Adam Vella
EPIDEMIOLOGY
Insulin-dependent diabetes mellitus (IDDM) is the most common endocrine disorder of childhood, with an estimated prevalence of 1 in 400.
As many as 27% to 40% of new-onset diabetics present with diabetic ketoacidosis (DKA).
In known diabetics, DKA is much less common and tends to be clustered in a small subset of patients, with 5% of diabetic children accounting for nearly 60% of DKA episodes.
DKA is the most common cause of death in diabetic patients under 24 years of age, and cerebral edema is the leading cause of mortality in DKA.
Mortality rates for children who develop cerebral edema are 40% to 90%, and only 14% to 57% of those children affected recover neurologically normal.
DKA is much more common in patients with type 1 diabetes, but patients with type 2 diabetes can develop hyperglycemic, hyperosmolar nonketotic (HHNK) syndrome with acidosis and depletion of total body water, potassium, and phosphorus.
About 4% of children with newly diagnosed type 2 diabetes present with HHNK syndrome, which has a case fatality rate of 12%.
PATHOPHYSIOLOGY
IDDM is an autoimmune disease caused by destruction of insulin-producing β (beta) cells of the islets of Langerhans in the pancreas.
Although a genetic predisposition for IDDM exists, no single gene has been identified.
DKA is caused by insulin-deficiency. The resultant elevation of counter-regulatory hormones (glucagon, cortisol, growth hormone, epinephrine, and norepinephrine) leads to increased glucose production. Ensuing glucosuria causes an osmotic diuresis, resulting in the loss of fluids and electrolytes. Dehydration, polydipsia, and resultant hyperosmolality occur as a result of fluid losses.
Lack of insulin and excess glucagon result in the production of ketone bodies from free fatty acids. Production of ketones, primarily β-hydroxybutyrate and acetoacetate, exceeds the capacity for peripheral utilization, contributing to metabolic acidosis and compensatory respiratory alkalosis. The presence of increased ketones and acidemia manifest as the classic fruity breath odor of ketosis.
CLINICAL FEATURES
Classic symptoms of IDDM include polyuria, polydipsia, and polyphagia; however, other common complaints include weight loss, secondary enuresis, anorexia, abdominal discomfort, visual changes, headache, and genital candidiasis in a toilet-trained child.
Physical examination may reveal signs of dehydration, abdominal tenderness, Kussmaul’s respirations, decreased level of consciousness, or coma.
DKA should be considered in patients with hyperventilation, fruity breath odor of ketosis, dehydration, lethargy, altered mental status, hyperglycemia, vomiting, abdominal pain, or polyuria.
Cerebral edema is the most dreaded complication of DKA and should be suspected in all comatose patients. Premonitory symptoms of cerebral edema occur in as few as 50% and include severe headache, declining mental status, seizures, and papilledema.
DIAGNOSIS AND DIFFERENTIAL
DKA is defined by hyperglycemia (blood glucose >250 milligrams/dL), ketonemia, and metabolic acidosis (pH <7.2 and plasma bicarbonate level <15 mEq/L), associated with glucosuria and ketonuria.
Laboratory tests required to diagnose and manage DKA include serum electrolytes, urinalysis, and venous blood gas analysis.
Cerebral edema in DKA is a clinical diagnosis based on altered mental status not attributed to hypovolemia, and treatment should begin prior to neuroimaging when suspected. CT can confirm the diagnosis, and intracranial pressure monitoring may be indicated.
Sepsis should be considered in the setting of fever when the cause of DKA is not apparent, and a complete blood count, a chest radiograph, and appropriate cultures should be obtained as clinically directed.
Other causative factors include trauma, vomiting, noncompliance, and stress.
The abdominal pain associated with DKA can mimic acute appendicitis or other surgical abdominal emergencies, which must be considered in the differential diagnosis.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
The treatment of DKA consists of judicious fluid resuscitation, insulin therapy, correction of electrolyte abnormalities, and close monitoring.
