ABSTRACT
BACKGROUND: Retrospective analysis of the transcriptomic host response in sepsis has demonstrated that sepsis can be separated into three endotypes-inflammatory (IE), adaptive (AE), and coagulopathic (CE), which have demonstrated prognostic significance. We undertook a prospective transcriptomic host response analysis in a subgroup of patients enrolled in the Outcomes of Metabolic Resuscitation Using Ascorbic Acid, Thiamine, and Glucocorticoids in the Early Treatment of Sepsis (ORANGES) trial. METHODS: Blood was obtained from 51 patients and profiled using a pre-established 33-mRNA classifier to determine sepsis endotypes. Endotypes were compared to therapy subgroups and clinical outcomes. RESULTS: We redemonstrated a statistically significant difference in mortality between IE, AE, and CE patients, with CE patients demonstrating the highest mortality (40%), and AE patients the lowest mortality (5%, p = 0.032). A higher CE score was a predictor of mortality; coronary artery disease (CAD) and elevated CE scores were associated with an increase in mortality (CAD: HR = 12.3, 95% CI 1.5-101; CE score: HR = 15.5 95% CI 1.15-211). Kaplan-Meier (KM) analysis of the entire cohort (n = 51) demonstrated a decrease survival in the CE group, p = 0.026. KM survival analysis of hydrocortisone, ascorbic acid, and thiamine (HAT) therapy and control patients not receiving steroids (n = 45) showed CE and IE was associated with a decrease in survival (p = 0.003); of interest, there was no difference in survival in CE patients after stratifying by HAT therapy (p = 0.18). These findings suggest a possible treatment effect of corticosteroids, HAT therapy, endotype, and outcome. CONCLUSION: This subset of patients from the ORANGES trial confirmed previous retrospective findings that a 33-mRNA classifier can group patients into IE, AE, and CE endotypes having prognostic significance. A novel finding of this study identifying an association between endotype and corticosteroid therapy warrants further study in support of future diagnostic use of the endotyping classifier.
ABSTRACT
Purpose: A review of the impact of pharmacists on appropriate medication selection, timing of administration, and as members of a multidisciplinary sepsis response team. Summary: Early goal-directed therapy (EGDT), currently recommended by the 2013 Surviving Sepsis Campaign guidelines for the management of patients with sepsis, includes the administration of appropriate antibiotics in patients with septic shock within the first hour. Multidisciplinary teams containing pharmacists have been shown to decrease time to antibiotic delivery, time to antibiotic administration, and patient mortality. The pharmacist can act as a drug information resource, expedite the medication verification and procurement process, and offer suggestions on how to better manage the patients. Pharmacists are often consulted for dosing and antibiotic selection recommendations for patients with sepsis, but they can also help increase the appropriateness of antibiotics selected. Additional recommendations and interventions made by pharmacists include fluid management and vasopressor facilitation for the more severe patients. A sepsis management team that included a pharmacist increased the number of patients receiving appropriate antibiotics within the first hour by as much as 22-fold. Another study has demonstrated that intensive care units with a pharmacist are associated with a 4% decrease in sepsis patient mortality compared to those without a pharmacist. Conclusion: Multidisciplinary teams containing pharmacists have been shown to decrease time to administration of antibiotics, increase appropriate selection of medications, and decrease mortality; they may also decrease overall health care costs.
