Management and Investigation of Diabetic Ketoacidosis (DKA)

Initial Diagnostic Workup

Obtain the following laboratory tests immediately upon presentation: plasma glucose, blood urea nitrogen/creatinine, serum ketones (preferably β-hydroxybutyrate), electrolytes with calculated anion gap, serum osmolality, urinalysis with urine ketones, arterial blood gases (or venous pH), complete blood count with differential, and electrocardiogram 1, 2.

Diagnostic criteria for DKA include: blood glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, and presence of ketonemia or ketonuria 2.
Direct measurement of β-hydroxybutyrate in blood is the preferred method for ketone monitoring, as the nitroprusside method only detects acetoacetic acid and acetone 2.
If infection is suspected, obtain bacterial cultures from urine, blood, and throat, and initiate appropriate antibiotics immediately 1, 2.
Identify precipitating factors: infection (most common), new diabetes diagnosis, insulin omission, myocardial infarction, stroke, pancreatitis, trauma, or SGLT2 inhibitor use 2, 3.

Fluid Resuscitation Protocol

Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in the average adult) during the first hour to restore intravascular volume and tissue perfusion 1, 2. This aggressive initial fluid replacement is critical for improving insulin sensitivity 2.

Subsequent fluid choice depends on hydration status, serum electrolyte levels, and urine output 2.
When serum glucose reaches 200-250 mg/dL, switch to 5% dextrose with 0.45-0.75% saline while continuing insulin infusion to prevent hypoglycemia and ensure complete ketoacidosis resolution 1, 2.
Total fluid replacement should aim to correct estimated deficits within 24 hours 2.

Potassium Management: Critical Safety Considerations

Do NOT start insulin if serum potassium is <3.3 mEq/L—this is an absolute contraindication due to risk of life-threatening cardiac arrhythmias and respiratory muscle weakness 1, 2.

If K+ <3.3 mEq/L:

Delay insulin therapy and aggressively replace potassium until levels reach ≥3.3 mEq/L 1, 2.
Begin isotonic saline at 15-20 mL/kg/hour while holding insulin 1.
Add 20-40 mEq/L potassium to IV fluids once renal function is confirmed (adequate urine output) 1.
Obtain electrocardiogram to assess for cardiac effects of hypokalemia 1.

If K+ 3.3-5.5 mEq/L:

Add 20-30 mEq potassium per liter of IV fluid using 2/3 KCl (or potassium-acetate) and 1/3 KPO₄ once adequate urine output is confirmed 1, 2.
Target serum potassium of 4-5 mEq/L throughout treatment 1, 2.

If K+ >5.5 mEq/L:

Withhold potassium initially but monitor closely, as levels will drop rapidly with insulin therapy 2.

Critical pitfall: Despite presenting with normal or elevated potassium, total body potassium depletion averages 3-5 mEq/kg body weight in DKA, and insulin therapy will unmask this depletion by driving potassium intracellularly 2. Check potassium levels every 2-4 hours during active treatment 1, 2.

Insulin Therapy Protocol

For moderate-to-severe DKA or critically ill/mentally obtunded patients, continuous intravenous regular insulin is the standard of care 4, 1, 2.

Standard IV Insulin Protocol:

Start with an IV bolus of 0.1 units/kg regular insulin, followed by continuous infusion at 0.1 units/kg/hour 1, 2.
Target glucose decline of 50-75 mg/dL per hour 1, 2.
If glucose does not fall by 50 mg/dL in the first hour, verify adequate hydration status; if acceptable, double the insulin infusion rate every hour until achieving steady decline 1, 2.
Continue insulin infusion until complete resolution of ketoacidosis (pH >7.3, serum bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L) regardless of glucose levels 1, 2.
When glucose reaches 200-250 mg/dL, reduce insulin infusion to 0.05-0.1 units/kg/hour and add dextrose to IV fluids 1, 2.

