Pediatric Diabetic Ketoacidosis
- Article Author:
- Noha EL-Mohandes
- Article Editor:
- Martin Huecker
- Updated:
- 10/15/2020 8:43:24 AM
- For CME on this topic:
- Pediatric Diabetic Ketoacidosis CME
- PubMed Link:
- Pediatric Diabetic Ketoacidosis
Introduction
Diabetic ketoacidosis (DKA) is a serious complication of relative insulin deficiency affecting primarily type-1 diabetes mellitus (DM). DKA can occur in type-2 DM when insulin levels fall far behind the body’s needs. DKA is so named due to high levels of water-soluble ketone bodies (KBs), leading to an acidotic physiologic state.[1][2]
Produced by the liver during fatty acid metabolism, KBs can be utilized by the brain, cardiac and skeletal muscle tissues as a fuel when the body is deficient in or cannot effectively import glucose.[3][4]
Etiology
Ketone bodies, while always present in blood, increase to pathologic levels when the body cannot utilize glucose: low blood glucose levels during fasting, starvation, vigorous exercise, or secondary to a defect in the insulin production. In type-2 DM, insulin production may be normal but below the level needed to shunt glucose into cells.[5][6]
Most body fat is stored as triglyceride (TG). When the body glucose storage sites are depleted, the liver dismantles the TG into three fatty acids (FAs) and a glycerol molecule. The FAs are used as a source of energy, while glycerol converts to glucose. In the presence of enough insulin, this glucose will be consumed by the different body tissues as a source of energy. Typically, this is what occurs in the case of starvation, fasting, and vigorous exercise. In the absence of insulin, the body cannot utilize the glucose released from the glycerol metabolism unused glucose rises to dangerous levels, with spillover into the urine.
When the blood glucose is low or cannot be used due to lack of insulin, ketones are the major source of energy for the brain. The brain does not have any fuel stores and has no other non-glucose-derived energy sources.
Muscles are different from the brain in that they have a large store of glycogen. Approximately 70% of the total body glycogen is stored in muscles and can be converted, when needed, to glucose in a process called glycogenolysis.
Epidemiology
Ketone bodies, while always present in blood, increase to pathologic levels when the body cannot utilize glucose: low blood glucose levels during fasting, starvation, vigorous exercise, or secondary to a defect in the insulin production. In type-2 DM, insulin production may be normal but below the level needed to shunt glucose into cells.[7]
Most body fat is stored as triglyceride (TG). When the body glucose storage sites are depleted, the liver dismantles the TG into three fatty acids (FAs) and a glycerol molecule. The FAs are used as a source of energy, while glycerol converts to glucose. In the presence of enough insulin, this glucose will be consumed by the different body tissues as a source of energy. This is typically what occurs in the case of starvation, fasting & vigorous exercise. In the absence of insulin, the body cannot utilize the glucose released from the glycerol metabolism unused glucose rises to dangerous levels, with spillover into the urine.
When the blood glucose is low or cannot be used due to lack of insulin, ketones are the major source of energy for the brain. The brain does not have any fuel stores and has no other non-glucose-derived energy sources.
Muscles are different from the brain in that they have a large store of glycogen. Approximately 70% of the total body glycogen is stored in muscles and can be converted, when needed, to glucose in a process called glycogenolysis.
Pathophysiology
The physiologic disturbance in DKA is due to several interrelated processes:
- Hyperglycemia, which leads to serum hyperosmolarity and osmotic diuresis.
- Glucosuria is the precursor to osmotic diuresis, hyperosmolarity, and dehydration. Free water losses can be substantial, with decompensation and impaired renal function.
- Ketones accumulate and cause metabolic acidosis. The body tries to compensate by hyperventilation to eliminate carbon dioxide.
- A transfer of potassium from the intracellular to the extracellular space in a switch with hydrogen ions that accumulate.extracellularly in acidosis causes blood potassium loss. Much of the shifted extracellular potassium is eliminated in urine, creating total body hypokalemia.
Histopathology
DM is a chronic illness. Episodes of DKA recur in poorly controlled patients. It is difficult to characterize the precise effect of these repeated episodes, but clearly, a poor HbA1c predicts micro-vascular and macro-vascular complications of diabetes.
In up to 1% of DKA patients, cerebral edema occurs when rapid osmolar shifts occur. Look for signs of sudden increased intracranial pressure: bradycardia, headache, papilledema, irritability, rising blood pressure and decreasing Glasgow coma scale (GCS). Cerebral edema mortally approaches 25%. Survivors suffer significant neurological morbidity.
Toxicokinetics
Three ketone molecules predominate in human physiology: beta-hydroxybutyrate (BHB), acetoacetate, and acetone.
Beta-hydroxybutyrate represents the most precise approach to measuring the severity of DKA, making up roughly 75% of ketones in DKA. Whole blood ketone test strips and serum laboratory tests quantify BHB. Most urine strips test for acetoacetate and acetone.
BHB can be confirmed in the blood up to 24 hours before acetone and acetoacetate appear in the urine, as BHB is converted into these molecules. Therefore, urine ketone testing can increase even after proper DKA treatment ceases the formation of BHB. Acetone, which is stored in adipose tissue, slowly releases in the blood and is excreted in the urine.
Serum ketone levels:
- Less than 0.6 mmol/L=normal
- Between 0.6 mmol/L to 1.5 mmol/L=low to moderate
- Between 1.6 mmol/L to 3.0 mmol/L=high with a risk of developing DKA
- Over 3.0 mmol/L: Likely DKA, requires immediate emergency treatment.
Urine ketone strip levels:
- Having no ketones in the urine is normal.
