RESUMEN
Acute respiratory distress syndrome (ARDS) is a serious respiratory condition that occurs in approximately 10% of patients entering intensive care units around the world, affecting nearly 190,000 patients annually in the United States. Owing to the severity of the condition, conventional methods of oxygenation are often insufficient. However, current alternate methods of oxygenation are associated with contraindications and a mortality rate near 50%. Therefore, a need exists for a safer and more effective method of oxygenation for patients with ARDS. In this work, the feasibility of using intraperitoneal perfusions of oxygen microbubbles-peritoneal microbubble oxygenation (PMO)-to treat lipopolysaccharide-induced ARDS was explored with the objective of showing restoration of normoxic conditions after a single bolus infusion of oxygen microbubbles. Male Wistar rats induced with ARDS via lipopolysaccharide inhalation were treated with PMO at 12-h intervals over a period of 48 h. Their physiological responses were monitored throughout the study, after which necropsy was performed. Response data were then compared with saline control and untreated groups. We conclude that rats experiencing moderate to severe ARDS that were treated with PMO experienced a survival rate 37% higher than animals not given treatment and exhibited increased peripheral blood oxygen saturation when compared with untreated and saline-treated groups. Moreover, those treated with PMO experienced a lower lung wet/dry ratio and less severe lung pathology, indicating a surprising improvement in lung health. Overall, this study demonstrates the ability of PMO to deliver life-sustaining supplemental oxygen to rats suffering from ARDS and warrants further work toward clinical translation.
Asunto(s)
Microburbujas , Oxígeno/administración & dosificación , Perfusión/métodos , Síndrome de Dificultad Respiratoria/terapia , Terapia Respiratoria/métodos , Animales , Modelos Animales de Enfermedad , Humanos , Lipopolisacáridos/toxicidad , Masculino , Ratas , Ratas Wistar , Síndrome de Dificultad Respiratoria/inducido químicamente , Síndrome de Dificultad Respiratoria/diagnóstico , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Purpose/Aim: In developing a novel peritoneal oxygenation therapy, catheters implanted into the peritoneal cavity became obstructed with omental tissue and prevented the infusion and removal of fluid from the peritoneal cavity. The obstruction of peritoneal catheters is a significant failure in researching various peritoneal treatments as further fluid administration is no longer possible. The purpose of this preliminary study was to determine the most effective catheter design for infusion and removal of fluid into the peritoneal cavity of rats. Materials and Methods: Four types of catheters were tested including the Jackson-Pratt, round fluted drain, flat fluted drain, and an original design. Three of each catheter type were surgically placed into the peritoneal cavity of rats (n = 12). In order to test the efficacy of each catheter, saline was infused and extracted twice daily. Catheters were scored on a weighted scale based on the amount of time they remained patent, the subjective force needed for extraction/infusion, and the amount of saline removed. Results: The round and flat fluted drain catheters remained patent for the full duration of the study (12 days) compared to the other models which failed after 7 days. These catheters also yielded a high average for extracted saline volume and an easy extraction/infusion. Conclusions: The round and flat fluted drain catheters were recognized as viable options to be used in rats for peritoneal drain studies of up to 12 days.
Asunto(s)
Obstrucción del Catéter , Catéteres de Permanencia/efectos adversos , Diseño de Equipo , Lavado Peritoneal/instrumentación , Animales , Drenaje , Humanos , Masculino , Modelos Animales , Lavado Peritoneal/métodos , Peritoneo/cirugía , Ratas , Insuficiencia Respiratoria/terapia , Terapia Respiratoria/instrumentación , Terapia Respiratoria/métodos , Factores de TiempoRESUMEN
Alternative extrapulmonary oxygenation technologies are needed to treat patients suffering from severe hypoxemia refractory to mechanical ventilation. We previously demonstrated that peritoneal microbubble oxygenation (PMO), in which phospholipid-coated oxygen microbubbles (OMBs) are delivered into the peritoneal cavity, can successfully oxygenate rats suffering from a right pneumothorax. This study addressed the need to scale up the procedure to a larger animal with a splanchnic cardiac output similar to humans. Our results show that PMO therapy can double the survival time of rabbits experiencing complete tracheal occlusion from 6.6 ±0.6 min for the saline controls to 12.2 ±3.0 min for the bolus PMO-treated cohort. Additionally, we designed and tested a new peritoneal delivery system to circulate OMBs through the peritoneal cavity. Circulation achieved a similar survival benefit to bolus delivery under these conditions. Overall, these results support the feasibility of the PMO technology to provide extrapulmonary ventilation for rescue of severely hypoxic patients.
Asunto(s)
Hipoxia/tratamiento farmacológico , Hipoxia/fisiopatología , Microburbujas/uso terapéutico , Oxígeno/administración & dosificación , Oxígeno/uso terapéutico , Cavidad Peritoneal/fisiología , Animales , Modelos Animales de Enfermedad , Hipoxia/mortalidad , Infusiones Parenterales , Estimación de Kaplan-Meier , Masculino , Pulso Arterial , ConejosRESUMEN
Severe hypoxemia refractory to pulmonary mechanical ventilation remains life-threatening in critically ill patients. Peritoneal ventilation has long been desired for extrapulmonary oxygenation owing to easy access of the peritoneal cavity for catheterization and the relative safety compared to an extracorporeal circuit. Unfortunately, prior attempts involving direct oxygen ventilation or aqueous perfusates of fluorocarbons or hemoglobin carriers have failed, leading many researchers to abandon the method. We attribute these prior failures to limited mass transfer of oxygen to the peritoneum and have designed an oxygen formulation that overcomes this limitation. Using phospholipid-coated oxygen microbubbles (OMBs), we demonstrate 100% survival for rats experiencing acute lung trauma to at least 2 h. In contrast, all untreated rats and rats treated with peritoneal oxygenated saline died within 30 min. For rats treated with OMBs, hemoglobin saturation and heart rate were at normal levels over the 2-h timeframe. Peritoneal oxygenation with OMBs was therefore shown to be safe and effective, and the method requires less equipment and technical expertise than initiating and maintaining an extracorporeal circuit. Further translation of peritoneal oxygenation with OMBs may provide therapy for acute respiratory distress syndrome arising from trauma, sepsis, pneumonia, aspiration, burns and other pulmonary diseases.