What is the management of diabetic ketoacidosis (DKA) according to Harrison's 22nd edition?

Management of Diabetic Ketoacidosis (DKA)

For critically ill patients with DKA, initiate continuous intravenous regular insulin at 0.1 units/kg/hour alongside aggressive fluid resuscitation with isotonic saline at 15-20 mL/kg/hour during the first hour, while closely monitoring potassium and adding replacement once levels fall below 5.5 mEq/L. 1, 2

Initial Assessment and Diagnosis

The diagnostic workup must include plasma glucose, blood urea nitrogen, creatinine, serum ketones (preferably β-hydroxybutyrate), electrolytes with calculated anion gap, osmolality, urinalysis, arterial blood gases, complete blood count with differential, and electrocardiogram. 2, 3

Key diagnostic criteria:

• Blood glucose typically >250 mg/dL (though euglycemic DKA can occur, especially with SGLT2 inhibitors) 2, 4
• Venous pH <7.3 1
• Serum bicarbonate <15-18 mEq/L 1, 2
• Elevated ketones (β-hydroxybutyrate preferred over nitroprusside method) 2, 4
• Anion gap >10 mEq/L 2

Fluid Resuscitation

Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour during the first hour to restore circulatory volume and tissue perfusion. 2, 3 Continue fluid replacement based on hemodynamic status, serum electrolyte levels, and urine output, with the goal of correcting estimated deficits within 24 hours. 2 The induced change in serum osmolality should not exceed 3 mOsm/kg/hour to prevent cerebral edema. 2

Monitor fluid input/output, hemodynamic parameters, and clinical examination continuously to assess progress. 2, 3

Insulin Therapy

Standard approach for critically ill patients:

• Continuous intravenous regular insulin infusion at 0.1 units/kg/hour without an initial bolus 2, 3
• If plasma glucose does not fall by 50 mg/dL in the first hour, double the insulin infusion hourly until achieving a steady decline of 50-75 mg/hour 2
• Target blood glucose of 100-180 mg/dL 2
• Monitor blood glucose every 2-4 hours 1, 3

For mild to moderate uncomplicated DKA: Subcutaneous rapid-acting insulin analogs may be used in emergency department or step-down units when combined with aggressive fluid management, which may be safer and more cost-effective than IV insulin. 1, 2 This requires adequate fluid replacement, frequent point-of-care glucose monitoring, treatment of concurrent infections, and appropriate follow-up. 1

Critical pitfall: Never interrupt insulin infusion when glucose levels fall. Instead, add dextrose-containing fluids (5% dextrose with 0.45-0.75% NaCl) to prevent hypoglycemia while continuing insulin to clear ketosis. 4 This is especially important in euglycemic DKA. 4

Electrolyte Management

Potassium

Total body potassium deficits are common despite potentially normal or elevated initial serum levels due to acidosis. 2, 3

Replacement protocol:

• Monitor potassium closely as insulin therapy and acidosis correction cause hypokalemia 2, 4
• Once renal function is assured and serum potassium falls below 5.5 mEq/L, add 20-40 mEq/L potassium to the infusion 2
• Use 2/3 KCl and 1/3 KPO₄ to maintain serum potassium between 4-5 mEq/L 2, 4
• If significant hypokalemia (<3.3 mEq/L) is present initially, delay insulin treatment until potassium is restored to avoid arrhythmias, cardiac arrest, and respiratory muscle weakness 2

Bicarbonate

Bicarbonate administration is generally not recommended for patients with pH >6.9, as studies show no difference in resolution of acidosis or time to discharge. 1, 2, 3

Only consider bicarbonate for:

• Adult patients with pH <6.9: administer 100 mmol sodium bicarbonate in 400 mL sterile water at 200 mL/hour 2
• Patients with pH 6.9-7.0: administer 50 mmol sodium bicarbonate in 200 mL sterile water at 200 mL/hour 2

Phosphate

Routine phosphate replacement has not shown beneficial effects on clinical outcomes. 2 Consider replacement only in patients with cardiac dysfunction, anemia, respiratory depression, or serum phosphate <1.0 mg/dL. 2

Monitoring During Treatment

Draw blood every 2-4 hours to determine serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH. 2, 3 Venous pH (typically 0.03 units lower than arterial pH) and anion gap can be followed to monitor resolution of acidosis. 2

Continuous cardiac monitoring is crucial in severe DKA to detect arrhythmias early, particularly given the risk of electrolyte-induced cardiac complications. 2, 3

Resolution Criteria

DKA is resolved when ALL of the following are met:

• Glucose <200 mg/dL 2
• Serum bicarbonate ≥18 mEq/L 2, 4
• Venous pH >7.3 2, 4
• Anion gap ≤12 mEq/L 2, 4

Transition to Subcutaneous Insulin

Critical timing: Administer basal insulin (intermediate or long-acting) 2-4 hours BEFORE stopping IV insulin to prevent recurrence of ketoacidosis and rebound hyperglycemia. 1, 2, 3 This is one of the most common and dangerous pitfalls in DKA management.

Recent evidence suggests that adding low-dose basal insulin analog (e.g., glargine) alongside IV insulin may prevent rebound hyperglycemia without increased risk of hypoglycemia. 1, 2

When the patient can eat, transition to a multiple-dose regimen using a combination of short/rapid-acting and intermediate/long-acting insulin at approximately 0.5-1.0 units/kg/day for newly diagnosed patients. 2

Identifying and Treating Precipitating Causes

Search for and treat underlying causes including sepsis, myocardial infarction, stroke, or other acute stressors. 1, 3 Obtain bacterial cultures of urine, blood, and other sites as needed and administer appropriate antibiotics if infection is suspected. 2

SGLT2 inhibitor consideration: These medications can cause euglycemic DKA and should be discontinued 3-4 days before surgery. 1, 2 Clinicians must maintain high suspicion for DKA in patients on SGLT2 inhibitors even with normal or mildly elevated glucose levels. 4

Special Considerations for Euglycemic DKA

In euglycemic DKA (glucose normal or only mildly elevated), add dextrose-containing fluids earlier in treatment to maintain adequate glucose levels while continuing insulin therapy to clear ketosis. 4 Never interrupt insulin infusion based on glucose levels alone—continue until complete resolution of ketosis. 4

Discharge Planning

A structured discharge plan must include:

• Identification of outpatient diabetes care provider 1
• Education on glucose monitoring, home glucose goals, and when to call provider 1
• Recognition, treatment, and prevention of hyperglycemia and hypoglycemia 1
• Sick-day management protocols 1
• Proper insulin administration technique and disposal of supplies 1
• Medication reconciliation to ensure no chronic medications are stopped 1
• Follow-up appointments scheduled before discharge 1

Discharge summaries should be transmitted to the primary care provider as soon as possible after discharge. 1