What are the causes and treatment of metabolic alkalosis?

From the Guidelines

Metabolic alkalosis should be managed by addressing the underlying cause, correcting fluid and electrolyte imbalances, and considering the use of potassium chloride supplementation and, in severe cases, acetazolamide, as supported by recent studies such as 1 and 1.

Causes and Presentation

Metabolic alkalosis is characterized by elevated blood pH due to increased bicarbonate levels in the body, often resulting from excessive loss of acid or excessive retention of bicarbonate. Common causes include prolonged vomiting, excessive use of diuretics, hypokalemia, and excessive intake of antacids containing bicarbonate. In rare cases, conditions like Bartter syndrome, as discussed in 1 and 1, can lead to hypokalemic metabolic alkalosis. The presentation of metabolic alkalosis can vary, with symptoms such as polyuria, hypochloremia, and hypokalemia being common, especially in conditions like Bartter syndrome.

Diagnosis and Differential Diagnosis

Diagnosing the underlying cause of metabolic alkalosis is crucial. The differential diagnosis for hypokalemia, a common accompaniment to metabolic alkalosis, is wide and includes renal and gastrointestinal potassium loss, as well as potassium shifts. Assessing urinary chloride excretion, through fractional chloride excretion or the urinary sodium/chloride ratio, can help distinguish between renal and extrarenal salt losses, as noted in 1. Genetic analysis has become a key tool in diagnosing rare tubulopathies like Bartter syndrome, making traditional diuretic tests less necessary, as advised against in 1.

Treatment Approach

Treatment of metabolic alkalosis focuses on addressing the underlying cause. For vomiting-induced alkalosis, antiemetics and IV fluid replacement with normal saline are often used. Potassium chloride supplementation is frequently necessary to correct hypokalemia, which both accompanies and perpetuates metabolic alkalosis. In cases caused by diuretics, discontinuing the offending medication and considering acetazolamide to promote bicarbonate excretion may be necessary. Patients with volume depletion require fluid resuscitation to correct the underlying cause of the alkalosis. Monitoring electrolyte levels, particularly potassium, chloride, and bicarbonate, is essential during treatment, as emphasized in the management of conditions leading to metabolic alkalosis, such as those discussed in 1 and 1.

Management Considerations

The body compensates for metabolic alkalosis through hypoventilation, which retains carbon dioxide and helps normalize pH, though this compensation is limited. In clinical practice, the focus should be on correcting the underlying cause and managing electrolyte imbalances, rather than relying on the body's compensatory mechanisms. For rare conditions like Bartter syndrome, understanding the specific characteristics, such as the age at onset, presence of polyhydramnios, and plasma Cl/Na ratio, as outlined in 1, can guide the management approach. However, the primary goal in managing metabolic alkalosis remains the correction of the underlying cause and the restoration of normal electrolyte and fluid balance, as supported by the most recent and highest quality evidence, such as 1 and 1.

From the FDA Drug Label

Acetazolamide is a potent carbonic anhydrase inhibitor, effective in the control of fluid secretion The diuretic effect of acetazolamide is due to its action in the kidney on the reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid The result is renal loss of HCO3 ion, which carries out sodium, water, and potassium. Alkalinization of the urine and promotion of diuresis are thus affected. Alteration in ammonia metabolism occurs due to increased reabsorption of ammonia by the renal tubules as a result of urinary alkalinization.

The use of acetazolamide can lead to metabolic acidosis, not metabolic alkalosis, due to the renal loss of HCO3 ion. However, the question is about metabolic alkalosis.

• The FDA label does not directly support the use of acetazolamide for the treatment of metabolic alkalosis.
• The mechanism of action of acetazolamide would not support its use in treating metabolic alkalosis, as it leads to a loss of bicarbonate ions, which would worsen metabolic acidosis, not alkalosis. 2

From the Research

Definition and Characteristics of Metabolic Alkalosis

• Metabolic alkalosis is defined by an increase in plasma HCO3- level (>26 mmol/L) and blood arterial pH (>7.43) 3.
• It is often accompanied by hypokalemia and can be caused by excessive hydrogen ion loss or exogenous base gain 3, 4.
• The condition is characterized by a primary elevation of serum bicarbonate and arterial pH, along with a compensatory increase in Pco2 consequent to adaptive hypoventilation 4.

Pathogenesis of Metabolic Alkalosis

• The pathogenesis of metabolic alkalosis involves either a loss of fixed acid or a net accumulation of bicarbonate within the extracellular fluid 4.
• The loss of acid may be via the gastrointestinal tract or the kidney, whereas the sources of excess alkali may be via oral or parenteral alkali intake 4.
• Factors that interfere with the kidney's ability to eliminate excess bicarbonate, such as volume contraction, low glomerular filtration rate, potassium deficiency, hypochloremia, aldosterone excess, and elevated arterial carbon dioxide, can promote the generation or impair the correction of metabolic alkalosis 4.

Clinical States Associated with Metabolic Alkalosis

• Major clinical states associated with metabolic alkalosis include vomiting, aldosterone or cortisol excess, licorice ingestion, chloruretic diuretics, excess calcium alkali ingestion, and genetic diseases such as Bartter syndrome, Gitelman syndrome, and cystic fibrosis 4.
• Metabolic alkalosis can be divided into four categories: chloride depletion alkalosis, mineralocorticoid excess syndromes, apparent mineralocorticoid excess syndromes, and excess alkali administration 5.

Treatment of Metabolic Alkalosis

• The cornerstone of treatment is the correction of existing depletions and the prevention of further losses 3.
• Treatment is usually supportive and based on the cause of the alkalosis 5.
• Acetazolamide has been used for diuretic-induced metabolic alkalosis, and intravenous acetazolamide may be preferred to treat diuretic-induced metabolic alkalosis in patients with heart failure 6.