Effect of Treatment With Balanced Crystalloids Versus Normal Saline on the Mortality of Critically Ill Patients With and Without Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Summary

Across 15 trials (n=35,207), balanced crystalloids reduced mortality versus saline in critically ill patients without TBI (OR 0.93) but increased mortality in those with TBI (OR 1.31), with minimal heterogeneity. In sepsis, balanced fluids showed a non-significant trend to lower mortality (OR 0.92). These data highlight illness-specific effects of fluid composition.

Key Findings

• In non-TBI critical illness, balanced crystalloids lowered mortality vs saline (OR 0.93; 95% CI 0.87–0.98; I2=0%).
• In TBI, balanced crystalloids increased mortality vs saline (OR 1.31; 95% CI 1.03–1.65; I2=0%).
• No consistent differences in secondary outcomes (e.g., renal complications, ICU therapies); data sparse for some TBI outcomes.
• In sepsis patients, balanced crystalloids showed a trend toward lower mortality (OR 0.92; 95% CI 0.83–1.02; I2=0%).

Clinical Implications

Avoid balanced crystalloids in TBI resuscitation and consider their preferential use in non-TBI critical illness, including sepsis, while awaiting more definitive sepsis-specific trials.

Limitations

• Some secondary outcomes in TBI lacked sufficient data for pooling
• Trial-level heterogeneity in fluid protocols and co-interventions may persist

Future Directions

Conduct sepsis-specific RCTs comparing balanced crystalloids and saline with predefined subgroups (e.g., hyperchloremia risk, AKI) and mechanistic endpoints; refine TBI-specific fluid guidelines.