Carbon Dioxide Breathing for Orthostatic Hypotension

Overseen By Rasha Hamzeh, RN

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Calgary

Must not be taking: Autonomic drugs

Disqualifiers: Somatization, Severe anxiety, Pregnancy, others

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

Compensation: Varies

Number of Visits: 5

Duration: 5 sessions

80 Participants Needed

Trial Summary

What is the purpose of this trial?

The Autonomic (or "automatic") Nervous System (ANS) regulates internal processes, including control of heart rate and blood pressure (BP). When someone stands, and gravity tries to pull blood away from the brain, the ANS works to maintain BP and brain blood flow. Neurogenic Orthostatic Hypotension (NOH) occurs when our "fight-or-flight" part ("sympathetic") of the ANS fails. BP can drop a lot when upright, reducing blood flow and oxygen delivery to the brain, and this can cause symptoms of light-headedness, nausea, and fainting. One solution to help counter the effects of NOH may be to increase sympathetic activity by breathing higher levels of carbon dioxide. In healthy volunteers, small increases in the amount of inhaled carbon dioxide has been shown to increase BP in the upright position, and this improves symptoms! The objectives of the current study are to apply carbon dioxide in patients with NOH and healthy controls to: (a) evaluate the effects of breathing carbon dioxide on BP and brain blood flow, and (b) determine if a device that increases carbon dioxide while standing will work as a new therapy

Will I have to stop taking my current medications?

The trial excludes participants taking medications that could interfere with autonomic function testing, so you may need to stop certain medications. It's best to discuss your specific medications with the trial team to see if they are allowed.

Is carbon dioxide therapy safe for humans?

The research does not provide specific safety data on carbon dioxide therapy, but it highlights that excessive oxygen therapy can be harmful, especially for patients with conditions like COPD, which may involve carbon dioxide retention. ^{1 2 3 4 5}

How does the treatment Sequential Gas Delivery for orthostatic hypotension differ from other treatments?

Sequential Gas Delivery, also known as Carbon Dioxide Therapy, is unique because it involves controlled breathing of carbon dioxide to manage orthostatic hypotension, which is different from traditional treatments that may not focus on gas delivery. This approach is novel as it uses the therapeutic effects of carbon dioxide, which is not a standard treatment for this condition. ^{3 6 7 8 9}

Research Team

Satish R Raj, MD

Principal Investigator

University of Calgary

Eligibility Criteria

This trial is for adults over 18 who can consent, travel to the University of Calgary, and are non-smokers. It's not for those with dementia, substance abuse issues, severe organ diseases, pregnant or breastfeeding women, people on certain medications affecting autonomic function or unable to wear a mask.

Inclusion Criteria

Able and willing to provide informed consent

I am 18 years old or older.

I am either male or female.

Exclusion Criteria

You have severe anxiety or somatization symptoms.

Other factors which in the investigator's opinion would prevent the participant from completing the protocol, including poor compliance during previous studies

I need portable oxygen for breathing, either at rest or during physical activity.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo Active Stand Tests with varying levels of CO2 and O2 to evaluate the effects on blood pressure and orthostatic tolerance

5 sessions

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Sequential Gas Delivery

Trial Overview The study tests if breathing in higher levels of carbon dioxide (Sequential Gas Delivery) can help manage low blood pressure when standing in patients with Neurogenic Orthostatic Hypotension by increasing blood pressure and brain blood flow.

Participant Groups

Group I: +5mmHg CO2 Experimental Treatment 1 Intervention

All participants will complete an active stand breathing +5mmHg of CO2 relative to baseline

Group II: +10mmHg CO2 + 50mmHg O2 Experimental Treatment 1 Intervention

All participants will complete an active stand breathing +10mmHg of CO2 relative to baseline and 50mmHg of O2

Group III: +10mmHg Experimental Treatment 1 Intervention

All participants will complete an active stand breathing +10mmHg of CO2 relative to baseline

Group IV: +0mmHg CO2 Clamped at baseline Experimental Treatment 1 Intervention

All participants will complete an active stand with their CO2 held constant at baseline

Group V: Room Air Active Control 1 Intervention

All participants will complete an active stand breathing room air with CO2 free to fluctuate

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Findings from Research

Oxygen is a crucial life-saving treatment for patients with severe hypoxemia, but its use has often been based on tradition rather than scientific evidence, leading to potential risks.

Excessive oxygen therapy can increase mortality rates in critically ill patients, even in those without conditions like COPD that predispose them to carbon dioxide retention, highlighting the need for more careful management of oxygen administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxygen Use in Critical Illness. O'Driscoll, BR., Smith, R.[2020]

The article emphasizes the importance of nurses understanding the safe administration of oxygen therapy, particularly for patients with chronic obstructive pulmonary disease (COPD) and type II respiratory failure.

