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The Impact of Balanced Crystalloids vs. Saline in ICU Patients: A New Meta-Analysis

Balanced Crystalloids vs. Saline in ICU Patients

In the world of critical care, the choice of intravenous fluids is pivotal to patient outcomes. A recent systematic review and individual patient data meta-analysis has shed light on the ongoing debate between the use of balanced crystalloids and saline in adult intensive care unit (ICU) patients. This post delves into the study's methodology, findings, and their implications for medical intensivists, aiming to offer actionable insights for clinical practice.

This meta-analysis aimed to assess whether balanced solutions, compared with 0.9% sodium chloride (saline), could decrease in-hospital mortality among adult ICU patients, including those in specific subgroups such as patients with traumatic brain injury [1].

Study Design

The study systematically reviewed databases such as PubMed, Embase, and CENTRAL up to September 1, 2023, selecting randomized controlled trials that compared balanced solutions with saline in adult ICU settings. The primary outcome was in-hospital mortality, with a particular focus on patients with traumatic brain injury as a prespecified subgroup.

Population and Intervention

The analysis encompassed data from 34,685 participants across six trials, divided nearly equally between those receiving balanced crystalloids and saline. The study's population was primarily adult ICU patients, with a mean age of 58.8 years and a gender distribution of 42.1% female and 57.9% male.

Key Findings

  • General ICU Population: In-hospital mortality was 16·8% in patients assigned to balanced solutions compared to 17·3% in patients assigned to saline. The odds ratio for in-hospital mortality was 0.962 in favor of balanced solutions [95% CI: 0·909 to 1·019], indicating a slight but not statistically significant reduction in mortality compared to saline. The absolute difference in mortality rates was a mere -0.4 percentage points, suggesting a modest benefit of balanced crystalloids over saline. The posterior probability that balanced solutions reduced mortality was 0·895

  • Patients with Traumatic Brain Injury: The study found that in this subgroup, balanced solutions were associated with a higher in-hospital mortality of 19.1% compared to saline with an in-hospital mortality of 14.7% (OR 1.424, CI [1·100 to 1·818]), suggesting an increased risk when using balanced crystalloids compared to saline. The probability that balanced solutions increased mortality in patients with traumatic brain injury was 0·975.

Implications for Clinical Practice

For medical intensivists, these findings highlight a nuanced approach to fluid therapy in critically ill patients:

  • Balanced Crystalloids: They may be more beneficial for the general ICU population, given their high probability of reducing in-hospital mortality, albeit with a small absolute risk reduction. This suggests that balanced crystalloids could be a preferable choice for fluid resuscitation and maintenance in many ICU patients.

  • Traumatic Brain Injury: The increased mortality risk associated with balanced solutions in this subgroup warrants caution. It suggests that saline might be a safer option for patients with traumatic brain injuries, underscoring the need for personalized fluid management strategies based on individual patient characteristics and conditions.

Is Balanced Crystalloid Fluid Really Better?

In a prior systematic review analyzing the same dataset through a frequentist statistical approach, the p-value for mortality difference slightly exceeded 0.05. This outcome indicates that, from a frequentist standpoint, the null hypothesis—that there is no difference—cannot be conclusively dismissed [2]. Conversely, a Bayesian analysis in this meta-analysis revealed an 89.5% probability that balanced crystalloids are beneficial. This presents a crucial question for clinicians: Does this level of probability of benefit justify integrating balanced crystalloids into clinical practice? Is the evidence of advantage strong enough to warrant a shift in treatment protocols?

Is the evidence of advantage strong enough to warrant a shift in treatment protocols?

  • 0%Yes

  • 0%No

  • 0%I do not know


The debate between balanced crystalloids and saline is far from settled, but this study contributes valuable insights into their relative merits and risks. While balanced crystalloids appear to offer a slight overall mortality benefit in the ICU, their use in patients with traumatic brain injuries may be contraindicated. These findings emphasize the importance of tailored treatment strategies in critical care, balancing the benefits and risks of fluid choices to optimize patient outcomes.


  1. Zampieri FG, Cavalcanti AB, Di Tanna GL et al. Balanced crystalloids versus saline for critically ill patients (BEST-Living): a systematic review and individual patient data meta-analysis. Lancet Respir Med.2023;(published online Nov 30.)

  2. Hammond NE, Zampieri FG, Di Tanna GL et al. Balanced crystalloids versus saline in critically ill adults—a systematic review with meta-analysis. NEJM Evidence.2022;1EVIDoa2100010

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