Complications of Parenteral Nutrition

Question 1

Stress-associated hyperglycemia in acutely ill and septic patients often develops as a result of insulin resistance, increased gluconeogenesis and glycogenolysis, and suppressed insulin secretion.

Answer 1

Note: In rare cases, hyperglycemia may be caused by chromium deficiency. Insulin is ineffective in pts w/ chromium def. Increasing the chromium dose in the PN formulation beyond the standard amt prepared commercially is indicated.

Question 2

1. What is the most common complication associated with PN administration?
2. What conditions are associated with excess carbohydrate administration?

Answer 2

1. Hyperglycemia

2. Hyperglycemia, hepatic steatosis and increased CO2 production.

Question 3

In acutely ill hospitalized pt, what are the recommendations for the initiation of PN?

Answer 3

PN should be initiated at 1/2 of the estimated energy needs or ~ 150 - 200g for the 1st 24hrs. Lesser CHO delivery (~100g dextrose) is indicated in hyperglycemic pt requiring insulin therapy or a hypoglycemic agent.

Question 4

What are the maximum dosages for CHO/dextrose administration in PN for adults?

Answer 4

7.2g/kg/day. (4 - 5 mg/kg/min)

Glucose concentration should be monitored every 6 hrs and more frequently in hyperglycemic patients.

Question 5

Bld gluc concentration can be controlled with regular insulin given subcutaneously or via PN. what is the recommendation for insulin given via PN?

Answer 5

An initial regimen of .05 to .1 units of insulin per gram of dextrose in PN solution is common or .15 to .2 units of insulin/g of dextrose in hyperglycemic patients.

Question 6

What situations can lead to hypoglycemia in PN?

Answer 6

1. Excess insulin administration via PN solution, IV drip or subcutaneous injection.
2. Abrupt discontinuation of PN can lead to rebound hypoglycemia.

Question 7

What measures should be taken to reduce the risk of rebound hypoglycemia in susceptible pts on PN?

Answer 7

1. a 1 - 2hr taper down of the infusion may be necessary
2. If PN solution must to be discontinue quickly, 10% dextrose solution should be infused for 1 - 2 hrs following PN discontinuation.
   NB. obtaining a bld glu after 30 - 1hr after PN discontinuation would help identify rebound hypoglycemia.

Question 8

Two polyunsaturated fatty acids, linoleic and alpha linolenic cannot be synthesize by the body and are considered essential.
The adult requirement of linoleic acid is met thru exogenous source or endogenously through the lipolysis of adipose tissue. However, when hypertonic dextrose is infused, insulin is secreted and lipolysis is reduced. Thus, an exogenous source of fat must be provided.

Answer 8

Biochemical evidence of EFAD is determine by a triene:tetraene ratio of >.4 and can occur within 1 - 3 wks in adults receiving IVFE free PN.
Clinical manifestations occur 1 - 3wks after biochemical detection, and include scaly dermatitis, alopecia, hepatomegaly, thrombocytopenia, fatty liver and anemia.

Question 9

What are the recommendation to prevent EFAD?

Answer 9

To prevent EFAD, 1-2% of daily energy requirements must come from linoleic acid and .5% of energy from linolenic acid. This translate into ~ 500ml of 10% IVFE or 250ml of 20%IVFE administered over 8 - 12hrs twice/wk. An alternate method is 500ml of 20% of IVFE administered once/wk.

Question 10

What situations can lead to hypertriglyceridemia in children and adults on PN?
What are some negative effects of Hypertriglyceridemia?

Answer 10

1. Hypertriglyceridemia can occur with dextrose overfeeding or with rapid administration rates of IVFE (>2.64g/kg/d in children-adults).
2. Hypertriglyceridemia may impair immune response, altered pulmonary dynamics, and increase risk of pancreatitis.

Question 11

What measures shld be taken to reduce the risk of Hypertriglyceridemia in PN patients?

Answer 11

1. Reduce the dose and/or lengthening the IVFE infusion time.
2. IVFE intake should be restricted from PN regimen if serum TG > 400mg/dl.

Question 12

Pancreatitis due to IVFE-induced hyperlipidemia is rare unless serum tg is >1000mg/dl.

Answer 12

IVFE is considered safe for use in patients with pancreatitis w/out Hypertriglyceridemia.

Question 13

What are the causes of prerenal azotemia?

