Lit Matters 3: Which crystalloid should we start with?

Normal saline can worsen hyperchloremic acidosis, renal vasoconstriction, and acute kidney injury in sepsis-induced hypotension. In early sepsis resuscitation, balanced crystalloids—especially lactated Ringer's—continue to outperform 0.9% saline on clinically meaningful outcomes, with survival curves separating early.

Initial Crystalloid Choice in Sepsis

• Balanced fluid rationale: Sepsis physiology is vulnerable to chloride load, and 0.9% saline is linked to hyperchloremic metabolic acidosis and renal vasoconstriction rather than any clear early resuscitation advantage.
• CLOVERS secondary analysis: This comparison draws from randomized CLOVERS data, asking whether the first crystalloid chosen for sepsis-induced hypotension changes outcomes even before longer ICU fluid exposure accumulates.
• Mortality signal: Lactated Ringer's was associated with lower 90-day in-hospital mortality than normal saline, with deaths in 12.2% versus 15.9% and an adjusted hazard ratio of 0.71.
• Early curve separation: The Kaplan-Meier curves split early, supporting the idea that initial fluid choice itself may matter acutely in sepsis rather than only after large cumulative volumes. We get into why that early divergence matters in the episode.
• Secondary outcome pattern: Hospital-free days favored lactated Ringer's, while acute kidney injury also trended lower at 7 days, reinforcing the broader direction of benefit even where significance was not reached.