Hyperglycemia is another problem that may be encountered in the NICU. Hyperglycemia is usually defined as a 150 mg/dl plasma glucose concentration or whole blood glucose value of 125 mg/dl (Stark & Simmons, 2019). Hyperglycemia is often asymptomatic and is frequently diagnosed on routine screening of an infant at risk. Signs and symptoms that may occur include polyuria, glycosuria, and dry, hot, flushed skin.
The major hyperglycemia causes are stress, sepsis, and transient diabetes mellitus. Some commonly used medications, such as methylxanthines and corticosteroids, may also contribute to hyperglycemia. Preterm infants, especially those under 30 weeks gestation and 1000 grams, are likely to experience hyperglycemia because of immature regulatory mechanisms (Stark & Simmons, 2019). These infants have a limited ability to secrete insulin from the pancreas, a decreased sensitivity to the insulin that is secreted, and an inability to suppress endogenous glucose production even when they receive an adequate exogenous supply. In general, the smaller the infant, the less likely he or she can tolerate maintenance rates of exogenous glucose. Critically ill infants, especially those with respiratory distress, hypoxia, or pain, are also at risk for hyperglycemia because these conditions cause increases in circulating catecholamine levels. Catecholamines cause increased lipolysis and glycogenolysis and antagonize the action of insulin.
Neonatal diabetes mellitus is "a rare disorder characterized by hypoinsulinism, progressive wasting, polyuria, and glycosuria during the neonatal period. It may be caused by deficiencies in insulin receptors or the synthesis of abnormal, poorly functioning insulin molecules (Stark & Simmons, 2019). Neonatal diabetes mellitus is usually transient. In contrast to insulin, glucagon stimulates gluconeogenic enzymes. A delicate balance must exist between glucagon and insulin to achieve glucose homeostasis.
The incidence of hyperglycemia varies depending on birth weight, gestational age, the severity of illness, and the glucose concentrations being infused. An estimated five and one-half percent of all infants receiving IV D10W experience hyperglycemia. The incidence in premature infants is markedly increased. Neonatal hyperglycemia can have undesirable consequences. For example, hyperglycemia has been associated with increased intraventricular hemorrhage, particularly in premature preterm infants. This hyperclycemia may occur because of changes in osmolality that result in fluid shifts within the germinal matrix.
Additionally, hyperglycemia can result in glycosuria and osmotic diuresis. Dehydration and electrolyte imbalance may also occur. A particular concern is a hypokalemia because it may cause fetal cardiac arrhythmia.
Premature infants may develop hyperglycemia related to group B strep or E-coli sepsis. Some infants with early sepsis have an increased need for glucose. Depression of insulin secretion and end organ receptor response may be important etiologies of hyperglycemia as the sepsis progresses. Thus infants with either hyperglycemia or a progressive need for increased glucose intake preceding hyperglycemia should be evaluated for infection (Stark & Simmons, 2019).
Certain factors involved in the care of sick newborns can cause hyperglycemia. Many infants are treated with theophylline or caffeine for apnea of prematurity or are on steroids for respiratory disease. These medications may cause an increase in blood glucose. Any stress, such as surgery, pain, or sepsis, may increase circulating catecholamines, which will result in hyperglycemia (Stark & Simmons, 2019). Serum glucose over 150 mg/dl indicates hyperglycemia, generally asymptomatic but may have serious complications. Hyperglycemia may cause an osmotic diuresis, which draws the fluid from the intracellular to the extracellular space and leads to dehydration. These fluids shifts may be a risk factor for intraventricular hemorrhage.
Glucose requirements depend on metabolic rate: the higher the metabolic rate, the higher the glucose requirement. The large energy requirement of the brain affects the metabolic rate, increasing the glucose need as the ratio of brain mass to body mass increases. Premature infants have a higher brain-to-body mass ratio than term infants, requiring more glucose. Unfortunately, because of the immature regulatory mechanisms, few infants who weigh less than 1,000 grams tolerate maintenance amounts of glucose, especially in the first week of life.
