What is the appropriate work‑up for a patient with a metabolic acidosis (pH 7.28, base excess –8.5 mEq/L) who has no ketosis or elevated lactate?

Investigation of Metabolic Acidosis with Base Excess -8.5 and pH 7.28 (Non-Ketotic, Non-Hyperlactataemic)

In a patient with metabolic acidosis (pH 7.28, base excess -8.5 mEq/L) who has no ketosis or elevated lactate, you must immediately calculate the anion gap to determine whether this is a high anion-gap or normal anion-gap (hyperchloremic) acidosis, as this single calculation directs the entire diagnostic pathway. 1

Initial Laboratory Assessment

Obtain the following measurements immediately:

• Serum electrolytes (sodium, potassium, chloride, bicarbonate) to calculate the anion gap 1, 2
• Serum creatinine and urea to assess renal function 2
• Serum albumin to calculate the albumin-corrected anion gap, as hypoalbuminemia can mask an elevated anion gap 3
• Serum glucose to exclude diabetic ketoacidosis 2
• Arterial blood gas (if not already obtained) to confirm pH, PaCO₂, and assess respiratory compensation 1, 2
• Urinalysis including urine pH, glucose, and protein 1

Calculate the Anion Gap

Anion gap = [Na⁺] - ([HCO₃⁻] + [Cl⁻]) with normal values of 10-12 mEq/L 2, 4

Calculate the albumin-corrected anion gap because every 1 g/dL decrease in albumin below 4 g/dL reduces the anion gap by approximately 2.5 mEq/L 3

Diagnostic Algorithm Based on Anion Gap

If Anion Gap is ELEVATED (>12 mEq/L):

High anion-gap metabolic acidosis indicates accumulation of unmeasured anions 3, 5, 4

Since ketones and lactate are already excluded, investigate:

• Renal failure - check creatinine, urea, and calculate eGFR for uremic acidosis 5, 4
• Toxic ingestions:
  • Ethylene glycol - check osmolar gap, urine calcium oxalate crystals 5
  • Methanol - check osmolar gap, visual symptoms 5
  • Salicylate - check salicylate level, look for tinnitus, tachypnea 5
  • Pyroglutamic acid (5-oxoproline) - history of chronic acetaminophen use 5
  • Propylene glycol - history of IV lorazepam or other propylene glycol-containing medications 5
• Calculate the strong ion gap if the above are negative, as 98% of ICU patients with metabolic acidosis have unmeasured anions 3

If Anion Gap is NORMAL (10-12 mEq/L):

Normal anion-gap (hyperchloremic) metabolic acidosis indicates bicarbonate loss or impaired renal acid excretion 5, 4

Measure urine pH and urine anion gap to differentiate:

• Urine pH >5.5 suggests renal tubular acidosis (RTA) 1

  • Type 1 (distal) RTA - urine pH persistently >5.5, hypokalemia 1
  • Type 2 (proximal) RTA - urine pH initially >5.5 then <5.5 with acidosis, hypokalemia 1
  • Type 4 RTA - hyperkalemia, often with diabetes or medications (ACE inhibitors, NSAIDs, heparin) 1, 5

• Urine pH <5.5 suggests gastrointestinal bicarbonate loss:

  • Diarrhea - most common cause of hyperchloremic acidosis 2, 5
  • Ileostomy or ureterosigmoidostomy 5
  • Small bowel fistula 5

• Iatrogenic causes:

  • Large-volume normal saline administration - check recent fluid history 2
  • Medications causing hyperkalemia - ACE inhibitors, ARBs, potassium-sparing diuretics, NSAIDs 5

• Early renal failure before uremia develops 5

Additional Specialized Testing

If the diagnosis remains unclear after initial workup:

• Urine anion gap = (urine Na⁺ + urine K⁺) - urine Cl⁻ to assess renal ammonium excretion 1

  • Positive urine anion gap suggests impaired renal acidification (RTA)
  • Negative urine anion gap suggests appropriate renal response to GI bicarbonate loss

• Serum osmolar gap if toxic ingestion suspected 5

• Urine organic acids if considering rare metabolic disorders 2

• Medication review for drugs causing RTA or hyperkalemia 1, 5

Critical Monitoring During Workup

• Serum potassium every 2-4 hours as correction of acidosis drives potassium intracellularly and can cause life-threatening hypokalemia 1, 6
• Repeat arterial or venous blood gases to assess progression and response to treatment 1
• Monitor for complications of severe acidosis including decreased cardiac output, arrhythmias, and altered mental status 4

Treatment Considerations During Investigation

The definitive treatment is identifying and correcting the underlying cause 1, 5, 4

Sodium bicarbonate is NOT indicated at pH 7.28 unless specific circumstances exist:

• pH falls below 7.1 with severe symptoms 1
• Life-threatening hyperkalemia requiring temporizing measures 1
• Tricyclic antidepressant or sodium channel blocker overdose 1

Common pitfall: Do not administer bicarbonate empirically before completing the diagnostic workup, as this can obscure the underlying diagnosis and cause complications including hypernatremia, hypokalemia, and paradoxical intracellular acidosis if ventilation is inadequate 1, 4