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.


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)



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

29 Responses to “Hypoxic Drive Theory, A Myth–The Why and How”
  1. Rebecca says:

    Thank you so much for this information. My mom has COPD and her doctor has told her she has CO2 build up. I am worried because she is so lethargic and tired lately and is not thinking to clearly at times. I believe it is due to the high levels of CO2. I have 2 questions:
    1. Does this tend to happen in COPD patients with this condition?
    2. Is there any other alternative then a tracheotomy?
    Any information will be very appreciated.
    Thank you,

    • Coxinha says:

      Hi Rebecca,

      I am glad you found what I’ve researched helpful. However, I am not yet a health care provider so I can’t answer those questions for you. But you can visit your family doctor for those questions. In terms of reading for interest in this topic, you can refer this link to a respiratory therapist. I’ve been reading his blog and he is very knowledgeable in the area of COPD, asthma, etc:

      Take care and stay safe.

  2. Alec says:

    Excellent article and very informative. Am a Paramedic in Australia. Recently attended a patient who had late stage COPD (Pink Puffer) – presented in Severe Respiratory Distress but SATs of 98% on home O2. I had not seen this kind of presentation before (two years on road) and was unsure whether High Flow O2 was appropriate given his Sats. From your article it would seem the Haldane Effect was at work and IPPB was the best approach. Thanks Coxinha. 🙂

  3. B says:

    I had a hypoxic drive on my morning EMR quiz today, and I had read this a few months ago before starting at JI this month. I was glad I did, I got it right thanks to you 🙂

  4. Alec says:

    Thanks so much for summarising so clearly the matter of “Hypoxic Drive” and COPD patients. Nice job Mate.

  5. rute says:

    it very useful and simple
    God bless you

  6. Paramedic says:

    Disagree, new gold standard tasmanian study out suggests to keep patients between 88-92% sp02, 2-4/L per minute nasal prongs or hudson and bronchodilator/anti-cholingergic bronchodil. However, if they’re going into respiratory failure, then supply with high oxygen. What they really need is cpap/bipap at the ED. Also have discussed with a pulmonary specialist at the respiratory unit at my local hospital and he agrees.

    All in all, keep their sp02 at those values unless you can clearly see they’re deteriorating or in respiratory failure.


    Australian paramedic

  7. Kathy says:

    It is really helpful in understanding the main problems COPD pt has. Thanks for your share!

  8. Ambrose says:

    Hi pocketmedic. This really is interesting. do you still have those articles that you had referenced. I am actually a nursing student that is currently doing research on this topic. hope to see your reply soon.

    • PocketMedic says:

      Hi Ambrose,

      Neat that you’re doing research in the topic. I believe most of my sources are accessible online, you can try by following the references at the end of my article. I’m currently working at my station and don’t have my old laptop with me (which I believe has the articles).

      Hope that helps 🙂

  9. Shelley says:

    I am going thru a situation regarding my oxygen level. My pulmo dr wants me on 6 liters when I am moving around etc. I have been passing out lately, not sure why yet, but I went to the hospital last week because of it. The hospital had me on room air mixed with 2 liters of pure oxygen. I didn’t understand this ut whatever they were doing, it was working and keeping my 02 level in the 90s. Today, I called to make an appt with a heart specialist because I also have mild CHF. The nurse called me and when she asked what my oxygen setting was and I told her 6 liters, she was not very happy about it. She said something about a person’s body thinking they have too much oxygen so it shuts down and turns the 02 into CO2. If I turn the oxygen down, my sat drop to 80s.

    • PocketMedic says:

      Hi Shelley,

      What your physician is referring to is the hypoxic drive in regards to your body thinking it has too much oxygen. I don’t know what your situation is and I’m not your doctor, so this is just some of my personal thoughts and by no means should it be taken as a medical professional advice. It seems what is most important isn’t what the numbers are but how you’re feeling. If you need a higher flow of oxygen to feel like you’re breathing okay and for you to function okay with no detrimental effects, I don’t see what the problem is. Likewise, if you feel fine with a lower oxygen setting, then there is no obvious reason to increase it. Ideally a person’s saturation level should be above 94%, although it does vary per person and their conditions. All in all, what matters most is how you feel and not get too entrapped with the numbers.

