Another take on balanced crystalloids vs. saline

It’s a familiar call ahead to the ED - an adult patient who is febrile, hypotensive, with suspicion towards infection.  While setting up the room, the patient’s bedside nursing team asks if you’d like them to get saline or lactated Ringer’s (LR) ready for resuscitation.  You wonder if there’s any new evidence examining the use of saline versus balanced crystalloids in the emergency department.


The SMART trial was an ICU based, unblinded, cluster randomized trial evaluating the impact of balanced crystalloid resuscitation solutions (LR, Plasma-lyte-A) versus saline on the composite outcome of death, new renal replacement therapy, or doubling of the serum creatinine in critically ill adults.  It ultimately found a small, but statistically significant difference favoring balanced crystalloids1.


A recently published secondary analysis of the SMART data evaluated a different question - is the greatest impact of the fluid selection seen on admission to the ICU (late) or on presentation to the ED (early)2.  To answer this, they utilized their study design. From June 2015-December 2015, the SMART trial initially only controlled the choice of fluid on admission to the medical ICU (the “ICU only period”).  From January 2016-March 2017, the choice of fluid was controlled beginning at presentation to the ED (ED & ICU period).  The primary outcome was 30 day in-hospital mortality and the secondary outcomes included ICU free days, vent free days, pressor free days, renal replacement free days, new renal replacement therapy, or major adverse kidney event within 30 days (MAKE30 - composite of death, new renal replacement therapy, or creatinine > 200% of basline). 


During the ICU only period, no difference in mortality was observed between patients receiving balanced versus saline resuscitation fluids (33.1% vs. 32.9%, OR 1.14[0.70-1.88]).  However, in the ED & ICU period, patients receiving balanced solutions fared better than patients receiving saline (24.9% mortality vs. 30.6%, OR 0.68[0.52-0.89]).  This would suggest the biggest impact when using balanced fluids is associated with early resuscitation in the ED rather than later resuscitation in the ICU.  The total volume administration in the 24 hours prior to ICU admission did not differ between the balanced and saline groups at either time point and there was relatively little crossover (patients in one group receiving the opposite assigned crystalloid).  The secondary outcome of ICU free days was also improved in patients who received early balanced resuscitation compared to later in the ICU.


Ultimately, the conversation within the literature is ongoing as to the impact of using balanced solutions over saline in the critically ill population.  While the data finding balanced solutions superior to saline is mixed in its conclusions, there is no data demonstrating saline as superior.  At worst, balanced solutions compared to saline are neutral regarding patient outcomes.  But we continue to see an ongoing signal pointing to their benefit.  As always, please recall that the trials examining balanced versus saline crystalloid did not include patients with brain injury or neurologic emergencies due to the concern for impacting cerebral edema.



1. Semler MW, Self WH, Wanderer JP, et al. Balanced Crystalloids versus Saline in Critically Ill Adults. New Engl J Medicine. 2018;378(9):829-839. doi:10.1056/nejmoa1711584

2. Jackson KE, Wang L, Casey JD, et al. Effect of Early Balanced Crystalloids before ICU Admission on Sepsis Outcomes. Chest. Published online 2020. doi:10.1016/j.chest.2020.08.2068