Chapter 17: Complications of Parenteral Nutrition

Azotemia can occur in what 2 situations?

1. Protein administration is excessive 2. Metabolic demand of disposing of the byproducts of protein metabolism increases

Interruptions in parenteral multivitamin product supply have been an ongoing issue in the US. ASPEN offers what 6 recommendations?

1. Reserve a supply of IV multivitamins for those patients receiving solely PN 2. Use oral or enterally administered multivitamins whenever possible 3. To ensure fair allocation of products nationwide do not stockpile parenteral multivitamins 4. Do not use pediatric IV multivitamins for adult patients 5. When all options to obtain IV multivitamins have been exhausted, ration use by reducing the dose by 50% or giving 1 dose 3 times per week 6. If IV multivitamins are no longer available, administer individual thiamin, ascorbic acid, pyridoxine and folic acid daily

What 2 things should be routinely monitored to manage fluid and electrolytes in PN patients?

1. Routinely monitor patients for fluid and electrolyte shifts between the intracellular and extracellular space or changes in total body water or electrolyte status 2. Evaluate concurrent IV fluids and medications provided during PN therapy

What are 6 Clinical manifestations of EFAD?

1. Scaly dermatitis 2. Alopecia 3. Hepatomegaly 4. Thrombocytopenia 5. Fatty liver 6. Anemia

Blood glucose concentrations can be controlled with insulin therapy, what are the 3 delivery options for PN patients?

1. Subcutaneously 2. Intravenously 3. Directly in the PN solution

Requirements for fluid and electrolytes vary depending on what 3 things?

1. The patient's renal, fluid and electrolyte status when starting PN 2. Underlying disease process 3. Any losses he or she may incur

Incidence of complications associated with ILE use is low, what are 2 potential reactions?

1. Allergic reactions 2. Infusion-related adverse reactions

What are the 2 reasons for risk of trace element toxicity in PN patients?

1. Available parenteral multi-trace element preparations may exceed actual requirements 2. Many of the components of the PN formulation may be contaminated with trace elements such as zinc, copper, manganese, chromium, selenium and aluminum

What are the laboratory monitors for parenteral patients?

1. Capillary glucose 2. Basic metabolic panel, phosphorus and magnesium 3. CBC with differential 4. Liver function (ALT, AST, ALP, total bilirubin, INR) 5. Serum triglycerides 6. Iron studies 7. 25-hydroxyvitamin D 8. Zinc, copper, selenium, manganese 9. Weight 10. Total fluid intake/output

Prerenal azotemia can result from what 3 causes?

1. Dehydration 2. Excess protein 3. Inadequate energy from non-protein sources (ie patients with anorexia nervosa)

Excess carbohydrate administration has been associated with what 3 complications?

1. Hyperglycemia 2. Hepatic steatosis 3. Increased CO2 production

Soy based ILE associated with what 3 consequences?

1. Immunosuppressive effects 2. Reticuloendothelial system dysfunction 3. Exaggerated systemic inflammatory response

Hyperglycemia is associated with worsened clinical outcomes, name 3.

1. Increased risk of infection 2. Poor wound healing 3. Inability to gain weight

What are the 4 treatment options for hypoglycemia?

1. Initiation of a 10% dextrose infusion 2. Administration of an ampule of 50% dextrose 3. Stopping any source of insulin administration 4. Oral carbohydrate (glucose gel or chewable tablets) Can be considered for management of mild hypoglycemia in suitable patients who are likely to tolerate it

Trace element deficiencies with PN occur when what 2 situations are present? Give 2 examples.

1. Intake is insufficient 2. Excretion is increased over a prolonged period Ex. patient with high intestinal losses may become zinc deficient Ex. cardiomyopathy caused by selenium deficiency has been reported in patients receiving long-term PN without selenium supplementation

2 PUFA cannot be synthesized by the body and are considered essential, which 2?

1. Linoleic 2. Alpha linolenic

PN associated complications categorized into what 3 categories?

