Which patient is most likely to be a candidate for total parenteral nutrition TPN rather than enteral nutrition?

Hyperalimentation (Total Parenteral or Enteral Nutrition)

Hyperalimentation (i.e., total parenteral nutrition [TPN]) consists of concentrating hypertonic glucose calories in the normal daily fluid requirements. The solutions contain protein hydrolysates, soybean emulsions (i.e., Intralipid), or synthetic amino acids (or any combination of these ingredients). The major benefits of TPN or enteral nutrition have been fewer complications postoperatively and shorter hospital stays for patients scheduled to have no oral feeding for 7 days or who were malnourished preoperatively.45,46 Starker and colleagues found that the response to TPN, as monitored by serum albumin levels, predicted the postoperative outcome.47 The group of patients demonstratingan increase in serum albumin concentrations from TPN had diuresis, weight loss, and fewer complications (1 of 15 patients) than did the group that gained weight and had a decrease in serum albumin (8 of 16 patients had 15 complications;Fig. 32.2). The Veterans Administration (former name for Veterans Affairs [VA used for both]) studies also found that the serum albumin level was one of the most powerful predictors of perioperative outcome.45

The major complications of TPN are infection, metabolic abnormalities, and longer duration of ICU stay.47a The central lines used for TPN require an absolutely aseptic technique and should not be used as an intravenous access or as a route for drug administration during anesthesia and surgery. Major metabolic complications of TPN relate to electrolyte deficiencies, and the development of hyperosmolar states. Complications of hypertonic dextrose can develop if the patient has insufficient insulin (diabetes mellitus) to metabolize the sugar or if insulin resistance occurs (e.g., because of uremia, burns, or sepsis).

A gradual decrease in the infusion rate of TPN prevents the hypoglycemia that can occur on abrupt discontinuance. Thus the infusion rate of TPN should be decreased the night before anesthesia and surgery, or should be continued throughout the operation at its current rate. The main reason for slowing or discontinuing TPN before anesthesia is to avoid intraoperative hyperosmolarity secondary to accidental rapid infusion of the solution or hypoglycemia if the infusion is discontinued because of high levels of endogenous insulin and lower levels of glucose present in the usual crystalloid solutions.45 Hypophosphatemia is a particularly serious complication that results from the administration of phosphate-free or phosphate-depleted solutions for hyperalimentation. The low serum phosphate level causes a shift of the oxygen dissociation curve to the left. The resulting low 2,3-diphosphoglycerate and adenosine triphosphatase levels mean that cardiac output must increase for oxygen delivery to remain the same. Hypophosphatemia of less than 1.0 mg/dL of blood may cause hemolytic anemia, cardiac failure, tachypnea, neurologic symptoms, seizures, and death. In addition, long-term TPN is associated with deficiencies in trace metals such as copper (refractory anemia), zinc (impaired wound healing), and magnesium.

Total Parenteral Nutrition

Total parenteral nutrition (TPN) is associated with the development of cholelithiasis and of acalculous cholecystitis. As early as three weeks after the initiation of TPN, biliary sludge often forms in the gallbladder because of prolonged fasting. In addition, the sphincter of Oddi may fail to relax, leading to preferential flow of bile into the gallbladder. Finally, approximately 45% of adults and 43% of children form gallstones after three to four months of TPN.30,31 Because patients receiving TPN often have serious medical problems and are not good candidates for abdominal surgery, prophylactic treatment to prevent gallstones should be prescribed if no contraindication exists. Cholecystokinin (CCK) octapeptide administered twice daily via an intravenous line to patients on long-term TPN has proved to be safe and cost effective32 and should be used routinely in TPN-treated patients.

Cholestasis Associated With Chronic Total Parenteral Nutrition

Total parenteral nutrition (TPN) can cause a variety of liver diseases, including hepatic steatosis, gallbladder and bile duct damage, and cholestasis. Cholestasis is the most severe complication and can lead to progressive fibrosis and cirrhosis. It is the major factor limiting effective long-term use of TPN in children and adults. Risk factors for TPN-associated cholestasis include prolonged duration of TPN (particularly soy-based lipids), prematurity, low birthweight, sepsis, necrotizing enterocolitis, and short bowel syndrome.

