Balanced Crystalloids versus Saline in Noncritically Ill Adults

Abstract

Background: Comparative clinical effects of balanced crystalloids and saline are uncertain, particularly in noncritically ill patients cared for outside an intensive care unit (ICU).

Methods: We conducted a single-center, pragmatic, multiple-crossover trial comparing balanced crystalloids (lactated Ringer's solution or Plasma-Lyte A) with saline among adults who were treated with intravenous crystalloids in the emergency department and were subsequently hospitalized outside an ICU. The type of crystalloid that was administered in the emergency department was assigned to each patient on the basis of calendar month, with the entire emergency department crossing over between balanced crystalloids and saline monthly during the 16-month trial. The primary outcome was hospital-free days (days alive after discharge before day 28). Secondary outcomes included major adverse kidney events 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: A total of 13,347 patients were enrolled, with a median crystalloid volume administered in the emergency department of 1079 ml and 88.3% of the patients exclusively receiving the assigned crystalloid. The number of hospital-free days did not differ between the balanced-crystalloids and saline groups (median, 25 days in each group; adjusted odds ratio with balanced crystalloids, 0.98; 95% confidence interval [CI], 0.92 to 1.04; P=0.41). Balanced crystalloids resulted in a lower incidence of major adverse kidney events within 30 days than saline (4.7% vs. 5.6%; adjusted odds ratio, 0.82; 95% CI, 0.70 to 0.95; P=0.01).

Conclusions: Among noncritically ill adults treated with intravenous fluids in the emergency department, there was no difference in hospital-free days between treatment with balanced crystalloids and treatment with saline. (Funded by the Vanderbilt Institute for Clinical and Translational Research and others; SALT-ED ClinicalTrials.gov number, NCT02614040 .).

Figure 1. Serum Electrolyte Concentrations in the First 72 Hours after Arrival in the Emergency Department (ED)

Lines and bands represent means and 95% confidence intervals, respectively. Plots were generated with the use of locally weighted scatterplot smoothing. The P values in the figure represent the overall difference between groups, calculated with the use of proportional-odds models. Over time, the separation between groups increased for chloride (P<0.001 for interaction) and bicarbonate (P<0.001 for interaction); interaction terms for the other variables were not significant. To convert the values for blood urea nitrogen to millimoles per liter, multiply by 0.357. To convert the values for creatinine to micromoles per liter, multiply by 88.4.

Figure 2. Heterogeneity of Treatment Effect

Shown are forest plots for hospital-free days to day 28, major adverse kidney events within 30 days, and acute kidney injury of stage 2 or higher according to Kidney Disease: Improving Global Outcomes creatinine criteria. The outcome of major adverse kidney events within 30 days was 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. Patients with end-stage renal disease who were receiving long-term renal-replacement therapy at the time of arrival in the emergency department (235 patients) were not eligible for the outcome of acute kidney injury; hence, the total sample size for the analysis of acute kidney injury was 13,112.