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Sepsis remains an unmet medical need, and sustained attempts by intensivists have indeed yielded an incremental improvement in outcomes. However, despite many attempts to introduce novel therapeutic molecules, there has been no step change in survival rates. Precision (or personalised) medicine (PM) has emerged in recent years as an approach that seeks to make use of person-specific, real-time data to choose a therapeutic regimen designed specifically for the individual patient. PM has been used most successfully in oncology where chemotherapy regimens can be tailored to specific cancer genotypes. This review considers the options for using PM to improve the outcome in sepsis. There are several challenges. The nature of omics technology is that it involves multiple analytes, each of which usually has a very modest effect; hence large numbers of patients need to be studied. Sophisticated bioinformatic analysis is required that is not suitable for routine clinical use. Sepsis is a fast-moving situation and it is likely that PM profiles would change quickly. This is a huge challenge, since it requires the physician to accurately place the patient in the appropriate cohort that is relevant to the test being used. Many septic patients have comorbidities that complicate data interpretation. Finally, the nature of PM is that it is designed for the individual patient, or at least for a homogeneous group of patients who share specific characteristics. As we have seen, that is difficult to achieve in sepsis, which is a heterogeneous condition. PM is likely to be harder to use in sepsis than in some other clinical settings.