Balanced versus unbalanced salt solutions: what difference does it make?

The infusion of crystalloid solutions is a fundamental part of the management of critically ill patients. These solutions are used to maintain the balance of water and essential electrolytes and replace losses when patients have limited gastrointestinal intake. They also act as carriers for intravenous infusion of medication and red cells. The most commonly used solution, 0.9% saline, has equal concentrations of Na(+) and Cl(-) even though the plasma concentration of Na(+) normally is 40 meq/L higher than that of Cl(-). The use of this fluid thus can produce a hyperchloremic acidosis in a dose-dependent manner, but it is not known whether this has clinical significance.

The first part of this article deals with the significance of Na(+) and Cl(-) in normal physiology. This begins with examination of their roles in the regulation of osmolality, acid-base balance, and generation of electrochemical gradients and why the concentration of Cl(-) normally is considerably lower than that of Na(+). The next part deals with how their concentrations are regulated by the gastrointestinal tract and kidney. Based on the physiology, it would seem that solutions in which the concentration of Na(+) is "balanced" by a substance other than Cl(-) would be advantageous. The final part examines the evidence to support that point.

There are strong observational data that support the notion that avoiding an elevated Cl(-) concentration or using fluids that reduce the rise in Cl(-) reduces renal dysfunction, infections, and possibly even mortality. However, observational studies only can indicate an association and cannot indicate causality. Unfortunately, randomized trials to date are far too limited to address this crucial issue. What is clear is that appropriate randomized trials will require very large populations. It also is not known whether the important variable is the concentration of Cl(-), the difference in concentrations of Na(+) and Cl(-), or the total body mass of Cl(-).