Chapter 79. Hypoglycemia and Metabolic Emergencies in Infants and Children

Hypoglycemia in children may be due to inadequate oral intake, excess insulin, low levels of hyperglycemic hormones (cortisol), inborn errors of metabolism, or systemic infection. Prompt recognition and treatment of hypoglycemia is essential to avoid potentially severe and permanent neurologic injury and bedside glucose testing should be considered absolutely essential in any infant or child with altered mental status.

Clinical Features

Neonates and infants with hypoglycemia typically present with altered mental status and nonspecific symptoms such as poor feeding, an abnormal or high-pitched cry, temperature instability, and irritability or lethargy. Hypoglycemic children may manifest symptoms related to adrenergic hormone release including tachycardia, diaphoresis, tremors, anxiety, irritability, and tachypnea. Severe hypoglycemia may result in apnea or seizures. Hypoglycemia often accompanies critical illness (sepsis) and the features of that illness may dominate the clinical picture, thereby masking the signs of hypoglycemia.

Diagnosis and Differential

Hypoglycemia is defined as a plasma glucose concentration less than 45 milligrams/dL in symptomatic children and less than 35 milligrams/dL in asymptomatic neonates. Bedside glucose testing is the most important diagnostic test in any neonate or infant who is critically ill or has altered mental status. Urine testing for ketones is important as ketonuria is associated with ketotic hypoglycemia, adrenal insufficiency and other inborn errors of metabolism. Absent urine ketones are associated with hyperinsulinemic states such as nesidioblastosis, infants of a diabetic mother, as well as disorders of fatty acid oxidation and mitochondria.

Emergency Department Care and Disposition

1. For neonates administer 5 mL/kg of 10% dextrose IV/IO/PO/NG. Treat infants with the same dose of 10% dextrose, or 2 mL/kg of 25% dextrose IV/IO/PO/NG. Give older children 2 mL/kg of 25% dextrose IV/IO/PO/NG.

2. Administer maintenance dextrose for persistent hypoglycemia using 10% dextrose at 1.5 times maintenance.

3. When intravenous access is not immediately available, consider glucagon 0.03 milligram/kilogram IM.

4. When standard therapy fails, give hydrocortisone 25 milligrams IV for neonates and infants, 50 milligrams for toddlers and smaller school aged children and 100 milligrams for everyone else. Steroids should be given early in patients with hypopituitarism and adrenal insufficiency.

Inborn errors of metabolism are challenging childhood disorders representing a broad spectrum of diseases with nonspecific signs and symptoms. Delay in accurate diagnosis and treatment can lead to significant morbidity and mortality. Despite the myriad etiologies, the principles of initial ED diagnosis and management are relatively simple. The sudden acute deterioration of a healthy neonate should always prompt consideration of metabolic disease, and making a definitive diagnosis is less important than having a high index of suspicion and implementing supportive care.

Clinical Features

Vomiting, altered mental status, and poor feeding are the most common features of metabolic emergencies. Seizures may accompany some metabolic crises. Tachypnea due to metabolic acidosis and tachycardia from dehydration as well as hypotension due to hypovolemia or adrenal insufficiency may be noted. Rarely, some metabolic disorders may be associated with characteristic body or urine odors or other phenotypic stigmata (eg, ambiguous genitalia and hyperpigmentation in congenital adrenal hyperplasia, as discussed separately below).

Diagnosis and Differential

Screening laboratories for suspected inborn errors of metabolism include a bedside glucose, urine for ketones, a blood gas analysis for metabolic acidosis, serum ammonia and calcium. Figure 79-1 details the diagnostic evaluation recommended in the emergency department. Additional laboratory tests for definitive diagnosis that should be considered based on initial screening results include liver function tests, CBC, aldolase, creatine kinase, serum amino acids and acylcarnitine profile, urine organic acids, and reducing substances. The differential diagnosis of shock in the neonate includes sepsis, congenital heart defects, and abdominal catastrophes.

Emergency Department Care and Disposition

Despite the diverse etiology and complexity of inborn errors of metabolism, ED resuscitation and stabilization of patients with these disorders is relatively simple. Neonates, infants, and children presenting in metabolic crisis, regardless of cause, show some combination of dehydration, metabolic acidosis, and encephalopathy, which must be immediately addressed. The goals of treatment are, to improve circulatory status by restoring circulatory volume, provide energy substrate to halt catabolism, remove the inciting metabolic substrate (formula or breast milk), and help eliminate toxic metabolites.

1. Restore circulation with 0.9% saline boluses of 20 mL/kg.

2. Make patients NPO, and correct hypoglycemia as above with D10 in neonates and infants or D25 in children.

3. Begin 10% dextrose infusion at twice maintenance rate.

4. Consider broad spectrum antibiotics.

5. Specific metabolic treatments are guided by the underlying defect and should be determined in consultation with a metabolic specialist. Substrates to facilitate shunting of metabolic pathways or hemodyalisis may be needed.

Patients with a newly diagnosed or suspected metabolic disorder and those who are dehydrated or otherwise decompensated require admission for dextrose and specific treatment. Transfer to a pediatric hospital may be required.

Congenital adrenal hyperplasia results from deficiency in 1 of the enzymes involved in the production of cortisol which leads to decreased cortisol levels sometimes accompanied by mineralocorticoid deficiency (“salt wasting syndrome”). Steroid precursors may be shunted to androgen production with virilization of females.

Clinical Features

Patients with salt-wasting adrenal hyperplasia typically present in the second to fifth week of life with nonspecific symptoms including shock, vomiting, lethargy, irritability, and poor feeding. On examination, females may have clitoromegaly and males may have a small penis or hypospadias. Hyperpigmentation may be noted on axillae and around the nipples.

Diagnosis and Differential

The most important laboratories include bedside glucose and electrolytes as hyponatremia and hyperkalemia are often present and suggest the diagnosis. Serum potassium levels of 6 to 12 mEq/kg are not unusual but are rarely associated with ECG abnormalities. Definitive diagnosis depends on analysis of blood hormone levels. If possible, blood should be obtained for analysis before treatment with exogenous steroids; however, treatment should not be delayed in the critically ill neonate. The differential diagnosis includes sepsis, congenital heart disease, and other inborn errors of metabolism.

Emergency Department Care and Disposition

1. Administer 0.9% saline boluses of 20 mL/kg IV/IO.

2. Treat hypoglycemia as above.

3. Administer hydrocortisone IV/IO/IM: 25 milligrams for neonates, 50 milligrams for toddlers and 100 milligrams for older children.

4. Treat hyperkalemia with calcium gluconate 100 milligrams/kilogram IV and bicarbonate 1 mEq/kilogram IV. Insulin should be avoided as it may cause profound hypoglycemia.

Neonates with adrenal crisis from adrenal hyperplasia require hospitalization. Those with a known diagnosis of adrenal hyperplasia who have normal vital signs and are able to tolerate oral intake may be discharged home after administration of hydrocortisone as above with instructions to triple their usual home dose of steroid until fever, vomiting, or diarrhea resolve when next-day follow-up can be assured.