Diabetic ketoacidosis in children

Diabetic ketoacidosis (DKA) is an acute, life-threatening complication of diabetes mellitus that occurs primarily in children with type 1 diabetes mellitus (T1DM). It is caused by insulin deficiency, often secondary to inadequate insulin therapy (e.g., insulin pump failure, missed doses), or increased insulin demand (e.g., infection, stress). DKA is frequently the first symptom in the initial diagnosis of T1DM in children. Early symptoms (e.g., dehydration, nausea, vomiting, fatigue) may be vague, especially in young and/or nonverbal children, but if untreated will progress to signs of severe metabolic acidosis (e.g., Kussmaul breathing), mental status changes, and/or circulatory compromise. DKA is confirmed in patients with hyperglycemia, ketosis, and acidosis and/or decreased bicarbonate. For patients with extremely elevated glucose but minimal or absent ketones, hyperglycemic hyperosmolar state (HHS) in children should be considered, although this is much rarer in children than adults. Management includes fluid resuscitation, insulin therapy, electrolyte repletion, careful monitoring (e.g., telemetry, serum ketones, venous blood gas), and assessing for complications (e.g., features of cerebral injury in pediatric DKA). Prompt recognition and treatment are necessary to prevent complications (e.g., permanent brain injury, death).

DKA in children is most commonly caused by insulin deficiency and/or increased insulin demand. ^[1]

• Insulin deficiency due to, e.g.:
  • Undiagnosed diabetes, usually T1DM ^[2]
  • Insulin pump failure
  • Poor adherence to insulin therapy
• Increased insulin demand due to, e.g.:
  • Infection (e.g., infectious gastroenteritis in children)
  • Certain medications (e.g., glucocorticoids)
  • Stress (e.g., trauma, surgery)

The pathophysiology of DKA is the same in children and adults.

Clinical features of DKA are similar in children and adults and include: ^[1]

• Clinical features of diabetes mellitus
• Clinical features of dehydration
• Tachypnea, Kussmaul breathing ^[2]
• Acetone breath (fruity odor)
• GI symptoms (e.g., nausea, vomiting, abdominal pain) without diarrhea
• Neurological symptoms (e.g., drowsiness, lethargy, irritability) ^[2]
• Signs of circulatory compromise and/or, in some cases, hypertension ^[1]

Maintain a high level of suspicion for DKA in preverbal children because early symptoms (e.g., polyuria, weight loss, fatigue) are easily overlooked. ^[2]

DKA is the initial manifestation in nearly one-third of children with T1DM. ^[2]

Euglycemic ketoacidosis in children ^[1]

• Definition: a form of DKA characterized by normal or modestly elevated blood glucose levels
• Causes include:
  • Starvation
  • Low-carbohydrate diet
  • Partial treatment with insulin
  • SGLT-2 inhibitors (used off-label in children)
• Management is similar to that for DKA with hyperglycemia, except that dextrose-containing fluids are started immediately after fluid resuscitation.

If DKA is suspected (e.g., high point of care blood glucose, ketonuria), perform diagnostic studies in conjunction with management.

Initial studies ^[1][2]

• Point of care glucose (POC glucose)
• Venous blood gas (VBG)
• Measurement of ketones ^[1]
  • Preferred: serum β-hydroxybutyrate
  • Alternative: urine dipstick
• BMP (correct sodium for hyperglycemia), magnesium, and phosphorus ^[1][2]
• CBC ^[2]
• Urinalysis
• Pregnancy test in patients who can become pregnant

Acute kidney injury occurs commonly in children with DKA. ^[2][3]

Diagnostic criteria and severity of DKA in children ^[1][2]

All of the following must be met to diagnose DKA:

• Hyperglycemia: glucose > 200 mg/dL
• Metabolic acidosis: venous pH < 7.3 OR serum bicarbonate < 18 mEq/L
• Ketosis:
  • Serum β-hydroxybuterate ≥ 31 mg/dL
  • Urine ketones ≥ 2+ (i.e., moderate or large)

Severity of DKA ^[1]

Severity is classified according to the most severe abnormality (venous pH or serum bicarbonate).

Additional studies

Obtain additional studies if indicated.