Patients should have continuous monitoring of cardiorespiratory status, and vascular access should be established.
Initially, hourly monitoring of electrolytes and pH is necessary.
Administer 10 to 20 mL/kg NS boluses until hemodynamically stable. Give an initial 20 mL/kg bolus of NS if the child is in shock and repeat if needed. Once vital signs have stabilized, resist the desire to correct the fluid deficit too rapidly, especially if there is a high calculated serum osmolarity (ie, >340 mOsm/L).
Begin regular insulin at 0.05 to 0.1 units/kg/h after the initial IV fluid bolus (if given). Adjust the rate to maintain correction of serum glucose of 50 to 100 milligrams/dL/h. Do not decrease insulin infusion below 0.05 unit/kg/h until ketonuria has resolved; dextrose may be added to the IVF when the serum glucose approaches 200 milligrams/dL if ketonuria persists. High-dose insulin therapy and insulin boluses increase the risk of complications and are not recommended.
Correction of serum sodium is accomplished by administration of NS and treatment of hyperglycemia. Patients with DKA typically have sodium deficits of 5 to 10 mEq/kg, although initial hyponatremia may be overestimated due to effects of hyperglycemia and hyperlipidemia on reported sodium levels. Monitor serum sodium closely, since a slower than expected increase in serum sodium is a risk factor for developing cerebral edema.
Patients with DKA have total body deficits of potassium that require careful management. Extracellular shifts of potassium occur with metabolic acidosis and initial serum potassium levels do not reflect total body stores. If the pH is 7.10 or less and the K+ level is normal or low, begin replacement therapy immediately: for initial [K+] 3.5 to 5.5 mEq/L with adequate urine output, add 30 to 40 mEq potassium per liter (half as KCl and half as potassium phosphate); for initial [K+] of 2.5 to 3.5 mEq/L, add 40 mEq [K+] per liter; consider adding more if the [K+] is <2.5 mEq/L. If the K+ level is elevated (>6.0 mEq/L) consider withholding K+ therapy until adequate urine output is achieved and monitor serum K+ closely.
The use of bicarbonate in the treatment of DKA is not recommended, as it does not improve outcome and it has been associated with a fourfold increase in the development of cerebral edema. Bicarbonate should be used only in life-threatening situations in which other therapy has failed (including adequate ventilation), such as cardiac dysrhythmias or dysfunction.
Add dextrose to IV fluids when blood glucose is <200 to 250 milligrams/dL. Serum glucose corrects faster than ketoacidosis, so insulin must be continued with supplemental glucose until ketoacidosis has resolved.
Measure serum electrolyte levels and glucose hourly initially, then electrolyte monitoring can be spaced to every 2 hours as the patient stabilizes.
Cerebral edema is a potentially fatal complication of DKA and typically occurs 6 to 10 hours after initiating therapy; it presents with mental status changes progressing to coma. Although the etiology of this complication is unknown, it is felt that several factors may contribute, including overly aggressive fluid therapy, rapid correction of blood glucose levels, bicarbonate therapy, and failure of the serum sodium level to increase with therapy.
Management of cerebral edema: patients with DKA and altered mental status suggestive of cerebral edema should be treated empirically with mannitol 0.5 to 1 gram/kg or 3% hypertonic saline, 10 mL/kg over 20 to 30 minutes. Restrict additional IV fluids to a minimum required to maintain IV access. Use caution if endotracheal intubation is required and avoid eucapnea, as severe metabolic acidosis requires compensatory respiratory alkalosis and a rise in CO2 may worsen systemic and intracellular acidosis.
Most patients with DKA require admission to the intensive care unit, even when stable, because of intensive monitoring needs. Furthermore, many hospitals restrict the use of insulin infusions to intensive care settings. Patients with cerebral edema require ICU admission and possible intracranial pressure monitoring. Consultation with the patient’s primary care physician and a pediatric endocrinologist should be made early in the course of therapy.
For further reading in Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed., see Chapter 139, “The Child with Diabetes,” by Adam Vella.