Strong Ion Difference

Reviewed and revised 5/5/12


  • aka the Stewart method (1980s) or the physicochemical method
  • pH is not only determined by the [H+] and [HCO3-] -> other ions in solution influence pH
  • there are dependent and independent variables determining pH


  • H+
  • OH-
  • HCO3-
  • CO32-
  • HA (weak acid)
  • A- (weak ions)


  • PCO2
  • ATOT (total weak non-volatile acids)
  • SID (net Strong Ion Difference)

The influence of the independent variables can be predicted through 6 simultaneous equations:

  1. [H+] x [OH-] = K ‘w (water dissociation equilibrium)
  2. [H+] x [A-] = KA x [HA] (weak acid)
  3. [HA] + [A-] = [ATOT] (conservation of mass for “A”)
  4. [H+] x [HCO3-] = KC x PCO2 (bicarbonate ion formation equilibrium)
  5. [H+] x [CO32-] = K3 x [HCO3-] (carbonate ion formation equilibrium)
  6. [SID] + [H+] – [HCO3-] – [A-] -[CO32-] – [OH-] = 0 (electrical neutrality)


  • strong ions = those ion that dissociate totally at the pH of interest in a particular solution.
  • in blood (pH 7.4): strong cations = Na+, K+, Ca2+, Mg2+ and strong anions = Cl- and SO42-
  • SID = the difference between the concentrations of strong cations and strong anions.

SID = (Na+ + K+ + Ca2+ + Mg2+) – (Cl- – other strong anions)

Abbreviated SID = (Na + K+) – (Cl-)

  • the number of positive and negative ions in a solution must be equal (SID = 0)
  • increased SID (>0) -> alkalosis (increase in unmeasured anions)
  • decreased SID (<0) acidosis
  • with normal protein levels SID is about 40mEq/L -> alkaline (any departure is roughly equivalent to the standard base-excess, although because SID doesn’t allow for Hb there is often a discrepancy)

The SID can be changed by two methods:

(1) Concentration change

  • dehydration -> concentrates the alkalinity -> increases SID
  • overhydration -> dilutes the alkaline state -> dilutional acidosis -> decreased SID

(2) Strong Ion changes

  • low Na+ -> decreased SID -> acidosis
  • high Na+ -> increased SID -> alkalosis
  • increased Cl- -> decreased SID -> acidosis (NAGMA)
  • increased in organic acids (lactate, formate, ketoacids) -> acidosis (RAGMA))


  • ATOT = total plasma concentration of inorganic phosphate, serum proteins and albumin (weak non-volatile acids)

ATOT = [PiTOT] + PrTOT] + albumin

  • hypoproteinaemia -> base excess


  • at a molecular level it is the concentration of CO2, not the partial pressure which governs its effect on other molecules and ions. However, in practice our warm blood means that CO2 is scarcely soluble and measured PCO2 can be used measure effect.


  • acknowledgement of the importance of other factors controlling pH
  • diminishes the importance of the HCO3- ion which is just a dependent variable


  • complex
  • calculation of small differences between large numbers of variables -> decreases accuracy
  • SID only reflect plasma (where as SBE reflects the whole body and Hb’s influence)
  • lack of clinical correlation to validate benefit
  • standard base excess accuracy has been well validated and accepted in clinical correlation

References and links

Journal articles and textbooks

  • Yentis, S.M., et al (2004)“Anaesthesia and Intensive Care A-Z: An Encyclopaedia of Principles and Practice” Elsevier, 3rd Edition (A-Z)

Social media and web resources

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  1. Greg Kelly says

    Chris, what are your thoughts on excluding the lactate (which is a strong anion) from the short form SID equation (i.e. using Na + K -- Cl rather than Na + K -- Cl -- lactate)? It’s convenient, but there are situations where it matters.

    Take Hartmann’s solution: the short form suggests that the SID of Hartmann’s solution is 29. Actually, it has a lactate of 29 and an SID close to 0. There are some people who maintain that the SID of Hartmann’s is 29. I’m not sure if this is dumb (because they’re missing 29mmols/L) or brilliant, as the lactate is converted to bicarb in vivo, and so the in vivo effect may be closer to a fluid with an SID of 29….

    • says

      Hey Kelly,
      It is true that lactate is a strong ion -- it fully dissociates at physiological pH. Technically I think it would be more correct to include lactate in the strong ion difference (SID) -- same with the other strong organic acids.
      I’m no expert but it seems to me that it is more convenient to treat lactate as an ‘unmeasured anion’ (at least if your background is in using the Henerson-Hasselbach/Boston method).
      This means that you can use SID (Na -- Cl) to immediately identify whether there is a metabolic alkalosis or a non-SIG metabolic acidosis (equivalent of NAGMA) present.
      Then the causes of a SIG metabolic acidosis are the same as for HAGMA: lactate, toxins, ketones and renal acids (LTKR = ‘left total knee replacement’).
      Scott Weingart’s approach to using the physico-chemical method follows the steps above (download his pdf here:
      I agree it also makes sense for Hartmann’s to have an SID of 29. Morgan et al showed that you need to give a solution with SID of 24 to maintain neutrality despite volume expansion (which dilutes strong ions, lessens the absolute SID and results in acidosis). Hartmann’s is close to this, but should cause an alkalosis if the SID is 29 -- which it does.

      • says


        You have intuited both the problem with most balanced solutions and the answer to your own question. The lactate in Hartmann’s is designed to take the place of bicarb. These fluids are designed to have metabolism of the buffer base (lactate in this case or acetate, citrate, etc.), so the SID is calculated with this assumption. However in a patient in the midst of hepatic failure with large volumes of Hartmann’s, the lactate may not be immediately metabolized. In this case, it becomes just another anion causing acidosis. The ultimate solutions would use bicarb itself as their buffer base to avoid this issue, but these solutions are not shelf stable. So in the pt with hepatic fx, should you include the lactate of the solution in the SID, probably not--the metab will be variable. You should just realzie that the pt may become acidotic just like they would with NS and further that their elevated lactate may be in part due to the fluid.

  2. Greg Kelly says

    Thanks both Chris and Scott, great answers. I also found this article which is the best I’ve seen on the clinical utility of the SID approach: Morgan, Critical Care 2005; 9: 204-11.

    I think the most accurate thing to say is “the in vitro SID of Hartmann’s is approximately 0, but the effective in vivo SID (given the conditions that Scott mentions) is close to 27.”

    • says

      Greg, I completely understand what you are saying and it probably is just semantics, but what you are going with is not the convention so people will either be confused or think you are wrong. SID of Harmann’s is 27. The in-vivo effects in an ahepatic patient may be an effective SID of 0.