Lactated Ringer's or Normal Saline for Initial Fluid Resuscitation in Sepsis-Induced Hypotension.

Summary

In this secondary analysis of CLOVERS (n=1,563), initial resuscitation with lactated Ringer’s was associated with lower 90-day mortality (adjusted HR 0.71) and more hospital-free days versus 0.9% saline. Normal saline was linked to hyperchloremia and lower bicarbonate.

Key Findings

• Among 1,563 CLOVERS participants with sepsis-induced hypotension, lactated Ringer’s was associated with lower 90-day mortality (12.2% vs 15.9%; adjusted HR 0.71, 95% CI 0.51–0.99; p=0.043).
• Lactated Ringer’s recipients had more 28-day hospital-free days (adjusted mean difference 1.6 days; p=0.009).
• Normal saline was associated with higher serum chloride and lower bicarbonate levels, consistent with hyperchloremic acidosis.

Clinical Implications

Prefer balanced crystalloids (e.g., lactated Ringer’s) for initial fluid bolus in sepsis-induced hypotension; avoid large saline loads given metabolic effects and potential mortality signal.

Limitations

• Non-randomized allocation of the initial fluid type introduces potential confounding despite adjustment
• Secondary analysis; findings hypothesis-generating and limited to U.S. centers

Future Directions

Prospective randomized comparisons of balanced crystalloids versus saline specifically at the earliest resuscitation step; mechanistic studies on chloride load and organ dysfunction.