Oxygen Gas for Inhalation for Respiratory Insufficiency

Recruiting in Palo Alto (17 mi)

Overseen by Anthony Doufas, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Stanford University

Must not be taking: Opioids

Disqualifiers: COPD, Neurological, Cardiopulmonary, Psychiatric, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

In this randomized-controlled trial the investigators will examine the effect of oxygen supplementation on the recovery of breathing for 90 minutes in the immediate post-anesthesia period starting from extubation of the trachea.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have a chronic pain condition treated with opioids, you would not be eligible to participate.

What data supports the effectiveness of the treatment Oxygen Gas for Inhalation for Respiratory Insufficiency?

The research indicates that oxygen therapy is essential for treating respiratory insufficiency when there is a significant lack of oxygen in the blood (hypoxemia), especially when levels are critically low. It is most effective when used in controlled and dosed amounts for patients with severe respiratory issues. ^{1 2 3 4 5}

Is oxygen gas safe for inhalation in humans?

The research articles primarily discuss nitrous oxide mixed with oxygen, which is generally considered safe for use in various medical settings, with no major adverse effects reported. However, these studies do not specifically address the safety of pure oxygen gas for inhalation. ^{6 7 8 9 10}

How is the treatment 'Oxygen Gas for Inhalation' unique for respiratory insufficiency?

Oxygen Gas for Inhalation is unique because it provides controlled, continuous oxygen through a nasopharyngeal catheter, which helps improve oxygen levels and overall respiratory function without the risk of worsening respiratory depression. This method allows for safe home use, unlike some other treatments that may require hospital settings. ^{3 4 9 11 12}

Research Team

Anthony Doufas, MD, PhD

Principal Investigator

Professor, Department of Anesthesiology, Stanford University Medical School

Eligibility Criteria

This trial is for adults in good to moderate health (ASA I-III), with a BMI under 40, who are scheduled for robotic-assisted kidney removal surgery. It's not open to those with chronic lung disease, severe brain/heart/lung conditions, major psychiatric or untreated thyroid issues, chronic pain on opioid treatment, low blood count or significant blood loss during surgery.

Inclusion Criteria

American Society of Anesthesiologists (ASA) physical status I-III

Your body mass index (BMI) is below 40 kg/m2.

You are planning to have a type of kidney surgery called robotic-assisted radical laparoscopic nephrectomy.

Exclusion Criteria

You have been diagnosed with severe COPD, neurological, cardiopulmonary, or psychiatric conditions, or untreated thyroid disorder.

You are currently taking prescription painkillers for a long-term pain problem.

Patients with a hematocrit lower than 30% at the end of surgery, or those with an excessive blood loss, requiring transfusion of blood products during surgery

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either conservative or liberal oxygen supplementation during the 90-minute post-anesthesia period

90 minutes

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Oxygen Gas for Inhalation (Gas)

Trial Overview The study tests if breathing high levels of oxygen after general anesthesia helps patients recover their normal breathing faster. Participants will be randomly assigned to receive extra oxygen or not after they wake up from anesthesia and will be monitored for 90 minutes.

Participant Groups

Group I: "Liberal O2 Supplementation" Experimental Treatment 1 Intervention

Oxygen administration will be titrated to an SpO2 \> 96%.

Group II: "Conservative O2 Supplementation" Active Control 1 Intervention

Oxygen administration will be titrated to a oxyhemoglobin saturation (SpO2) between 90 and 94%.

Oxygen Gas for Inhalation is already approved in Canada for the following indications:

Approved in Canada as Oxygen for:

• Anoxia
• Hypoxia
• Dyspnea
• Respiratory distress
• Post-anesthesia recovery

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Dr. Richard A. Miller

Stanford University

Chief Executive Officer since 2023

Stanford University, MD

Dr. Robert Schott

Stanford University

Chief Medical Officer since 2021

University of Michigan, MD

Findings from Research

Inhaled nitric oxide (iNO) significantly improved oxygen levels in patients with severe hypoxemia, with arterial oxygen partial pressure (PaO2) increasing from 60.7 to 72.3 mm Hg after treatment (P=.008).

The use of iNO allowed for safe transport of patients to a tertiary care center, with 60.2% of those treated surviving to discharge, compared to a 50% survival rate in patients transported without iNO.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled nitric oxide to improve oxygenation for safe critical care transport of adults with severe hypoxemia. Teman, NR., Thomas, J., Bryner, BS., et al.[2020]

Inhaled nitric oxide (iNO) therapy is more effective in ARDS patients with a greater amount of normal lung tissue surrounding small consolidated areas, as indicated by a significant correlation between the morphology of lung injury and the response to iNO.

Patients who did not respond to iNO therapy had larger, more coherently consolidated lung regions, suggesting that the distribution of lung injury plays a crucial role in the efficacy of iNO treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Computed tomographic criteria as expected effect to inhaled nitric oxide in patients with severe acute respiratory distress syndrome]. Röttgen, R., Busch, T., Lohbrunner, H., et al.[2020]

Inhaled nitric oxide (INO) was used in a study of 163 children in the pediatric ICU, showing that early preterm infants (born <32 weeks) had better outcomes, including more ventilator-free days and lower mortality rates compared to late preterm and full-term infants.

The study suggests that INO was initiated for less severe lung disease in early preterm infants, indicating a need for future clinical trials to standardize criteria for starting INO therapy and to consider the history of prematurity when evaluating its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled Nitric Oxide Use and Outcomes in Critically Ill Children With a History of Prematurity. Maddux, AB., Mourani, PM., Banks, R., et al.[2023]

Inhaled nitric oxide (iNO) was effectively utilized in a NICU setting, leading to a significant reduction in costs per patient from $21,620 to $10,580, demonstrating improved management of hypoxemic respiratory failure.

