Intrapulmonary shunting is a key contributor to hypoxia in COVID-19: An update on the pathophysiology.

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.

Non-invasive assessment of intrapulmonary shunt and ventilation to perfusion ratio in children with hepatopulmonary syndrome before and after liver transplantation.

OBJECTIVES: To use the oxyhaemoglobin dissociation curve (ODC) to non-invasively measure the ventilation perfusion ratio (VA/Q) and right-to-left intrapulmonary vascular shunt before and after liver transplantation (LT) in children with hepatopulmonary syndrome (HPS). To investigate whether the right-to-left shunt derived by ODC correlated with the shunt derived by technetium-99 labelled macroaggregated albumin lung perfusion scan (MAA). METHODS: A retrospective cohort study at King's College Hospital NHS Foundation Trust, London, UK was performed between 1998 and 2016. The VA/Q and right-to-left shunt were non-invasively measured pre and post LT. The pre-LT right-to-left intrapulmonary shunt was also measured by MAA. The non-invasively derived pre-LT shunt was correlated with the shunt derived by MAA. RESULTS: Fifteen children with HPS were studied with a median (IQR) age at LT of 8.8 (6.6-12.9) years. The median (IQR) pre-LT VA/Q [0.49 (0.42-0.65)] was lower compared to the post-LT VA/Q [0.61 (IQR 0.54-0.72), p = 0.012]. The median (IQR) pre-LT shunt was 19 (3-24) % which decreased to zero in all but one children post-LT, (p = 0.001). The MAA-derived shunt was significantly positively correlated with the ODC-derived shunt (r = 0.783, p = 0.001). The mean (SD) difference between shunt derived by ODC and shunt derived by MAA was 0.5 (7.2) %. CONCLUSIONS: Ventilation/perfusion impairment reverses but not completely resolves after liver transplantation in children with hepatopulmonary syndrome. The non-invasive method for estimating intrapulmonary shunting could be used as an alternative to the macroaggregated albumin scan in this population.