Management of Diabetic Ketoacidosis
Begin immediate fluid resuscitation with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour for the first hour, followed by continuous IV regular insulin at 0.1 units/kg/hour once potassium is ≥3.3 mEq/L, and aggressively replace potassium to maintain levels between 4-5 mEq/L throughout treatment. 1, 2
Initial Diagnostic Workup
Obtain the following laboratory tests immediately 3, 1:
- Arterial or venous blood gases (venous pH is typically 0.03 units lower than arterial and is sufficient for monitoring) 3, 1
- Plasma glucose, serum ketones, electrolytes with calculated anion gap, osmolality 1, 2
- Complete blood count with differential, urinalysis with urine ketones 1, 2
- Blood urea nitrogen, creatinine, electrocardiogram 3, 1
- Bacterial cultures (blood, urine, throat) if infection is suspected 1, 2
DKA diagnostic criteria: Blood glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, and positive serum/urine ketones 1, 2
Fluid Resuscitation Protocol
Start with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in average adults) during the first hour to restore intravascular volume and renal perfusion 1, 2, 4. This aggressive initial fluid replacement is critical for improving insulin sensitivity 1.
After the first hour, adjust fluid rate based on 1, 2:
- Hydration status assessment
- Corrected serum sodium (add 1.6 mEq to measured sodium for each 100 mg/dL glucose above 100 mg/dL) 3
- Urine output adequacy
When plasma glucose reaches 250 mg/dL, switch to 5% dextrose with 0.45-0.75% saline while continuing insulin infusion 1, 2. This prevents hypoglycemia while allowing continued insulin administration to clear ketoacidosis 1, 2.
Total fluid replacement should approximate 1.5 times the 24-hour maintenance requirements 2, 4.
Insulin Therapy
Critical Pre-Insulin Check: Potassium Level
DO NOT start insulin if serum potassium is <3.3 mEq/L 1, 4. Delay insulin therapy and aggressively replace potassium first to prevent life-threatening cardiac arrhythmias and respiratory muscle weakness 1, 4.
Standard Insulin Protocol
Initiate continuous IV regular insulin infusion at 0.1 units/kg/hour WITHOUT an initial bolus for moderate to severe DKA 1, 2, 4. This is the standard of care for critically ill and mentally obtunded patients 1, 4.
Target glucose decline: 50-75 mg/dL per hour 1, 2. If plasma glucose does not fall by 50 mg/dL in the first hour 3, 1, 2:
- Verify adequate hydration status
- If hydration is acceptable, double the insulin infusion rate every hour until achieving steady glucose decline of 50-75 mg/hour 3, 1
When glucose reaches 250 mg/dL: Decrease insulin infusion to 0.05-0.1 units/kg/hour (3-6 units/hour) and add dextrose to IV fluids 3, 1, 2.
Alternative Approach for Mild-Moderate Uncomplicated DKA
For hemodynamically stable, alert patients with mild-moderate DKA, subcutaneous rapid-acting insulin analogs combined with aggressive fluid management are equally effective, safer, and more cost-effective than IV insulin 1, 2. This approach requires 1:
- Adequate fluid replacement
- Frequent point-of-care glucose monitoring
- Treatment of concurrent infections
- Appropriate follow-up
Potassium Management: The Hidden Killer
Despite total body potassium depletion averaging 3-5 mEq/kg body weight, many patients present with normal or elevated potassium due to acidosis-induced extracellular shift 1, 4. Insulin therapy will unmask this depletion by driving potassium intracellularly 1, 4.
Potassium Replacement Protocol
If K+ <3.3 mEq/L: Hold insulin, give 40-60 mEq potassium per hour until K+ ≥3.3 mEq/L 1, 4
If K+ 3.3-5.5 mEq/L: Add 20-30 mEq potassium per liter of IV fluid (use 2/3 KCl and 1/3 KPO₄) once adequate urine output is confirmed 3, 1, 2, 4
If K+ >5.5 mEq/L: Withhold potassium initially but monitor closely every 2 hours, as levels will drop rapidly with insulin therapy 1, 4
Target serum potassium: 4-5 mEq/L throughout treatment 1, 2, 4. Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA 1.
Bicarbonate: Generally NOT Recommended
DO NOT administer bicarbonate for pH >6.9-7.0 1, 2, 4. Multiple studies show no difference in resolution of acidosis or time to discharge with bicarbonate use 1, 2.
