What is the comprehensive approach to assessing Diabetic Ketoacidosis (DKA)?

Comprehensive Approach to Assessment of Diabetic Ketoacidosis (DKA)

Definition

DKA is diagnosed when all three criteria are present: blood glucose >250 mg/dL (though euglycemic DKA exists), venous pH <7.3, serum bicarbonate <15 mEq/L, and moderate ketonuria or ketonemia. 1

• Severity classification:

  • Mild DKA: pH 7.25-7.30, bicarbonate 15-18 mEq/L, alert mental status 1
  • Moderate DKA: pH 7.00-7.24, bicarbonate 10-15 mEq/L, drowsy mental status 1
  • Severe DKA: pH <7.00, bicarbonate <10 mEq/L, stupor/coma 1

• Anion gap >10-12 mEq/L calculated as [Na+] - ([Cl-] + [HCO3-]) 1

• Direct measurement of β-hydroxybutyrate in blood is preferred over nitroprusside method 1

Differential Diagnosis

DKA must be distinguished from other causes of high anion gap metabolic acidosis and other forms of ketoacidosis. 2

• Starvation ketosis: Glucose rarely >250 mg/dL, bicarbonate usually not <18 mEq/L 2
• Alcoholic ketoacidosis: Glucose mildly elevated to hypoglycemic, profound acidosis possible 2
• Lactic acidosis: Measure blood lactate levels 2
• Toxic ingestions: Salicylate, methanol (osmolar gap), ethylene glycol (calcium oxalate crystals in urine), paraldehyde (characteristic breath odor) 2
• Chronic renal failure: Typically hyperchloremic acidosis rather than high anion gap 2

History

Key Characteristics to Elicit:

• Polyuria and polydipsia (most common symptoms) 3
• Nausea, vomiting, abdominal pain (up to 25% have emesis, may be coffee-ground) 2
• Weight loss, severe fatigue, dyspnea 3
• Preceding febrile illness or infection 3
• Fruity odor on breath, drowsy feeling, flushed face, thirst, loss of appetite 4

Red Flags:

• Altered mental status ranging from drowsiness to coma (more common in severe DKA and HHS) 2
• Hypothermia (poor prognostic sign) 2
• Abdominal pain (may be result or cause of DKA; requires further evaluation if not resolving) 2
• Normothermia or hypothermia despite infection (due to peripheral vasodilation) 2

Risk Factors/Precipitating Events:

• Infection (most common precipitating factor) 2
• Newly onset type 1 diabetes or discontinuation/inadequate insulin in established diabetes 2
• Cerebrovascular accident, myocardial infarction, trauma, pancreatitis 2
• Alcohol abuse 2
• Drugs affecting carbohydrate metabolism: corticosteroids, thiazides, sympathomimetic agents (dobutamine, terbutaline) 2
• SGLT2 inhibitor use (modestly increases risk of euglycemic DKA) 3
• Elderly individuals with newly onset diabetes or those unable to take fluids 2

Physical Examination (Focused)

• Vital signs: Assess for hypotension, tachycardia, tachypnea (Kussmaul breathing), hypothermia 2
• Volume status: Signs of dehydration (dry mucous membranes, poor skin turgor, sunken eyes) 2
• Mental status: Alert, drowsy, stuporous, or comatose 2
• Cardiovascular: Assess perfusion, signs of shock 2
• Respiratory: Deep, labored breathing (Kussmaul respirations), fruity breath odor 2
• Abdominal: Tenderness, guarding, rebound (may indicate precipitating cause or DKA itself) 2
• Neurological: Level of consciousness, focal deficits suggesting stroke 2
• Skin: Injection sites for lipoatrophy/lipohypertrophy, signs of infection 4

Investigations and Expected Findings

Initial Laboratory Evaluation:

Obtain immediately upon presentation: 2, 1

• Plasma glucose: >250 mg/dL (classic DKA); may be <250 mg/dL in euglycemic DKA 1
• Venous blood gas: pH <7.3 (arterial pH not necessary after initial diagnosis) 1
• Serum bicarbonate: <15 mEq/L 1
• Serum ketones (β-hydroxybutyrate preferred): Elevated 1
• Electrolytes with calculated anion gap: >10-12 mEq/L 1
• Corrected sodium: Add 1.6 mEq/L for every 100 mg/dL glucose above 100 1
• Serum osmolality: Calculate as 2[measured Na] + glucose/18 2
• Blood urea nitrogen/creatinine: Assess renal function and hydration 2
• Complete blood count with differential: Leukocytosis common even without infection 2
• Urinalysis and urine ketones by dipstick 2
• Electrocardiogram: Assess for myocardial infarction, electrolyte abnormalities 2

Additional Tests to Consider:

• HbA1c: Distinguish acute episode vs. poorly controlled diabetes 2
• Bacterial cultures (blood, urine, throat) if infection suspected 2, 1
• Chest X-ray if indicated 2
• Amylase, lipase: If pancreatitis suspected 3
• Hepatic transaminases, troponin, creatine kinase: If indicated 3