The pathogenesis of TPN-associated cholestasis is multifactorial. Sepsis; excess caloric intake; high amounts of protein, fat, or carbohydrate; specific amino acid toxicities; nutrient deficiencies; and toxicities related to components such as manganese, aluminum, and copper can all contribute to hepatic injury. The type (soy based), volume, and frequency of lipid administered may be a significant factor. Prolonged enteral fasting compromises mucosal integrity and increases bacterial mucosal translocation. Fasting also decreases release of cholecystokinin, which promotes bile flow. This leads to biliary stasis, cholestasis, and formation of biliary sludge and gallstones, which exacerbates hepatic dysfunction. Sepsis, in particular due to Gram-negative bacteria and associated endotoxins, can also exacerbate liver damage.

Early histologic findings include macrovesicular steatosis, canalicular cholestasis, and periportal inflammation. These changes can regress after cessation of short-term TPN. Prolonged duration of TPN is marked by bile duct proliferation or ductopenia, portal fibrosis, and expansion of portal triads, and it can progress to cirrhosis and end-stage liver disease.

Clinical onset is typically marked by gradual onset of cholestasis, developing after more than 2 wk of TPN. In low birthweight infants, the onset of jaundice can overlap the phase of physiologic (unconjugated) hyperbilirubinemia. Any icteric infant who has received TPN for more than 1 wk should have bilirubin fractionated. With prolonged duration, hepatic enlargement or splenomegaly can develop. Serum bile acid concentrations can increase. Rises in serum aminotransferase levels may be a late finding. An elevation in serum AP activity may be due to rickets, a common complication of TPN in low birthweight infants.

In addition to cholestasis, biliary complications of intravenous nutrition include cholelithiasis and the development of biliary sludge, associated with thick, inspissated gallbladder contents. These may be asymptomatic. Hepatic steatosis or elevated serum aminotransferase levels can also occur in the absence of cholestasis, particularly in older children. This is generally mild and resolves after TPN is discontinued. Serum bilirubin and bile acid levels remain within the normal range. Other causes of liver disease should also be considered, especially if evidence of hepatic dysfunction persists despite weaning from TPN and initiating enteral feeds. If serum AP or aminotransferase levels remain elevated, liver biopsy may be necessary for accurate diagnosis.

Total Parenteral Nutrition (TPN)-Associated Hepatopathy

Total parenteral nutrition (TPN) is commonly associated with liver injury in neonates (26). TPN-associated hepatopathy typically manifests as cholestasis that resolves once intravenous alimentation is discontinued. In some infants, hepatic recovery may take several months, and others may develop permanent liver injury or liver failure requiring liver transplantation. Concomitant infection (e.g., sepsis), gastrointestinal surgery, and prematurity are often confounding factors in determining the precise cause of hepatic dysfunction. Because of these factors, the pathogenesis of TPN-associated hepatopathy is poorly understood. The primary treatment of these neonates and infants is the withdrawal of TPN with institution of judicious enteral feeds when practical.

Total Parenteral Nutrition Versus Enteral Nutritiona

Enteral and parenteral nutrition have been compared in a number of conditions in critically ill patients in randomized controlled trials; these have confirmed the utility of using enteral nutrition whenever possible. Furthermore, in acute pancreatitis, enteral nutrition was associated with reduced risks for death, multiple organ failure, systemic infection, and local septic complications as well as reduced length of stay.70 For severe pancreatitis, the reduction in mortality for enteral versus parenteral nutrition was greater than 80% (RR, 0.18; 95% CI, 0.06–0.58).70 Thus the adage of “if the gut works, use it” appears applicable across the breadth of critical care patient populations, and enteral nutrition should be used whenever possible. Total parenteral nutrition can be useful in patients for whom enteral nutrition cannot be applied. Data from an international survey of nearly 3000 critically ill patients suggested a strong inverse relationship between 60-day mortality and ventilator-free days with total daily calorie intake, particularly in patients with a BMI less than 25 or greater than 35, and this was true even in the 25% of patients who received total parenteral nutrition alone or in combination with enteral nutrition to achieve caloric goals.71 Randomized controlled studies in both adult and pediatric critically ill patients show that delayed initiation of parenteral nutrition does not change overall mortality and leads to decreased rates of infection.72,73

