Balanced Crystalloids versus Saline in Critically Ill Adults

Abstract

Background: Both balanced crystalloids and saline are used for intravenous fluid administration in critically ill adults, but it is not known which results in better clinical outcomes.

Methods: In a pragmatic, cluster-randomized, multiple-crossover trial conducted 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 a major adverse kidney event within 30 days - a composite of death from any cause, new renal-replacement therapy, or persistent renal dysfunction (defined as an elevation of the creatinine level to ≥200% of baseline) - all censored at hospital discharge or 30 days, whichever occurred first.

Results: Among the 7942 patients in the balanced-crystalloids group, 1139 (14.3%) had a major adverse kidney event, as compared with 1211 of 7860 patients (15.4%) in the saline group (marginal odds ratio, 0.91; 95% confidence interval [CI], 0.84 to 0.99; conditional odds ratio, 0.90; 95% CI, 0.82 to 0.99; P=0.04). In-hospital mortality at 30 days was 10.3% in the balanced-crystalloids 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 renal dysfunction was 6.4% and 6.6%, respectively (P=0.60).

Conclusions: Among critically ill adults, the use of balanced crystalloids for intravenous fluid administration resulted in a lower rate of the composite outcome of death from any cause, new renal-replacement therapy, or persistent renal dysfunction than the use of saline. (Funded by the Vanderbilt Institute for Clinical and Translational Research and others; SMART-MED and SMART-SURG ClinicalTrials.gov numbers, NCT02444988 and NCT02547779 .).

Figure 1. Volume of Intravenous Isotonic Crystalloid Administered According to Group

The cumulative volume of intravenous balanced crystalloids (solid line) and 0.9% sodium chloride (dotted line) between admission to the intensive care unit (ICU) and hospital discharge is shown for patients in the balanced-crystalloids group (Panel A) and the saline group (Panel B). I bars indicate 95% confidence intervals.

Figure 2. Plasma Chloride and Bicarbonate Concentration According to Group

The mean and 95% confidence interval (denoted by gray shading) for the first measurement of plasma chloride concentration (Panel A) or bicarbonate concentration (Panel B) on the first 7 days since admission to the intensive care unit (ICU) are shown for patients in the balanced-crystalloids group and in the saline group with locally weighted scatterplot smoothing. Plasma chloride and bicarbonate concentrations were similar between groups at presentation (Table S3 in the Supplementary Appendix), but because fluid therapy in the emergency department and operating room was coordinated with the ICU to which patients were being admitted, plasma chloride concentration differed between the balanced-crystalloids and saline groups at the time of ICU admission.

Figure 3. Subgroup Analysis of Rates for the Composite Outcome of Death, New Receipt of Renal-Replacement Therapy, or Persistent Renal Dysfunction

The odds ratio and 95% confidence interval are shown overall and according to subgroup for the percentage of patients in the balanced-crystalloids group and the saline group who met the criteria for the composite outcome of death from any cause, new renal-replacement therapy, or persistent renal dysfunction. Normal kidney function refers to patients who had no acute kidney injury, chronic kidney disease, or renal-replacement therapy before enrollment. Acute kidney injury refers to patients without chronic kidney disease whose first creatinine level after enrollment was at least 200% of the baseline value or was both greater than 4.0 mg per deciliter (350 μmol per liter) and had increased at least 0.3 mg per deciliter (27 μmol per liter) from the value at baseline. Chronic kidney disease refers to patients with a glomerular filtration rate less than 60 ml per minute per 1.73 m² as calculated according to the Chronic Kidney Disease Epidemiology Collaboration equation with the value for the patient’s baseline creatinine level. Previous renal-replacement therapy refers to patients known to have received any form of renal-replacement therapy before enrollment.