Unpacking the sepsis controversy

Despite its many definitions and revisions, consensus statements and clinical guidelines, the term 'sepsis' continues to be referred to as a discrete clinical entity that is often claimed to be a direct cause of mortality. The assertion that sepsis can be defined as a 'life-threatening organ dysfunction caused by a dysregulated host response to infection,' has led to a field dominated by failed clinical trials informed by host-centered, pathogen-agnostic, animal experiments in which animal models do not recapitulate the clinical condition. The observations from the National Health Service from England that claim that 77.5% of sepsis deaths occur in those aged 75 years or older and those from the USA indicating that most patients dying of sepsis have also been diagnosed with 'hospice qualifying conditions,' seem to refute the assertion that sepsis is caused by, rather than associated with, a 'dysregulated host response.' This piece challenges the current conceptual framework that forms the basis of the sepsis definition. Here we posit that as a result of both its definition and the use of inappropriate animal models, ineffective clinical treatments continue to be pursued in this field.