Strong Ion Difference (SID) Formulas and Calculations
Apparent Strong Ion Difference (SIDa)
The apparent SID is calculated as the difference between measured strong cations and measured strong anions in plasma. 1
SIDa = ([Na+] + [K+] + [Ca2+] + [Mg2+]) - ([Cl-] + [Lactate])
- This represents the charge difference between the sum of measured strong cations (sodium, potassium, calcium, and magnesium) and measured strong anions (chloride and lactate) 1
- A simplified version using only the major strong ions is: SIDa = [Na+] - [Cl-], which represents the most quantitatively important contributors to the strong ion difference 1
- Normal SIDa values are approximately 40-42 mEq/L 2
Effective Strong Ion Difference (SIDe)
The effective SID represents the strong ion difference required to balance the negative charges from weak acids (albumin and phosphate) and bicarbonate. 3, 4
SIDe = [HCO3-] + [Albumin charge] + [Phosphate charge]
Or more specifically:
SIDe = [HCO3-] + [A-]
Where [A-] is the negative charge on albumin and phosphate 3
- The albumin contribution can be calculated as: 0.343 mmol/g of total protein or 0.622 mmol/g of albumin 5
- The net protein charge of plasma is approximately 10.5 mEq/L, equivalent to 0.19 mEq/g of total protein or 0.34 mEq/g of albumin 5
- This value represents the buffer base component of the acid-base system 3
Strong Ion Gap (SIG)
The SIG detects the presence of unmeasured anions in plasma and is calculated as the difference between the apparent and effective SID. 3, 2
SIG = SIDa - SIDe
Or expanded:
SIG = ([Na+] + [K+] + [Ca2+] + [Mg2+]) - ([Cl-] + [Lactate]) - ([HCO3-] + [Albumin charge] + [Phosphate charge])
- Normal SIG values should be close to 0 mEq/L (mean 0.5 ± 1.5 mEq/L) 3
- An elevated SIG indicates the presence of unmeasured strong anions such as ketoacids, uremic toxins, or other organic acids 2, 5
- Unlike the traditional anion gap, the SIG remains stable across extreme variations in PCO2 and pH, making it more reliable in complex acid-base disturbances 3
Clinical Application and Advantages
- The SIG is superior to the traditional anion gap for detecting unmeasured anions when serum albumin or phosphate concentrations are markedly abnormal 2
- A decrease in SID results in an acidifying effect on plasma, while an increase in plasma chloride relative to sodium decreases the plasma SID and lowers pH 1
- The SIG is not affected by severe respiratory acidosis and alkalosis, unlike the anion gap which shows direct correlation with pH (R² = 0.51-0.65) 3
- The strong ion approach is mechanistic rather than descriptive, making it valuable for determining the underlying cause of acid-base disturbances in critically ill patients 2
Important Caveats
- The anion gap may overestimate severity with concomitant acute kidney injury or ketoacidosis, or underestimate severity with hypoalbuminemia 6, 7
- While the SIG provides mechanistic insight, traditional markers (pH, base excess, lactate) remain important for prognostic assessment and should not be abandoned 8
- The SIG requires accurate measurement of multiple electrolytes and calculation of weak acid charges, which may limit its practical utility in some clinical settings 2, 5