COPD and the Myth of the “Hypoxic Drive Mediated Sudden Hyperoxic Death Oh My!”
Dear Dr. Busko
My question is regarding the use of high flow 02 in a patient with a Hx of COPD (Bronchitis or Emphysema) whom is acutely in respiratory distress. How often will this subsequently induce Hypoxic Drive in an emergency setting (if at all). We are taught never to with hold high-flow O2 in a patient that is distressed (cyanotic, pallor, accessory muscle use, poor O2 saturation), only to meet the occasional emerg nurse that pulls the standard face mask off the patient with the all-needed lecture to the paramedic.
Thanks!
Steve,
Paramedic, BC, Canada
Steve,
Thanks for an excellent question. We’ve all been there. 62 year old male, COPD history, respiratory distress with wheezing, sats in the high 80’s, we give him an albuterol neb (powered by oxygen at 8 LPM to really make it bubble) and the patient suddenly goes apneic and dies and it’s all our fault….
Except that doesn’t happen. The theory of the hypoxic drive mediated sudden hyperoxic death is a work of intellectual beauty, eloquence, and unfortunately, not actually an accurate description of anything that happens in the real world.
To give this whole discussion context, I’m going to make a simple statement that underlies all airway management: “Hypoxia kills, hypercarbia happens.” In other words, if your carbon dioxide levels are high (to certain limits), the resulting increased acid levels of the blood (respiratory acidosis) are not overly harmful and the body can compensate for them. On the other hand, if your oxygen levels are too low, you die. Each organ has a different minimum oxygen level it tolerates, but the heart and brain are highly sensitive to low oxygen levels.
So again: Hypoxia kills. Hypercarbia happens. Sick COPD patients die first and foremost of hypoxia, and while, as we will discuss, sudden increases in hypercarbia may contribute to sudden cardiac arrest, they are not the result of oxygen induced apnea. Instead, by believing that the only way these people will die is if they go apneic from the oxygen, we completely miss that the respiratory failure is what kills them and forget that assisted mechanical ventilation and not just oxygen is the treatment of choice for respiratory failure.
Now, the short answer to the question is that the fact that people act based on the myth of the “hypoxic drive oxygen induced apnea” is actually far more lethal than the oxygen. Patients with COPD (or chronic asthma) have a whole body oxygen deficit at baseline and are essentially in compensated respiratory distress. Now worsen their pulmonary function and they go into decompensating and ultimately decompensated respiratory failure and die of hypoxia. We have 3 (common) ways in EMS to support patients in decompensating respiratory failure: face mask ventilation, CPAP / BiPAP, and invasive (intubation, LMA ®, King ®, Cobra PLA ®, etc, etc.) mechanical ventilation. If someone didn’t have COPD, we wouldn’t withhold oxygen. Why do we insist on withholding oxygen in ill patients who at baseline are hypoxic? The power and fear of the myth are the dangers to these patients, not appropriate oxygenation. If you were looking for an answer just for yourself, you can stop reading now. However, if you have to defend this position, then please keep reading for a little support.
Let’s start with a discussion of why we breathe. The short answer is that carbon dioxide, oxygen, and muscle stretch receptors in our chest drive respiration.
About 85% of our drive to breathe comes from carbon dioxide receptors that “measure” (through a number of mechanisms) carbon dioxide levels in the blood. The receptors are in the brainstem and measures blood acid level (which is related to the carbon dioxide level). After 24 hours of elevated carbon dioxide levels (“chronic ventilatory failure”), the body’s compensation system (using something called bicarbonate) changes the pH (a measure of acid level) at the carbon dioxide receptor and (insert mysterious action at which we can only guess at the wonders of the human body here) either decreases carbon dioxide sensitivity or, like a thermostat, increases the CO2 level necessary to drive respiration. Either way, the CO2 receptors in these chronically hypercarbic patients still appear to have some function in the real world (which is where we take care of our patients).
About 10 - 15% of our drive to breathe comes from oxygen receptors located in the carotid arteries and the aortic arch. Normally, your oxygen pressure (a way of measuring oxygen levels) in your arteries (PaO2) is 80-100 mm Hg (millimeters mercury, a common pressure measurement). For most people, when the PaO2 drops to 60 mm Hg or below, there is a drive to breathe. However, there are a number of factors including CO2 levels, acid levels, and insert even more mysterious actions at which we can only guess at the wonders of the human body here, which can change this level. In other words, in people with COPD, this response to breathe may be triggered at higher oxygen levels (PaO2 above 60 mm Hg). At a PaO2 above 170 mmHg, this trigger theoretically turns off since you are no longer hypoxic (however, read the Aubier article for a great study which shows just how smart our bodies really are).
Finally, there are a variety of conscious and unconscious triggers that also drive you to breathe. These include stretch receptors in your chest wall, a concern that you’re going to die if you don’t keep breathing, and people telling you to breathe.
So, what happens when a COPD patient becomes ill, either from a COPD exacerbation or from other causes? Regardless of cause, they almost always become even more systemically hypoxic (low oxygen levels throughout the body). Every organ is under stress, particularly the heart and the brain. They are initially in compensated respiratory failure; that is, they are skating on the edge but no longer truly capable of adequately oxygenating. Their PaO2 drops and they breathe harder to try to oxygenate; they also blow off excess carbon dioxide and change blood flow in their lungs to maximize perfusion (blood flow) with oxygenation (open, working alveoli). When we apply oxygen, a number of really complex events occur that actually increase the PaCO2 (level of carbon dioxide in arterial blood). For an excellent description of this, see http://home.pacbell.net/whitnack/The_Death_of_the_Hypoxic_Drive_Theory.htm. However, it is important to understand that the rise in PaCO2 is mostly from normal physiologic response to restoration of alveolar oxygen levels, increased deadspace, changes in pulmonary capillary blood flow, and decreased CO2 elimination; only a small amount in a minority of individuals can be blamed on decreased minute volume. This sudden increase in CO2 can be harmful (possibly even fatal) but remember, we have ways of helping people get rid of CO2; those methods are known as assisted or mechanical ventilation. But before we starting blaming ourselves for not expecting this sudden non-apneic increase in CO2, remember that these patients started out in respiratory failure and while high flow oxygen may improve their oxygenation status, respiratory failure is much bigger than just oxygen levels and that little bit of oxygen you’ve added doesn’t fix the respiratory failure.
