What is the stepwise management of diabetic ketoacidosis (DKA)?

Management of Diabetic Ketoacidosis (DKA) - Stepwise Protocol Using Canadian Lab Units

Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour for the first hour, followed by continuous intravenous regular insulin at 0.1 units/kg/hour once potassium is ≥3.3 mmol/L, and continue insulin until complete resolution (pH >7.3, bicarbonate ≥18 mmol/L, anion gap ≤12 mmol/L) regardless of glucose levels. 1, 2, 3

Step 1: Initial Assessment and Diagnosis

Diagnostic Criteria

• Confirm DKA with: blood glucose >13.9 mmol/L (250 mg/dL), arterial pH <7.3, serum bicarbonate <15 mmol/L, and presence of ketonemia or ketonuria 2, 3
• Note that euglycemic DKA (glucose normal or mildly elevated) is increasingly recognized, particularly with SGLT2 inhibitor use, so do not exclude DKA based on glucose alone 1, 4

Laboratory Evaluation

• Draw immediately: plasma glucose, electrolytes with calculated anion gap, serum ketones (β-hydroxybutyrate preferred), blood urea nitrogen/creatinine, osmolality, arterial blood gases, complete blood count, urinalysis, and electrocardiogram 2, 3
• Direct measurement of β-hydroxybutyrate is superior to nitroprusside method, which only detects acetoacetic acid and acetone, missing the predominant ketone body 1, 2

Identify Precipitating Factors

• Obtain bacterial cultures (blood, urine, throat) if infection suspected and start appropriate antibiotics 2, 3
• Consider other triggers: myocardial infarction, stroke, pancreatitis, trauma, insulin omission, or SGLT2 inhibitor use 5, 2

Step 2: Fluid Resuscitation (FIRST Priority)

Initial Fluid Bolus

• Administer isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in average adult) during the first hour 1, 2, 3
• This aggressive initial resuscitation restores circulatory volume, improves tissue perfusion, and enhances insulin sensitivity 2

Subsequent Fluid Management

• Continue isotonic saline based on hydration status, electrolyte levels, and urine output 2, 3
• When glucose reaches 13.9 mmol/L (250 mg/dL), switch to 5% dextrose with 0.45-0.75% NaCl to prevent hypoglycemia while continuing insulin to clear ketosis 1, 2, 3
• Critical pitfall: Never interrupt insulin when glucose falls; instead add dextrose to maintain glucose while clearing ketones 1, 2
• Total fluid replacement should correct estimated deficits within 24 hours 2

Step 3: Potassium Management (BEFORE Insulin)

Pre-Insulin Potassium Assessment

• If K+ <3.3 mmol/L: DO NOT start insulin - aggressively replace potassium first to prevent life-threatening arrhythmias and respiratory muscle weakness 2
• If K+ 3.3-5.5 mmol/L: add 20-30 mEq/L potassium (2/3 KCl and 1/3 KPO₄) to IV fluids once adequate urine output confirmed 1, 2, 3
• If K+ >5.5 mmol/L: withhold potassium initially but monitor closely, as levels will drop rapidly with insulin therapy 2

Ongoing Potassium Monitoring

• Maintain serum potassium between 4-5 mmol/L throughout treatment 1, 2, 3
• Insulin therapy and acidosis correction both drive potassium intracellularly, causing potentially dangerous hypokalemia 1, 2
• Inadequate potassium monitoring is a leading cause of mortality in DKA 2

Step 4: Insulin Therapy

Initiation

• Start continuous intravenous regular insulin infusion at 0.1 units/kg/hour WITHOUT an initial bolus (bolus increases cerebral edema risk) 1, 2, 3, 6
• This is the standard of care for moderate to severe DKA and critically ill patients 5, 2

