Applying Applied Physiology to COVID: Silent Hypoxia and The Work of Breathing

Enough time has passed and enough clinical experience with the behavior of COVID gained that we can now apply some applied physiology to our understanding of this aweful illness.  I don't have the answers any more than the next person, but I do know that whatever the behavior of COIVD, it can be viewed through the lens of what we do know about applied lung physiology, and some inferences can be made.  This post will be about that physiology and those inferences, using the frameworks in these lectures about applied physiology.

One of the striking early observations about patients presenting with COVID was their apparent lack of distress despite very low oxygen saturations.  This was termed "silent hypoxia" at some point, and I leave it to internet sleuths to trace its origins.  It led to a policy of early intubation of some COVID patients:

“Never in my life have I had to ask a patient to get off the telephone because it was time to put in a breathing tube,” said Dr. Richard Levitan, who recently spent 10 days at Bellevue Hospital Center in Manhattan.

There are two simple explanations for the observed phenomenon of silent hypoxia: first is that hypoxia is not nearly as potent a stimulus of respiration as is hypercarbia, as I took great pains to explain in the Applied Physiology lectures, using the example of shallow water breath hold divers who do not pre-oxygenate and emerge with sats on the order of 50%, the same as climbers on Mt Everest.  (See also this post on the boy in the wheel well, unpressurized, from California to Hawaii.)  I thank Matt Wong (@EM_phile on Twitter) for pointing me to this video which provides a striking illustration of lack of dyspnea with sudden and severe hypoxemia.  This video is compulsory viewing:

Dyspnea is driven far more by ventilation demands and the work of breathing than it is by hypoxia alone.  This is underrecognized.  I wager this stems in part from the fact that in most diseases that cause hypoxia, there is significantly elevated work of breathing because of parenchymal disease/infiltration (elastic loads) and airway secretions (resistive loads), combined with minute ventilation loads from high CO2 production, dead space ventilation (Vd/Vt) and metabolic acidosis.  If COVID does not have all of those loads, patients may not experience substantial subjective dyspnea despite low oxygen.

Are the "Vent Protocols" causing harm in COVID?

Here is a response to Deborah Mayo's excellent blog post posing this question.  I encourage you to first read her post.  Here, I explicate my view of the problems that are raised in that post.  I don't have time for a lot of hot links and stuff, so post your specific comments below.

There is a lot correct here, and @learnfromerror has done a far better job of summarizing it than I could ever explain a normal distribution. But there is a lot missing, because the commentators have not gotten to the crux, and have made slogans for their points that are distracting and misguided if not totallly incorrect.

First, and this is very very important, is that *there are NO protocols for intubation* as the NYC ER doctor suggests. I talk about that on my other blog a lot. ARDS trials enroll patients who are *already intubated* and the criteria for that intubation are absent from the study protocols. It is assumed in an ARDS study that if you are intubated, you were appropriately intubated. Therefore, there is no “problem with the protocols” for ventilators, there is a glaring and longstanding problem with the criteria (or the absence of criteria) for intubating patients. Is it blood gas values, or vital signs, or physical examination signs, or subjective distress or some combination? There is ZERO standardization in this area. COVID has brought this underappreciated problem to the fore.

Why is this just coming out now? Ah, that’s another crux of the problem and a reason that COVID has become a perfect storm for ventilator management. Usually, if you intubate a little old lady with influenza, even if you do it for shaky reasons, she can be extubated (tube removed) in a couple of days or a week with little harm done (or with a level of harm that we take for granted, probably mistakenly). Not so with COVID. The natural history of the disease has 2 important features that make the decision to intubate likely to culminate in a massive therapeutic misadventure: 1.) the duration of the illness is protracted, two to perhaps as long as four weeks; and 2.) the level of sedation needed to counteract the massive air hunger these patients have, for the duration they need it, is through the roof.  This problem is compounded by the mandate to use small tidal volumes which are poorly tolerated in the face of massive air hunger. So, 2 weeks after intubation, they are veritable zombies, cannot be weaned from sedatives (a prerequisite from being weaned from the ventilator), and are stuck on the vent, assuming that before this stage other complications have not set in and/or death ensued.

Another facet of the perfect storm, which I think is also the Rosetta Stone, and a key to untangling this giant mess we find ourselves in, is that this normal lung compliance that people are talking about is *the reason why* there is this so-called “silent hypoxemia” of the type mentioned by the ER doc in Mayo’s post. Failure to recognize this connection betrays a common misunderstanding of respiratory physiology (my attempt to disabuse people of these errors can be found here: https://pulmccm.org/ards-review/great-lecture-applied-respiratory-physiology/). Dyspnea is not driven by hypoxemia as much as it is by hypercarbia, which can be compensated for by hyperventilation which these patients are doing! To a person who has a firm grasp on applied respiratory physiology, this is no surprise – the patients have compliant lungs, so they don’t have workload imbalance and can sustain ventilation in the face of significant hypoxemia (which is a MINOR driver of dyspnea) very well. In sum, I am not surprised by these clinical presentations, nor am I surprised that this quagmire has allowed problems with the understanding of applied respiratory physiology to surface.

This disease is very difficult for these and many other reasons. When the choice is let a hypoxemic person who is defending her CO2 - like the little old lady the ER doc talks about - ride it out (which she can probably do for a very long time, see my tweets about sustaining very high Ve indefinitely [50% of the 15-second MVV]), versus intubating her for a marginal gain in gas exchange accompanied by a massive cost in sedation and paralysis, the choice is clear, let them ride it out, don't incur that cost.

The problem is not with the “vent protocols” the problem lies in a widespread lack of understanding of applied respiratory physiology which leads to questionable calls regarding intubation which are usually, in non-pandemic times, lost in the signal and noise of the fray. Not so with COVID – premature or unnecessary intubations precipitate a cascade of status iatrogenicus.