What is metabolic acidosis and how is it treated?

Metabolic Acidosis: Comprehensive Overview and Treatment

Definition and Pathophysiology

Metabolic acidosis is characterized by a primary reduction in serum bicarbonate (<22 mmol/L) associated with blood pH <7.35, where the body attempts to compensate by increasing ventilation to eliminate CO2. 1

The disorder develops when acid-base homeostatic mechanisms are overwhelmed or impaired through three primary mechanisms: 2

• Rapid production of nonvolatile acids (e.g., lactic acid, ketoacids) that consume bicarbonate 3
• Loss of bicarbonate from the gastrointestinal tract or kidneys 3
• Impaired renal acid excretion due to kidney dysfunction 2

The kidneys normally maintain acid-base balance by eliminating 50-80 millimoles of hydrogen ions per 24 hours while simultaneously regenerating bicarbonate to replenish buffer stores. 4 In chronic kidney disease, this process is impaired as the kidneys lose their ability to excrete hydrogen ions and synthesize ammonia, leading to acid accumulation. 1

Diagnostic Approach

Initial Classification by Anion Gap

The first critical step is calculating the serum anion gap: [Na+] - ([HCO3-] + [Cl-]) to categorize the acidosis. 5

High Anion Gap Metabolic Acidosis (anion gap >12 mEq/L) indicates accumulation of endogenous acids: 3

• Lactic acidosis (tissue hypoxia, shock)
• Ketoacidosis (diabetic, alcoholic, starvation)
• Renal failure (uremic acidosis)
• Toxic ingestions (ethylene glycol, methanol, salicylates, pyroglutamic acid, propylene glycol)

Normal Anion Gap (Hyperchloremic) Metabolic Acidosis indicates bicarbonate loss or impaired renal acidification: 3, 4

• Gastrointestinal bicarbonate loss (diarrhea, fistulas)
• Renal tubular acidosis
• Early renal failure
• Drug-induced hyperkalemia
• Administration of acidifying chloride salts

Key Laboratory Parameters

Serum bicarbonate levels define severity and treatment thresholds: 1

• Normal range: 22-26 mmol/L
• <22 mmol/L: Metabolic acidosis present
• <18 mmol/L: Pharmacological treatment threshold in chronic kidney disease
• 15-18 mmol/L: Mild diabetic ketoacidosis
• <15 mmol/L: Moderate to severe diabetic ketoacidosis

Additional diagnostic tests to obtain: 1, 6

• Arterial blood gas (pH, PaCO2) for complete acid-base assessment in complex cases
• Serum electrolytes, particularly potassium (acidosis causes transcellular shift leading to hyperkalemia)
• Blood glucose and ketones if diabetic ketoacidosis suspected
• Lactate level if lactic acidosis suspected
• Osmolal gap if toxic ingestion suspected

Treatment Strategies

Etiology-Specific Management

The cornerstone of treating metabolic acidosis is addressing the underlying cause, not simply administering bicarbonate. 7, 3

Diabetic Ketoacidosis (DKA)

For DKA, focus on insulin therapy, fluid resuscitation, and electrolyte replacement rather than bicarbonate administration. 6

• Continuous intravenous insulin is the standard of care for critically ill and mentally obtunded patients 6
• Restoration of circulatory volume and tissue perfusion is the primary goal 6
• Bicarbonate administration has NOT been shown to improve resolution of acidosis or time to discharge in DKA 6
• Bicarbonate therapy is generally not needed unless pH falls below 7.0 1
• Monitor arterial or venous blood gases to assess treatment response 1

Lactic Acidosis

The only effective treatment for lactic acidosis is cessation of acid production via improvement of tissue oxygenation. 3

• Focus on improving oxygen delivery to tissues 7
• Treat underlying shock or hypoperfusion
• Sodium bicarbonate has failed to reduce morbidity and mortality despite improving acid-base parameters 3

Chronic Kidney Disease-Associated Acidosis

Pharmacological treatment with sodium bicarbonate is recommended when serum bicarbonate is consistently <18 mmol/L to prevent bone and muscle metabolism abnormalities. 6