Infants generally require a minimum of 5 - 6 mg/kg/minute of glucose to maintain homeostasis. Infants not receiving enteral feedings should receive IV fluids with ten percent dextrose concentration on the first day of life with an infusion rate of 4 – 6 mg/kg/minute of glucose. Most full-term infants will initially tolerate 8 – 10 mg/kg/minute. The rate or concentration should be increased gradually (by 1 – 2 mg/kg/minute/day) so that by day two or three of life, glucose intake is at least 6.5 mg/kg/minute for preterm infants and 8 – 10 mg/kg/minute for term infants (Stark & Simmons, 2019). Whether to increase the rate of infusion or concentration of glucose will depend on the fluid requirements of the infant and the route of administration (peripheral vs. central). Too rapid an increase in glucose intake may exceed an infant's carbohydrate tolerance and result in hyperglycemia.
Despite slow incremental increases in glucose intake, most infants 800gm and 40 percent of infants between 800 gm and one kg become hyperglycemic between the fifth and seventh day of life if full caloric intake is attempted. All infants at risk for hyperglycemia should be closely assessed for signs of the condition. Glucose levels should be assessed every four to eight hours. Urine output, urine glucose, and urine specific gravity should be assessed at least every eight hours. Normal urine output should be 1 -3 mL/kg/hr. Urine output 5 mL/kg/hr, urine glucose 2+, or specific gravity 1.010 may indicate glucose intolerance and osmotic diuresis. Blood glucose levels may need to be assessed as often as every two hours if any signs present. Weight should be monitored daily as it is a sensitive indicator of fluid balance. Serum electrolyte levels should be checked daily until stable, especially for extremely low birth weight infants.
In many cases, decreasing the amount of glucose in the intravenous solution will be sufficient to correct hyperglycemia. This decrease may not be a desirable long-term treatment because adequate calories may not be provided. If hyperglycemia occurs in the range of 150 – 200 mg/dl, and if the infant is not experiencing osmotic diuresis, glucose infusions may be decreased to maintain blood sugars between 50 and 150 mg/dl between 50 mg/dl and that level where glycosuria is 2+. Glucose infusions should not be decreased to levels that compromise nutritional and growth requirements for an extended period. The low birth weight infant has only a few days of stored calories and depends on increasing caloric intake. Glucose infusions of 50 kcal/kg/day will result in inadequate caloric intake and subsequent negative nitrogen balance and tissue catabolism. Glucose concentrations should not be decreased to five percent or less because the solution will be hypotonic, which should be avoided to prevent problems with hypo-osmolality. Other osmoles, such as sodium chloride, need to be added to produce an isotonic solution, and the additional sodium may adversely affect fluid and electrolyte balance. Lipid infusions also cause an increase in serum glucose levels. The lipid dose may have to be reduced or discontinued.
If severe hyperglycemia persists despite a reduction in glucose infusion or if nutrition and growth are being compromised by trying to maintain normoglycemia, insulin administration should be considered. Insulin is also indicated for infants with neonatal diabetes. There is some controversy regarding the blood glucose level at which treatment should begin. One rationale for the early use of insulin is that it will allow the infant to tolerate higher glucose infusions, which will help to meet calories for growth. Insulin may be administered subcutaneously (rarely used in neonates) or IV routes. A continuous infusion of 0.05 to 0.1 unit/kg/hour of recombinant human-derived regular insulin (Humulin) is suggested (Stark & Simmons, 2019). An initial IV dose of 0.1 to 0.5 units/kg may be given before continuous infusion. Insulin requirements vary greatly in small infants. A rule of thumb for initiating insulin infusions is 1 unit 10 gm of glucose.
Insulin may bind to the polyvinyl IV tubing, causing fluctuations in the amount of insulin delivered, despite constant flow rates. Interventions to decrease the amount of insulin that binds to the IV tubing include flushing the tubing with the insulin solution and using special IV tubing. The most cost-effective method of administration is to use small-volume tubing, flush the tubing with the insulin solution, and administer via a syringe pump.
Insulin is compatible with saline solution and dextrose solution, including total parenteral nutrition (TPN). Although insulin may be added to most maintenance fluids, a separate IV line should be used whenever possible to titrate dosage. It is best to calculate dosages to give the insulin in as little fluid as possible. A more dilute solution will allow the administration of smaller doses and facilitate weaning the insulin infusion in small doses to avoid rebound hyperglycemia. Glucose levels should be monitored every one to two hours during an insulin infusion. Serum potassium and phosphate levels should also be followed daily. Insulin facilitates an extracellular-to-intracellular shift of potassium and phosphate and may lead to hypokalemia and hypophosphatemia. Urine output should be closely monitored and assessed for the presence of glucose or elevated specific gravity (1.010).