Pulmonary vascular dilation may cause hypoxemia in COVID-19-related pneumonia

Pulmonary vascular dilation appears to play a role in hypoxemia in patients with COVID-19-related pneumonia, researchers reported in a new study published in the American Journal of Respiratory and Critical Care Medicine.

Researchers conducted a cross-sectional pilot study of contrast-enhanced transcranial doppler (Lucid Robotic System, Nova Signal Corp.) of the bilateral middle cerebral arteries after injection of agitated saline in adults with severe COVID-19 pneumonia who were on mechanical ventilation. The study included 18 adults (mean age, 59 years; 61% men; mean PaO2:FiO₂ ratio, 127 mm Hg) in two COVID-19 ICUs who were not receiving extracorporeal membrane oxygenation support or continuous renal replacement therapy.

The aim was to determine whether mechanisms of hypoxemia in patients with severe COVID-19 pneumonia are different from mechanisms in patients with classical acute respiratory distress syndrome.

Patients were injected with agitated saline via a peripheral IV in the upper extremity or a central line in the internal jugular vein. Then, the researchers used the system software to count the number of microbubbles over 20 seconds, which was then confirmed manually.

Lung compliance was low in the measured 16 patients (median, 22 mL/cmH₂O). No patient had a history of chronic liver disease or preexisting intracardiac shunt.

According to the results, contrast-enhanced transcranial doppler detected a median of eight microbubbles. Fifteen patients (83%) had detectable microbubbles. The researchers found an inverse correlation with PaO2:FiO2 ratio and number of microbubbles (P = .02), and also an inverse correlation with number of microbubbles and lung compliance (P = .01).

“This study implicates abnormally dilated blood vessels of the lung as a major cause of low oxygen levels in COVID-19 respiratory failure,” Hooman Poor, MD, assistant professor of medicine in the division of pulmonary, critical care and sleep medicine at the Icahn School of Medicine at Mount Sinai and director of pulmonary vascular disease at Mount Sinai-National Jewish Health Respiratory Institute, told Healio.

“Strangely, many patients with COVID-19 pneumonia have very low oxygen levels, but do not appear to be in respiratory distress; this phenomenon has recently been dubbed as ‘happy hypoxia.’ Additionally, many patients with COVID-19 respiratory failure on mechanical ventilation have very low oxygen levels but have only minimally affected compliance. This study demonstrates that abnormal vasodilation of the blood vessels of the lungs is playing a role in the low oxygen levels and helps explain the disconnect between very low oxygen levels and helps explain the disconnect between very low oxygen levels and relatively preserved lung compliance,” Poor said.

While further investigation is needed, Poor told Healio that there are multiple implications of the current study findings. One, he said, is that therapies that target the blood vessels of the lungs will need to be studied, in particular those that constrict the blood vessels of the lungs. Further, if the current study results are confirmed, Poor said the presence of the microbubbles detected by contrast-enhanced transcranial doppler may become a marker of disease severity and possibly serve as a surrogate endpoint in clinical trials.

“Additionally, this finding may have implications for optimal timing of intubation and ventilator management, in that strategies used for classical ARDS may need to be tweaked,” Poor said.

Research is ongoing to assess the presence and severity of the “bubble transit” in patients with less-severe disease and also to track the degree of bubble transit in patients when they improve or worsen clinically to determine whether it is a marker of disease severity, Poor said.

For more information:

Hooman Poor, MD, can be reached at Hooman.poor@mountsinai.org.