The hypoxic drive theory: The CO2 retainer

(This is part three of a six post series. To go to part one click here.)

Today I would like to add to our discussion of why people breath. In particular, today's post will delve further into the topic of oxygen induced hypoventilation.

As we described earlier, the body will continually try to make sure that gases in the body are balanced in order to maintain a normal pH, and in this way maintain a certain level of homeostasis within the body.

Usually, increases and decreases in carbon dioxide levels detected by the central chemo receptors is what causes people to breath. When a person is in respiratory failure, and the carbon dioxide level is high, decreasing levels of oxygen as detected by the peripheral chemo receptors then takes over as the drive to breath.

Thus, if a person has a chronically high carbon dioxide level, and you give this person 100% oxygen, you knock out their drive to breath. This, my friends, is what we call the hypoxic drive theory. Actually, this is the gold standard of respiratory care. It is what helped to establish us as a profession.

According to Donald Egan's "Fundamentals of Respiratory Care," when a healthy person "breathes 100% oxygen, the peripheral chemo receptors remain essentially inactive. However, because blood oxygen levels are high, there is less reduced hemoglobin available to carry carbon dioxide. This causes a slight rise in (carbon dioxide) CO2, which in turn stimulates the medullary respiratory center (at the base of the brain)." This in turn causes a person to breath faster.

Now, if you have a patient who has a chronically low level of oxygen and high level of CO2, breathing high levels of oxygen (FiO2) can cause a person to slow down his breathing (per the theory). In essence, the "high blood O2 (oxygen) levels suppress these peripheral chemo receptors, thereby depressing ventilatory drive."

Since a person's breathing is how they blow off excess CO2, you can see how this could be detrimental to a person who already has a high CO2 level.

Thus, since the high FiO2 (say 100%) is signalling the peripheral chemo receptors to slow down breathing, a person with a chronically high CO2 may end up with a critically high CO2. In cases like this, I've seen CO2s in COPD patients as high as 110. This is not good. And usually these patients become lethargic. Yet many times they surprise us and they do not lose consciousness.

Usually, according to William A. French, "Hypoxic Drive Theory Revisited," rtmagazine.com (Issue: February/March 2000), CO2 must generally reach a level above 90 mm Hg for" a patient to become lethargic.

However, sometimes these patients are so used to high CO2 levels, that they remain conscious even with a high CO2 level. If you have ever seen a COPD patient in this situation, you will observe that they are usually blue, and this is where we get the term blue bloaters from. The patient is blue due to low oxygen.

And they also are jittery or shaky. That is the high CO2 at work. If they are lethargic, that is usually due to the high CO2 level, but as the hypoxic drive theory states, it may also be due to the high level of oxygen the medical staff provided to the patient.

That is the theory. Keep in mind it is a theory that doctors believe in to the point of ad nauseam. I personally think it is inhumane to allow a person's oxygen to stay low, when this could kill them. However, that's just my opinion.

This brings me to my next point. According to Egan himself, right in his book. And I think it is these next two paragraphs that will help me disprove the hypoxic drive theory, of which I will attempt to do in my next couple posts.

Egan writes that "the rise in PaCO2 that is observed in some patients is due mainly to impaired gas exchange, not depression of ventilation."

And, he writes:

"Regardless of mechanism then, hyperventilation is a potential hazard of O2 therapy in patients with chronic lung disease, however, this harmful effect should never stop us from giving oxygen to a patient in need. Preventing hypoxia should always be the first priority."

Thus, according to Egan, "in order to prevent hypoxia but avoid hypoventilation (breathing to slow down) in these patients, we should aim for an arterial PO2 between 50 and 60 torr. Generally, this approach provides adequate oxygenation, while minimizing the likelihood of hypoventilaiton."

In layman's terms, a normal blood PO2 is over 100. A PO2 of 100 would usually generate a sat (SPO2) of about 98% (this is the % of oxygen in inspired air that gets to the arteries). A PO2 of 50 to 60 would therefore generate a sat of 80 to 90%. So, if you werent' familiar with these medical terms, now you are. And now you know what to look for on the monitor besides heartrate, respiratory rate and blood pressure.

To maintain a sat of 80 to 90%, usually we RTs use 2-3 LPM via nasal cannula. Or, if a patient needs more oxygen, or is breathing laboriously, we will use a venti-mask at no more than 30 to 40% FiO2 (oxygen). (For the record, there is 21% oxygen in the air you breath).

However, what happens if a chronic COPD patient is on a 40% venti-mask and the sat on the monitor still reads 70%? Now what do you do. You give them more oxygen. You give them 100% oxygen if they need it.

Or, as I've seen many times, you walk up to the doctor to get an order for more oxygen, and he says, "keep it right where it is. We don't want to knock out his drive to breath." And he looks at you like you are an idiot.

Or, another scenario is you do a blood gas that shows a PO2 of 45 and a CO2 100. The patient is awake and alert and talking to you just fine. The doctor says, "decrease the oxygen. We need to see if we can get that CO2 down."

This is where you roll your eyes in frustration.

(To view part four click here. To return to part one click here.)

The hypoxic drive theory: Why do we breathe?

(This is part two of a six post series. To return to part one, click here.)

When you are thinking about it, you can control your breathing on your own. Most of the time you are alive, however, you will have other things to think about, yet your breathing continues.

So, how does this work?

(For further reading you can click here.)

