Diabetic Ketoacidosis: Comprehensive Evaluation and Management
Diagnostic Criteria
DKA is confirmed when all three criteria are present: blood glucose >250 mg/dL (though euglycemic DKA exists), venous pH <7.3, serum bicarbonate <18 mEq/L, and positive ketones (preferably β-hydroxybutyrate in blood). 1, 2
Severity Classification
- Mild DKA: Venous pH 7.25-7.30, bicarbonate 15-18 mEq/L, alert mental status 2
- Moderate DKA: Venous pH 7.00-7.24, bicarbonate 10-15 mEq/L, drowsy mental status 2
- Severe DKA: Venous pH <7.00, bicarbonate <10 mEq/L, stuporous/comatose, requires intensive monitoring including possible central venous and intra-arterial pressure monitoring 2
Initial Laboratory Evaluation
Obtain immediately upon presentation: 1, 3
- Plasma glucose
- Venous blood gas (arterial not necessary after initial diagnosis) 2
- Complete metabolic panel with calculated anion gap: [Na⁺] - ([Cl⁻] + [HCO₃⁻]), should be >10-12 mEq/L 2
- β-hydroxybutyrate (blood)—this is the preferred ketone measurement, NOT urine ketones or nitroprusside-based tests 2, 3
- Serum osmolality
- Complete blood count with differential
- Urinalysis
- Electrocardiogram with continuous cardiac monitoring in severe DKA 3
- Bacterial cultures (blood, urine, throat) if infection suspected 2, 3
Critical pitfall: Never rely on urine ketones or nitroprusside methods—they only measure acetoacetate and acetone, completely missing β-hydroxybutyrate (the predominant ketoacid). During treatment, β-hydroxybutyrate converts to acetoacetate, making nitroprusside tests paradoxically appear worse even as the patient improves. 2
Corrected Sodium Calculation
Calculate corrected sodium: [measured Na (mEq/L)] + [glucose (mg/dL) - 100]/100 × 1.6 2, 3
Immediate Management Protocol
Step 1: Fluid Resuscitation (FIRST PRIORITY)
Begin with isotonic (0.9%) saline at 15-20 mL/kg/hour during the first hour to restore circulatory volume and tissue perfusion. 1, 2, 3 Some evidence suggests balanced electrolyte solutions may achieve faster DKA resolution, though normal saline remains standard. 3, 4
After initial resuscitation: 1, 2
- 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
- Total fluid replacement should correct estimated deficits within 24 hours
- Induced change in serum osmolality must not exceed 3 mOsm/kg/hour to prevent cerebral edema 3
Monitor closely: Fluid input/output, hemodynamic parameters, clinical examination for signs of fluid overload (especially in renal or cardiac compromise) 2, 3
Step 2: Potassium Replacement (BEFORE INSULIN IF SEVERELY LOW)
Critical decision point based on initial potassium level: 1, 2, 3
- If K⁺ <3.3 mEq/L: DELAY insulin therapy and aggressively replace potassium FIRST to prevent fatal cardiac arrhythmias, cardiac arrest, and respiratory muscle weakness 2, 3
- If K⁺ 3.3-5.5 mEq/L: Add 20-40 mEq/L potassium to IV fluids (2/3 KCl and 1/3 KPO₄) once adequate urine output confirmed 1, 2, 3
- If K⁺ >5.5 mEq/L: Hold potassium replacement but recheck frequently; levels will drop rapidly with insulin therapy 2
Target serum potassium: 4-5 mEq/L throughout treatment. 1, 2 Total body potassium deficits are common despite potentially normal or elevated initial levels due to acidosis-induced extracellular shift. 3
Step 3: Insulin Therapy
For critically ill, mentally obtunded, or severe DKA patients: Continuous IV regular insulin is the standard of care. 5, 1, 3
Standard IV Insulin Protocol:
- Start continuous IV regular insulin infusion at 0.1 units/kg/hour WITHOUT an initial bolus 1, 3 (though some protocols use 0.15 U/kg bolus followed by 0.1 U/kg/hour infusion 3)