Bicarbonate may worsen outcomes by 1, 2:
- Worsening ketosis
- Causing hypokalemia
- Increasing cerebral edema risk
Exception: Consider bicarbonate only if pH <6.9, or when pH <7.2 in peri-intubation period to prevent hemodynamic collapse from apnea 5.
Monitoring Protocol
Glucose Monitoring
Check blood glucose every 1-2 hours 2
Comprehensive Metabolic Monitoring
Draw blood every 2-4 hours for 3, 1, 2, 4:
- Serum electrolytes (especially potassium)
- Glucose
- Blood urea nitrogen, creatinine
- Osmolality
- Venous pH (adequate for monitoring; arterial blood gases generally unnecessary after initial assessment) 3, 1
Follow venous pH and anion gap to monitor resolution of acidosis 1, 2.
Ketone Monitoring: Critical Pitfall
Direct measurement of β-hydroxybutyrate in blood is the preferred method for monitoring DKA 1, 2.
DO NOT rely on nitroprusside method (urine or serum ketone strips) as it only measures acetoacetic acid and acetone, not β-hydroxybutyrate (the predominant ketone in DKA) 3, 1. During therapy, β-hydroxybutyrate converts to acetoacetic acid, which may falsely suggest worsening ketosis 3.
Resolution Criteria
DKA is resolved when ALL of the following are met 1, 2, 4:
- Glucose <200 mg/dL
- Serum bicarbonate ≥18 mEq/L
- Venous pH >7.3
- Anion gap ≤12 mEq/L
Continue insulin infusion until complete resolution of ketoacidosis, regardless of glucose levels 1, 2. This is a critical point: stopping insulin when glucose normalizes is a common cause of persistent or worsening ketoacidosis 1.
Transition to Subcutaneous Insulin
Administer basal insulin (intermediate or long-acting) 2-4 hours BEFORE stopping IV insulin infusion 1, 2, 4. This overlap period is essential to prevent recurrence of ketoacidosis and rebound hyperglycemia 1, 2.
Recent evidence shows adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk 1.
For patients who remain NPO (intubated) after DKA resolution: Continue IV insulin and fluid replacement, supplementing with subcutaneous regular insulin every 4 hours as needed 1, 4.
When patient can eat: Start multiple-dose schedule using combination of short/rapid-acting and intermediate/long-acting insulin 3, 1, 2.
Identify and Treat Precipitating Factors
Obtain bacterial cultures and administer appropriate antibiotics if infection is suspected 1, 2. Common precipitating factors include 1, 2:
- Infection (most common)
- Myocardial infarction
- Stroke
- Pancreatitis
- Trauma
- Insulin omission or inadequacy
- SGLT2 inhibitor use (can cause euglycemic DKA) 1
Discontinue SGLT2 inhibitors immediately and do not restart until 3-4 days after metabolic stability is achieved 1.
Critical Pitfalls to Avoid
Premature termination of insulin therapy before complete resolution of ketosis leads to DKA recurrence 1, 2. Continue insulin until ALL resolution criteria are met, not just glucose normalization 1, 2.
Stopping IV insulin without prior basal subcutaneous insulin causes rebound hyperglycemia and ketoacidosis 1. Always give basal insulin 2-4 hours before stopping IV infusion 1, 2, 4.
Failure to add dextrose when glucose falls below 250 mg/dL while continuing insulin is a common cause of persistent ketoacidosis 1. The goal is glucose 150-200 mg/dL until DKA resolves, not normoglycemia 1.
Inadequate potassium monitoring and replacement can cause life-threatening hypokalemia 1, 4. Check potassium every 2-4 hours and maintain 4-5 mEq/L 1, 2, 4.
Overly rapid correction of osmolality increases cerebral edema risk, particularly in children and adolescents 1, 2. Use gradual correction of glucose and osmolality 2.
Special Considerations for Cerebral Edema
Cerebral edema occurs more commonly in children and adolescents than adults and is one of the most dire complications of DKA 1. Monitor closely for 1:
- Altered mental status
- Headache
- Neurological deterioration
Prevent cerebral edema by avoiding overly rapid correction of hyperglycemia and hyperosmolality 1, 2.