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Balanced crystalloid versus saline for resuscitation in adult sepsis: a systematic review and meta-analysis

In brief

Balanced crystalloids cut sepsis mortality by about 8%

In a meta-analysis of eight trials involving 8,173 adults with sepsis, using balanced crystalloid fluids lowered death rates compared with normal saline and also reduced acute kidney injury, hyperchloremia, and need for dialysis. The benefit came with more ICU-, ventilator- and vasopressor-free days, supporting balanced solutions as the preferred resuscitation fluid.

Journal
Frontiers in medicine (Q1)
Published
21 August 2026
Study design
Systematic review / meta-analysis of RCTs
Evidence level
Level 1, High (CEBM 1a)
Authors
Lipeng Liu, Binrong Cai, Bin He
PMID
42698512
DOI
10.3389/fmed.2026.1906761

Why clinicians should know about it

Abstract

BACKGROUND: Fluid resuscitation is the cornerstone of sepsis management, however, the choice between balanced crystalloid solutions and normal saline remains debated. This meta-analysis aimed to compare the efficacy of balanced solutions versus saline for fluid resuscitation in adult patients with sepsis. METHODS: A systematic literature search was performed in PubMed, Embase, Scopus, and other relevant sources. Retrieved studies were rigorously screened according to predefined inclusion and exclusion criteria. Data from the included studies were extracted for analysis. The primary outcome was defined as mortality rate. Secondary outcomes included acute kidney injury (AKI), hyperchloremia, renal replacement therapy (RRT), ICU-free days, ventilator-free days, vasopressor-free days. The study protocol was registered with PROSPERO (CRD420261368142). RESULTS: A total of eight studies (8,173 patients; 4,056 assigned to balanced solutions, 4,117 to saline) met the inclusion criteria. In the primary analysis restricted to seven randomized controlled trials, balanced solutions were associated with significantly lower mortality than saline (RR 0.92; 95% CI 0.86-0.98; P = 0.01; I2 = 37%), and a sensitivity analysis incorporating a post-hoc observational study yielded consistent results (RR 0.91; 95% CI 0.85-0.97). Balanced solutions were also associated with lower incidences of AKI (RR 0.86; 95% CI 0.78-0.96; P = 0.004), hyperchloremia (RR 0.68; 95% CI 0.52-0.90; P = 0.007), and RRT requirement (RR 0.74; 95% CI 0.56-1.00; P = 0.05), and with a greater number of ICU-free, ventilator-free, and vasopressor-free days (all P < 0.05). CONCLUSION: In adult patients with sepsis, treatment with balanced crystalloid solutions for fluid resuscitation significantly reduces mortality (moderate certainty), decreases kidney-related adverse events, and better maintains electrolyte balance, thereby improving patient outcomes. These findings support the preferential use of balanced crystalloids over saline in this population. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261368142, identifier CRD420261368142.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.