The Effect of Fluid Resuscitation Timing in Early Sepsis Resuscitation

Purpose The dose and timing of early fluid resuscitation in sepsis remains a debated topic. The objective of this study is to evaluate the effect of fluid timing in early sepsis management on mortality and other clinical outcomes. Methods Single-center, retrospective cohort study of emergency-department-treated adults (>18 years, n = 1032) presenting with severe sepsis or septic shock. Logistic regression evaluating the impact of 30 mL/kg crystalloids timing and mortality-versus-time plot controlling for mortality in emergency department sepsis score, lactate, antibiotic timing, obesity, sex, systemic inflammatory response syndrome criteria, hypotension, and heart and renal failures. This study is a subanalysis of a previously published investigation. Results Mortality was 17.1% (n = 176) overall and 20.4% (n = 133 of 653) among those in septic shock. 30 mL/kg was given to 16.9%, 32.2%, 16.2%, 14.5%, and 20.3% of patients within ≤1, 1 ≤ 3, 3 ≤ 6, 6 ≤ 24, and not reached within 24 h, respectively. A 24-h plot of adjusted mortality versus time did not reach significance, but within the first 12 h, the linear function showed a per-hour mortality increase (odds ratio [OR] 1.29, 95% confidence interval [CI] 1.02-1.67) which peaks around 5h, although the quadratic function does not reach significance ( P = .09). When compared to patients receiving 30 mL/kg within 1 h, increased mortality was observed when not reached within 24 h (OR 2.69, 95% CI 1.37-5.37) but no difference when receiving this volume between 1 and 3 (OR 1.11, 95% CI 0.62-2.01), 3 and 6 (OR 1.83, 95% CI 0.97-3.52), or 6 and 24 h (OR 1.51, 95% CI 0.75-3.06). Receiving 30 mL/kg between 1 and 3 versus <1 h increased the incidence of delayed hypotension (OR 1.83, 95% CI 1.23-2.72) but did not impact need for intubation, intensive care unit admission, or vasopressors. Conclusions We observed weak evidence that supports that earlier is better for survival when reaching fluid goals of 30 mL/kg, but benefits may wane at later time points. These findings should be viewed as hypothesis generating.