Hypoxic Drive Theory, A Myth–The Why and How

So I was attending one of the SJA (St. John Ambulance) meetings and that day we were going over airways, related diseases, treatment, OPAs, NPAs, oxygen, BVMs, NRBs etc.  We were discussing COPD when the discussion of hypoxic drive came up.  Now in all the books I’ve read, including the Emergency Medical Responder book by Limmer et al., they always say, be careful of hypoxic drive, but never deny a COPD patient of oxygen.  Here’s what Limmer et al., wrote under the COPD section on p.224:

“Both emphysema and chronic bronchitis patients may develop a hypoxic drive to breathe.  Healthy people get their drive to breathe from the amount of carbon dioxide in the blood.  Patients who have emphysema or chronic bronchitis build up consistently high levels of carbon dioxide.  Because of this, the body looks to the levels of oxygen, rather than carbon dioxide, to determine the need to breathe.  If oxygen levels are low, they breathe faster to get more oxygen.

Giving oxygen to a patient with hypoxic drive can be a problem.  After oxygen is administered, its level in the blood increases.  In the patient with a true hypoxic drive, increased levels of oxygen may signal the body to slow down or even stop breathing.  However, this is rarely encountered in the field.”

So when I was asked to explain the hypoxic drive theory to the class, that was exactly what I said.  If you give a COPD pt high concentrations of O2 , they will stop breathing and could possibly go into respiratory failure.  To my surprise, our Superintendent stepped in to clarify that the Hypoxic Drive Theory is only a myth and that there are no strong evidence suggesting that it happens.  That was the first time I’ve ever heard of the Hypoxic Drive Theory as a myth.  I was curious as to why it was a myth and why the textbooks I’ve read did not clarify this topic. When I thought about it a bit more, I did see the irony in the theory:  The pt is having trouble breathing and can’t get enough O2 and may die, so we need to give him O2 so he can live, but then…wait….he has COPD so we can’t give him the amount of O2 he needs…..so now what?  We give him O2, he dies, we don’t give him O2, he dies.  Could it be that respiratory failure is from the build up of CO2 in the lungs and not from having high O2 saturation?  But what about the body’s buffering system?  COPD pts still have functioning chemoreceptors that detect low pH levels, which would release bicarbonate and technically alleviate the acid build-up.  What is really going in the body?  So, I decided to do some research.

Through researching, I found quite a few good articles discussing this topic.  However, the reading material was definitely not written in the lay tongue (thank goodness I took all those HKIN Exercise Physiology courses) and the articles used a lot of respiratory physiology terms such as VE, FiO2, Pb, V/Q, PaCO2, PaO2 etc.  I will try to keep my writing to the simplest possible (as lay as possible), but this topic does delve a lot into physiology, so I wrote up a glossary:  here (you can also click on the words which will lead you to the glossary).

Note:  There is still a lot of controversy about this topic.  What I have written here is solely based on my research findings.

Hypoxic Drive vs Hypoxic Drive Theory

So first thing’s first.  It is important to understand that Hypoxic Drive does exist, it is not a myth, but the Hypoxic Drive Theory is a myth.  So let me differentiate the two:

Hypoxic Drive–This is when a person’s body relies on low levels of O2 to signal them to breathe faster.  People without COPD normally relies on high levels of CO2 to signal them to increase their breathing rate.

Hypoxic Drive Theory–When you give a person with COPD high concentrations of O2, say 100% O2, it will cause their hypoxic drive (their need to breathe) to shut off and they may stop breathing, go into respiratory failure, and die because of too much oxygen.

So the Hypoxic Drive Theory is wrong because literature has shown that patients do not go into respiratory failure and die because of high O2 saturation levels.  Now it is important to know that there are consequences to giving O2 to a COPD pt.  According to Dr. John Hoyt in his article Debunking Myths of Chronic Obstructive Lung Disease:

“It is true that administration of oxygen to a patient with an exacerbated chronic obstructive lung disease and acute respiratory failure may lead to an increased CO2.  It is true that the hypercarbia may become severe and be associated with cardiorespiratory arrest.  The problem is with interpreting the cause of the events…”

So what does that mean?  It means that O2 is not the most important underlying mechanism leading to the build up of CO2 and causing death.  So what is?  Before we can get to that, we have to understand the hypoxic drive and what physiological responses it causes in COPD patients.

