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About 14% of critically ill patients receiving electrolyte-balanced crystalloids either developed kidney failure, needed kidney-replacement therapy or died compared with 15% receiving normal saline. This small but statistically significant benefit was only apparent when combining outcomes; there was no difference between fluids for the three individual outcomes analysed separately.

A solution of 0.9% sodium chloride (normal saline) is the most commonly used intravenous (IV) fluid, but it can cause biochemical imbalance. Alternative crystalloids like Ringer's lactate or Hartmann’s solution contain an electrolyte composition closer to normal blood fluid and are often seen as preferable.

This US trial compared 30-day outcomes for over 15,000 critical patients randomised to either fluid type. The difference in outcomes between fluid types was very small, but there is a difference in cost.

The small benefit perhaps argues against routine use of balanced crystalloids in all patients. Though what is most important is that the fluid and electrolyte needs of the individual are recognised and met.

Why was this study needed?

Many hospital patients need IV fluid replacement and maintenance, but errors in use are common. NICE states that many staff have inadequate knowledge of the composition of different fluids or of the needs of individual patients.

The 1999 National Confidential Enquiry into Perioperative Deaths reportedly found that up to 1 in 5 patients receiving IV fluid and electrolytes suffer complications due to improper use. Their 2011 report estimated that 30-day mortality was 20% for high-risk patients with poor fluid management before surgery compared with 5% with good fluid management.

Some observational studies suggest that balanced crystalloids are associated with lower rates of kidney failure and death compared with normal saline, but other evidence is conflicting.

A recent Cochrane review found insufficient evidence that balanced crystalloids give any benefit in terms of mortality or organ failure for surgical patients. This trial assesses this for medical and surgical patients in intensive care.

What did this study do?

The SMART cluster-randomised trial included 15,802 adults admitted to five intensive care units over a two-year period at one US medical centre.

Each month intensive care units were assigned to use 0.9% saline or balanced crystalloids (lactated Ringer’s solution or Plasma-Lyte A) for any patients who needed IV crystalloids. An electronic system checked for any patient contraindications to the assigned fluids (e.g. low potassium) before prescribing. Clinicians could also override the system if they felt a particular crystalloid was required for an individual patient.

The main outcome was a major adverse kidney event within 30 days, a composite of death, new kidney-replacement therapy or persistent kidney dysfunction (creatinine more than double the baseline level).

Neither patients nor assessors were aware of group assignment. The study was large enough to detect 1.9% difference in outcome rates between groups.

What did it find?

  • Balanced crystalloids just slightly reduced the risk of the composite outcome of a major kidney event within 30 days. 14.3% (1,139/7,942) of the crystalloids group experienced this outcome compared with 15.4% (1,211/7,860) of the saline group (odds ratio [OR] 0.91, 95% confidence interval [CI] 0.84 to 0.99).
  • Differences for the three individual outcomes fell short of statistical significance:
    • In-hospital death: 10.3% crystalloids vs 11.1% saline (OR 0.90, 95% CI 0.80 to 1.01).
    • Kidney-replacement therapy: 2.5% vs 2.9% (OR 0.84, 95% CI 0.68 to 1.02).
    • Persistent kidney dysfunction: 6.4% vs 6.6% (OR 0.96, 95% CI 0.84 to 1.11).
  • By subgroup, balanced crystalloids had the most effect in people with sepsis. Major kidney events occurred in 33.8% of people in this group who received crystalloids (395/1,167) compared with 38.9% (455/1,169) who received saline (OR 0.80, 95% CI 0.67 to 0.94).

What does current guidance say on this issue?

Recently updated NICE guidelines (2017) outline the principles of intravenous fluid therapy. Practitioners are recommended to follow protocols for assessment, fluid resuscitation if needed, followed by routine maintenance.

If the person has signs of low circulating blood volume (shock) and needs resuscitation, an initial 500ml of crystalloid (containing 130-154mmol/l sodium) is recommended with further management directed by the response and underlying cause.

If a person needs ongoing intravenous fluids, daily maintenance requirements are in the region of 25-30ml/kg water, 1mmol/kg sodium, potassium and chloride, and 50-100g glucose. Routine maintenance may need to be adjusted if the person has an imbalance of electrolytes or abnormal fluid distribution (e.g. into the tissues).

The NICE guideline (2017 update) used these costs per litre: 0.9% sodium chloride £0.70; Hartmann's £0.85; Ringer's lactate £1.25.

What are the implications?

Like other trials, these results suggest that balanced crystalloids make little difference to the risk of kidney dysfunction compared with normal saline. From an organisations perspective, the small benefit may need considering against the increased cost of using crystalloids routinely for all critically ill patients.

Any treatment decision will depend on the reason for admission, underlying condition and characteristics of the patient, use of other drugs and the total volume of fluid needed.

What seems most important is that all patients are viewed on an individual basis with regular monitoring of their individual fluid and electrolyte needs.

Citation and Funding

Semler MW, Self WM, Wanderer JP et al. Balanced crystalloids versus saline in critically ill adults. N Engl J Med;378;9:829-39.

This project was funded by the Vanderbilt Institute for Clinical and Translational Research.



Bampoe S, Odor PM, Dushianthan A, et al. Perioperative administration of buffered versus non-buffered crystalloid intravenous fluid to improve outcomes following adult surgical procedures. Cochrane Database Syst Rev. 2017;9:CD004089.

NCEPOD. Peri-operative care: knowing the risk. London: National Confidential Enquiry into Patient Outcomes and Deaths. 2011.

NICE. Intravenous fluid therapy in adults in hospital. CG174. London: National Institute for Health and Care Excellence; 2013, updated May 2017.

Produced by the University of Southampton and Bazian on behalf of NIHR through the NIHR Dissemination Centre


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