Why COVID-19 Silent Hypoxemia Is Baffling to Physicians

Abstract

Patients with coronavirus disease (COVID-19) are described as exhibiting oxygen levels incompatible with life without dyspnea. The pairing-dubbed happy hypoxia but more precisely termed silent hypoxemia-is especially bewildering to physicians and is considered as defying basic biology. This combination has attracted extensive coverage in media but has not been discussed in medical journals. It is possible that coronavirus has an idiosyncratic action on receptors involved in chemosensitivity to oxygen, but well-established pathophysiological mechanisms can account for most, if not all, cases of silent hypoxemia. These mechanisms include the way dyspnea and the respiratory centers respond to low levels of oxygen, the way the prevailing carbon dioxide tension (Pa_CO2) blunts the brain's response to hypoxia, effects of disease and age on control of breathing, inaccuracy of pulse oximetry at low oxygen saturations, and temperature-induced shifts in the oxygen dissociation curve. Without knowledge of these mechanisms, physicians caring for patients with hypoxemia free of dyspnea are operating in the dark, placing vulnerable patients with COVID-19 at considerable risk. In conclusion, features of COVID-19 that physicians find baffling become less strange when viewed in light of long-established principles of respiratory physiology; an understanding of these mechanisms will enhance patient care if the much-anticipated second wave emerges.

Keywords: COVID-19; control of breathing; dyspnea; hypoxemia; pulse oximetry.

Figure 1.

The ventilatory response to progressive isocapnic hypoxia in a healthy subject. Little change in $\dot{\text{V}}$e is noted until alveolar oxygen tension (Pa_O2) falls to 60 mm Hg, and thereafter the response is very steep. Each data point represents the mean value for Pa_O2 and $\dot{\text{V}}$e for three successive breaths. Adapted by permission from Reference . STPD = standard temperature and pressure dry.

Figure 2.

Scatterplot of the relationship between estimated oxygen saturation from pulse oximetry (Sp_O2) and Sa_O2 from blood gas analysis in healthy subjects exposed to profound hypoxemia in a hypobaric chamber (Pa_O2, 21.6–27.8 mm Hg). Each subject is represented by a different symbol. The dashed line is the line of identity, and the solid line is the regression line. Adapted by permission from Reference .

Figure 3.

Relationship between arterial oxygen tension (Pa_O2) and percentage saturation of hemoglobin with oxygen (Sa_O2) at temperature 37°C (continuous line) and 40°C (dashed line), with a constant pH 7.40 and Pco₂ of 40 mm Hg (generated with digital subroutine of Kelman [31]). At a Pa_O2 of 60 mm Hg, Sa_O2 is 91.1% at 37°C and decreases to 85.8% at 40°C. At a Pa_O2 of 40 mm Hg, Sa_O2 is 74.1% at 37°C and decreases to 64.2% at 40°C.