How should diabetic ketoacidosis be managed, including initial assessment, fluid resuscitation, insulin therapy, potassium replacement, bicarbonate administration, monitoring, treatment of precipitating factors, and transition to maintenance therapy?

Management of Diabetic Ketoacidosis

Begin with isotonic saline at 15-20 mL/kg/hour for the first hour, then start continuous IV regular insulin at 0.1 units/kg/hour (with a 0.1 units/kg bolus) once potassium is ≥3.3 mEq/L, add 20-30 mEq/L potassium to fluids once renal function is confirmed, switch to dextrose-containing fluids when glucose reaches 250 mg/dL while continuing insulin until acidosis resolves, and administer basal subcutaneous insulin 2-4 hours before stopping the IV infusion. 1

Initial Assessment and Diagnosis

• Confirm DKA with plasma glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, and presence of ketonemia or ketonuria 2
• Obtain plasma glucose, electrolytes with calculated anion gap, serum ketones, blood urea nitrogen, creatinine, osmolality, arterial blood gases, complete blood count, urinalysis with urine ketones, and electrocardiogram 1, 2
• Measure β-hydroxybutyrate in blood directly rather than using nitroprusside-based urine ketone tests, as nitroprusside only detects acetoacetate and acetone, missing the predominant ketone body 1, 3
• Obtain bacterial cultures from urine, blood, and throat if infection is suspected, and order chest X-ray if clinically indicated 1
• Search for precipitating factors: infection, myocardial infarction, stroke, pancreatitis, trauma, insulin omission, or SGLT2 inhibitor use 1, 2

Fluid Resuscitation Protocol

• Start with isotonic saline (0.9% NaCl) at 15-20 mL/kg body weight per hour during the first hour to restore intravascular volume and tissue perfusion 1, 2, 3
• Continue fluid replacement at rates sufficient to correct estimated deficits within 24 hours, targeting approximately 1.5 times the 24-hour maintenance requirements 1
• When plasma glucose falls to 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
• Limit the rate of osmolality change to no more than 3 mOsm/kg/hour to reduce cerebral edema risk 3

Insulin Therapy

Standard IV Insulin Protocol

• Do not start insulin if serum potassium is <3.3 mEq/L—this is an absolute contraindication; aggressively replete potassium first to prevent life-threatening cardiac arrhythmias 1, 2
• Once potassium is ≥3.3 mEq/L, administer an IV bolus of regular insulin at 0.1 units/kg body weight 1, 3
• Immediately follow with continuous IV infusion of regular insulin at 0.1 units/kg/hour using only regular (short-acting) insulin, never rapid-acting analogs intravenously 1
• Target a glucose decline of 50-75 mg/dL per hour 1
• If glucose does not fall by 50 mg/dL in the first hour, verify adequate hydration status, then double the insulin infusion rate every hour until achieving steady decline 1
• Continue insulin infusion until complete DKA resolution (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L) regardless of glucose levels 1, 2
• When glucose reaches 250 mg/dL, add dextrose to IV fluids but maintain the same insulin infusion rate—never stop insulin when glucose normalizes, as this is a common error leading to persistent ketoacidosis 1, 2

Alternative Subcutaneous Protocol for Mild-Moderate Uncomplicated DKA

• For hemodynamically stable, alert patients with mild-moderate DKA, subcutaneous rapid-acting insulin analogs at 0.1-0.2 units/kg every 1-2 hours combined with aggressive fluid management are equally effective, safer, and more cost-effective than IV insulin 1, 2
• This approach requires adequate fluid replacement, frequent point-of-care glucose monitoring, and treatment of concurrent infections 1
• Continuous IV insulin remains mandatory for critically ill, mentally obtunded, or hemodynamically unstable patients 1, 2

Potassium Replacement

• Total body potassium depletion averages 3-5 mEq/kg body weight in DKA, and insulin therapy will unmask this by driving potassium intracellularly 2
• If potassium <3.3 mEq/L: Hold insulin therapy and aggressively replete potassium until levels reach ≥3.3 mEq/L to prevent cardiac arrhythmias, respiratory muscle weakness, and death 1, 2
• If potassium 3.3-5.5 mEq/L: Once renal function is confirmed (adequate urine output), add 20-30 mEq/L potassium to each liter of IV fluid using 2/3 potassium chloride (or potassium acetate) and 1/3 potassium phosphate 1, 3
• If potassium >5.5 mEq/L: Withhold potassium initially but monitor closely every 2-4 hours, as levels will drop rapidly with insulin therapy 2, 3
• Maintain serum potassium between 4-5 mEq/L throughout treatment 1, 3

Bicarbonate Administration

• Bicarbonate is NOT recommended for DKA patients with pH >6.9-7.0, as multiple studies show no difference in resolution of acidosis or time to discharge 1, 2, 3
• Bicarbonate may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 1, 2
• Consider bicarbonate only if pH <6.9: administer 100 mmol sodium bicarbonate in 400 mL sterile water at 200 mL/hour 3
• For pH 6.9-7.0, if bicarbonate is used, give 50 mmol sodium bicarbonate in 200 mL sterile water at 200 mL/hour 3

