Pancreas/Insulin

Hypoglycemia

Hypoglycemia is routinely anticipated as a potential problem in ICU patients. In children, hypoglycemia has been defined by a number of investigators. The definition suggested by Cornblath and Schwartz^[258] is generally accepted: for premature infants, blood sugar less than 20 mg/dL; for term infants up to 3 days, blood sugar less than 30 mg/dL; and for children older than 3 days, blood sugar less than 40 mg/dL.

The usual symptoms of hypoglycemia include the early changes of tachycardia, diaphoresis, and weakness, followed by mental clouding, seizures, and coma. In children, hypoglycemia can be precipitated by a number of specific diseases not commonly encountered in adults. Causes can be subdivided into disorders of increased utilization and disorders of decreased production. Transient hypoglycemia of the newborn from decreased or immature hepatic gluconeogenesis is a condition that self-corrects within hours to days. If the hypoglycemia persists, hepatic enzyme deficiencies, endocrine problems, or hyperinsulinism (i.e., pancreatic cell abnormalities, infants of diabetic mothers) must be considered. Other causes of hypoglycemia in the neonatal period include sepsis, hypothermia, hypoxia, and transplacental exposure to maternal hypoglycemic drugs.

In older children, hypoglycemia is associated with ketotic hypoglycemia, ^[259] hepatic enzyme abnormalities, hyperinsulinism, hepatic failure, and Reye's syndrome, and it is a side effect of certain drugs.^[260] Regardless of cause, the initial treatment of hypoglycemia is the administration of adequate glucose. The initial emergency dose is 0.5 g/kg given as 50% or 25% dextrose in water. This dose should be followed by a dextrose infusion that meets the metabolic requirements of the child (see the later section on the gastrointestinal system).

Diabetic Ketoacidosis

The most serious acute complication of diabetes mellitus is DKA, a syndrome of glucose and ketone overproduction and underutilization that results in hyperglycemic ketoacidosis. The clinical syndrome includes dehydration and hypovolemic shock resulting from the forced hyperglycemic osmotic diuresis, compensatory hyperventilation (Kussmaul pattern), life-threatening electrolyte depletion, and in cases of severe metabolic imbalance, neurologic obtundation and coma.^[261] Laboratory evaluation demonstrates elevated blood glucose concentrations, severe metabolic acidosis despite a compensatory hypocapnia, increased osmolality, hyperlipidemia, and a normal or low sodium level (usually fictitiously low because of the hyperlipidemia). Total-body depletion of potassium and possibly phosphate occurs, but levels may be falsely normal because of the metabolic acidosis.

Treatment of DKA requires careful correction of the metabolic derangements with meticulous monitoring of the multisystem complications of DKA, as well as the complications of therapy. Adequate intravascular volume is restored with the administration of an isotonic glucose-free solution. Regular insulin is given as an intravenous infusion of 0.1 U/kg/hr. The goal is to decrease blood glucose at a rate of 75 to 100 mg/dL/hr. This infusion is continued until blood glucose reaches 250 to 300 mg/dL, at which time 5% dextrose in normal saline (D₅ NS) is added to the infusate. This regimen of simultaneous glucose and insulin infusion can be continued until the patient is able to tolerate oral nutrient intake and routine subcutaneous insulin administration. Most clinicians continue the insulin infusion until the acidosis is nearly corrected. During any fluid administration, potassium should be closely monitored. These children have total-body potassium depletion, and potassium should be added to any infusion as soon as urine output is demonstrated. The need for phosphate may be more theoretical than real, but in most situations, half the potassium is given as a phosphate salt. The severe metabolic acidosis is usually corrected with volume and insulin administration.

The use of bicarbonate is generally avoided because of concern of precipitating or worsening the patient's neurologic status. In severe DKA, brain cells have a tendency to reduce their intracellular volume as the patient becomes dehydrated and hyperosmolar. In an attempt to maintain their normal size, brain cells generate osmotically active idiogenic osmoles (e.g., inositol). These particles attract more water into the intracellular compartment to help the cells retain their size. As systemic rehydration and correction of the hyperosmolar state begin, the brain cells tend to swell until the added idiogenic osmoles are metabolized or cleared. Consequently, rapid osmolar correction can lead to significant brain edema.^[262] In addition, rapid correction of the metabolic acidosis may produce worsening neurologic dysfunction. The pH of the brain is determined by the CSF bicarbonate level as well as by the CO₂ content; the CSF CO₂ content equilibrates much more rapidly with the vascular space than the bicarbonate level does. Therefore, with systemic correction of the acidosis, respiratory hyperventilation decreases and causes a rise in PaCO₂ ; if this rise is precipitous, the CSF acidosis could worsen until the increased bicarbonate equilibrates with the CSF space. Because rapid correction of pH is problematic, bicarbonate administration is not advocated in DKA unless cardiovascular instability is present. Even then, the doses administered are small. Unfortunately, despite very careful and slow correction of the hyperosmolar and acidotic state, hyperosmolar coma with fulminant brain edema can occur.^[263] The pathophysiology of brain swelling in DKA is poorly understood. There is radiographic evidence that subclinical brain swelling may in fact be relatively common in children with DKA.^[264] If the swelling is significant, the therapeutic

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