- One plus (+) ketones in urine ketones strips are equal to low/moderate blood ketones levels.
- Two plus (++) ketones in urine are equal to a high blood level of ketones.
- Three plus (+++) ketones in urine are equal to severe blood ketones level.
- False positive ketones in urine can occur with the intake of some medications like captopril and valproate. False negative ketones in urine can occur with the expired urine strips or delayed testing of urine. As above, blood ketone levels should be the first choice to monitor the treatment If blood testing is not available, urine ketones levels can help make the diagnosis but are of low yield in monitoring response to treatment.
History and Physical
Ill patients with type-1 DM should be evaluated for DKA. DKA could cause the critical symptoms or occur secondarily to another illness. In newly diagnosed diabetic children, there may be a history of polydipsia, polyuria, weight loss, fatigue, lack of concentration, poor school performance, or recurrent infection. Abdominal pain, nausea, and vomiting are also common; some children in the first DKA episode may be misdiagnosed as viral gastroenteritis.
The metabolic acidosis will lead to rapid, deep breathing (Kussmaul respirations). The breath may have a fruity odor due to respiratory acetone elimination. Investigate for underlying causes of the DKA exacerbation: infection, trauma, among others. DKA patients will have an ileus and have vague, diffuse abdominal pain. Dehydration, thirst, and polyuria are common at the time of presentation due to glucosuria and osmotic diuresis.
Evaluation
DKA is definitively diagnosed by blood testing, with metabolic acidosis and typically hyperglycemia. Ketone testing can be helpful but is not necessary. Low serum bicarbonate (below 18 mmol/L) with elevated anion gap (AG) will be present and can obviate the need for blood gas testing. The anion gap is calculated as follows: (Na+K)-(Cl+HCO3). Ketoacids (primarily BHB) are unmeasured ions, leading to the “gap” in anions. The AG is normally between 6 mEq/L to 12 mEq/L, with levels above 15 typically present in DKA.[8][9][10]
BHB is usually above 3 mmol/L in these patients.
If blood gas testing is performed, venous blood will give enough information. A pH below 7.2 is very concerning.
Blood glucose is usually elevated above generally above 200 mg/dL (11 mmol/l) and may be above 1000 mg/dL. The pediatric patient can be in DKA with very slight elevations in blood glucose.
Urinary ketone levels over “three plus” are used to diagnose but not to monitor the treatment.
Usually, blood osmolality is elevated in DKA. Blood osmolality = 2 x (Na+K) + urea + glucose (all in mmol/L). Normal serum range is between 285 mOsm/L to -295 mOsm/L. Calculated plasma osmolality can greatly minimize the true value of DKA. The osmolar gap is the lab measured osmolality minus the calculated osmolality. When the gap exceeds 10, it presents the presence of an excess osmotically active substance as blood glucose.
Treatment / Management
Treatment for DKA begins with ABCs and fluid resuscitation.Insulin therapy, usually by continuous infusion, can begin once the patient is stabilized.[1][11][12][13]
- General resuscitation (ABC): Secure the airway with 100% oxygen and consider intubation if needed. Insert a nasogastric tube and urinary catheter for comatose patients. Reliable intravenous (IV) access (preferably 2) should be obtained, one for insulin treatment and the other for blood samples and other medications
- Full clinical assessment: Complete history and physical exam for signs of infection or other precipitating cause.
- A precise weight of the patient for calculation of insulin and another medication dosing
- IV fluids: to treat shock, acidosis, and dehydration. Strict “ins and outs” fluid balance assessments should be kept
- Check potassium regularly (and other electrolytes) to avoid hypokalaemia. Place patients on the cardiac monitor to observe early changes in the T-waves for early intervention. Most sources recommend obtaining a serum potassium before any insulin dosing and replacing potassium if below 4
- Short-acting or Regular insulin should be administered as a continuous IV infusion to treat hyperglycemia and clear ketonemia. Bolus dosing of insulin has NO role in DKA treatment in children
- High-level nursing and frequent clinical assessments; biochemical blood markers every two hours
- Once acidosis is resolved, anion gap has closed, and the patient is improving clinically, diet can be reintroduced, and insulin can be switched to subcutaneous injection
- Prevention: Determine the cause of the acute DKA episode and work closely with the child and caregivers on a regime.
Differential Diagnosis
- Asthma
- Hypokalemia
- Metabolic acidosis
- Pneumonia
- Respiratory acidosis
- Respiratory distress syndrome
- Salicylate toxicity
- Acute abdomen
- Gastroenteritis
Pearls and Other Issues
Recurrent DKA is a particular problem in adolescents and may be fatal. Early help is advised as soon as the DKA diagnosis is made.
It may be precipitated by:
- Poor compliance with insulin therapy either in the frequency of boluses injection or the calculated dose
- Infections
- Alcohol and substances misuse
- Stress, For example, exams time
- Continuous lifestyle changes, for example, traveling
- Psychiatric disorders including the eating disorder and psychological difficulties
Enhancing Healthcare Team Outcomes
Pediatric diabetic ketoacidosis is a life-threatening disorder that is best managed by an interprofessional team that includes an emergency nurse, an emergency department physician, endocrinologist, an infectious disease expert, pediatrician, and intensivist. These individuals are best managed in the ICU and monitored by nurses. Once hydration and correction of the acidosis have taken place, the cause of the ketoacidosis must be sought. The key is to prevent this disorder from recurring. The primary caregiver and the diabetic nurse must work closely with the caregiver to ensure that the patient is compliant with the insulin.
The outlook for pediatric patients with DKA is guarded. [14][8][15](Level V)