Answer 13

Prerenal azotemia can result from dehydration, excess protein, and/or inadequate nonprotein calories.
NB: Increased blood urea (BUN) may occur as a result of intolerance to protein load. Pts with hepatic or renal disease are prone to developing azotemia bcuz of the impaired ability to metabolize and eliminate urea. When urea clearance is impaired, dialysis may be required to assist with the elimination of urea and allow for adequate intake of protein.

Question 14

Pts who develop signs of a.a intolerance such as prerenal azotemia, hepatic encephalopathy, or hyperammonemia may benefit from a reduced a.a dose

Answer 14

The use of high branched chain, low aromatic a.a formulations in pts w/ hepatic failure and hepatic encephalopathy has provided inconsistent results.

Question 15

Vitamins are essential for effective nutrient utilization. Adults patients receiving PN shld should receive a standard daily dose of parenteral mvi.
PN supplementation w/ additional thiamin (25-100mg/d) is reasonable in PN pts w/ a h/o alcohol abuse, especially if the pt did not receive thiamin upon hospital admission.

Answer 15

Pts receiving both PN and warfarin therapy require close monitoring of the desired anticoagulation level bcuz of the inclusion of vit K in the parenteral mvi preparation.

Question 16

Iron supplementation is not routinely recommended in pt receiving PN. It shld be limited to conditions of Fe deficiency when the oral route is ineffective or not tolerated. When PN fe is provided, especially as chronic supplementation, routine monitoring of Fe status (eg, serum ferritin every 1-3mths) is necessary to prevent Fe load.

Answer 16

Trace elements deficiencies are relatively uncommon in pts receiving PN, but can occur when there is insufficient intake or increased utilization or excretion over a prolong period of time.

Question 17

What is refeeding syndrome?

Answer 17

Refeeding syndrome refers to the metabolic and physiological shift of fluid, electrolytes and minerals (e.g P, K, Mg) that occur as a result of aggressive nutrition support. CHO delivery stimulate insulin secretion, which causes an intracellular shift of these electrolytes and minerals which the potential of sever hypophosphatemia, hypokalemia and hypomagnesemia.

Question 18

What symptoms are characterized by refeeding syndrome?

Answer 18

Generalized fatigue, lethargy, muscle weakness, edema, cardiac arrhythmia, and hemolysis.

Question 19

Disorders of the liver and biliary systems are complications commonly reported in PN pts. There are 3 types of hepatobiliary disorders associated with PN therapy: steatosis, cholestasis, an gallbladder sludge/stones.

Answer 19

Steatosis or hepatic fat accumulation is predominantly in adults and generally benign. It is characterized as modest elevations of serum aminotransferase conc that occur within 2 wks of PN therapy and may return to normal, even when PN is continued. Steatosis seems to be a complication of overfeeding. It is generally a non-progression lesion but can progress to fibrosis and cirrhosis in long-term PN patients.

Question 20

What is PN-associated cholestasis (PNAC)?

Answer 20

PNAC is a condition of impaired bile secretion or frank biliary obstruction that predominantly occur in children, but may also occur in adult pts on long-term PN.

Question 21

What biochemical markers indicates PNAC?

Answer 21

PNAC typically presents as an elevation of alkaline phosphatase, gamma-glutamyl transpeptidase (GGT) and conjugated (direct) bilirubin conc w/ or w/out jaundice.

Question 22

alkaline phosphatase, (GGT) and conjugated (direct) bilirubin conc are markers for PNAC but with one is the prime indicator and why?

Answer 22

Elevated serum conc of conjugated bilirubin is the prime indicator of PNAC and defined as > 2mg/dl. Elevated alkaline phosphatase and GGT are sensitive markers for hepatobiliary disease, but they lack specificity because they may be elevated in other diseases as well. NB: PNAC is a serious complication bcuz it may progress to cirrhosis and liver failure.

Question 23

Gallbladder stasis during PN therapy ma lead to the development of gallstones or gallbladder sludge w/ subsequent cholecystitis. It is related more to the lack of enteral feeding than the PN infusion.Explain!

Answer 23

The lack of oral intake leads to decreased cholecystokinin (CCK) release and impaired bile flow and gallbladder contractility. The duration of PN therapy seems to correlate with the development of biliary sludge. Biliary sludge may progress to acute cholecystitis in the absence of gallstones. This condition is also referred to as acalculous cholecystitis.

Question 24

Development of liver disease in PN patients is particularly concerning because its occurrence and severity seems to increase w/ longer duration of PN usage.