1. Mechanical 2. Metabolic 3. Infectious

Tissue elevations of what 3 trace elements have been noted on autopsy in patients receiving long term PN?

1. copper 2. manganese 3. chromium

What are 2 possible causes of hypertriglyceridemia with PN administration?

1. dextrose overfeeding 2. rapid administration rates of ILE (> than 0.11 g/kg/h)

What are the 8 symptoms of an ILE infusion-related adverse reactions?

1. dyspnea 2. cyanosis 3. flushing 4. sweating 5. dizziness 6. headache 7. back or chest pain 8. nausea and vomiting

Hyperlipidemia may lead to what 3 physiological consequences?

1. impair immune response 2. Alter pulmonary hemodynamics 3. Increase the risk of pancreatitis

What 2 populations are at risk for potential trace element toxicity with PN?

1. long-term PN 2. Those with hepatobiliary disease

How has soy-bean based oil been theorized to suppress the immune system?

18 carbon omega-6 fatty acid preparation (linoleic acid) has been postulated to suppress the immune response by activating the arachidonic pathway

Withholding or limiting soy-based ILE in critically ill patients for the first week of PN Has been suggested as a strategy to reduce immunosuppression complications, what is the evidence behind this recommendation? What are the problems with the evidence?

2016 ASPEN SCCM guidelines for nutrition support therapy in the adult critically ill patient support this recommendation, Quality of evidence a very low rating Recommendation is primarily based on research from one study involving trauma patients receiving fat-free PN over the first 10 days of hospitalization Study reported that elimination of ILE from the PN improved clinical outcomes (decreased infectious morbidity, decreased hospitalization, shortened ICU LOS, shortened duration of mechanical ventilation) This study is more than 20 years old and has not been duplicated. Criticized in part because the goals for energy delivery in the study were based on nonprotein calories (not total calories). The total amount of energy delivered was greater than reported, and overfeeding may have contributed to the complications associated with the PN with ILE

If a PN solution is discontinued quickly what should be done to prevent rebound hypoglycemia?

A dextrose-containing fluid should be infused for 1 or 2 hours following PN discontinuation to avoid a possible rebound hypoglycemia. Obtaining a capillary blood glucose concentration 30 min to 1 hour after the PN solution is discontinued will help identify rebound hypoglycemia

Patients who develop prerenal azotemia may benefit from what MNT?

A reduction in the amount of amino acids provided

In patients who do not tolerate ILE how can EFAD be prevented?

A trial of topical skin application or oral ingestion of oils may be given to alleviate biochemical EFAD

Which of the following is the most common metabolic complication associated with PN? A. Hyperglycemia B. Essential fatty acid deficiency (EFAD) C. Azotemia D. Hyperammonemia

A. Hyperglycemia Hyperglycemia is the most common metabolic complication that occurs with PN. Hyperglycemia is associated with overfeeding, also common in appropriately fed patients, where it is attributed to insulin suppression and resistance as well as gluconeogenesis from stress and infection. Nondiabetic hospitalized patients receiving IV dextrose infusions at rates greater than 4 mg/kg/min have a 50% chance of developing hyperglycemia. EFAD is associated with fat-free PN, can be avoided by administering minimal amounts of ILE. Azotemia usually associated with renal or hepatic dysfunction or protein overfeeding. Hyperammonemia rarely occurs now that crystalline amino acids are used in PN.

What target blood glucose concentration range does ASPEN recommend for the adult hospitalized patient receiving nutrition support?

ASPEN recommends target blood glucose concentrations between 140 to 180 mg/dL for the adult hospitalized patients receiving nutrition support

What level of triglycerides should contraindicate ILE per ASPEN recommendations? What should you do clinically if triglycerides are this high?

ASPEN recommends that serum triglyceride concentrations greater than 400 mg/dL be avoided when infusing ILE Clinicians should reduce the dose or discontinue ILE if this level of hypertriglyceridemia occurs

What is necessary to appropriately manage fluids and electrolytes in PN?

