Definition of DKA

DKA occurs when there is a disruption in the homeostatic balance between insulin and counter-regulatory hormones secondary to a deficiency in circulating insulin and an increase in levels of catecholamines, glucagon, growth hormone, and cortisol. The result is a state of hyperglycemia, hyperosmolarity, increased lipolysis, ketonemia, and metabolic acidosis secondary to increased ketone body production. Osmotic diuresis, dehydration, and loss of electrolytes are further consequences of the hyperglycemia and acidosis.

The major biochemical diagnostic criteria for DKA include hyperglycemia (blood glucose: >11 mmol/L [approximately 200 mg/dL]) with a venous pH less than 7.3 or bicarbonate less than 15 mmol/L. There are associated minor criteria including glycosuria, ketonuria, and ketonemia. DKA is classified further by the degree of the acidosis:

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  Mild (venous pH: <7.30; HCO3: <15 mmol/L)

  
  
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  Moderate (pH: <7.2; HCO3: <10 mmol/L)

  
  
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  Severe (pH: <7.1; HCO3: <5 mmol/L)

Clinical features of DKA include dehydration, Kussmaul breathing, severe abdominal pain, nausea, and vomiting; additionally, patients may have fever if infection is also present.

Frequency of DKA

The more prevalent type I diabetes mellitus (TIDM) is in a given region, the less likely it is for DKA to be present at diagnosis. It is more common to see DKA at the onset of diabetes in children less than 4 years of age, children who do not have a first-degree relative with TIDM, and children from families of lower socioeconomic status or without ready access to medical care. Certain medications including glucocorticoids, atypical antipsychotics, and Diazoxide have been indicted as causative agents of DKA in patients not previously diagnosed with TIDM.

Factors such as poor metabolic control, a history of DKA, poor family structure, a psychiatric history, or being a peripubertal or adolescent female increase the risk of DKA in patients with TIDM. The most common reason for the occurrence of DKA (75% of cases) in these patients is either incorrect insulin dosing or absence of insulin. Other causes include insufficient amounts of insulin during stress or illness to balance counter-regulatory hormones and inappropriate cessation of insulin pump therapy.

Cerebral Edema

The first signs of cerebral edema (CE) can be subtle and nonspecific and include headache, mental status changes, bradycardia, and hypertension. Studies have shown that CE usually occurs 4 to 12 hours after management of DKA has begun, but it can occur any time before or during treatment. The incidence of CE is up to 1% in all cases of DKA.

Increased risk for CE is seen in patients who present with DKA at diagnosis, are younger, and have symptoms of DKA for a longer amount of time. Other risk factors include degree of acidosis at presentation, greater hypocapnia at presentation after adjusting for the severity of acidosis, bicarbonate treatment during DKA, elevated serum urea nitrogen at presentation, and a slower rise in measured serum sodium concentrations during treatment of DKA. Neither the severity of hyperglycemia at presentation of DKA nor the concentration of sodium in intravenous fluids has been shown to increase the risk of cerebral edema.

Management of DKA

Mild cases of DKA, in which patients have hyperglycemia and ketosis, but can tolerate oral (PO) and are not dehydrated, do not require inpatient or emergency room management. Patients who are vomiting, cannot tolerate fluids by mouth, or are dehydrated should be evaluated in an emergency room or inpatient setting. Admission to an ICU should be advised in children with severe DKA (prolonged duration of symptoms, mental status changes, or vascular compromise) or patients who are at increased risk of cerebral edema.

The initial assessment of DKA requires a detailed history and physical examination. Degree of dehydration should be assessed using weight, pulse, blood pressure and respiratory effort, capillary refill, and skin turgor. Samples for measurement of glucose, electrolytes, osmolality, venous or arterial pH and pCO2, hemoglobin and hematocrit, and HbA1c should be obtained, as well as a urinalysis for ketones.

Management of DKA in the ICU should include hourly measurement of the vital signs including strict fluid input and output, capillary blood glucose, and neurologic examinations (looking for Cushing’s triad and other signs of cerebral edema). Every 2 to 4 hours, blood gases and chemistries should be done to evaluate electrolytes, serum urea nitrogen (BUN), hematocrit, and blood glucose. More frequent testing is warranted if the patient is critically ill. An electrocardiogram should be considered if potassium measurement is delayed.

