Intra-pulmonary and intra-cardiac shunts in adult COVID-19 versus non-COVID ARDS ICU patients using echocardiography and contrast bubble studies (COVID-Shunt Study): a prospective, observational cohort study

Abstract

Importance: Studies have suggested intra-pulmonary shunts may contribute to hypoxemia in COVID-19 ARDS and may be associated with worse outcomes. Objective: To evaluate the presence of right-to-left (R-L) shunts in COVID-19 and non-COVID ARDS patients using a comprehensive hypoxemia work-up for shunt etiology and associations with mortality. Design, Setting, Participants: We conducted a multi-centre (4 Canadian hospitals), prospective, observational cohort study of adult critically ill, mechanically ventilated, ICU patients admitted for ARDS from both COVID-19 or non-COVID (November 16, 2020-September 1, 2021). Intervention: Contrast-enhanced agitated-saline bubble studies with transthoracic echocardiography/transcranial Doppler (TTE/TCD) ± transesophageal echocardiography (TEE) assessed for the presence of R-L shunts. Main Outcomes and Measures: Primary outcomes were shunt incidence and association with hospital mortality. Logistic regression analysis was used to determine association of shunt presence/absence with covariables. Results: The study enrolled 226 patients (182 COVID-19 vs. 42 non-COVID). Median age was 58 years (interquartile range [IQR]: 47-67) and APACHE II scores of 30 (IQR: 21-36). In COVID-19 patients, the incidence of R-L shunt was 31/182 patients (17.0%; intra-pulmonary: 61.3%; intra-cardiac: 38.7%) versus 10/44 (22.7%) non-COVID patients. No evidence of difference was detected between the COVID-19 and non-COVID-19 shunt rates (risk difference [RD]: -5.7%, 95% CI: -18.4-7.0, p=0.38). In the COVID-19 group, hospital mortality was higher for those with R-L shunt compared to those without (54.8% vs 35.8%, RD: 19.0%, 95% CI 0.1-37.9, p=0.05). But this did not persist at 90-day mortality, nor after regression adjustments for age and illness severity. Conclusions: There was no evidence of increased R-L shunt rates in COVID-19 compared to non-COVID controls. Right-to-left shunt was associated with increased in-hospital mortality for COVID-19 patients, but this did not persist at 90-day mortality or after adjusting using logistic regression.

Unraveling the Underlying Molecular Mechanism of ‘Silent Hypoxia’ in COVID-19 Patients Suggests a Central Role for Angiotensin II Modulation of the AT1R-Hypoxia-Inducible Factor Signaling Pathway

“…The most common mechanism of hypoxia is perfusion through areas that are not well ventilated as a consequence of ventilation–perfusion mismatch (imbalance between the volume of gas expired by the alveoli and the pulmonary capillary blood flow) [ 16 ]. Another important cause of hypoxia is left-to-right shunt—a condition in which there is a transfer of blood from the left side of the heart to the right side as a result of a hole in the walls separating the upper chambers (atrium) or lower chambers (ventricles) [ 17 , 18 ]. Hypoxia can also be caused by right ventricular dysfunction following pericardiocentesis [ 19 ].…”