Impact of Vasopressor Initiation and Discontinuation Sequence on Mortality in Septic Shock: A Retrospective Review

Background: Little data exists guiding clinicians on how or when to initiate and discontinue the second vasoactive agent in the setting of septic shock refractory to norepinephrine monotherapy. Methods: This retrospective cohort study evaluated patients with a primary diagnosis of septic shock admitted to the intensive care unit receiving norepinephrine in addition to concomitant vasopressors. The primary endpoint was the incidence of all-cause in-hospital mortality when adding adjunctive vasopressors to norepinephrine either before the dose reached 2 mcg/kg/min (early adjunctive vasopressor) or after (late adjunctive vasopressor). Secondary endpoints included the incidence of clinically significant hypotension when discontinuing norepinephrine before or after vasopressin in the same population. Results: Forty-six patients were included (early adjunctive vasopressor [n=36]; late adjunctive vasopressor [n=10]), with a median age of 69 years and APACHE II score of 27. Fewer patients in the early adjunctive vasopressor cohort had malignancy prior to admission (16.7% vs. 60%, p=0.0117), however, more patients were managed in the surgical ICU (44.4% vs. 0%, p=0.0202) with intra-abdominal infection (33.3% vs. 0%, p=0.0439). The primary endpoint of all-cause in-hospital mortality was not statistically different between the early and late adjunctive vasopressor groups (75% vs. 90%, respectively, p=0.4203). Longer ICU and hospital length of stay in the early adjunctive vasopressor cohort was observed (9 days vs 3 days, p=0.0061; 11 days vs 3 days, p=0.0026, respectively). Twenty-two patients were included in analysis of vasopressor discontinuation sequence with no significant differences in mortality, incidence of hypotension, or ICU/hospital length of stay. Conclusion: Among patients with septic shock on multiple vasopressors, addition of adjunctive vasopressor before reaching a norepinephrine dose of 2 mcg/kg/min was associated with longer in-hospital and ICU survival but exhibited no difference in overall mortality. Discontinuation of vasopressin before norepinephrine led to longer total vasopressor duration without a difference in rates of hypotension. Future prospective studies are warranted.