What is the approach to assessing and managing metabolic alkalosis?

Assessment and Management of Elevated Bicarbonate (43 mEq/L)

Definition

Metabolic alkalosis is defined by elevated serum bicarbonate (>26 mEq/L) and arterial pH >7.45, with compensatory increase in PaCO2. 1, 2 A bicarbonate of 43 mEq/L represents severe metabolic alkalosis requiring urgent evaluation and treatment, as arterial pH ≥7.55 is associated with significantly increased mortality in critically ill patients. 2

Classification

Metabolic alkalosis is classified into two main categories based on urinary chloride concentration: 1, 2

Saline-Responsive (Chloride-Depletion) Alkalosis

• Urinary chloride <20 mEq/L 3
• Causes include:
  • Vomiting or nasogastric suction (gastric H+ loss) 1, 4
  • Diuretic therapy (loop or thiazide diuretics) 4, 2
  • Post-hypercapnic state 2
  • Volume contraction 2

Saline-Resistant Alkalosis

• Urinary chloride >20 mEq/L 3
• Causes include:
  • Mineralocorticoid excess (primary hyperaldosteronism, Cushing syndrome) 1, 2
  • Severe hypokalemia (K+ <2.0 mEq/L) 2
  • Bartter or Gitelman syndrome 2
  • Licorice ingestion (apparent mineralocorticoid excess) 1, 2
  • Excess alkali administration 1, 2

Differential Diagnosis

Evaluate for specific precipitating conditions: 1, 2

• Gastrointestinal losses: Vomiting, nasogastric suction, villous adenoma, congenital chloride diarrhea 2
• Renal losses: Diuretics (most common in hospitalized patients), primary hyperaldosteronism, Cushing syndrome, renal artery stenosis 4, 2
• Genetic disorders: Bartter syndrome, Gitelman syndrome, cystic fibrosis 2
• Exogenous alkali: Milk-alkali syndrome, massive blood transfusions, sodium bicarbonate administration 2, 5
• Congestive heart failure: Neurohormonal activation amplifies alkalosis tendency 4

Investigations and Expected Findings

Initial Laboratory Assessment

• Arterial blood gas: pH >7.45, elevated PaCO2 (compensatory hypoventilation), bicarbonate 43 mEq/L 2
• Serum electrolytes with anion gap calculation: Expect hypochloremia, assess for hypokalemia 2
• Urinary chloride concentration: <20 mEq/L (saline-responsive) vs >20 mEq/L (saline-resistant) - this is the critical test to guide treatment 3
• Serum potassium: Often depleted; severe hypokalemia (<2.0 mEq/L) can maintain alkalosis 2
• Serum magnesium: Hypomagnesemia commonly coexists 2
• BUN/creatinine: Assess volume status and renal function 2

Additional Testing Based on Clinical Context

• Urine potassium: Elevated in renal potassium wasting disorders 2
• Plasma renin and aldosterone: If primary hyperaldosteronism suspected 2
• 24-hour urine cortisol or dexamethasone suppression test: If Cushing syndrome suspected 2
• ECG: Assess for arrhythmias related to hypokalemia and alkalosis 6

Expected Findings in Severe Metabolic Alkalosis

• Serum bicarbonate >40 mEq/L 2
• Arterial pH potentially ≥7.55 (critical threshold for increased mortality) 2
• Compensatory PaCO2 elevation (approximately 0.7 mmHg increase per 1 mEq/L bicarbonate rise) 2
• Hypokalemia and hypochloremia in most cases 2

Empiric Treatment

For Saline-Responsive Alkalosis (Urinary Cl <20 mEq/L)

Administer isotonic saline (0.9% NaCl) to restore volume and chloride, which allows the kidney to excrete excess bicarbonate. 1, 2

• Potassium chloride supplementation is essential: Replete to maintain K+ >4.0 mEq/L, as hypokalemia perpetuates alkalosis 6, 2
• Magnesium repletion: Correct hypomagnesemia to facilitate potassium repletion 2
• Stop or reduce diuretics if clinically feasible 4, 2

