(1646) Timing of Peak Vasopressor Exposure in Refractory Septic Shock

Introduction: Progression to refractory septic shock is associated with metabolic derangements, unsatisfactory hemodynamic response despite high doses of vasopressors, impaired perfusion, and unacceptably high mortality. The objective of this study was to evaluate the effect of the timing of peak vasopressor dose exposure on morbidity and mortality in patients with vasopressor-refractory septic shock.

Methods: This was a single-center, retrospective cohort study of adults who required a vasopressor dose ≥ 0.5 mcg/kg/min norepinephrine-equivalents in the first 24 hours of septic shock. The study median time to peak vasopressor dose was used to stratify patients into ‘early’ and ‘late’ groups. Multivariable Cox proportional hazards regression was used to assess the impact of time to peak vasopressor exposure on the primary outcome of 28-day mortality. Secondary outcomes included days alive and free from organ-support therapies and adverse effects.

Results: The early (n = 351) and late (n = 351) groups were defined by the study median time to peak vasopressor exposure of 6 (3, 13) hours. The peak dose exposure achieved in the first 24 hours was 0.65 (0.53, 0.90) and 0.70 (0.60, 1.15) mcg/kg/min norepinephrine-equivalents in the early and late groups, respectively (p < 0.001). The overall mortality at 28 days was 58%. After adjusting for confounding variables, the early group was less likely to die within 28 days (HR 0.76, 95% CI 0.58-0.99). The early group was also more likely to liberate from vasopressors earlier (HR 1.40, 95% CI 1.17-1.69). The early group experienced significantly more days alive and free from renal replacement therapy (10.3 vs. 1.4, p < 0.001), vasopressors (14.2 vs. 0.0, p < 0.001), and mechanical ventilation (10.0 vs. 0.5, p < 0.001) in 28 days. Adverse vasopressor-related effects, including mesenteric ischemia (0.6% vs. 2.6%, p = 0.033) and new-onset arrhythmias (30% vs. 39%, p = 0.017) were less frequent in the early group.

Conclusions: Reaching peak vasopressor dose exposure within the first six hours of septic shock onset was associated with less mortality and more days alive and free from organ-support therapies in patients with refractory septic shock. Late peak vasopressor dose exposure was associated with more adverse effects.