• Oral sodium bicarbonate 2-4 g/day (25-50 mEq/day) effectively increases serum bicarbonate concentrations 6
• Target: Maintain serum bicarbonate ≥22 mmol/L 1, 6
• Monitor serum bicarbonate monthly in CKD stages 3-5 and maintenance dialysis patients 1, 6
• Correction of acidemia increases serum albumin, decreases protein degradation, and increases branched chain amino acids 6

Dietary modification is an important adjunct: 1

• Increase fruit and vegetable intake to provide potassium citrate salts that generate alkali
• This approach may also decrease systolic blood pressure and body weight compared to sodium bicarbonate alone
• Avoid citrate-containing alkali salts in CKD patients exposed to aluminum salts (increases aluminum absorption) 6

Renal Tubular Acidosis in Children

Normalization of serum bicarbonate is critical for normal growth parameters in children with renal tubular acidosis. 6

Severe Malaria in Children

Metabolic acidosis in severe malaria resolves with correction of hypovolemia and treatment of anemia by adequate blood transfusion. 8

• No evidence supports the use of sodium bicarbonate 8
• Dichloroacetate reduces lactic acidosis in African children, but effect on mortality is unknown 8

Bicarbonate Therapy: When and How

Bicarbonate therapy should be reserved for severe metabolic acidosis (pH <7.2) and administered cautiously in a stepwise fashion. 7, 9

Indications for Bicarbonate Administration

• Severe acute metabolic acidosis with pH <7.2 7
• Chronic kidney disease with bicarbonate <18 mmol/L 1, 6
• Cardiac arrest (where risks from acidosis exceed those of hypernatremia) 9

Dosing Protocols (from FDA Label)

For cardiac arrest: 9

• Initial rapid IV dose: 1-2 vials of 50 mL (44.6-100 mEq)
• Continue at 50 mL (44.6-50 mEq) every 5-10 minutes as indicated by arterial pH and blood gas monitoring

For less urgent metabolic acidosis in adults and older children: 9

• 2-5 mEq/kg body weight over 4-8 hours depending on severity
• Initially infuse 2-5 mEq/kg over 4-8 hours for measurable improvement
• Subsequent doses depend on clinical response

Critical dosing principles: 9

• It is unwise to attempt full correction of low total CO2 during the first 24 hours
• Target total CO2 of approximately 20 mEq/L at end of first day (usually associated with normal blood pH)
• Values brought to normal or above normal within the first day are very likely associated with grossly alkaline blood pH
• Therapy should be monitored by measuring blood gases, plasma osmolarity, arterial lactate, hemodynamics, and cardiac rhythm in shock-associated acidosis

Important Caveats and Pitfalls

Bicarbonate administration carries significant risks that must be monitored: 6

• May worsen intracellular acidosis (paradoxical CNS acidosis)
• Reduces ionized calcium (can precipitate tetany or arrhythmias)
• Produces hyperosmolality (bicarbonate solutions are hypertonic)
• Can cause undesirable rise in plasma sodium concentration 9
• May produce unrecognized alkalosis due to delayed readjustment of ventilation 9
• Monitor electrolytes closely, particularly potassium levels 6

Avoid excessive bicarbonate supplementation to prevent alkalosis. 7

Monitoring During Treatment

Regular reassessment is essential to ensure appropriate response and avoid complications: 1, 6

• Measure arterial or venous blood gases to assess pH and PaCO2
• Monitor serum bicarbonate levels regularly (monthly in CKD patients)
• Check serum electrolytes, especially potassium
• Assess blood pressure and fluid status
• Monitor for signs of alkalosis (target bicarbonate toward but not exceeding normal range)

Adverse Effects of Untreated Metabolic Acidosis

Acute Metabolic Acidosis

Acute acidosis produces severe cardiovascular and systemic complications: 5

• Decreased cardiac output
• Arterial dilatation with hypotension
• Altered oxygen delivery
• Decreased ATP production
• Predisposition to arrhythmias
• Impairment of immune response

Chronic Metabolic Acidosis

Chronic acidosis leads to progressive tissue catabolism and bone disease: 5, 1

• Increased muscle degradation and protein catabolism leading to malnutrition
• Abnormal bone metabolism and demineralization (renal osteodystrophy)
• Growth retardation in children with CKD
• Bone dissolution due to altered homeostatic relationships between ionized calcium, PTH, and vitamin D