Background: Bacterial pneumonia is a major cause of morbidity and mortality worldwide despite the use of antibiotics, and novel therapies are urgently needed. Building on previous work, we aimed to 1) develop a baboon model of severe pneumococcal pneumonia and sepsis with organ dysfunction; and 2) test the safety and efficacy of a novel extracorporeal blood filter to remove pro-inflammatory molecules and improve organ function. Methods: After a dose-finding pilot study, twelve animals were inoculated with S. pneumoniae (5x109 CFU), given ceftriaxone at 24 hours post-inoculation, and randomized to extracorporeal blood purification using a filter coated with surface-immobilized heparin sulfate (n=6) or sham treatment (n=6) for 4 hours at 30 hours post-inoculation. For safety analysis, four uninfected animals also underwent purification. At 48 hours, necropsy was performed. Results: Inoculated animals developed severe pneumonia and septic shock. Compared with sham animals, septic animals treated with purification displayed significantly less kidney injury, metabolic acidosis, hypoglycemia, and shock (P<0.05). Purification blocked the rise in peripheral blood S. pneumoniae DNA, attenuated BAL CCL4, CCL2, and IL-18 levels, and reduced renal oxidative injury and classical NLRP3-inflammasome activation. Purification was safe in both uninfected and infected animals and produced no adverse effects. Conclusions: We demonstrate that heparin-based blood purification significantly attenuates levels of circulating S. pneumoniae DNA and BAL cytokines, and is renal-protective in baboons with severe pneumococcal pneumonia and septic shock. Purification was associated with less severe acute kidney injury, metabolic derangements, and shock. These results support future clinical studies in critically ill septic patients.
Extracorporeal Blood Purification and Organ Support in the Critically Ill Patient during COVID-19 Pandemic: Expert Review and Recommendation
