The End of "One Size Fits All" Sepsis Therapies: Toward an Individualized Approach

Abstract

Sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to an infection, remains a major challenge for clinicians and trialists. Despite decades of research and multiple randomized clinical trials, a specific therapeutic for sepsis is not available. The evaluation of therapeutics targeting components of host response anomalies in patients with sepsis has been complicated by the inability to identify those in this very heterogeneous population who are more likely to benefit from a specific intervention. Additionally, multiple and diverse host response aberrations often co-exist in sepsis, and knowledge of which dysregulated biological organ system or pathway drives sepsis-induced pathology in an individual patient is limited, further complicating the development of effective therapies. Here, we discuss the drawbacks of previous attempts to develop sepsis therapeutics and delineate a future wherein interventions will be based on the host response profile of a patient.

Keywords: biomarker; host response; personalized medicine.

Figure 1

Each patient follows their own trajectory of immune response activation during the course of sepsis, rather than all following the same pattern. The early response is usually proinflammatory and the later response immunosuppressive, but there are exceptions, and the time course can vary substantially from one patient to the other. The arrows indicate some examples of time points at which an anti-inflammatory strategy may be beneficial (1 and perhaps 2) and others when it may be harmful (3 and 4).