Supine Versus Upright Exercise in Patients With Hepatopulmonary Syndrome and Orthodeoxia: Study Protocol for a Randomized Controlled Crossover Trial

Abstract

Background: The hepatopulmonary syndrome (HPS) is a pulmonary complication of liver disease found in 10 to 32% of patients with cirrhosis and characterized by intrapulmonary vascular dilatations and abnormal oxygenation. Liver transplantation is the only effective therapy for this disease. Patients with HPS have significant exercise limitation, 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.Methods: We propose a randomized controlled cross-over trial in patients with HPS and orthodeoxia, comparing the effect of supine versus upright position on exercise. Participants will be randomized to cycle ergometry in either the supine or upright position, followed by a crossover to the alternate position after a minimum of 1 day to a maximum of 4 weeks. 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 stopping time between exercise positions.Discussion: HPS patients have hypoxemia leading to significant exercise limitation. 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 registration: The ClinicalTrials.gov Protocol Registration and Results System (PRS): NCT04004104. Registered on 1st July 2019. https://clinicaltrials.gov/ct2/show/NCT04004104