Phenotypes

Little progress has been made in the identification of novel pharmacological therapies for critically ill patients with sepsis, acute kidney injury, and acute respiratory distress syndrome. This lack of progress can likely be explained in part by inherent heterogeneity in the critically ill population, including but not limited to the dynamic state of the host response. Homogeneity can be improved by grouping patients with similar characteristics. Currently, multiple subphenotypes have been identified in which the markers of dysregulated host response are central to patient classification. In this chapter, we elaborate on this biologic heterogeneity in the critically ill, introduce the principles of phenotyping and precision medicine, and discuss the identified data-driven subphenotypes and the role of the dysregulated immune response in it. The role of the immune response as a common thread is apparent in and between all subphenotypes. Targeting a more generalizable component in the immune response identified in a subphenotype might be beneficial not only for that specific subphenotype, but also for other identified subphenotypes with the same characteristics. This approach may open up new therapeutic opportunities, but it also highlights the complexity in performing clinical trials in the critically ill.