Findings from two trials comparing the use of balanced crystalloid solutions versus saline may spur systemic changes in IV fluid management. The results of the SMART trial in ICUs and the SALT-ED trial in the ED indicate that a shift to balanced crystalloids could save up to 1 in 100 patients receiving fluids from suffering new renal dysfunction, dialysis or death.
With approximately 30 million patients receiving IV fluids each year in the US, that adds up to a huge impact.
“Administering IV fluids is the most common intervention received by hospital patients – more common than oxygen,” said chief investigator Matthew Semler, M.D., assistant professor of medicine at Vanderbilt University Medical Center. “We have known for a long time that saline can cause hyperchloremic metabolic acidosis, and potentially hemodynamic instability and acute kidney injury. Yet it took a large study to show how balanced crystalloids may be able to prevent dialysis and save lives.”
SMART and SALT-ED Studies
The Isotonic Solutions and Major Adverse Renal Events (SMART) trial, a 23-month, cluster-randomized, multiple-crossover study funded by the Vanderbilt Institute for Clinical and Translational Research, examined 15,802 adult ICU patients. Five Vanderbilt ICU units each administered either saline or one of two balanced crystalloids (lactated Ringer’s or Plasma-lyte A) over a series of alternating one-month periods. They evaluated patient outcomes at 30 days, or at discharge, whichever came first.
The primary outcome measured was the combined incidence of new renal replacement therapy, persistent renal dysfunction and death. 15.4 percent of the saline group patients experienced this outcome versus 14.3 percent for those receiving balanced crystalloids.
In parallel, Semler and his colleagues studied non-critical care patients in the ED who required IV fluids, and who were admitted to the hospital (but not to ICU). 13,347 patients met the study criteria in this Saline Against Lactated Ringer’s (SALT-ED) trial.
A similar yardstick was used to evaluate primary use of saline versus balanced crystalloids, with a statistically significant proportion of patients in the saline group (5.6 percent) found to suffer more major adverse kidney events (including fatalities) within 30 days than in the balanced crystalloids group (4.7 percent).
Focusing on Clinical Indications and Product Selection
While some benefits of balanced crystalloids are clear, and the cost and availability are comparable to saline, there are questions yet to be answered before recommending universal use. For example, saline may be contraindicated in cases of head trauma and may be incompatible with some medical infusions.
Semler notes that safety and efficacy for other specific subgroups, such as those with hyperkalemia, require additional research. Current subgroup analyses of the ICU trial are underway. Semler hopes that results of another study to be completed in 2021 will provide additional insights.
“While we are cautious about saying who benefits most, I think it’s going to be older patients with acute kidney injury, especially those with sepsis,” Semler said. “There may be patients in the middle for whom it doesn’t matter much, and a small group of patients for whom saline is a reasonable first choice, until further data proves otherwise.”
Which balanced crystalloids are best? The current choice is between a lactate balanced fluid, like lactated Ringer’s, or an acetate balanced fluid. “We have ongoing research to try and determine if one of those is better,” said Semler.
Closing the Time Gap Between Research and Practice
“Making this change in our fluid use may prevent around 100 ICU deaths each year in our hospital alone.”
The Vanderbilt ICU and ED teams are already operationalizing knowledge gained from the trials. Prior to the trials, the medical ICU used 75 to 80 percent saline, then 50 percent during the trials, and now they use less than 5 percent saline.
“We do this research in the context of something we’re calling a learning healthcare system, which focuses on clinical investigations that have an immediate translation into practice,” Semler said. “Based on our research, making this change in our fluid use may prevent around 100 ICU deaths each year in our hospital alone.”