For Saline-Resistant Alkalosis (Urinary Cl >20 mEq/L)

Provide potassium supplementation as the primary intervention, addressing the underlying cause rather than relying on saline administration. 6

• Acetazolamide 250-500 mg IV/PO: Promotes renal bicarbonate excretion by inhibiting proximal tubule bicarbonate reabsorption 6, 4, 2
• Aldosterone antagonist (spironolactone 25-100 mg daily): Particularly in heart failure or mineralocorticoid excess 4
• Treat underlying cause: Address hyperaldosteronism, Cushing syndrome, or genetic disorders 2

For Severe Life-Threatening Alkalosis (pH ≥7.55)

When rapid correction is needed or conventional therapy cannot be tolerated: 5

• Dilute hydrochloric acid (0.1-0.2 N HCl): Administer via central venous catheter in patients with hepatic dysfunction or when rapid correction needed 5
• Ammonium chloride: Alternative for patients with normal hepatic function, but requires hepatic conversion 5
• Low-bicarbonate hemodialysis: For patients with concurrent renal failure 4, 2

Critical Treatment Principles

• Never administer bicarbonate: It is contraindicated and will worsen metabolic alkalosis 6
• Address volume contraction: This is a key maintenance factor preventing renal bicarbonate excretion 2
• Correct hypokalemia aggressively: Potassium depletion impairs the kidney's ability to excrete bicarbonate 6, 2
• Monitor for complications: Hypokalemia can cause cardiac arrhythmias and muscle weakness 6

Indications to Refer

Immediate Referral to ICU/Critical Care

• Arterial pH ≥7.55 (associated with significantly increased mortality) 2
• Severe symptoms: Altered mental status, seizures, cardiac arrhythmias 2
• Requirement for central venous HCl administration 5
• Hemodynamic instability 2

Nephrology Consultation

• Refractory alkalosis despite appropriate treatment 2
• GFR <30 mL/min requiring consideration of dialysis 4, 2
• Suspected genetic disorders (Bartter, Gitelman syndrome) 2
• Need for low-bicarbonate dialysis 4

Endocrinology Consultation

• Suspected primary hyperaldosteronism (elevated aldosterone-to-renin ratio) 2
• Suspected Cushing syndrome (clinical features plus biochemical evidence) 2
• Apparent mineralocorticoid excess syndromes 1, 2

Critical Pitfalls

Diagnostic Pitfalls

• Failing to measure urinary chloride: This is the single most important test to differentiate saline-responsive from saline-resistant alkalosis and guide treatment 3
• Overlooking hypokalemia: Severe potassium depletion (<2.0 mEq/L) can independently maintain alkalosis regardless of volume status 2
• Missing occult vomiting: Patients may not volunteer history of self-induced vomiting or surreptitious diuretic use 2
• Ignoring medication review: Diuretics are the most common cause in hospitalized patients 4, 2

Treatment Pitfalls

• Administering bicarbonate: This worsens metabolic alkalosis and is absolutely contraindicated 6
• Giving saline to saline-resistant alkalosis: Will not correct the alkalosis and may worsen volume overload, particularly in heart failure 6, 4
• Inadequate potassium repletion: Attempting to correct alkalosis without addressing hypokalemia will fail 6, 2
• Neglecting magnesium: Hypomagnesemia prevents effective potassium repletion 2
• Overly aggressive fluid administration in heart failure: Balance need for chloride repletion with risk of volume overload 4
• Using acetazolamide in volume-depleted patients: Can worsen hypovolemia; ensure adequate volume repletion first 2

Monitoring Pitfalls

• Underestimating severity: pH ≥7.55 carries significant mortality risk and requires aggressive intervention 2
• Inadequate monitoring in elderly: Particularly vulnerable to falls from muscle weakness and arrhythmias from hypokalemia 6
• Failing to identify maintenance factors: Volume contraction, hypokalemia, hypochloremia, and low GFR all prevent renal bicarbonate excretion 2