Critical Care Commentary

Balanced crystalloids vs saline for critically ill patients


If you work in an ICU, chances are good that you frequently order IV fluids (IVF). Between resuscitation, maintenance, and medication carriers, nearly all ICU patients receive IVF. Historically, much of this IVF has been 0.9% sodium chloride (“saline” or “normal saline”). Providers in the United States alone administer more than 200 million liters of saline each year (Myburgh JA, et al. N Engl J Med. 2013;369[13]:1243). New evidence, however, suggests that treating your ICU patients with so-called “balanced crystalloids,” rather than saline, may improve patient outcomes.

Dr. Matthew Semler

Dr. Matthew Semler

For over a century, clinicians ordering IV isotonic crystalloids have had two basic options: saline or balanced crystalloids (BC). Saline contains water and 154 mmol/L of sodium chloride (around 50% more chloride than human extracellular fluid). In contrast, BCs, like lactated Ringer’s (LR), Hartman’s solution, and others, contain an amount of chloride resembling human plasma (Table 1). BC substitute an organic anion such as bicarbonate, lactate, acetate, or gluconate, in place of chloride – resulting in lower chloride level and a more neutral pH.

Over the last 2 decades, evidence has slowly accumulated that the different compositions of saline and BC might translate into differences in patient physiology and outcomes. Research in the operating room and ICU found that saline administration caused hyperchloremia and metabolic acidosis. Studies of healthy volunteers found that saline decreased blood flow to the kidney (Chowdhury AH, et al. Ann Surg. 2012;256[1]:18). Animal sepsis models suggested that saline might cause inflammation, low blood pressure, and kidney injury (Zhou F, et al. Crit Care Med. 2014;42[4]:e270). Large observational studies among ICU patients found saline to be associated with increased risk of kidney injury, dialysis, or death (Raghunathan K, et al. Crit Care Med. 2014 Jul;42[7]:1585). These preliminary studies set the stage for a large randomized clinical trial comparing clinical outcomes between BC and saline among acutely ill adults.

Between June 2015 and April 2017, our research group conducted the Isotonic Solutions and Major Adverse Renal Events Trial (SMART) (Semler MW, et al. N Engl J Med. 2018;378[9]:819). SMART was a pragmatic trial in which 15,802 adults in five ICUs were assigned to receive either saline (0.9% sodium chloride) or BC (LR or another branded BC [PlasmaLyte A]). The goal was to determine whether using BC rather than saline would decrease the rates of death, new dialysis, or renal dysfunction lasting through hospital discharge. Patients in the BC group received primarily BC (44% LR and 56% another branded BC [PlasmaLyte A]), whereas patients in the saline group received primarily saline. The rate of death, new dialysis, or renal dysfunction lasting through hospital discharge was lower in the BC group (14.3%) than the saline group (15.4%) (OR: 0.90; 95% CI, 0.82-0.99; P=0.04). The difference between groups was primarily in death and new dialysis, not changes in creatinine. For every 100 patients admitted to an ICU, using BC rather than saline would spare one patient from experiencing death, dialysis, or renal dysfunction lasting to hospital discharge (number needed to treat). The benefits of BC appeared to be greater among patients who received larger volumes of IVF and patients with sepsis. In fact, among patients with sepsis, mortality was significantly lower with BC (25.2%) than with saline (29.4%) (P=.02).

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