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Monday, October 17, 2016

Debunking The Hypoxic Drive Theoery: The Truth About The Affects Of Oxygen On COPD

Originally published January 6, 2016.

I was recently interviewed by Rebecca Knutsen, a staff writer working for Advance for Respiratory Therapists.  She said she was working on a brief article that explores when to administer oxygen to hypoxemic patients with chronic obstructive pulmonary disorder.

The following are her questions followed by my answers.  

1.  Please describe hypoxic and hypercapnic drive:

Hypercapnic Drive: The central chemoreceptors on the medulla monitors the partial pressure of arterial CO2 (PaCO2). A normal PaCO2 level is 35-45 mmHG. When PaCO2 is high (>45 mmHg) a signal is sent to the medulla oblongata at the base of the brain to speed up breathing in order to blow off excess PaCO2. When PaCO2 levels are low (<35 mmHg) a signal is sent to the medulla oblongata at the base of the brain to decrease breathing in order to allow PaCO2 to accumulate. This is the main drive to breathe.

Hypoxic Drive: The peripheral chemoreceptors located at the bifurcations of the aortic arteries and the aortic arch monitor partial pressure of arterial oxygen (PaO2). This drive only becomes active when the PaO2 is less than 60 mmHg. This hypoxic response is far slower than signals sent by central chemoreceptors, and therefore the hypoxic drive has only a minor role in breathing.

2.  What tests does your organization use and what do they measure?

ABG: This is a blood draw from the radial, brachial or femoral artery that measures PaO2, PaCO2 and arterial pH.

Pulse oximeter: It’s a noninvasive device that slips over a finger, toe, or ear lobe. It determines the SpO2, which is an estimation of hemoglobin in the blood that are saturated with oxygen. This percentage can be used to estimate PO2. Generally, an SpO2 of 90 indicates the PO2 is about 60.

End Tidal CO2 Monitor: It’s a noninvasive device that can be connected to special nasal cannulas or endotracheal tubes. It determines the ETCO2, which is an estimation of the amount of CO2 exhaled. This percentage can be used to estimate PaCO2. In a person with healthy lungs, the EtCO2 is about 2-5 mmHg less than PaCO2.

3.  When is it recommended to administer oxygen to hypoxemic patients with COPD? 

Most medical experts now recommend administering the lowest amount of oxygen needed to maintain an SpO2 of 88-92%, or as directed by a physician.

4.  Why is hypoxic drive so controversial? 

The hypoxic drive is not controversial, it’s the hypoxic drive theory that’s controversial. To understand why it is so controversial it’s important to understand a little of the history of it. 

Back in the late 1940s and 50s, when oxygen first started to be used for patients with chronic obstructive pulmonary disease, it was observed that some of them became lethargic or lapsed into a coma after receiving high levels of oxygen.

Initial studies showed a decrease in ventilation in 26 of 35 patients with COPD given oxygen therapy, with a rise in CO2 and a fall in pH. A further study showed that stopping and starting oxygen therapy led to a fall and rise in CO2 respectively.

The concern became so great that in the 1950s a study was performed that ultimately lead Dr. EJM Campbell to give a lecture to pulmonologists in 1960 about the dangers of giving too much oxygen to COPD patients. It was this lecture that forever linked hypoxic drive with COPD, and gave birth to the hypoxic drive theory.

What is the hypoxic drive theory? The hypoxic drive theory states that some patients with COPD develop chronically elevated arterial CO2 levels, and so their hypercapnic drive becomes blunted, so they use their hypoxic drive to breathe instead. 

Therefore, giving high amounts of oxygen to these patients may blunt the hypoxic drive as well, thus completely blunting their drive to breathe. This may cause PaCO2 levels to rise to critical levels, resulting in narcosis and possible death. For this reason, COPD patients with suspected CO2 retention are limited to 2-3 lpm by nasal cannula, or 40% by venturi mask.

What’s wrong with this theory? The problem with this theory is that it’s a myth concocted on incomplete evidence. The study cited by Campbell included only four patients with COPD, and later studies failed to validate this theory. Yet it has continued to be a gold standard theory when dealing with COPD patients.

Under the guise of this theory, many patients who desperately need higher levels of supplemental oxygen to survive are deprived of it. Plus, as many respiratory therapists, nurses, and physicians have observed, when these patients are given the oxygen they need, rarely does this lead to complications.

When these patients go into respiratory failure, it’s going to happen regardless of how much oxygen they receive. And while higher levels of oxygen may cause CO2 to rise, it’s not due to oxygen blunting their hypoxic drive, which the hypoxic drive theory postulates, it’s due to either the Haldane effect or V/Q mismatching.

The Haldane effect: This was postulated by John Haldane, a pioneer in oxygen therapy. He proved that the Deoxygenation of arterial blood increases its ability to carry carbon dioxide. In other words, as fewer oxygen molecules are attaching to hemoglobin, more CO2 are attaching to hemoglobin.

Oxygen is more soluble in water and therefore has a higher affinity for hemoglobin, so if you increase oxygen in the blood, CO2 molecules are forced off hemoglobin and oxygen takes its place. This causes an increase PaCO2.

Add into this the fact that patients with COPD have limited reserves to increase their respiratory rate to blow off excessive CO2. Also add into this that many COPD patients already have an elevated hemoglobin levels, and so these patients are going to have lots of extra arterial CO2 molecules.

Out of respect for this theory, COPD patients should be maintained on the lowest level of oxygen required to maintain an oxygen saturation between 88-92%.

The Haldane effect was proven by a study described in 1996 in Critical Care Medicine, "Causes of hypercarbia with oxygen therapy in patients with chronic obstructive pulmonary disease."

V/Q Mismatching: The air passages of COPD lungs become narrow due to remodeling, increased mucus production, and bronchospasm. Where this occurs the lungs are perfused but poorly ventilated. CO2 returning to these areas remain in arterial bloodstream, thus causing PaCO2 to rise.

Add into this that when alveoli are poorly ventilated the vasculature around them will constrict so oxygen goes to alveoli that are ventilated well. This is how these patients make efficient use of their diseased lungs.

Now add 100% oxygen and you screw up this naturally occurring phenomenon. Now the vasculature around that non-ventilating alveoli dilates, and this causes blood to be sent to the non functioning alveoli. Now you have even greater V/Q mismatching and more CO2 that doesn't get out of arterial blood. The end result is an increase in PaCO2.

If a patient with COPD is going to fail this is going to be the reason. If they need oxygen you give it to them, because doing otherwise will further compromise them. If they go into respiratory failure, you treat it with either noninvasive ventilation or mechanical ventilation.

V/Q Mismatching was proven via a study completed in 1980 and reported in American Review of Respiratory Disorders, "Effects of the administration of O2 on ventilation and blood gases in patients with chronic obstructive pulmonary disease during acute respiratory failure,"

Conclusion: Modern evidence suggests that the hypercapnic drive is never completely blunted, and therefore even COPD patients with chronically elevated PaCO2 will not stop breathing in the presence of higher oxygen levels. There is such a thing as the hypoxic drive, but the hypoxic drive theory is a myth.

To read the final published version of my interview read "Oxygen and COPD: Debunking the hypoxic drive theory."

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