What are the criteria and treatment for Diabetic Ketoacidosis (DKA)?

Diagnostic Criteria for Diabetic Ketoacidosis (DKA)

DKA is diagnosed when all three core criteria are simultaneously present: blood glucose >250 mg/dL, venous pH <7.3, and serum bicarbonate <15 mEq/L, along with elevated blood ketones (preferably β-hydroxybutyrate). 1, 2

Core Diagnostic Parameters

All three components must be present simultaneously for DKA diagnosis: 2

• Blood glucose >250 mg/dL is the traditional threshold, though this has been de-emphasized in recent guidelines due to increasing incidence of euglycemic DKA, particularly in patients on SGLT2 inhibitors 2, 3
• Venous pH <7.3 reflects the severity of ketoacidosis and is required for diagnosis 1, 2
• Serum bicarbonate <15 mEq/L indicates metabolic acidosis 1, 2
• Elevated blood β-hydroxybutyrate (β-OHB) is the preferred ketone measurement—not urine ketones or nitroprusside-based tests 2

Essential Laboratory Workup

Obtain immediately upon presentation: 1, 2

• Complete metabolic panel including sodium, potassium, chloride, bicarbonate, BUN, creatinine, and glucose 2
• Venous blood gas with pH, pCO2, and bicarbonate 2
• Blood β-hydroxybutyrate (gold standard for ketone measurement) 2
• Complete blood count with differential 2
• Urinalysis 2
• Serum osmolality 2
• Electrocardiogram 2
• Anion gap calculation: [Na⁺] - ([Cl⁻] + [HCO₃⁻]) should be >10-12 mEq/L in DKA 1, 2
• Corrected serum sodium: Add 1.6 mEq/L for every 100 mg/dL glucose above 100 1

If infection is suspected, obtain bacterial cultures of urine, blood, and throat 1

Severity Classification

DKA severity determines monitoring intensity and prognosis: 2

Mild DKA

• Venous pH: 7.25-7.30 1, 2
• Bicarbonate: 15-18 mEq/L 1, 2
• Anion gap: >10 mEq/L 2
• Mental status: Alert 1, 2

Moderate DKA

• Venous pH: 7.00-7.24 1, 2
• Bicarbonate: 10-15 mEq/L 1, 2
• Anion gap: >12 mEq/L 2
• Mental status: Drowsy/lethargic 1, 2

Severe DKA

• Venous pH: <7.00 1, 2
• Bicarbonate: <10 mEq/L 1, 2
• Anion gap: >12 mEq/L 2
• Mental status: Stuporous or comatose 2
• Associated with higher morbidity and mortality; often requires central venous and intra-arterial pressure monitoring 1, 2

Clinical Presentation

Classical presentation includes: 2

History:

• Polyuria and polydipsia (98% of cases) 2
• Weight loss (81%) 2
• Fatigue (62%) 2
• Dyspnea (57%) 2
• Vomiting (46%) 2
• Preceding febrile illness (40%) 2
• Abdominal pain (32%) 2
• Up to 25% may have coffee-ground emesis due to hemorrhagic gastritis 2

Physical findings:

• Poor skin turgor 2
• Kussmaul respirations (deep, rapid breathing) 2
• Tachycardia 2
• Hypotension 2
• Fruity breath odor 2, 4
• Altered mental status 2

Treatment Overview

Fluid Resuscitation

Begin aggressive fluid resuscitation with isotonic saline at 15-20 mL/kg/hour to restore circulatory volume and tissue perfusion 1

• Subsequent fluid choice depends on hydration state, serum electrolytes, and urine output 1
• Total fluid replacement should correct estimated deficits within 24 hours 1
• Monitor for fluid overload in patients with renal or cardiac compromise 1

Insulin Therapy

Start continuous IV regular insulin infusion at 0.1 units/kg/hour without an initial bolus 1

• If glucose does not fall by 50 mg/dL in the first hour, double the insulin infusion rate hourly until a steady decline of 50-75 mg/dL per hour is achieved 1
• When blood glucose falls below 200-250 mg/dL, add dextrose 5% to IV fluids while continuing insulin infusion to clear ketones 1, 5
• Target glucose between 150-200 mg/dL until DKA resolution 5
• Do not discontinue insulin therapy prematurely—ketonemia typically takes longer to clear than hyperglycemia 1, 5

Potassium Replacement

Critical to prevent fatal cardiac arrhythmias: 1

• If initial potassium <3.3 mEq/L: Delay insulin therapy and aggressively replace potassium first 1
• Once potassium <5.5 mEq/L and adequate urine output confirmed: Add 20-30 mEq potassium per liter of IV fluid to maintain serum potassium 4-5 mEq/L 1
• Include potassium in IV fluids until patient can tolerate oral supplementation 1

Bicarbonate Therapy

Not recommended except when pH <6.9; if used, add to IV fluids rather than giving as IV bolus 1

Special Considerations

• Euglycemic DKA (glucose <250 mg/dL with ketoacidosis): Start D5 alongside 0.9% NaCl at the beginning of insulin treatment 5
• Monitor closely for cerebral edema during treatment, especially with overly aggressive fluid resuscitation 1

Monitoring During Treatment

Draw blood every 2-4 hours to measure: 1, 2, 5

• Electrolytes (sodium, potassium, chloride, bicarbonate) 1
• Glucose 1
• Venous pH 1
• β-hydroxybutyrate 1
• Anion gap 1
• BUN and creatinine 1
• Serum osmolality 1

Venous pH is sufficient for monitoring—repeat arterial blood gases are generally unnecessary after initial diagnosis, as venous pH typically runs 0.03 units lower than arterial 1, 5

Resolution Criteria

DKA is resolved when ALL of the following are met: 5

• Glucose <200 mg/dL 5
• Venous pH >7.3 5
• Serum bicarbonate ≥18 mEq/L 5
• Anion gap ≤12 mEq/L 5

Ketonemia typically takes longer to clear than hyperglycemia, requiring continued monitoring and insulin therapy even after glucose normalizes 5

Transition to Subcutaneous Insulin

Once DKA is resolved and patient can eat: 5

• Administer basal insulin (NPH, detemir, glargine, or degludec) 2-4 hours before stopping IV insulin to prevent rebound hyperglycemia 1, 5
• Start a multiple-dose schedule using a combination of short/rapid-acting and intermediate/long-acting insulin 5
• Continue IV insulin infusion for 1-2 hours after starting subcutaneous insulin to ensure adequate plasma insulin levels 5

If patient is NPO after DKA resolution: 5

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

Critical Pitfalls to Avoid

• Do not rely on urine ketones or nitroprusside-based tests for diagnosis or monitoring—they only measure acetoacetate and acetone, not β-hydroxybutyrate (the predominant ketoacid in DKA) 1, 2
• Do not discontinue insulin therapy when glucose falls below 250 mg/dL—this is a common cause of persistent or worsening ketoacidosis; instead, add dextrose to IV fluids 1, 5
• Do not delay potassium replacement if initial potassium <3.3 mEq/L—insulin therapy must be delayed until potassium is repleted to avoid fatal arrhythmias 1
• Do not repeat arterial blood gases unnecessarily—venous pH adequately monitors acidosis resolution after initial diagnosis 1, 5
• Do not fail to identify and treat the underlying precipitating cause of DKA, as this can lead to recurrence 1

Differential Diagnosis

DKA must be distinguished from other causes of high anion gap metabolic acidosis: 2

• Lactic acidosis (measure blood lactate) 2
• Toxic ingestions (salicylate, methanol, ethylene glycol) 2
• Chronic renal failure 2
• Metformin use 2