- Email: [email protected]
Basics in clinical nutrition: Metabolic complications of parenteral nutrition
e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism 4 (2009) e120–e122
Contents lists available at ScienceDirect
e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism journal homepage: http://intl.elsevierhealth.com/journals/espen
Educational Paper
Basics in clinical nutrition: Metabolic complications of parenteral nutrition Lubos Sobotka a, Maria E. Camilo b a b
Charles University, Hradec Kralove, Czech Republic Institute of Molecular Medicine, Lisbon, Portugal
a r t i c l e i n f o Article history: Received 13 January 2009 Accepted 27 January 2009 Keywords: Metabolic Biochemical monitoring Metabolic complications
1. Learning objectives – To describe basic acute and long-term metabolic complications connected with parenteral nutrition – To raise awareness that metabolic complications may arise from administration of inadequate or excessive nutrients – To become familiar with criteria to define clinically relevant metabolic complications and the substrates involved – To be able to implement protocols for prevention and surveillance of metabolic complications.
2. Introduction Metabolic complications of parenteral nutrition can be divided into deficiency states, acute metabolic complications and chronic (long-term) metabolic complications (Table 1). Acute complications may occur during parenteral nutrition (PN) whenever the administered nutrients do not take into account: – detailed clinical, nutritional and biochemical assessment of each patient – subsequent evaluation of nutrient requirements and the potential need for water and electrolyte correction prior to PN initiation – careful prescription based on the patient’s metabolic capacity One must be aware that PN always requires biochemical assessment and correction of any electrolyte disorders prior to the prescription in order to avoid potentially fatal acute complications.
E-mail address: [email protected] (Editorial Office).
Chronic complications of PN are more problematical. The aetiology of these long-term side effects is multiple and often not fully understood (see below). Metabolic complications are more likely to occur in the absence of a nutrition support team, in patients with severe malnutrition, organ dysfunction, or when physicians do not perceive parenteral nutrition as a powerful adjunct therapy and instead use it as urgent and ‘‘life-saving’’. In short bowel syndrome the length of remaining bowel is an important factor predicting the frequency of parenteral nutrition associated liver disease (PNALD). 3. Clinically relevant acute metabolic complications These complications are associated with life-threatening functional disturbances; the most common are summarized in Table 2. 3.1. Complications due to nutrient deficiencies Failure to administer a balanced and sufficient amount of macro and micronutrients may lead, in the short or long-term, to deficiencies. Nutrient requirements of patients are often difficult to define precisely; age (infants, children, elderly), disease severity and poor nutritional status are all risk factors. In long-term PN, any deficiency of essential nutrients is detrimental; the most commonly cited relate to: linoleic acid, zinc, copper, chromium, selenium, fat or water-soluble vitamins. Amongst the acute deficiencies, two deserve special emphasis: – Hypoglycaemia, may result from changes in insulin secretion, insulin sensitivity or administration, or sudden discontinuation of a high glucose infusion rate.
1751-4991/$ - see front matter Ó 2009 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.eclnm.2009.01.001
L. Sobotka, M.E. Camilo / e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism 4 (2009) e120–e122
e121
Table 1 Metabolic complications of parenteral nutrition.
Table 3 Some acute metabolic complications due to nutrient overloading.
Deficiencies
Nutrient Excess effect
Recommendations
Glucose Hyperglycaemia
Glucose infusion rate 4–5 mg kg1 min1 Provide exogenous insulin if glycamia > 7 mmol l1 Correct slowly to avoid cerebral oedema
Fat
Hypertriglyceridaemia
Lipid infusion rate 1.5 g kg1 day1. Check for sepsis or dyslipidaemia.
Hypersensitivity (cutaneous rash, chills, fever)
Immediate disappearance with discontinuation of feed.