It highlights potential complications that can arise from oxygen delivery in these patients, underscoring the need for careful monitoring and management during acute care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Administration of oxygen therapy. McGloin, S.[2008]

Intermittent negative pressure ventilation (INPV) combined with increasing oxygen concentrations was tested on 17 male patients with severe COPD, successfully raising arterial oxygen levels without worsening carbon dioxide retention.

This method not only improved oxygen levels significantly (from 47.2 mm Hg to 61.5 mm Hg) but also reduced carbon dioxide levels (from 74.4 mm Hg to 65.6 mm Hg), suggesting it could be a safer alternative to intubation and mechanical ventilation for patients with severe respiratory failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent short-term negative pressure ventilation and increased oxygenation in COPD patients with severe hypercapnic respiratory failure. Sauret, JM., Guitart, AC., Rodríguez-Froján, G., et al.[2019]

A quality improvement pilot study showed that implementing a structured protocol for oxygen therapy significantly increased the proportion of patients with a prescribed target oxygen saturation range from 85% to 95%.

The improvement in oxygen target range prescribing was sustained at 96% even 12 months after the protocol was introduced, indicating effective long-term practice change in critical care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementing target range oxygen in critical care: A quality improvement pilot study. Heartshorne, R., Cardell, J., O'Driscoll, R., et al.[2022]

Oxygen therapy should start with the minimum effective dose, with initial FiO2 levels ranging from 24% to 100% based on the patient's condition, particularly in cases of COPD exacerbations and chronic hypercapnia.

High FiO2 levels can be safely administered for limited durations, with guidelines suggesting that 100% oxygen is safe for less than six hours, while 70% can be used for up to 24 hours, and 45% should be the upper limit for longer durations to prevent oxygen toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxygen therapy and oxygen toxicity. Tinits, P.[2022]

Long-term oxygen therapy is beneficial for patients with chronic obstructive lung disease (COPD), improving their quality of life and survival rates, but it requires careful patient selection due to its complexity and cost.

The article discusses the necessary tests and criteria for prescribing long-term oxygen therapy, highlighting advancements in delivery methods, particularly the use of transtracheal catheters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ambulatory long-term oxygen therapy]. Michel, F., Perruchoud, AP.[2016]

In a study of 12 patients with chronic lung disease, most retained their ability to respond to carbon dioxide levels during sleep, suggesting that oxygen therapy is generally safe for these patients.

While some patients experienced a significant increase in carbon dioxide levels with oxygen therapy, the majority showed only a minor increase, indicating that careful monitoring can help manage oxygen therapy effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of oxygen administration during sleep on skin surface oxygen and carbon dioxide tensions in patients with chronic lung disease. Hazinski, TA., Hansen, TN., Simon, JA., et al.[2013]

A new comprehensive approach to managing altitude mountain sickness (AMS) includes the use of hyperbaric oxygenation (HBO2) therapy, which can effectively treat hypoxaemia by providing oxygen under high pressure, potentially reducing AMS symptoms more effectively than traditional methods.

This method utilizes advanced hyperbaric treatment profiles developed for military and NASA applications, which can prevent AMS rebound effects that often occur with standard treatments, especially in elderly populations who may not tolerate conventional therapies well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Altitude mountain sickness among tourist populations: a review and pathophysiology supporting management with hyperbaric oxygen. Butler, GJ., Al-Waili, N., Passano, DV., et al.[2011]

In a study of 24 hypoxaemic patients with acute exacerbations of COPD, only 3 patients experienced clinically significant CO2 retention while receiving controlled oxygen therapy, indicating a low risk of worsening hypercapnia with this treatment.

The patients who did develop CO2 retention had more severe hypercapnia but still required only low-flow oxygen, suggesting that controlled oxygen therapy can be safely administered to most COPD patients with careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlled oxygen therapy and carbon dioxide retention during exacerbations of chronic obstructive pulmonary disease. Moloney, ED., Kiely, JL., McNicholas, WT.[2015]

References

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

Oxygen Use in Critical Illness. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Administration of oxygen therapy. [2008]

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

Intermittent short-term negative pressure ventilation and increased oxygenation in COPD patients with severe hypercapnic respiratory failure. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Implementing target range oxygen in critical care: A quality improvement pilot study. [2022]

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

Oxygen therapy and oxygen toxicity. [2022]

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

[Ambulatory long-term oxygen therapy]. [2016]

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

Effect of oxygen administration during sleep on skin surface oxygen and carbon dioxide tensions in patients with chronic lung disease. [2013]

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

Altitude mountain sickness among tourist populations: a review and pathophysiology supporting management with hyperbaric oxygen. [2011]

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

Controlled oxygen therapy and carbon dioxide retention during exacerbations of chronic obstructive pulmonary disease. [2015]