BACKGROUND: The pathophysiology of COVID-19 remains poorly understood. We aimed to estimate the contribution of intrapulmonary shunting and ventilation-to-perfusion (VA/Q) mismatch using a mathematical model to construct oxygen-haemoglobin dissociation curves (ODCs). METHODS: ODCs were constructed using transcutaneous pulse oximetry at two different fractions of inspired oxygen (FiO2). 199 patients were included from two large district general hospitals in the South East of England from 1st to 14th January 2021. The study was supported by the National Institute of Health Research (NIHR) Clinical Research Network. RESULTS: Overall mortality was 29%. Mean age was 68.2 years (SEM 1·2) with 46% female. Median shunt on admission was 17% (IQR 8-24.5); VA/Q was 0.61 (IQR 0.52-0.73). Shunt was 37.5% higher in deaths (median 22%, IQR 9-29) compared to survivors (16%, 8-21; p = 0.0088) and was a predictor of mortality (OR 1.04; 95% CI 1.01-1.07). Admission oxygen saturations were more strongly predictive of mortality (OR 0.91, 95% CI 0.87-0.96). There was no difference in VA/Q mismatch between deaths (0.60; IQR 0.50-0.73) and survivors (0.61; IQR 0.52-0.73; p = 0.63) and it was not predictive of mortality (OR 0.68; 95% CI 0.18-2.52; p = 0.55). Shunt negatively correlated with admission oxygen saturation (R -0.533; p<0.0001) whereas VA/Q was not (R 0.1137; p = 0.12). INTERPRETATION: Shunt, not VA/Q mismatch, was associated with worsening hypoxia, though calculating shunt was not of prognostic value. This study adds to our understanding of the pathophysiology of hypoxaemia in COVID-19. Our inexpensive and reliable technique may provide further insights into the pathophysiology of hypoxia in other respiratory diseases.
BACKGROUND: The pathophysiology of COVID-19 remains poorly understood. We aimed to estimate the contribution of intrapulmonary shunting and ventilation-to-perfusion (VA/Q) mismatch using a mathematical model to construct oxygen-haemoglobin dissociation curves (ODCs). METHODS: ODCs were constructed using transcutaneous pulse oximetry at two different fractions of inspired oxygen (FiO2). 199 patients were included from two large district general hospitals in the South East of England from 1st to 14th January 2021. The study was supported by the National Institute of Health Research (NIHR) Clinical Research Network. RESULTS: Overall mortality was 29%. Mean age was 68.2 years (SEM 1·2) with 46% female. Median shunt on admission was 17% (IQR 8-24.5); VA/Q was 0.61 (IQR 0.52-0.73). Shunt was 37.5% higher in deaths (median 22%, IQR 9-29) compared to survivors (16%, 8-21; p = 0.0088) and was a predictor of mortality (OR 1.04; 95% CI 1.01-1.07). Admission oxygen saturations were more strongly predictive of mortality (OR 0.91, 95% CI 0.87-0.96). There was no difference in VA/Q mismatch between deaths (0.60; IQR 0.50-0.73) and survivors (0.61; IQR 0.52-0.73; p = 0.63) and it was not predictive of mortality (OR 0.68; 95% CI 0.18-2.52; p = 0.55). Shunt negatively correlated with admission oxygen saturation (R -0.533; p<0.0001) whereas VA/Q was not (R 0.1137; p = 0.12). INTERPRETATION: Shunt, not VA/Q mismatch, was associated with worsening hypoxia, though calculating shunt was not of prognostic value. This study adds to our understanding of the pathophysiology of hypoxaemia in COVID-19. Our inexpensive and reliable technique may provide further insights into the pathophysiology of hypoxia in other respiratory diseases.
Authors: Harry Knights; Nikhil Mayor; Kristina Millar; Matthew Cox; Evgeniya Bunova; Morgan Hughes; Jack Baker; Sanju Mathew; David Russell-Jones; Aleksandra Kotwica Journal: Clin Med (Lond) Date: 2020-07-24 Impact factor: 2.659
Authors: Marcin F Osuchowski; Martin S Winkler; Tomasz Skirecki; Sara Cajander; Manu Shankar-Hari; Gunnar Lachmann; Guillaume Monneret; Fabienne Venet; Michael Bauer; Frank M Brunkhorst; Sebastian Weis; Alberto Garcia-Salido; Matthijs Kox; Jean-Marc Cavaillon; Florian Uhle; Markus A Weigand; Stefanie B Flohé; W Joost Wiersinga; Raquel Almansa; Amanda de la Fuente; Ignacio Martin-Loeches; Christian Meisel; Thibaud Spinetti; Joerg C Schefold; Catia Cilloniz; Antoni Torres; Evangelos J Giamarellos-Bourboulis; Ricard Ferrer; Massimo Girardis; Andrea Cossarizza; Mihai G Netea; Tom van der Poll; Jesús F Bermejo-Martín; Ignacio Rubio Journal: Lancet Respir Med Date: 2021-05-06 Impact factor: 30.700
Authors: Peter Horby; Wei Shen Lim; Jonathan R Emberson; Marion Mafham; Jennifer L Bell; Louise Linsell; Natalie Staplin; Christopher Brightling; Andrew Ustianowski; Einas Elmahi; Benjamin Prudon; Christopher Green; Timothy Felton; David Chadwick; Kanchan Rege; Christopher Fegan; Lucy C Chappell; Saul N Faust; Thomas Jaki; Katie Jeffery; Alan Montgomery; Kathryn Rowan; Edmund Juszczak; J Kenneth Baillie; Richard Haynes; Martin J Landray Journal: N Engl J Med Date: 2020-07-17 Impact factor: 91.245
Authors: Anderson Brito-Azevedo; Eduardo Costa Pinto; Gabriel Angelo de Cata Preta Corrêa; Eliete Bouskela Journal: J Med Virol Date: 2020-08-02 Impact factor: 20.693
Authors: Alexandra S Reynolds; Alison G Lee; Joshua Renz; Katherine DeSantis; John Liang; Charles A Powell; Corey E Ventetuolo; Hooman D Poor Journal: Am J Respir Crit Care Med Date: 2020-10-01 Impact factor: 21.405