Saline and Electrolyte Solutions Show Similar Benefits for ICU Patients

Heidi Splete

January 19, 2022

The use of balanced multielectrolyte solution or saline had no significant impact on the risk of acute kidney injury or death in critically ill hospitalized patients, based on data from more than 5037 individuals.

A 0.9% sodium chloride solution has long been the first-line fluid for patients in intensive care units worldwide; however, recent concerns that saline may increase the risk of acute kidney injury or death in ICU patients has prompted consideration and increased use of balanced salt solutions, wrote Simon Finfer, MD, of the George Institute for Global Health, Newtown, Australia, and colleagues. Previous studies to determine a benefit of balanced solutions over sodium chloride have been inconsistent, they said.

In the Plasma-Lyte 148 versus Saline (PLUS) study, published in the New England Journal of Medicine, the researchers identified critically ill patients aged 18 years and older who were admitted to 1 of 53 intensive care units (ICUs) in Australia and New Zealand from September 2017 through December 2020. The researchers randomly assigned 2515 patients to receive a balanced multielectrolyte solution (BMES) and 2522 to receive saline solution (0.9% sodium chloride). The mean age of the patients was 61.9 years, and approximately 39% were women. "The trial patients were representative of patients treated in the participating ICUs," the researchers write.

The primary outcome was all-cause mortality within 90 days of randomization. Secondary outcomes included new renal-replacement therapy and a maximum increase in creatinine levels while patients were in the ICU.

"Most deaths occurred in the ICU and were due to distributive shock, hypoxic respiratory failure, cardiogenic shock, or neurologic injury," the researchers note.

Overall, the 90-day mortality rate was 21.8% in the BMES group (530 of 2433 patients) and 22.0% in the saline group (530 of 2413 patients); the difference of –0.15 percentage points was not significant (P = 0.90).

A total of 306 of 2403 patients in the BMES group and 310 of 2394 patients in the saline group underwent new renal-replacement therapy. The difference in new renal-replacement therapy initiation was also insignificant between the groups, nor was the difference in mean maximum increase in serum creatinine levels significant for the BMES group (36.6±94.0 μmol/L [0.41±1.06 mg/dL]) and the saline group (36.1±90.2 μmol/L [0.41±1.02 mg/dL]).

Although arterial blood pH was significantly higher and serum chloride level was significantly lower in BMES patients compared with saline patients, this had no apparent effect on kidney function; levels of serum creatinine, hemoglobin, lactate, and potassium were similar between the groups.

Other markers of healthcare resource use including survival, length of hospital stay, and time spent in the ICU were similar between the groups, as were the number of adverse and serious adverse events.

The findings were limited by several factors including reduced patient recruitment and the lack of mortality data for some patients, the researchers note. Additional limitations included the possible impact of additional saline used in the ICU for the delivery of other medications and the lack of control for all fluids that patients received beyond the ICU setting, they say.

"We did not examine the effects of BMES as compared with saline in patients with traumatic brain injury because we considered saline or a fluid with equivalent tonicity to be indicated in such patients," the researchers add.

However, the results were strengthened by the multicenter, double-blind, randomized design, as well as the longer duration and volume of fluids received by patients compared with previous studies, they say.

The findings were consistent with some previous studies but inconsistent with others, the researchers note. Data from a recent meta-analysis that included the current study findings suggest that balanced salt solutions may be beneficial for particular subgroups, such as patients with diabetic ketoacidosis.

"Further trials are needed to confirm these benefits and to establish whether balanced solutions improve outcomes in patients with other metabolic or electrolyte disturbances," the researchers write, as are studies of the safety of balanced solutions for patients with nontraumatic acute brain injury, they conclude.

The study was supported by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand. The researchers have disclosed no relevant financial relationships.

N Engl J Med. Published online January 18, 2022. Abstract

Heidi Splete is a freelance medical journalist with 20 years of experience.

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