What is the recommended treatment protocol for diabetic ketoacidosis in an adult?

Treatment of Diabetic Ketoacidosis in Adults

Begin immediate fluid resuscitation with isotonic saline at 15-20 mL/kg/hour (approximately 1-1.5 L in the first hour), followed by continuous IV regular insulin at 0.1 units/kg/hour once potassium is ≥3.3 mEq/L, and add dextrose to IV fluids when glucose reaches 250 mg/dL while continuing insulin until complete resolution of ketoacidosis. 1

Initial Assessment and Diagnosis

Obtain the following laboratory studies immediately upon presentation 1:

• Plasma glucose, arterial or venous pH, serum electrolytes with calculated anion gap
• β-hydroxybutyrate (preferred over urine ketones)
• BUN, creatinine, effective serum osmolality (2 × [Na] + glucose/18)
• Urinalysis with ketones, complete blood count with differential
• Electrocardiogram
• Blood, urine, and throat cultures if infection is suspected

Diagnostic criteria for DKA: blood glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, moderate ketonuria or ketonemia, and anion gap >12 mEq/L 2, 1. Note that euglycemic DKA (glucose <250 mg/dL) can occur, particularly with SGLT2 inhibitor use 3.

Fluid Resuscitation Protocol

First Hour

Start with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour to restore intravascular volume and renal perfusion 2, 1. This aggressive initial fluid replacement is critical for improving insulin sensitivity 1.

After First Hour

Calculate corrected serum sodium by adding 1.6 mEq/L for each 100 mg/dL glucose above 100 mg/dL 1:

• If corrected sodium is normal or elevated: switch to 0.45% NaCl at 4-14 mL/kg/hour 1
• If corrected sodium is low: continue 0.9% NaCl at 4-14 mL/kg/hour 1

When Glucose Reaches 250 mg/dL

Change IV fluids to 5% dextrose with 0.45-0.75% NaCl while continuing the insulin infusion 2, 1. This prevents hypoglycemia while ensuring complete ketoacidosis resolution. Never stop insulin when glucose normalizes—this is the most critical error in DKA management 3.

Target total fluid replacement to correct estimated deficits (typically 6-9 L) within 24 hours, limiting the change in serum osmolality to ≤3 mOsm/kg/hour to reduce cerebral edema risk 1.

Potassium Management

Total body potassium depletion is universal in DKA (3-5 mEq/kg) despite potentially normal or elevated initial serum levels due to acidosis 2, 1. This is a high-risk scenario requiring aggressive monitoring and replacement.

Potassium Replacement Algorithm

• If K⁺ <3.3 mEq/L: Hold insulin and replace potassium aggressively at 20-40 mEq/hour until K⁺ ≥3.3 mEq/L to prevent life-threatening arrhythmias, cardiac arrest, and respiratory muscle weakness 1
• If K⁺ 3.3-5.5 mEq/L: Add 20-30 mEq/L potassium (2/3 KCl and 1/3 KPO₄) to IV fluids once adequate urine output is confirmed 2, 1
• If K⁺ >5.5 mEq/L: Withhold potassium initially but monitor every 2-4 hours, as levels will fall rapidly with insulin therapy 1

Target serum potassium: 4-5 mEq/L throughout treatment 1. Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA 1.

Insulin Therapy

Standard IV Protocol (Moderate-Severe DKA)

Confirm serum potassium ≥3.3 mEq/L before starting insulin 1. Begin continuous IV regular insulin at 0.1 units/kg/hour without an initial bolus 2. An optional bolus of 0.1-0.15 units/kg may be given 1.

Target glucose decline: 50-75 mg/dL per hour 1. If glucose does not fall by at least 50 mg/dL in the first hour despite adequate hydration, double the insulin infusion rate each subsequent hour until steady decline is achieved 1.