Deficiency
Prevention and treatment
Electrolyte deficiency: K, Mg, P, Ca Monitoring of plasma and urinary levels
Prevention of depletion state Trace element deficiency: Fe, Zn, Cu, Control of signs of deficiency (skin Se, etc. changes, haematological changes)
Adequate provision Vitamin deficiency: B1, B2, B6, B12, C, Control of signs of deficiency folic acid, A, E Adequate provision Essential fatty acid deficiency
Application of 500 ml 20% LCT lipid emulsion per week minimally
Acute metabolic complications Complication
Amino Hyperazotaemia acids
Infusion rate 1.7 g protein/kg (BW)/day. Reduce infusion rate, check for possible hypohydration, renal function impairment or catabolic states.
Calcium Hypercalcaemia
Measure ionised calcium, if high: check amount of calcium or vitamin D toxicity, check for bone metastases; reduce/stop calcium or vitamin D, increase phosphorus intake
Vitamin Hypercalcaemia (rare) D
Measure ionised calcium, if high: stop vitamin D; good hydration, diuretics.
Prevention and treatment
Water and electrolyte disorders
Adequate control of water and mineral metabolism. Daily weighing and regular biochemical monitoring. Hyperglycaemia or hypoglycaemia Continuous TPN, blood glucose monitoring and, if necessary, insulin infusion to maintain normoglycaemia. Hypercalciuria Rehabilitation, avoiding vitamin D toxicity Hypertriglyceridemia Control of serum lipid level and adjust lipid emulsion dosage according to tolerance Liver steatosis Decrease carbohydrate intake, avoid
hyperalimentation. Use cyclical parenteral nutrition Long-term metabolic complications Complication
Prevention and treatment
Parenteral nutrition associated liver Stimulate intestine (enteral nutrition), prevent disease (PNALD) bacterial overgrowth, taurin, ursodeoxycholic acid, cholecystokinin, vitamin E Bone disease Adjust vitamin D dosage, rehabilitation, avoid aluminium toxicity
– Hypophosphataemia, may be lethal. Symptoms include paraesthesiae, muscular weakness, confusion, convulsions, coma (see refeeding syndrome); serum phosphate concentrations must be corrected prior to initiating PN.
Table 2 Definition of relevant acute metabolic complications. Complications
Evidence
>12 mmol l1 (even this may be too high) <3 mmol l1 Arterial pH 7.30 þ 2 dipstick for urinary or serum ketones Hyperosmolar hyperglycaemic Very high blood glucose þ serum osmolarity non-ketosis >305 mOsm l1 þ absence of urinary ketones Sodium, potassium, chloride, Serum values outside the reference range ionised calcium, magnesium, phosphate disorders Hypertriglyceridaemia >150% of upper reference limit measured >8 h after lipid emulsion (check milky plasma) > Twice upper limit of reference Hyperazotaemiaa Hyperchloraemic acidosis Serum Cl >115 mmol l1 þ arterial pH 7.30 Hepatic dysfunction: aAST, ALT, >Twice the upper limit of reference alkaline phosphatase, bilirubin Fluid overload Heart failure, oedema or weight gain > 0.45 Kg/ d for 3 or more consecutive days Coagulopathy Prothrombin time and/or partial thromboplastin time >150% of upper limit of reference Hyperglycaemia Hypoglycaemia Ketoacidosis
a Concentrations >twice baseline values may reflect nutrient overload. Adapted from Buzby et al. Am J Clin Nutr 1988; 47: 366–81.
