Severe Metabolic Alkalosis: Definition and Treatment
Severe metabolic alkalosis is defined as an arterial pH >7.55 with elevated serum bicarbonate, and treatment centers on identifying chloride-responsive versus chloride-resistant causes, with aggressive fluid resuscitation, potassium chloride replacement, and acetazolamide or potassium-sparing diuretics as first-line pharmacologic interventions.
Definition
Severe metabolic alkalosis is characterized by:
- Arterial pH >7.55 with elevated plasma bicarbonate levels 1, 2
- Life-threatening cases may present with pH >7.70 2
- Associated with significant morbidity and mortality requiring urgent intervention 2
Initial Assessment and Classification
Measure urinary chloride to distinguish treatment approach:
- Chloride-responsive (urinary Cl <20 mEq/L): Volume depletion, vomiting, diuretic use 2, 3
- Chloride-resistant (urinary Cl >20 mEq/L): Mineralocorticoid excess, Bartter syndrome, Gitelman syndrome 4, 3
Check for contributing factors:
Treatment Algorithm
Step 1: Fluid and Electrolyte Replacement (First-Line for Chloride-Responsive)
Aggressive fluid resuscitation with normal saline:
- Corrects volume depletion and provides chloride for renal bicarbonate excretion 6, 3
- Most cases resolve with fluid and electrolyte therapy alone 1, 6
Potassium chloride supplementation (essential):
- Doses of 20-60 mEq/day frequently required to maintain serum potassium 4.5-5.0 mEq/L 4
- Use only potassium chloride, not potassium citrate, which worsens alkalosis 4
- Correct to >3.5 mmol/L 5
Step 2: Pharmacologic Interventions
First-line pharmacologic options when fluid/electrolyte therapy insufficient:
Acetazolamide (carbonic anhydrase inhibitor):
- Useful in heart failure patients with diuretic-induced alkalosis and adequate kidney function 4, 3
- Promotes renal bicarbonate excretion 3
Potassium-sparing diuretics (preferred alternative):
- Amiloride is most effective: Start 2.5 mg daily, titrate to 5 mg daily 4
- Spironolactone: Start 25 mg daily, titrate to 50-100 mg daily 4
- Particularly helpful for diuretic-induced metabolic alkalosis 4
- Avoid combining with ACE inhibitors without close monitoring due to hyperkalemia risk 4
- Contraindicated in significant renal dysfunction or existing hyperkalemia 4
Step 3: Advanced Therapies for Refractory Cases
When rapid correction needed or conventional therapy not tolerated:
Intravenous acid administration:
- Ammonium chloride is primary drug of choice for patients with normal hepatic function 1
- Dilute hydrochloric acid (0.1-0.2 N) via central venous catheter for patients with hepatic or severe renal dysfunction 1
- Reserved for life-threatening cases where pH-based therapy alone is insufficient 6
Hemodialysis:
- Low-bicarbonate/high-chloride dialysate is treatment of choice for refractory cases with concurrent renal failure 4, 7
- Particularly important in end-stage kidney disease patients 7
Step 4: Address Underlying Cause
Discontinue or reduce causative agents:
- Stop or reduce diuretic doses if possible 4
- Consider switching to longer-acting loop diuretics or adding potassium-sparing diuretics 4
Special populations:
- Bartter/Gitelman syndrome: Sodium chloride supplementation (5-10 mmol/kg/day), NSAIDs for symptomatic patients, gastric acid inhibitors with NSAIDs 4
- Heart failure patients: Add aldosterone antagonist (spironolactone) to diuretic regimen 4
Critical Pitfalls to Avoid
- Never administer sodium bicarbonate or alkalinization strategies - these are contraindicated and worsen alkalosis 4
- Do not use potassium salts other than potassium chloride (e.g., potassium citrate worsens alkalosis) 4
- Avoid routine use of dangerous therapies (exogenous acid, dialysis, forced respiratory depression) based on pH alone without thoughtful supportive care 6
- Do not overlook Bartter syndrome in patients with unexplained chloride-resistant alkalosis, especially with history of polyhydramnios and premature birth 4