Abstract
Introduction: In patients with septic shock, vasopressors are required to maintain hemodynamics while patients receive treatment for the underlying etiology. Two vasopressors, norepinephrine and vasopressin, are recommend by guidelines for the management of septic shock in the intensive care unit (ICU). However, limited data exist evaluating outcomes associated with the need for a third vasopressor, as well as risk factors for mortality for patients requiring three vasopressors. Evaluation of these risk factors may help with prognostication and goals of care discussions. Methods: The MIMIC-IV and eICU-CRD databases were queried for patients who were, 1) admitted to any ICU, 2) administered at least three vasopressors for at least two hours, and 3) identified to have sepsis based on the Sepsis-3 criteria. Data collected included demographics such as age, sex, and race as well as objective data such as serum creatinine, lactate, Richmond Agitation Sedation Scale (RASS) score, and Sequential Organ Function Assessment (SOFA) score. A generalized additional model (GAM) was developed to evaluate risk factors for in-hospital mortality in the MIMIC-IV and validated using the eICU-CRD. Results: A total of 1,347 and 2,100 patients met inclusion criteria from the MIMIC and eICU databases, respectively. Septic shock requiring three or more vasopressors was associated with a 57.6% in-hospital mortality rate. The model developed from the MIMIC-IV identified increased age (OR [95% CI]: 3.5 [2.3-5.3]), serum creatinine (1.6 [1.5-1.6]), lactate (2.6 [2.5-2.6]), and SOFA score (1.8 [1.1-2.9]) as risk factors for mortality with statistical significance. This model found consistent results within the eICU-CRD. Conclusions: This study demonstrates that patients started on three or more vasopressors face an exceptionally high mortality burden while identifying indicators for those at the highest risk of mortality. These findings may inform management including end-of-life discussions. Future studies should evaluate differences in mortality outcomes based on timing and choice of third-line vasopressor.
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