3.2. Metabolic complications from overfeeding Overfeeding represents a metabolic burden, ill-understood by many. Continued overloading leads to organ dysfunction; the only effective way of prevention relies on a careful patient evaluation and planning a stepwise increment of nutrient amounts along with careful and regular monitoring. The frequency of both must be flexible and patient-centered. Some examples and recommendations for overcoming the complications are shown in Table 3. The refeeding syndrome is an acute complication often reported in severely malnourished patients. 4. Biochemical monitoring Measurement of concentrations of serum and sometimes urinary parameters are important for preventing acute metabolic complications. The time interval for the biochemical surveillance depends on the patient’s clinical/nutritional status and the stage of parenteral nutrition, i.e., all patients should have a complete blood and urinary laboratory evaluation prior to the initiation in order to correct relevant electrolyte deficiencies, register baseline data for later comparisons, and evaluate organ dysfunction, e.g. liver or renal. During the early phase (3–5 days) of parenteral nutrition, when stepwise increments of macronutrients are delivered until estimated and/or tolerated nutrient requirements, blood glucose, urea, sodium, potassium, magnesium, phosphorus, ionised calcium should be obtained daily together with arterial blood gass measurements which may be necessary in severely ill patients. Thereafter the full set of initial laboratory parameters should be obtained 2–3 lines weekly; for home PN, the intervals between measurements could be extended. The monitoring of concurrent drug therapy that may affect electrolyte and acid-base balance is within the responsibility of the nutrition support pharmacist, who should clarify, the potential current drug-associated risks. 5. Long-term metabolic complications 5.1. Liver steatosis Liver steatosis is a frequent complication of TPN. It is associated with elevation of plasma aminotransferases and liver enlargement
e122
L. Sobotka, M.E. Camilo / e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism 4 (2009) e120–e122
(modified structure of liver parenchyma on ultrasonography). It is usually caused by overfeeding, particularly with glucose. According to some authors its frequency can be decreased by cyclic parenteral nutrition (TPN period is followed by 6–8 h without i.v. feeding). Decreasing the energy supply required to meet consumption limits this complication. 5.2. Cholestatic liver disease Cholestatic liver disease is a serious complication, which may progress to cirrhosis and to liver failure. This complication is more frequent in TPN treated children and neonates. Patients suffering from jaundice, hyperbilirubinaemia and increases in gammaglutamyl transferase and alkaline phosphatase are apparent in serum. On histology, cholestasis associated with periportal and portal infiltration and extensive fibrosis can be seen; cirrhosis is seen during the final state of the disease. Aetiology of this disease is not known but core contributing factors are: – decrease in enterohepatic cycle of bile acids (short bowel syndrome, fistulas). This can lead to depletion of bile acids and increase in litogenicity of bile. – bacterial overgrowth with portal endotoxaemia (e.g. in blind loop). This can lead to production of secondary bile acids in small bowel (especially litocholic acid), which can be hepatotoxic and directly increase intrahepatic cholestasis. Bacterial overgrowth is also followed by rise in endotoxin (LPS) in portal blood with subsequent stimulation of cytokine production and decrease in bile transport. – products of lipid peroxidation and lack of vitamin E – decreased motility of gallbladder (see part Cholelithiasis and acalculous cholecystitis) – phospholipid part of lipid emulsion. The content and composition of phospholipids can be somehow responsible for liver injury connected with parenteral nutrition. Change of lipid emulsion can treat cholestatic injury. – glucose overfeeding. This decreases oxidation of fatty acids in the liver and subsequently leads to an accumulation of reesterified fatty acids in hepatocytes (liver steatosis). Some authors also discuss de novo synthesis of fatty acids from exogenous glucose.
gallbladder contraction has been proposed as a treatment to prevent this complication, or the giving of small amounts of oral or enteral nutrition to stimulate the gallbladder. 5.4. Bone disease Bone disease related to parenteral nutrition is associated with a loss of bone calcium (apparent also on bone histology), an increase in serum alkaline phosphatase, hypercalciuria, bone pain and fractures. Etiological factors are: – – – – – – – –
long-term immobilization with bone demineralization vitamin D toxicity low phosphate intake excess of amino acids in TPN (especially sulphur containing) aluminium contamination lack of magnesium in TPN heparin or corticoid intake in some patients low calcium and vitamin D intake.