There are basically two reasons for breathing. One is to maintain homeostasis (balance) within the body, and the other is for the exchange of gas. By homeostasis I mean maintaining a normal level of oxygen (PO2), carbon dioxide (CO2) and acid base balance (pH or hydrogen ions). By exchanging gas, I mean breathing in oxygen, and blowing out CO2.

According to Donald F. Egan's "Fundamentals of Respiratory Care", breathing is controlled by the Central Nervous System, and originates "in the brain stem, mainly from neurons located in the Medulla Oblongata. For the most part, and skipping a bunch of crummy detail, this gland controls breathing by messages it receives from Chemo receptors.

There are two sets of chemo receptors: the central and the peripheral. The central sit right on the Medulla, and the peripheral are located in the "bifurcations" of both carotid arteries and the arch of the aorta, or somewhere between your shoulders and above your heart.

These chemo receptors send messages to the brain (the Medulla) based on changes in CO2 and PO2. However, for the most part, the main driver of non-spontaneous breathing is carbon dioxide (CO2) way more so than oxygen (PO2).

Allow me to put it simple, when CO2 goes up above a certain point, your breathing speeds up. This is evident quite often in COPD and asthma patients who are suffering an exacerbation. They are having great trouble breathing, and ultimately they start to poop out, and their CO2 starts to build up. Thus, their breathing speeds up.

A normal CO2 is 40. Say it goes up to 100. By this point, when CO2 is 20% or greater above the normal value, CO2 starts to act like a sedative, and slows breathing down. Thus, as CO2 continues to rise, this is a sign doctors watch out for that a person is pooping out, and may need aggressive therapy.

The majority of the time, the central chemo receptors send signals to the brain that control breathing. The peripheral chemo receptors only have a minor roll during normal respirations, and only send a signal to breathe when the PO2 is less than 60. Either way, this response is far slower than the signal sent by the central chemoreceptors. Thus, the peripheral chemoreceptors only play a minor role in breathing, unless a patient is a chronic CO2 retainer (so the theory goes), of which we will discuss in a moment.

Thus, we will focus on the central chemo receptors for purposes of simplicity.

Let me confuse you a minute. The real drive of breathing is actually hydrogen ions . As hydrogen ions increase, your breathing speeds up. But, since hydrogen ions are not allowed to cross the blood brain barrier so that the pH of the brain can be different from the pH of the body, it cannot directly be used to stimulate breathing.

Thus, CO2 is used. CO2 is allowed to cross the blood brain barrier. Excess levels of CO2 arrive in the brain and are received by the Central Chemo receptors. Thus, "elevations in CO2... cause rapid diffusion of the gas into the CSF (Cerebral Spinal Fluid), where it dissociates into hydrogen ions and lowers the CSF, thereby stimulating the central chemo receptors. The central chemo receptors, in turn, signal the medulary centers to increase ventilation."

So you can see, CO2 "indirectly" causes changes in respiration's.

If the CO2 becomes chronic, or is still hanging at a high level after a day or two, according to Egan, the stimulatory effect of the high CO2 diminishes because the kidneys will try to compensate for the high CO2 by creating more buffers (bicarbonate or HCO3), thus causing the pH of the CSF to go back to normal. The medulla thus receives a signal that CO2 is normal, even though it is actually elevated.

It therefore is easy to tell which patients are chronic retainers because their HCO3 level will usually be high, and usually something greater than 30.

And, in Chronic COPD patients, this CO2 level may stay high while at the same time maintaining homeostasis (a normal pH), and, thus, CO2 has less of an effect on breathing as it would on a normal person (in theory anyway).

In effect, it may be normal for a COPD patient to have a CO2 of 50, and a PO2 of 50. We call these guys members of the 50/50 club, or chronic CO2 retainers or simply chronic retainers.

Changes in PO2 have no direct effect on Central Chemo receptors.

As anything in life, this process is far more complicated than I just explained, but you can see from what I have described here why in many COPD patients CO2 may lose its ability to stimulate a person's drive to breath, especially when CO2 is chronically elevated (or so the theory will have it).

And this is where the gold standard of RT comes into play. As, when a patient has a chronically elevated CO2, it is believed that it stops being the drive to breath. In these patients, it is believed that oxygen becomes their main drive to breath.

Thus, we must take a look at peripheral chemo receptors. According to Egan, "Peripheral chemo receptors are not very sensitive to CO2 changes... their primary role appears to be in response to hypoxia."

Normal PO2 is 104. It does not effect the peripheral chemo receptors until it is less than 60. To put this in perspective, a PO2 of 60 will usually generate a sat (SPO2) of about 90%. As the PO2 falls from 60 to 30 torr (SPo2 of 90% to 60%), the rate of breathing should be expected to be increased due to signals sent from the peripheral chemo receptors.

Now, as we've explained, CO2 is normally the drive to breath. But, if a patient with COPD is having so much trouble breathing that there is no way possible that he can speed up his breathing further to blow off that excess CO2 "regardless of patient effort," CO2 no longer is the drive to breathe, and PO2 becomes the drive to breathe.

This is called the hypoxic drive theory.

And this, my fellow readers, is why doctors soooooo do not want to put a COPD patient on more than 2LPM even though their oxygen levels continue to be low.

This is why many COPD patients are allowed by many doctors to have sats in the mid to low 80s even though low levels of oxygen may be deadly to the heart. This is why many doctors refuse to put many COPD patients on 100% oxygen, because they are afraid they will knock out their drive to breath. They are afraid the patient will become lethargic and die.

The hypoxic drive theory is the gold standard of respiratory therapy, but is it a fallacy or a reality? This is a debate that may be ending.

(To view part three click here. To return to part one click here.)