Time to vasopressor initiation and organ failure progression in early septic shock

Objective: Research evaluating the relationship between vasopressor initiation timing and clinical outcomes is limited and conflicting. We investigated the association between time to vasopressors, worsening organ failure, and mortality in patients with septic shock. Methods: This was a retrospective study of patients with septic shock (2013–2016) within 24 hours of emergency department (ED) presentation. The primary outcome was worsening organ failure, defined as an increase in Sequential Organ Failure Assessment (SOFA) score ≥2 at 48 hours compared to baseline, or death within 48 hours. The secondary outcome was 28-day mortality. Time to vasopressor initiation was categorized into 6, 4-hour intervals from time of ED triage. Multiple logistic regression was used to identify predictors of worsening organ failure. Results: We analyzed data from 428 patients with septic shock. There were 152 patients with the composite primary outcome (SOFA increase ≥2 or death at 48 hours). Of these, 77 patients died in the first 48 hours and 75 patients had a SOFA increase ≥2. Compared to the patients who received vasopressors in the first 4 hours, those with the longest time to vasopressors (20–24 hours) had increased odds of developing worsening organ failure (odds ratios [OR] = 4.34, 95% confidence intervals [CI] = 1.47–12.79, P = 0.008). For all others, the association between vasopressor timing and worsening organ failure was non-significant. There was no association between time to vasopressor initiation and 28-day mortality. Conclusions: Increased time to vasopressor initiation is an independent predictor of worsening organ failure for patients with vasopressor initiation delays >20 hours.