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Randomized Controlled Trial
. 2025 May 1;53(5):e1140-e1144.
doi: 10.1097/CCM.0000000000006601. Epub 2025 Feb 19.

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

Georg Gelbenegger  1 , Nathan I Shapiro  2 , Markus Zeitlinger  1 , Bernd Jilma  1 , Ivor S Douglas  3 , Anselm Jorda  1
Affiliations
Randomized Controlled Trial

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

Georg Gelbenegger et al. Crit Care Med. .

Abstract

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.

Keywords: acidosis; balanced crystalloid; hyperchloremia; multibalanced.

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Conflict of interest statement

Dr. Gelbenegger disclosed this article was prepared with data from the National Heart, Lung, and Blood Institute (NHLBI) Biologic Specimen and Data Repository Information Coordinating Center. Drs. Shapiro and Douglas received support for article research from the National Institutes of Health. Dr. Jilma received funding from Sanofi and Looplab. Dr. Douglas’ institution received funding from the NHLBI. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Figures

Figure 1.
Figure 1.
Kaplan-Meier curves of the time to death before discharge home by day 90 between the lactated Ringer’s solution group and the 0.9% saline group. HR = hazard ratio.
See this image and copyright information in PMC

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