Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) is Highly Associated With Mortality and Persistent Organ Dysfunction in the Critically Ill: a Cohort Study
Abstract Background. The triggering receptor expressed on myeloid cells-1 (TREM-1) mediates fatal septic shock in murine models, but studies linking the soluble form of TREM-1 (sTREM-1) to mortality in clinical sepsis are inconclusive, and few have examined its relationship to organ dysfunction. We sought to identify associations between circulating sTREM-1 and both mortality and organ dysfunction among a broad cohort of critically ill medical, post-surgical and trauma patients. Methods. We enrolled a prospective cohort of patients who met two or more criteria for the systemic inflammatory response syndrome (SIRS) within 24 hours of intensive care unit (ICU) admission at a large academic medical center. sTREM-1 concentrations were measured at study enrollment. We used relative risk regression, adjusted for age, sex, and Charlson comorbidity index, to determine associations between sTREM-1 and the primary outcome of 28-day mortality. We also examined secondary outcomes of prevalent organ dysfunction on enrollment, and composites of persistent organ dysfunction or death at day 7. Results. Among 231 critically ill patients, non-survivors (n=19, 8%) had a higher proportion of pre-existing comorbidities, mechanical ventilation (79% vs. 44%) and shock (58% vs. 28%) compared to survivors. At study enrollment, increasing sTREM-1 was associated with a higher risk of severe acute kidney injury (AKI), shock, and acute hypoxemic respiratory failure requiring mechanical ventilation. sTREM-1 was higher among non-survivors than survivors (885 vs 336 pg/mL); each doubling of sTREM-1 concentration was associated with a 2.41-fold higher risk of 28-day mortality (95% CI 1.57, 3.72). Among 92 patients with shock on enrollment, doubling of sTREM-1 was associated with a 3.89-fold higher risk of persistent shock or death by day 7 (95% CI 1.85, 8.17). Higher sTREM-1 was also associated with a higher risk of both persistent AKI and persistent hypoxemic respiratory failure or death. Conclusions. Elevated plasma sTREM-1 is highly associated with 28-day mortality and organ dysfunction across a diverse critically ill population. These data support that early activation of the innate immune system plays a role in the development of organ dysfunction and death. Further studies should address whether modulation of the TREM-1 pathway might be beneficial in critically ill patients.