Our Need to Breathe

According to John Hoyt, CO2 receptors are responsible for 85% of our drive to breath, while 10-15% of our drive to breath come from our O2 receptors (hypoxic drive).  Normal PaO2 is 80-100mmHg.  If our PaO2 drops to 60mmHg or lower, it triggers hypoxic drive and increases our breathing rate.  Conversely, if our PaO2 is greater than 170mmHg it tells our body to stop because we have enough O2 in our blood.  In other words, the lower the PaO2, the greater the hypoxic drive.  COPD patients are already breathing at their maximum limit due to their inability to exhale CO2 resulting in CO2 getting trapped in their lungs.  When you give a COPD patient O2, there are several ways in which it can increase CO2 according to Jeff Whitnack’s The Death of Hypoxic Drive Theory:

1.  Haldane Effect:  Describes the property of Hbg.  The idea to this is that if Hbg is carrying a lot of O2 (oxygenated blood) then it has a lower capacity to carry CO2.  It works in reverse too:  if Hbg is carrying very few O2 (deoxygenated blood) then it can take on more CO2.

Okay, so now that we understand Haldane Effect, how does it affect our COPD pt?  Well lets say we have a COPD pt who’s having a tough time breathing, and we hook him up to a NRB at 15L/min.  He’s already got a very high level of CO2 in his blood because of his COPD, now we give him lots of oxygen, which means Hbg is now carrying lots of O2, so it has a lower capacity to carry CO2.  CO2 can be transported in three ways:  1.  Dissolved in plasma (7%), 2. Bonding to Hbg (23%), 3. Via HCO3- in blood (70%); so it causes an increase in PaCO2 in the pt.  Normally we “blow off” CO2, but the COPD pt can’t, so all the CO2 gets trapped and increases.

2.  Hypoxic Pulmonary Vasoconstriction (HPV):  This occurs when the alveoli in the lungs are poorly ventilated and causes the pulmonary arteries to constrict in order to divert more blood to the oxygen starved alveoli to better ventilate it.  However, if we give 100% O2 to the pt, it fools our body, and this constriction does not happen, and CO2 will continue to build and be trapped in the alveoli.  This causes a V/Q mismatch and increase physiological dead space in some patients (New, 2006).

The Most Important Mechanism
So we now know that Haldane Effect and HPV, which leads to V/Q mismatch and increase in physiological dead space, plays a role in increasing CO2 within a COPD pt.  But how big of a role does it play?  Well, according to Irven H Young:

“…worsening ventilation-perfusion mismatching and an accompanying increase in dead space ventilation contribute about 50% of the increase in carbon dioxide levels.”

So now you’re probably thinking.  So why is this important?  Doesn’t this still mean that giving a patient high levels of oxygen can lead them into retaining more CO2 from the Haldane Effect, HPV, V/Q mistmatch and increase in deadspace?  Well understanding these effects are important because it shifts our focus of the possible exacerbation of respiratory failure in COPD patients from giving oxygen to CO2 being trapped.  We all know that if we don’t get O2, we become hypoxic and we die.  So how does it make any sense that our COPD patient who needs oxygen and we deny him of sufficient oxygen?  It doesn’t.  Sure a build up of CO2 and a continued increase of that build up can cause respiratory arrest.  However, hypercapnia develops at a slower rate than hypoxaemia (New.  2006).  As Dr. Busko wonderfully summarizes,

“Hypoxia kills, hypercapnia happens”.

So what does this all mean?  It means we should give COPD pts high concentrations of O2 because they need it, but we should do something about the CO2 build up.  We need to help them blow off the CO2.  We can do this by mechanical ventilation (Busko).

