BaSICS: Balanced Solution vs. Saline in Critically Ill Patients (2021)

“Among critically ill patients, the use of a balanced solution, as compared with saline, did not reduce the risk of death at 90 days. The rate of infusion of crystalloids also had no effect on 90-day mortality.”

  • The BaSICS investigators and the BRICNet

1. Publication Details

  • Trial Title: Balanced Crystalloids versus Saline in Critically Ill Patients
  • Citation: Zampieri FG, Machado FR, Biondi RS, et al. Effect of Intravenous Fluid Treatment With a Balanced Solution vs 0.9% Saline Solution on 90-Day Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial. JAMA. 2021;326(9):1-12. DOI: 10.1001/jama.2021.11684
  • Published: August 10, 2021, in The Journal of the American Medical Association (JAMA)
  • Author: Fernando G. Zampieri, M.D., Ph.D.
  • Funding: Brazilian Ministry of Health

2. Keywords

  • Critical Care, Fluid Resuscitation, Balanced Crystalloids, Saline, Sepsis, Randomized Controlled Trial

3. The Clinical Question

  • In a broad population of critically ill adult patients (Population), does the use of a balanced crystalloid solution (Intervention) compared to 0.9% saline (Comparison) reduce 90-day all-cause mortality (Outcome)? A second question was whether a slower infusion rate was superior to a faster one.

4. Background and Rationale

  • Existing Knowledge: The choice of crystalloid fluid for resuscitation was a major clinical debate. 0.9% saline, while widely used, has a high chloride content that can cause hyperchloremic metabolic acidosis and potentially lead to acute kidney injury. Balanced solutions like Plasma-Lyte have a more physiologic composition. The SMART trial (2018) had suggested a benefit for balanced solutions, but other studies were neutral, and further high-quality evidence was needed.
  • Knowledge Gap: A large, pragmatic trial was needed to provide a more definitive answer on whether the choice of crystalloid (balanced vs. saline) or the speed of its administration affects survival in a general ICU population.
  • Proposed Hypothesis: The authors hypothesized that the use of a balanced solution would be superior to saline in reducing 90-day mortality.

5. Study Design and Methods

  • Design: A multicenter, pragmatic, 2×2 factorial, randomized controlled trial (used to test the effectiveness of interventions).
  • Setting: 75 intensive care units (ICUs) in Brazil.
  • Trial Period: Enrollment ran from May 2017 to March 2020.
  • Population:
    • Inclusion Criteria: Adult patients (≥18 years) admitted to the ICU who required at least one fluid bolus for expansion.
    • Exclusion Criteria: Included patients with traumatic brain injury (where saline is often preferred) or those with an immediate life-threatening electrolyte abnormality.
  • Intervention: Patients were randomized in a factorial design to two interventions:
  • Fluid Type: Balanced solution (Plasma-Lyte 148) vs. 0.9% saline.
  • Infusion Rate: Slower rate (333 mL/h) vs. Faster rate (999 mL/h).
  • Control: The control groups were 0.9% saline and the faster infusion rate, respectively.
  • Management Common to Both Groups: The assigned study fluid was used for all subsequent fluid needs (resuscitation, maintenance, and dilution). All other aspects of ICU care were at the discretion of the treating clinicians.
  • Power and Sample Size: The authors calculated that a sample size of 11,000 patients would provide 90% power to detect a 2.5% absolute risk reduction in 90-day mortality. (Power is a study’s ability to find a real difference between treatments if one truly exists; 90% power means the study had a 90% chance of detecting the specified effect, which is considered very high).
  • Outcomes:
    • Primary Outcome: All-cause mortality at 90 days.
    • Secondary Outcomes: Included the need for renal-replacement therapy (RRT), SOFA scores at day 7, and ventilator-free days.

6. Key Results

  • Enrollment and Baseline: 10,520 patients were randomized and included in the primary analysis. The groups were well-matched at baseline.
  • Trial Status: The trial was completed as planned.
  • Primary Outcome: There was no significant difference in 90-day mortality between the fluid type groups. 1399 of 5282 patients (26.5%) in the balanced-solution group died, compared with 1422 of 5238 patients (27.2%) in the saline group (p=0.47). There was also no difference in mortality based on infusion speed.
  • Secondary Outcomes: There were no significant differences between the groups in the need for RRT or in SOFA scores at day 7.
  • Adverse Events: The incidence of serious adverse events was similar in both groups.

