Comparative Effectiveness of Second Vasoactive Agents in Septic Shock Refractory to Norepinephrine

We aim to identify the appropriate vasoactive agent in patients with septic shock who are refractory to optimal doses of norepinephrine.

In this retrospective observational cohort study over a 4-year period, patients who received norepinephrine within 24 hours of ICU admission and a second agent within 48 hours were enrolled.

Among 2640 patients screened, 234 patients were enrolled, aged 60.8 ± 17.8 years, Acute Physiology and Chronic Health Evaluation IV 98.3 ± 27.5, 81.6% mechanically ventilated, and 65.8% in-hospital mortality. Within 96 hours, 2.8 ± 1.0 vasoactive agents were administered. Fifty, 50, 66, and 68 patients received dobutamine, dopamine, phenylephrine, and vasopressin as the second agent, with crude in-hospital mortality 40.0%, 66.0%, 74.2%, and 76.5%, respectively, P < .001. Survival analysis showed a statistically significant difference in survival time by second vasoactive agent, P < .001. After adjusting for confounding variables, dobutamine showed significant decreased odds ratio (OR) for mortality compared to vasopressin: OR 0.34 (95% confidence interval 0.14-0.84, P = .04). The relative risk of dying was 55.8% lower in patients receiving dobutamine versus vasopressin, P < .01.

Dobutamine is associated with decreased mortality compared to other second vasoactive agents in septic shock when norepinephrine is not sufficient. A prospective randomized trial examining the outcome impact of the second vasoactive agent is needed.