Hypoglycemia is a common, treatable, and often preventable cause of encephalopathy in children. Glucose is a critical substrate for energy production in the brain; when its availability is interrupted, significant CNS dysfunction results. The signs and symptoms of CNS dysfunction include convulsions and coma, but they may be less severe, involving confusion, irritability, listlessness, headache, eye rolling, and agitation. Night terrors also may accompany hypoglycemia in some patients. In addition, affected children may evidence hunger, tachycardia, or sweating, the last being especially noticeable on the brow and hands, which may be cold and clammy to the touch. Although the heart depends on fatty acids for its primary energy supply, glucose represents an important substrate; therefore, cardiomegaly with or without overt cardiac failure may be associated with hypoglycemia. Symptoms in neonates and young infants may include poor feeding, a weak or high-pitched cry, limpness, cyanosis, and vomiting. Signs and symptoms should resolve rapidly with normalization of the blood glucose level, unless the episode has been sufficiently profound or prolonged to result in dysfunction extending beyond the hypoglycemic episode. In such cases, the possibility of developing long-term sequelae is significant.

Hypoglycemia has been defined classically as a whole-blood glucose level of less than 20 mg/dL or a serum or plasma glucose level of less than 25 mg/dL in preterm or low-birth-weight infants during the first week of life; a blood glucose level of less than 30 mg/dL or a serum glucose level of less than 35 mg/dL in full-sized or term neonates from birth to 72 hours; and a blood glucose level of less than 40 mg/dL or a serum glucose level of less than 46 mg/dL thereafter. Other physicians suggest that these definitions represent population norms rather than physiologically acceptable glucose concentrations and that a blood glucose level of less than 40 mg/dL or a serum glucose level of less than 45 to 50 mg/dL should be considered hypoglycemia regardless of the age of the individual. The differential diagnosis of hypoglycemia is extensive, but the history and clinical assessment can be helpful in narrowing the possibilities (Table 412.1). Specific diagnostic testing is recommended for these disorders to tailor management, prevent recurrences, and treat the hypoglycemia effectively.

The primary complication of hypoglycemia is irreversible CNS damage. The goal of diagnosis and treatment is to prevent acute and chronic hypoglycemia, with its attendant CNS compromise. A severe acute insult may result in respiratory compromise and death from status epilepticus or coma. The clinician must carry out the diagnostic evaluation with care and discretion so as to prevent hypoglycemia. For example, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency may be diagnosed by the measurement of octanoylglycine and other organic acids using tandem mass spectrometry (MS/MS) (e.g., as part of the newborn screen) without risk to the patient, whereas a fast or a fat challenge may lead to significant hypoglycemia and the risk of developing sequelae.

To avoid repeated hypoglycemic episodes, if a definitive diagnosis has not been made, and the risk of spontaneous or challenge-induced hypoglycemia exists, the diagnostic plan should be worked out well ahead of time so that the necessary information may be obtained if the child becomes symptomatic. A secure intravenous line should be in place in any hospitalized patient who is at risk for developing iatrogenic or spontaneous hypoglycemia, and the blood glucose should be measured at an appropriate frequency to attempt to anticipate and prevent symptomatic episodes and their sequelae.

The treatment of an acute hypoglycemic episode involves the rapid restoration of normoglycemia to supply this substrate to the CNS. If venous access is readily available, the most rapid and effective therapy is the administration of intravenous glucose delivered at a rate of 0.5 to 1.0 g/kg, or 2 to 4 mL/kg of a 25-g/dL (25%) dextrose solution given at a rate of 1 mL/minute. The glucose infusion should continue at a rate of 8 to 10 mg/kg/minute, with frequent measurement taken of the blood glucose concentration and necessary adjustments made in the infusion rate to maintain a normal blood glucose level. If hypoglycemia persists despite increasing glucose infusion rates, hyperinsulinism should be considered. After the blood glucose level has stabilized and feeding has been reinitiated, the infusion rate may be decreased slowly but never discontinued abruptly. Even in the absence of pathologic hyperinsulinemia, the insulin level will rise physiologically in response to the administration of glucose; therefore, the glucose infusion must be tapered slowly (by decrements of 4 to 6 mg/kg/minute at 4- to 6-hour intervals) to prevent rebound hypoglycemia.

Hypoglycemia is a medical emergency and, if percutaneous venous access is not achieved rapidly, a cutdown should be performed by someone who is skilled in this technique; alternatively, in the young child, interosseous access should be considered. Additional supportive measures, including endotracheal intubation, may be necessary.

For the child with milder hypoglycemia, oral glucose may be beneficial, but care must be taken to protect against aspiration if the child is becoming obtunded. Glucagon (0.03 to 0.30 mg/kg, up to a maximum total dose of 1 mg intramuscularly) may be given, but with the knowledge that if it is effective, the benefit may be only transient. For patients with certain glycogen storage diseases, ketotic hypoglycemia, and other disorders in which glycogen has been depleted or is unavailable, it may have a minimal effect or none at all. Diazoxide, an antihypertensive agent that also suppresses insulin release, may be useful in certain patients with hyperinsulinemia. The usual starting dosage of diazoxide is 8 to 12 mg/kg/day, given orally in divided doses every 8 to 12 hours, but the dose may range between 5 and 20 mg/kg/day. Marked hypertrichosis is a prominent side effect that should be discussed with the parents at the time the drug is started because it may become objectionable enough to them to interfere with compliance. The hypertrichosis is reversible when the drug is discontinued. Hemoglobin A₁c may be used to monitor the magnitude of hyperglycemic excursions. Small, frequent feedings are useful for many patients with hypoglycemia, although the composition of the feedings differs according to the underlying disorder. Feedings may be supplemented with a slow-release glucose in the form of uncooked cornstarch, starting at 1.6 g/kg every 4 hours for children younger than 2 years of age and 1.75 to 2.50 g/kg every 6 hours in older children. Water or diet drinks are the preferred vehicles for suspension of the uncooked cornstarch (weight-to-volume ratio, 1:2) because these liquids avoid other sugars, which is important for certain hypoglycemic disorders, and do not contain natural amylases, such as may be present in some natural juices.

Home glucose monitoring may be valuable for many patients because of the variable course and response of any individual. With proper education and oversight, home monitoring will provide reassurance to patients and families and can reduce the risk of developing hypoglycemia.

With severe and prolonged hypoglycemia, permanent encephalopathy is not an unusual event, particularly in young children. Learning disability, attention deficit disorder, developmental delay, ataxia, spasticity, or seizures may be seen. Seizures associated with normal blood glucose concentrations should be treated with the usual anticonvulsant medications. The family of a child with sequelae should be counseled regarding infant stimulation and special education. Most families have concerns regarding the genetic risk of recurrence, although they may not voice their concerns to the physician; therefore, this topic should be addressed with all families.