• ECG: if electrolytes (especially potassium) are abnormal or electrolyte results are delayed
• HbA1c for patients with: ^[1]
  • No previous diagnosis of diabetes
  • Uncertain duration of hyperglycemia
• Workup for suspected underlying infection, e.g.:
  • Diagnostics for sepsis in children
  • Diagnostics for pediatric CAP
  • Diagnostics for UTI in children
• Diagnostics for altered mental status in case of diagnostic uncertainty

Approach

• Initiate management simultaneously with diagnostics. ^[1][2]
• Consult a pediatrician experienced in managing DKA.
• Begin initial stabilization, including:
  • IV access
  • Initial fluid resuscitation
  • Monitoring
  • Treatment of acute underlying causes
  • Management of significant electrolyte abnormalities (if results are available)
• Start insulin therapy after ≥ 1 hour of fluid therapy. ^[1]
• Most children require admission for monitoring and further management.
  • Admit to PICU if any of the following features are present: ^[1]
    • Severe DKA with prolonged duration of symptoms, reduced consciousness, and/or signs of hemodynamic compromise
    • Risk factors for cerebral injury in pediatric DKA
  • Children with mild DKA who meet all the following criteria may be considered for discharge after initial emergency department management: ^[2]
    • Improved laboratory parameters following treatment with insulin and fluids
    • Able to tolerate oral intake
    • Able to be monitored at home with close follow-up
• Discuss prevention of recurrent DKA in children with patient and/or caregivers before discharge.

• Perform an ABCDE assessment; in preverbal children, use the modified pediatric Glasgow coma scale (pGCS).
  • If the patient is obtunded, establish airway protective measures. ^[1]
    • Insert a nasogastric tube with continuous suction.
    • Avoid intubation and mechanical ventilation in children when possible due to the risk for decompensation.
  • Start oxygen therapy for children as needed.
  • Place at two peripheral IV lines; avoid central venous catheters (CVC).
• Start monitoring with: ^[1]
  • Continuous telemetry
  • Hourly monitoring of vital signs, fluid intake and output, POC glucose, and for features of cerebral injury in pediatric DKA
  • VBG, BMP, and serum β-hydroxybuterate every 2 hours ^[1]
• Administer an initial IV fluid bolus. ^[1]
  • No signs of shock: 10–20 mL/kg bolus ^[1]
  • Signs of shock: 20mL/kg bolus , repeated as needed ^[1]
• Start electrolyte management in pediatric DKA immediately if there are significant electrolyte deficiencies, e.g.:
  • Potassium < 3.5 mEq/L
  • Phosphate is < 1 mg/dL
• Assess for signs of pediatric sepsis and initiate antibiotic therapy if present (see "Management of pediatric sepsis").
• Nausea and vomiting
  • Nausea and vomiting are physiological responses to ketoacidosis and typically resolve with treatment. ^[4]
  • Consider antiemetics in children if other causes are suspected (e.g., chemotherapy, gastroenteritis).

Intubation can lead to decompensation in severe acidosis. Consult an experienced clinician before deciding to intubate. ^[1]

Prioritize volume repletion during initial stabilization. Do not start insulin therapy until ≥ 1 hour after starting IV fluids. ^[1]

For children with a high body weight, limit fluid boluses to 1 L and infusion rates to 500 mL/hour. ^[1]

Fluid resuscitation in pediatric DKA ^[1][2][5]

Initial fluid resuscitation ^[1][2][5]

• See "Initial stabilization in pediatric DKA."
• Boluses of 10–20 mL/kg 0.9% NaCl are recommended.

If potassium level is < 3.5 mEq/L, begin potassium management in pediatric DKA alongside initial fluid resuscitation. ^[1]

Ongoing fluid replacement ^[1][2]

• Calculate fluid deficit.
  • Clinical features of dehydration and hypovolemia and vital signs may be unreliable indicators of volume status in children with DKA. ^[1]
  • Assume the following percent of fluid deficit based on DKA severity: ^[1]
    • Mild: 5%
    • Moderate: 7%
    • Severe: 10%
  • Additionally assess for features of severe dehydration, e.g.: ^[1]
    • Blood urea nitrogen > 20 mg/dL
    • pH < 7.1
    • Impalpable peripheral pulses, hypotension, and/or oliguria suggest ≥ 10% volume depletion
  • Fluid deficit (L) = body weight (kg) × percent deficit
• Deduct fluids used in initial stabilization and replace the remaining deficit over 24–48 hours. ^[1]
  • Use 0.45–0.9% NaCl or a balanced crystalloid (e.g., lactated Ringers).
  • Maximum infusion rate: 500 mL/hour ^[1]
• Include maintenance IV fluid until oral intake has resumed.
• Add 5–10% dextrose to IV fluid when: ^[1][2]
  • Serum glucose is < 250–300 mg/dL
  • OR serum glucose falls at a rate > 90 mg/dL per hour
• Regularly assess vital signs and fluid status, and evaluate for signs of cerebral injury in pediatric DKA. ^[1]
• Discontinue IV fluid when ketosis resolves and oral intake is tolerated.

Electrolyte management in pediatric DKA ^[1]

• Measure electrolytes (e.g., potassium, phosphate, calcium, magnesium) at the time of DKA diagnosis.
• Depletion of phosphate and potassium is common in DKA.
• Phosphate repletion can cause hypocalcemia and hypomagnesemia.
• Monitor electrolytes every 2 hours after starting fluid therapy and replete as needed.