Answer 24

Risk factors of PNALD which are unrelated to PN are:

1. bacterial and fungal infections (associated with cholestasis)
2. Sepsis (causes liver inflammation)
3. Small intestine bacterial overgrowth that results from bacteria which normally confined to the colon and lower small intestine populate the upper small intestines. These bacteria can produce hepatotoxins and cause liver disease.
4. Massive intestinal resection (e.g <50cm left of small bowel has been associated with chronic cholestasis.

Question 25

PN-related risk factors:
1. Calories: the development of steatosis during PN administration is primarily due to excessive calories. Overfeeding combined or individual energy substrates (dextrose,fat,a.a) can contribute to liver complications.The administration of excessive calories is thought to promote hepatic fat deposition by stimulating insulin release, which, in turn, promote lipogenesis and inhibit fatty acid oxidation.

Answer 25

Not only do excess CHO deposit in the liver as fat, but dextrose based PN formulation (which little or no fat) may result in EFAD. EFAD may lead to impaired lipoprotein formation and triglyceride secretion, resulting in steatosis.
Providing balanced dextrose and fat calories seems to decrease the incidence of steatosis, possibly by decreasing hepatic triglyceride uptake, and promoting fatty acid oxidation.

Question 26

There are various concerns regarding the role of IVFE in the development of liver complications, including the fat source, the phytosterol content, and the dose. More research is needed for the 1st 2, but in regards to the dose, liver complications are associated with both insufficient IVFE (EFAD) and excessive.

Answer 26

Steatosis can occur when IVFE infusion exceeds the liver ability to clear the phospholipids and fatty acids, leading to direct deposit in the liver.
Cholestasis may also be associated with high IVFE doses, esp in long-term use.
Research have shown that chronic cholestasis and severe PNALD was strongly associated with IVFE intake greater than 1g/kg/d in long-term PN pts.

Question 27

Carnitine plays an important role in fat metabolism. Primary carnitine def has been associated with the development of steatosis. Carnitine supplementation has been shown to help mobilize hepatic fat stores and prevent steatosis in neonates on PN. However, low serum carnitine conc do no necessarily correlate to hepatic dysfunction in adults. Therefore the role of carnitine in the prevention and treatment in PNALD in adults remains to be established.

Answer 27

It is assumed that choline is endogenously synthesized from methionine containing in the crystalline a.a solution. However, this conversion may be less efficient when methionine is given via PN compare to the oral route. Low plasma-free choline conc have been reported in long-term PN pts and have been associated with elevated serum hepatic aminotransferase conc. Steatosis reportedly resolved following choline suppl but more research is needed.

Question 28

What is the difference between cyclic and continuous PN infusion. Which one has less chances of causing liver complications?

Answer 28

1. Cyclic PN infusion refers to the infusion of a PN formulation over a period less that 24 hrs ( in continuous PN infusion) (generally 8-12hrs), thus allowing time off of PN.
2. Cyclic PN infusion has been shown to reduce serum liver enzymes and conjugated bilirubin conc when compared to continuous PN. The latter can result in hyperinsulinemia and fat deposits in the liver and, thereby, potentially increase the risk of liver complications.

Question 29

A critical review of the PN formulation is indicated whenever liver complications develop. Although PN therapy may not be implicated as the cause of the complication, it may contribute or exacerbate the problem.

Answer 29

Possible steps to modify PN

1. If overfeeding, decrease calories. Providing a balance energy source by adjusting the CHO-FAT ratio to give more IVFE (but check tg levels) may improve serum liver enzymes that are elevated bcuz of steatosis. A balanced PN formulation shld provide 70-85% of non-PRO calories as CHO and 15-30% as fat. NB. Max CHO infusion rate: 7g/kg/day for adults.
2. Infusing PN over a cyclic period rather than a 24 -hr continuous infusion rate may be beneficial in reducing the risk of PNALD.

Question 30

In long-term PN patients who develop cholestasis, what is the recommendation for fat infusion rate

Answer 30

Standard adult guidelines for fat are 2.5g/kg/d but there is evidence that infusion rates over 1g/kg/d is associated with development of PNAC.

Question 31

What are the general strategies to manage PN-associated liver complications?