Hydration Status and Fluid Replacement

Hemodynamic instability and shock are rare in pediatric DKA. Chemical measurements, as a means of assessing fluid deficit, can be unreliable at diagnosis. The extracellular fluid has higher osmolality and fluid shifts from the intracellular to extracellular compartments. Therefore, sodium measured on a blood chemistry is usually lower than the total body sodium. The effective osmolality at the time of presentation is usually in the range of 300 to 350 mOsm/L. Hemoconcentration leads to an increased BUN and hematocrit and may help to differentiate severe extracellular fluid (ECF) contraction from true hyponatremia.

Goals of therapy in DKA include replacement of diminished circulatory volume, repletion of electrolytes, recovery of the glomerular filtration rate (GFR) to further eliminate glucose and ketones from the circulation, and avoidance of complications including cerebral edema. Slower correction of overall fluid deficit with isotonic or near-isotonic fluids can lead to quicker resolution of acidosis. The risk of using large amounts of normal saline is hyperchloremic metabolic acidosis. There is no evidence supporting the use of colloids over crystalloids for DKA therapy.

Fluids given to the child before assessment should be factored into calculation of deficit. Initial intravenous fluid administration should begin immediately with an isotonic solution, which can be given if needed in a 10 to 20 cc/kg bolus over 1 to 2 hours. The remainder replacement intravenous fluid should be given evenly over at least 48 hours. Subsequent fluid management should be with a solution with a tonicity greater than or equal to 0.45% saline. In addition to clinical assessment of dehydration, calculation of effective osmolality may be valuable to guide fluid and electrolyte therapy. Because the severity of dehydration may be difficult to determine and can be overestimated, fluid infusion should not exceed a rate of 1.5 to 2 times the usual daily requirement based on age, weight, or body surface area. Urinary losses should not be added to the calculation of replacement fluids.

Insulin

After the fluid deficit and electrolyte losses are calculated, low-dose intravenous insulin administration is standard of care. The goal of insulin therapy is to inhibit lipolysis and ketogenesis and decrease the blood glucose levels. A bolus of insulin is not necessary, and its use is controversial. The dose of insulin should be maintained at 0.1 U/kg/h until resolution of ketoacidosis (pH: >7.30; HCO3: >15 mmol/L) or until the anion gap is closed. If the patient has hypoglycemia on maximum amounts of intravenous dextrose, then the insulin drip should be lowered, but not less than 0.05 U/kg/h.

To prevent hypoglycemia, glucose should be added to the intravenous fluid when the plasma glucose falls to approximately 14 to 17 mmol/L (250 to 300 mg/dL), because the resolution of acidemia usually takes longer than the normalization of blood glucose. Five percent glucose can be used initially and then slowly increased to maintain euglycemia on the insulin drip. Reassessment of the patient, review of insulin therapy, and consideration of other possible causes of impaired response to insulin should be considered (eg, infection, errors in insulin preparation, or adhesion of insulin to tubing with very dilute solutions) if biochemical parameters of ketoacidosis do not improve. In the rare event that intravenous insulin cannot be given, insulin may be administered subcutaneously or intramuscularly every hour at the same dose.

Electrolyte Replacement

In DKA, potassium is lost from the intracellular compartment as a result of insulin deficiency, hypertonicity, and the exchange of hydrogen ions within the cell. Potassium also is lost secondary to vomiting and osmotic diuresis. Therefore, serum levels of potassium are not reliable in the initial work-up of DKA. Once insulin is given, potassium will move from the extracellular to intracellular space, and serum levels will decrease. Repletion of potassium is necessary and should be started once the serum levels are no longer elevated and the patient has urinated.

In DKA, phosphate deficit also occurs as a result of osmotic diuresis and movement across the cell. Treatment with insulin results in movement of phosphate back into the intracellular space and a subsequent drop in serum phosphate. Although studies have not shown significant clinical benefit from phosphate repletion in DKA and its use remains controversial, potassium phosphate may be used safely together with potassium chloride to avoid hyperchloremia. Calcium levels should be monitored closely.

Acidosis

Fluid replacement and insulin are the first-line agents for treating acidosis. Insulin prevents ketoacid production and breaks it down into bicarbonate. Fluid replacement improves tissue perfusion and increases GFR to aid in acid excretion.

The use of bicarbonate in treating DKA remains controversial. Some studies have shown that bicarbonate may worsen electrolyte abnormalities in DKA by contributing to hypokalemia and hypernatremia via increased sodium load. Bicarbonate also can increase the synthesis of ketones in the liver and thereby slow down the time to recovery from ketoacidosis. Still, a subset of patients with severe DKA (arterial pH: <6.9) who have impaired cardiac contractility, peripheral vasodilatation, poor tissue perfusion, and life-threatening hyperkalemia may benefit from judicious use of bicarbonate.

