DKA is a complex endocrine condition caused by an absolute or relative lack of insulin. It is characterized by hyperglycemia, dehydration, ketosis, and metabolic acidosis.
The annual incidence of DKA in the United States ranges from 4.6 to 8 episodes per 1000 patients with diabetes. Diabetes is one of the most common diseases occurring in teenagers. DKA is seen as the initial presentation of diabetes in approximately 25% of young children.1 The risk of DKA in children and adolescents with type 1 diabetes is 1 to 10 per 100 persons per year.2–5 In young patients, DKA accounts for 70% of diabetes-related deaths.
In DKA, a lack of insulin and stress lead to increase in the levels of counterregulatory hormones—glucagon, epinephrine, cortisol, and growth hormone. Gluconeogenesis and glycogenolysis occur in the liver and proteolysis occurs in peripheral tissues. Lipolysis occurs in fatty tissues, forming the ketoacids, β-hydroxybutyrate, and acetoacetic acid. The combination of hyperglycemia and ketoacidosis causes a hyperosmolar diuresis that results in loss of fluids and electrolytes. The combination of ketonemia and hypoperfusion then results in high anion gap metabolic acidosis.
DKA is precipitated by a variety of causes. DKA at diagnosis is more common in children younger than 5 years and families with poor access to health care.2 In adolescents, noncompliance with insulin is a main cause of DKA. The risk of DKA is increased in peripubertal and adolescent girls, children with clinical depression or eating disorders, and those on insulin pump therapy (due to use of short-acting insulin).2,5,6
DKA is often insidious in onset with slow progression of the illness. Symptoms can include fatigue and malaise, nausea/vomiting, abdominal pain, polydipsia, polyuria, polyphagia, significant weight loss, and sometimes fever.
Physical findings can include altered mental status characterized by drowsiness, progressive obtundation, and loss of consciousness without evidence of head trauma. The patient will usually have tachycardia, tachypnea or deep, rapid, sighing respirations (Kussmaul respiration), normal or low blood pressure. The child may also have poor perfusion, delayed capillary refill, and other signs of dehydration. The child may have lethargy and weakness, an acetone odor of the breath reflecting metabolic acidosis. Fever may be present if infection precipitated the episode.
Initial laboratory studies include a complete blood count, serum electrolytes, glucose, calcium, phosphorus, and serum acetone. The patient may have a nonspecific elevation of serum amylase. An arterial blood gas and bedside tests for blood sugar and urine ketones can be done for rapid diagnosis of DKA. An initial electrocardiogram can be performed to assess for T-wave changes.
Definition of DKA (biochemical criteria)8 is as follows: hyperglycemia with a blood glucose >200 mg/dL; venous pH <7.3 or bicarbonate <15 mmol/L; ketonemia and ketonuria.
DKA can be classified by the degree of acidosis into mild, moderate, and severe.9
Mild: Venous pH <7.3 or bicarbonate <15 mmol/L
Moderate: pH <7.2, bicarbonate <10 mmol/L
Severe: pH <7.1, bicarbonate <5 mmol/L
In type 2 diabetes mellitus, HHS can occur.10 This is defined by the following: plasma glucose concentration >600 mg/dL; arterial pH >7.30; serum bicarbonate >15 mmol/L; small ketonuria and absent or mild ketonemia; serum osmolarity ≥320 mOsm/kg; stupor or coma.
Treatment of DKA consists of rapid assessment, replacement of the patient's fluid and electrolyte deficit, and reversal of the central pathophysiologic process by the administration of insulin.
Assessment includes performing a quick clinical assessment and bedside tests to confirm the diagnosis. Weigh the patient and use weight for calculation of fluid and electrolyte therapy as well as assess the level of dehydration. Assess the level of consciousness using the Glasgow Coma Scale. Then obtain blood samples and start peripheral IV line and obtain an ECG. Provide supportive measures including airway management for obtunded or comatose patients and oxygen at 100% concentration to patients in respiratory or circulatory failure and shock. Maintain good peripheral or central IV access. Continuous cardiac monitoring is to be used for assessment of T-wave changes 11.
After obtaining samples for cultures, intravenous antibiotics are to be started as soon as possible for patients with DKA precipitated by febrile illness. As soon as hemodynamic stability is achieved, the child should be transferred to an intensive care unit to be managed by a pediatric intensive care specialist with consultation from a pediatric endocrinologist.
