Phosphate Dosing - Units and Terminology Confusion

A previous discussion was about selecting a phosphate repletion product.  Selecting a drug product can be confusing because of the similar names of the various formulations - which are not interchangeable.  Harm can come if one is unaware of the other electrolytes (sodium and potassium) that are necessarily included in the phosphate salt drug.  This discussion aims to clarify further confusion that is possible with regards to terminology and also units (and yes, we'll include just a bit of math).  We will also give a clear example where a published trial could lead someone to a wrong conclusion if they do not mind their units.

 

Terminology

Let's take a moment to see how to use the terms surrounding hypophosphatemia correctly - because seeing phosphorus, phosphate, phosphorous, and organic/inorganic phosphate can be daunting.

• Phosphorus - this refers to the atom (the multivalent nonmetal element on the periodic table).  It doesn't really exist in our bodies (or otherwise in nature) in this form because it is highly reactive.
• This is often used when referring to serum concentrations.
  
• Phosphorous (with an additional "o" compared to the element) - this refers to something related to or containing phosphorus and is an adjective for phosphorus. Think poisonous or anxious - related to or containing poison or anxiety, respectively.
  
• Phosphate^Ref is the molecule (PO4^3-) and exists in our bodies either as organic or inorganic forms.
  
• Organic is most of the phosphate in the body - think of the phospholipid bilayer of cell membranes.
• Inorganic is the form of almost all of the phosphate in the extracellular space.  It is mostly the free ion but a smaller amount is bound to proteins or other electrolytes (think calcium-phosphate precipitation).
  
• In the United States, laboratories technically measure the inorganic phosphate but express the result in mg/dL of phosphorus in laboratory results.  
• When comparing phosphate to phosphorus in mmol/L, the values are the same (because there are equal atoms per given volume).
• When changing between phosphate & phosphorus in mmol & mg per a unit volume or dose, there are two conversion factors that are useful. Here they are, plus one example each where they apply clinically.
• One conversion factor is 3.1 (or 0.323, the inverse - depending on if you feel like multiplying or dividing).
• This one is used when changing between mmol/L of phosphate and mg/dL of phosphorus - note both the numerator unit and the volume are changing.
• Example: You're reading an article that for some reason is looking at critically ill patients with phosphate in the serum <0.6 in mmol/L. You realize this is odd because at your institution, in the United States, serum concentrations are usually phosphorus in mg/dL. You realize the need to convert from mmol/L to mg/dL so you multiply the 0.6 mmol/L that the study used by 3.1 and get 1.86 mg/dL phosphorus.  This is exactly what this study did.  They replaced phosphate in the ICU and provided a simple equation which might help estimate what to give an individual patient.  But note, their equation also uses serum phosphate concentration in mmol/L so you have to translate this to mg/dL phosphorus if that is how your laboratory gives you results.  I'll do that for you here:
• Dose (in mmol) = 0.5 x body weight (kg) x (3.875 - serum phosphorus [in mg/dL])
• 3.875 is there because it was their goal (1.25 from the study x 3.1 conversion factor).  The volume of distribution was 0.5 L/kg so the equation is just: Dose = Vd x desired concentration change. This is a simple pharmacokinetic equation, rearranged (conc = dose/Vd)
  
• Another conversion factor is 30.9 (which is simply the molecular weight [mg/mmol] of phosphorus).
  
• This one allows us to change between mg of phosphorus and mmol but without changing the volume/dose.
  
• Example: If you're picking a drug product and the label says it contains 250 mg phosphorus per tablet (e.g., K-PHOS No2), you would just divide 250 mg by 30.9 and get 8 mmol.  This is exactly what you find on a number of the medication labels discussed in the previous post.
• Milliequivalents are not used when describing measurements of phosphate or for dosing (as they are with other electrolytes).  This is because mEq depends on valence.  For something like sodium, with a valence consistently of 1, 1 mmol equals 1 mEq.  But for phosphate, the valence changes based on pH so the conversion will be different depending on the sample and it's impractical to apply pH-appropriate valences to every sample we draw. Here is some extra help if you really want to grasp this concept.
  

Dosing

Here is this author's opinion about dosing.  When you pick a phosphate repletion product, realize the dose you are selecting is likely the amount of phosphate and is best thought of in "mmol" of phosphate.  In other words, when you select potassium phosphate IV and select 15 mmol from the drop-down menu, you're getting 15 mmol of phosphate, yes, but you're also unavoidably getting a significant amount of potassium (22 mEq exactly - see the previous post for the full table). For the oral products, especially, if you actually pull out a product and look at the label, you are going to see all sorts of salt formulations and details.  For example, K-PHOS No 2 says "Each tablet contains potassium acid phosphate 305 mg and sodium acid phosphate, anhydrous, 700 mg. Each tablet yields approximately 250 mg of phosphorus, 88 mg of potassium or 2.3 mEq and 134 mg of sodium or 5.8 mEq."  Ignore anything about this or that acid and anything about milligrams.  Just look at the table from the previous post and realize each tablet has 8 mmol of phosphate, 5.8 mEq of sodium, and 2.3 mEq of potassium.

 

Take home points:

• Phosphorus and phosphate concentrations in laboratory work are not 1:1 conversions if one is in mmol and the other is in mg. Pay attention to units!
• Conversion factor 3.1 allows you to go from mg/dL phosphorus to phosphate (multiplying 3.1 times the phosphate in mmol/L to get mg/dL phosphorus).
• The amount of phosphate in various products can be confusing.  Consult the table, pick the product based on mmol phosphate, and don't forget there will be sodium/potassium joining your phosphate (there is no way around this!).
   

References:

Iheagwara OS, Ing TS, Kjellstrand CM, Lew SQ. Phosphorus, phosphorous, and phosphate. Hemodial Int. 2013 Oct;17(4):479-82. doi: 10.1111/hdi.12010. Epub 2012 Dec 20. PMID: 23279081.

Bech A, Blans M, Raaijmakers M, Mulkens C, Telting D, de Boer H. Hypophosphatemia on the intensive care unit: individualized phosphate replacement based on serum levels and distribution volume. J Crit Care. 2013 Oct;28(5):838-43. doi: 10.1016/j.jcrc.2013.03.002. Epub 2013 Apr 30. PMID: 23642477.

photo by Joshua Kuhn (no changes made)