OBJECTIVES: To assess whether initial fluid resuscitation with lactated Ringer's solution compared with 0.9% saline is associated with improved clinical outcomes in patients with sepsis-induced hypotension. DESIGN: Secondary analysis of the randomized controlled Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) trial. SETTING: ICUs and emergency departments in 60 U.S. centers from March 2018 to January 2022. PATIENTS: Participants from the CLOVERS trial. Adult patients with a suspected or confirmed infection and hypotension caused by sepsis. INTERVENTIONS: Participants received 1-3 L of crystalloid fluid for initial fluid resuscitation before randomization. In this analysis, participants were categorized into a lactated Ringer's group and a 0.9% saline group based on the fluid type predominantly used for the initial fluid resuscitation (i.e., ≥ 95% of pre-randomization fluid). MEASUREMENTS AND MAIN RESULTS: Of 1563 participants with sepsis-induced hypotension included in the CLOVERS trial, 622 (39.8%) received lactated Ringer's solution and 690 (44.1%) received 0.9% saline as solution for the initial fluid bolus. Death before discharge home by day 90 occurred in 76 of 622 participants (12.2%) in the lactated Ringer's group and in 110 of 690 participants (15.9%) in the 0.9% saline group, resulting in an adjusted hazard ratio of 0.71 (95% CI, 0.51-0.99
p = 0.043). Patients receiving lactated Ringer's solution had more hospital-free days at 28 days than those receiving 0.9% saline (16.6 ± 10.8 vs. 15.4 ± 11.4, respectively
adjusted mean difference, 1.6 d [95% CI, 0.4-2.8 d
p = 0.009]). Treatment with 0.9% saline was associated with higher levels of serum chloride and decreased levels of serum bicarbonate. CONCLUSIONS: Initial fluid resuscitation with lactated Ringer's solution, compared with 0.9% saline, might be associated with improved survival in patients with sepsis-induced hypotension.