What is the recommended management of diabetic ketoacidosis?

Management of Diabetic Ketoacidosis

Begin with isotonic saline at 15–20 mL/kg/hour for the first hour, followed by continuous IV regular insulin at 0.1 units/kg/hour (after confirming potassium ≥3.3 mEq/L), and add 20–30 mEq/L potassium to fluids once urine output is adequate. 1

Initial Assessment and Laboratory Workup

Obtain the following labs immediately to confirm DKA and guide management: 1, 2

• Plasma glucose, arterial blood gases (or venous pH), serum ketones (β-hydroxybutyrate preferred), electrolytes with calculated anion gap, serum osmolality 1, 2
• Blood urea nitrogen, creatinine, complete blood count with differential, urinalysis with urine ketones, electrocardiogram 1, 2
• If infection suspected: blood cultures, urine cultures, throat cultures, and chest X-ray if respiratory symptoms present 1

DKA diagnostic criteria: glucose >250 mg/dL (though euglycemic DKA can occur with glucose <200–250 mg/dL, especially with SGLT2 inhibitors), pH <7.3, bicarbonate <15–18 mEq/L, anion gap >10–12 mEq/L, and ketonemia/ketonuria 2, 3

Fluid Resuscitation Protocol

Hour 1: Administer isotonic saline (0.9% NaCl) at 15–20 mL/kg/hour (approximately 1–1.5 L in average adult) to restore intravascular volume and tissue perfusion 1, 2, 4

Subsequent hours: Continue fluid replacement based on hemodynamic status, electrolyte levels, and urine output; total fluid replacement should approximate 1.5 times the 24-hour maintenance requirement 1

When 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

Critical Pitfall

Never stop insulin when glucose falls below 250 mg/dL—instead add dextrose to IV fluids while maintaining insulin infusion to clear ketones 1

Potassium Management Algorithm

Before starting insulin, check serum potassium: 1, 2

• If K⁺ <3.3 mEq/L: Do NOT start insulin—this is an absolute contraindication due to risk of life-threatening cardiac arrhythmias and death; aggressively replete potassium with 20–40 mEq/L in IV fluids until K⁺ ≥3.3 mEq/L, confirm adequate urine output first 1, 2
• If K⁺ 3.3–5.5 mEq/L: Add 20–30 mEq/L potassium to each liter of IV fluid (use 2/3 KCl or potassium-acetate and 1/3 KPO₄) once adequate urine output confirmed 1, 2
• If K⁺ >5.5 mEq/L: Withhold potassium initially but monitor closely every 2–4 hours, as levels will drop rapidly with insulin therapy 2

Target serum potassium: Maintain 4–5 mEq/L throughout treatment 1, 2

Total body potassium depletion averages 3–5 mEq/kg body weight in DKA despite potentially normal or elevated initial levels due to acidosis 2, 4

Insulin Therapy Protocol

Standard IV Insulin Regimen (Moderate-to-Severe DKA)

Only use regular (short-acting) insulin for IV infusion—never use rapid-acting analogs intravenously 1

Initial dosing: 1, 2

• IV bolus: 0.1 units/kg regular insulin as direct push
• Continuous infusion: 0.1 units/kg/hour via IV pump
• Preparation: Add 100 units regular insulin to 100 mL normal saline (concentration 1 unit/mL)

Target glucose decline: 50–75 mg/dL per hour 1, 2

If glucose does not fall by 50 mg/dL in first hour: 1

1. Verify adequate hydration status
2. If hydration acceptable, double the insulin infusion rate every hour until achieving steady decline of 50–75 mg/dL/hour

Alternative Subcutaneous Approach (Mild-to-Moderate Uncomplicated DKA)

For hemodynamically stable, alert patients with mild-moderate DKA, subcutaneous rapid-acting insulin analogs (0.1–0.2 units/kg every 1–2 hours) combined with aggressive IV fluid replacement are equally effective, safer, and more cost-effective than IV insulin 1, 2, 4

Requirements for subcutaneous approach: Patient must be hemodynamically stable, alert, able to tolerate frequent monitoring, and have adequate fluid replacement 1, 2

Continuous IV insulin remains mandatory for: Critically ill patients, mentally obtunded patients, severe DKA, or hemodynamic instability 1, 2, 4

Monitoring Protocol

Check every 2–4 hours until stable: 1, 2, 4

• Blood glucose (bedside and laboratory)
• Serum electrolytes (especially potassium)
• Venous pH (typically 0.03 units lower than arterial pH)
• Serum bicarbonate
• Anion gap
• Blood urea nitrogen, creatinine, serum osmolality

Preferred ketone monitoring: Direct measurement of β-hydroxybutyrate in blood—nitroprusside-based urine/serum tests miss β-hydroxybutyrate (the predominant ketone) and should not be used 1, 2

