What are the steps for managing Diabetic Ketoacidosis (DKA)?

Management of Diabetic Ketoacidosis: Step-by-Step Protocol

Begin with aggressive isotonic saline resuscitation at 15-20 mL/kg/hour for the first hour, followed by continuous IV insulin at 0.1 units/kg/hour once potassium is ≥3.3 mEq/L, and continue insulin until complete resolution of ketoacidosis regardless of glucose levels. 1, 2

Step 1: Initial Assessment and Diagnosis

Confirm DKA diagnosis when all three criteria are present: 1, 2

• Blood glucose >250 mg/dL
• Arterial pH <7.3
• Serum bicarbonate <15 mEq/L with positive ketones

Obtain immediate laboratory studies: 3, 1

• Plasma glucose, electrolytes with calculated anion gap, serum ketones
• Blood urea nitrogen/creatinine, arterial blood gases
• Complete blood count with differential, urinalysis, urine ketones
• Electrocardiogram
• HbA1c to determine if this represents poor chronic control or acute decompensation 3

Identify precipitating factors: 1, 2

• Obtain bacterial cultures (blood, urine, throat) if infection suspected
• Evaluate for myocardial infarction, stroke, pancreatitis, trauma
• Review medications, particularly SGLT2 inhibitors
• Assess for insulin omission or inadequacy

Step 2: Fluid Resuscitation (FIRST PRIORITY)

Hour 1 - Aggressive initial resuscitation: 3, 1, 2

• Administer isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 liters in average adult)
• This restores intravascular volume, improves renal perfusion, and enhances insulin sensitivity

Subsequent fluid management (after hour 1): 3, 1

• If corrected serum sodium is normal or elevated: use 0.45% NaCl at 4-14 mL/kg/hour
• If corrected serum sodium is low: continue 0.9% NaCl at similar rate
• Correct serum sodium for hyperglycemia: add 1.6 mEq to sodium value for each 100 mg/dL glucose above 100 mg/dL 3

When glucose reaches 250 mg/dL: 1, 4

• Change fluid to 5% dextrose with 0.45-0.75% NaCl
• This prevents hypoglycemia while continuing insulin to clear ketones
• Critical pitfall: Failure to add dextrose at this threshold while continuing insulin is a common cause of hypoglycemia 1, 4

Step 3: Potassium Management (BEFORE INSULIN)

Check initial potassium level and act accordingly: 1, 2

• If K+ <3.3 mEq/L: Hold insulin therapy completely and aggressively replace potassium until ≥3.3 mEq/L to prevent life-threatening arrhythmias and respiratory muscle weakness 1, 2

• If K+ 3.3-5.5 mEq/L: Add 20-30 mEq potassium per liter of IV fluid (use 2/3 KCl and 1/3 KPO₄) once adequate urine output confirmed 3, 1

• If K+ >5.5 mEq/L: Withhold potassium initially but monitor closely, as levels will drop rapidly with insulin therapy 1

Target serum potassium 4-5 mEq/L throughout treatment - hypokalemia occurs in approximately 50% of patients during treatment and is a leading cause of mortality in DKA. 1, 2

Step 4: Insulin Therapy

For moderate to severe DKA (critically ill, mentally obtunded): 1, 2

• Start continuous IV regular insulin at 0.1 units/kg/hour
• This is the standard of care for severe cases

For mild-to-moderate uncomplicated DKA: 1

• Subcutaneous rapid-acting insulin analogs combined with aggressive fluid management are equally effective and potentially safer than IV insulin
• More cost-effective option when appropriate

Monitor insulin response: 1

• Target glucose decline of 50-75 mg/dL per hour
• If glucose does not fall by 50 mg/dL in first hour, check hydration status; if acceptable, double insulin infusion rate hourly until steady decline achieved

Critical principle: Never stop insulin when glucose normalizes 1, 4

• Continue insulin infusion until complete resolution of ketoacidosis
• Target glucose 150-200 mg/dL until DKA resolved
• Ketonemia takes longer to clear than hyperglycemia 4
• Interruption of insulin when glucose falls is a common cause of persistent or worsening ketoacidosis 1, 4

Step 5: Monitoring During Treatment

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

• Serum electrolytes, glucose, blood urea nitrogen, creatinine
• Osmolality and venous pH (adequate for monitoring; typically 0.03 units lower than arterial pH)
• Anion gap to confirm ketoacid clearance

Preferred ketone monitoring: 1, 4

• Direct measurement of β-hydroxybutyrate in blood is preferred
• Nitroprusside method only measures acetoacetic acid and acetone, not β-hydroxybutyrate, and should not guide treatment response

Step 6: Bicarbonate Therapy (Generally NOT Recommended)

Do NOT administer bicarbonate if pH >6.9-7.0 1, 2

• Studies show no difference in resolution time or outcomes
• May worsen ketosis, cause hypokalemia, and increase cerebral edema risk
• Only consider if pH <6.9 with severe acidosis

Step 7: Resolution Criteria

DKA is resolved when ALL of the following are met: 1, 4, 2

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

Step 8: Transition to Subcutaneous Insulin

Timing is critical to prevent recurrence: 1, 2

• Administer basal insulin (intermediate or long-acting) 2-4 hours BEFORE stopping IV insulin infusion
• This overlap prevents recurrence of ketoacidosis and rebound hyperglycemia
• Critical pitfall: Premature termination of IV insulin before basal insulin takes effect leads to DKA recurrence 1

If patient is NPO after DKA resolution: 4

• Continue IV insulin and fluid replacement
• Supplement with subcutaneous regular insulin every 4 hours as needed
• Give 5-unit increments for every 50 mg/dL increase above 150 mg/dL (up to 20 units for glucose 300 mg/dL)

When patient can eat: 1, 4

• Start multiple-dose regimen combining short/rapid-acting and intermediate/long-acting insulin
• Continue IV insulin for 1-2 hours after starting subcutaneous insulin to ensure adequate plasma levels

Special Considerations and Pitfalls

SGLT2 inhibitor-associated DKA: 1, 2, 5

• Discontinue SGLT2 inhibitors 3-4 days before any planned surgery
• Monitor for euglycemic DKA (normal or mildly elevated glucose with ketoacidosis)
• If euglycemic DKA present, start D5 alongside 0.9% NaCl at beginning of insulin treatment 4

Common causes of treatment failure: 1, 4

• Inadequate potassium monitoring and replacement
• Interruption of insulin infusion when glucose normalizes
• Failure to add dextrose when glucose falls below 250 mg/dL
• Overzealous insulin without glucose supplementation leading to hypoglycemia
• Not treating underlying precipitating cause (infection, MI, medication issues)

Total body deficits to replace over 24 hours: 3

• Water: 6 liters in DKA
• Sodium: 7-10 mEq/kg
• Potassium: 3-5 mEq/kg
• Chloride: 3-5 mEq/kg