What does serum carbon dioxide (CO2) tell us about a patient's acid-base balance?

Serum Carbon Dioxide as an Indicator of Acid-Base Balance

Serum carbon dioxide (CO2) is a critical laboratory value that primarily reflects the bicarbonate concentration in blood and serves as a key indicator of metabolic acid-base status, with values below 22 mmol/L suggesting metabolic acidosis and values above 29 mmol/L indicating metabolic alkalosis. 1

Understanding Serum CO2 Measurement

Serum CO2 measurement is typically included in basic metabolic panels and primarily reflects:

• Bicarbonate (HCO3-) concentration (the predominant component)
• Dissolved CO2
• Carbonic acid
• Carbamino compounds

Key points about serum CO2 measurement:

• Normal range: 22-29 mmol/L 1
• Primary method: Direct measurement of total serum CO2 concentration in basic metabolic panels 2
• Alternative method: Indirect calculation via Henderson-Hasselbalch equation using pH and pCO2 2
• Potential confounders: Increased serum lipids or proteins (as in multiple myeloma) can cause falsely low readings 2

Interpretation of Serum CO2 Values

Low Serum CO2 (<22 mmol/L)

Low serum CO2 typically indicates metabolic acidosis, which can be classified as:

1. Anion gap metabolic acidosis (anion gap >12 mEq/L) 1

   • Causes: Diabetic ketoacidosis, lactic acidosis, toxic alcohol ingestion, renal failure
   • Further evaluation: Calculate osmolal gap, perform gap-gap analysis 3

2. Non-anion gap metabolic acidosis (normal anion gap 8-12 mEq/L) 1

   • Causes: Renal tubular acidosis, diarrhea, ureterosigmoidostomy
   • Further evaluation: Calculate urine anion gap 3

3. Severity classification based on total CO2 level: 1

   • Mild: ≥19 mmol/L
   • Moderate to Severe: <19 mmol/L

High Serum CO2 (>29 mmol/L)

Elevated serum CO2 typically indicates metabolic alkalosis:

• Causes: Vomiting, nasogastric suction, diuretic use, hypokalemia
• Evaluation: Measure urine chloride levels to determine if chloride-responsive or chloride-resistant 3

Clinical Significance and Impact

Chronic Kidney Disease (CKD)

• Chronic metabolic acidosis contributes to osteodystrophy in CKD patients 4
• Steps to maintain serum CO2 >22 mmol/L are warranted for:
  • Improvement in bone histology
  • Amelioration of excess protein catabolism 4
  • More effective therapy of osteodystrophy 4

Bone Health

• Chronic metabolic acidosis (low serum CO2) is associated with:
  • Bone dissolution and fractures
  • Reduced bone mineral density
  • Decreased bone formation rates 4
  • Impaired linear growth in children 4

Exercise Physiology

• Premature metabolic acidosis during exercise (indicated by low anaerobic threshold) can occur in:
  • COPD
  • Interstitial lung disease
  • Pulmonary vascular disease
  • Heart failure
  • Mitochondrial myopathy
  • Deconditioning 4

Clinical Applications

Monitoring Recommendations

• Regular monitoring of serum CO2 is recommended in:
  • CKD Stages 3,4, and 5
  • Patients on maintenance dialysis 4
  • Kidney transplant recipients 4

Treatment Considerations

When low serum CO2 indicates metabolic acidosis:

• Mild acidosis (CO2 ≥19 mmol/L): Monitor and address underlying cause
• Moderate to severe acidosis (CO2 <19 mmol/L): 1
  • Initial fluid resuscitation with isotonic saline (15-20 mL/kg/hr)
  • Consider bicarbonate therapy for severe acidosis (pH <7.2)
  • Target serum bicarbonate ≥22 mmol/L with alkali replacement therapy

Pitfalls and Caveats

• Pseudohypobicarbonatemia: Falsely low serum CO2 can occur in patients with paraproteinemias (e.g., multiple myeloma) 2
• Mixed acid-base disorders: Serum CO2 alone may not reflect complex acid-base disturbances; arterial blood gas analysis may be needed 3
• Compensation: Respiratory compensation for metabolic disorders can affect interpretation; evaluate pH and pCO2 alongside serum CO2 5
• Citrate-containing alkali salts: Should be avoided in CKD patients exposed to aluminum salts as they may increase aluminum absorption 4

Algorithm for Interpreting Low Serum CO2

1. Confirm low serum CO2 (<22 mmol/L)
2. Calculate anion gap: [Na+] - ([Cl-] + [HCO3-])
3. If anion gap >12 mEq/L: Evaluate for anion gap metabolic acidosis
4. If anion gap normal (8-12 mEq/L): Evaluate for non-anion gap metabolic acidosis
5. Assess for respiratory compensation (expected pCO2 = 1.5 × [HCO3-] + 8 ± 2)
6. Consider arterial blood gas analysis for complex cases
7. Target treatment to maintain serum CO2 ≥22 mmol/L