For a ubiquitous intervention such as intravenous fluid resuscitation, it’s a surprise to see reassessment continuing apace. Since the inception of early goal-directed therapy, emergency departments (EDs) have been dumping fluids, typically 0.9 percent sodium chloride solution, into patients in ever-increasing quantities. Even as early goal-directed therapy has fallen out of favor, its ongoing evolution has discarded only the most invasive bits, while keeping early antibiotics and aggressive resuscitation.

0.9 percent sodium chloride is hardly physiologically equivalent to the intravascular circulation, nor does it specifically address electrolyte losses or variance in the setting of critical illness. The popularized treatment alternative remains so-called balanced crystalloid solutions. These solutions typically include some small amount of sodium chloride, but may also include sodium gluconate, sodium acetate, sodium lactate, calcium chloride, potassium chloride, or potentially even magnesium chloride. The pH of these solutions is closer to the normal physiologic value of 7.4, rather than the pH of roughly 5.5 seen with 0.9 percent sodium chloride.

Many trials have been published comparing the two types of electrolyte solutions, including those in the ED and in the intensive care unit (ICU). Just this spring, such a comparison has been published, and again, no statistically significant difference could be detected between 0.9 percent saline and a balanced solution, in this case Plasma-Lyte 148.¹ The most notable difference in thinking following this most recent randomized controlled trial is its accompanying updated systematic review and meta-analysis of the same topic.² Taking stock of the entirety of all the high-quality randomized controlled trials, the authors of the meta-analysis pooled nearly 35,000 ICU patients together to develop a more precise estimate of any treatment effect associated with use of balanced crystalloid solutions. Despite this larger sample size, no statistically significant difference in mortality could be identified.

However, the story does not quite end there. The risk ratio from their pooled low-bias study cohort was 0.96 [95 percent CI 0.91 to 1.01], non-significantly favoring the balanced solutions. The authors then utilize a Bayesian approach to assessing the probability that balanced fluid solutions are superior. Based on a vague assumption that the prevailing observational evidence and opinion is insufficient to strongly tilt the results of any analysis, the authors conclude there is an 89.5 percent posterior probability that balanced crystalloids reduce mortality.

Considering that this analysis encompasses 35,000 patients and is only able to eke out such a minor advantage to treatment with balanced fluids, the absolute magnitude of any treatment effect must be quite small. Then, these pooled studies are all from the ICU, limiting their generalizability to the ED. The simple way out is to say, “It doesn’t matter, and, if it matters, it only matters a tiny amount.” Conversely, sepsis is implicated as a leading cause of death worldwide, and significant volumes of intravenous fluid are given in emergency departments each day. Even a miniscule relative improvement in mortality—a rather important patient-oriented outcome—becomes a significant absolute excess in survival when multiplied across millions of lives. Whenever the option exists to choose a balanced solution, it is likely the ever-so-slightly better choice.