7. Medical Statistics

  • Analysis Principle: The trial was analyzed using an intention-to-treat principle.
  • Statistical Tests Used: The primary outcome was analyzed using a Cox proportional-hazards model.
  • Primary Outcome Analysis: The primary outcome was a time-to-event analysis of 90-day mortality.
  • Key Statistic(s) Reported: Adjusted Hazard Ratio (HR) for death at 90 days for balanced solution vs. saline: 0.97 (95% CI, 0.90 to 1.05; P-value: 0.47).
  • Interpretation of Key Statistic(s):
    • Hazard Ratio (HR):
      • Formula: Conceptually, HR = (Hazard Rate in Intervention Group) / (Hazard Rate in Control Group).
      • Calculation: The paper reports the adjusted result as 0.97.
      • Clinical Meaning: An HR of 0.97 suggests a non-significant 3% lower risk of death at any given time point in the balanced-solution group.
    • Confidence Interval (CI):
      • Formula: Conceptually, CI = (Point Estimate) ± (Margin of Error).
      • Calculation: The 95% CI was 0.90 to 1.05.
      • Clinical Meaning: Since this range crosses the line of no effect (1.0), it confirms that the result is not statistically significant. Clinically, this means the true effect could range from a 10% benefit to a 5% harm.
    • P-value: The p-value of 0.47 is much higher than the 0.05 threshold, indicating the result is not statistically significant and very likely due to chance (a result is conventionally considered statistically significant if the p-value is less than 0.05).
  • Clinical Impact Measures: As the trial was neutral, ARR and NNT are not applicable.
  • Subgroup Analyses: In a pre-specified subgroup analysis of patients with sepsis, there was a suggestion of benefit with balanced solutions, but this was not statistically significant after adjustment for multiple comparisons.

8. Strengths of the Study

  • Study Design and Conduct: The very large, multicenter, pragmatic, factorial randomized design provided high-quality evidence on two important questions simultaneously.
  • Generalizability: The pragmatic design and inclusion of 75 diverse ICUs make the findings highly generalizable to a broad population of critically ill patients in similar settings.
  • Statistical Power: The study was very large and adequately powered to confidently rule out a small but clinically important mortality benefit.
  • Patient-Centered Outcomes: The primary outcome of 90-day mortality is a robust and patient-centered endpoint.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The study was open-label (unblinded), which introduces a risk of performance bias.
  • External Validity (Generalizability): The study was conducted exclusively in Brazil, and the results may not be fully generalizable to healthcare systems with different resources or patient populations.
  • Other: The median volume of fluid administered was relatively low (around 1.5L in the first 24 hours), which may have been insufficient to show a difference between the fluid types.

10. Conclusion of the Authors

  • Among critically ill patients, the use of a balanced solution did not reduce 90-day mortality compared with saline. The rate of fluid infusion also had no effect on mortality.

11. To Summarize

  • Impact on Current Practice: This large, high-quality trial provides strong evidence that in a general ICU population, there is no significant survival difference between using a balanced crystalloid and 0.9% saline.
  • Specific Recommendations:
    • Patient Selection: For a broad population of adult ICU patients requiring fluid resuscitation.
    • Actionable Intervention: The results suggest that either balanced crystalloids or saline are acceptable choices for fluid therapy, and there is no evidence to support a slower infusion rate over a faster one.
  • What This Trial Does NOT Mean: This trial does NOT mean that saline is harmless. The potential for hyperchloremic acidosis and kidney injury with large volumes of saline is still a valid concern, even if it did not translate to a mortality difference in this trial.
  • Implementation Caveats: While the choice of fluid may not affect mortality in a general population, a balanced solution may still be preferred in patients at high risk for acidosis or kidney injury.

12. Context and Related Studies

  • Building on Previous Evidence: The BaSICS trial (2021) was designed to provide a more definitive answer to the question raised by the SMART trial (2018), which had suggested a benefit for balanced solutions.
  • Influence on Subsequent Research: The neutral findings of BaSICS, along with the concurrent PLUS trial (2022) which also found no difference, have largely settled the “crystalloid wars.” They suggest that while there may be small physiological differences, the choice between balanced solutions and saline does not appear to have a major impact on survival for most ICU patients.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: The key unresolved question is whether there are specific subgroups of patients (e.g., those with severe sepsis or traumatic brain injury) who might still benefit from one type of crystalloid over another.
  • Future Directions: Future research is focused on more nuanced questions, such as the optimal volume and timing of fluid administration, rather than just the type of fluid.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The research question was highly relevant, addressing a very common and fundamental aspect of ICU care.
  • Methods: The large, multicenter, factorial RCT design was a major strength, allowing two questions to be answered efficiently. The main methodological weakness is the open-label design.
  • Results: The study reported a clear neutral finding for its primary outcome, with a confidence interval that was narrow and centered on the null value, providing strong evidence against a meaningful clinical benefit of balanced solutions in this population.
  • Conclusions and Applicability: The authors’ conclusion is a direct and fair reflection of the data. The high external validity of this pragmatic trial means its findings are broadly applicable. This trial, along with PLUS, provides strong evidence that for the majority of ICU patients, the choice between balanced crystalloids and saline is unlikely to have a major impact on patient-centered outcomes.

16. Disclaimer and Contact

  • This summary is provided by the Academic Committee of ESBICM (ACE) to facilitate the understanding of this study; readers are advised to refer to the original trial document for a deeper understanding. If you find any information incorrect, or missing, or it needs an update or have a request for a specific critical care trial summary, kindly write to us at academics[at]esbicm.org.
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