Practice Essentials
Diabetic ketoacidosis (DKA) is a complex metabolic state of hyperglycemia, ketosis, and acidosis. [1, 2] Diabetic ketoacidosis results from untreated absolute or relative deficiency of insulin in type 1 or type 2 diabetes mellitus, respectively.
Signs and symptoms
The classic symptoms of diabetic ketoacidosis, which are often insidious, include the following:
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Fatigue and malaise
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Nausea/vomiting
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Abdominal pain
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Polydipsia
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Polyuria
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Polyphagia
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Weight loss
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Fever
Physical examination may reveal the following findings:
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Altered mental status without evidence of head trauma
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Tachycardia
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Tachypnea or hyperventilation (Kussmaul respirations)
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Normal or low blood pressure
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Increased capillary refill time
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Poor perfusion
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Lethargy and weakness
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Fever
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Acetone odor of the breath reflecting metabolic acidosis
See Presentation for more detail.
Diagnosis
Laboratory studies
The following laboratory studies are indicated in patients with diabetic ketoacidosis:
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Serum glucose level
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Serum potassium level
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Arterial blood gas levels
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Glycosylated hemoglobin level
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Complete blood cell count
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Serum sodium, chloride, bicarbonate, blood urea nitrogen, creatinine, magnesium, calcium, and phosphate levels
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Urine glucose, ketones, and osmolality
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Serum osmolality
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Blood, urine, and throat cultures
Imaging studies and other tests
Obtain imaging studies appropriate for suspected infection, obstructive abdominal processes, or cerebral edema. An electrocardiogram (ECG) is especially helpful when results of serum potassium concentration are not rapidly available.
See Workup for more detail.
Management
Multiple goals are noted for the acute treatment of diabetic ketoacidosis, including the following:
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Volume resuscitation
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Identification and treatment of the precipitant event
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Insulin therapy
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Hourly monitoring of serum markers of diabetic ketoacidosis
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Prevention of complications from rapid decreases in serum osmolarity
See Treatment and Medication for more detail.
Pathophysiology
Hyperglycemia results from impaired glucose uptake because of insulin deficiency and excess glucagon with resultant gluconeogenesis and glycogenolysis. Glucagon excess also increases lipolysis with the formation of ketoacids. Ketone bodies provide alternative usable energy sources in the absence of intracellular glucose. The ketoacids (acetoacetate, beta-hydroxybutyrate, acetone) are products of proteolysis and lipolysis.
Hyperglycemia causes an osmotic diuresis that leads to excessive loss of free water and electrolytes. Resultant hypovolemia leads to tissue hypoperfusion and lactic acidosis.
Ketosis and lactic acidosis produce a metabolic acidosis; however, supplemental bicarbonate is not recommended. Acidosis usually resolves with isotonic fluid volume replenishment and insulin therapy. [3] A pediatric trial of bicarbonate in severe metabolic acidosis during DKA (pH < 7.15) showed no benefit when compared with placebo. [4] Indeed, multiple studies suggest that bicarbonate therapy may cause paradoxical intracellular acidosis, worsening tissue perfusion and hypokalemia, and cerebral edema. [5]
As acidosis corrects, acetoacetate and acetone levels increase in proportion to beta-hydroxybutyrate. As it worsens, the reverse occurs. Routine laboratory testing for ketones measures only the presence of acetoacetate and acetone, not beta-hydroxybutyrate. Therefore, ketosis may appear to be absent in early diabetic ketoacidosis and to worsen as severe diabetic ketoacidosis resolves.
Electrolyte imbalances are the consequences of hyperglycemia, hyperosmolality, and acidosis.
Despite what may be severe total body potassium depletion, apparent serum hyperkalemia is often observed in patients with diabetic ketoacidosis prior to volume resuscitation. Serum hyperkalemia occurs as potassium ions shift from the intracellular to extracellular space because of acidosis from insulin deficiency and decreased renal tubular secretion. Similar decreases in serum phosphate and magnesium concentrations are the result of ion shifts.
Hyponatremia results from a dilutional effect as free water shifts extracellularly because of high serum osmolarity. True serum sodium values can be calculated by adjusting measured sodium levels upward 1.6 mEq/L for every 100 mg/dL increase in serum glucose concentration.
