The hypoxic drive theory: debunked

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

All my fellow RTs have whitnessed it: the CO2 retainer who is breathing normal, is not in respiratory distress, has his oxygen turned up, and nothing bad happens. The patient does not stop breathing. Why is that?

It is because the hypoxic drive theory is not true. If it were, we'd have many more COPD patients dying each day.

What is really going on?1

The hypoixic drive is real, but it is not what causes CO2 to rise. There are essentially two different reasons why CO2 might rise in COPD retainers.

Reason #1: V/Q mismatching. Allow me to quote Jeff Whitnack from over at Jeff Whitnack's RT Page (actually, I believe he is paraphrasing a chapter by Robert Lodato in Martin Tobin's book, "Principles and Practices of Mechanical Ventilation," (pages838-9):

Imagine the worst ventilated alveoli. The local CO2 pressure there may be 100 or more. On room air the local O2 pressure will surely be less than 60 torr. At this level of local hypoxemia, the adjacent pulmonary vasculature will constrict. Blood will then be sent to the alveoli which is ventilating more effectively. Ventilation/ perfusion matching is enhanced. But if 100% O2 is given the O2 pressure will not drop below 60, the pulmonary vasculature will not constrict, and V/Q matching will not be optimized. Just as giving Nipride may drop the PaO2 as hypoxic pulmonary vasoconstriction is released, so giving 100% O2 may also raise the PaCO2. This also can happen to patients in an asthmatic crisis given 100% O2. It’s not that we knock out a hypoxic drive, so much as we drive in a hypercarbic potential. Then further compromise ventilation through increased V/Q mismatching.

For the patients I described at the top of this post, it is this -- V/Q mismatching -- that is causing the patient's CO2 to be high, and therefore it is actually safe to have this patient on 100% FiO2 without causing that patient to become lethargic or to die.

If we simply clung to the hypoxic drive theory, and didn't give these patients the oxygen they need to maintain a healthy heart and brain, they are more likely to die than if we given them oxygen.

Reason #2: The Haldane Effect:

Unsaturated hemoglobin carries CO2. A patient in crisis may arrive in the ER with an SpO2 on room air of 75%, the unmeasured mixed venous saturation may then in turn also be much lower than the 75% norm. All this unsaturated hemoglobin is then carrying an extra CO2 load. This is in the setting whereby the patient has an already elevated PaCO2, perhaps has an elevated Hgb (hemoglobin) after years of hypoxemia, and is “topped off” on their ability to ventilate. So for every rise in their SpO2 we are driving more CO2 into the plasma. If this were you or I, we would simply then ventilate this extra CO2 out via the lungs. But their lungs can’t and don’t, therefore the CO2 shows up in the “downstream” ABG.

This is why you will see a rising CO2 in many CO2 patients when they are placed on increased amounts of oxygen, and they can still talk to you. They are in no respiratory distress, yet the doctor is thinking, "Turn down the oxygen."

If the Haldane effect is causing a person's CO2 to be high, then we need to be on the lookout for impending respiratory failure, and have our BiPAP or ETT ready.

If a patient is on 100% Fio2 you should be concerned that the CO2 might go up, especially if his sat of 100%. What you should do here is back off on the oxygen until you have an SpO2 of 92%, which is where most of our doctors like to keep that sat per our oxygen protocol on non COPD patients.

So why do we make COPD patients suffer with a sat of 88%? It's because most of our doctors believe in the hypoxic drive theory.

Usually the patient will only become lethargic with excessive O2 therapy when he is already compromised, he is pooped out (fatigued), and he cannot blow off the excess CO2 because he has no more pulmonary capacity of which to increase his minute ventilation. It is these patients whose CO2 increases to greater than 90, and of whom are prone to pass out due to too high of a CO2.

And we have all seen this happen. It's about 30% of COPD patients.

So keep an eye on them. Have your airway box ready. But don't make them suffer with an SpO2 in the low 80s just because of the hypoxic drive theory.

Many times we have a patient on the vent and have to get them down to 88% SpO2 because "that's what they live with at home on 2lpm." So, why not send them home on 4lpm with an SpO2 of 92%? This is exactly what is recommended on this slide (source unknown):

• Give oxygen, maintain SpO2 >92%
• Close observation for changes in mental status
• Use of non-invasive CO2 monitoring
• Early use of non-invasive ventilation if needed

At least we could try them on 4lpm and do an ABG an hour or so later. If the CO2 doesn't go up and you have the PO2 you want, then by golly send the patient home on 4lpm. Likewise, if the CO2 does go up slightly, and the patient is still talking to you, then by golly send the patient home on 4lpm.

But you know what? We never do this study on patients. I've never done it once in my 10 year career as an RT. Why? Because doctors don't need to do this oxygen study, because they have already bought into the hypoxic drive theory.

But, as Whitnack writes, "if that same patient is at home and resting while watching the ball game on TV as their O2 accidentally gets turned up by 1 l/m -- well, they won't stop breathing and that's why I've never met an ambulance with such a patient on board."

Great point I say.

Consider this example he gives. I've seen it, and so have you more than likely:

Picture the COPDer whom arrives in the ER SOB with a RR 45 and initial PaO2 44, PaCO2 66, pH 7.35 on RA. So someone places them on 8 l/m simle mask and draws another ABG-- now they are PaO2 110, PaCO2 80, pH 7.25. The patient's RR is now 26 and the patient's respiratory effort is much less labored. Did we knock out that patient's drive to breathe? Or did we relieve the patient's hypoxemia sufficient that the patient could practice their own form of permissive hypercapnea? If we intubated the patient and considered his auto-peep, we may be happy with the latter ABGs also.

Which is also a reason why we should never panic and rush to intubate someone.

Why is it that we never hear about the COPD patient dying who is stable in his room, but accidentally has his oxygen increased from 2lpm to 5lpm? If the hypoxic drive were true, shouldn't that patient become lethargic, and maybe even go into cardiopulmonary arrest.

Instead, he's in his room watching the Detroit Tigers and munching on gram crackers.

Now we know why.

Click here for a neat slideshow regarding the hypoxic drive myth. Rather, it's now called Oxygen Induced Hypercapnia, not hypoxic drive.

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