Treatment of Cerebral Edema

The clinician should have high suspicion for CE in patients with DKA, and therapy should commence immediately once diagnosed. The head of the bed should be elevated. Intravenous fluids should be reduced, and intravenous mannitol should be given. If Mannitol is not available, 3% hypertonic saline may be used instead. Mechanical ventilation may be required if the patient’s respiratory status is compromised. Studies have shown poor outcomes in patients with CE associated with DKA who were aggressively ventilated (pCO2 <22 mm Hg). The role of glucocorticoids in treatment of CE in DKA has not been supported.

Prevention of DKA

Education and early detection remain the ultimate tools in prevention. Genetic and immunologic diagnostic testing in patients at higher risk for T1DM has been shown to decrease the occurrence of DKA at onset of diabetes. In patients with TIDM, studies have shown that comprehensive health care and education including plans for sick day management and continuous subcutaneous insulin pump malfunction can help to decrease the incidence of DKA.

Definition

ISS was defined as

“a height more than two standard deviation scores (SDS) below the corresponding mean for a given age, sex, and population group without evidence of systemic, endocrine, nutritional, or chromosomal abnormalities”

This includes constitutional delay of growth and puberty (CDGP) and familial short stature. Children born small for gestational age, children with syndromes involving short stature, and children with chronic medical conditions that interfere with growth should be excluded from this definition.

ISS can be subdivided into two groups based on the midparental height (calculated by average of parents’ heights + 6.5 cm for boys/- 6.5 cm for girls.) One group is children whose adult height is about the same as the midparental height, and the other is children whose adult height is below the midparental height.

Assessment of the Short Child

Each evaluation of a short child should begin with a comprehensive history:

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  Birth history (including in utero events, anthropomorphic data at birth, amniocentesis, gestational age, and complications)

  
  
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  Medical history including hospitalizations, surgeries, medications, chronic diseases, dietary history, developmental history including dentition, which can parallel bone maturation

  
  
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  Family history focusing on stature, onset of puberty, and chronic diseases of first- and second-degree family members; consanguinity should be documented

  
  
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  Pubertal history of the patient

  
  
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  Prior growth point or curves

The physical examination should include the general appearance, any dysmorphic features, and body disproportions. A length should be obtained in all children under 3 years of age with a recumbent stadiometer. A standing stadiometer can be used in cooperative children over 3 years of age. Arm span, sitting height or upper-to-lower segment ratios, body mass index (BMI), and for children younger than 4 years measurement of the head circumference should be included. Pubertal status using Tanner staging should be documented.

Definition

ISS was defined as

“a height more than two standard deviation scores (SDS) below the corresponding mean for a given age, sex, and population group without evidence of systemic, endocrine, nutritional, or chromosomal abnormalities”

This includes constitutional delay of growth and puberty (CDGP) and familial short stature. Children born small for gestational age, children with syndromes involving short stature, and children with chronic medical conditions that interfere with growth should be excluded from this definition.

ISS can be subdivided into two groups based on the midparental height (calculated by average of parents’ heights + 6.5 cm for boys/- 6.5 cm for girls.) One group is children whose adult height is about the same as the midparental height, and the other is children whose adult height is below the midparental height.

Assessment of the Short Child

Each evaluation of a short child should begin with a comprehensive history:

• 
  

  Birth history (including in utero events, anthropomorphic data at birth, amniocentesis, gestational age, and complications)

  
  
• 
  

  Medical history including hospitalizations, surgeries, medications, chronic diseases, dietary history, developmental history including dentition, which can parallel bone maturation

  
  
• 
  

  Family history focusing on stature, onset of puberty, and chronic diseases of first- and second-degree family members; consanguinity should be documented

  
  
• 
  

  Pubertal history of the patient

  
  
• 
  

  Prior growth point or curves

The physical examination should include the general appearance, any dysmorphic features, and body disproportions. A length should be obtained in all children under 3 years of age with a recumbent stadiometer. A standing stadiometer can be used in cooperative children over 3 years of age. Arm span, sitting height or upper-to-lower segment ratios, body mass index (BMI), and for children younger than 4 years measurement of the head circumference should be included. Pubertal status using Tanner staging should be documented.