Bicarbonate therapy is not recommended unless patients have life-threatening hyperkalemia or pH < 6.9 with impaired cardiac contractility. ^[1]

Potassium ^[1]

• Management depends on potassium level.
• If potassium level is not readily available, obtain ECG to evaluate for signs of hyperkalemia and hypokalemia.

Phosphate ^[1]

• If the level is < 1 mg/dL, replete phosphate immediately.
• Consider routine replacement, especially in children with severe DKA.
• Monitor serum calcium and magnesium during phosphate replacement and replete as needed.

Initial insulin therapy

• Insulin therapy is indicated for all children with DKA 1 hour after initial fluid resuscitation.
  • Preferred: insulin IV infusion ^[1]
  • Alternative: rapid-acting subcutaneous insulin ^[1]
• While patient receives insulin therapy, monitor the following:
  • POC glucose hourly ^[1]
  • Venous pH and serum β-hydroxybutyrate every 2 hours ^[1]

Insulin boluses are not recommended for children with DKA. ^[1][2]

Delay insulin infusion in children with serum potassium < 3.5 mEq/L until a potassium bolus has been given. ^[1]

Transition from infusion to subcutaneous insulin ^[1]

• Indicated when ketoacidosis is resolved (i.e., pH > 7.3, serum bicarbonate > 18 mEq/L, and β-hydroxybutyrate < 10 mg/dL) and the patient is tolerating oral nutrition ^[1][2]
• Administer initial subcutaneous insulin before discontinuing insulin infusion, e.g.: ^[1]
  • Long-acting insulin: Administer in the evening, decrease insulin infusion overnight, and stop in the morning.
  • Short-acting insulin: 15–30 minutes before discontinuing infusion
• Consider initiating short and long-acting insulin simultaneously. ^[1]

Other causes of metabolic acidosis ^[6]

• Starvation ketosis
• Alcoholic ketoacidosis
• Lactic acidosis (e.g., from sepsis, shock, severe hypoxia)
• Toxic ingestions (e.g., salicylates, methanol, ethylene glycol, isopropyl alcohol)
• Inborn errors of metabolism (e.g., fatty acid metabolism disorders, cystinosis)

Hyperglycemic hyperosmolar state in children ^[1]

Hyperglycemic hyperosmolar state (HHS) is severe hyperglycemia and hyperosmolality without ketosis and is more commonly associated with T2DM.

• Clinical features ^[1]
  • Dehydration
  • Polydipsia, polyuria
  • Lethargy
  • Confusion
  • Behavior change
  • Seizures
• Diagnostic criteria for HHS in children ^[1]
  • Plasma glucose > 600 mg/dL
  • Venous pH > 7.25 OR arterial pH > 7.30
  • Serum bicarbonate > 15 mEq/L
  • Effective serum osmolality > 320 mOsmol/kg H₂O
  • No or very mild ketones
• Management: HHS is rare in children and is usually managed by a specialist in an intensive care setting. ^[1]
  • Fluid resuscitation
    • Bolus 20 mL/kg 0.9% NaCl; repeat as needed to restore perfusion.
    • Replace the remaining fluid deficit (typically 12–15% of body weight) over 24–48 hours with hypotonic saline (0.45–0.75%). ^[1]
    • Give maintenance fluids until patients are able to eat and drink normally.
  • Electrolyte management (e.g, potassium, phosphate, magnesium)
  • Begin insulin therapy (e.g., continuous insulin infusion) when the rate of serum glucose decline slows to < 50 mg/dL/hr with IV fluid administration alone.

The differential diagnoses listed here are not exhaustive.

• Acute kidney injury, kidney failure
• Severe electrolyte disturbances
• Pneumonia
• Pulmonary edema
• Pneumothorax
• Thrombosis
• Mucormycosis
• Rhabdomyolysis
• Cerebral injury in pediatric DKA
• Death

Cerebral injury in pediatric DKA ^[1]

• Incidence: < 1% ^[1]
• Cause: cerebral edema ^[1][2]
• Risk factors for cerebral injury in pediatric DKA include: ^[1]
  • Age < 5 years
  • Serum pH < 7.1
  • pCO₂< 21 mm Hg
  • BUN > 20 mg/dL
• Diagnosis is clinical; criteria have been proposed to aid diagnosis. ^[1]

• Treatment: hyperosmolar agents (e.g., mannitol)
• Mortality: 21–25% ^[1]

We list the most important complications. The selection is not exhaustive.

• Educate the patient and/or caregiver on the following: ^[6]
  • Increasing glucose and ketone monitoring during acute illness
  • Keeping basal insulin in case of pump failure
• Prevent recurrent DKA by providing the following interventions: ^[1]
  • Identify the cause of the current DKA event (e.g., interrupted use of insulin, infection).
  • Interrogate the insulin pump to ensure proper operation.
  • If insulin omission is suspected:
    • Explore risk factors for poor adherence.
    • Consider referral to a social worker or clinical psychologist in case of deliberate omission.