Total Parenteral Nutrition

Total parenteral nutrition (TPN) is used frequently for nutritional support in premature infants and other neonates with disorders of the gastrointestinal tract. It is used rarely in adults who cannot tolerate a full enteral intake. The common complications of TPN include gastrointestinal mucosal atrophy, reduced gastrointestinal hormone secretion, and liver dysfunction. Since the introduction of TPN in the 1960s, TPN-induced liver injury has been a common complication. The path of physiology of TPN-induced liver injury is not exactly certain. Recent studies have speculated that lipids, an important component of TPN that provides essential fatty acids, are causative factors in oxidative stress, leading to apoptosis in several tissues.17

The hepatic complications in infants treated with TPN were first reported by Peden and colleagues.18 Since then, they have been reported in both infants and adults.19,20 In infants, the incidence of TPN-associated complications correlates inversely with gestational age and birth weight and is also related to the duration of treatment. Although the exact etiology is uncertain, it is thought to be multifactorial. The histologic abnormalities seen with TPN-associated injury are heterogeneous. The changes are mostly nonspecific and can be extremely variable. The most prevalent findings are cholestasis, bile duct proliferation, periportal inflammation, and extramedullary hematopoiesis (Fig. 40-3A and B). Steatosis is infrequent (see Fig. 40-3C). Bile plugs and cholestatic rosettes are frequently observed. The periportal inflammation is composed of mixed inflammatory infiltrates.19–22

In adults, TPN-related complications are usually transient and are accompanied by altered hepatic function tests. The morphologic findings include intrahepatic cholestasis, macrovesicular steatosis, and portal and periportal fibrosis.23,24 Periportal inflammation can also be observed. Progressive fibrosis can lead to cirrhosis (see Fig. 40-3D). Nonalcoholic steatohepatitis has also been reported with long-term TPN.25

Total Parenteral Nutrition-Associated Cholestasis

Total parenteral nutrition (TPN) has an important role in pediatric nutrition, especially for low-birth-weight premature neonates and for infants with short-gut syndrome secondary to extensive intestinal resection (because of congenital anomalies of the gut or necrotizing enterocolitis). In these patients, however, prolonged TPN has important hepatobiliary consequences that range from asymptomatic elevation of liver enzymes and reversible fatty liver to severe cholestasis and cirrhosis. Although the incidence and severity of TPN-associated hepatic dysfunction have decreased because of improvements in clinical management, hepatobiliary complications of TPN remain a major cause of morbidity and mortality in these patients. Hepatobiliary abnormalities not only may be caused by TPN but also may reflect underlying disease or effects of pharmacological agents. Despite these confounding factors, current evidence suggests that TPN contributes to intrahepatic cholestasis and biliary sludge in infants, and it may lead to steatosis, steatohepatitis, biliary sludge, cholelithiasis, and cholestasis in adults.140

Cholestasis is the most frequent, predictable complication, especially in premature, low-birth-weight infants.141–143 In a series of 62 premature infants receiving TPN, cholestasis (defined as an elevated bilirubin level) was present in 23% of patients, with an incidence of 80% if exclusive TPN was used for more than 60 days, and 90% if used more than 90 days.144 Abnormal liver test results are first evident within 2 weeks after TPN therapy is initiated and resolve in approximately 4 weeks following discontinuation of TPN therapy.141,145 Continuance of TPN promotes persistence of cholestasis.141,144,146 The onset of jaundice in infants receiving TPN is often associated with systemic illnesses and multisystem involvement, in which cholestasis is detected as part of routine laboratory tests. The increase in bilirubin, bile acids, and transaminases is insidious, and hepatomegaly may also be present147–149; sludge has been reported in 44% of neonates receiving TPN for a mean duration of 10 days150 and in all adults receiving TPN for more than 6 weeks.151

