I. The Why
How many of our protocols for COPD and oxygen administration look something like this?
I think it is ubiquitous no matter where you work in EMS or EM. This begs the greater question of:
WHY do we target these SpO2 values in COPD patients?
The answer is simple, right? It is because of the hypoxic drive!
Under normal, healthy physiologic conditions (i.e. someone without COPD) our stimulus to breathe is driven by carbon dioxide. However, in abnormal physiologic conditions (like someone with COPD) there are chronically elevated CO2 levels and our body becomes “desensitized” to the high amounts of CO2. Thus, our stimulus shifts to oxygen levels instead of CO2. And if we give high flow oxygen to our COPD patients then we “knock out” their hypoxic drive with too much oxygen. Instead, we titrate their oxygen levels to a low SpO2 so they still retain some stimulus to breathe on their own.
Well, I hate to break it to you, but a hypoxic drive actually doesn’t exist and this thought process is inherently flawed. I theorize that this term was used long ago to help explain the true concept of why we target lower SpO2 values and the mental learning shortcut of the “hypoxic drive” stuck around for years and years and years.
II. The How & Why – COPD review
I am not about to explain that COPD is composed of emphysema and chronic bronchitis. This was hammered home during EMT and medic school. What I care more about is how does this condition affects our carbon dioxide and why it is bad.
It is important to understand that when carbon dioxide levels rise, a series of events begin to occur. Carbon dioxide is an acid and when elevated, contributes to respiratory acidosis. Hence a low pH and a high PaCO2 on an ABG is respiratory acidosis. But, as the levels of CO2 continue to rise, they exert a profound narcosis effect on our central nervous system. It essentially makes our patients sleepy; and what happens to our respiratory rate when we sleep? It goes down. As our respiratory rate drops, we can no longer off-gas that excess CO2 and it just keeps building up. Eventually, we start seeing end-tidal values into the 80's or 90’s. This cycle looks something like this:
So how does COPD contribute to this CO2 spiral of death?
The bronchitis component of COPD has everything to do with resistance. There aren’t as many issues getting air IN, but there are always issues getting air OUT. Sometimes, you may hear COPD and asthmatics grouped together as “obstructive pathology” patients. That is what it means -- issues getting obstructed air from resistance OUT that leads to air trapping. Therefore, the bronchitis component contributes to retaining CO2 because of the inflamed bronchus and its resistance to airflow.
For those that care, this resistance is generated by something known as the “Hagan-Poiseuille Law”. This law states that as the diameter of a tube decreases by half, the resistance within that tube increases by 16 times! This law also helps explain IV flow rates. If the diameter of an IV catheter is doubled, the resistance to flow drops 16-fold. Less resistance means more flow. In COPD terms, more resistance means less flow out of the lungs.
Maybe this quick video might help to compare two saline flushes. Notice one has no needle on the end (resembling a normal lung) and the other has a small diameter catheter on the end (resembling the airflow restriction in COPD patients). Watch when I push down on the plunger, which is going to resemble exhalation…
Notice how much of the flush is left over in the COPD lung, that excess saline is our “trapped” CO2. And guess what that trapped CO2 leads to??? That CO2 spiral of death.
Now onto the emphysema component… emphysema is nothing more than an inflammatory response to more often than not, cigarette smoking. Put simply, with inflammation comes excess fluid to bring these immune cells into the area of concern. Cigarette smoke triggers this inflammatory response and over years and years of smoking packs a day, we start to flood our alveolar-capillary membrane with white blood cells and fluid (edema).
This constant flood into the alveolar-capillary membrane disrupts the core concept of ventilation. Carbon dioxide cannot diffuse from the pulmonary capillaries into the alveoli if it is flooded with white blood cells and edema. So, because of emphysema, CO2 tends to stay within the capillaries – No diffusion takes place if emphysema exists.
Remember, CO2 is an acid and once it begins to accumulate in the pulmonary capillaries it contributes to acidosis and lower pH. Rising CO2 eventually causes the narcosis effect we discussed earlier and then into that CO2 death spiral.
III. The Hypoxic Drive Does Not Exist!!
With these rising CO2 levels, the hypoxic drive theory states that we become “desensitized” to hypercarbia. We then switch our drive to breathe based on our oxygen concentration. As I eluded to earlier, this theory is flawed.
It is my assumption that the hypoxic drive was used as a general, blanket teaching term that actually encompassed two more confusing terms:
a. Hypoxic Pulmonary Vasoconstriction
AND
b. The Haldane Effect
The combining mechanisms of these two formulated much of what we, mistakenly, understand today as the hypoxic drive.
A. Hypoxic Pulmonary Vasoconstriction
This mechanism has everything to do with the ventilation and perfusion ratio within our lungs. Ventilation referring to the amount of gas exchange at the alveolar level (O2 diffusing from alveoli into the capillaries and CO2 going in the opposite direction). Perfusion is a measure of how much blood flow exists within these pulmonary capillaries. Under normal physiologic conditions, these two values are relatively equal and system operations are normal.
However, under stress and hypoxia or shock, these values become skewed and we either get adequate ventilation (V) with poor perfusion (Q) OR adequate perfusion with poor ventilation OR both are down in the dumps. This is eloquently referred to as a V/Q mismatch.