Alternative Approach for Mild-to-Moderate Uncomplicated DKA:

For hemodynamically stable, alert patients with mild-to-moderate DKA, subcutaneous rapid-acting insulin analogs combined with aggressive fluid management are equally effective, safer, and more cost-effective than IV insulin 4, 1, 2. This approach requires adequate fluid replacement, frequent point-of-care glucose monitoring, and treatment of concurrent infections 1, 2.

Bicarbonate Administration: Generally NOT Recommended

Bicarbonate is NOT recommended for DKA patients with pH >6.9-7.0 4, 2. Multiple studies show no difference in resolution of acidosis or time to discharge with bicarbonate use, and it may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 4, 2, 5.

Bicarbonate can be considered only if serum pH falls below 6.9, or when pH is <7.2 and/or bicarbonate <10 mEq/L pre- and post-intubation to prevent hemodynamic collapse 6.

Monitoring During Treatment

Check blood glucose every 1-2 hours initially, then every 2-4 hours once stable 1, 2.

Measure serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH every 2-4 hours 1, 2.
Venous pH is typically 0.03 units lower than arterial pH and is acceptable for monitoring 2.
Follow anion gap to monitor resolution of acidosis 2.

DKA Resolution Criteria

DKA is resolved when ALL of the following criteria are met: glucose <200 mg/dL, serum bicarbonate ≥18 mEq/L, venous pH >7.3, and anion gap ≤12 mEq/L 1, 2.

Transition to Subcutaneous Insulin: Critical Timing

Administer basal insulin (glargine or detemir) 2-4 hours BEFORE stopping the IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia 4, 1, 2. This is the most common error leading to DKA recurrence 1.

Transition Protocol:

Ensure DKA has completely resolved (all resolution criteria met) and patient can tolerate oral intake 1, 2.
Administer long-acting basal insulin subcutaneously 2-4 hours before discontinuing IV insulin 1, 2.
Continue IV insulin for 1-2 hours after subcutaneous insulin is given 1, 2.
Start a multiple-dose regimen with combination of short/rapid-acting and intermediate/long-acting insulin 1, 2.

Calculating Subcutaneous Insulin Doses:

Total daily dose = 0.5 units/kg/day for metabolically stable patients 7.
For patients in metabolic stress or with infection, doses up to 0.65-1.0 units/kg/day may be necessary 7.
Divide total daily dose into 50% basal insulin (once daily) and 50% prandial insulin (divided equally before three meals) 7.
Alternative method: Total daily dose = Average hourly IV insulin rate from last 12 hours × 24 hours 7.

Critical pitfall: Never use correction-only (sliding scale) insulin alone without basal coverage—this approach leads to worse outcomes and higher complication rates 7.

Special Considerations and Pitfalls

SGLT2 Inhibitors:

Discontinue SGLT2 inhibitors immediately and do not restart until infection is resolved and patient is metabolically stable 4, 7. These should have been stopped 3-4 days before any acute illness to prevent DKA 4, 7.

Cerebral Edema Prevention:

Cerebral edema occurs more commonly in children and adolescents but can occur in adults 2.
Avoid overly rapid correction of osmolality and hyperglycemia 2.
Monitor closely for altered mental status, headache, or neurological deterioration 2.

Common Management Errors:

Premature termination of IV insulin before complete resolution of ketosis 8.
Stopping IV insulin without prior basal insulin administration 1, 2.
Insufficient timing or dosing of subcutaneous insulin before discontinuing IV insulin 8.
Failure to add dextrose when glucose falls below 250 mg/dL while continuing insulin therapy 2.
Inadequate potassium monitoring and replacement 2.

Discharge Planning

Before discharge, ensure the following:

Identify outpatient diabetes care providers 2.
Educate patient and family on glucose monitoring, insulin administration, recognition and treatment of hyperglycemia/hypoglycemia, and sick day management 1, 2.
Schedule follow-up appointments prior to discharge 2.
Provide structured discharge planning that begins at admission 1.

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