At this point, we have a patient who probably feels a little better because his heart and brain are finally getting oxygen. But he’s still fatigued, the underlying pathology still exits, he’s still in decompensating or decompensated respiratory failure and his CO2 levels are increasing because of blood and gas redistribution in the lungs (but not from decreased minute ventilation or apnea). The patient might stop breathing because of the fatigue, the bronchoconstriction, etc, (but not from normal oxygen levels). Therefore, now that we’ve oxygenated the patient, we need to intervene in the respiratory failure. Non-invasive ventilation is a key first step to keep the patient from fulfilling the mythical legacy of hyperoxic apneic death. It’s all about cause and effect. Your oxygen won’t be the cause of the patient’s apnea and death. Your failure to intervene for the respiratory failure and rapidly increasing CO2 levels just might be.
Clinical bottom line? Patients in respiratory distress, whether CO2 retainers (COPD patients) or not, need oxygen. Patients in compensated or decompensated respiratory failure, whether CO2 retainers (COPD patients) or not, need ventilatory support. Patients with COPD who are otherwise healthy will, with very few exceptions, tolerate supplemental oxygen without any effects and the rare group who does have an effect don’t go apneic but rather breathe a bit more shallow than before and become a bit sleepier. If your COPD patient does go apneic when you apply oxygen and you didn’t expect it, then you probably failed to recognize just how sick they really were.
Be safe, play well with others and remember: we help people.
References:
Aubier M. 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.
Nice study that demonstrated that even when you blew through the upper limits of the hypoxic drive (PaO2 of 225 mm Hg), the respiratory muscles did just fine and while ther was an intial decrease in minute ventilation by 15 minutes there was essentially no difference.
Caruana-Montaldo B, Gleeson K, Zwillich GW. The control of breathing in clinical practice. Chest 2000;117:205-225.
A good review of how and why we breathe normally and in various disease states.
Crossley DJ, McGuire GP, Barrow PM, Houston PL. Influence of inspired oxygen concentration on deadspace, respiratory drive, and PaCO2 in intubated patients with chronic obstructive pulmonary disease. Crit Care Med 1997; 25(9): 1522-1526.
A great study using intubated but spontaneously breathing COPD patients that demonstrated both that apnea did not occur and provided further confirmation of the mechanism of increased CO2 which has nothing to do with apnea or descreaed minute ventilation.
Hoyt JW. Debunking myths of chronic obstructive pulmonary disease. Crit Care Med 1997;25:1450-1451.
A good summary discussion of the Crossley manuscript.
Nunn JF: The pulmonary circulation. In: Nunn’s Applied Respiratory Physiology. Fourth Edition. Nunn JF (Ed). Oxford, UK, Butterworth-Heinemann, 1993, p 145.
A nice summary of the way pulmonary circulation actually works.
http://www.rtmagazine.com/issues/articles/2000-02_17.asp (accessed 2/27/9).
A nice summary of the issue plus a really interesting discussion of the subset of patients who do decrease (minimally) their respiratory rate and level of consciousness at an FiO2 of .3 (academically interesting).
http://home.pacbell.net/whitnack/The_Death_of_the_Hypoxic_Drive_Theory.htm (Accessed 2/27/9)
Another interesting summary of the issue from the perspective of a respiratory therapist.
Tags: Clinical
July 2nd, 2009 at 8:30 pm
Dr Busko,
As a respiratory therapist with 14 years clinical experience, I read your essay with great interest and found myself laughing more than once at the clever ways you successfully made your point time and again. Surprisingly, I think I have something worthwhile to add which could help ease the friction while helping the hypoxic patient at the same time: Explain to the nurse that it’s not the FiO2 that even matters; rather, it would be the PaO2. Many times I have been in the exact same situation as Steve, the paramedic in B.C. Canada has: placing a decompensating COPD patient on a non-rebreather or other high flow oxygen device, only to be challenged by a well-intentioned, albeit misinformed, nurse. Fact is, even IF the patient was being stimulated to breathe by hypoxia, chemoreceptors have no idea what FiO2 is being delivered. Give enough O2 to reach the target SpO2, and then begin backing down on the FiO2. This way, the patient is happy (oxygen needs are being more adequately met) and the nurse is happy (the patient is no longer receiving a ‘lethal’ dose of O2).
Stefan,
Great point. I also think it’s worth considering that oxygen is like any other drug we use in the prehospital setting. There are indications for its use and there are lots of different doses that are used for different reasons. In the patient without respiratory distress or hypoxia, there is no indication for high FiO2 oxygen so don’t give it. Conversely, I like to think about COPD patients in moderate to severe respiratory distress / insufficiency as being similar to a patient I’m about to paralyze and intubate. Both of them have impending respiratory failure and I’d much rather have them stop breathing with their entire lung volume full of oxygen (which wil continue to drive oxygen in to the blood stream for quite some time based on the concentration gradient) than to have them stop breathing with a lung full of room air. Its the underlying principle of right drug, right time, right indication, and use your judgment. Thanks for the great comment.
JMB