Impact of Fluid Composition on Mortality and Kidney Injury in Sepsis: A Literature Review

Background Fluid resuscitation is a cornerstone of early sepsis management. While normal saline (NS) has been widely used, emerging evidence suggests that balanced crystalloids such as lactated Ringer’s and Plasma-Lyte may offer improved renal outcomes and reduced mortality by avoiding hyperchloremic metabolic acidosis. Hypothesis In adult patients with sepsis, initial resuscitation with balanced crystalloids reduces mortality and the incidence of acute kidney injury (AKI) compared to normal saline. Methods A literature review was conducted using PubMed and MEDLINE databases focusing on randomized controlled trials and meta-analyses published from 2010–2024. Key studies included the SMART, SALT-ED, BaSICS, and PLUS trials. The primary outcomes evaluated were 30- and 90-day mortality, development of AKI, and need for renal replacement therapy (RRT). Results The SMART and SALT-ED trials demonstrated a reduction in major adverse kidney events with balanced fluids. The SMART trial also showed lower in-hospital mortality among septic patients receiving balanced crystalloids. However, more recent large-scale trials such as BaSICS and PLUS did not show a mortality benefit. Variability in trial design, patient populations, and definitions of sepsis may account for differences in outcomes. Subgroup analyses suggest potential benefits of balanced fluids in specific patient populations. Conclusion While balanced crystalloids may reduce the incidence of AKI in septic patients, mortality benefits remain inconsistent across trials. Current evidence supports the consideration of balanced fluids as the initial resuscitation fluid in sepsis, but further targeted research is needed to define the populations most likely to benefit.