Intravenous balanced solutions: from physiology to clinical evidence

Balanced solutions are commonly defined as intravenous fluids having an electrolyte composition close to that of plasma. As such, they should minimally affect acid-base equilibrium, as compared to the commonly reported 0.9% NaCl-related hyperchloremic metabolic acidosis. Recently, the term "balanced" solution has been also employed to indicate intravenous fluids with low chloride content, being the concentration of this electrolyte the most altered in 0.9% NaCl as compared to plasma, and based upon a suggested detrimental alteration of renal function associated with hyperchloremia. Despite efforts made towards its identification, the ideal balanced solution, with minimal effects on acid-base status, low chloride content, and adequate tonicity, is not yet available. After the accumulation of pre-clinical and clinical physiologic data, in the last three years, several clinical trials, mostly observational and retrospective, have addressed the question of whether the use of balanced solutions has beneficial effects as compared to the standard of care, sometimes even suggesting an improvement in survival. Nonetheless, the first large randomized controlled trial comparing the effects of a balanced vs. unbalanced solutions on renal function in critically-ill patients (SPLIT trial, the 0.9% saline vs. Plasma-Lyte 148 for Intensive Care Unit Fluid Therapy), just recently published, showed identical equipoise between the two treatments. In the present review, we offer a comprehensive and updated summary on this issue, firstly, by providing a full physiological background of balanced solutions; secondly, by summarizing their potential pathophysiologic effects; and lastly, by presenting the clinical evidence available to support their use at the present time.