Peter Malamet DO
On a daily basis in the emergency care setting, we see patients that require fluid
replacement. From sepsis, diabetic ketoacidosis, dehydration, etc., we obtain intravenous
access and give a few boluses (along with the cocktail of antibiotics, insulin, or
vasopressors that is appropriate for the clinical scenario). However, disagreement exists as
to which type of fluid is best to use for replacement. This pearl aims to summarize the
current evidence comparing the most common crystalloid fluids - Normal Saline and
Lactated Ringers.
Intravenous fluids were first used in 1832 when Robert Lewens administered an
alkalized salt solution to patients with Cholera in an effort to replace lost serum.1 He noted
that the amount of fluids that patients needed appeared to be proportional to the amount
of fluids lost.1 In 1885, Alexis Hartman started giving a modified salt solution to children
with gastroenteritis.1 In 1941, Human Albumin was used as a resuscitative fluid for
patients burned during the Pearl Harbor attack.1 Since then, there have been multiple types
of fluids created in an attempt to replicate human plasma.
The ideal replacement fluid has a composition close to extracellular fluid, is
metabolized and excreted without accumulation, has no adverse effects and is cost
effective.1 Of course, this fluid does not exist. The two categories of fluids created to best
meet the aforementioned requirements are colloids and crystalloids.
Colloids are suspensions of molecules that do not cross a healthy capillary
membrane.1 Popular examples include Albumin and Hyperoncotic Startch.1 These fluids are
not widely used as they have not shown a clear benefit over crystalloids, are expensive and
can be harmful.1,2,3,4,5,6 For these reasons the rest of the discussion will focus on
crystalloids.
Crystalloids are the most frequently used fluids in resuscitation. They are made of
freely permeable ions, such as sodium and chloride, that determine tonicity.1,7 The two
most common types are 0.9% Normal Saline (NS) and Lactated Ringers (LR). These two
types of fluids in particular have been the subject of debate over many years.
Despite the name “normal”, 0.9% Normal Saline has a 10% higher sodium
concentration and 50% higher chloride concentration compared to human serum.7 It was
originally described by Jacob Hamburber, who carried out red blood cell lysis studies in the
early 1880s to determine that it was close to physiologic fluid.1,7 Today, we continue to call
0.9% NS “normal” based on in vitro studies from the 1880’s. The main argument against
normal saline is the adverse effect of a hyperchloremic metabolic acidosis.1,7 This can result
in organ dysfunction, and in particular, renal dysfunction.7
A proposed solution to the problems associated with 0.9% NS were the “Balanced”
or “Physiologic” crystalloid solutions, Lactacted Ringers (LR) or PlasmaLyte. These are
meant to have an electrolyte composition similar to that of human plasma.1,8 Lactated
Ringers are hypotonic to human plasma and also contain potassium, calcium and lactate.1
PlasmaLyte is also hypotonic and contains magnesium, acetate, gluconate without the
addition of lactate.1 For this discussion we will focus on LR, since it is commonly used in the
latest research.
Proponents of LR claim that it will help avoid the metabolic acidosis and renal injury
seen during large volumes of crystalloid infusion.8 However, large volumes of LR can cause
a metabolic alkalosis and hypotonicity.8 A common argument against the use of LR is the
theoretical risk of increasing the potassium level in a hyperkalemic patient. Studies have
shown this to not only be false, but in fact it is normal saline that has a greater risk of
causing hyperkalemia due to pH shifts.7,9,10 Furthermore, the lactate in LR has also been
shown to be beneficial. Research has shown that lactate is one of the preferred substrates
used by the body in energy crisis conditions, such as septic shock and acute heart failure.8,11
Until 2018, the best study comparing 0.9% Normal Saline and Balanced Solutions
was the SPLIT trial. Published in 2015, it was a prospective, blinded, cluster randomized,
crossover study performed in four New Zealand Intensive Care Units.12 Their primary
outcome was the proportion of patients with AKI.12 There were 2278 patients enrolled and
assigned to either buffered crystalloid or normal saline.12 This trial did not find any
significant difference in outcome between the two fluids. However, most patients were
admitted from surgery with only 316 of the patients coming from the Emergency
Department. Furthermore, on average, the study patients only received approximately 2
liters of crystalloid. 12
This year, 2018, delivered two articles that looked at balanced crystalloid versus
saline in critical and non-critical patients. The Isotonic Fluids and Major Adverse Renal
Events Trial (SMART) and the Saline Against Lactated Ringers or PlasmaLyte in the
Emergency Department (SALT-ED) are both large, single center, randomized trials looking
at the two types of fluids.13,14 The SMART trial studied a primary outcome of major adverse
kidney events within 30 days.13 Out of the more than 15,000 patients, there was a
statistically significant difference in these events, 14.3% vs 15.4% (Balanced Solution to
Normal Saline, respectively).13 The SALT-ED trial enrolled over 13,000 patients with a
primary outcome of hospital free days (which was not statistically significant) but did have
a secondary outcome of Major Adverse Kidney Events within 30 days, which was 4.7% vs
5.6% in favor of balanced solutions.14 It should be noted that the Major Adverse Kidney
Events within 30 days is a composite outcome. A composite outcome combines multiple
endpoints (in this case: death, initiation of Renal Replacement Therapy and persistent renal
dysfunction) and uses them as a primary outcome. This type of statistical analysis does add
some ambiguity to the results. Both trials do have some methodological flaws (non blinded,
single center, most patients receiving LR rather than Plasma-Lyte); however, it is some of
the highest quality of data we have at this point.
