What is the cause of rebound metabolic acidosis after sodium bicarbonate (NaHCO3) administration?

From the Guidelines

The use of bicarbonate in patients with diabetic ketoacidosis (DKA) is generally not recommended, as several studies have shown that it makes no difference in the resolution of acidosis or time to discharge 1.

Rebound Acidosis After Bicarbonate Administration

Rebound acidosis can occur after bicarbonate administration when the body's compensatory mechanisms overreact to the sudden increase in pH.

• When sodium bicarbonate is given to treat metabolic acidosis, it initially raises the blood pH by providing bicarbonate ions that neutralize excess hydrogen ions.
• However, this can trigger several problematic responses, including:
  • Rapid alkalization, which can stimulate increased production of lactic acid and other organic acids as the body attempts to restore acid-base balance.
  • Bicarbonate therapy can cause carbon dioxide retention, especially in patients with impaired ventilation, as bicarbonate is converted to carbon dioxide which must be exhaled.
  • The sodium load from sodium bicarbonate can cause fluid overload and dilution of serum bicarbonate.

Management of DKA

To minimize rebound acidosis and effectively manage DKA, the following approaches are recommended:

• Bicarbonate administration should be reserved for severe acidosis (pH < 7.1) or when acidosis is causing hemodynamic instability.
• Continuous monitoring of blood gases and electrolytes is essential during treatment.
• Alternative buffering agents like THAM (tromethamine) may be considered in patients with impaired ventilation or when sodium load is a concern.
• Management goals include restoration of circulatory volume and tissue perfusion, resolution of hyperglycemia, and correction of electrolyte imbalance and acidosis.
• Individualization of treatment based on a careful clinical and laboratory assessment is needed, taking into account the variability in presentation of DKA and hyperosmolar hyperglycemic states.

Key Considerations

• The most recent and highest quality study, published in 2024 1, supports the recommendation against the use of bicarbonate in patients with DKA, highlighting the importance of individualized treatment and careful monitoring.
• The use of continuous intravenous insulin is the standard of care for critically ill and mentally obtunded patients with DKA or hyperosmolar hyperglycemia.
• Successful transition from intravenous to subcutaneous insulin requires administration of basal insulin 2–4 h before the intravenous insulin is stopped to prevent recurrence of ketoacidosis and rebound hyperglycemia.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Intravenous sodium bicarbonate therapy increases plasma bicarbonate, buffers excess hydrogen ion concentration, raises blood pH and reverses the clinical manifestations of acidosis. Plasma concentration is regulated by the kidney through acidification of the urine when there is a deficit or by alkalinization of the urine when there is an excess. Bicarbonate anion is considered "labile" since at a proper concentration of hydrogen ion (H+) it may be converted to carbonic acid (H2CO3) and thence to its volatile form, carbon dioxide (CO2) excreted by the lung

The FDA drug label does not answer the question about rebound acidosis after bicarbonate administration.

From the Research

Rebound Acidosis after Bicarbonate Administration

• Rebound acidosis is a potential complication of bicarbonate therapy, where the patient's condition worsens after the treatment is stopped 2.
• The use of bicarbonate therapy in patients with severe metabolic acidosis is controversial, and its benefits are limited to specific cases, such as patients with accompanying acute kidney injury 3, 4.
• In patients with acute lactic acidosis and ketoacidosis, lactate and ketone bodies can be converted back to bicarbonate if the clinical situation improves, but bicarbonate therapy should be individualized and restrained unless the clinical situation clearly suggests benefit 4.
• The treatment of acute metabolic acidosis, particularly organic forms such as lactic acidosis, is controversial, and the use of sodium bicarbonate has failed to reduce morbidity and mortality despite improving acid-base parameters 5.
• After recovery from metabolic acidosis, metabolic alkalosis is common, and decreased bicarbonate excretion plays an important role in its pathogenesis, which may be the result of potassium or chloride loss, or both 2.
• The administration of base for the treatment of chronic metabolic acidosis is associated with improved cellular function and few complications, but its use in acute metabolic acidosis is controversial due to a lack of definitive benefit and potential complications 6.