• State of severe metabolic derangement that occurs in patients with insulin-dependent diabetes mellitus secondary to insulin deficiency and stress hormone excess.
• Hyperglycemia (blood glucose >200 mg/dL)
• Ketonemia (>3 mmol in serum or ketonuria)
• Acidosis (pH <7.3 or HCO₃ >15 mEq/L)

• Insulin deficiency and excess of the counter-regulatory hormones glucagon, cortisol, and epinephrine lead to unregulated catabolism.
• Glycogenolysis and gluconeogenesis lead to hyperglycemia.
• Lipolysis and ketone production lead to metabolic acidosis.
• Hyperosmolar state leads to osmotic diuresis, dehydration, and electrolyte loss.

• 30% of new diabetic children present in diabetic ketoacidosis (DKA); higher percentage in children under 5 years.
• Overall mortality ~3% to 5% per episode
• 65% of all hospital admissions in diabetic children under 19 years old
• Most common cause of death (>50%) in diabetic children

• Cardiovascular collapse
  • Caused by osmotic diuresis and dehydration
  • Treated with prompt initiation of fluid resuscitation
• Overwhelming acidosis
  • From ketoacid accumulation
  • Treated with bicarbonate and insulin infusion
• Hypoglycemia from insufficient dextrose supplementation, treated by increasing dextrose
• Hypokalemia
  • Caused by loss of potassium in the urine and correction of acidosis with insulin
  • Treated by intravenous potassium supplementation
• Cerebral edema
  • Most serious complication of DKA and most frequent cause of death
  • Rapid changes in serum osmolarity lead to influx of water into brain tissue
  • Occurs 6 to 18 hours after initiation of therapy, as patient is improving
  • Heralded as headache, change in mental status, or abnormal neurological signs
  • May progress rapidly to brain herniation and death
  • Treatment is supportive, aimed at reducing intracranial pressure with mannitol, and hyperventilation

• Overall, 5% mortality with each episode of DKA

• Gastroenteritis
• Severe intraabdominal process (e.g., ulcer, pancreatitis, appendicitis)
• Urinary tract infection
• Pneumonia
• Stress hyperglycemia
• Hypercalcemia
• Salicylate ingestion
• Inborn error of metabolism
• Non-ketotic hyperosmolar coma

Question: Polyuria, polydipsia, and polyphagia with weight loss
Significance: Symptom of hyperosmolar state.

Question: Nausea, vomiting, abdominal pain
Significance: Related to acidosis and electrolyte disturbance.

Question: Changes in breathing patterns (Kussmaul respirations)
Significance: Related to acidosis and respiratory correction.

Question: Precipitating event, such as an intercurrent illness or psychosocial stress
Significance: Increased need for insulin in these states.

Finding: Vital signs—tachycardia, hypotension
Significance: Seen in dehydration

Finding: Dry mucous membranes, sunken eyes, poor skin turgor, poor distal perfusion, weak pulses
Significance: Dehydration

Finding: Fruity odor to breath indicates ketosis
Significance: Ketosis

Finding: Deep, sighing, hyperpneic (Kussmaul) respirations
Significance: Respiratory regulation of acid base disturbance

Finding: Abdominal tenderness
Significance: Related to electrolyte disturbance and increased lipids

Finding: Altered mental status
Significance: Acidosis and hyperglycemia

Test: Glucose more than 200 mg/dL
Significance: Indicates insulin deficiency

Test: Urinalysis—glycosuria and ketonuria
Significance: Glucose level exceeds renal threshold

Test: Sodium—serum levels low
From electrolyte losses and artifact of hyperlipidemia; actual Na level = measured Na +1.6 ×
Significance: [glucose – 200)/100]

Test: Potassium—serum levels may be elevated, normal, or low; total body is potassium-depleted.
Significance: Potassium deletion from hyperaldosterone. Serum level is dependent on state of hydration.

