What is diabetic ketoacidosis (DKA), its diagnostic approach, management, complications, differential diagnosis, and prognosis?

Diabetic Ketoacidosis: Diagnostic Approach, Management, Complications, Differential Diagnosis, and Prognosis

Diabetic ketoacidosis (DKA) is a serious, acute, and life-threatening hyperglycemic emergency that requires prompt diagnosis and treatment to prevent significant morbidity and mortality. 1

Definition and Diagnostic Criteria

DKA is characterized by the following diagnostic criteria:

• Hyperglycemia (blood glucose >250 mg/dL), though approximately 10% of cases present as euglycemic DKA (glucose <200 mg/dL) 2, 3
• Metabolic acidosis (arterial pH <7.30, serum bicarbonate <18 mEq/L) 4
• Increased anion gap 4
• Presence of ketones in blood or urine 4

DKA severity can be classified as:

Parameter	Mild	Moderate	Severe
Arterial pH	7.25-7.30	7.00-7.24	<7.00
Serum bicarbonate (mEq/L)	15-18	10-<15	<10
Anion gap	>10	>12	>12
Mental status	Alert	Alert/drowsy	Stupor/coma
[4]

Clinical Presentation

Common presenting symptoms and signs include:

• Polyuria, polydipsia, polyphagia, weight loss 2
• Vomiting (occurs in up to 25% of cases, may be coffee-ground in appearance) 2
• Abdominal pain 2
• Dehydration (poor skin turgor) 2
• Kussmaul respirations (deep, rapid breathing) 2
• Tachycardia, hypotension 2
• Altered mental status ranging from full alertness to profound lethargy or coma 2
• Patients may be normothermic or hypothermic despite infection due to peripheral vasodilation 2

Risk Factors and Precipitating Events

Common precipitating factors include:

• Infections (responsible for approximately 50% of cases, particularly urinary tract infections and pneumonia) 5, 6
• Insulin omission or poor compliance with antidiabetic treatment 6, 2
• Newly diagnosed diabetes 2
• Acute illness (myocardial infarction, stroke, trauma) 2
• Medications (particularly SGLT2 inhibitors) 2
• Alcohol consumption 3
• Pregnancy 2

Risk factors for developing DKA include:

• Type 1 diabetes or absolute insulin deficiency 2
• Younger age 2
• Prior history of hyperglycemic crises 2
• Prior history of hypoglycemic crises 2
• Presence of other diabetes complications 2
• Presence of other chronic health conditions 2
• Presence of behavioral health conditions 2
• Alcohol and/or substance use 2
• High A1C level 2
• Social determinants of health 2

Diagnostic Approach

Initial diagnostic evaluation should include:

• Arterial blood gases to assess pH and bicarbonate levels 4
• Complete blood count with differential 4
• Urinalysis (for ketones) 4
• Plasma glucose 4
• Blood urea nitrogen, electrolytes, chemistry profile, and creatinine levels 4
• Electrocardiogram 4
• Chest X-ray and cultures as needed to identify infection 4
• Measurement of β-hydroxybutyrate in blood (preferred method for monitoring DKA) 2

Differential Diagnosis

DKA must be distinguished from:

• Other causes of high anion gap metabolic acidosis:
  • Lactic acidosis 2
  • Salicylate, methanol, ethylene glycol, or paraldehyde ingestion 2
  • Chronic renal failure 2
• Hyperglycemic hyperosmolar state (HHS) 2
• Mixed DKA-HHS states 2
• Starvation ketosis 3
• Alcoholic ketoacidosis 3

Management

Fluid Therapy

• Initial fluid therapy aims to expand intravascular and extravascular volume and restore renal perfusion 2
• For adults without cardiac compromise, administer isotonic saline (0.9% NaCl) at 15-20 ml/kg/hour (1-1.5 L in average patient) during the first hour 2, 4
• Follow with 0.45-0.9% NaCl at 4-14 ml/kg/hour based on corrected serum sodium and hemodynamic status 4
• Add dextrose to hydrating solution when glucose falls below 200-250 mg/dL while continuing insulin infusion 4

Insulin Therapy

• For moderate to severe DKA, administer intravenous regular insulin with an initial bolus of 0.15 units/kg body weight, followed by continuous infusion at 0.1 unit/kg/hour 4
• For mild DKA, subcutaneous or intramuscular regular insulin every hour may be effective 2
• Continue insulin until DKA resolves (glucose <200 mg/dL, serum bicarbonate ≥18 mEq/L, venous pH >7.3, and anion gap ≤12 mEq/L) 4
• Transition to subcutaneous insulin by administering basal insulin 2-4 hours before stopping intravenous insulin to prevent recurrence of ketoacidosis 2, 4

Electrolyte Management

• Monitor potassium levels closely and include 20-30 mEq/L potassium in the infusion once serum potassium falls below 5.5 mEq/L 4, 7
• Monitor phosphate levels and replace if necessary 1
• Bicarbonate therapy is generally not recommended as studies have shown it makes no difference in the resolution of acidosis or time to discharge 2

Treatment of Precipitating Factors

• Identify and treat underlying causes, particularly infections 2
• For patients on SGLT2 inhibitors, discontinue medication and monitor for euglycemic DKA 2

Complications

Acute Complications

• Cerebral edema (rare but potentially fatal, occurring in 0.7-1.0% of children with DKA) 1
• Hypokalemia during treatment due to insulin administration and correction of acidosis 1
• Hypophosphatemia during insulin therapy 1
• Hypoglycemia due to overzealous insulin treatment 1
• Hyperchloremic metabolic acidosis from excessive saline administration 1
• Cardiac arrhythmias due to electrolyte imbalances 7
• Acute respiratory distress syndrome 8
• Thromboembolism 8

Long-term Complications

• Increased risk of recurrent DKA 1
• Higher incidence of psychiatric illness, especially depression 1
• Cognitive impairment with repeated episodes 8

Special Populations

Pregnancy

• Up to 2% of pregnancies with pregestational diabetes are complicated by DKA 2
• Pregnant individuals may present with euglycemic DKA, making diagnosis challenging 2
• DKA in pregnancy carries significant risk of fetal and maternal harm 1

SGLT2 Inhibitor Users

• Risk factors for DKA in patients taking SGLT2 inhibitors include very-low-carbohydrate diets, prolonged fasting, dehydration, and excessive alcohol intake 2
• These patients often present with euglycemic DKA 3

Prognosis

• Overall mortality for children with DKA is <1% in the United States 1
• Mortality is higher in patients with severe DKA (pH ≤7.1 and bicarbonate ≤5) 1
• Independent mortality predictors include:
  • Age ≥65 years 6
  • Depressed mental state in the first 24 hours 6
  • High insulin requirements (≥50 units in 12 hours) 6
  • Fever in the first 24 hours 6
  • Shock in the first 24 hours 6
  • Persistent hyperglycemia despite treatment 6
  • High fluid requirements (≥6 L in first 24 hours) 6
  • Severe acidosis (pH <7.2, bicarbonate <15 mmol/L) at presentation 6

Prevention

• Public awareness of signs and symptoms of untreated diabetes 1
• Education of caregivers about signs and symptoms of early DKA 1
• Recognition that insulin omission due to psychological problems and financial constraints is the most common cause of DKA in established diabetes 1
• Improved detection of families at risk 1
• Education about ketone monitoring 1
• 24-hour telephone availability for healthcare team contact when blood glucose levels are high or ketones are present 1
• Individuals at risk for DKA should measure urine or blood ketones when symptomatic or during potential precipitating events 2