The authors have hypothesized that this exercise desaturation is the result of increased shunt physiology, worsening diffusion due to increased pulmonary blood flow with reduced capillary transit time (a physiologic phenomenon called the “diffusion-perfusion defect”), and a reduced mixed venous oxygen content, the impact of which on arterial oxygen saturation is magnified by the former two effects. Formal exercise testing data are available in four small reports and one large cross-sectional study and demonstrate reduced exercise capacity and profound exercise desaturation in HPS (Table 1). Exercise tolerance is further impaired in patients with HPS, who have more dyspnea and a reduced New York Heart Association functional class, compared to patients with cirrhosis who do not have HPS. Participants with liver disease have reduced exercise capacity compared to normal controls due to a combination of deconditioning, malnutrition-associated muscle weakness, and anemia. Liver transplantation is the only known effective therapy for this disease. It is defined by the combination of liver dysfunction or portal hypertension, intrapulmonary vascular dilatations, and abnormal oxygenation. The hepatopulmonary syndrome (HPS) is a pulmonary complication of liver disease found in 10 to 32% of patients with cirrhosis. Trial registrationĬ Protocol Registration and Results System (PRS) NCT04004104. Future studies could explore the corresponding effects of a supine exercise training regimen on physiologic variables such as long-term exercise capacity, quality of life, dyspnea, and liver transplantation outcomes. If our study is positive, a supine exercise regimen could become a routine prescription for patients with HPS and orthodeoxia, enabling them to exercise more effectively. HPS patients have hypoxemia leading to significant exercise limitations. ![]() P < 0.05 will be considered statistically significant. The model will be adjusted for period effects. The primary outcome will be the difference in the stopping time between exercise positions, compared with a repeated measures analysis of variance method with a mixed effects model approach. Exercise will be performed at a constant work rate of 70–85% of the predicted peak work rate until the “stopping time” is reached, defined by exhaustion, profound desaturation, or safety concerns (drop in systolic blood pressure or life-threatening arrhythmia). After a short washout period (a minimum of 1 day to a maximum of 4 weeks), participants will crossover and perform an exercise in the alternate position. Participants will be randomized to cycle ergometry in either the supine or upright position. Patients with pulmonary hypertension, FEV1/FVC ratio < 0.65, significant coronary artery disease, disorders preventing or contraindicating use of a cycle ergometer, and/or moderate or severe ascites will be excluded. We propose a randomized controlled crossover trial in patients with moderate HPS (PaO 2 4 mmHg) comparing the effect of supine vs upright position on exercise. We hypothesize that exercise capacity will be superior in the supine compared to the upright position in such patients. Many patients with HPS exhibit orthodeoxia-an improvement in oxygenation in the supine compared to the upright position. ![]() Patients with HPS have significant exercise limitations, impacting their quality of life and associated with poor liver transplant outcomes. Liver transplantation is the only effective therapy for this disease. The hepatopulmonary syndrome (HPS) is a pulmonary complication of liver disease found in 10 to 32% of patients with cirrhosis and is characterized by intrapulmonary vascular dilatations and abnormal oxygenation.
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