In COPD exacerbations, the issue revolves around the ventilatory component of the V/Q mismatch. As CO2 is unable to be offloaded it backs up in the alveoli. As it backs into the alveoli, it starts to leak down its concentration gradient into the pulmonary capillaries. This leads to hypercarbia… then narcosis… you get the gist.
But what about oxygen in this situation? That whole process described in the last paragraph doesn’t really leave a whole lot of room for oxygen. As the alveoli are flooded with CO2, they slowly become hypoxic. The body recognizes this hypoxia within the alveoli and the lungs go into triage mode. If an alveoli has become hypoxic, the lung essentially “writes off” those alveoli and starts shunting blood away from that alveoli. Importantly, it shunts blood towards the healthier alveolar units. The theory is that if they reroute the blood flow (the perfusion of the V/Q mismatch) to functional units, it could clear out some of this backed-up CO2. This entire concept is known as hypoxic pulmonary vasoconstriction!
This was a long-winded explanation, so I do apologize but the important take-home point is this: Our body uses the hypoxic pulmonary vasoconstriction mechanism in order to combat hypercarbia. It redistributes blood flow to healthy alveoli in order to clear the excess CO2.
B. The Haldane Effect
The Haldane effect largely answers the question of why we titrate to a SpO2 of 88-92%.
The Haldane effect states that deoxygenated hemoglobin has a high affinity to carry CO2. Hemoglobin wants to carry something, it would prefer to carry oxygen but in the absence of oxygen it readily takes in CO2. We can break this down a bit more for a better understanding…
Patients suffering from COPD exacerbation will have high carbon dioxide levels (PaCO2). This is due to the air-trapping from bronchitis and the breakdown of the alveolar-capillary membrane from emphysema. Our body will compensate for this by utilizing the hypoxic pulmonary vasoconstriction in an attempt to redirect the blood flow carrying the excess CO2 to the healthy alveolar units in an effort to off-gas that CO2.
The Haldane effects comes into play when we introduce oxygen to these patients. As oxygen enters, our hemoglobin sees the O2 molecule and would much rather shack up with it. So, it kicks off the CO2 for the oxygen instead. This is the Haldane effect.
However, the kicked-off CO2 doesn’t just disappear, it still contributes to a rise in arterial concentration of carbon dioxide and continues worsening the acidosis. We want that CO2 to be bound to the hemoglobin because it should eventually make its way to a healthy alveolar unit to be exhaled (via the hypoxic pulmonary vasoconstriction compensatory mechanism). But if it is not bound to hemoglobin, it’ll never get there… and a rising PaCO2 leads to…. That vicious death spiral again.
The Haldane effect contributes to hypercarbia by forcing hemoglobin to kick off CO2 to exchange it for the readily available oxygen we just administered. There is a small caveat to this though… oxygen flow is different than the fraction of inspired oxygen (FiO2). In relation to the Haldane effect, it is not the flow we are concerned with but rather the FiO2 we administer to the patient. In the absence of a vent, there is not much we can control. However, we should never withhold oxygen from a hypoxic patient in the fear of inducing the Haldane effect! We should be targeting a lower SpO2 between 88-92% in order for some CO2 to remain bound all the while providing adequate oxygenation. It is a balance game of sorts.
IV. Final Take-home Points
· COPD is more than just bronchitis and emphysema! Understanding how these conditions, independently, contribute to rising carbon dioxide levels is the key to understanding this disease process.
· The hypoxic drive never existed and is nothing but a medical myth, instead it is a combination of the hypoxic pulmonary vasoconstricting mechanism and the Haldane effect.
· Once again, never withhold oxygen from a hypoxic patient. But we should be targeting an SpO2 of 88-92% to balance adequate oxygenation with the Haldane effect to allow the CO2 to off-gas through the healthy alveoli.
References
Aubier, M., Murciano, D., Milic-Emili, J., Touaty, E., Daghfous, J., Pariente, R., & Derenne, J. P. (1980). Effects of the Administration of O2on Ventilation and Blood Gases in Patients with Chronic Obstructive Pulmonary Disease During Acute Respiratory Failure1–3. American Review of Respiratory Disease, 122(5), 747–754. https://doi.org/10.1164/arrd.1980.122.5.747
Cosgriff, C. (2017, April 12). Oxygen Saturation Target of 88-92% in COPD: Evidence-based Medicine? – Clinical Correlations. Clinicalcorrelations.org. https://www.clinicalcorrelations.org/2017/04/12/oxygen-saturation-target-of-88-92-in-copd-evidence-based-medicine/
Glatt, J. (2016, September 28). Oxygen-Induced Hypercapnia in COPD: What is the Mechanism? – Clinical Correlations. Clinicalcorrelations.org. https://www.clinicalcorrelations.org/2016/09/28/oxygen-induced-hypercapnia-in-copd-what-is-the-mechanism/
Wilson, A., & Lee, H. (2012, October 29). Oxygen-induced hypercapnia in COPD: myths and facts. Critical Care (London, England). https://pubmed.ncbi.nlm.nih.gov/23106947/
