Effect of Intravenous Fluid Treatment With a Balanced Solution vs 0.9% Saline Solution on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial

Abstract

Importance: Intravenous fluids are used for almost all intensive care unit (ICU) patients. Clinical and laboratory studies have questioned whether specific fluid types result in improved outcomes, including mortality and acute kidney injury.

Objective: To determine the effect of a balanced solution vs saline solution (0.9% sodium chloride) on 90-day survival in critically ill patients.

Design, setting, and participants: Double-blind, factorial, randomized clinical trial conducted at 75 ICUs in Brazil. Patients who were admitted to the ICU with at least 1 risk factor for worse outcomes, who required at least 1 fluid expansion, and who were expected to remain in the ICU for more than 24 hours were randomized between May 29, 2017, and March 2, 2020; follow-up concluded on October 29, 2020. Patients were randomized to 2 different fluid types (a balanced solution vs saline solution reported in this article) and 2 different infusion rates (reported separately).

Interventions: Patients were randomly assigned 1:1 to receive either a balanced solution (n = 5522) or 0.9% saline solution (n = 5530) for all intravenous fluids.

Main outcomes and measures: The primary outcome was 90-day survival.

Results: Among 11 052 patients who were randomized, 10 520 (95.2%) were available for the analysis (mean age, 61.1 [SD, 17] years; 44.2% were women). There was no significant interaction between the 2 interventions (fluid type and infusion speed; P = .98). Planned surgical admissions represented 48.4% of all patients. Of all the patients, 60.6% had hypotension or vasopressor use and 44.3% required mechanical ventilation at enrollment. Patients in both groups received a median of 1.5 L of fluid during the first day after enrollment. By day 90, 1381 of 5230 patients (26.4%) assigned to a balanced solution died vs 1439 of 5290 patients (27.2%) assigned to saline solution (adjusted hazard ratio, 0.97 [95% CI, 0.90-1.05]; P = .47). There were no unexpected treatment-related severe adverse events in either group.

Conclusion and relevance: Among critically ill patients requiring fluid challenges, use of a balanced solution compared with 0.9% saline solution did not significantly reduce 90-day mortality. The findings do not support the use of this balanced solution.

Trial registration: ClinicalTrials.gov Identifier: NCT02875873.

Figure 1.. Flow of Patients in the Trial Comparing a Balanced Solution vs Saline Solution (0.9% Sodium Chloride)

^aThere was no screening log; therefore, the number of patients assessed for eligibility cannot be presented. ^bData for the primary outcome were imputed.

Figure 2.. Volume of Infused Fluids at Days 1, 2, 3, and 7 and Boxplot of Serum Chloride Levels

A, The y-axis represents the total volume of infused fluids given on each day. Open crystalloids refer to open label (nonstudy fluid) use. The proportion of each fluid for each day is shown inside the bars. B, Data are expressed as the median serum chloride levels, first and third quartiles (boxes), and range (lines) at baseline and days 1, 2, 3, and 7 for both groups. Saline solution is 0.9% sodium chloride.

Figure 3.. Cumulative Incidence of the Primary Outcome of 90-Day Survival for a Balanced Solution vs Saline Solution (0.9% Sodium Chloride)

The median follow-up was 90 days (interquartile range, 59.2-90.0 days) for the balanced solution group and 90 days (interquartile range, 54-90 days) for the saline solution group.

Figure 4.. Forest Plot for the Primary Outcome of 90-Day Survival in the Prespecified Subgroup Analyses

^aThe denominators do not match the data presented in Table 1 because the data in this figure were imputed. Additional details appear in the statistical analysis plan in Supplement 2. ^bSaline solution is 0.9% sodium chloride. ^cKDIGO indicates Kidney Disease: Improving Global Outcomes. Stage 1 is defined by an increase in serum creatinine level by 0.3 mg/dL or greater within 48 hours or an increase in serum creatinine level to 1.5 times or greater than baseline, which is known or presumed to have occurred within the prior 7 days, or a urine output of less than 0.5 mL/kg/h for 6 hours. Stage 2 is defined by an increase in serum creatinine level of 2.0 to 2.9 times baseline or a urine output of less than 0.5 mL/kg/h for 12 hours or longer. Stage 3 is defined by an increase in serum creatinine level 3.0 times or greater than baseline or to 4.0 mg/dL or greater, initiation of kidney replacement therapy, or a urine output of less than 0.3 mL/kg/h for 24 hours or longer or anuria for 12 hours or longer. To convert creatinine to μmol/L, multiply by 88.4. ^dAPACHE II indicates the Acute Physiology and Chronic Health Evaluation II. APACHE II scores can range from 0 to 71; a higher value indicates greater illness severity.