Timing of administration of epinephrine predicts the responsiveness to epinephrine in norepinephrine-refractory septic shock: a retrospective study.

BACKGROUND

Currently, the appropriate method of management of patients with refractory septic shock remains unclear. This study aimed to evaluate the factors associated with response to epinephrine in norepinephrine-refractory septic shock.

METHODS

A retrospective single-center observational study was performed using data from adult patients (≥ 18 years old) admitted to our emergency and medical intensive care unit (ICU) from January 2014 to December 2017 who had received epinephrine to treat norepinephrine-refractory septic shock. The response was considered positive if there was increase in mean arterial pressure of 10 mmHg or decrease in arterial lactate level 3 h after epinephrine administration.

RESULTS

Forty-one patients were included: 24 responders (59%) and 17 non-responders (41%). Responders showed higher rate of survival from shock (92% vs. 18%;  < 0.001), and 28-day survival (83% vs. 18%;  < 0.001). In multivariable analysis, time of epinephrine administration after ICU admission (odds ratio [OR] 0.48; 95% confidence interval [CI] 0.27-0.87;  = 0.011) and SOFA score (OR 0.19; 95% CI 0.04-0.88;  = 0.034) were associated with epinephrine response. Time of epinephrine administration was also significantly associated with survival from shock (OR 0.42;  = 0.005) and 28-day survival (OR 0.14;  = 0.006), while SOFA score did not. Using inverse probability of treatment weighing (IPTW) adjustment of propensity score, epinephrine administration later than 24 h after ICU admission was associated with poor response (OR 0.07; 95% CI 0.02-0.21;  < 0.001).

CONCLUSIONS

Early administration of epinephrine after ICU admission (i.e., within 24 h) is associated with better hemodynamic status in patients with refractory septic shock.