Sepsis is a life-threatening clinical syndrome defined as the systemic inflammatory response to infection. Sepsis in cats is associated with severe morbidity, prolonged hospitalization and very high mortality rates. Although sepsis in cats is less common than in dogs, cats have a higher risk of death. In contrast to people and dogs, sepsis in cats typically manifests as bradycardia, hypothermia, hypotension and abdominal pain.

It is not known why cats respond differently or have worse outcomes. It is these unique aspects of feline sepsis that are the basis for our proposal. We will enroll cats with naturally occurring sepsis and examine multiple facets of the syndrome to provide insights into feline sepsis pathophysiology. This will identify how cats with sepsis behave differently to other species and will ultimately yield novel diagnostic and therapeutic avenues for cats with this devastating syndrome. We will also include a comparative aspect to the study, measuring similar parameters in samples biobanked from septic dogs to help identify what makes feline sepsis unique.

In preliminary studies, we analyzed samples from six cats with naturally occurring sepsis presented to the CUHA and compared them to six healthy cats. We evaluated neutrophil extracellular trap formation, plasma cell-free DNA concentrations, acute phase protein levels and markers of endothelial damage. Median plasma concentrations of all analytes were higher in septic cats compared to healthy cats, and there were significant differences in two of the eight analytes assessed. Sample size calculations suggest that studying 20 cats in each group will be sufficient to detect significant differences in key measures of the pathogenesis of sepsis.

Our investigations will assess the immune, endocrine and cardiovascular systems, evaluate markers of inflammation and coagulation function, and provide detailed metabolic profiles. Key analyses will include measurement of acute phase proteins; blood cell-free DNA and neutrophil respiratory burst generation; thyroid, adrenal and pancreatic function; glucose and calcium homeostasis; echocardiography and NT-proBNP measurement; protein C concentrations, fibrinolysis markers and platelet activation parameters and high-sensitivity metabolic profiling by liquid-chromatography-mass spectrometry techniques.