What is the step‑by‑step management of diabetic ketoacidosis?

Stepwise Management of Diabetic Ketoacidosis

Step 1: Confirm Diagnosis and Assess Severity

Establish the diagnosis using the American Diabetes Association criteria: blood glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, and presence of ketonemia or ketonuria. 1

• Obtain immediate laboratory workup: plasma glucose, venous or arterial blood gas, serum electrolytes with calculated anion gap, β-hydroxybutyrate (preferred over urine ketones), BUN/creatinine, urinalysis, complete blood count, and ECG 1, 2
• Calculate anion gap: [Na⁺] - ([Cl⁻] + [HCO₃⁻]); should be >10-12 mEq/L in DKA 1
• Classify severity to guide monitoring intensity:
  • Mild DKA: pH 7.25-7.30, bicarbonate 15-18 mEq/L, alert mental status 3
  • Moderate DKA: pH 7.00-7.24, bicarbonate 10-15 mEq/L, drowsy 3
  • Severe DKA: pH <7.00, bicarbonate <10 mEq/L, stupor/coma—requires ICU-level monitoring 3
• Obtain bacterial cultures (blood, urine, throat) if infection is suspected and start appropriate antibiotics 1, 2

Step 2: Initiate Aggressive Fluid Resuscitation

Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in the first hour) for all patients to restore intravascular volume and tissue perfusion. 1, 2

• The typical total body water deficit in DKA is 6-9 liters; plan to correct this over 24 hours 1
• After the first hour, adjust fluid choice based on corrected serum sodium (add 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
  • If corrected sodium is low: continue 0.9% NaCl at 4-14 mL/kg/hour
• Monitor closely for fluid overload in patients with cardiac or renal compromise 1

Step 3: Correct Potassium BEFORE Starting Insulin

Total body potassium depletion is universal in DKA (3-5 mEq/kg), and insulin will drive potassium intracellularly, causing rapid decline. 1

• If serum K⁺ <3.3 mEq/L: HOLD insulin and aggressively replace potassium until K⁺ ≥3.3 mEq/L to prevent life-threatening arrhythmias 1, 3
• If K⁺ 3.3-5.5 mEq/L: Add 20-30 mEq/L potassium to IV fluids (use 2/3 KCl and 1/3 KPO₄) once adequate urine output is confirmed 1, 2
• If K⁺ >5.5 mEq/L: Withhold potassium initially but monitor every 2-4 hours as levels will drop rapidly with insulin therapy 1
• Target serum potassium: 4-5 mEq/L throughout treatment 1, 2

Step 4: Start Continuous Intravenous Insulin

For moderate-to-severe DKA or critically ill/mentally obtunded patients, continuous IV regular insulin at 0.1 units/kg/hour is the standard of care. 1, 2

• Confirm serum potassium ≥3.3 mEq/L before initiating insulin 1
• Start continuous IV regular insulin infusion at 0.1 units/kg/hour (no initial bolus needed) 1, 2
• Target glucose decline: 50-75 mg/dL per hour 1, 2
• If glucose does NOT fall by 50 mg/dL in the first hour and hydration is adequate, double the insulin infusion rate every hour until steady decline achieved 1, 2

Alternative for mild-to-moderate uncomplicated DKA: Subcutaneous rapid-acting insulin analogs combined with aggressive fluid management are equally effective, safer, and more cost-effective for hemodynamically stable, alert patients 1

Step 5: Add Dextrose When Glucose Falls

When plasma glucose reaches 250 mg/dL, change IV fluids to 5% dextrose with 0.45-0.75% NaCl while continuing insulin infusion. 1, 2

• This prevents hypoglycemia while allowing insulin to continue clearing ketones 1, 2
• Target glucose: 150-200 mg/dL until DKA resolution parameters are met 1
• Critical pitfall: Stopping insulin when glucose normalizes (instead of adding dextrose) is a common cause of persistent or recurrent ketoacidosis 1, 2

Step 6: Monitor Closely During Treatment

Draw blood every 2-4 hours for serum electrolytes, glucose, BUN, creatinine, osmolality, and venous pH. 1, 2

• Follow venous pH (typically 0.03 units lower than arterial pH) and anion gap to monitor acidosis resolution 1, 2
• Use β-hydroxybutyrate measurements (blood) for monitoring ketosis—this is the preferred method 1, 2
• Avoid nitroprusside-based urine or serum ketone tests; they only measure acetoacetate and acetone, missing β-hydroxybutyrate (the predominant ketone body) 1, 2
• Check blood glucose every 1-2 hours 2

Step 7: Avoid Bicarbonate (Usually)

Bicarbonate is NOT recommended for DKA patients with pH >6.9-7.0, as studies show no benefit in resolution time or outcomes. 1

• Bicarbonate may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 1
• Reserve bicarbonate only for pH <6.9 1, 2

Step 8: Confirm DKA Resolution

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

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

Continue insulin infusion until complete resolution of ketoacidosis, regardless of glucose levels. 1, 2

Step 9: Transition to Subcutaneous Insulin

Administer basal insulin (intermediate or long-acting) 2-4 hours BEFORE stopping IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia. 1, 2

• Once the patient can eat, start a multiple-dose schedule using a combination of short/rapid-acting and intermediate/long-acting insulin 1
• If the patient remains NPO after DKA resolution, continue IV insulin and fluid replacement, supplementing with subcutaneous regular insulin as needed 1
• Critical pitfall: Stopping IV insulin without prior administration of basal subcutaneous insulin causes rebound hyperglycemia and ketoacidosis 1

Step 10: Identify and Treat Precipitating Causes

Common precipitants include infection (most frequent), myocardial infarction, stroke, pancreatitis, insulin omission, SGLT2 inhibitor use, and glucocorticoid therapy. 1

• Treatment of the underlying cause must occur simultaneously with correction of metabolic derangements 1
• If SGLT2 inhibitors are involved, discontinue immediately and do not restart until 3-4 days after metabolic stability is achieved 1

Special Considerations

Euglycemic DKA

• Defined by blood glucose <200-250 mg/dL with pH <7.3, bicarbonate <15-18 mEq/L, anion gap >12 mEq/L, and ketonemia/ketonuria 1
• SGLT2 inhibitors are the leading contemporary cause; incidence 0.6-4.9 events per 1,000 patient-years with relative risk 2.46 versus placebo 1
• Management is identical to hyperglycemic DKA, but add dextrose earlier to prevent hypoglycemia while continuing insulin 1

Cerebral Edema Risk

• Occurs more commonly in children and adolescents than adults 1
• Avoid overly rapid correction of osmolality (limit to ≤3 mOsm/kg H₂O per hour) 1
• Monitor continuously for altered mental status, headache, or neurological deterioration 1

Critically Ill Patients

• Continuous IV insulin remains the standard of care for patients with altered mental status or hemodynamic instability 1
• Consider endotracheal intubation for Glasgow Coma Scale <8, pH <7.15 with respiratory acidosis, or severe respiratory distress 3

Common Pitfalls to Avoid

• Starting insulin before correcting hypokalemia (K⁺ <3.3 mEq/L) can cause fatal arrhythmias 1, 3
• Stopping insulin when glucose falls to 250 mg/dL instead of adding dextrose leads to recurrent ketoacidosis 1, 2
• Premature termination of insulin therapy before complete resolution of ketosis 1, 2
• Using nitroprusside-based ketone tests for monitoring misses β-hydroxybutyrate and delays appropriate therapy 1, 2
• Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA 1