How to manage persistent normal anion gap acidosis in the recovery phase of diabetic ketoacidosis (DKA)?

From the Guidelines

Management of persistent normal anion gap acidosis during DKA recovery requires addressing the underlying hyperchloremic metabolic acidosis while continuing insulin therapy, with the most recent guidelines from 2025 1 suggesting that the use of bicarbonate is generally not recommended. The goal is to restore circulatory volume and tissue perfusion, resolve ketoacidosis, and correct electrolyte imbalance and acidosis. Key steps include:

• Maintaining insulin infusion at 0.05-0.1 units/kg/hour until the acidosis resolves
• Providing adequate fluid replacement with isotonic saline to support renal bicarbonate regeneration
• Monitoring electrolytes every 2-4 hours, particularly potassium, and supplementing as needed to maintain levels between 4.0-5.0 mEq/L
• Considering administration of sodium bicarbonate only if the pH remains below 7.0 despite other interventions, as excessive bicarbonate can worsen hypokalemia and potentially cause paradoxical CNS acidosis, as noted in recent studies 1. The condition generally resolves within 24-48 hours as the kidneys excrete excess chloride and regenerate bicarbonate, so patience with supportive care is often the best approach unless severe acidosis persists. It is essential to individualize treatment based on a careful clinical and laboratory assessment, as there is considerable variability in the presentation of DKA and hyperosmolar hyperglycemic states, ranging from euglycemia or mild hyperglycemia and acidosis to severe hyperglycemia, dehydration, and coma 1. 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, as recommended in the 2025 guidelines 1.

From the FDA Drug Label

In metabolic acidosis associated with shock, therapy should be monitored by measuring blood gases, plasma osmolarity, arterial blood lactate, hemodynamics and cardiac rhythm. In general, it is unwise to attempt full correction of a low total CO2 content during the first 24 hours of therapy, since this may be accompanied by an unrecognized alkalosis because of a delay in the readjustment of ventilation to normal Treatment of metabolic acidosis should, if possible, be superimposed on measures designed to control the basic cause of the acidosis - e.g., insulin in uncomplicated diabetes, blood volume restoration in shock.

The management of persistent normal anion gap acidosis in the recovery phase of diabetic ketoacidosis (DKA) involves:

• Monitoring of blood gases, plasma osmolarity, arterial blood lactate, hemodynamics, and cardiac rhythm 2
• Avoiding full correction of low total CO2 content during the first 24 hours of therapy to prevent unrecognized alkalosis 2
• Controlling the basic cause of the acidosis, such as administering insulin in uncomplicated diabetes 2
• Bicarbonate therapy may be considered, but it should be planned in a stepwise fashion, with the degree of response from a given dose not being precisely predictable 2

From the Research

Management of Persistent Normal Anion Gap Acidosis

To manage persistent normal anion gap acidosis in the recovery phase of diabetic ketoacidosis (DKA), several key points should be considered:

• The use of hyperchloraemic fluids may aggravate the condition, as noted in a case report from 3.
• Measurement of the anion gap remains an important part of the assessment of diabetic acid-base disturbances, highlighting the need for careful monitoring 3.
• The mainstays of treatment for DKA include restoration of circulating volume, insulin therapy, electrolyte replacement, and treatment of any underlying precipitating event, which may also apply to managing the recovery phase 4.

Treatment Approaches

Different treatment approaches have been studied:

• The use of lactated Ringer's solution instead of normal saline may help in managing DKA and potentially reducing the risk of hyperchloremic acidosis, as suggested by a study comparing lactated Ringer's to normal saline in the acute management of DKA 5.
• A study on hyperchloremic acidosis during the recovery phase of diabetic ketosis found that failure to normalize serum bicarbonate is attributed to excretion of ketone anions in the urine, indicating the need for careful fluid and electrolyte management 6.

Considerations for Patient Care

When managing patients with persistent normal anion gap acidosis in the recovery phase of DKA:

• It is crucial to monitor for the development of hyperchloremic acidosis, especially when using certain types of fluids for resuscitation 3, 6.
• The choice of fluid for resuscitation may impact the resolution of acidosis, with balanced crystalloids potentially offering advantages over normal saline 5.
• Early diagnosis and management of DKA, including its complications, are paramount to improve patient outcomes 4.