Critical Principle

Continue insulin infusion until complete DKA resolution regardless of glucose levels 2, 1. When glucose reaches 250 mg/dL, add dextrose to IV fluids while maintaining insulin 2. Premature discontinuation of insulin is a frequent cause of recurrent ketoacidosis 1.

Alternative for Mild-Moderate Uncomplicated DKA

For hemodynamically stable, alert patients with mild-moderate DKA, subcutaneous rapid-acting insulin analogs at 0.15 units/kg every 2-3 hours combined with aggressive fluid management are equally effective, safer, and more cost-effective than IV insulin 1. However, continuous IV insulin remains the standard for critically ill and mentally obtunded patients 1.

Monitoring During Treatment

Draw blood every 2-4 hours for 2, 1:

• Serum electrolytes, glucose, BUN, creatinine, calculated osmolality
• Venous pH (typically 0.03 units lower than arterial pH)
• Anion gap to assess resolution

Check blood glucose hourly 2. Measure β-hydroxybutyrate in blood as the preferred method for monitoring ketosis resolution; nitroprusside-based tests miss the predominant ketone body and may delay appropriate therapy 1, 3.

Resolution Criteria

DKA is resolved when ALL of the following are met 2, 1:

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

Transition to Subcutaneous Insulin

Administer basal insulin (glargine, detemir, or NPH) 2-4 hours BEFORE stopping the IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia 1. Recent evidence shows that adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk 1.

Once the patient can eat, start a multiple-dose schedule using a combination of short/rapid-acting and intermediate/long-acting insulin 1. For newly diagnosed patients, start with approximately 0.5-1.0 units/kg/day 1.

Bicarbonate Administration

Bicarbonate is NOT recommended for DKA patients with pH >6.9-7.0 1. Multiple studies show no difference in resolution of acidosis or time to discharge with bicarbonate use, and it may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 1. Consider bicarbonate only if pH <6.9 1.

Identification and Treatment of Precipitating Causes

Actively search for and treat precipitating factors concurrently 1:

• Infection (most common): obtain cultures and start appropriate antibiotics 1
• Myocardial infarction, cerebrovascular accident
• Insulin omission or inadequacy
• Pancreatitis, trauma
• SGLT2 inhibitor use: discontinue immediately and do not restart until 3-4 days after metabolic stability 1
• Glucocorticoid therapy
• Pregnancy

Common Pitfalls to Avoid

• Starting insulin before correcting hypokalemia (K⁺ <3.3 mEq/L) can cause life-threatening arrhythmias 2, 1
• Stopping insulin when glucose falls to 250 mg/dL instead of adding dextrose leads to recurrent ketoacidosis 2, 1
• Overly rapid correction of hyperglycemia and hyperosmolality (>3 mOsm/kg/hour) increases cerebral edema risk 2, 1
• Not overlapping IV insulin with subcutaneous insulin during transition causes rebound hyperglycemia 2
• Using nitroprusside-based ketone tests for monitoring misses β-hydroxybutyrate and delays therapy 1, 3
• Inadequate potassium replacement leading to arrhythmias 2

Special Considerations

Euglycemic DKA

When glucose is <250 mg/dL at presentation (common with SGLT2 inhibitors), immediately add dextrose 5-10% to IV fluids while starting insulin infusion 3. The fundamental principle remains: insulin therapy must continue until ketoacidosis resolves, not until glucose normalizes 3.

Cerebral Edema

Cerebral edema occurs more commonly in children and adolescents than adults 1. Monitor closely for altered mental status, headache, or neurological deterioration. Prevent by limiting osmolality change to ≤3 mOsm/kg/hour 1.

Discharge Planning

Before discharge 1:

• Identify outpatient diabetes care providers
• Educate on glucose monitoring, insulin administration, recognition and treatment of hyperglycemia/hypoglycemia
• Ensure appropriate insulin regimen with attention to medication access and affordability
• Schedule follow-up appointments
• Provide sick-day management instructions: never stop basal insulin, measure ketones when glucose >200 mg/dL or during illness 1