ArticleSAGE open medicine2026
Timing of lactated Ringer's administration relative to Sepsis-3 diagnosis and 28-day mortality: A retrospective propensity score-matched cohort study.
Article in SAGE open medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Balanced crystalloids are preferentially recommended over saline for sepsis resuscitation; however, the optimal timing of administration remains to be defined. Methods: This retrospective cohort study utilized the Medical Information Mart for Intensive Care IV (MIMIC-IV) database to analyze adult patients meeting Sepsis-3 criteria. Patients were stratified by Lactated Ringer's (LR) administration timing relative to documented Sepsis-3 onset: Group A (LR initiation ≤24 h after onset), Group B (LR initiation ≤24 h before onset), Group C (LR initiation 24-48 h after onset), and Group D (reference: no LR exposure during intensive care unit [ICU] admission). The primary outcome was 28-day all-cause mortality. To address confounding, Group B patients were 1:1 Propensity-Score Matched (PSM) with Group D counterparts, followed by multivariable Cox regression and sensitivity analyses. Results: PSM generated a balanced cohort of 3,876 patients (1,938 in Group B vs. 1,938 untreated Group D counterparts). Multivariable Cox regression analysis showed that pre-onset LR exposure remained associated with lower 28-day mortality after adjustment for clinical covariates. In additional post-PSM sensitivity analyses, this association persisted after further adjustment for elective surgery and total recorded fluid volume during the 24 hours preceding Sepsis-3 onset. To address timing-related bias, we also compared the ICU admission-to-SOFA time interval and performed a 24-hour ICU-admission landmark analysis; the association remained in the landmark cohort. Kidney outcomes were mixed: any acute kidney injury (AKI) was more frequent in Group B, whereas Kidney Disease: Improving Global Outcomes (KDIGO) stage 3 AKI and renal replacement therapy were less frequent. Conclusion: Pre-diagnosis LR exposure within 24 hours before Sepsis-3 onset was associated with lower 28-day mortality in adult patients with sepsis. These observational findings are hypothesis-generating and should not be interpreted as evidence supporting prophylactic LR administration before Sepsis-3 onset.
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