Titration

• If glucose does not fall by 2.8 mmol/L (50 mg/dL) in the first hour, check hydration status; if acceptable, double insulin infusion rate hourly until steady glucose decline of 2.8-4.2 mmol/L/hour (50-75 mg/dL/hour) achieved 2, 3
• When glucose reaches 13.9 mmol/L (250 mg/dL), decrease insulin to 0.05-0.1 units/kg/hour AND add dextrose to IV fluids 3

Duration

• Continue insulin infusion until COMPLETE resolution of ketoacidosis regardless of glucose levels: pH >7.3, bicarbonate ≥18 mmol/L, and anion gap ≤12 mmol/L 1, 2, 3
• Premature termination before ketosis resolution is a common cause of recurrent DKA 1, 2, 3

Alternative for Mild-Moderate Uncomplicated DKA

• Subcutaneous rapid-acting insulin analogs combined with aggressive fluid management may be equally effective, safer, and more cost-effective than IV insulin for uncomplicated cases 5, 2
• This approach requires adequate fluid replacement, frequent point-of-care glucose monitoring, and appropriate follow-up 5

Step 5: Monitoring During Treatment

Glucose Monitoring

• Check blood glucose every 1-2 hours 1, 3
• Target glucose 8.3-11.1 mmol/L (150-200 mg/dL) until DKA resolution parameters met 2

Laboratory Monitoring

• Draw blood every 2-4 hours for: serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH 1, 2, 3
• Follow venous pH (typically 0.03 units lower than arterial pH) and anion gap to monitor acidosis resolution 2, 3
• Monitor β-hydroxybutyrate levels if available for most accurate assessment of ketosis clearance 1, 2

Step 6: Bicarbonate Administration (Generally NOT Recommended)

• Do NOT administer bicarbonate if pH >6.9-7.0 - studies show no benefit in resolution time or outcomes, and may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 5, 2, 6, 7
• Consider bicarbonate only if pH <6.9 or in hemodynamically unstable patients with pH <7.2 and bicarbonate <10-12 mmol/L 6, 7
• Never give bicarbonate to children with DKA except in very severe acidemia with hemodynamic instability refractory to saline 6

Step 7: Resolution Criteria

DKA is Resolved When ALL of the Following Are Met:

• Glucose <11.1 mmol/L (200 mg/dL) 2, 3
• Serum bicarbonate ≥18 mmol/L 1, 2, 3
• Venous pH >7.3 1, 2, 3
• Anion gap ≤12 mmol/L 1, 2, 3

Step 8: Transition to Subcutaneous Insulin

Timing and Overlap

• Administer basal insulin (intermediate or long-acting) 2-4 hours BEFORE stopping IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia 5, 1, 2, 3
• This overlap period is essential - premature termination of IV insulin causes recurrent DKA 1, 2
• Consider adding low-dose basal insulin analog during IV insulin infusion to prevent rebound hyperglycemia 5, 1

Post-Resolution Management

• If patient is NPO (nothing by mouth), continue IV insulin and fluid replacement with subcutaneous regular insulin supplementation as needed 2
• When patient can eat, start multiple-dose schedule using combination of short/rapid-acting and intermediate/long-acting insulin 2

Critical Pitfalls to Avoid

• Starting insulin before correcting severe hypokalemia (K+ <3.3 mmol/L) - causes life-threatening arrhythmias 2, 6
• Interrupting insulin when glucose falls - perpetuates ketosis; add dextrose instead 1, 2
• Premature termination of insulin before complete ketosis resolution - leads to recurrent DKA 1, 2, 3
• Overly rapid correction of osmolality - increases cerebral edema risk, especially in children 2, 6, 8
• Using insulin bolus - increases cerebral edema risk 6
• Inadequate potassium monitoring and replacement - leading cause of DKA mortality 2
• Relying on nitroprusside method for ketone measurement - misses β-hydroxybutyrate, the predominant ketone 1, 2, 3
• Stopping IV insulin without 2-4 hour overlap with subcutaneous basal insulin - causes rebound hyperglycemia and recurrent ketoacidosis 5, 1, 2, 3