Early Goal-Directed Therapy for Sepsis: A Novel Solution for Discordant Survival Outcomes in Clinical Trials.

Objectives: Early goal-directed therapy has shown discordant survival outcomes in sepsis studies. We aim to find the reasons for this discordance. Design: Random-effects and Bayesian hierarchical analyses. Setting: Studies that evaluated early goal-directed therapy. Subjects: Patients with severe sepsis and/or septic shock. Interventions: Early goal-directed therapy. Measurements and Main Results: A total of 19,998 patients were included in the main analysis: 31 observational (n = 15,656) and six randomized (n = 4,342) studies. The analysis from 37 studies showed that early goal-directed therapy was associated with a 23% reduction in the risk of death: relative risk = 0.77 (95% CI, 0.71-0.83); p value of less than 0.0001. Mortality reduction was seen with observational studies: relative risk = 0.73 (0.67-0.80); p value of less than 0.0001 but not with randomized studies: relative risk = 0.92 (0.78-1.07); p = 0.268. Meta-regression analysis showed lower risk of death in observational compared with randomized studies: relative risk = 0.81 (0.68-0.95); p = 0.01. Differences in age, country, hospital location, era, systolic pressure, mean arterial pressure, lactate, bundle compliance, amount of fluid administered, and hemodynamic goal achievements were not associated with survival differences between studies. Factors associated with mortality differences between early goal-directed therapy and control included Acute Physiology and Chronic Health Evaluation II (relative risk = 1.05 [1.02-1.09]; p = 0.003), Sequential Organ Failure Assessment (relative risk = 1.09 [1.00-1.18]; p = 0.04), presence of shock (relative risk = 1.007 [1.002-1.013]; p = 0.006), time-to-first antibiotic (relative risk = 1.22 [1.09-1.36]; p = 0.0006), antibiotic administration within 6 hours (relative risk = 0.20 [0.09-0.45]; p = 0.0001), 4 hours (relative risk = 0.16 [0.06-0.39]; p = 0.0001), and 3 hours (relative risk = 0.09 [0.03-0.27]; p

from Emergency Medicine via xlomafota13 on Inoreader http://ift.tt/2iW2YVk