Abstract
Rationale: A central component of septic shock treatment is the infusion of vasopressors, most commonly starting with norepinephrine. However, the optimal approach and practice patterns for initiating adjunctive vasopressors and corticosteroids are unknown. Objectives: To characterize practice pattern variation in the norepinephrine dose at which secondary vasopressors and adjunctive corticosteroids are initiated and to identify factors associated with a treatment strategy favoring secondary vasopressors compared with factors associated with a treatment strategy favoring adjunctive corticosteroids among patients with septic shock on norepinephrine. Methods: We used a multicenter intensive care unit (ICU) database to identify patients with septic shock who were started on norepinephrine followed by an additional vasopressor or corticosteroids. We used multilevel models to determine the hospital risk-adjusted norepinephrine dose at which additional vasopressors and corticosteroids were started, the percentage of variation in the norepinephrine dose at the time of adjunctive treatment associated with the hospital of admission, and the factors associated with choosing an "additional-vasopressor-first" strategy versus a "corticosteroid-first" strategy. Results: Among 4,401 patients with septic shock on norepinephrine, 1,940 (44.0%) were started on adjuncts (1,357 received an additional-vasopressor-first strategy, and 583 received a corticosteroid-first strategy). The hospital risk-adjusted norepinephrine dose at which vasopressors were initiated ranged from 6.4 μg/min (95% confidence interval [CI], 5.9-7.0 μg/min) to 92.6 μg/min (95% CI, 72.8-113.0 μg/min). The hospital risk-adjusted norepinephrine dose at which corticosteroids were initiated ranged from 3.0 μg/min (95% CI, 2.4-3.8 μg/min) to 32.7 μg/min (95% CI, 24.9-43.0 μg/min). Of the variation in the norepinephrine dose at which additional vasopressors were initiated, 25.1% (intraclass correlation coefficient 95% CI, 24.8-25.5%) was explained by the hospital site after adjusting for all hospital- and patient-level covariates. The hospital of admission was strongly associated with receiving an additional-vasopressor-first strategy over a corticosteroid-first strategy (median odds ratio, 3.28 [95% CI, 2.81-3.83]). Conclusions: Practice patterns for adjunctive therapies to norepinephrine during septic shock are variable and are determined in large part by the hospital of admission. These results inform several future studies seeking to improve septic shock management.
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