Fewer Kidney Problems With IV Balanced Crystalloids vs Saline

Veronica Hackethal, MD

February 28, 2018

Two new trials have tried to answer a long-standing question: which intravenous (IV) fluid is better, normal saline or balanced crystalloids?

The trials, both conducted at Vanderbilt University in Nashville, Tennessee, show that the use of balanced crystalloids in critically ill and noncritically ill hospitalized patients resulted in a lower incidence of major adverse kidney events. The results were presented this week at the Meeting of the Society of Critical Care Medicine and were published online on February 27 in the New England Journal of Medicine.

Although IV fluid administration is one of the most common medical therapies used in hospitals, little is known about how different types of IV fluids affect outcomes. Use of these fluids is based on physiologic principles, rather than hard evidence from clinical trials. None of the different types of IV fluids has been thoroughly evaluated for safety and efficacy.

In the United States, 0.9% normal saline is the most commonly used IV fluid, but it contains higher concentrations of chloride than human blood. That can cause kidney injury and can negatively affect patient outcomes. Some studies have suggested that use of IV saline may result in higher rates of acute kidney injury, renal dialysis, and death compared to use of balanced crystalloids.

On the other hand, crystalloid solutions, such as lactated Ringer's and Plasma-Lyte A, contain electrolyte concentrations that are closer to what's found in human blood. Yet even these solutions are not truly "balanced" relative to some body fluids, and their use has been associated with metaboloic alkalosis.

To evaluate the effect of these fluids on patient outcomes, Todd W. Rice, MD, an associate professor of medicine at Vanderbilt University, and colleagues conducted two separate open-label studies in two different groups of patients: critically ill patients in the intensive care unit (ICU), and noncritically ill patients admitted to the hospital from the emergency department (ED).

The first study, called the Isotonic Solutions and Major Adverse Renal Events Trial (SMART), was conducted at five ICUs at Vanderbilt University hospital. The researchers enrolled 15,802 critically ill adults and randomly assigned them to receive either normal saline (n = 7860) or balanced crystalloid (lactated Ringer's solution or Plasma-Lyte A, n = 7942).

Results showed that significantly fewer patients in the balanced-crystalloids group (n = 1139; 14.3%), compared to the saline group (n = 1211; 15.4%), met the primary endpoint of major adverse kidney events (a composite of death from any cause, new kidney dialysis, or persistent kidney dysfunction) within 30 days of hospital discharge or enrollment in the study (marginal odds ratio, .91; 95% confidence interval [CI], .84 - .99; conditional odds ratio, .90; 95% CI, .82 -.99; P = 0.04).

The authors caution, though, that the study did not include patients with traumatic brain injury, because of concern that balanced crystalloids may increase intracranial pressure. Therefore, the results may not apply to this group.

The second study, called the Saline Against Lactated Ringer's or Plasma-Lyte in the Emergency Department (SALT-ED) trial, included 13,347 adults who were initially seen in the ED (where 88.3% received balanced crystalloids) and who were then hospitalized outside the ICU. Upon admission, these patients were randomly assigned to receive either balanced crystalloids (n = 6708) or normal saline (n = 6639).

Results showed that for both groups, times to hospital discharge (the primary outcome) were similar; the median was 25 days for both groups (adjusted odds ratio with balanced crystalloids, .98; 95% CI, .92 - 1.04; P = .41).

As in the SMART trial, results also showed that fewer patients in the balanced-crystalloids group (315; 4.7%), compared to the saline group (370; 5.6%), met the secondary outcome of major adverse kidney events within 30 days, also a composite of death, new kidney dialysis, or persistent kidney dysfunction (adjusted odds ratio,.82; 95% CI, .70 - .95; P =.01).

Because more than 95% of patients in the balanced-crystalloids group received lactated Ringer's, the study cannot determine which is better, lactated Ringer's or Plasma-Lyte A.

Further analysis for both studies suggested that use of balanced crystalloids rather than normal saline could prevent major adverse kidney events in 1 of every 94 patients admitted to the ICU and in 1 of every 111 noncritically ill patients.

Although these numbers may seem modest, the authors point out that millions of patients nationwide receive these fluids annually. On a national level, any effects associated with the difference could be substantial.

In a linked editorial, John Myburgh, MD, PhD, of the University of New South Wales, the George Institute for Global Health, and St. George Hospital, Sydney, Australia, urges caution when interpreting the results.

Whereas both studies showed that balanced crystalloids were associated with a reduction in the composite outcome of adverse kidney events, he notes that no significant differences between balanced crystalloids and saline were found for short-term mortality or kidney dialysis.

"What clinicians need to consider is whether the results of an open-label trial conducted in a single, major US medical center can be generalized to the ways in which their own patients survive, feel, and function," he writes.

He emphasizes that none of the resuscitation fluids are physiologic and that questions about their safety and efficacy remain despite these results.

"[O]utcomes and health economics are fundamental to informing clinicians about their choice of resuscitation fluids in critically ill patients. The trials presented here inform that thinking but do not provide unequivocal clinical direction," he concludes.

The studies were supported by the Vanderbilt Institute for Clinical and Translational Research and by grants from the National Center for Advancing Translational Sciences. One or more authors report receiving grants, advisory board fees, consulting fees, and/or travel support from one or more of the following: the National Institutes of Health, Vanderbilt Center for Kidney Disease, the Department of Veterans Affairs, Venaxis, Cempra Pharmaceuticals, Ferring Pharmaceuticals, Biotest, Abbott Point of Care, Gilead Sciences, Cumberland Pharmaceuticals, and Avisa Pharma. Dr Myburgh has received nonfinancial grants or other support from the following: Baxter Healthcare, CSL Bioplasma, Fresenius Kabi, and the National Health and Medical Research Council.

N Engl J Med. Published online February 28, 2018. Full text, Editorial

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