DKA Resolution Criteria

All of the following must be met simultaneously: 1, 2

• Glucose <200 mg/dL
• Serum bicarbonate ≥18 mEq/L
• Venous pH >7.3
• Anion gap ≤12 mEq/L

Transition to Subcutaneous Insulin

Critical timing to prevent DKA recurrence: 1, 2, 4

1. Administer long-acting basal insulin (glargine or detemir) subcutaneously 2–4 hours BEFORE stopping IV insulin infusion—this is the most common error leading to DKA recurrence 1, 2
2. Continue IV insulin for 1–2 hours after subcutaneous basal dose to ensure adequate absorption and prevent coverage gap 1, 2
3. Patient must be able to tolerate oral intake before transition 1

Subcutaneous insulin dosing calculation: 1

• Basal insulin: Use 50% of total 24-hour IV insulin amount as single daily dose of long-acting insulin
• Prandial insulin: Divide remaining 50% equally among three meals as rapid-acting insulin

Alternative approach: Recent evidence shows adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk 2, 4

Bicarbonate Administration

Bicarbonate is NOT recommended 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, and it may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 1, 2, 4

Consider bicarbonate only if: pH <6.9 or when pH <7.2 and/or bicarbonate <10 mEq/L pre- and post-intubation to prevent hemodynamic collapse from apnea during intubation 5

Special Considerations

Euglycemic DKA

Definition: Blood glucose <200–250 mg/dL with pH <7.3, bicarbonate <15–18 mEq/L, anion gap >12 mEq/L, and ketonemia 2

Leading cause: SGLT2 inhibitors (incidence 0.6–4.9 events per 1,000 patient-years, relative risk 2.46 versus placebo) 2

Management modifications: 2

• Start 5% dextrose with normal saline from the outset of insulin therapy
• Discontinue SGLT2 inhibitors immediately
• Do not restart SGLT2 inhibitors until 3–4 days after metabolic stability achieved
• Measure β-hydroxybutyrate for diagnosis and monitoring

Other risk factors: Pregnancy (≈2% of pregnancies in women with pre-gestational diabetes), acute illness with reduced oral intake, prolonged fasting, very-low-carbohydrate diets, excessive alcohol intake 2

Pregnancy

Pregnant individuals may present with euglycemic DKA and mixed acid-base disturbances, especially with hyperemesis; high risk of fetal-maternal harm requires prompt recognition and treatment 2

Comorbidities Requiring Modified Approach

Renal disease: More cautious potassium repletion if anuric/oliguric; consider nephrology consultation 2

Congestive heart failure: Adjust fluid resuscitation rate to avoid volume overload 6

Acute coronary syndrome/stroke: Rapid glucose control may be warranted due to known harms of hyperglycemia in ischemic events 4

Older age: Increased risk of complications; closer monitoring required 6

Identifying and Treating Precipitating Causes

Common precipitants: 1, 2, 7

• Infection (most common)—obtain cultures and start appropriate antibiotics
• New diagnosis of diabetes
• Insulin omission or nonadherence
• Myocardial infarction (can both precipitate and be masked by DKA)
• Cerebrovascular accident
• Pancreatitis
• SGLT2 inhibitor use
• Glucocorticoid use
• Trauma

Treatment of underlying cause must occur simultaneously with metabolic correction 2, 4

Common Pitfalls to Avoid

• Never stop IV insulin without prior basal insulin administration 2–4 hours earlier—this causes rebound hyperglycemia and DKA recurrence 1, 2, 4
• Never hold insulin when glucose falls—add dextrose instead while maintaining insulin to clear ketones 1
• Never start insulin if potassium <3.3 mEq/L—replete potassium first 1, 2
• Never rely on urine ketones or nitroprusside-based tests—they miss β-hydroxybutyrate and lag behind serum clearance 1, 2
• Never stop insulin before complete resolution of metabolic acidosis—premature termination leads to DKA recurrence 2, 4
• Never use rapid-acting insulin analogs intravenously—only regular insulin is appropriate for IV use 1

Discharge Planning

Before discharge, ensure: 2, 4

• Appropriate insulin regimen prescribed with attention to medication access and affordability
• Patient education on insulin administration, glucose monitoring, home glucose goals (typically 80–180 mg/dL)
• Recognition and treatment of hyperglycemia and hypoglycemia
• Sick-day management instructions (never stop basal insulin, check ketones when glucose >200 mg/dL or during illness)
• For SGLT2 inhibitor users: discontinue during any acute illness, check ketones even if glucose normal, avoid prolonged fasting and very-low-carbohydrate diets
• Identification of outpatient diabetes care providers
• Follow-up appointments scheduled prior to discharge
• Prescriptions and supplies provided to avoid gaps in care