Effect of Early Balanced Crystalloids Before ICU Admission on Sepsis Outcomes

Chest. 2021 Feb;159(2):585-595. doi: 10.1016/j.chest.2020.08.2068. Epub 2020 Aug 31.


Background: Studies suggest that using balanced crystalloids (lactated Ringer's solution or Plasma-Lyte A) rather than saline (0.9% sodium chloride) may improve outcomes for patients with sepsis in the ED and ICU.

Research question: What is the relative impact on sepsis outcomes of fluid composition during early resuscitation in the ED vs after ICU admission?

Study design and methods: We performed a secondary analysis of the Isotonic Solutions and Major Adverse Renal Events Trial (SMART) data set, examining medical ICU patients with a diagnosis of sepsis (n = 1,641). SMART was a cluster-crossover trial comparing balanced crystalloids vs saline among critically ill adults. During the first 7 months of SMART, fluid choice was controlled only in the ICU ("ICU-only period"). In the final 15 months, fluid choice was coordinated between the ED and ICU ("ED and ICU period"). We performed logistic regression modeling for 30-day in-hospital mortality with an interaction term between randomized group (balanced crystalloids vs saline) and study period (ICU-only period vs ED and ICU period).

Results: Three hundred and sixty-seven patients with sepsis were enrolled during the ICU-only period and 1,274 were enrolled during the ED and ICU period. Thirty-day in-hospital mortality occurred in 47 of 142 patients (33.1%) in the balanced crystalloid group vs 74 of 225 patients (32.9%) in the saline group during the ICU-only period (OR, 1.14; 95% CI, 0.70-1.88) and in 170 of 682 patients (24.9%) in the balanced crystalloid group vs 181 of 592 patients (30.6%) in the saline group in the ED and ICU period (OR, 0.68; 95% CI, 0.52-0.89) (P value for interaction, .07), consistent with a beneficial effect of balanced crystalloid primarily in the ED and ICU period.

Interpretation: Among patients with sepsis, the effect of balanced crystalloids vs saline on mortality was greater among patients for whom fluid choice was controlled starting in the ED compared with starting in the ICU.

Keywords: balanced crystalloids; critical care; sepsis.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Critical Illness*
  • Cross-Over Studies
  • Crystalloid Solutions / administration & dosage*
  • Emergency Service, Hospital
  • Female
  • Fluid Therapy / methods*
  • Hospital Mortality
  • Hospitalization
  • Humans
  • Intensive Care Units
  • Male
  • Middle Aged
  • Sepsis / mortality
  • Sepsis / therapy*


  • Crystalloid Solutions