Monitoring During Treatment

• Check blood glucose every 2-4 hours throughout treatment 1, 2
• Measure serum electrolytes (especially potassium), blood urea nitrogen, creatinine, osmolality, and venous pH every 2-4 hours until the patient is stable 1, 2, 3
• Follow venous pH (typically 0.03 units lower than arterial pH) and anion gap to monitor resolution of acidosis 2, 3
• Monitor β-hydroxybutyrate levels serially when available, as reduction in blood β-hydroxybutyrate is the most accurate marker of successful treatment 2, 3
• Maintain continuous cardiac monitoring in severe DKA to detect arrhythmias early 3

DKA Resolution Criteria

• All of the following must be met: glucose <200 mg/dL, serum bicarbonate ≥18 mEq/L, venous pH >7.3, and anion gap ≤12 mEq/L 1, 2, 3
• Target glucose range of 150-200 mg/dL until full resolution parameters are achieved 1, 2

Transition to Subcutaneous Insulin

Critical Timing to Prevent Recurrence

• Administer long-acting basal insulin (glargine or detemir) subcutaneously 2-4 hours BEFORE stopping the IV insulin infusion—this is the most critical step to prevent recurrence of ketoacidosis and rebound hyperglycemia 1, 2, 3
• Continue the IV insulin infusion for an additional 1-2 hours after administering the subcutaneous basal dose to ensure adequate absorption and prevent a coverage gap 1
• Stopping IV insulin without prior basal insulin administration is the most common error leading to DKA recurrence 1

Dose Calculation

• Calculate basal insulin dose as approximately 50% of the total 24-hour IV insulin amount, given as a single daily injection of long-acting insulin 1
• Divide the remaining 50% of the 24-hour IV insulin amount equally among three meals as rapid-acting prandial insulin 1
• For newly diagnosed patients, initiate a multidose regimen at approximately 0.5-1.0 units/kg/day total daily dose 2, 3

Alternative Approach with Concurrent Basal Insulin

• Recent evidence suggests adding low-dose subcutaneous basal insulin analog (e.g., glargine) alongside IV insulin during DKA treatment may prevent rebound hyperglycemia and shorten hospital stays without increasing hypoglycemia risk 1, 2, 3

Treatment of Precipitating Factors

• Administer appropriate antibiotics immediately if infection is suspected based on cultures 1, 3
• Evaluate for myocardial infarction, especially in older patients, as it can both precipitate and be masked by DKA 2, 4
• Assess for cerebrovascular accident with focal neurological examination 2
• Discontinue SGLT2 inhibitors immediately if they are the precipitating cause, and do not restart until 3-4 days after metabolic stability is achieved 1, 2, 3
• Treat underlying conditions (pancreatitis, trauma, glucocorticoid-induced hyperglycemia) concurrently with metabolic correction 2

Special Considerations

Euglycemic DKA

• Euglycemic DKA is defined by glucose <200-250 mg/dL with pH <7.3, bicarbonate <15-18 mEq/L, anion gap >12 mEq/L, and ketonemia 2
• SGLT2 inhibitors are the leading contemporary cause, with an incidence of 0.6-4.9 events per 1,000 patient-years and relative risk of 2.46 versus placebo 2
• Start dextrose-containing fluids from the outset while continuing insulin therapy to clear ketones 1
• Check urine or blood ketones during any illness even if glucose is normal in patients on SGLT2 inhibitors 2

Phosphate Replacement

• Routine phosphate replacement has not shown beneficial effects on clinical outcomes in DKA 3
• Consider phosphate replacement only in patients with cardiac dysfunction, anemia, respiratory depression, or serum phosphate <1.0 mg/dL 3

Cerebral Edema Prevention

• Cerebral edema occurs in 0.7-1.0% of children with DKA and is a rare but frequently fatal complication 3
• Avoid overly rapid correction of osmolality and hyperglycemia 3
• Higher blood urea nitrogen at presentation is a risk factor for cerebral edema 3
• Monitor closely for altered mental status, headache, or neurological deterioration 2

Discharge Planning and Prevention

• Identify outpatient diabetes care providers before discharge 2
• Educate patients on glucose monitoring, insulin administration, recognition and treatment of hyperglycemia/hypoglycemia, and sick-day management 1, 2
• Provide detailed instructions to never stop basal insulin even when oral intake is limited 2
• Instruct patients to measure ketones when glucose exceeds 200 mg/dL or during any illness with DKA symptoms 2
• Ensure appropriate insulin regimen is prescribed with attention to medication access and affordability 2
• Schedule follow-up appointments prior to discharge 2
• For patients on SGLT2 inhibitors, counsel to avoid prolonged fasting, very-low-carbohydrate diets, and excessive alcohol intake 2