Test: Bicarbonate less than 15 mEq/L
Significance: Acidosis

Test: Phosphate—low, secondary to osmotic diuresis
Significance: Acidosis

Test: ABG—low pH (<7.3), low pCO₂, and low HCO₃
Significance: Acidosis

Test: CBC—elevated WBC count even in the absence of infection
Significance: Strep reaction

• Resuscitation
  • Assess adequacy of airway and breathing.
  • Restore circulation if necessary with normal saline bolus of 10 to 20 mL/kg.
  • Cannot gauge hydration status initially by urine output because of osmotic diuresis.
  • Avoid aggressive fluid resuscitation—too-rapid correction of hyperosmolarity increases risk of cerebral edema.
• Monitoring
  • ICU admission for infants, toddlers, initial pH <7.1, hemodynamic, or neurological instability
  • ECG monitoring for hypokalemia or hyperkalemia
  • Serial neurological examinations q1h, with special attention to headache, declining mental status, any neurological symptoms
  • Serial blood sugars hourly
  • pH and electrolytes q1–2h until stable
• Fluids
  • Assume 10% dehydration, 15% in infants
  • Aim to replace losses plus maintenance fluids evenly over 48 hours
  • Replacement fluids should always be normal saline, not ½ normal saline
  • Ongoing renal losses greater than 3 mL/kg/h may be replaced if significant
• Electrolytes
  • Assume Na and K losses of approximately 5 to 10 mEq/kg
  • Hyponatremia will correct as fluids and insulin are given
  • Continued drop in Na is associated with increased risk of cerebral edema
  • Replace potassium as an equal mixture with chloride and phosphate:
    K+ > 5.5, 20 mEq/L in replacement fluids
    K+ = 4.0–5.5, 40 mEq/L
    K+ < 4.0, 60 mEq/L
  • Potassium replacement should never exceed 0.5 mEq/kg/h
• Acidosis
  • Usually corrects once adequate insulin and fluids are given
  • Consider bicarbonate if arterial pH <7.1 or there is inadequate respiratory compensation rule of thumb: (i.e., if pCO₂ > (1.5 × [HCO₃]) + 8)
  • Give as slow infusion over 1 to 2 hours at dose of 1 to 2 mEq/kg
• Insulin
  • Prompt initiation critical in terminating ongoing ketone and acid production
  • Initial dose is 0.1 U/kg/h as continuous intravenous infusion
  • Do not give subcutaneously in DKA, as skin perfusion may be suboptimal
  • Aim to lower serum glucose by 50 to 100 mg/dL/h
• Glucose
  • Add 5% dextrose to intravenous stock when blood glucose <300 mg/dL
  • Change to 10% dextrose when blood glucose <200 mg/dL
• Duration
  • Stop infusion when pH > 7.3, HCO₃ > 15, glucose < 300, and patient is tolerating oral fluids
  • Convert to subcutaneous therapy by adding up total insulin given over 24 hours and dividing into two to four injections or return to usual home regimen of with frequent monitoring and extra insulin as needed

• New diabetics should be followed closely after hospital discharge to assess adequacy of insulin regimen.
• Children with recurrent DKA shoud be evaluated for treatment failure (familial dysfunction, knowledge gaps).

• Timely referral for children with symptoms of polyuria, polydipsia, and weight loss
• Surveillance with frequent blood sugar and urine ketone monitoring, supplemental insulin dosing, phone contact with pediatrician or endocrinologist should avert almost all episodes of DKA in children known to have diabetes.

Q: What are the usual triggers for DKA?
A: Intercurrent illnesses, such as gastroenteritis, urinary tract infections, pneumonia; psychosocial stressors; failure to take insulin on schedule.

Q: Does an episode of DKA mean that the insulin regimen is inadequate?
A: DKA always implies insulin deficiency; insulin regimen may be adequate when child is well, but additional stresses of illness or psychosocial factors often require supplemental insulin.

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Kecskes S. Diabetic ketoacidosis. Pediatr Clin North Am 1993;40(2):355–363.

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