Monitoring During Treatment:

• Every 2-4 hours: Electrolytes, glucose, BUN, creatinine, osmolality, venous pH, β-hydroxybutyrate 1, 5
• Venous pH and anion gap: Adequate for monitoring acidosis resolution (venous pH typically 0.03 units lower than arterial) 1, 5

Empiric Treatment

Fluid Resuscitation:

Begin aggressive fluid resuscitation with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (1-1.5 L in average adult) during first hour. 2, 1

• Subsequent fluid choice depends on hydration state, serum electrolytes, and urine output 2
• When glucose reaches 250 mg/dL, change to 5% dextrose with 0.45-0.75% NaCl 1, 5
• Target glucose 150-200 mg/dL until DKA resolution 5
• Total fluid replacement should correct estimated deficits within 24 hours 1

Insulin Therapy:

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

• If glucose does not fall by 50 mg/dL in first hour, double insulin infusion rate hourly until steady decline of 50-75 mg/dL per hour achieved 1
• Continue insulin infusion even after glucose normalizes to clear ketones (ketonemia takes longer to clear than hyperglycemia) 1, 5
• Add dextrose to IV fluids when glucose <250 mg/dL while continuing insulin 1, 5

Potassium Replacement:

Once serum potassium <5.5 mEq/L and adequate urine output confirmed, add 20-30 mEq/L potassium to IV fluids to maintain serum potassium 4-5 mEq/L. 1

• If initial potassium <3.3 mEq/L, delay insulin therapy and aggressively replace potassium first (to prevent fatal cardiac arrhythmias) 1

Bicarbonate Therapy:

Bicarbonate therapy is NOT recommended except when pH <6.9. 1

Transition to Subcutaneous Insulin:

• Give basal insulin (NPH, detemir, glargine, or degludec) 2-4 hours before stopping IV insulin to prevent rebound hyperglycemia 1
• Start multiple-dose regimen combining short/rapid-acting and intermediate/long-acting insulin once patient can eat 1, 5
• Continue IV insulin for 1-2 hours after starting subcutaneous insulin 5

Treatment of Precipitating Cause:

• Obtain bacterial cultures and give appropriate antibiotics if infection suspected 1
• Address other precipitating factors identified in history 2

Resolution Criteria

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

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

Indications to Refer/Admit

All patients with DKA require hospital admission for continuous monitoring and treatment. 2

• Severe DKA (pH <7.00, bicarbonate <10 mEq/L): Requires ICU admission with consideration for central venous and intra-arterial pressure monitoring 1
• Altered mental status, stupor, or coma 2
• Hemodynamic instability or shock 2
• Significant comorbidities: Cardiac or renal compromise requiring specialized monitoring 2
• Suspected cerebral edema (especially in children and adolescents) 1
• Inability to identify or treat precipitating cause in outpatient setting 2

Critical Pitfalls

Diagnostic Pitfalls:

• Relying on urine ketones or nitroprusside method for diagnosis or monitoring: These only measure acetoacetate and acetone, NOT β-hydroxybutyrate (the predominant ketoacid); during treatment, β-hydroxybutyrate converts to acetoacetate, making tests paradoxically appear worse as patient improves 1, 5
• Missing euglycemic DKA: Glucose may be <250 mg/dL, especially with SGLT2 inhibitor use 3
• Assuming abdominal pain is always from DKA: May indicate precipitating cause (pancreatitis, infection); requires further evaluation if not resolving 2
• Interpreting normothermia as absence of infection: Patients can be normothermic or hypothermic despite infection due to peripheral vasodilation 2

Treatment Pitfalls:

• Discontinuing insulin prematurely when glucose normalizes: Ketoacidosis requires continued insulin therapy even after glucose falls; add dextrose instead of stopping insulin 1, 5
• Inadequate potassium monitoring and replacement: Insulin drives potassium intracellularly, risking fatal arrhythmias 1
• Starting insulin when potassium <3.3 mEq/L: Must replace potassium first 1
• Overly aggressive fluid resuscitation: Monitor closely for cerebral edema, especially in children 1
• Stopping IV insulin before adequate subcutaneous insulin levels: Continue IV insulin 1-2 hours after subcutaneous dose 5
• Failing to identify and treat precipitating cause: Leads to recurrence 1
• Repeating arterial blood gases unnecessarily: Venous pH suffices for monitoring after initial diagnosis 1
• Using bicarbonate therapy routinely: Not recommended unless pH <6.9 1

Monitoring Pitfalls:

• Infrequent monitoring: Check electrolytes, glucose, pH, and β-hydroxybutyrate every 2-4 hours until stable 1, 5
• Not monitoring for cerebral edema: Especially critical in pediatric patients 1
• Inadequate patient education post-discharge: Failure to educate on recognition, prevention, and sick-day management leads to recurrence 1