- If glucose does not fall by 50 mg/dL in the first hour: Double the insulin infusion rate hourly until steady decline of 50-75 mg/dL per hour is achieved 2, 3
- When glucose falls to 200-250 mg/dL: Add dextrose (D5W) to IV fluids to prevent hypoglycemia while continuing insulin infusion to clear ketones 2
- Target glucose decline: 50-75 mg/dL per hour 3
Critical pitfall: Never discontinue IV insulin when glucose normalizes—ketoacidosis takes longer to resolve than hyperglycemia. Premature insulin cessation causes recurrence. 2, 3
Alternative for Uncomplicated Mild-Moderate DKA:
Subcutaneous rapid-acting insulin analogs combined with aggressive fluid management may be used in emergency department or step-down units—this approach may be safer and more cost-effective than IV insulin. 5, 1 For mild DKA, subcutaneous regular insulin every 4 hours (5-unit increments for every 50 mg/dL increase above 150 mg/dL, up to 20 units for glucose 300 mg/dL) is acceptable. 3
Contraindication for subcutaneous insulin: Altered mental status, severe DKA, hemodynamic instability. 2
Emerging Evidence:
British guidelines suggest adding subcutaneous glargine (basal insulin) alongside continuous IV regular insulin, which has shown faster DKA resolution and shorter hospital stays compared to IV insulin alone. 4 This is not yet standard in American guidelines but represents a promising approach.
Step 4: Bicarbonate Therapy (Generally NOT Recommended)
Bicarbonate use is NOT recommended for DKA patients with pH >6.9-7.0, as it provides no benefit in resolution of acidosis or time to discharge and may worsen ketosis, cause hypokalemia, and increase cerebral edema risk. 5, 1, 2, 3
Exception—consider bicarbonate only if: 2, 3
- pH <6.9: Give 100 mmol sodium bicarbonate in 400 mL sterile water at 200 mL/hour
- pH 6.9-7.0: Give 50 mmol sodium bicarbonate in 200 mL sterile water at 200 mL/hour
- Pre- and post-intubation when pH <7.2 or bicarbonate <10 mEq/L to prevent hemodynamic collapse from apnea during intubation 4
Step 5: Phosphate Replacement (Selective)
Routine phosphate replacement is NOT recommended, as studies show no beneficial effects on clinical outcomes. 2, 3
Consider phosphate replacement ONLY if: 3
- Cardiac dysfunction present
- Anemia present
- Respiratory depression present
- Serum phosphate <1.0 mg/dL
When indicated, use 1/3 of potassium replacement as KPO₄ (the other 2/3 as KCl). 2, 3
Monitoring During Treatment
Frequency of Monitoring:
- Blood glucose: Every 1-2 hours 1
- Comprehensive metabolic panel (electrolytes, glucose, BUN, creatinine, osmolality), venous pH, β-hydroxybutyrate: Every 2-4 hours 1, 2, 3
- Continuous cardiac monitoring in severe DKA to detect arrhythmias early 3
After initial diagnosis, venous pH (typically 0.03 units lower than arterial) and anion gap adequately monitor acidosis resolution—repeated arterial sticks are unnecessary. 2, 3
Resolution Criteria
DKA is resolved when ALL of the following are met: 1, 2, 3
- Glucose <200 mg/dL
- Serum bicarbonate ≥18 mEq/L
- Venous pH >7.3
- Anion gap ≤12 mEq/L
Note: Ketonemia (β-hydroxybutyrate) typically takes longer to clear than hyperglycemia—continue monitoring until β-hydroxybutyrate normalizes (<0.5 mmol/L). 2
Transition to Subcutaneous Insulin
Administer basal subcutaneous insulin (NPH, detemir, glargine, or degludec) 2-4 hours BEFORE stopping IV insulin to prevent recurrence of ketoacidosis and rebound hyperglycemia. 5, 1, 2, 3 This overlap period is absolutely critical.
