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Hyperglycemia in patients receiving PN is primarily the result of excessive dextrose infusion. Factors that exacerbate glucose intolerance include sepsis, surgery, diabetes, pancreatitis, prematurity, and corticosteroid therapy. Elevated blood glucose levels may coincide with PN initiation, but endogenous insulin secretion usually adapts within 48 to 72 hours. Untreated hyperglycemia causes osmotic diuresis that can lead to hyperosmolar, hyperglycemic, nonketotic dehydration with electrolyte disturbances, impaired phagocytosis (42), and liver steatosis (43). The first effort in managing hyperglycemia is to decrease the dextrose load or reduce the infusion rate. However, this may compromise nutritional intake as dextrose is the major source of calories in PN. If reducing dextrose does not improve hyperglycemia, insulin therapy is then indicated. Because infants have variable responses to insulin therapy, adding insulin to the PN solution should be avoided. Instead, a regular insulin drip via alternative IV access should be initiated and titrated based on serial serum glucose checks.

Hypoglycemia with PN is usually the result of a sudden reduction of the PN infusion rate. In patients who receive PN over a portion of the day (“cycled”), hypoglycemia may be avoided by gradually reducing the rate over 1 to 2 hours prior to discontinuation. Premature infants are at higher risk for hypoglycemia due to their underdeveloped metabolic response and often do not tolerate cycling (44). If PN must be unavoidably discontinued, intravenous administration of dextrose 10% in water will prevent symptomatic hypoglycemia (3).

High concentrations of dextrose in the infusate is the primary cause of hypertriglyceridemia in PN patients. Excessive carbohydrate intake enhances hepatic and adipose tissue lipogenesis (45). Other factors that predispose to hypertriglyceridemia in pediatric patients receiving PN include prematurity, lipid overfeeding, critical illness, and sepsis (46).

Although the tendency is to reduce lipid infusion in this circumstance, a reduction in dextrose infusion is far more effective. If hypertriglyceridemia persists despite reducing the glucose intake, the lipid emulsion dose and rate should be decreased to keep triglyceride levels below 275 mg per dL. A lipid dose of 0.5 to 1 g per kg per day in children prevents essential fatty acid deficiency. If the 10% lipid emulsion is used, switching to the 20% lipid emulsion is recommended due to its better clearance (47). Carnitine deficiency may also be a cause of hypertriglyceridemia (as previously mentioned).

Metabolic acidosis may result from excessive chloride or amino acid load in PN. The addition of cysteine hydrochloride to the PN solution to improve calcium and phosphate solubility may also cause acidemia (7). Premature infants and patients with liver or renal disease are at increased risk for metabolic acidosis and should be closely monitored for acid–base changes.

Hypokalemia, hypomagnesemia, and hypophosphatemia may result from increased requirements during anabolism and protein synthesis (refeeding syndrome). This is particularly common in the severely malnourished patient and should be monitored during very slow advancement of feeding (33). Phosphate is also required intracellularly for generation of high-energy phosphates and bone formation. Intracellular shift of phosphate occurs with carbohydrate infusion. Hyperkalemia, hypermagnesemia, and hyperphosphatemia may result from increased intake in combination with decreased renal function and hypercatabolism. Apparent hypocalcemia in malnourished patients is often secondary to a reduced serum albumin concentration with a proportionally low total serum calcium.

Metabolic bone disease, including osteopenia, osteomalacia, and rickets, are well-described complications in PN-dependent patients. Diagnosis is usually incidental and biochemical markers may reveal elevated serum alkaline phosphatase concentrations, hypercalciuria, low to normal plasma parathyroid hormone (PTH) levels, and low 1,25 dihydroxyvitamin D. Several factors predispose to PN-associated metabolic bone disease, including calcium and phosphorus deficiency, excessive vitamin D intake (48), and aluminum toxicity (49). Maximizing calcium and phosphorus intake is most important to improve bone mineralization. Calcium deficit is the result of limited calcium supplementation and the resultant hypercalciuria from amino acids and metabolic acidosis. Aluminum, a contaminant of PN solution, is another possible cause of metabolic bone disease. Aluminum causes bone remodeling by impairing calcium fixation in bones (50), impairing PTH secretion, or reducing the formation of active vitamin D. Premature infants and patients with renal failure are at highest risk for aluminum toxicity due to their reduced ability for aluminum elimination. Additional vitamin D administration may actually be dangerous because vitamin D may also play a role in the pathogenesis of metabolic bone disease; however, the exact mechanism is unknown. Withdrawing vitamin D from PN has led to improvement in bone demineralization, resolution of bone pain, positive calcium balance (48), and normalization of plasma active vitamin D and PTH concentrations (51) in those situations.

Hepatobiliary complications associated with PN include cholestasis, steatosis, and cholelithiasis. Multiple factors may predispose to PN-associated hepatobiliary complications, including prematurity, overfeeding, PN dependence, absence of enteral endogenous stimulation for gall bladder contraction, short bowel syndrome, and recurrent sepsis (52,53). Cholestasis is the most common hepatobiliary complication in children receiving PN. Jaundice may occur 2 to 3 weeks after PN initiation. A serum conjugated bilirubin concentration greater than or equal to 2 mg per dL is commonly used as a biochemical marker of cholestasis (53). Strategies to prevent or reduce PN-associated cholestasis include initiation of enteral feeding, weaning PN, avoiding overfeeding, balancing calories (54), “cycling” PN (55), and avoiding and promptly treating sepsis (54). Table 7-7 offers specific guidance for vitamin supplementation in total parenteral nutrition (TPN)-dependent patients with cholestasis. Pharmacological interventions include improving bile flow with the administration of exogenous ursodeoxycholic acid. This may alleviate the clinical symptoms of cholestasis (56). Cholecystokinin octapeptide is another pharmacological agent that has been used on investigational basis to induce gallbladder contraction and increase hepatic bile flow (57). Oral antibiotics, such as oral gentamicin and metronidazole, have been used to decrease intestinal bacterial overgrowth and reduce bacterial translocation (58). A rapid rise in direct bilirubin is a strong predictor of impending hepatic failure. In infants with short bowel syndrome, a direct bilirubin greater than 2.5 mg per dL for more than 4 months was associated with an 80% mortality, and suggests a potential criteria for referring patients for transplant evaluation (59).