Prevention of this disease is not known, but increase in phosphate and magnesium intake, exercise and alteration in vitamin D intake together with adequate calcium intake seem to be useful. 6. Summary Parenteral nutrition can be complicated by many metabolic problems, which may arise from inadequate or excessive amounts or from an inappropriate composition of nutrients. The most severe complications are cholestatic liver disease and bone disease. The list of most frequent complications together with preventive steps is in table. In every day practice, it is difficult to ascertain every patient nutrient requirement, hence nutrition support must be closely monitored and adjusted to the patient’s metabolic profile. Conflict of interest There is no conflict of interest. Further reading
Prevention of hepatic dysfunction may ensue from decreasing the amount of macronutrients, providing cyclic PN and most important to promote some oral/enteral nutrition; the type of amino acids provided, e.g. taurine, may prove beneficial. Fortunately, with time and improvements in knowledge and technique, the incidence of this serious complication decreases. Progression of end stage liver disease due to TPN in short bowel syndrome may be an indication for both intestinal and liver transplantations. 5.3. Cholelithiasis and acalculous cholecystitis Gallbladder stasis during TPN may be important in the development of gallstones or gallbladder sludge with subsequent cholecystitis. Administration of cholecystokinin (CCK) to stimulate
1. Angelico M, Della Guardia P. Hepatobiliary complications associated with total parenteral nutrition. Aliment Pharmacol Ther 2000;14(Suppl. 2):54. 2. Payne-James J, Grimble G, Silk D, editors. Artificial nutrition support in clinical practice. 2nd ed.; 2001. 3. Cavicchi M, Beau P, Crenn P, Degott C, Messing B. Prevalence of liver disease and contributing factors in patients receiving home parenteral nutrition for permanent intestinal failure. Ann Intern Med 2000;132:525. 4. Honasoge M, Rao DS. Metabolic bone disease in gastrointestinal, hepatobiliary, and pancreatic disorders and total parenteral nutrition. Curr Opin Rheumatol 1995;7:249. 5. Kowdley KV. Ursodeoxycholic acid therapy in hepatobiliary disease. Am J Med 2000;108:481. 6. Morikawa N, Suematsu M, Kyokane T, Guda N, Kumamoto Y, Okitsu T, et al. Discontinuous total parenteral nutrition prevents postischemic mitochondrial dysfunction in rat liver. Hepatology 1998;28:1289. 7. Manual Pra´tico de Nutriça˜o Clı´nica no Adulto. [Pocket manual of clinical nutrition] [in portuguese]. In: Camilo ME, editor. Dinalivro; 2001.
Contents lists available at ScienceDirect
e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism journal homepage: http://intl.elsevierhealth.com/journals/espen
Educational Paper
Basics in clinical nutrition: Metabolic complications of parenteral nutrition Lubos Sobotka a, Maria E. Camilo b a b
Charles University, Hradec Kralove, Czech Republic Institute of Molecular Medicine, Lisbon, Portugal
a r t i c l e i n f o Article history: Received 13 January 2009 Accepted 27 January 2009 Keywords: Metabolic Biochemical monitoring Metabolic complications
1. Learning objectives – To describe basic acute and long-term metabolic complications connected with parenteral nutrition – To raise awareness that metabolic complications may arise from administration of inadequate or excessive nutrients – To become familiar with criteria to define clinically relevant metabolic complications and the substrates involved – To be able to implement protocols for prevention and surveillance of metabolic complications.
2. Introduction Metabolic complications of parenteral nutrition can be divided into deficiency states, acute metabolic complications and chronic (long-term) metabolic complications (Table 1). Acute complications may occur during parenteral nutrition (PN) whenever the administered nutrients do not take into account: – detailed clinical, nutritional and biochemical assessment of each patient – subsequent evaluation of nutrient requirements and the potential need for water and electrolyte correction prior to PN initiation – careful prescription based on the patient’s metabolic capacity One must be aware that PN always requires biochemical assessment and correction of any electrolyte disorders prior to the prescription in order to avoid potentially fatal acute complications.
E-mail address: [email protected] (Editorial Office).
