How to Calculate SIDe (Effective Strong Ion Difference)
The effective strong ion difference (SIDe) is calculated as the sum of bicarbonate and the negative charges on albumin and phosphate: SIDe = [HCO3⁻] + [Albumin charge] + [Phosphate charge]. 1
Formula Components
The complete calculation requires three elements 1:
- Bicarbonate concentration (measured or calculated from blood gas analysis)
- Albumin charge contribution: [Albumin (g/L)] × (0.123 × pH - 0.631)
- Phosphate charge contribution: [Phosphate (mmol/L)] × (0.309 × pH - 0.469)
Complete Equation
SIDe = [HCO3⁻] + [Albumin (g/L) × (0.123 × pH - 0.631)] + [Phosphate (mmol/L) × (0.309 × pH - 0.469)] 2
Alternatively expressed as: SIDe = (1,000 × 2.46 × 10⁻¹¹ × PaCO2/10⁻pH) + [Albumin × (0.123 × pH - 0.631)] + [Phosphate × (0.309 × pH - 0.469)] 2
Clinical Context and Interpretation
Relationship to SIDa (Apparent Strong Ion Difference)
SIDa represents the measured strong cations minus strong anions: SIDa = [Na⁺] + [K⁺] + [Ca²⁺] + [Mg²⁺] - [Cl⁻] - [Lactate] 1, 3
In simplified form when only sodium and chloride are considered: SIDa ≈ [Na⁺] - [Cl⁻] 1
Strong Ion Gap (SIG)
The strong ion gap quantifies unmeasured anions and is calculated as: SIG = SIDa - SIDe 3, 2, 4
- Normal SIG values range from approximately 0 to 3 mEq/L 3, 4
- Elevated SIG indicates the presence of unmeasured anions (e.g., ketones, uremic toxins, toxic alcohols, salicylates) 3, 2, 5
Clinical Applications
Critical Illness and Acid-Base Assessment
In critically ill patients with apparently normal pH, underlying mixed metabolic disorders are common, characterized by:
- Low SIDa from hyperchloremia (acidifying effect) 3
- Elevated SIG from unmeasured anions (acidifying effect) 3
- Low albumin (alkalinizing effect through reduced ATOT) 3
Prognostic Value
Elevated SIG on admission predicts mortality in burn patients 2, 5:
- In adult burn patients, admission SIG has an odds ratio of 1.11 for mortality 2
- In pediatric burn patients with severe injuries, nonsurvivors had SIG of 33.9 ± 14 mEq/L versus 14.9 ± 0.3 mEq/L in survivors 5
Advantages Over Anion Gap
SIG remains stable across extreme pH changes (pH 6.85 to 7.55), unlike the anion gap which correlates directly with pH (R² = 0.51-0.65) 4. This pH stability makes SIG superior for detecting unmeasured anions in patients with severe respiratory acid-base disturbances 4.
Important Caveats
pH-Dependent Calculations
The albumin and phosphate charge calculations are pH-dependent, requiring simultaneous measurement of arterial pH 2, 6. Changes in pH alter protein ionic binding and cause transerythrocyte ion shifts that affect plasma SID without changing whole blood strong ion difference 6.
Expected SID Changes
During acidosis, plasma SID increases predictably due to electrolyte redistribution (albumin ionic-binding and transerythrocyte chloride shifts) 6. In experimental acidosis, plasma SID increased by 7.8-12.7 mEq/L depending on albumin and hemoglobin concentrations, but these changes reflected redistribution rather than true metabolic derangement 6.
Dialysis Considerations
In hemodialysis patients, SIDe tracks alkalinization more accurately than SIDa 7. During a typical hemodialysis session, SIDe increases by approximately 5.3 mEq/L while SIDa increases only 1.3 mEq/L, with SIDe fully accounting for the observed pH change 7.