BACKGROUND:: Both balanced crystalloids and saline are used for intravenous fluid administration among critically ill adults. Which results in better clinical outcomes remains unknown.

METHODS:: In a pragmatic, cluster-randomized, multiple-crossover trial in five intensive care units at an academic center, we assigned 15,802 adults to receive saline (0.9% sodium chloride) or balanced crystalloids (lactated Ringer’s solution or Plasma-Lyte A®), according to the randomization of the unit to which they were admitted. The primary outcome was Major Adverse Kidney Events within 30 days (MAKE30), i.e., the composite of death, new renal replacement therapy, or persistent creatinine elevation ≥ 200% of baseline – all censored at the first of hospital discharge or 30 days.

RESULTS:: In the balanced crystalloid group, 1,139 patients (14.3%) experienced MAKE30, compared to 1,211 patients (15.4%) in the saline group (marginal odds ratio, 0.91; 95% confidence interval, 0.84–0.99; conditional odds ratio, 0.90; 95% confidence interval, 0.82–0.99; P=0.04). Thirty-day in-hospital mortality was 10.3% in the balanced crystalloid group and 11.1% in the saline group (P=0.06). The incidence of new renal replacement therapy was 2.5% and 2.9% respectively (P=0.08), and the incidence of persistent creatinine elevation was 6.4% and 6.6% respectively (P=0.60).

CONCLUSIONS:: Among critically ill adults, the use of balanced crystalloids for intravenous fluid administration appeared to reduce the composite outcome of in-hospital mortality, new renal replacement therapy, and persistent renal dysfunction compared with the use of saline. (SMART-MED and SMART-SURG ClinicalTrials.gov numbers, NCT02444988 and NCT02547779.)