CLINICAL QUESTION: In hospitalized patients, does IV administration of lactated Ringer’s solution (LR) reduce mortality or readmission compared to normal saline (NS)?
BACKGROUND: Crystalloid fluid administration, most often LR or NS, is one of the most common interventions performed in the inpatient setting. There has been concern regarding the chloride load associated with NS administration and increased risk of resultant hyperchloremic acidosis and acute kidney injury that is not associated with balanced fluids like LR. Previous studies have largely evaluated emergency department and intensive-care unit patients with mixed results. Recently, a systematic review and meta-analysis of almost 39,000 intensive care unit (ICU) patients showed no difference in mortality, but a Bayesian meta-analysis of almost 35,000 ICU patients concluded there is a high probability of LR being associated with lower in-hospital mortality. This study sought to compare LR to NS as the hospital-wide IV solution of choice in all patients with respect to 90-day mortality and readmission
STUDY DESIGN: Cluster-randomized crossover trial
SETTING: Seven academic and community hospitals in Ontario, Canada
SYNOPSIS: In this cluster-randomized cross-over trial, seven hospitals were randomized to either LR or NS as the hospital-wide default IV fluid. From 2016 to 2020, 43,626 patients were included (22,017 received LR, 21,609 received NS). The trial included two 15-week periods consisting of a one-week run-in, 12- week analysis, and a two-week washout. The 15-week process was repeated with the other fluid three weeks later. The primary outcome was a composite of death or readmission to the hospital within 90 days. The primary outcome was not statistically significant, with a mean incidence (averaged across seven hospitals) of 20.3%, +/-3.5%, in the LR group and 21.4%, +/-3.3%, in the NS group, with an adjusted absolute difference of –0.53% (95% CI. –1.85 to 0.79%) favoring LR. Secondary outcomes were also not statistically significant. Limitations included early termination of enrollment due to COVID-19 (originally targeted 16 hospitals and 144,000 patients for the power to detect a 1% absolute difference), limited individual-patient data, and relatively low adherence in the LR group (78.2%).
BOTTOM LINE: Hospital-wide administration of LR versus NS did not result in a significant difference in 90-day mortality or readmission to the hospital, and hospital-wide institution of a default IV crystalloid solution may not change meaningful patient outcomes.
CITATION: McIntyre L, et al. A crossover trial of hospital-wide lactated Ringer’s solution versus normal saline. N Engl J Med. 2025;393(7):660-670. doi: 10.1056/NEJMoa2416761.
Dr. Rupp
Dr. Rupp is a hospitalist at the Nebraska Medical Center and assistant professor in the department of internal medicine at the University of Nebraska Medical Center, both in Omaha, Neb.