Answer 31

1. R/O non PN factors: Hepatotoxins meds, herbal suppl, biliary obstruction, hepatitis and sepsis.
2. Consider PN modifications: ↓ dextrose, ↓ IVFE ( <1g/kg/d), provide a balance of dextrose & IVFE, cyclic PN infusion.
3. Maximize enteral intake: Encourage po intake, T.F even at slow rate.
4. Prevent/treat bacterial overgrowth: enteral antibiotics, and in chronic intestinal psuedo-obstruction (CIPO) use agents to enhance motility.
5. Pharmacotherapy: Aggressive treatment of infection
6. Intestinal transplant: consider for patients w/ PN failure.

Question 32

Metabolic Bone disease (MBD)
Osteoporosis and osteomalacia have been associated w/ long-term PN use. The former is the most common form of MBD and is defined as a loss of bone mass and microarchitectual deterioration of the skeleton leading to increased risk of fractures.

Answer 32

MBD continued
Osteomalacia is characterized as softening and bending of the bones that occur because the bones contains osteoid tissue that has failed to calcify. This generally occur because of Vit D def.

Question 33

MBD continued
Ca plays a vital role in maintaining bone integrity by decreasing bone turnover and slowing bone loss. Pts receiving PN are very vulnerable to (-) Ca balance bcuz of limited intake and increased urinary loss.
Not only is Ca suppl in the PN formulation limited by physical incompatibility w/ phosphorus, but there seems to be a threshold for Ca intake parenterally. Higher Ca doses is offset by ↑ing urinary losses. The recommended daily intake of Ca gluconate added to PN formulation = 10 to 15mEq.

Answer 33

MBD continued
An inadequate P dose may also ↑urinary Ca excretion. P seems to enhance Ca reabsorption by the renal tubules and therefore promote a (+) Ca balance.
The recommended daily intake of P added to PN formulation = 20 to 40 mmol.
↑er PRO doses (2g/kg/d as compared to 1g/kg/d) in PN formulation has been associated with ↑er urinary Ca excretion. So reducing PRO intake if possible to maintenance doses whenever possible is recommended.

Question 34

MBD continued
Chronic metabolic acidosis has been associated with hypercalcuria and MBD. Correction of metabolic acidosis w/ acetate in PN formulation has been shown to reduce urinary Ca excretion.

Answer 34

MBD continued
Cyclic PN infusion has been shown to result in ↑er urinary Ca losses when compared to continuous infusion. However, this potential disadvantage should be measured against the potential benefits to the liver and it convenience in long-term PN pts when compared to continuous infusion.

Question 35

MBD continued
Both Vit D def and vit D toxicity can result in bone disease. The adult mvi preparation used in PN formulation contains 200IU of vit D (ergocalciferol or cholecalciferol).Vit D can be detrimental to the bone when excessive doses are given because it can suppress parathyroid hormone (PTH) secretions and directly promote bone resorption.

Answer 35

Although vit D removal may be beneficial in certain pts, such as those with a low serum PTH concentration, it is impractical because there are no commercially available injectable mvi preparations w/out vit D. Bcuz vit D def can also result in MDB, it seems reasonable to provide PN pts with the maintenance vit D dose.

Question 36

MBD continued…
Hpocalcemia is a prominent manifestation of Mg deficiency. Mg def results in a ↓ mobilization of Ca from bone because several mechanisms:
1. Hypomagnesemia causes an increased release of Mg ions at the bone surface in exchange for increased bone uptake of Ca ions from the serum.
2. Chronic severe hypomagnesemia inhibits PTH release, resulting in inappropriate low PTH levels for the degree of hypocalcemia.

Answer 36

The bone response to PTH can also be deminished, resulting in functional hypoparathyroidism.

3. Hypomagnesemia hypocalcemia should be treated with Mg supplements because it is often refractory to Ca therapy alone.
4. Mg def can also lead to hypophosphatemia because of increased P excretion.

Question 37

Prevention and Management for MBD
Strategies to prevent osteoporosis shld be considered in all pts who required long-term PN. PN modifications are:
1. Avoid high doses of PRO which increases Ca urinary excretion (minimal hypercalcemia).
2. Provide adequate Ca: Ca gluconate 10 -15mEq/d.
3. Adequate P: 20 - 40 mmol/d
4. Treat metabolic acidosis with acetate in PN formulation
5. Maintain adequate Mg and Cu intake (Cu def impairs bone formation.
6. Minimize aluminum conc
7. Avoid adding heparin

Answer 37

Medications used in the treatment/prevention of osteoporosis that decrease bone resorption includes bisphosphonates, the selective estrogen-receptor modulator (SERM) raloxifene, calcitonin, estrogen. Teriparatide is the only approved med at this time that stimulate bone formation.