Impact of Balanced Crystalloids vs Saline by Resuscitation Strategy in Sepsis: A Secondary Analysis of the Crystalloid Liberal or Vasopressor Early Resuscitation in Sepsis Trial.

Summary

In this secondary analysis of a randomized sepsis resuscitation trial, 1,563 patients were classified according to predominant early crystalloid exposure and randomized fluid strategy. Balanced crystalloids were associated with lower mortality than saline or mixed fluids in the liberal-resuscitation arm, but this association was not observed with a restrictive strategy, suggesting an interaction between fluid composition and resuscitation intensity.

Key Findings

• Among 1,563 patients, 423 received predominantly balanced crystalloids, 226 received predominantly normal saline, and 914 received mixed fluids during the first 24 hours.
• The association between fluid type and mortality varied by randomized resuscitation strategy.
• In the liberal-resuscitation arm, balanced crystalloids were associated with lower mortality than normal saline or mixed fluids; this pattern was not observed in the restrictive arm.

Clinical Implications

When a liberal fluid-resuscitation strategy is selected for sepsis, balanced crystalloids may be preferable to saline based on this analysis. The findings do not establish a universal benefit across all patients or strategies and should be integrated with renal, electrolyte, acid-base, and hemodynamic considerations.

Limitations

• The type of crystalloid was not randomized, so residual confounding by clinician choice and patient characteristics may remain.
• The abstract does not provide complete effect estimates for mortality and secondary outcomes, limiting assessment of precision and absolute clinical benefit.

Future Directions

Future randomized trials should factorially evaluate crystalloid composition and resuscitation intensity, with prespecified renal, acid-base, electrolyte, and mortality outcomes.