IV Fluids
Aiya Almogaber, PharmD
A large crossover trial evaluating hospital-wide use of lactated Ringer’s solution versus normal saline found no significant difference in patient outcomes. Published June 12, 2025, in NEJM, the FLUID trial adds to growing evidence suggesting that while balanced crystalloids may offer theoretical advantages, they may not significantly impact clinical outcomes across general hospitalized populations.
The findings come at a time when institutions are reassessing resuscitation strategies in light of previous studies linking high-chloride fluids like saline to kidney injury and acidosis. The results seem to reinforce a need for a more individualized approach rather than sweeping system-wide changes.
Findings suggest that both lactated Ringer’s and normal saline remain reasonable options, with no compelling reason to favor one over the other for most patients. Differences in chloride content and acid-base effects may still influence bedside choices, especially in patients with kidney disease or metabolic acidosis.
The trial
Unlike prior fluid studies that have targeted specific patient groups, FLUID—a cluster-randomized, open-label crossover study—evaluated crystalloid use across entire hospitals. Assigned fluids made up at least 80% of each site’s crystalloid inventory during the study period.
The trial included seven academic and community hospitals in Ontario, Canada. Each hospital used either lactated Ringer’s solution or normal saline for a 12-week period, followed by a washout and crossover to the alternate fluid.
Researchers analyzed outcomes for 43,626 eligible patients. The primary outcome, a composite of death or hospital readmission within 90 days, occurred in 20.3% of the lactated Ringer’s group and 21.4% of the normal saline group. The adjusted absolute difference was not statistically significant.
Secondary outcomes, including mortality, dialysis initiation, emergency department visits, and discharge to a facility also showed no meaningful differences.
While clinicians could override default fluid orders when necessary, most patients were expected to receive the assigned fluid throughout their hospitalization.
Hospital adherence was 78.2% for lactated Ringer’s and 93.6% for normal saline. No serious adverse events related to either fluid were reported. The trial was originally designed to include 16 hospitals but was halted early due to the COVID-19 pandemic. Investigators acknowledged that the reduced sample may have limited the ability to detect small—but potentially meaningful—differences in outcomes.
Subgroups analyses
Although previous studies and meta-analyses have indicated possible benefits of balanced fluids in critical care settings, the FLUID trial did not demonstrate an advantage in subgroups, such as with patients admitted to the ICU, those with infection, or those undergoing surgery.
The findings are consistent with the overall population-level results.
Notably, earlier single-center and emergency department studies suggested that balanced fluids might reduce AKI or major adverse kidney events. However, translating those benefits to hospital-wide policy appears less certain when applied across diverse patient groups.
Further research may help clarify whether specific high-risk populations—such as those with sepsis or traumatic brain injury—derive greater benefit from balanced solutions. Until then, hospital-wide replacement of saline with lactated Ringer’s is unlikely to offer broad advantages. ■