The quality improvement project not only optimized the use of iNO by ensuring appropriate indications and timely weaning but also successfully implemented these strategies across multiple NICUs, enhancing overall treatment efficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A quality improvement project improving the value of iNO utilization in preterm and term infants. Fischer, H., Singh, T., Devlin, L., et al.[2021]

Oxygen therapy is crucial for treating respiratory insufficiency, particularly indicated by low levels of oxygen in the blood (PaO2), with specific thresholds defining absolute (PaO2 < 40 mm Hg), urgent (PaO2 < 30 mm Hg), and relative (PaO2 > 50 mm Hg) indications based on a study of 100 patients.

Using oxygen therapy when PaO2 is above 70 mm Hg or for preventive measures without hypoxemia can be harmful, and in cases where oxygen treatment is ineffective, mechanical ventilation should be considered, especially for patients in respiratory coma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Indications and contraindications for oxygen therapy of respiratory insufficiency]. Patarinski, D.[2009]

Nitrous oxide is a safe and effective anesthetic and analgesic for use outside of hospital settings, making it suitable for emergency medical services (EMS).

Its use is regulated and requires a physician's prescription, which means it can only be utilized in EMS systems that have received approval from local or state authorities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prehospital pharmacology: nitrous oxide. Jaslow, D., Lemecha, D.[2017]

Nitrous oxide mixed with oxygen is a safe and effective pain relief option that is underutilized in community settings for painful procedures.

The author successfully implemented the use of nitrous oxide/oxygen in her clinical practice after reviewing existing literature, leading to positive outcomes, highlighting the need for greater awareness and training in its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Entonox in the community for control of procedural pain. Evans, A.[2019]

Premixed 50% nitrous oxide and oxygen, known as Entonox, has been effectively used for pain relief since its introduction in 1961, and its use is experiencing a revival in France due to its effectiveness in managing pain during medical procedures.

The use of this gas mixture has a low incidence of side effects (less than 10%), making it a safe option for pain management in various settings, both in hospitals and outside, with specific guidelines for administration and precautions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Premixed 50% nitrous oxide and oxygen: theoretical recalls and practical modalities]. Boulland, P., Favier, JC., Villevieille, T., et al.[2017]

In a study involving 10 subjects exposed to high altitudes of 6553 m (21,500 ft), the risk of decompression sickness (DCS) was found to be 25%, with minor cases occurring after less than 90 minutes, indicating a significant risk for aircrew at these altitudes.

Breathing a gas mixture with 56% oxygen reduced the latency of venous gas emboli (VGE), suggesting that higher oxygen concentrations in the breathing gas can enhance safety and reduce the risk of DCS during high-altitude flights.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decompression sickness risk at 6553 m breathing two gas mixtures. Connolly, DM., Lee, VM., D'Oyly, TJ.[2019]

Nitrous oxide:oxygen mixtures are safe and effective for sedation and pain relief in emergency medicine, particularly in prehospital care due to their rapid onset and short duration of action.

The self-administered 50:50 mixture is the most acceptable method, and while it has shown no major adverse effects in various clinical settings, further research is needed to explore its use in combination with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrous oxide sedation/analgesia in emergency medicine. Stewart, RD.[2019]

Heliox, a mixture of helium and oxygen, reduces breathing resistance and work, making it beneficial for managing airway obstruction in neonatal and pediatric patients.

Inhaled nitric oxide acts as a selective pulmonary vasodilator, while hypoxic gas and carbon dioxide are used to manage pulmonary and systemic vascular resistance in infants with congenital heart defects, ensuring adequate oxygenation and tissue perfusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic gases for neonatal and pediatric respiratory care. Myers, TR.[2016]

In a study of 63 patients with global respiratory insufficiency, controlled oxygen treatment significantly improved oxygen levels (PaO2) by an average of 12 mmHg within 30 minutes and maintained these levels over 24 hours.

The treatment also led to a decrease in carbon dioxide levels (PaCO2) by an average of 8 mmHg, along with improved respiratory and cardiac function, suggesting that patients adapted well to the oxygen therapy, making it safer for potential home use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adaptation to oxygen breathing]. Patarinski, D.[2013]

References

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

Inhaled nitric oxide to improve oxygenation for safe critical care transport of adults with severe hypoxemia. [2020]

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

[Computed tomographic criteria as expected effect to inhaled nitric oxide in patients with severe acute respiratory distress syndrome]. [2020]

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

Inhaled Nitric Oxide Use and Outcomes in Critically Ill Children With a History of Prematurity. [2023]

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

A quality improvement project improving the value of iNO utilization in preterm and term infants. [2021]

5. Bulgaria pubmed.ncbi.nlm.nih.gov

[Indications and contraindications for oxygen therapy of respiratory insufficiency]. [2009]

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

Prehospital pharmacology: nitrous oxide. [2017]

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

Use of Entonox in the community for control of procedural pain. [2019]

8. France pubmed.ncbi.nlm.nih.gov

[Premixed 50% nitrous oxide and oxygen: theoretical recalls and practical modalities]. [2017]

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

Decompression sickness risk at 6553 m breathing two gas mixtures. [2019]

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

Nitrous oxide sedation/analgesia in emergency medicine. [2019]

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

Therapeutic gases for neonatal and pediatric respiratory care. [2016]

12. Bulgaria pubmed.ncbi.nlm.nih.gov

[Adaptation to oxygen breathing]. [2013]