Testing oxygenated microbubbles via intraperitoneal and intrathoracic routes on a large pig model of LPS-induced acute respiratory distress syndrome.

With a mortality rate of 46% before the onset of COVID-19, acute respiratory distress syndrome (ARDS) affected 200,000 people in the US, causing 75,000 deaths. Mortality rates in COVID-19 ARDS patients are currently at 39%. Extrapulmonary support for ARDS aims to supplement mechanical ventilation by providing life-sustaining oxygen to the patient. A new rapid-onset, human-sized pig ARDS model in a porcine intensive care unit (ICU) was developed. The pigs were nebulized intratracheally with a high dose (4 mg/kg) of the endotoxin lipopolysaccharide (LPS) over a 2 h duration to induce rapid-onset moderate-to-severe ARDS. They were then catheterized to monitor vitals and to evaluate the therapeutic effect of oxygenated microbubble (OMB) therapy delivered by intrathoracic (IT) or intraperitoneal (IP) administration. Post-LPS administration, the PaO2 value dropped below 70 mmHg, the PaO2 /FiO2 ratio dropped below 200 mmHg, and the heart rate increased, indicating rapidly developing (within 4 h) moderate-to-severe ARDS with tachycardia. The SpO2 and PaO2 of these LPS-injured pigs did not show significant improvement after OMB administration, as they did in our previous studies of the therapy on small animal models of ARDS injury. Furthermore, pigs receiving OMB or saline infusions had slightly lower survival than their ARDS counterparts. The OMB administration did not induce a statistically significant or clinically relevant therapeutic effect in this model; instead, both saline and OMB infusion appeared to lower survival rates slightly. This result is significant because it contradicts positive results from our previous small animal studies and places a limit on the efficacy of such treatments for larger animals under more severe respiratory distress. While OMB did not prove efficacious in this rapid-onset ARDS pig model, it may retain potential as a novel therapy for the usual presentation of ARDS in humans, which develops and progresses over days to weeks.

Development of a multi-patient ventilator circuit with validation in an ARDS porcine model.

PURPOSE: The COVID-19 pandemic threatens our current ICU capabilities nationwide. As the number of COVID-19 positive patients across the nation continues to increase, the need for options to address ventilator shortages is inevitable. Multi-patient ventilation (MPV), in which more than one patient can use a single ventilator base unit, has been proposed as a potential solution to this problem. To our knowledge, this option has been discussed but remains untested in live patients with differing severity of lung pathology. METHODS: The objective of this study was to address ventilator shortages and patient stacking limitations by developing and validating a modified breathing circuit for two patients with differing lung compliances using simple, off-the-shelf components. A multi-patient ventilator circuit (MPVC) was simulated with a mathematical model and validated with four animal studies. Each animal study had two human-sized pigs: one healthy and one with lipopolysaccharide (LPS) induced ARDS. LPS was chosen because it lowers lung compliance similar to COVID-19. In a previous study, a control group of four pigs was given ARDS and placed on a single patient ventilation circuit (SPVC). The oxygenation of the MPVC ARDS animals was then compared to the oxygenation of the SPVC animals. RESULTS: Based on the comparisons, similar oxygenation and morbidity rates were observed between the MPVC ARDS animals and the SPVC animals. CONCLUSION: As healthcare systems worldwide deal with inundated ICUs and hospitals from pandemics, they could potentially benefit from this approach by providing more patients with respiratory care.