The pathogenesis of TPN-associated cholestasis is poorly defined. Multiple factors have been considered, including direct toxicity of TPN to the liver, hepatic nutritional deficiencies resulting from the nutritional inadequacies of TPN, complications related to lack of enteral intake, and inadequate stimulation of the enterohepatic circulation and bowel function.152 In premature infants, immaturity of the biliary secretory system probably plays a major role in the development of cholestasis.153 The decreased size of the bile acid pool and the less well-developed hepatic mitochondrial function may make premature neonates more susceptible to the development of cholestasis.142,154,155 Enteral starvation followed by a lack of cholecystokinin release contributes to production of biliary sludge, because a decreased emptying of the gallbladder promotes stasis of bile in the gallbladder.156–158 The immature liver has lower basal and bile acid-stimulated bile flow rates and decreased response to choleretic hormones (secretin and glucagon).159,160 Immature hepatocytes also produce abnormal, potentially toxic bile acid metabolites (monohydroxy bile acids, such as lithocholate).143 There may be sequelae of hypoperfusion, by-products of intestinal injury such as bacterial toxins, or alterations in bile acid metabolism.143 No consistent data clearly incriminate the absolute or relative concentration of glucose or fat, but free oxygen radicals generated from peroxidation of infused lipids may play a role.161 There is indirect evidence for a deleterious effect of infused protein.143,162 Liver biopsy specimens show fatty changes early in the course of TPN-associated cholestasis.143,163–165 Other findings include accumulation of bile pigment in liver cells, canalicular bile plugs, and a mild, chronic inflammatory portal infiltrate. Portal expansion, ductular proliferation, and portal and lobular fibrosis similar to that seen in biliary atresia have been reported.166 Overall, these clinical, biochemical, and histological criteria are not specific; and the diagnosis of TPN-associated cholestasis is made when these findings are present in the appropriate clinical setting (premature infant, short-gut syndrome, and so on) and a search for other causes of cholestasis is unrevealing. Approximately 10% of patients have an alternative, specific cause such as cystic fibrosis and galactosemia.167

In the neonatal setting, TPN can often be discontinued as the respiratory and multisystem diseases improve; clinical and histological changes are reversible if TPN has been used for less than 90 days.164,165 The significant hepatobiliary consequences are seen in infants and children in whom TPN is the primary mode of nutrition (those with extensive intestinal resection or total aganglionosis). Every attempt should be made to initiate oral feeding; even continuous, slowly administered small volumes of any oral intake might aid in halting the progression to cholestasis or decrease the severity of hepatobiliary complications.168,169 Interventions used to prevent TPN-related liver disease can be instituted even after liver abnormalities (discovered with liver testing) have developed. The caloric needs; constituents such as carbohydrates, proteins, and lipids; and the ratios of carbohydrates to lipids and calories to nitrogen need to be carefully assessed and readjusted. There should be an adequate calorie-to-nitrogen ratio in the infusate and no excessive parenteral infusion of nutrients. Cycling TPN to mimic physiological feeding and fasting stages resolves liver test abnormalities and reduces hepatomegaly.140 Pharmacological stimulation of bile flow with UDCA, l-glutamine, glucagon, or cholecystokinin may decrease hepatic steatosis165,171 and prevent biliary sludge.156 UDCA supplementation enriches the bile acid pool and reduces the potentially toxic lithocholic acid, favorably influencing cholestasis.172 In TPN-related hepatic dysfunction, UDCA decreases liver enzymes, but its usefulness in reversing cholestasis is unproved.140 Patients receiving TPN who lack enteral alimentation experience bacterial overgrowth. Altered mucosal defense mechanisms173 and increased bacterial translocation174,175 result in accumulation of hepatotoxic substances, such as endotoxin and bacterial by-products. Bowel decontamination with metronidazole or other possible antibiotics may decrease hepatic lipid accumulation.176–178 With continued TPN in the face of progressive cholestasis, the cholestasis persists and may lead to severe portal fibrosis and micronodular cirrhosis.165,179 Liver transplantation is a therapeutic option, but the outcome depends on the correction of the associated intestinal disease; improved outcome might be seen in combined liver plus small intestinal transplantation.

