Abstract
Significant practice variation exists when selecting between hydrocortisone and vasopressin as second line agents in patients with septic shock in need of escalating doses of norepinephrine. The goal of this study was to assess differences in clinical outcomes between these two agents. This was a multicenter, retrospective, observational study conducted across ten hospitals within Ascension Health. Adult patients with presumed septic shock receiving norepinephrine prior to initiation of hydrocortisone or vasopressin between December 2015 and August 2021 were assessed for inclusion. The primary outcome, mortality within 28 days of study drug initiation, was assessed using multivariable logistic regression and propensity score matching performed with a 1:1 ratio. A total of 768 patients were included with a median (interquartile range) SOFA score of 10 (8-13), norepinephrine dose of 0.3 mcg/kg/min (0.1-0.5 mcg/kg/min), and lactate of 3.8 mmol/L (2.4-7.0 mmol/L) at initiation of the study drug. A significant difference in 28-day mortality was noted favoring hydrocortisone as an adjunct to norepinephrine after controlling for potential confounding factors (OR 0.46 [95% CI, 0.32-0.66]); similar results were seen following propensity score matching. Compared to vasopressin, hydrocortisone initiation was also associated with a higher rate of hemodynamic responsiveness (91.9% vs. 68.2%, p<0.01), improved resolution of shock (68.8% vs. 31.5%, p<0.01), and reduced recurrence of shock within 72 hours (8.7% vs. 20.7%, p<0.01). Addition of hydrocortisone to norepinephrine was associated with a lower 28-day mortality in patients with septic shock, compared to the addition of vasopressin.
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