Okay, so now you’re saying that’s a great theory and it makes sense.  But what are the evidences that back up giving COPD pts high concentrations of O2 without them falling dead in my hands?  Well, according to Aubier, et al., and Gomersall, et al.’s studies, both noticed that giving high concentrations of oxygen to COPD pts had no significant adverse effects.  Aubier et al.’s, study noted that when COPD pts were given 100% O2 during acute respiratory failure, there was an initial decrease in respiratory tidal volume and frequency (hypoxic drive theory), but after 15min, minute ventilation rose to a level close to the control group’s value.  In other words, health care providers should not be afraid to administor high concentrations of O2 to COPD patients.

The Golden Nugget

The Hypoxic Drive Theory creates a tunnel vision focusing on how bad oxygen is, what needs to change is to shift the focus from oxygen to helping COPD patients get rid of CO2.  In that sense, the Hypoxic Drive Theory is truly a myth, and a hazardous myth, since it prevents COPD pts from getting the proper care they need.

References

Aubier M, et al. Effects of the administration of O2 on ventilation and blood gases in patients with chronic obstructive pulmonary disease during acute respiratory failure. Am Rev Respir Dis 1980;122:747-754.

Busko.  http://www.learnmoresavelives.com/blog/copd-and-myth-hypoxic-drive-mediated-sudden-hyperoxic-death-oh-my (Accessed 11/05/09)

Gomersall, Charles D., et al.  Oxygen Therapy for hypercapnic patients with chronic obstructive pulmonary disease and acute respiratory failure:  A randomized, controlled pilot study. Crit Care Med 2002;30(1):113-116

Hoyt JW. Debunking myths of chronic obstructive pulmonary disease. Crit Care Med 1997;25:1450-1451.

Irving, H Young.  Revisiting oxygen therapy in patients with exacerbation of chronic obstructive pulmonary disease. MJA 2007;186(5):239

Limmer et al.  (2006).  Emergency Medical Responder A Skills Approach.  New Jersey: Prentice Hall.

Robinson TD, et al.  The role of hypoventilation and ventilation-perfusion redistribution in oxygen-induced hypercapnia during acute exacerbations of chronic obstructive pulmonary disease. Am J Resp Crit Care Med. 2000 May;161(5):1524-9

New, A.  Oxygen:  kill or cure?  Prehospital hyperoxia in the COPD patient. Emerg Med J 2006; 23: 144-146.

Sassoon CS, et al.  Hyperoxic-induced hypercapnia in stable chronic obstructive pulmonary disease. Am Rev Respir Dis 1987 Apr;135(4):907-11.

Whitnack, Jeff.  http://home.pacbell.net/whitnack/The_Death_of_the_Hypoxic_Drive_Theory.htm (Accessed 11/05/09)

 

Glossary

pt = patient

O2 = oxygen

CO2 = Carbon Dioxide

COPD = Chronic Obstructive Pulmonary Disease

Hypoxic = Insufficient oxygen perfusion (reaching the body tissues)

Hypercarbia = Excess carbon dioxide in blood

Hypoaxemia = Below normal levels of oxygen in blood

PaO2 = Partial pressure of oxygen in arterial blood

PaCO2 = Partial pressure of carbon dioxide in arterial blood

Hbg = Hemoglobin

NRB/NRM = Non-rebreather mask

Alveoli = Small air sacs found in our lungs where oxygen and carbon dioxide exchange occurs

Ventilate = The gas exchange of oxygen and carbon dioxide

Perfusion = The process of delivery nutrients (oxygen, glucose etc. ) via arterial blood to a capillary bed in body tissue

V/Q mismatch = Ventilation-perfusion mismatch (the amount of ventilation is not evenly matched with the amount of perfusion)

Physiological dead space = Air that is inhaled into the body but does not participate in gas exchange

Mechanical ventilation = Mechanical equipment used to assist or to replace spontaneous breathing

Minute ventilation = The total volume of gas in liters exhaled from the lungs per minute