  10. Thanks to my father who told me on the topic of this weblog, this blog is
    in fact remarkable.

  11. K Cox says:

    A paramedic in North Caroplina; I recently had a COPD P with O2 sat in high 90s but presenting with severe respiratory distress. My initial contact with the PT, who was on Bipap and removed the it because she could not breath. Once headed toward the hospital, I initiated CPAP. Within about 5-8 min, PT’s O2 dropped into the high 70s and continued to drop while increasing the PT’s respiratory effort. I removed the CPAP and placed a NRB at 15Lpm. Additionally, I administered albuertol to clear upper airway wheezing. Pt’s effort to breath only increased. By the time I reach the hospital, Pt was going into respiratory arrest. Transport time was about 25 minutes. I am uncertain as to how I could have corrected Pt status. I did not have EtCO2 measuring available. Hum?

    • PocketMedic says:

      Hi K,

      I will get back to you on this one, I do know an RT (Respiratory Therapist) friend who may provide you with a better answer than I can.


    • PocketMedic says:

      Hi K,

      Sorry for the late response back, I have been busy. I have spoke with my RT friend and here is a summary of what she thinks (she has requested her name be kept anonymous).

      From the information given, it seems that your patient is not suffering from Hypoxic Drive and perhaps from some other respiratory issue. The key being that as you give the pt high concentrations of oxygen, the hypoxic drive will cause the pt’s respiratory rate to decrease and the respiratory effort should also decrease. Whereas in your scenario, it seems that your patient’s respiratory effort increased.

      Here’s the response to your question from a Respiratory Therapist:
      “If the incredibly rare hypoxic drive did happen, if O2 was applied to an extreme COPD’er, the patient would have stopped making respiratory efforts all together, becoming unresponsive instead of increasing work of breathing.

      I noticed that the terms CPAP/Bipap were both used. Here’s where I’m a bit confused. In the scenario you described it sounded like the Bipap’s support may not have been high enough, or the patient may have been having problems triggering it – in either case, it could cause increased WOB (Work of Breathing). Or if she was unable to breathe, she could have just been really SOB, requiring nebulizers. Straight CPAP is generally not enough support for someone in severe respiratory distress, often they’ll need Bipap for the extra support.

      If at the point where the patient is on bipap and sats were dropping, that would be the point to either increase the oxygen or the support. If it’s a patient’s home bipap unit, its probably not strong enough to give the patient the support they need in respiratory distress.

      When mentioned as above that the O2 sats started dropping – once the patient on the non rebreather, the patient was not receiving any support to their breathing. When nebs were applied what has to be realized is that nebs are only able to run at 8Lpm, so already you’re giving the patient 7Lpm less of oxygen. A bit problematic if the patient’s sats aren’t great on a 15L NRB.

      In this situation I don’t think the EtCo2 would have been a very reliable tool. We use it to trend. So if the patient was becoming nonresponsive due to hypoxic failure, the patients EtCO2 would be trending upwards as they became drowsier. In this case if the patient has increased work of breathing and is in respiratory distress, the EtCo2 would be trending downwards as the patient’s RR would be elevated.

      If this patient presented intially in the ER with a decent O2 sat (90’s), and had increased work of breathing, if they were wheezy at this point, i would give them a neb of 5mg Ventolin and 0.5 mg Atrovent. If this was a clear cut case of COPD, A couple rounds of Atrovent and Ventolin usually help to clear up . If they are still quite wheezy with minimal/moderate improvement, that’s when the doctor will usually order IV steroids. If there’s increased work of breathing, then we will usually initiate Bipap at a standard level of IPAP 12/ EPAP 8, increasing support until the patient starts to look like they’re comfortable. We’ll usually leave the COPD’er on bipap for several hours before trialling them off, and in some cases we’ll do a baseline ABG when they are admitted initially and then another one after being on the bipap to see if we need to adjust any of our settings. At this point we’ll also do labwork and a CXR to see if anything else is going on (Pneumonia/CHF?) If the patient is still not improving, we’ll start talking about intubating them.

