Purpose: The specific norepinephrine dose at which epinephrine should be added in septic shock is unclear. This study sought to determine the norepinephrine-equivalent dose at epinephrine initiation that correlated with hemodynamic stability.
Methods: Septic shock patients receiving both norepinephrine and epinephrine were included in this study. Classification and regression tree analysis was conducted to determine breakpoints in norepinephrine-equivalent dose predicting hemodynamic stability, with two cohorts identified. The primary outcome was hemodynamic stability, and secondary outcomes were shock-free survival, time to achieve hemodynamic stability, and change in SOFA score.
Results: Optimal dose group was identified as initiating epinephrine when norepinephrine-equivalent dose was between 37 and 133 μg/min. A total of 138 and 61 patients were classified in optimal and non-optimal dose groups, respectively. Baseline characteristics were similar between groups except vasopressin use was more frequent in the optimal dose group. More patients in optimal dose group versus non-optimal dose group achieved hemodynamic stability (40 [29%] vs. 9 [14.8%]), absolute risk difference 14.2% [95% CI 2.5-25.9%]; p = .03). On multivariable analysis, initiating epinephrine within the optimal norepinephrine-equivalent dose range was independently associated with higher odds of hemodynamic response (OR 3.06 [95% CI 1.2-7.6]; p = .02). No differences were observed in other secondary outcomes.
Conclusions: Initiation of epinephrine when patients were receiving norepinephrine-equivalent doses of 37-133 μg/min was associated with a higher rate of hemodynamic stability.
Keywords: Epinephrine; Norepinephrine; Sepsis; Septic shock; Vasopressors.
Copyright © 2019 Elsevier Inc. All rights reserved.