'Silent' Presentation of Hypoxemia and Cardiorespiratory Compensation in COVID-19

Philip E. Bickler, M.D., Ph.D.; John R. Feiner, M.D.; Michael S. Lipnick, M.D.; William McKleroy, M.D.


Anesthesiology. 2021;134(2):262-269. 

In This Article

Hypoxemia and Breathlessness: Variability in Humans

Hypoxemia can present in a highly variable manner, with some patients dyspneic with labored breathing and panicked, and others calm, despite oxygen saturations in the 70% range or below. The processes that produce intrapulmonary shunt do not necessarily decrease lung compliance or produce dyspnea. For many hypoxemic patients, oxygen saturations less than 70% can be tolerated for some time with only moderate and transient alterations in mentation or other signs and symptoms.[30] Dyspnea may only occur with exertion, although decreased exercise tolerance is a nonspecific symptom in acute illness. Decreased lung compliance contributes to dyspnea, but as previously discussed, early COVID-19 pneumonia may present with shunt and normal lung compliance.[26] In our experience with profound experimental hypoxemia to oxygen saturations as low as 50% in healthy humans, subjective symptoms of hypoxia may go unnoticed in some individuals, with no appearance of discomfort and minimal hyperpnea.[30] Given this variability in individual responses to hypoxemia, it is not surprising that some COVID-19 patients have been described as asymptomatic "silent" or "happy hypoxia."[3] Tobin et al. recently reviewed some of the factors accounting for reduced dyspnea in COVID-19 patients.[4]

One of the key reasons that COVID-19 patients may not present with marked dyspnea is that the main gas exchange abnormality involves shunt. Intrapulmonary shunt and V/Q mismatch has minimal effects on carbon dioxide excretion compared to oxygen uptake.[31] Thus, even mild hyperventilation is capable of significantly reducing arterial carbon dioxide and decreasing respiratory drive mediated by both the carotid and central chemoreceptors[32] (Figure 1). Carbon dioxide retention is more strongly correlated with breathlessness in lung disease than is hypoxemia.[33] In patients who can increase breathing and lower arterial partial pressure of carbon dioxide, breathlessness will be limited.[34] This is similar to what is experienced by most people on ascent to high altitude: arterial hypoxemia is present but subjective breathlessness is limited by subtle, often unnoticed increases in the respiratory rate that helps the lungs "blow off" enough arterial carbon dioxide to mitigate the sensation of dyspnea.[35]

Breathing responses to hypoxia are experimentally quantified by the hypoxic ventilatory response,[36] a response largely mediated by the carotid chemoreceptors. The hypoxic ventilatory response in humans is highly variable: some will greatly increase the respiratory rate and tidal volume when exposed to hypoxia while others will have little response[37](Figure 1B). Breathing responses to both hypoxia and hypercapnia (the hypercapnic ventilatory response) are also significantly reduced in older adults. Multiple studies have found 40 to 50% reductions in the hypoxic and hypercapnic ventilatory responses between young (22 to 30 yr) and older (64 to 73 yr) subjects.[38,39] Hypoxic ventilatory response varies with ethnicity[37] and is blunted by chronic hypoxia, as in chronic obstructive pulmonary disorder and sleep apnea, as well as in obesity,[40,41] placing these patients at higher risk of more profound hypoxemia at time of clinical presentation.