A recent article in the American
Journal of Respiratory and Critical Care Medicine about hypoxemia
and covid-19 concludes with this:
In conclusion, COVID-19 has engendered
many surprises, but features that baffle physicians are less strange
when contemplated through the lens of long-established principles of
respiratory physiology.
Read this paper when you're well rested
and well fed and you will find it a great exercise in the physiology
of hypoxemia. It's much more about that, and the misconceptions
derived from our current obsession with pulse oximetry, than it is
about covid.
First let's list what I think are some
of the main ideas in the paper.
There was widespread
over-reliance and misunderstanding of pulse oximetry.
There
is not a simple correlation between dyspnea and hypoxemia.
The threat of hypoxemia is poorly
understood by clinicians.
The seeming paradox of
asymptomatic hypoxemia is not unique to covid-19 but is explained by
well established principles of respiratory physiology.
Dyspnea is mediated by hypercapnia,
afferent signals produced by inflammatory stimuli, mechanical
properties of the lungs and, least of all, hypoxemia. As will
be brought out in the physiology below, multiple conditions
seem to have a permissive effect on the dyspnea produced by
hypoxemia.
Hypercapnia is a very important cause
of dyspnea. It has a permissive effect on hypoxemia
as a cause of dyspnea. Hypercapnia causes a drop in pH in the blood
perfusing the CNS respiratory control center. An acute
increase in pCO2 of 10 mm Hg quickly causes profound dyspnea. The
situation is different for hypoxemia. As pO2 falls there
appears to be a threshold of 60 mm Hg below which stimulation
of ventilation and dyspnea occur. (The so called hypoxic drive). In
terms of mechanism, hypoxemia stimulates the carotid bodies which
send messages to the respiratory control center. From there impulses
are relayed to the cortex cruising the sensation of dyspnea. The
correlation between dyspnea and the ventilatory response to hypoxemia
is poor. This response to hypoxemia is blunted if the pCO2 is 39 or
below. These responses are blunted in individuals with diabetes
and individuals over 65 which constitute a high portion patients
presenting clinically with covid.
Could covid have effects on the brain
that blunt the dyspnea response? A similar question has been asked
regarding the symptom of anosmia. ACE2, the receptor for
covid-19, is expressed both in the carotid bodies and the nasal
mucosa so mucosal effects rather than brain involvement could account
for these manifestations. This is a question yet to be
answered.
The authors imply that our usual
concerns about low pulse oximeter readings are misdirected.
Another quote from the article:
Physicians are fearful of hypoxemia,
and many view saturations between 80% and 85% as life threatening. We
served as volunteers in an experiment probing the effect of hypoxemia
on breathing patterns; our pulse oximeter displayed an SpO2 of
80% for over an hour, and we were not able to sense differences
between an SpO2 of
80% and an SpO2 of
90% (24).
In investigations on control of breathing and oximeter accuracy,
subjects experience an SpO2 of
75% (12),
or briefly 45% (25),
without serious harm. Tourists on drives to the top of Mount Evans
near Denver experience oxygen saturations of 65% for prolonged
periods; many are comfortable, whereas some sense dyspnea (25).
The finding of a low pulse oximetry
reading does not enable a complete physiological assessment.
Instead it should lead the clinician to ask: what's going on?
Pitfalls in the interpretation of pulse oximetry were cited in the
article. Correlation with blood gas readings deteriorates at lower
levels of saturation. Accuracy of pulse oximetry is less in
critically ill patients than in normal volunteers. The oxyhemoglobin
dissociation curve should factor into any interpretation of pulse
oximetry readings but this is seldom the topic of bedside
discussions. Fever and low pH, common in critically ill patients,
cause a shift of the curve to the right. This leads to lower
saturation readings at a given pO2. It is an adaptive mechanism by
which hemoglobin unloads oxygen more readily. Herein lies another
reason why oxygen saturation correlates poorly with dyspnea: the
carotid bodies respond to changes in pO2 but not to oxygen
saturation.
Further complicating the discussion is
the definition of terms. Though not addressed in the article,
there is the common confusion between hypoxemia and hypoxia. Low pO2
or saturation readings indicate hypoxemia. However, to diagnose
hypoxia, which is a reduction in oxygen delivery to the tissues,
one must apply the oxygen delivery equation. This equation takes into
account hemoglobin bound oxygen, oxygen dissolved in plasma,
hemoglobin concentration and cardiac output. As to the
definition of hypoxemia the authors point out that it has been an
evolving concept. The definition of hypoxemia is not essential, but
rather a matter of usage and convention. For example, in the 1990s it
was often defined as the raw number without regard to the FiO2.
Recently hypoxemia is more often referred to in terms of the oxygen
requirement. Both are important: the former for estimating oxygen
delivery and the latter for making an assessment of ventilation and
gas exchange.
After reading this article I have the
following concluding thoughts:
We over rely on pulse
oximetry. Blood gases are underutilized.
Misunderstanding
of pulse oximetry readings is widespread.
The hypoxemia of
covid-19 is not as unique as popularly believed.
