Critical Care, Critical Care Alert

Critical Care Alert: Balanced Crystalloids vs. Saline in Critically Ill Adults (the SMART Trial)

Critical Care Alert

Semler MW, Self WH, Wanderer JP, et al, for the SMART Investigators and the Pragmatic Critical Care Research Group. Balanced Crystalloids versus Saline in Critically Ill AdultsN Engl J Med. 2018;378(9):829-839.

IV crystalloid solutions are commonly administered to critically ill patients. Normal saline (0.9% sodium chloride) is the most commonly administered IV fluid. However, many observational studies and experimental modes have suggested that normal saline administration might be associated with hyperchloremic metabolic acidosis, AKI, and death. This study investigated whether the administration of balance crystalloids, compared with saline, reduced a 30-day composite outcome of death, new renal replacement therapy, or persistent renal dysfunction.   


  • Pragmatic, non-blinded, cluster-randomized, multiple-crossover study
  • 15,802 patients randomized in 5 ICUs at a single academic center
  • Inclusion Criteria
    • Adults 18 years of age and older
    • Admission to 1 of 5 participating ICUs during trial period
    • Exclusion Criteria
      • Age < 18 years
      • Relative contraindications to balanced crystalloids: hyperkalemia and brain injury – administration by physician discretion
      • Randomization
        • All patients admitted to 1 of 5 ICUs at one academic center were assigned to received saline (0.9% sodium chloride) or balanced crystalloids (lactated Ringers solution or Plasma-Lyte A)  
        • ICUs were randomly assigned to use saline during and balanced crystalloids, alternatingly from month to month
        • The trial was coordinated with the emergency department and the operating rooms


  • 15,802 patients from 5 ICUs – 7,942 received balanced crystalloids; 7,860 received normal saline – with no significant differences in baseline characteristics between the two groups
  • Median Age: 58 years
  • Gender: 57.6% male


  • Primary
    • Major adverse kidney event in 30 days (MAKE-30)
      A composite of death from any cause, new renal-replacement therapy, or persistent renal dysfunction (elevation in sCr to ≥ 200% of baseline). These were censored at 30 days or hospital discharge, whichever occurred first.
    • Secondary
      • Clinical outcomes
        In-hospital death before ICU discharge or at 30 days or at 60 days; ICU free days; ventilator-free days; vasopressor-free days; days alive and free of renal-replacement therapy during the 28 days after enrollment
      • Renal outcomes
        New real-replacement therapy; persistent renal dysfunction; acute kidney injury stage 2 or higher; highest creatinine level during hospital stay; change from baseline to the highest creatinine level; final creatinine level before hospital discharge


  • Primary Outcome
    • Major adverse kidney event in 30 days (MAKE-30)
      14.3% in balanced crystalloid group vs. 15.4% saline group (P=0.04)
      The difference is more pronounced among patients receiving larger volumes of crystalloids and among patients with sepsis
    • Secondary Outcomes
      • In-hospital mortality at 30 days: 10.3% in balanced-crystalloid group vs. 11.1% in saline group (P=0.06)
      • Incidence of new renal-replacement therapy: 2.5% in balanced-crystalloid group vs. 2.9% in saline group (P=0.08)
      • Incidence of persistent renal dysfunction: 6.4% in balanced crystalloid group compared to 6.6% in normal saline group (P=0.60)

The study concludes that among critically ill adults, the use of balanced crystalloids resulted in a lower rate of composite outcome of death from any cause, new renal-replacement therapy, or persistent renal dysfunction with a NNT of 94. Given that the study was conducted at a single academic center, the generalizability of the findings might be limited. Furthermore, the treating physicians were unblinded, which may lead to conscious and unconscious biases. It is important to note that the patients in the study received relatively small volumes of fluid (median 1000 mL for balanced crystalloids group, 1020 mL for the saline group). As stated in the study, the difference in primary outcome was more prominent in the analysis of subgroup who received larger volume of fluid. The use of balanced crystalloids might be safer compared to saline in resuscitating critically ill patients who require massive amount of fluid resuscitation.

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