As serum osmolarity increases from hyperglycemia, intracellular osmolality in the brain also increases. Overly rapid correction of serum hyperglycemia and osmolarity may create a large gradient between intracerebral and serum osmolarity. Free water then shifts into the brain and may cause cerebral edema with herniation. Therefore, fluid resuscitation and correction of hyperglycemia should be gradual and closely monitored.
Etiology
Diabetic ketoacidosis is the presenting complaint in approximately one fourth of newly diagnosed patients with type 1 diabetes mellitus.
Infection is the most frequent cause of diabetic ketoacidosis, particularly in patients with known diabetes. Aggressive evaluation for infection is always warranted. Strongly consider empiric antibiotic therapy until cultures return.
Other causes of diabetic ketoacidosis are as follows:
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Poor compliance with existing insulin regimens
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Underlying endocrine changes of adolescence (thelarche, adrenarche, menarche)
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Caregiver's lack of competence
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Pump failure (insulin pumps are increasingly in use)
Epidemiology
United States statistics
The incidence of type 1 diabetes mellitus is 2 per 1000. The exact incidence of diabetic ketoacidosis is unknown but is estimated to be 4-8 per 1000. Diabetic ketoacidosis occurring at the time of diagnosis of diabetes mellitus is more common in younger children. [6] In the United States, the rate of diabetic ketoacidosis is about 25% at the time of diagnosis.
International statistics
The exact incidence is unknown. In a study from Germany and Austria that included on 28,770 children aged 19 years or younger, the highest risk of diabetic ketoacidosis in established cases of type 1 diabetes mellitus was during early adolescence. [7]
Race-related demographics
Because of an association with human leukocyte antigen (HLA) groups DR3 and DR4 (which occur more commonly in White populations), type 1 diabetes mellitus and diabetic ketoacidosis are more common in White children. The exact racial frequency is unknown.
Prognosis
With current medical therapy, diabetic ketoacidosis has a 2-5% mortality rate. Mortality results from the precipitating underlying cause, which is primarily cerebral edema. Cerebral edema occurs in 0.3-1% of all episodes of diabetic ketoacidosis.
The prognosis is excellent if aggressive fluid and insulin therapy commence in the first few hours of diagnosis.
Complications
Cerebral edema
Cerebral edema occurs in 0.7-1% of children with diabetic ketoacidosis. It is an important cause of mortality and long-term morbidity in these patients. [8] Mortality is approximately 20-25%, and permanent neurologic deficits occur in 35% or more of survivors. [9] The causes of cerebral edema in patients with diabetic ketoacidosis are multifactorial but may include too-rapid infusion of fluids and electrolytes, overhydration, and overly aggressive correction of acidosis or hyperglycemia. Treatment includes intubation, hyperventilation, and mannitol 0.25-1 g/kg intravenously.
Hypoglycemia
Causes include increased sensitivity to exogenous insulin and insufficient serum glucose for insulin to metabolize. Treatment includes adding 5-10% dextrose to intravenous fluids when serum glucose level is 250-300 mg/dL.
Hypokalemia
Serum potassium begins to reflect actual total body potassium depletion as volume depletion and acidosis resolve. Add potassium to intravenous fluids (see Emergency Department Care) when urine output is present and results of serum potassium level are available.
Cardiac dysrhythmia
Causes include hyperkalemia, hypokalemia, and hypocalcemia. Treatment involves correcting the specific cause.
Pulmonary edema
Causes include low plasma oncotic pressure and increased pulmonary capillary permeability. Treatment includes oxygen and diuresis.
Other complications
Acute kidney injury (AKI) can occur in patients with type 1 diabetes mellitus and diabetic ketoacidosis. A study that included 165 children hospitalized for diabetic ketoacidosis reported that 106 (64.2%) developed AKI (AKI stage 1, 37 [34.9%]; AKI stage 2, 48 [45.3%]; and AKI stage 3, 21 [19.8%]). [10] AKI and adverse neurocognitive outcomes are more common in patients with greater acidosis and circulatory volume depletion. [11]
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Sample diabetic ketoacidosis flow sheet.
