Acute respiratory distress syndrome (ARDS) is a life-threatening respiratory injury with multiple physiological sequelae. Shunting of deoxygenated blood through intra-and extrapulmonary shunts may complicate ARDS management. Therefore, we conducted a systematic review to determine the prevalence of sonographically detected shunts, and their association with oxygenation and mortality in patients with ARDS.DATA SOURCES: Medical literature analysis and retrieval system online, Excerpta Medica dataBASE, Cochrane Library, and database of abstracts of reviews of effects databases on March 26, 2021. STUDY SELECTION:Articles relating to respiratory failure and sonographic shunt detection.DATA EXTRACTION: Articles were independently screened and extracted in duplicate. Data pertaining to study demographics and shunt detection were compiled for mortality and oxygenation outcomes. Risk of bias was appraised using the Joanna-Briggs Institute and the Newcastle-Ottawa Scale tools with evidence rating certainty using Grading of Recommendations Assessment, Development and Evaluation methodology.DATA SYNTHESIS: From 4,617 citations, 10 observational studies met eligibility criteria. Sonographic detection of right-to-left shunt was present in 21.8% of patients (range, 14.4-30.0%) among included studies using transthoracic, transesophageal, and transcranial bubble Doppler ultrasonographies. Shunt prevalence may be associated with increased mortality (risk ratio, 1.22; 95% CI, 1.01-1.49; p = 0.04, very low certainty evidence) with no difference in oxygenation as measured by Pao 2 :Fio 2 ratio (mean difference, -0.7; 95% CI, -18.6 to 17.2; p = 0.94, very low certainty).CONCLUSIONS: Intra-and extrapulmonary shunts are detected frequently in ARDS with ultrasound techniques. Shunts may increase mortality among patients with ARDS, but its association with oxygenation is uncertain.
Objectives: Acute respiratory distress syndrome (ARDS) is a life-threatening respiratory injury with multiple physiological sequalae. Shunting of deoxygenated blood through intra and extra-pulmonary shunts is one consequence that may complicate ARDS management. Therefore, we conducted a systematic review to determine the prevalence of sonographically detected shunt and its association with oxygenation and mortality in patients with ARDS. Data Sources: We searched MEDLINE, EMBASE, Cochrane Library and DARE databases on March 26, 2021 Study Selection: Articles relating to respiratory failure and sonographic shunt detection. Data Extraction: Articles were independently screened and extracted in duplicate. Data pertaining to study demographics and shunt detection were compiled for mortality and oxygenation outcomes. Risk of bias was appraised using the Joanna Briggs Institute and Newcastle-Ottawa Scale tools with evidence rating certainty using GRADE methodology. Data Synthesis: From 4,617 citations, 10 observational studies met eligibility criteria. Sonographic detection of right-to-left shunt was present in 21.8% of patients (range: 14.4-30.0%) amongst included studies using transthoracic, transesophageal and transcranial bubble Doppler sonography. Shunt prevalence may be associated with increased mortality (risk ratio: 1.22, 95% CI: 1.01-1.49, p=0.04, very low certainty evidence) with no difference in oxygenation as measured by PaO2:FiO2 ratio (mean difference -0.7, 95% CI: -18.6 to 17.2, p=0.94, very low certainty evidence). Conclusions: Intra- and extra-pulmonary shunts are detected frequently in ARDS with ultrasound techniques. Shunts may increase mortality amongst patients with ARDS, but its association with oxygenation is uncertain. Future research should explore the role of shunt in ARDS, their association with mortality, and whether targeted precision medicine interventions can improve outcomes. PROSPERO Registration Number: CRD42021245194 (March 26, 2021)
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.
OBJECTIVES: Studies have suggested intrapulmonary shunts may contribute to hypoxemia in COVID-19 acute respiratory distress syndrome (ARDS) with worse associated outcomes. We evaluated the presence of right-to-left (R-L) shunts in COVID-19 and non-COVID ARDS patients using a comprehensive hypoxemia workup for shunt etiology and associations with mortality. DESIGN: Prospective, observational cohort study. SETTING: Four tertiary hospitals in Edmonton, Alberta, Canada. PATIENTS: Adult critically ill, mechanically ventilated, ICU patients admitted with COVID-19 or non-COVID (November 16, 2020, to September 1, 2021). INTERVENTIONS: Agitated-saline bubble studies with transthoracic echocardiography/transcranial Doppler ± transesophageal echocardiography assessed for R-L shunts presence. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were shunt frequency and association with hospital mortality. Logistic regression analysis was used for adjustment. The study enrolled 226 patients (182 COVID-19 vs 42 non-COVID). Median age was 58 years (interquartile range [IQR], 47–67 yr) and Acute Physiology and Chronic Health Evaluation II scores of 30 (IQR, 21–36). In COVID-19 patients, the frequency of R-L shunt was 31 of 182 COVID patients (17.0%) versus 10 of 44 non-COVID patients (22.7%), with no difference detected in shunt rates (risk difference [RD], –5.7%; 95% CI, –18.4 to 7.0; p = 0.38). In the COVID-19 group, hospital mortality was higher for those with R-L shunt compared with those without (54.8% vs 35.8%; RD, 19.0%; 95% CI, 0.1–37.9; p = 0.05). This did not persist at 90-day mortality nor after adjustment with regression. CONCLUSIONS: There was no evidence of increased R-L shunt rates in COVID-19 compared with non-COVID controls. R-L 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.
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