Children with DKA are at least 5% to 10% dehydrated.12,13 Because clinical estimates are usually inaccurate,14 it is practical to estimate for moderate DKA, 5% to 7% dehydration, and for severe DKA, 7% to 10% dehydration.1 The initial fluid resuscitation is with normal saline at a dose of 20 mL/kg over 1 to 2 hours. After the initial bolus, the patient's cardiovascular status is reevaluated and a second bolus may be administered. The association between rate of fluid resuscitation and development of cerebral edema is not convincing.15
After the initial fluid resuscitation, rehydration is continued with normal saline or Ringer lactate for 4 to 6 hours depending on state of hydration, serum sodium, and hemodynamic status of the patient.16 Subsequently, the remaining fluid deficit should be replaced slowly over 48 hours with a solution of tonicity greater or equal to half normal saline with added potassium chloride, potassium phosphate, or potassium acetate.16–18
In addition to assessment of dehydration, calculation of effective osmolarity can guide fluid and electrolyte therapy. In patients with extreme hyperosmolarity, some recommend continuing therapy with isotonic fluids until serum osmolarity decreases below 320 mOsm/L. The formula for serum osmolality is as follows (blood urea is not included because of low osmolality):
The absolute or relative lack of insulin and increase in counterregulatory hormones causes hyperglycemia and DKA. With initial fluid resuscitation, there is some decrease in blood glucose;20,21 however, normalization of blood glucose and suppression of lipolysis requires low-dose, continuous, intravenous insulin infusion.22 This provides slow, reliable, and titratable systemic absorption of insulin. An initial bolus of insulin is unnecessary and can increase the risk for cerebral edema.23,24 The starting dose is 0.1 U/kg/h and this should continue till resolution of DKA (pH >7.3, bicarbonate >15 mmol/L). On occasion, the infusion may have to be decreased to 0.05 U/kg/h when there is marked sensitivity to insulin or conversely it may need to be increased to 0.15 to 0.2 U/kg/h to lower the serum glucose and reverse the ketosis if the patient's serum glucose is unresponsive to the initial starting dose of 0.1 U/kg/h. The goal of therapy is to decrease the serum glucose by 75 to 100 mg/dL per hour. When the serum glucose reaches 250 mg/dL, 5% glucose is added to the infusing fluid. If the serum glucose is dropping precipitously, a glucose solution of ≥10% may need to be administered. It is dangerous to discontinue the insulin infusion completely if the patient has moderate-to-large serum ketones, since this can worsen the ketoacidosis.
During the initial resuscitation phase, the patient should be given nothing by mouth. As the patient improves, oral intake of water or ice may be provided and advanced to clear liquids as tolerated. When the serum glucose normalizes, metabolic acidosis improves and serum ketones decrease to trace, the insulin infusion is discontinued and switched to subcutaneous insulin and oral intake of liquids or solids. Subcutaneous insulin is administered 30 minutes prior to discontinuing the insulin infusion to allow for absorption of the subcutaneous insulin dose and hence prevent rebound hyperglycemia and ketoacidosis.
If low-dose IV insulin cannot be administered, then subcutaneous (SC) or intramuscular intermittent doses of short- or rapid-acting insulin analog may be used.25 The initial dose is 0.3 U/kg followed in 1 h by SC insulin lispro or as part at 0.1 U/kg every hour or 0.15 to 20 units/kg every 2 hours. If blood sugar falls to below 250 mg/dL before resolution of DKA, then start 5% glucose IV and continue as before. When DKA resolves and blood sugar is <250 mg/dL, reduce insulin to 0.05 U/kg to keep blood sugar at about 200 mg/dL.
Children with DKA are potassium-depleted with a deficit of 3 to 6 mEq/L/kg.13This loss is primarily intracellular potassium, which is drawn out of the cells by hypertonicity and in exchange for hydrogen ions and also by efflux during glycogenolysis and proteolysis. Potassium is also lost by vomiting and osmotic diuresis.26 Although there is total body depletion of potassium, the initial serum potassium can be normal, increased, or decreased.27 When the insulin infusion is started, potassium is driven back into the cells with decrease in serum levels.28 Hypokalemia is most common after several hours of rehydration. Both severe hypo- and hyperkalemia can cause life-threatening cardiac arrhythmias; therefore, it is essential that the patient's serum potassium be determined as soon as possible. Alternatively, an ECG can be used to determine if the child has evidence of hyper- or hypokalemia.11 Serum potassium levels should be checked every 2 to 4 hours. Replacement therapy is started once normal or low serum potassium is ensured and urine output is established. The usual dose of potassium is twice-daily maintenance (Table 76-1) or 3 to 4 mEq/kg per 24 hours provided as 40 mEq/L in the IV fluids, with half as potassium chloride or potassium acetate and half as potassium phosphate. The maximum recommended rate of IV potassium is usually 0.5 mEq/kg/h.
