What is intractable acidosis in critically ill patients with conditions such as diabetic ketoacidosis, lactic acidosis, or renal tubular acidosis?

Intractable Acidosis in Critically Ill Patients

Intractable acidosis refers to severe, persistent metabolic acidosis (typically pH <7.1-7.2 or bicarbonate <10-15 mEq/L) that fails to respond to standard treatment of the underlying cause and may require extraordinary interventions such as continuous renal replacement therapy, extracorporeal CO2 removal, or high-dose bicarbonate therapy. 1

Defining Features

Intractable acidosis is characterized by:

• Severe acidemia with pH <7.0-7.1 despite aggressive treatment of the underlying disorder 1, 2
• Persistent elevation of organic anions (lactate >5-10 mmol/L, ketones) or accumulation of acids that cannot be cleared by normal physiologic mechanisms 3, 4
• Failure to respond to standard therapy including fluid resuscitation, insulin (in DKA), restoration of tissue perfusion, and discontinuation of offending agents 1, 3
• Progressive deterioration with worsening anion gap despite appropriate interventions 5

Clinical Context and Causes

Diabetic Ketoacidosis (DKA)

In DKA, intractable acidosis manifests as:

• pH <7.0 with bicarbonate <10 mEq/L representing severe DKA that may warrant bicarbonate therapy 1
• Persistent ketoacidosis despite adequate insulin and fluid therapy, suggesting complications such as concurrent lactic acidosis, sepsis, or renal failure 1, 5
• Development of hyperchloremic acidosis during treatment (pH 5.6 during acidemia), which may indicate transient renal tubular acidosis and requires specific management 6

The key pitfall is administering bicarbonate prematurely in DKA—bicarbonate therapy is generally NOT indicated unless pH falls below 6.9-7.0, as insulin and fluid resuscitation correct the underlying ketoacidosis. 1, 3

Lactic Acidosis

Intractable lactic acidosis occurs when:

• Lactate levels exceed 10 mmol/L (considered life-threatening) with pH <7.1 despite restoration of tissue perfusion 3, 4
• Tissue hypoxia persists from shock states, severe hypoxemia, or mitochondrial dysfunction that cannot be reversed 3, 4
• Lactate clearance is impaired due to liver failure (major site of lactate removal) or severe renal dysfunction 3
• Drug-induced mitochondrial toxicity from metformin (especially with eGFR <30 mL/min/1.73m²) or NRTIs (stavudine, didanosine) causes ongoing lactate production 3

Critical management principle: Sodium bicarbonate should NOT be used to treat lactic acidosis from tissue hypoperfusion or sepsis, as it does not improve hemodynamics, may increase lactate production, and has never been shown to improve survival. 3 The focus must be on restoring tissue perfusion with fluid resuscitation (15-20 mL/kg/h isotonic saline initially), treating sepsis aggressively, and discontinuing offending medications. 3

Renal Tubular Acidosis (RTA)

In critically ill patients, RTA contributing to intractable acidosis presents as:

• Hyperchloremic (non-anion gap) metabolic acidosis with normal anion gap but severe acidemia 4, 6
• Inability to acidify urine appropriately (urine pH >5.5 during systemic acidemia in distal RTA) 6
• Reduced bicarbonate threshold in proximal RTA, causing persistent bicarbonate wasting 6
• Type IV RTA with hyperkalemia in CKD patients, where impaired ammonia secretion prevents adequate acid excretion 7

When Extraordinary Interventions Are Needed

Continuous Renal Replacement Therapy (CRRT)

CRRT becomes necessary for intractable acidosis when:

• Bicarbonate-based dialysate is preferred over lactate in patients with lactic acidosis and/or liver failure to avoid worsening acidosis 1
• High-volume hemofiltration may be required, with bicarbonate buffer preferred over lactate in this setting 1
• Citrate anticoagulation requires careful monitoring of systemic acid-base balance in patients at high risk for citrate accumulation, as it can cause both metabolic alkalosis and metabolic acidosis 1

Bicarbonate Therapy Considerations

Bicarbonate should only be administered in highly specific circumstances:

• DKA with pH <6.9-7.0: This is the only clear indication in DKA, with goal of achieving pH 7.2-7.3, not normalization 1, 3
• Severe acidosis with pH <7.1 from non-lactic causes where the underlying disorder cannot be immediately corrected 8
• Metformin-associated lactic acidosis: Hemodialysis is the definitive treatment and often reverses symptoms, as it removes both metformin and lactate 3

The bicarbonate deficit calculation can guide dosing: Bicarbonate deficit (mEq) = 0.5 × body weight (kg) × (desired HCO3 - actual HCO3), but only half should be given initially with frequent reassessment. 7

Prognostic Implications

Contrary to traditional teaching, recent evidence shows:

• Severe acidosis (pH <6.8) does not uniformly predict fatal outcomes—32% of patients survived at least 30 days, and 28.6% were discharged home and returned to pre-hospitalization activity 2
• Multivariate analysis identified hyperkalemia, APACHE II score, and Glasgow Coma Scale as determinants for ICU death after severe acidosis, not pH alone 2
• The underlying disease process (septic shock, cardiac arrest, rhabdomyolysis) drives mortality more than the degree of acidemia itself 4, 2

Monitoring and Management Algorithm

For any critically ill patient with suspected intractable acidosis:

1. Obtain arterial blood gas to determine pH, PaCO2, and calculate anion gap: [Na+] - ([Cl-] + [HCO3-]), with high anion gap >12 mEq/L 1, 9
2. Measure serum lactate (>2 mmol/L elevated, >5 mmol/L abnormal, >10 mmol/L life-threatening) 3
3. Check serum/urine ketones in diabetic patients or those with suspected starvation/alcoholic ketoacidosis 1
4. Assess renal function (BUN, creatinine, eGFR) and electrolytes (particularly potassium) 1, 7
5. Calculate serum osmolal gap if toxic ingestion suspected (methanol, ethylene glycol) 9

Treatment priorities:

• Restore tissue perfusion first: 15-20 mL/kg/h isotonic saline in first hour if shock present 1, 3
• Treat underlying cause aggressively: Insulin for DKA, antibiotics/source control for sepsis, discontinue metformin/NRTIs immediately 1, 3
• Add potassium 20-30 mEq/L (2/3 KCl, 1/3 KPO4) to fluids once urine output established and renal function assured 1
• Monitor bicarbonate and pH every 2-4 hours initially to assess response 1, 7
• Consider CRRT with bicarbonate-based dialysate if pH remains <7.1 despite maximal medical therapy and underlying cause cannot be immediately corrected 1

Common pitfalls to avoid:

• Do not give bicarbonate for lactic acidosis from sepsis/shock—it worsens outcomes 3
• Do not give bicarbonate in DKA unless pH <6.9-7.0—insulin and fluids are the treatment 1
• Do not ignore hyperkalemia during alkalinization—potassium shifts intracellularly and can cause life-threatening hypokalemia 1, 3
• Do not use lactate-containing fluids in patients with lactic acidosis or liver failure—use bicarbonate-based solutions 1