Benjamin S. Terry
Date of this Version
Zollinger, Nathaniel. "Device Development for the Treatment of Acute Respiratory Distress Syndrome with Oxygen Microbubbles." Thesis, University of Nebraska-Lincoln, 2020.
Acute respiratory distress syndrome (ARDS) is a life-threatening condition that is characterized by hypoxemia, a reduced capacity to eliminate carbon dioxide, and by reduced lung volumes and compliance. About 10% of patients admitted to intensive care units (ICU) around the world meet the criteria for ARDS. It has been estimated that there are 190,600 ARDS cases per year in the United States. Depending on the severity, the mortality rate of ARDS is 27-45%. Currently available treatments, such as mechanical ventilation and extra-corporeal membrane oxygenation (ECMO), are linked to ventilator-induced injury, thrombosis, and hemorrhage. A new treatment option uses oxygen microbubbles (OMB) to provide supplemental oxygen to the body. Intra-peritoneal infusions of OMB have been shown to increase the survival time of rats suffering from a right pneumothorax, rabbits experiencing complete tracheal occlusion, and rats with ARDS. Our objective is to demonstrate that extra-pulmonary oxygenation via an OMB infusion is a viable treatment option for patients with ARDS.
We created an LPS-induced ARDS model in large animals that replicated the pathologies of severe, rapidly progressing, and fatal ARDS. The injury model was ICU-dependent and focused on oxygen depression. Traditional ICU oxygenation techniques were excluded from the model to isolate the OMB benefit. We demonstrated the safety of intra-pleural infusions of OMB using a benchtop device that reproduced the physiological conditions of that cavity. Then we utilized the large animal ARDS model to evaluate OMB therapy for increased survival and increased systemic oxygenation. An OMB infusion was tested using both intra-peritoneal and intra-pleural infusion routes, but no significant increase in oxygenation or survival was observed. With a rapid onset of severe ARDS, there appears to be a percentage of patients that will die regardless of the aggressiveness of the interventions provided. A low cavity surface area to body mass ratio or insufficient oxygen transfer could be contributing factors limiting this therapy’s ability to rescue a crashing patient. This presents a challenge to the development of a model to evaluate a new treatment. Ideally, this OMB treatment would be used on a more stable patient with maximized ventilator setting or supplemental oxygen.
Adviser: Benjamin Terry