Total Parenteral Nutrition–Associated Cholestasis

Total parenteral nutrition (TPN) has an important role in the nutrition of low-birth-weight premature neonates, infants with short gut syndrome secondary to extensive intestinal resection (because of congenital anomalies of the gut or necrotizing enterocolitis), and children with intestinal failure secondary to dysmotility.127 Prolonged TPN administration results in the development of liver disease, with a spectrum that ranges from asymptomatic elevation of liver enzyme levels and steatosis to severe cholestasis and cirrhosis. Although the incidence and severity of TPN-associated hepatic dysfunction have decreased because of improvements in clinical management and early initiation of enteral feeding, hepatobiliary complications of TPN remain a major cause of morbidity and mortality in these patients.128,129 Hepatobiliary abnormalities may reflect underlying disease or effects of pharmacological agents130; current evidence suggests that TPN itself contributes to intrahepatic cholestasis and biliary sludge in infants, and it may lead to steatosis, steatohepatitis, biliary sludge, cholelithiasis, and cholestasis in adults.131,132

Cholestasis is the most frequent manifestation of TPN-associated liver disease,133 especially in premature, low-birth-weight infants.134,135 In a series of 62 premature infants receiving TPN, cholestasis (defined as direct bilirubin level > 1.5 mg/dL) was present in 23% of patients, with an incidence of 80% if exclusive TPN was used for more than 2 months, and 90% if used more than 3 months.136 Abnormal liver test results are first evident within 2 weeks after TPN is initiated and resolve in approximately 4 weeks following discontinuation of TPN.136,137 Continuation of TPN promotes persistence of cholestasis.134,137 The onset of jaundice in infants receiving TPN is often associated with systemic illnesses, and cholestasis is detected as part of routine laboratory tests.138 The increase in serum bilirubin, bile acid, and aminotransferase levels is insidious, and hepatomegaly may also be present.139 Sludge has been reported in 44% of neonates receiving TPN for a mean duration of 10 days,140 and in all adults receiving TPN for more than 6 weeks.141

The pathogenesis of TPN-associated cholestasis is poorly defined. Multiple factors have been considered, including direct toxicity of TPN to the liver because of contaminants and other nonnutrient substances present in parenteral nutrition formulations, such as phytosterol in lipid emulsion,142 aluminum,143 and di(2-ethylhexyl) phthalate–containing infusion systems.144 Proposed mechanisms for phytosterols-induced cholestasis include reduction of bile acid–dependant bile flow, impairment of the function of important transport proteins involved in the secretion of bile because of the increased phytosterol content in the cell membrane, and inhibition of cholesterol 7-α-hydroxylase.145 Molecular studies demonstrated that phytosterols contribute to bile acid–induced hepatocyte damage by antagonizing FXR (NR1H4), a nuclear receptor involved in hepatoprotection from excess bile acid.146 Some nutrients added to the TPN such as manganese and copper127,138 might be hepatotoxic; therefore these elements are usually withheld in patients with evidence of liver dysfunction. Hepatic nutritional deficiencies resulting from the nutritional inadequacies of TPN such as choline and taurine deficiency132,147 and free oxygen radical generation from peroxidation of infused lipids may play a role in TPN-associated liver disease.148 Calorie excess caused by glucose and lipid overload may result in liver toxicity, thus causing hepatic steatosis and cholestasis.149 The infusion of lipids in doses higher than 1 g/kg/day correlates with liver dysfunction.150,151 The introduction of neonatal-specific amino acid parenteral nutrition allowed infants to receive higher concentrations of protein. Although protein calories are often out of proportion of nonprotein calories, the protein-to-nonprotein-calorie ratio was not found to be a contributing factor in the development of cholestasis in low-birth-weight infants receiving TPN.152 Lack of enteral intake and inadequate stimulation of the enterohepatic circulation and bowel function leading to reduction of gut hormone secretion, bile flow, and biliary stasis may be important mechanisms in the development of cholestasis, biliary sludge, and cholelithiasis.138,153

