Abstract
BackgroundThe 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. Liver transplantation is the only effective therapy for this disease. Patients with HPS have significant exercise limitations, impacting their quality of life and associated with poor liver transplant outcomes. Many patients with HPS exhibit orthodeoxia—an improvement in oxygenation in the supine compared to the upright position. We hypothesize that exercise capacity will be superior in the supine compared to the upright position in such patients.MethodsWe propose a randomized controlled crossover trial in patients with moderate HPS (PaO2 < 80 mmHg) and orthodeoxia (supine to upright PaO2 decrease > 4 mmHg) comparing the effect of supine vs upright position on exercise. 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. Participants will be randomized to cycle ergometry in either the supine or upright position. 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. 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). 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. The model will be adjusted for period effects. P < 0.05 will be considered statistically significant.DiscussionHPS patients have hypoxemia leading to significant exercise limitations. 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. 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.Trial registrationClinicalTrials.gov Protocol Registration and Results System (PRS) NCT04004104. Registered on 1 July 2019
Highlights
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
*Analysis performed in patients at the Toronto site of the Canadian HPS Database with a Partial pressure of arterial oxygen (PaO2) < 80 mmHg, absence of significant concurrent lung disease contributing to hypoxemia, and absence of concurrent portopulmonary hypertension †All studies defined “upright” as the sitting position, except for Krowka 1993 [32] and the current study, which defined it as the standing position ‡All studies defined orthodeoxia as a drop in partial pressure of arterial oxygen (PaO2) of greater than 5% or 4 mmHg in the upright compared to the supine position, except Martinez 1999 [33], which defined it as a drop in PaO2 greater than 10 mmHg in the upright compared to the supine position currently meet the inclusion criteria
Our study aims to investigate the effect of position change on exercise capacity in HPS patients with orthodeoxia
Summary
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. 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 [9] These studies support the concept that an abnormal pulmonary circulation contributes to exercise limitation in HPS and that patients with HPS experience severely reduced aerobic capacity, beyond that found in those with cirrhosis without HPS [7,8,9, 11, 12]
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