Elusive answer : Balanced fluids vs saline in critical care

In a late breaking abstract in the CHEST meeting in Toronto, Matthew Semler, Wesley Self, Todd Rice et el presented finding of their SMART(The Isotonic Solutions and Major Adverse Renal Events Trial) trial.

They reported that  total of 1,139 patients (14.3%) in the balanced crystalloid group experienced the primary outcome of MAKE30(Major Adverse Kidney Events within 30 days), compared with 1,211 patients (15.4%) in the saline group (adjusted odds ratio, 0.90; 95% confidence interval, 0.82 to 0.99; P=0.04). A total of 818 patients (10.3%) in the balanced crystalloid group died prior to hospital discharge or 30 days, compared with 875 (11.1%) in the saline group (adjusted odds ratio, 0.90; 95% confidence interval, 0.80 to 1.01; P=0.06).  They claim that among critically ill adults, use of balanced crystalloids for intravenous fluid administration reduced the composite of death, new renal replacement therapy, and persistent renal dysfunction compared with use of saline.

However, the answer is still elusive.

Age old argument of saline vs ringer has been going on since the start of use of IVF in medicine. In recent years, focus has been on chloride content of the IVFs.

And an earlier study published in the American Journal of Respiratory and critical care medicine in respiratory by same authors(SALT trial), there was no difference in 2 groups(Saline versus balanced crystalloid) in terms of renal failure( 24.7% vs. 24.6%; P = 0.98).

Sen A, Keener CM, Sileanu FE et el looked at the chloride content of Resuscitation fluid and a single center study of about 4,710 patients and found that each 100 mEq increase in chloride load was associated with a 5.5% increase in the hazard of death. Crude rates of hyperchloremic acidosis, acute kidney injury, and hospital mortality all increased significantly as chloride load increased (p < 0.001).

Bampoe S, Odor PM, Dushianthan A, Bennett-Guerrero et el published a cochrane review of  Perioperative administration of buffered versus non-buffered crystalloid intravenous fluid to improve outcomes following adult surgical procedures. They found that current evidence is insufficient to show effects of perioperative administration of buffered versus non-buffered crystalloid fluids on mortality and organ system function in adult patients following surgery.

In the latest study by Semler, Rice et el, the difference between the two groups is only 20meq and account for far significant difference in renal failure, and mortality than any previously reported study. Given it is a single center study, it will be prudent to have multi- center randomized trial prior to blaming everything on chloride in the IV fluids.


About 100 yrs ago, Hamburger found that erythrocytes maintained their shape when suspended in saline compared with suspension in more concentrated or dilute solutions. Use of saline started after that for replacement fluid.

Physiologically balanced crystalloids such as Ringer’s lactate or Hartmann’s have electrolyte contents closer to human plasma.

Picture below explains possible mechanism of damage due to chloride

Following is the composition of various IVF we use in clinical practice.

Given the conflicting results from various studies, search for an “ideal crystalloid” is still elusive.


  1. What is the ideal crystalloid? Karthik Raghunathan, Patrick Nailer Curr Opin Crit Care 2015, 21:309–314
  2. Intravenous balanced solutions Thomas Langer et al., Anaesthesiology Intensive Therapy 2015, vol. 47, s78–s88
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