Based on the current data, it seems unlikely that the choice of NS vs. LR will have a
major effect on mortality. The data does seem to lean towards LR when it comes to
outcomes like acute kidney injury. LR will not cause a metabolic acidosis, has less chance of
renal injury, does not cause hyperkalemia and may have a benefit by way of the included
lactate. The difference in cost between the two is negligible and both are usually well
stocked. Therefore, this author would suggest that LR is likely the better choice for fluid
resuscitation, especially when using large volumes.
1. Myburgh, J. A., & Mythen, M. G. (2013). Resuscitation fluids. New England Journal of
Medicine, 369(13), 1243-1251.
2. Roberts I, Blackhall K, Alderson P, Bunn F, Schierhout G. Human albumin solution for
resuscitation and volume expansion in critically ill patients. Cochrane Database of Systematic
Reviews. 2011, Issue 11. Art. No.: CD001208. DOI: 10.1002/14651858.CD001208.pub4.
3. SAFE Study Investigators. "Impact of albumin compared to saline on organ function and mortality of patients with severe sepsis." Intensive care medicine 37.1 (2011): 86-96.
4. Wiedermann, Christian J., et al. "Hyperoncotic colloids and acute kidney injury: a meta-analysis of randomized trials." Critical Care 14.5 (2010): R191.
5. Mutter TC, Ruth CA, Dart AB. Hydroxyethyl starch (HES) versus other fluid therapies: effects on
kidney function. Cochrane Database of Systematic Reviews 2013, Issue 7. Art. No.: CD007594.
DOI: 10.1002/14651858.CD007594.pub3
6. Gattas, David J., et al. "Fluid resuscitation with 6% hydroxyethyl starch (130/0.4 and 130/0.42) in acutely ill patients: systematic review of effects on mortality and treatment with renal replacement therapy." Intensive care medicine 39.4 (2013): 558-568.
7. Li H, Sun S, Yap JQ, Chen J, Qian Q. 0.9% saline is neither normal nor physiological. Journal of
Zhejiang University Science B. 2016;17(3):181-187. doi:10.1631/jzus.B1500201.
8. Ichai, Carole, Jean-Christophe Orban, and Eric Fontaine. "Sodium lactate for fluid resuscitation:
the preferred solution for the coming decades?." Critical Care 18.4 (2014): 163.
9. Khajavi, Mohammad Reza, et al. "Effects of normal saline vs. lactated ringer's during renal
transplantation." Renal failure30.5 (2008): 535-539.
10. Modi, Manisha P., et al. "A comparative study of impact of infusion of Ringer's Lactate solution
versus normal saline on acid-base balance and serum electrolytes during live related renal
transplantation." Saudi Journal of Kidney Diseases and Transplantation 23.1 (2012): 135.
11. Nalos, Marek, et al. "Half-molar sodium lactate infusion improves cardiac performance in acute
heart failure: a pilot randomised controlled clinical trial." Critical Care 18.2 (2014): R48.
12. Young, Paul, et al. "Effect of a buffered crystalloid solution vs saline on acute kidney injury among patients in the intensive care unit: the SPLIT randomized clinical trial." Jama 314.16 (2015): 1701- 1710.
13. Semler, Matthew W., et al. "Balanced crystalloids versus saline in critically ill adults." New England Journal of Medicine378.9 (2018): 829-839.
14. Self, Wesley H., et al. "Balanced crystalloids versus saline in noncritically ill adults." New England Journal of Medicine378.9 (2018): 819-828