Chronic complications of PN are more problematical. The aetiology of these long-term side effects is multiple and often not fully understood (see below). Metabolic complications are more likely to occur in the absence of a nutrition support team, in patients with severe malnutrition, organ dysfunction, or when physicians do not perceive parenteral nutrition as a powerful adjunct therapy and instead use it as urgent and ‘‘life-saving’’. In short bowel syndrome the length of remaining bowel is an important factor predicting the frequency of parenteral nutrition associated liver disease (PNALD). 3. Clinically relevant acute metabolic complications These complications are associated with life-threatening functional disturbances; the most common are summarized in Table 2. 3.1. Complications due to nutrient deficiencies Failure to administer a balanced and sufficient amount of macro and micronutrients may lead, in the short or long-term, to deficiencies. Nutrient requirements of patients are often difficult to define precisely; age (infants, children, elderly), disease severity and poor nutritional status are all risk factors. In long-term PN, any deficiency of essential nutrients is detrimental; the most commonly cited relate to: linoleic acid, zinc, copper, chromium, selenium, fat or water-soluble vitamins. Amongst the acute deficiencies, two deserve special emphasis: – Hypoglycaemia, may result from changes in insulin secretion, insulin sensitivity or administration, or sudden discontinuation of a high glucose infusion rate.
1751-4991/$ - see front matter Ó 2009 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.eclnm.2009.01.001
L. Sobotka, M.E. Camilo / e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism 4 (2009) e120–e122
e121
Table 1 Metabolic complications of parenteral nutrition.
Table 3 Some acute metabolic complications due to nutrient overloading.
Deficiencies
Nutrient Excess effect
Recommendations
Glucose Hyperglycaemia
Glucose infusion rate 4–5 mg kg1 min1 Provide exogenous insulin if glycamia > 7 mmol l1 Correct slowly to avoid cerebral oedema
Fat
Hypertriglyceridaemia
Lipid infusion rate 1.5 g kg1 day1. Check for sepsis or dyslipidaemia.
Hypersensitivity (cutaneous rash, chills, fever)
Immediate disappearance with discontinuation of feed.
Deficiency
Prevention and treatment
Electrolyte deficiency: K, Mg, P, Ca Monitoring of plasma and urinary levels
Prevention of depletion state Trace element deficiency: Fe, Zn, Cu, Control of signs of deficiency (skin Se, etc. changes, haematological changes)
Adequate provision Vitamin deficiency: B1, B2, B6, B12, C, Control of signs of deficiency folic acid, A, E Adequate provision Essential fatty acid deficiency
Application of 500 ml 20% LCT lipid emulsion per week minimally
Acute metabolic complications Complication
Amino Hyperazotaemia acids
Infusion rate 1.7 g protein/kg (BW)/day. Reduce infusion rate, check for possible hypohydration, renal function impairment or catabolic states.
Calcium Hypercalcaemia
Measure ionised calcium, if high: check amount of calcium or vitamin D toxicity, check for bone metastases; reduce/stop calcium or vitamin D, increase phosphorus intake
Vitamin Hypercalcaemia (rare) D
Measure ionised calcium, if high: stop vitamin D; good hydration, diuretics.
Prevention and treatment
Water and electrolyte disorders
Adequate control of water and mineral metabolism. Daily weighing and regular biochemical monitoring. Hyperglycaemia or hypoglycaemia Continuous TPN, blood glucose monitoring and, if necessary, insulin infusion to maintain normoglycaemia. Hypercalciuria Rehabilitation, avoiding vitamin D toxicity Hypertriglyceridemia Control of serum lipid level and adjust lipid emulsion dosage according to tolerance Liver steatosis Decrease carbohydrate intake, avoid
hyperalimentation. Use cyclical parenteral nutrition Long-term metabolic complications Complication
Prevention and treatment
Parenteral nutrition associated liver Stimulate intestine (enteral nutrition), prevent disease (PNALD) bacterial overgrowth, taurin, ursodeoxycholic acid, cholecystokinin, vitamin E Bone disease Adjust vitamin D dosage, rehabilitation, avoid aluminium toxicity
– Hypophosphataemia, may be lethal. Symptoms include paraesthesiae, muscular weakness, confusion, convulsions, coma (see refeeding syndrome); serum phosphate concentrations must be corrected prior to initiating PN.
