What is the treatment for diabetic ketoacidosis (DKA)?

Treatment of Diabetic Ketoacidosis (DKA)

Begin immediate treatment with aggressive isotonic saline resuscitation at 15-20 mL/kg/hour in the first hour, followed by continuous intravenous regular insulin at 0.1 units/kg/hour once potassium is ≥3.3 mEq/L, while simultaneously identifying and treating the precipitating cause. 1, 2

Initial Assessment and Diagnostic Confirmation

• Confirm DKA diagnosis with: blood glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, and presence of ketonemia or ketonuria 1
• Obtain comprehensive laboratory evaluation: plasma glucose, BUN/creatinine, serum ketones, electrolytes with calculated anion gap, osmolality, urinalysis, urine ketones, arterial blood gases, complete blood count, and electrocardiogram 1, 2
• Identify precipitating factors immediately: infection (obtain bacterial cultures from urine, blood, throat if suspected), cerebrovascular accident, myocardial infarction, pancreatitis, trauma, insulin omission/inadequacy, or SGLT2 inhibitor use 1, 2
• Administer appropriate antibiotics if infection is identified as the trigger 1

Fluid Resuscitation Protocol

• Start with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in average adult) during the first hour to restore circulatory volume and tissue perfusion 1, 2
• After the first hour, adjust fluid choice based on hydration status, serum electrolyte levels, and urine output 1
• 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 ketones 1
• Plan total fluid replacement to correct estimated deficits within 24 hours 1
• Monitor fluid input/output and perform frequent clinical examinations to assess progress 2

Insulin Therapy

• Do NOT start insulin if potassium <3.3 mEq/L—aggressively replace potassium first to prevent life-threatening cardiac arrhythmias and respiratory muscle weakness 1
• For critically ill and mentally obtunded patients: use continuous intravenous regular insulin infusion at 0.1 units/kg/hour (standard of care) 1, 2
• For mild-to-moderate uncomplicated DKA: subcutaneous rapid-acting insulin analogs combined with aggressive fluid management are equally effective, safer, and more cost-effective than IV insulin 1, 2
• If plasma glucose does not fall by 50 mg/dL in the first hour, verify adequate hydration; if acceptable, double the insulin infusion rate hourly until achieving steady glucose decline of 50-75 mg/dL/hour 1
• 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
• Target glucose between 150-200 mg/dL until DKA resolution parameters are met 1

Electrolyte Management

Potassium Replacement (Critical)

• If K⁺ <3.3 mEq/L: delay insulin therapy and aggressively replace potassium until levels reach ≥3.3 mEq/L 1
• If K⁺ 3.3-5.5 mEq/L: add 20-30 mEq/L potassium (2/3 KCl and 1/3 KPO₄) to IV fluid once adequate urine output is confirmed 1
• If K⁺ >5.5 mEq/L: withhold potassium initially but monitor closely, as levels will drop rapidly with insulin therapy 1
• Target serum potassium of 4-5 mEq/L throughout treatment 1
• Total body potassium depletion is universal in DKA despite potentially normal or elevated initial levels due to acidosis 1

Bicarbonate (Generally NOT Recommended)

• Do NOT administer bicarbonate for DKA patients with pH >6.9-7.0, as studies show no difference in resolution of acidosis or time to discharge 1, 2
• Bicarbonate may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 1

Monitoring During Treatment

• Draw blood every 2-4 hours to determine serum electrolytes, glucose, BUN, creatinine, osmolality, and venous pH 1, 2
• Monitor blood glucose every 1-2 hours until stable, then every 4 hours 2
• Follow venous pH (typically 0.03 units lower than arterial pH) and anion gap to monitor resolution of acidosis 1
• Direct measurement of β-hydroxybutyrate in blood is the preferred method for monitoring DKA (nitroprusside method only measures acetoacetic acid and acetone) 1

Resolution Criteria

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

Transition to Subcutaneous Insulin

• Administer basal insulin (intermediate or long-acting) 2-4 hours BEFORE stopping IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia 1, 2
• This overlap period is essential—premature termination of IV insulin is a common cause of DKA recurrence 1
• Adding low-dose basal insulin analog during IV insulin infusion can help prevent rebound hyperglycemia without increased hypoglycemia risk 1
• Once patient can eat, start multiple-dose schedule using combination of short/rapid-acting and intermediate/long-acting insulin 1

Critical Pitfalls to Avoid

• Premature termination of insulin therapy before complete resolution of ketosis leads to DKA recurrence—ketosis may persist even after glucose normalization 1
• Interruption of insulin infusion when glucose falls is a common cause of persistent or worsening ketoacidosis—add dextrose instead 1
• Failure to add dextrose when glucose falls below 250 mg/dL while continuing insulin therapy 1
• Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA 1
• Overzealous treatment with insulin without glucose supplementation leads to hypoglycemia 1
• Overly rapid correction of osmolality (not exceeding 3 mOsm/kg/h) increases cerebral edema risk, particularly in children 1, 3

Special Populations and Considerations

Pregnancy

• Up to 2% of pregnancies with pregestational diabetes are complicated by DKA 4
• Pregnant individuals may present with euglycemic DKA (glucose <200 mg/dL) 4
• Diagnosis may be hindered by mixed acid-base disturbances, particularly with hyperemesis 4
• Due to significant risk of feto-maternal harm, pregnant individuals at risk should be counseled on DKA signs/symptoms and seek immediate medical attention 4

SGLT2 Inhibitor Use

• SGLT2 inhibitors increase DKA risk (relative risk 2.46 in type 2 diabetes) 4
• Discontinue SGLT2 inhibitors 3-4 days before any planned surgery to prevent euglycemic DKA 1
• Risk factors include very-low-carbohydrate diets, prolonged fasting, dehydration, excessive alcohol intake, and presence of autoimmunity 4

Cardiac Compromise

• Avoid excessive fluid administration in patients with congestive heart failure or reverse Takotsubo cardiomyopathy 3
• Consider administering IV regular insulin without bolus in patients with cardiac compromise 3

Prevention of Recurrence

• Individuals on intensive insulin therapy should NEVER stop or hold basal insulin even if not eating—provide detailed instructions on insulin dose adjustments during illness or fasting 4
• Individuals at risk should measure urine or blood ketones when symptomatic or when glucose exceeds 200 mg/dL 4
• When hemodynamically stable, able to tolerate oral hydration, and able to administer subcutaneous insulin, individuals may treat mild DKA at home with frequent monitoring, noncaloric hydration, and subcutaneous insulin 4
• Seek immediate medical attention if unable to tolerate oral hydration, blood glucose does not improve with insulin, altered mental status occurs, or any signs of worsening illness 4
• Access to CGM may decrease risk of DKA recurrence 4