How to manage diabetic ketoacidosis (DKA) with an increasing anion gap after starting long and short-acting insulin, such as aspart (insulin aspart) or lispro (insulin lispro)?

From the Guidelines

To manage diabetic ketoacidosis (DKA) with an increasing anion gap despite insulin therapy, intensify treatment by increasing the insulin infusion rate to 0.1-0.14 units/kg/hour while continuing intravenous fluid resuscitation with normal saline at a clinically appropriate rate aiming to replace 50% of the estimated fluid deficit in the first 8–12 h, as recommended by the most recent guidelines 1. This approach is based on the latest standards of care in diabetes, which emphasize the importance of aggressive fluid replacement and insulin therapy in the management of DKA.

• Key considerations in the management of DKA with an increasing anion gap include:
  • Closely monitoring blood glucose, electrolytes, and pH every 1-2 hours to adjust treatment as needed.
  • Ensuring adequate potassium replacement (typically by giving K+ in each liter of i.v. fluid as needed to keep serum K+ between 4 and 5 mmol/L) when serum potassium falls below 5.0 mEq/L to prevent hypokalemia.
  • Adding dextrose (D5W or D10W) to IV fluids when blood glucose reaches 200-250 mg/dL while continuing insulin to clear ketones.
  • Addressing any underlying precipitating factors such as infection, medication non-adherence, or acute illness. An increasing anion gap despite insulin therapy suggests either insufficient insulin dosing or ongoing ketogenesis due to severe insulin resistance, dehydration, or untreated triggers.
• It is crucial not to discontinue insulin until the anion gap normalizes (<12 mEq/L) and ketosis resolves, even if blood glucose normalizes, and to consider consulting endocrinology if the anion gap continues to rise despite these interventions, as this represents a treatment-resistant case requiring specialized management, as supported by previous studies 1.

From the Research

Managing Diabetic Ketoacidosis (DKA) with Increasing Anion Gap

• The treatment of DKA typically involves the administration of insulin, such as aspart (insulin aspart) or lispro (insulin lispro), to help lower blood glucose levels and reduce the production of ketones 2.
• However, in some cases, the anion gap may continue to increase despite the initiation of insulin therapy, indicating a worsening of the metabolic acidosis.
• A study published in 1977 discussed the clinical use of the anion gap and its alteration in various disorders, including metabolic acidosis 3.
• In the context of DKA, an increasing anion gap may suggest the presence of a high-anion gap metabolic acidosis, which can be caused by a variety of factors, including lactic acidosis, ketoacidosis, or other organic acidoses 3.
• A case report published in 2020 described a patient with type 1 diabetes mellitus who presented with signs and symptoms of DKA, but was later found to have a high-anion gap hyperchloremic acidosis 4.
• The patient did not respond to traditional DKA treatment, but showed significant improvement after the addition of sodium bicarbonate infusion to the treatment regimen 4.

Treatment Considerations

• The treatment of DKA with an increasing anion gap should involve a comprehensive approach, including the administration of insulin, fluids, and electrolytes, as well as the identification and treatment of any underlying causes of the metabolic acidosis 5.
• The use of low-dose insulin regimens, such as those described in a 1979 study, may be effective in managing DKA, but may not be sufficient to address the increasing anion gap 5.
• The addition of sodium bicarbonate infusion, as described in the 2020 case report, may be considered in cases where the anion gap is increasing despite traditional DKA treatment 4.
• However, the use of bicarbonate therapy in high-anion gap hyperchloremic metabolic acidosis is not well established, and further research is needed to determine its efficacy and safety in this context 4.