higher concentration masks failed to deliver the expected oxygen levels due to decreased O2 concentration at high flow rates and insufficient Venturi effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oxygen therapy with an oxygen concentrator]. Bosi, GP., Dotti, A., Tassi, GF., et al.[2008]

Breathing 100% oxygen can significantly improve comfort and efficiency in patients with COPD experiencing acute respiratory failure by reducing lung hyperinflation and allowing for better tidal volume and breathing rates.

This method not only helps stabilize respiratory mechanics but also protects vital organs from hypoxic injury, providing critical time for physicians to consider further interventions like intubation or bronchodilation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uses of oxygen in the treatment of acute respiratory failure secondary to obstructive lung disease. Wasserman, K.[2016]

References

1. United States pubmed.ncbi.nlm.nih.gov

Short-term administration of a high oxygen concentration is not injurious in an ex-vivo rabbit model of ventilator-induced lung injury. [2014]

2. Germany pubmed.ncbi.nlm.nih.gov

[Oxygen therapy in emergency and intensive care medicine]. [2021]

3. Australia pubmed.ncbi.nlm.nih.gov

Evaluation of inpatient oxygen therapy in hypercapnic chronic obstructive pulmonary disease. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Oxygen Targets During Mechanical Ventilation in the ICU: A Systematic Review and Meta-Analysis. [2022]

5. China pubmed.ncbi.nlm.nih.gov

[Observation of the curative effect of conservative oxygen therapy in mechanical ventilation of patients with severe pneumonia]. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

[Oxygen toxicity in acute care settings]. [2019]

7. England pubmed.ncbi.nlm.nih.gov

'Safe oxygen' in acute asthma: prospective trial using 35% Ventimask prior to admission. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Controlled oxygen therapy at 60% concentration. Why and how. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Randomised controlled trial of high concentration versus titrated oxygen therapy in severe exacerbations of asthma. [2013]

10. Italy pubmed.ncbi.nlm.nih.gov

[Oxygen therapy with an oxygen concentrator]. [2008]

11. Italy pubmed.ncbi.nlm.nih.gov

Uses of oxygen in the treatment of acute respiratory failure secondary to obstructive lung disease. [2016]