Is Saline the Best Choice? New Study Questions Fluid Therapy in Intensive Care
"A meta-analysis reveals that saline might not be the safest option for critically ill patients, prompting a rethink on balanced crystalloid solutions."
For decades, saline has been a staple for fluid resuscitation and maintenance in intensive care units (ICUs). However, like all medical treatments, its safety and effectiveness warrant ongoing scrutiny. Recent insights into fluid physiology and potential complications like hyperchloremia, metabolic acidosis, and acute kidney injury have stirred debate about its routine use.
Balanced crystalloid solutions, designed to more closely mimic the electrolyte composition of plasma, have emerged as a potential alternative. These solutions offer the theoretical benefit of reducing the risk of complications associated with high chloride levels, prompting many clinicians to consider them a safer option.
However, studies comparing saline to balanced solutions have yielded mixed results. While some suggest that balanced solutions reduce the risk of acute kidney injury, the need for renal replacement therapy, and blood transfusions, others have found no significant advantage. To clarify this uncertainty, a new meta-analysis has investigated the impact of saline versus balanced crystalloids on mortality in ICU patients.
Mortality Results Remain Close
In the trial titled “Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults,” death within 90 days occurred in 530 of 2,433 patients (21.8%) receiving balanced multielectrolyte solution (BMES) and 530 of 2,413 (22.0%) receiving saline. The difference was −0.15 percentage points (95% CI, −3.60 to 3.30; P=0.90), so the trial did not show a significant mortality difference. A 2026 meta-analysis addressed the still-debated comparison of balanced crystalloid solutions and saline for fluid resuscitation in adults with sepsis, but the provided source snippet gives no results.
From Circulation Theory to Crystalloids
A historical review traces intravenous fluid administration from William Harvey’s circulation theory and Christopher Wren’s pioneering venous injections through fluid replacement efforts during cholera epidemics. It identifies Sydney Ringer’s electrolyte solutions as a milestone in this development. A separate 2023 review describes the use of intravenous fluids for maintenance and resuscitation in pediatric critical care as universal and notes growing interest in multielectrolyte solutions that more closely resemble plasma.
Does Saline Increase Mortality Risk in the ICU?
A comprehensive meta-analysis, featured in Revista Española de Anestesiología y Reanimación, sought to evaluate the effects of saline compared to balanced crystalloids on patient mortality within intensive care settings. This study pooled data from multiple clinical trials to provide a more robust understanding of the risks and benefits associated with each type of fluid.
- Adult patients (18 years or older) admitted to the ICU.
- Intervention: Administration of crystalloid fluids (balanced or unbalanced) for maintenance or resuscitation.
- Primary Outcome: All-cause mortality in the ICU or hospital, typically measured at 28 or 60 days.
Evidence Points to a Small, Uncertain Benefit
The BEST-Living systematic review and individual patient data meta-analysis reported a high probability that balanced solutions reduce in-hospital mortality in critically ill patients, while rating the certainty of evidence as moderate and the absolute risk reduction as small. The 2021 Surviving Sepsis Campaign guideline cites the SMART trial, a single-center, multiple-crossover study of 15,802 patients. In its prespecified subgroup of patients admitted with sepsis, 30-day mortality was lower with balanced solutions than with saline (OR 0.80; 95% CI, 0.67–0.94). These findings provide evidence relevant to the comparison, but the sources describe different analyses and outcomes.
Evidence Is Not Uniform
A review of fluid-resuscitation research priorities reports that recent meta-analyses conflict on whether balanced crystalloids are superior to saline for individual outcomes such as mortality and acute kidney injury, both in critical illness generally and in sepsis. A separate meta-analysis focused exclusively on critically ill patients notes limitations in prior reviews, including patient-population heterogeneity, small sample sizes, and few studies limited to critically ill patients. The SPLIT randomized clinical trial’s report calls for further large trials to assess efficacy in higher-risk populations and measure outcomes such as mortality. Together, these sources caution against treating superiority as settled.
Differences Among Balanced Fluids
A systematic comparison of balanced crystalloid solutions reports that Plasma-Lyte may result in fewer metabolic abnormalities than other balanced crystalloid solutions. However, the review found insufficient data to assess whether choosing among different balanced crystalloids affects patient-important outcomes, including mortality and length of hospitalization. Thus, the possible metabolic distinction does not establish that one balanced fluid improves those outcomes over another.
The Implications for Clinical Practice
This meta-analysis adds to a growing body of evidence suggesting that saline may not be the optimal fluid choice for critically ill patients. The findings underscore the importance of considering balanced crystalloid solutions as a potentially safer alternative, especially given their alignment with the body's natural electrolyte composition. As research evolves, healthcare providers should stay informed and critically evaluate their fluid therapy practices to ensure the best possible outcomes for their patients.
Context Matters in Fluid Choices
A 2025 synthesis of expert opinions addresses human albumin solutions compared with crystalloids for volume expansion in critically ill adults with sepsis. It notes potential oncotic and anti-inflammatory benefits attributed to albumin, while describing an ongoing debate and an absence of definitive empirical evidence. The review focuses on perspectives from healthcare professionals recognized in critical care or sepsis management, including emergency physicians. The available source material does not establish a preferred fluid choice.
Research and Individualized ICU Care
A December 2024 review says its findings support preferential use of balanced crystalloids in critically ill patients and emphasizes individualized fluid-management strategies in the ICU. It also states that further research is needed to confirm the benefits and optimize protocols across diverse ICU populations. Separately, a market report estimates the global intravenous solutions market at about USD 13.09 billion in 2025 and anticipates growth during 2026–2034, citing hospitalization rates, surgical procedures, and demand for emergency and critical-care therapies as supporting factors. The market projection is not evidence about which fluid improves patient outcomes.
Crystalloids Serve Many Clinical Roles
Crystalloid solutions are described as being used for fluid resuscitation in hypovolaemic states and fluid replacement in redistributive states. The source also lists their use as carriers for electrolyte replacement therapy and total parenteral nutrition, and for maintaining hydration and electrolytes when patients cannot take food or water orally. A 2024 review identifies distinctions between colloids and crystalloids and between chloride-rich and balanced solutions as topics in recent fluid-therapy research. The provided snippets do not quantify the relative impact of these choices across the listed uses.
Potential Kidney Effects and Clinical Outcomes
A source on 0.9% saline reports that microperfusion experiments and real-time imaging studies demonstrated reduced renal perfusion and kidney-volume expansion following saline infusion, compromising oxygen delivery to the renal parenchyma. A separate multicenter randomized clinical trial compared colloids with crystalloids for fluid resuscitation in ICU patients with hypovolemic shock, stratifying participants by sepsis, trauma, or hypovolemic shock without sepsis or trauma. The provided trial snippet describes its objective and design but gives no results, so it does not support a conclusion about which fluid altered mortality.