What is the management of diabetic ketoacidosis (DKA)?

Diabetic Ketoacidosis: Pathophysiology and Management

Pathophysiology

DKA results from absolute or relative insulin deficiency combined with counter-regulatory hormone excess (glucagon, cortisol, catecholamines), leading to three key metabolic derangements: hyperglycemia from increased hepatic glucose production and decreased peripheral glucose utilization, ketoacidosis from accelerated lipolysis and hepatic ketogenesis, and osmotic diuresis causing severe dehydration and electrolyte losses. 1

• The metabolic acidosis occurs specifically because insulin deficiency triggers unrestrained lipolysis, releasing free fatty acids that undergo hepatic oxidation to ketone bodies (β-hydroxybutyrate and acetoacetate), which accumulate faster than tissues can metabolize them 1
• Hyperglycemia develops despite elevated blood glucose because cells cannot utilize glucose without insulin, while hepatic gluconeogenesis and glycogenolysis proceed unchecked 1
• The osmotic diuresis from glycosuria causes profound losses of water, sodium, potassium, phosphate, and magnesium, with total body potassium depletion averaging 3-5 mEq/kg despite initially normal or elevated serum levels 1

Diagnosis

Diagnostic criteria require arterial pH <7.3, serum bicarbonate <18 mEq/L (some sources use <15 mEq/L), positive serum or urine ketones, and traditionally blood glucose >250 mg/dL, though euglycemic DKA (normal or mildly elevated glucose) is increasingly recognized, particularly with SGLT2 inhibitor use. 2, 3, 4

Essential Laboratory Evaluation

• Obtain plasma glucose, blood urea nitrogen/creatinine, serum ketones (preferably β-hydroxybutyrate), electrolytes with calculated anion gap, osmolality, urinalysis, arterial blood gases, complete blood count, and electrocardiogram 2, 3
• Direct measurement of β-hydroxybutyrate in blood is strongly preferred over the nitroprusside method, which only detects acetoacetate and acetone, missing the predominant ketone body in DKA 5, 3
• Obtain bacterial cultures (blood, urine, throat) if infection is suspected, as infection is a common precipitating factor 2, 3

Management Protocol

Fluid Resuscitation (First Priority)

Begin immediately with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour during the first hour to restore intravascular volume and tissue perfusion before starting insulin. 5, 2, 3

• Fluid administration should precede insulin by 1-2 hours to prevent cardiovascular collapse from rapid glucose shifts 6
• After initial resuscitation, continue with 0.45% saline at rates determined by hydration status, electrolyte levels, and urine output 2, 3
• When serum glucose reaches 250 mg/dL, switch to 5% dextrose with 0.45-0.75% NaCl to prevent hypoglycemia while continuing insulin therapy to clear ketosis—this is critical and a common error point. 5, 2, 3

Insulin Therapy (Second Priority)

Start continuous intravenous regular insulin infusion at 0.1 units/kg/hour WITHOUT an initial bolus for moderate to severe DKA; this is the standard of care for critically ill patients. 7, 2, 3

• If plasma glucose does not fall by 50 mg/dL in the first hour, double the insulin infusion rate hourly until achieving a steady decline of 50-75 mg/hour 2, 3
• Never interrupt insulin infusion when glucose levels fall—instead, add dextrose-containing fluids to maintain glucose 150-200 mg/dL while continuing insulin until ketoacidosis resolves. 5, 2, 3
• Continue insulin infusion until ALL resolution criteria are met: pH >7.3, serum bicarbonate ≥18 mEq/L, AND anion gap ≤12 mEq/L, regardless of glucose levels 5, 2, 3

Electrolyte Replacement (Concurrent Priority)

Potassium replacement is mandatory and must begin early, as insulin therapy drives potassium intracellularly and can cause life-threatening hypokalemia despite total body potassium depletion. 2, 3

• Once urine output is established and serum potassium is <5.3 mEq/L, add 20-30 mEq/L potassium to IV fluids (typically 2/3 KCl and 1/3 KPO₄) 5, 2, 3
• Maintain serum potassium between 4-5 mmol/L throughout treatment with frequent monitoring 5, 2, 3
• Bicarbonate administration is NOT recommended for pH >6.9-7.0, as studies show no benefit in resolution time or outcomes, and it may worsen hypokalemia, paradoxically worsen CNS acidosis, and increase cerebral edema risk. 2, 3

Monitoring Requirements

Draw blood every 2-4 hours to measure serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH (which is typically 0.03 units lower than arterial pH and is adequate for monitoring). 2, 3

• Check blood glucose every 1-2 hours to guide insulin and dextrose adjustments 5, 2
• Follow venous pH and anion gap as the primary markers of ketoacidosis resolution, not just glucose normalization 5, 2, 3
• Monitor for cerebral edema, particularly in children and adolescents, which presents with headache, altered mental status, bradycardia, and increased blood pressure 6

Transition to Subcutaneous Insulin

When DKA resolves (glucose <200 mg/dL, bicarbonate ≥18 mEq/L, pH >7.3, anion gap ≤12 mEq/L), administer basal insulin (intermediate or long-acting) 2-4 hours BEFORE stopping IV insulin to prevent rebound ketoacidosis and hyperglycemia. 7, 5, 2, 3

• This overlap period is essential because subcutaneous insulin requires time to reach therapeutic levels while IV insulin has a half-life of only 4-6 minutes 7, 3
• Transition to a multiple-dose regimen combining rapid/short-acting with intermediate/long-acting insulin once the patient can eat 3

Critical Pitfalls to Avoid

• Premature termination of insulin before complete resolution of ketosis (all three criteria: pH, bicarbonate, AND anion gap normalized) leads to recurrent DKA 5, 2, 3
• Stopping insulin when glucose normalizes without adding dextrose perpetuates ketoacidosis—glucose and ketone clearance occur at different rates 5, 3
• Inadequate potassium monitoring and replacement causes dangerous hypokalemia, the most common cause of death in DKA treatment 2, 3
• Using nitroprusside method alone for ketone measurement misses β-hydroxybutyrate and underestimates ketosis severity 5, 3
• Overly aggressive fluid administration, particularly hypotonic fluids, increases cerebral edema risk in children 6
• Failing to identify and treat precipitating causes (infection, MI, medication non-adherence, SGLT2 inhibitors) leads to recurrent episodes 3, 4

Special Considerations

• For mild to moderate uncomplicated DKA in alert patients, subcutaneous rapid-acting insulin analogs combined with aggressive fluid management are equally effective and safer than IV insulin, and may be more cost-effective 7, 3
• SGLT2 inhibitors must be discontinued 3-4 days before planned surgery to prevent euglycemic DKA 3
• Euglycemic DKA requires earlier addition of dextrose-containing fluids to maintain adequate glucose while clearing ketosis 5