Table 2 Definition of relevant acute metabolic complications. Complications
Evidence
>12 mmol l1 (even this may be too high) <3 mmol l1 Arterial pH 7.30 þ 2 dipstick for urinary or serum ketones Hyperosmolar hyperglycaemic Very high blood glucose þ serum osmolarity non-ketosis >305 mOsm l1 þ absence of urinary ketones Sodium, potassium, chloride, Serum values outside the reference range ionised calcium, magnesium, phosphate disorders Hypertriglyceridaemia >150% of upper reference limit measured >8 h after lipid emulsion (check milky plasma) > Twice upper limit of reference Hyperazotaemiaa Hyperchloraemic acidosis Serum Cl >115 mmol l1 þ arterial pH 7.30 Hepatic dysfunction: aAST, ALT, >Twice the upper limit of reference alkaline phosphatase, bilirubin Fluid overload Heart failure, oedema or weight gain > 0.45 Kg/ d for 3 or more consecutive days Coagulopathy Prothrombin time and/or partial thromboplastin time >150% of upper limit of reference Hyperglycaemia Hypoglycaemia Ketoacidosis
a Concentrations >twice baseline values may reflect nutrient overload. Adapted from Buzby et al. Am J Clin Nutr 1988; 47: 366–81.
3.2. Metabolic complications from overfeeding Overfeeding represents a metabolic burden, ill-understood by many. Continued overloading leads to organ dysfunction; the only effective way of prevention relies on a careful patient evaluation and planning a stepwise increment of nutrient amounts along with careful and regular monitoring. The frequency of both must be flexible and patient-centered. Some examples and recommendations for overcoming the complications are shown in Table 3. The refeeding syndrome is an acute complication often reported in severely malnourished patients. 4. Biochemical monitoring Measurement of concentrations of serum and sometimes urinary parameters are important for preventing acute metabolic complications. The time interval for the biochemical surveillance depends on the patient’s clinical/nutritional status and the stage of parenteral nutrition, i.e., all patients should have a complete blood and urinary laboratory evaluation prior to the initiation in order to correct relevant electrolyte deficiencies, register baseline data for later comparisons, and evaluate organ dysfunction, e.g. liver or renal. During the early phase (3–5 days) of parenteral nutrition, when stepwise increments of macronutrients are delivered until estimated and/or tolerated nutrient requirements, blood glucose, urea, sodium, potassium, magnesium, phosphorus, ionised calcium should be obtained daily together with arterial blood gass measurements which may be necessary in severely ill patients. Thereafter the full set of initial laboratory parameters should be obtained 2–3 lines weekly; for home PN, the intervals between measurements could be extended. The monitoring of concurrent drug therapy that may affect electrolyte and acid-base balance is within the responsibility of the nutrition support pharmacist, who should clarify, the potential current drug-associated risks. 5. Long-term metabolic complications 5.1. Liver steatosis Liver steatosis is a frequent complication of TPN. It is associated with elevation of plasma aminotransferases and liver enlargement
e122
L. Sobotka, M.E. Camilo / e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism 4 (2009) e120–e122
(modified structure of liver parenchyma on ultrasonography). It is usually caused by overfeeding, particularly with glucose. According to some authors its frequency can be decreased by cyclic parenteral nutrition (TPN period is followed by 6–8 h without i.v. feeding). Decreasing the energy supply required to meet consumption limits this complication. 5.2. Cholestatic liver disease Cholestatic liver disease is a serious complication, which may progress to cirrhosis and to liver failure. This complication is more frequent in TPN treated children and neonates. Patients suffering from jaundice, hyperbilirubinaemia and increases in gammaglutamyl transferase and alkaline phosphatase are apparent in serum. On histology, cholestasis associated with periportal and portal infiltration and extensive fibrosis can be seen; cirrhosis is seen during the final state of the disease. Aetiology of this disease is not known but core contributing factors are: – decrease in enterohepatic cycle of bile acids (short bowel syndrome, fistulas). This can lead to depletion of bile acids and increase in litogenicity of bile. – bacterial overgrowth with portal endotoxaemia (e.g. in blind loop). This can lead to production of secondary bile acids in small bowel (especially litocholic acid), which can be hepatotoxic and directly increase intrahepatic cholestasis. Bacterial overgrowth is also followed by rise in endotoxin (LPS) in portal blood with subsequent stimulation of cytokine production and decrease in bile transport. – products of lipid peroxidation and lack of vitamin E – decreased motility of gallbladder (see part Cholelithiasis and acalculous cholecystitis) – phospholipid part of lipid emulsion. The content and composition of phospholipids can be somehow responsible for liver injury connected with parenteral nutrition. Change of lipid emulsion can treat cholestatic injury. – glucose overfeeding. This decreases oxidation of fatty acids in the liver and subsequently leads to an accumulation of reesterified fatty acids in hepatocytes (liver steatosis). Some authors also discuss de novo synthesis of fatty acids from exogenous glucose.