For Newly Diagnosed Patients:
Initiate multidose regimen of short/rapid-acting and intermediate/long-acting insulin at approximately 0.5-1.0 units/kg/day. 3
For Known Diabetics:
Resume prior insulin regimen or adjust based on hospital course. 5
Identification and Treatment of Precipitating Causes
Common precipitating factors to identify and treat: 1, 2, 3, 6, 7
- Infections (most common)—obtain cultures and administer appropriate antibiotics 2, 3
- Insulin omission or inadequacy (especially in type 1 diabetes)
- New diagnosis of diabetes
- Myocardial infarction—check troponin 7
- Stroke
- Pancreatitis—check amylase, lipase 7
- Trauma
- SGLT2 inhibitor use—can cause euglycemic DKA; discontinue 3-4 days before surgery 2, 3
- Pregnancy
- Medications (corticosteroids, antipsychotics)
Critical Complications to Monitor and Prevent
Cerebral Edema (Rare but Frequently Fatal)
Occurs in 0.7-1.0% of children with DKA; less common in adults but devastating when it occurs. 3
- Rapid overcorrection of hyperglycemia
- Overly aggressive fluid resuscitation
- Higher BUN at presentation
- Young age
- New-onset diabetes
- Limit induced change in serum osmolality to <3 mOsm/kg/hour
- Use judicious isotonic or hypotonic saline (avoid excessive hypotonic fluids)
- Avoid excessive insulin dosing
- Monitor neurological status closely
Signs of cerebral edema: Headache, altered mental status, bradycardia, hypertension, seizures. If suspected, give mannitol or hypertonic saline immediately and obtain emergent CT. 4
Hypoglycemia
When glucose falls below 200-250 mg/dL, add dextrose to IV fluids (D5W or D10W) while continuing insulin infusion. 2 Never stop insulin to treat hypoglycemia—this will cause ketoacidosis recurrence.
Hypokalemia
Most dangerous complication during treatment. Total body potassium is always depleted despite potentially normal initial levels. Aggressive replacement and frequent monitoring (every 2-4 hours) are essential to prevent fatal arrhythmias. 1, 2, 3
Airway Management in Critically Ill DKA Patients
For impending respiratory failure: 4
- Bilevel positive airway pressure (BiPAP) is NOT recommended due to aspiration risk
- Intubation and mechanical ventilation are recommended with careful monitoring and management of acid-base and fluid status
- Consider bicarbonate pre- and post-intubation if pH <7.2 to prevent hemodynamic collapse from apnea 4
Nutritional Support
Early initiation of oral nutrition (once patient can tolerate) has been shown to reduce ICU and overall hospital length of stay. 4 Do not delay nutrition until complete resolution of acidosis if patient is alert and able to eat.
For continuous enteral or parenteral nutrition, use regular insulin every 6 hours or rapid-acting insulin every 4 hours, starting with 1 unit per 10-15 g carbohydrate. 5
Discharge Planning and Prevention
Structured discharge plan should include: 5, 3
- Appropriate insulin regimen with clear dosing instructions
- Education on recognition, prevention, and management of DKA
- Sick-day rules (never omit insulin, check ketones when glucose >250 mg/dL)
- Scheduled outpatient follow-up (ideally within 1 week)
- Transmission of discharge summary to primary care provider as soon as possible 5
- Patient education on adherence to insulin therapy
- Instructions to contact physician early during illness
- Ensuring uninterrupted access to insulin and diabetes supplies
- Blood β-hydroxybutyrate testing at home for high-risk patients (superior to urine ketones for early detection) 2
- Extended phone services, telemedicine, public campaigns 6
For patients on SGLT2 inhibitors: Discontinue 3-4 days before surgery and educate about euglycemic DKA risk. 2, 3
Special Populations
Older Adults
Insulin-treated patients ≥80 years are more than twice as likely to visit the emergency department for insulin-related hypoglycemia. 5 Consider oral therapy in place of insulin for some patients in long-term care to lower hypoglycemia risk. 5
Patients with Type 2 Diabetes
DKA occurs in almost one-third of cases among those with type 2 diabetes, particularly obese Black patients. 8 Do not assume DKA only occurs in type 1 diabetes.
Youth with New-Onset Diabetes
The distinction between type 1 and type 2 diabetes may be unclear initially. Continue subcutaneous insulin therapy until metabolic compensation is established and islet autoantibody results become available. 2