      When this patient arrived at the hospital in respiratory arrest, the patient probably would have been placed immediately on Bipap. If the Bipap seemed to be helping, we’d do bloodgases, maintain bipap for a couple hours and trial off. If in the next hour or two if the patient wasn’t improving then we’d start thinking about intubating them.”

      I found my friend’s response very insightful, hopefully it helped answer some of your questions as well.

  12. keith says:

    Thanks very much for the reply and thank your RT freind too. I got about the same answer from my RT friend. I believe the PT had been in a COPD state for an extended period of time, while failing to contact EMS until the situation became absolutely desparate and life threatening.

    • PocketMedic says:

      You’re welcome Keith 🙂 I’m curious from your initial question. Was the Bipap the patient’s home bipap? Also in Carolina, you carry CPAP on car?

      • Keith Cox says:

        Yes to both questions; PT’s own BiPAP and we have CPAP generators on the trucks.. I had CPAP on the PT for about 10 mins when I noticed O2 sat dropping and resp effort increasing. That is when I removed it and placed the NRB back on. My RT friend stated the person was probably “circling the drain” long before my intervention. Do not know the PT outcome. Thanks again for the blog.

  13. Olsen says:

    Great summation in simple easy to understand terms. What ever the mechanism there are some patients who stop breathing when given too much oxygen. These patients are no very common but do exist. I have been doing slot of reading in the area of oxygen and its clinical use and there are 2 common conclusions that are true for all patients; 1. too much oxygen is bad and 2. too little oxygen is bad. So what is safe? According to the British Guidelines for the emergency use of Oxygen any amount of oxygen to keep oxygen saturations 92 to 98 percent ideally around 94 percent.

  14. tim thannisch says:

    Excellent work and thanks. Most of the nurses here are so ignorant about this and really believe that old myth to the point of being a danger to the patients. It drives me crazy that they refuse to listen and educate themselves. They prefer the easy way out and I truly believe they just hate being proved wrong. I wish that just some of them would read your article and others. To me it just seems obvious and makes so much sense.
    Tim T.

  15. Jun Li Kanashii says:

    Wow super informative and well written. I learned more from this than I did from my textbooks.

  16. firetacmedic says:

    Reblogged this on Life in the Fast Lane and commented:
    An excellent summery of Hypoxic Drive

  17. Hypoxic Drive

    You’re in control of your breathing
    Well that’s not exactly true,
    Granted you can hold your breath
    Allow me to explain this to you.

    When you’re fast asleep in bed
    Your breathing still goes on,
    Your not in control of breathing now
    And your precious life has not gone.

    You’re still in the land of living
    Although you’re asleep in bed,
    The stimulus for you to breathe
    Is all controlled in your head.

    The respiratory centre in brain
    Is governed by C02,
    Higher the level in the blood
    Faster, deeper breathing you’ll do.

    People with chronic illnesses
    Their C02 levels are high,
    If respiratory centre stayed the same?
    Exhausted they’d become and could die.

    So brain has to change calculation
    Oxygen replaces C02,
    So when oxygen levels now rise
    This is what their brain will do.

    Patient is put onto oxygen
    Their oxygen levels will rise,
    Brain now sends a message
    To lungs! It’s no surprise.

    Sorry guys you’re not needed
    I’ve enough oxygen here for me,
    So you can slow down for now
    And that’s what lungs do you see.

    The C02 levels start rising
    Lungs not blowing it away,
    Think! If you’re going to give oxygen?
    A little bit extra? NO WAY!

    1 medical rhyme from my kindle ebook

    First Aid in Rhyme

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