gallbladder contraction has been proposed as a treatment to prevent this complication, or the giving of small amounts of oral or enteral nutrition to stimulate the gallbladder. 5.4. Bone disease Bone disease related to parenteral nutrition is associated with a loss of bone calcium (apparent also on bone histology), an increase in serum alkaline phosphatase, hypercalciuria, bone pain and fractures. Etiological factors are: – – – – – – – –
long-term immobilization with bone demineralization vitamin D toxicity low phosphate intake excess of amino acids in TPN (especially sulphur containing) aluminium contamination lack of magnesium in TPN heparin or corticoid intake in some patients low calcium and vitamin D intake.
Prevention of this disease is not known, but increase in phosphate and magnesium intake, exercise and alteration in vitamin D intake together with adequate calcium intake seem to be useful. 6. Summary Parenteral nutrition can be complicated by many metabolic problems, which may arise from inadequate or excessive amounts or from an inappropriate composition of nutrients. The most severe complications are cholestatic liver disease and bone disease. The list of most frequent complications together with preventive steps is in table. In every day practice, it is difficult to ascertain every patient nutrient requirement, hence nutrition support must be closely monitored and adjusted to the patient’s metabolic profile. Conflict of interest There is no conflict of interest. Further reading
Prevention of hepatic dysfunction may ensue from decreasing the amount of macronutrients, providing cyclic PN and most important to promote some oral/enteral nutrition; the type of amino acids provided, e.g. taurine, may prove beneficial. Fortunately, with time and improvements in knowledge and technique, the incidence of this serious complication decreases. Progression of end stage liver disease due to TPN in short bowel syndrome may be an indication for both intestinal and liver transplantations. 5.3. Cholelithiasis and acalculous cholecystitis Gallbladder stasis during TPN may be important in the development of gallstones or gallbladder sludge with subsequent cholecystitis. Administration of cholecystokinin (CCK) to stimulate
1. Angelico M, Della Guardia P. Hepatobiliary complications associated with total parenteral nutrition. Aliment Pharmacol Ther 2000;14(Suppl. 2):54. 2. Payne-James J, Grimble G, Silk D, editors. Artificial nutrition support in clinical practice. 2nd ed.; 2001. 3. Cavicchi M, Beau P, Crenn P, Degott C, Messing B. Prevalence of liver disease and contributing factors in patients receiving home parenteral nutrition for permanent intestinal failure. Ann Intern Med 2000;132:525. 4. Honasoge M, Rao DS. Metabolic bone disease in gastrointestinal, hepatobiliary, and pancreatic disorders and total parenteral nutrition. Curr Opin Rheumatol 1995;7:249. 5. Kowdley KV. Ursodeoxycholic acid therapy in hepatobiliary disease. Am J Med 2000;108:481. 6. Morikawa N, Suematsu M, Kyokane T, Guda N, Kumamoto Y, Okitsu T, et al. Discontinuous total parenteral nutrition prevents postischemic mitochondrial dysfunction in rat liver. Hepatology 1998;28:1289. 7. Manual Pra´tico de Nutriça˜o Clı´nica no Adulto. [Pocket manual of clinical nutrition] [in portuguese]. In: Camilo ME, editor. Dinalivro; 2001.