The high prevalence of TPN-associated cholestasis in premature infants is attributed to the relative immaturity of the hepatic canalicular transporters mediating bile secretion.54 Premature neonates have a decreased bile acid pool and impaired hepatic mitochondrial function.129 The immature liver has lower basal and bile acid–stimulated bile flow rates and decreased response to choleretic hormones (secretin and glucagon). Immature hepatocytes also produce abnormal, potentially toxic bile acid metabolites (monohydroxy bile acids, such as lithocholate).154 Lack of the physiological effect of enteral intake culminates in the pathogenesis of TPN-induced cholestasis through the loss of cholecystokinin release contributing to bile stasis and biliary sludge formation,155,156 lack of enteral alimentation results in intestinal stasis, enterocyte hypoplasia, and impaired gut immunity,157 predisposing to bacterial overgrowth and increased bacterial translocation,158 with subsequent accumulation of hepatotoxic substances such as endotoxin and increased production of secondary toxic bile acids such as lithocholic acid.

Liver biopsy specimens show accumulation of bile pigment in liver cells, canalicular bile plugs, and a mild, chronic inflammatory portal infiltrate. Portal expansion, ductular proliferation, and portal and lobular fibrosis similar to that seen in biliary atresia have been reported.159,160 A progression in the severity of histopathological changes in relation to duration of TPN administration was reported. Whereas patients with TPN of less than 2 weeks had no fibrosis or only mild degrees of fibrosis, patients with more than 6 weeks of TPN developed moderate to severe fibrosis.161

Overall these clinical, biochemical, and histological criteria are not specific. Parenteral nutrition–related cholestasis remains a diagnosis of exclusion; affected infants must be evaluated for treatable causes of cholestasis. Approximately 10% of patients have an alternative, specific cause such as cystic fibrosis and galactosemia.162 In the neonatal setting, TPN can often be discontinued as the respiratory and multisystem diseases improve; clinical and histological changes are reversible if TPN has been used for less than 90 days.159 The significant hepatobiliary consequences are seen in infants with poor intrauterine growth, low birth weight, young gestational age, delayed institution of enteral feedings, necrotizing enterocolitis, and sepsis161,163 and in children with extensive intestinal resection or total aganglionosis. Every attempt should be made to initiate oral feeding; even continuous, slowly administered small volumes of any enteral intake might aid in halting the progression to cholestasis or decrease the severity of hepatobiliary complications.164,165

Interventions used to prevent TPN-related liver disease can be instituted even after liver abnormalities have developed. The specific caloric needs; constituents such as carbohydrates, proteins, and lipids; and the ratios of carbohydrates to lipids need to be carefully assessed and readjusted. Although the initial study was promising,166 cholecystokinin was not proven to be effective in the prevention of parenteral nutrition–associated cholestasis when used in high-risk neonates on TPN.167 UDCA supplementation enriches the bile acid pool and reduces the potentially toxic lithocholic acid, favorably influencing cholestasis. In TPN-related hepatic dysfunction, UDCA improved conjugated bilirubin and liver enzyme levels, but its usefulness in reversing cholestasis was not proven.168,169 In a case series of patients with TPN-induced cholestasis, serum bilirubin levels decreased markedly after the parenteral administration of an omega-3 fatty acids–based fat emulsion.170 Patients tolerated this therapy, and no adverse reactions attributed to its use were observed. The use of parenteral omega-3 fatty acids has contributed to a paradigm shift in the management of TPN–associated liver disease. Their use in patients with short bowel syndrome allowed, in some cases, avoidance of liver transplantation because of improvement of liver function while receiving the omega-3 fatty acids–based lipid emulsion.171 Similar improvements also occurred by withholding or reducing standard lipid emulsions. Concerns exist regarding possible untoward effects of an inadequate supply of omega-6 fatty acids with parenteral fish oil only. Clearly the observed improvement of parenteral nutrition–associated cholestasis on the omega-3 fatty acids–based lipid emulsion deserves further exploration.172 A randomized controlled trial was recently completed to gain evidence of efficacy and safety of fish oil–based emulsions in parenteral nutrition–associated cholestasis.173

