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IV Fluid Selection - Part 1 (Resuscitative IV Fluids)

Neda Frayha, MD and Maj Cina, MD

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Most of us order normal saline for our inpatients as easily as we breathe the air around us. But it’s not always the best choice for our patients, even in resuscitation scenarios. In this segment, Maj Cina and Neda Frayha discuss the evidence behind colloids vs crystalloids and then, within crystalloids, emerging evidence in favor of balanced fluids instead of normal saline.


  • For the sick patient who needs fluid resuscitation, crystalloids (water with electrolytes of some sort like normal saline, lactated ringers, pPlasma-lLyte) are preferred over colloids (ie: starches, albumin).

  • When thinking about crystalloids, the evidence (SMART and SALT-ED trial) are in favor of balanced solutions like lactated ringers or pPlasma-lLyte over normal saline.

  • Stay tuned next month for a fluid talk on maintenance fluids!


  • Why does IV fluid selection even matter?

    • Fluids are like any other drug so we need to consider the impact of them on our patients.

  • Crystalloids vs. colloids:

    • Crystalloids imply water with added electrolytes or buffers for making the fluid basic.

    • Colloids are usually synthetic or purified from other animals (ie: albumin). Designed to have more oncotic pressure and resuscitate intravascular volume with lesser quantities.

  • How to decide between crystalloids vs. colloids:

    • Colloids have NOT been shown to be superior to crystalloids in most cases and in some cases have been shown to be harmful (ie: hyper-oncotic starches like the hydroxyethyl starch) leading to acute kidney injury, renal replacement therapy or even mortality.

    • For most studies the outcomes are similar. A meta-analysis in 2001 and another study in NEJM 2004 showed no significant benefit to 4% albumin to normal saline.

      • Finfer S et. al.  A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004 May 27;350(22):2247-56. PMID: 15163774.

    • The Crystal Study in JAMA 2013 (randomized control trial) showed colloids may be superior to crystalloids for patient with hypovolemic shock with fewer ventilation days, fewer vasopressor days and a lower 90-day mortality but no difference in 28-day mortality or need for 90-day renal replacement therapy.  Authors noted “this finding should be considered exploratory”.

      • Annane D et. al. Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial. JAMA. 2013 Nov 6;310(17):1809-17. PMID: 24108515.

    • Generally, the different medical societies don’t recommend colloid as first-line therapy and recommend their use as adjunctive.

    • Colloids are also more expensive

  • Crystalloids:

    • 0.9% sodium chloride and water (“normal saline”, NS)

      • Higher chloride concentration than lactated ringers and physiologic range

        • Hyperchloremia induces renal vasoconstriction, diminishing GFR and increasing the risk for acute kidney injury. This has been shown in many observational cohort studies.

      • pH 5.5 (normal human pH 7.4), which can lead to hyperchloremic acidosis and in return cause a shift of intracellular potassium (via the H+-K+ exchange pump) to the serum

    • Lactated ringers (LR) solution

      • Around for decades but several decades ago we started to add lactate to it to make it more alkaline relative to normal saline.

      • Chloride concentrations close to physiologic range

      • pH 6.5

      • Contains 4-5mEq of potassium (which is about where you want your patient’s potassium level)

        • Pearl: This is often the reason behind fear of LR, especially in patient prone to hyperkalemia such as those with renal failure. However, in reality LR is closer to physiology and the acidity of NS may actually worsen hyperkalemia.

      • Does it change your lactate level, a common marker we use to guide sepsis management?

        • Little evidence around this issue but one small trial that looked at pre- and post-LR administration showed no difference in serum lactate levels. Whether or not this holds for an acutely ill patient is unknown.

    • Plasma-lyte:

      • pH closer to 7.4

      • K of 5mEq

      • Buffered with acetate with some theoretical risk of cardiotoxicity in large volumes that is unproven

  • The SALT-ED trial:

    • Method: “Randomized” control trial of all patients who came to the ED at Vanderbilt University over a period of 16 months. Each month NS or a balanced solution (mostly LR) was given in rotation for patients who got at least 500ml of resuscitative fluid and were then admitted. Data gathered with intention-to-treat.

      • 13,000 patients were enrolled

      • Once admitted to the medical floor (not ICU), fluids were not controlled.

      • Primary outcome: number of hospital-free days

      • Secondary outcome: composite of adverse kidney events (death and dialysis) + persistent renal dysfunction within 30 days (creatinine double the baseline)

    • Outcome:

      • No difference in primary outcome

      • 5.6% risk of secondary outcome in NS group and 4.7% in LR group with a number-needed-to-treat (NNT) of 111.

        • In other words, if you use LR over NS for 111 patients, you will save one patient from the secondary outcome (renal complications) with no change in the primary outcome (number of hospital-free days.

      • Largest benefit came in those patients who received large volume resuscitation and those with a diagnosis of sepsis.

    • Bottomline: A balanced solution (LR, Plasma-lyte, Hartman’s solution) should be your go-to rather than normal saline.

    • Self W et. al. Balanced Crystalloids versus Saline in Noncritically Ill Adults. N Engl J Med. 2018 Mar 1;378(9):819-828. PMID: 29485926.

  • The SMART Trial:

    • Method: Sixteen different ICU’s from Vanderbilt were assigned a different rotating crystalloid resuscitation fluid for a month at a time over a 16 month period.

      • 15,800 patients were enrolled

      • Primary outcome: composite of adverse kidney events (death and dialysis) + persistent renal dysfunction within 30 days (creatinine double the baseline) or at time of discharge

    • Outcomes:

      • 14.3% risk of primary outcome in NS group and 15.4% in LR group with a number-needed-to-treat (NNT) of 94.

      • Trend toward mortality benefit with a p of 0.06, NNT 125.

      • Largest benefit came in those patients who received large volume resuscitation and those with a diagnosis of sepsis.

        • These patients had 29.4% in NS group vs. 25.2% in the LR group, NNT 24.

    • Bottomline: There wasn’t a harm in using balanced fluids and if anything a benefit.

    • Semler MW et. al. Balanced Crystalloids versus Saline in Critically Ill Adults. N Engl J Med. 2018 Mar 1;378(9):829-839. PMID: 29485925.

  • Cost difference between NS and balanced solutions is minimal in most hospitals.

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A Hyperthyroid Fetus Full episode audio for MD edition 181:09 min - 85 MB - M4AHippo Primary Care RAP June 2018 Written Summary 1 MB - PDF