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

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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. Key Points Question Does right-to-left shunt incidence increase with COVID-19 ARDS compared to non-COVID, and is there association with shunt incidence and mortality? Findings In this prospective, observational cohort study, we showed no statistically significant difference in shunt prevalence between COVID-19 ARDS patients (17.0%) and non-COVID patients (22.7%). However, in COVID-19 patients, there was a difference in hospital mortality for those with shunt (54.8%) compared to those without shunt (35.8%), but this difference did not persist at 90-day mortality, nor after regression adjustments for age and illness severity. Meaning There was no evidence of increased R-L shunt rates in COVID-19 compared to non-COVID or historical controls. Right-to-left shunt presence was associated with increased hospital mortality for COVID-19 patients, but this did not persist for 90-day mortality or after adjustment using logistic regression.

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