Development of a Novel Ambulatory Pulmonary Assist System and Anticoagulation Strategy for Long-term Respiratory Support
Creators: name: Hong, Yeahwa
Publisher: name: Carnegie Mellon University
Year: 2024
Subjects: Biomedical Engineering not elsewhere classified

description:  Chronic lung disease is the sixth leading cause of death in the United States,  claiming over 150,000 lives each year. Despite the high demand for lung transplantation  among these patients, fewer than 3,000 lung transplants are performed annually in the  United States. This significant gap between the demand and supply of transplantable  lungs underscores the pressing and ongoing need for an alternative, long-term mode of  respiratory support therapy. Extracorporeal membrane oxygenation (ECMO) has  emerged as a viable alternative therapy for individuals with end-stage lung disease and  is increasingly being employed as a bridge to recovery or transplantation. Ambulation and  physical rehabilitation during ECMO support have been associated with improved post?transplant outcomes. Moreover, a portable ECMO system could provide cost-effective  outpatient management, substantially enhancing patient quality of life. However, the  development and implementation of long-term, ambulatory ECMO therapy are  challenging, primarily due to the suboptimal biocompatibility of existing gas exchangers  (commonly referred to as oxygenators) and the bulky, heavy nature of circuit components. 
Current ECMO oxygenators utilize densely-packed hollow fiber bundles with a  large surface area, a design highly prone to clot formation and eventual device failure.  Consequently, these oxygenators typically fail within a mere 1-3 weeks of use. To mitigate  this issue, systemic anticoagulation is administered to slow clot formation and reduce the  risk of thromboembolic complications. However, conventional anticoagulants must be  carefully monitored and titrated by skilled clinicians to prevent bleeding complications.  The cumbersome nature of monitoring and the continuous intravenous delivery of  anticoagulants pose significant barriers to ECMO support outside of hospital settings.   Additionally, the bulky size of current ECMO systems, along with the continuous power  supply requirements for mechanical pumps, further impedes their application in  ambulatory settings without substantial assistance from medical personnel. 
The purpose of this dissertation is to develop and test a novel ambulatory  pulmonary assist system (PAS) that can provide long-term respiratory support therapy for  patients with chronic lung disease, potentially serving as a destination therapy. The  components of the PAS include a highly biocompatible gas exchanger (PAS-GE) and a  compact, lightweight, axial-flow mechanical pump (AFP) with portable battery packs.  Furthermore, an alternative oral anticoagulation strategy, devoid of cumbersome and  frequent monitoring, was also investigated to fully facilitate the transition of the PAS into  a home-based therapy.  
The AFP is the first lightweight, battery-powered axial-flow mechanical pump  designed to be used in ECMO circuits with direct tubing connections. In the first study  (Chapter 2), the hemocompatibility of the AFP was assessed and compared to other  commercially available mechanical pumps within the PAS. The results from this study  demonstrated that the AFP exhibits equivalent hemocompatibility to other contemporary  mechanical pumps with a reduced level of hemolysis. With the confirmation of sufficient  hemocompatibility of the AFP, the second study (Chapter 3) evaluated the  biocompatibility and performance of the full PAS in a long-term in vivo model. This study  demonstrated that the PAS can provide five days of stable, uncomplicated, wearable  respiratory support with adequate gas transfer, low gas exchanger blood flow resistance,  minimal hematologic changes, and normal organ function. The last study (Chapter 4)  evaluated the feasibility of using rivaroxaban for selective, oral artificial lung anticoagulation in an ovine model of ECMO. This study demonstrated that sheep are a  viable animal model for emulating rivaroxaban's effects in humans. Moreover, the  currently approved doses of rivaroxaban in human subjects can achieve comparable  artificial surface anticoagulation efficacy to conventional heparin. The work done on this  dissertation is a promising step towards developing a safe, wearable respiratory assist  system and anticoagulation strategy for patients with chronic lung disease.