Intrapulmonary Shunt and Alveolar Dead Space in a Cohort of Patients with Acute COVID-19 Pneumonitis and Early Recovery.

BACKGROUND: Pathological evidence suggests that COVID-19 pulmonary infection involves both alveolar damage (causing shunt) and diffuse micro-vascular thrombus formation (causing alveolar dead space). We propose that measuring respiratory gas exchange enables detection and quantification of these abnormalities. We aimed to measure shunt and alveolar deadspace in moderate COVID-19 during acute illness and recovery. METHODS: We studied 30 patients (22 males, age: 49.9±13.5 years) 3-15 days from symptom onset and again during recovery, 55±10 days later (n=17). Arterial blood (breathing ambient air) was collected while exhaled O2 and CO2 concentrations were measured, yielding alveolar-arterial differences for each gas (AaPO2, aAPCO2) from which shunt and alveolar dead space were computed. MEASUREMENTS AND MAIN RESULTS: For acute COVID-19 patients, group mean (range) for AaPO2 was 41.4 (-3.5 to 69.3) mmHg; aAPCO2 was 6.0 (-2.3 to 13.4) mmHg. Both shunt (% cardiac output) at 10.4 (0 to 22.0)%, and alveolar dead space (% tidal volume) at 14.9 (0 to 32.3)% were elevated (normal: <5% and <10%, respectively), but not correlated (p=0.27). At recovery, shunt was 2.4 (0 to 6.1)% and alveolar dead space was 8.5 (0 to 22.4)% (both p<0.05 versus acute); shunt was marginally elevated for 2 patients, however, 5 (30%) had elevated alveolar dead space. CONCLUSIONS: We speculate impaired pulmonary gas exchange in early COVID-19 pneumonitis arises from two concurrent, independent and variable processes (alveolar filling and pulmonary vascular obstruction). For most patients these resolve within weeks, however, high alveolar dead space in ∼30% of recovered patients suggests persistent pulmonary vascular pathology.

Using pulmonary gas exchange to estimate shunt and deadspace in lung disease: theoretical approach and practical basis.

The common pulmonary consequence of SARS-CoV-2 infection is pneumonia, but vascular clot may also contribute to COVID pathogenesis. Imaging and hemodynamic approaches to identifying diffuse pulmonary vascular obstruction (PVO) in COVID (or acute lung injury generally) are problematic particularly when pneumonia is widespread throughout the lung and hemodynamic consequences are buffered by pulmonary vascular recruitment and distention. Although stimulated by COVID-19, we propose a generally applicable bedside gas exchange approach to identifying PVO occurring alone or in combination with pneumonia, addressing both its theoretical and practical aspects. It is based on knowing that poorly (or non) ventilated regions, as occur in pneumonia, affect O2 more than CO2, whereas poorly (or non) perfused regions, as seen in PVO, affect CO2 more than O2. Exhaled O2 and CO2 concentrations at the mouth are measured over several ambient-air breaths, to determine mean alveolar Po2 and Pco2. A single arterial blood sample is taken over several of these breaths for arterial Po2 and Pco2. The resulting alveolar-arterial Po2 and Pco2 differences (AaPo2, aAPco2) are converted to corresponding physiological shunt and deadspace values using the Riley and Cournand 3-compartment model. For example, a 30% shunt (from pneumonia) with no alveolar deadspace produces an AaPO2 of almost 50 torr, but an aAPco2 of only 3 torr. In contrast, a 30% alveolar deadspace (from PVO) without shunt leads to an AaPO2 of only 12 torr, but an aAPco2 of 9 torr. This approach can identify and quantify physiological shunt and deadspace when present singly or in combination.NEW & NOTEWORTHY Identifying pulmonary vascular obstruction in the presence of pneumonia (e.g., in COVID-19) is difficult. We present here conversion of bedside measurements of arterial and alveolar Po2 and Pco2 into values for shunt and deadspace-when both coexist-using Riley and Cournand's 3-compartment gas exchange model. Deadspace values higher than expected from shunt alone indicate high ventilation/perfusion ratio areas likely reflecting (micro)vascular obstruction.

Non-invasive Measurement of Pulmonary Gas Exchange Efficiency: The Oxygen Deficit.

The efficiency of pulmonary gas exchange has long been assessed using the alveolar-arterial difference in PO2, the A-aDO2, a construct developed by Richard Riley ~70years ago. However, this measurement is invasive (requiring an arterial blood sample), time consuming, expensive, uncomfortable for the patients, and as such not ideal for serial measurements. Recent advances in the technology now provide for portable and rapidly responding measurement of the PO2 and PCO2 in expired gas, which combined with the well-established measurement of arterial oxygen saturation via pulse oximetry (SpO2) make practical a non-invasive surrogate measurement of the A-aDO2, the oxygen deficit. The oxygen deficit is the difference between the end-tidal PO2 and the calculated arterial PO2 derived from the SpO2 and taking into account the PCO2, also measured from end-tidal gas. The oxygen deficit shares the underlying basis of the measurement of gas exchange efficiency that the A-aDO2 uses, and thus the two measurements are well-correlated (r 2~0.72). Studies have shown that the new approach is sensitive and can detect the age-related decline in gas exchange efficiency associated with healthy aging. In patients with lung disease the oxygen deficit is greatly elevated compared to normal subjects. The portable and non-invasive nature of the approach suggests potential uses in first responders, in military applications, and in underserved areas. Further, the completely non-invasive and rapid nature of the measurement makes it ideally suited to serial measurements of acutely ill patients including those with COVID-19, allowing patients to be closely monitored if required.