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. Tonicity vs Osmolality: Where Do Fluids Go?

1. What is the difference between Osmolality and Tonicity?
   1. Osmolality is the concentration of how much “stuff” is in a solution. Tonicity is a measure of how many of those particles are “effective osmoles” and exert osmotic pressure.
   2. Effective Osmoles are those that are able to move or hold onto water in the extracellular space
   3. For example, Na and Cl are effective osmoles that help maintain fluid in the extracellular space. Urea is an example of an ineffective osmole that diffuses freely among all the fluid spaces in the body, and therefore urea does not contribute to water movement
2. Body Fluid Distribution
   1. Of total body water, Two-thirds are intracellular and one-third is extracellular
   2. Of the extracellular space, only one quarter is intravascular, and the rest is interstitial. So the intravascular space is one quarter of one third, or one twelfth of total body water.
3. Where do fluids go?
   1. Isotonic fluids (e.g. Normal Saline, Lactated Ringers): Similar tonicity to plasma, ~280 mOsm
      1. Effective osmoles maintain the fluid in the extracellular space only
      2. Since they distribute across the whole extracellular space, only one quarter remains in the intravascular space. For example, for every 1L of NS, only 250cc remains in intravascular space
   2. Free water: Tonicity of 0
      1. No effective osmoles, so distributes to all spaces, intracellular and extracellular
      2. Since it distributes to all body water, only one twelfth remains in the intravascular space. For example, for every 1L of free water, only 83cc remains in intravascular space
   3. Half normal saline: Tonicity ~154 mOsm
      1. Somewhere in between! As a rough estimate, for every 1L of half NS, 167cc remains in intravascular space

. Hypotonic Fluids: Water or Sugar?

1. What is D5W?
   1. Free water with 5% dextrose, or 50g of dextrose per liter.
   2. Dextrose added to make the solution initially isotonic to prevent red cell lysis. But dextrose is rapidly metabolized, and it becomes free water with tonicity of 0.
2. How much sugar is that?
   1. 50g of sugar is about 2 candy bars. One pint of Ben and Jerry’s is 6.5L of D5W.
   2. May raise the glucose, but more important to give free water if needed–you can always treat the hyperglycemia with insulin
   3. D5 maintenance fluids only provides a few candy bars a day and doesn’t provide much nutrition
3. Does D5W cause volume overload?
   1. Remember from pearl 1: for every liter of D5W, only 83cc remains intravascularly. Only one third as much as an isotonic fluid like NS
   2. Unless given in huge volumes, rarely clinically causes fluid overload or pulmonary edema
4. How do you think about half NS?
   1. Can think of this as half isotonic fluid and half free water
   2. Use then when patient is both hypovolemic and hypernatremic, trying to fix two things at once

. Isotonic Fluids: Embrace the Debate

1. Contents of isotonic fluids
   1. Normal Saline: Just salt and water
      1. 154 mEq of sodium and 154 mEq of chloride
      2. Isotonic, but has way more chloride than plasma, which is ~100 mEq/L
   2. Balanced solutions: try to match normal plasma
      1. Main examples are Lactated Ringers and Plasma-Lyte
      2. Have sodium, chloride, and potassium concentrations similar to plasma, as well as a buffer
      3. Buffers are different–LR uses sodium lactate and Plasma-Lyte uses acetate–but both buffers are metabolized into bicarbonate in the body
2. Normal Saline vs Balanced Solutions–does it really matter?
   1. SALT-ED and SMART trials:
      1. Large single center studies in the ED and ICU comparing NS vs LR for resuscitation. They showed decreased mortality and better renal outcomes with LR
   2. BASICS and PLUS trials:
      1. BASICS: Multicenter study in ICU patients in Brazil comparing NS and Plasma-Lyte, found no difference in mortality or renal outcomes
      2. PLUS: Multicenter study in ICU patients in Australia and New Zealand comparing NS and Plasma-Lyte, found no difference in mortality or renal outcomes
   3. Meta-analysis
      1. Large meta-analysis pooling 13 RCTs and >35,000 patients comparing NS and balanced solutions in ICU patients found a trend toward improved mortality and renal outcomes with balanced solutions, but did not quite reach significance
   4. Proposed mechanisms of difference: too much chloride!
      1. High chloride in NS causes non-gap metabolic acidosis
      2. The macula densa in the distal tubule uses chloride delivery as a proxy to measure flow in the tubule. Supraphysiologic chloride delivery “tricks” the kidney into thinking flow is very high, causing tubuloglomerular feedback to reduce GFR
   5. Given possible improved outcomes, many providers now favor LR and other balanced solutions over NS, but more data is needed
3. Truths and Myths for when to avoid LR
   1. Hyperkalemia: Potassium in LR is a drop in the bucket, minimally affects serum potassium
   2. Elevated lactate: LR contains sodium lactate, not lactic acid. Sodium lactate is actually metabolized into bicarbonate. It does not cause acidemia
   3. Hypercalcemia: LR contains a small amount of calcium. Expert opinion remains mixed on whether to avoid any calcium in hypercalcemia, or whether just like in hyperkalemia, this calcium is a drop in the bucket compared to total body calcium

Colloid

1. What is oncotic pressure? How is it different from tonicity?
   1. Tonicity is used for salts and describes effective osmoles between extracellular and intracellular spaces.
   2. Oncotic Pressure (or Colloid Osmotic pressure) is used instead for large molecules like proteins. Oncotic pressure determines water flow within that extracellular space, i.e. between the intravascular and interstitial spaces.
   3. Proteins, like albumin, remain in the intravascular space and can draw water from the interstitium back into blood vessels
2. Are colloids, like albumin, better for volume resuscitation?
   1. Because of its ability to draw water into the intravascular space, 25g of albumin expands intravascular space by 450cc!
      1. Compare this to only 250cc of intravascular fluid for 1L of LR or NS
   2. Studies have repeatedly shown that colloids like albumin are no better than isotonic fluids in sepsis or in the ICU.
   3. Likely due to short half-life of the true profound intravascular expansion.
      1. Inflammation further reduces this effect by increasing vascular permeability and reducing benefit of albumin

Blood

1. Blood as an intravascular expander
   1. 1U pRBC contains about ~300cc, but that all stays in the intravascular space. (compared to only 250cc for 1L of LR or NS)
   2. Unlike albumin, blood is not an oncotic force and does not draw more fluid into the vasculature. In terms of number of particles, there are many fewer blood cells than molecules of albumin, so pRBC is actually hypo-oncotic.

Contributors

Zach Avigan, MD - Author, Host
Samira Farouk, MD - Author, Expert on Air
Matt Sparks, MD - Author, Expert on Air
Shreya Trivedi, MD, ACP Member - Host
Jeffrey Williams, MD - Author, Expert on Air

Reviewers

Swapnil Hiremath, MD, MPH
Helbert Rondon, MD, FACP

Those named above, unless otherwise indicated, have no relevant financial relationships to disclose with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.  All relevant relationships have been mitigated.

Release Date: April 28, 2022

Expiration Date: April 28, 2025

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