TABLE 76-1Loss of Fluids and Electrolytes in DKA and Maintenance Requirements in Normal Children ||Download (.pdf) TABLE 76-1 Loss of Fluids and Electrolytes in DKA and Maintenance Requirements in Normal Children
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Average Loss (kg)
24-h Maintenance Requirements (kg)
70 mL (30–100)
<10 kg: 100 mL/kg/24 h
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11–20 kg: 1000 mL + 50 mL/kg/24 h for each kg over 10
>20 kg: 1500 mL + 20 mL/kg/24 h for each kg over 2019
For children over 10 kg: body surface area can be used (1500 mL/m2/24 h)
6 mEq (5–13)
5 mEq (3–6)
4 mEq (3–9)
The osmotic diuresis usually induces sodium depletion in patients with DKA. In DKA, both the hyperglycemia and hyperlipidemia cause pseudohyponatremia. In addition, the osmotic movement of water into the extracellular space causes dilutional hyponatremia.29,30 Therefore, corrected serum sodium should be used for monitoring changes during therapy. The formula for corrected serum sodium is as follows:
The corrected serum sodium should not be allowed to drop faster than 10 to 12 mEq/L per 24 hours. If significant hyponatremia is present, the first 6 to 8 hours of correction should occur with normal saline. During the continuing resuscitation, sodium levels are monitored every 4 hours and as the glucose falls, the reported level of serum sodium should increase. A fall in serum sodium during continued fluid resuscitation may indicate excess accumulation of free water and may be a risk factor for the development of cerebral edema. If this happens, the sodium content of the fluid may need to be increased.31,32
Depletion of phosphate during DKA occurs as a result of osmotic diuresis.12,13 Clinically significant hypophosphatemia can cause impaired cardiac function and insulin resistance. Usually, after starting insulin, serum phosphate decreases and clinically significant hypophosphatemia can occur if food is not started after 24 hours of fluid therapy.12,13 Prospective studies have not shown clinical benefit from phosphate replacement.33,34 Supplementation is indicated if the serum level is <2 mEq/L and can be administered with potassium replacement as potassium phosphate alone or with potassium chloride. During phosphate replacement, monitor serum calcium for development of hypocalcemia.35,36
The acidosis that is fundamental to DKA is usually reversible with fluid resuscitation and insulin therapy. Controlled trials have shown no clinical benefit from bicarbonate administration.37,38 Bicarbonate causes paradoxical CNS acidosis, rapid onset hypokalemia, and increase in serum osmolality.39,40 Despite these adverse effects and lack of clinical benefit, its cautious use may be considered in patients with severe acidosis (pH <6.9 or serum bicarbonate <5 mEq/L) and hyperkalemia, which are associated with insulin resistance and cardiac arrhythmias. If bicarbonate is considered necessary, administer 1 to 2 mEq/kg over 60 minutes.26
Complications of DKA therapy include the following: inadequate rehydration, hypoglycemia, hypokalemia, hyperchloremic acidosis, and cerebral edema. Hypoglycemia is common, especially in young diabetics, who tend to be extremely sensitive to insulin and labile. Adjusting the insulin infusion and providing supplemental intravenous and oral glucose according to the principles outlined above will successfully correct this.
Hypokalemia occurs within several hours of initiation of therapy and can lead to arrhythmias. Therefore, cardiac monitoring is essential during therapy for DKA. Treatment is with potassium replacement, as discussed above.
Cerebral edema occurs in 0.5% to 0.9% of DKA patients and the mortality rate is 21% to 24%.41,42 The predisposing factors are younger age, new onset diabetes, and longer duration of symptoms.43,44 Other risk factors that may be identified at diagnosis or during therapy include administration of insulin in the first hour of fluid replacement, high fluid volume replacement within the first 4 hours,24 severe acidosis, and hypocarbia at presentation after adjusting for acidosis,42 high serum urea nitrogen, attenuated rise of corrected serum sodium during treatment,31 and the use of bicarbonate.42
The warning signs of cerebral edema are as follows: headache and slowing of the heart rate; change in neurological status (restlessness, irritability, increased drowsiness, and incontinence); focal neurological signs (cranial nerve palsy), rising blood pressure; decrease in O2 saturation.
Diagnostic criteria for use in the bedside evaluation of neurological state for the early diagnosis of cerebral edema include the following45:
Abnormal motor or verbal response to pain
Decorticate or decerebrate posture
Cranial nerve palsy (III, IV, and VI)
Abnormal respiratory pattern (grunting, tachypnea, Cheyne-Stokes breathing, and apnea)
Altered mentation or fluctuating level of consciousness
Sustained deceleration of the heart rate
Age inappropriate incontinence
One diagnostic criterion and two major criteria or one major and two minor criteria have a sensitivity of 92% for the diagnosis of cerebral edema in DKA.
Treatment of Cerebral Edema
Treatment of cerebral edema includes fluid restriction by one-third, the use of IV mannitol 0.5 to 1 g/kg over 20 minutes to be repeated if there is no response in 30 minutes46,47 and hypertonic saline 3%, 5 to 10 mL/kg over 30 minutes.48 Elevate the head of the bed. Consider hyperventilation to maintain a PCO2 <22 mm Hg, although aggressive hyperventilation may be associated with poor outcome.49 After treatment of cerebral edema, a CT scan should be performed to rule out other causes of neurological deterioration such as thrombosis or hemorrhage.
All patients presenting with DKA as the initial presentation of diabetes are hospitalized at a center where a physician trained in management of pediatric DKA and/or a pediatric endocrinologist are available for consultation. Patients with severe acidosis are best treated in a pediatric intensive care unit for reasons of close monitoring and need for repeated blood sampling.
Children with prolonged illness, decreased level of consciousness, and those at increased risk for cerebral edema at presentation must be admitted to a pediatric intensive care unit for management.8,50 Occasionally, children with recurrent and mild DKA, with good family support, may be treated in the emergency department and discharged and followed up as an outpatient in consultation with their endocrinologist.8