Stephanie Smith, BS, BA
Nominated From: University of Minnesota
Research Site: Universidad Peruana Cayetano Heredia
Research Area: Chronic Mountain Sickness
Primary Mentor: Joseph Zunt, MD, MPH
Research Project
Conventional Phlebotomy versus Isovolumetric Hemodilution for Chronic Mountain Sickness: A Randomized Controlled Trial to Develop Evidence-Based Treatment Protocol in High-Altitude Peru
Chronic Mountain Sickness (CMS) affects approximately 80 million people living above 2,500m worldwide, with particularly high prevalence in Peru where 30% of men and up to 80% of post-menopausal women are affected. CMS is characterized by excessive erythrocytosis and severe hypoxemia, causing debilitating symptoms including dyspnea, palpitations, neurologic dysfunction, pulmonary hypertension, and increased cardiovascular and stroke risk. Current treatments are limited by cost and accessibility. Therapeutic phlebotomy, while traditionally used, has limited evidence-based protocols and demonstrates hematocrit rebound above baseline levels in some studies. This study aims to compare the efficacy and safety of conventional phlebotomy (CP) versus isovolumetric hemodilution (IVHD) in CMS management and to elucidate underlying disease mechanisms through investigation of diffusion-limited oxygen delivery. We will employ a crossover trial design to compare CP and IVHD to track hematological, vascular, and biochemical parameters over time. This study creates the foundation for evaluating the comparative effectiveness of CP versus IVHD in sustained hematocrit suppression and symptom improvement. This study aims to develop cost-effective, evidence-based protocols to improve health outcomes for highland populations worldwide while advancing our understanding of oxygen transport disorders in hypoxic environments.
Research Significance
Worldwide, approximately 80 million people live at high-altitude above 2,500m (8,200 ft) and are at risk for Chronic Mountain Sickness (CMS). CMS is a syndrome that develops in individuals who reside long term at high-altitude and experience chronic hypoxia. It is characterized by excessive erythrocytosis and severe, symptomatic hypoxemia. In Peru alone, approximately 10 million people live at high altitude where CMS affects 30% men and up to 80% post-menopausal women. Symptoms of this life-long systemic illness include shortness of breath, palpitations, headache, sleep disturbances, neurologic dysfunction, pulmonary hypertension, and increased risk of myocardial infarction and stroke. Disease burden is equivalent to losing 3 months of healthy life annually, therefore adequate treatments are critically necessary. Definitive management of CMS involves relocation to lower altitudes, though for those whose permanent residence and employment is at high-altitude, this is not a practical long-term solution. Use of long-term pharmacological interventions are expensive and only have limited evidence. Over generations, therapeutic phlebotomy has been commonly used to treat CMS without rigorous guidelines. The clinical basis for phlebotomy has been drawn predominantly from small studies. There is a need to establish age and sex stratified protocols for refined interventions that maximally suppress hematocrit and improve symptom burden in individuals with CMS.
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