When continued over a duration of 6 weeks, TPN-induced cholestasis persists and may lead to advanced fibrosis and micronodular cirrhosis.12,161,174 Liver transplantation is a therapeutic option for TPN-induced end-stage liver disease; an improved outcome can be achieved via combined liver and small bowel transplantation in patients with short bowel syndrome or intestinal failure.

1. CLINICAL FEATURES

TPN is used for those individuals in whom disease of the bowel is so severe that oral feeding cannot achieve adequate nutrition. Most patients commencing TPN do so after years of chronic bowel disease, and therefore are likely to have pre-existing bone disease. This section is primarily concerned with the effects of TPN per se on the bone.

TPN may not provide all the nutrients or micronutrients required and historically calcium and phosphate were omitted from solutions, resulting in rickets in some children [99]. However, the major iatrogenic bone lesion resulted from the contamination of casein hydrolysate by aluminum at concentrations of up to 1 mg/l [100]. Serum samples from these patients contained large amounts, and bone contained more than 30 times the normal level of aluminum [99]. It is not surprising, therefore, that bone biopsies in most of these patients showed signs of osteomalacia. Clinically, the problem presented with peri-articular bone pains, especially in the legs, back, and ribs, and was only improved by cessation of TPN [101]. The disease has largely disappeared following the substitution of casein by amino acids [102]. Several biochemical abnormalities were found, but these may have been related to the amount of protein present in the feed. Hypercalciuria, low PTH, and low 1,25(OH)2D values returned to normal when purified amino acids were introduced. However, hypercalciuria persists if the amino acid content is kept too high [103]. The bone disease seen in these patients is mainly osteopenia [104,105], probably related at least in part to bone changes before TPN was commenced.

Total Parenteral Nutrition and Central Venous Catheters

Total parenteral nutrition (TPN) is a hyperosmolar glucose-containing lipid emulsion that provides an ideal medium in which bacteria can thrive. Much of the evidence regarding the administration of TPN through CVCs dates from the 1970s and 1980s and is well established. Assimilating these data, the CDC guidelines from 2002 state that if a multilumen catheter is used to administer parenteral nutrition, a single, specifically designated lumen should be used. Administration sets should be changed every 96 hours,46 although a more frequent changing should be considered with lipid emulsions.

Kemp and colleagues retrospectively studied 192 patients with 3334 catheter-days over 6 months.47 They found that femoral catheters were significantly more likely to become infected if multilumen (but not single lumen) and used for TPN. Likewise, Ishizuka and colleagues,48 looking at 423 catheters in 350 surgical patients who had catheters and had undergone colorectal surgery, found that the use of a femoral venous catheter was an independent risk factor for catheter-related bloodstream infection (OR, 3.175; 95% CI, 1.103 to 9.139; P = .0322).

Single-lumen catheters used solely for TPN were compared with multiuse catheters (i.e., used for fluids, pressors, antibiotics) in 260 critically ill inpatients. The result was a fivefold lower risk for infection (HR, 0.19; 95% CI, 0.04 to 0.83).49 This was a single-lumen catheter used only for TPN placed only in the subclavian vein and cared for by a dedicated multidisciplinary team.

This result demonstrates that TPN need not increase risk when other known risk factors are modified (Table 39-5).