Accurate intake and output records are necessary

How does acute thiamin deficiency present?

Acute thiamin deficiency can result in alterations in mental status and peripheral nervous system dysfunction (Wernicke's encephalopathy)

How frequently should adult PN patients receive PN multivitamins?

Adult patients receiving PN should receive a standard daily dose of parenteral multivitamins. Clinicians should not delay IV multivitamin therapy until a patient develops clinical signs of vitamin deficiencies and must take measures to address product shortages.

How are adult requirements for linoleic acid usually met? Why doesn't this happen during PN therapy?

Adult requirements for linoleic acid are met through exogenous sources or endogenously through the lipolysis of adipose tissue When hypertonic dextrose is infused, insulin is secreted and lipolysis is reduced. Exogenous sources of fat must be provided.

What should be considered when prescribing the PN formulation with regards to fluid?

All fluids being infused should be considered when the PN formulation is prescribed. If the patient has excessive losses, fluid and electrolyte replacement with separate IV fluids outside of the PN formulation may be necessary.

What is the benefit of alternative oil-based ILEs? Are they safe to use?

Alternative oil-based ILEs have demonstrated fewer proinflammatory and immunosuppressive properties compared with soy-based ILEs Alternative oil based products are safe and effective Further research is necessary to determine which patient populations and medical conditions will benefit from them

One day after initiating PN in a critically ill adult patient, laboratory values: potassium 3.1 mEq/L, serum phosphorus 1.6 mg/dL, serum magnesium normal. PN regimen is providing protein 90 g, dextrose 150 g, no lipid, minimum volume, potassium 80 mEq, phosphate 40 mmol and standard doses of sodium, magnesium, calcium, vitamins and trace elements. Patient weighs 60 kg, BMI 18. Most appropriate response to these laboratory data is: A. Increase potassium and phosphate in the PN, decrease macronutrient doses with tonight's PN bag B. Provide supplemental intravenous (IV) doses of potassium and phosphate today, but do not change the macronutrient doses with tonight's PN bag C. Increase potassium and phosphate in the PN and advance dextrose to 225 g with tonight's PN bag D. Provide supplemental IV doses of potassium and phosphate today, and advance dextrose to 225 g with tonight's PN bag

B. Provide supplemental intravenous (IV) doses of potassium and phosphate today, but do not change the macronutrient doses with tonight's PN bag Management and prevention of refeeding syndrome and hypophosphatemia involve: identifying patients at risk, serum electrolyte monitoring with aggressive replacement and slowly increasing energy intake. Initiation of PN, the electrolyte abnormalities should be treated quickly with supplemental, IV replacement doses. Energy intake from PN should not be advanced until the electrolyte deficiencies are corrected.

How frequently should serum triglycerides be monitored in PN patients? long term therapy?

Baseline if patient is at risk for hypertriglyceridemia Long term therapy Not routine, done on as-needed basis

How frequently should CBC with differential be monitored in PN patients? long term therapy?

Baseline then 1-2 times/week Long term therapy Monthly then decrease frequency in stable patients

How frequently should LFTs be monitored in PN patients? long term therapy?

Baseline, then weekly Long term therapy Monthly then decrease frequency in stable patients

Patients receiving both PN and warfarin therapy require close monitoring, why?

Because the vitamin K (150 mcg) included in the 13 vitamin preparation interacts with warfarin and can result in therapeutic failure

Which of the following measures would be considered most beneficial in a patient who develops cholestasis while receiving long-term PN that is infused over 12 hours nightly? A. stop all oral and enteral intake B. switch from a cyclic to continuous method of PN administration C. decrease lipid injectable emulsion (ILE) dose from 1.5 g/kg/d to 1 g/kg twice weekly D. increase protein dose from 1 g/kg/d to 2 g/kg/d

C. decrease lipid injectable emulsion (ILE) dose from 1.5 g/kg/d to 1 g/kg twice weekly cholestasis has been associated with ILE doses greater than 1 g/kg/d in adult patients who receive long-term PN, and the patient may therefore benefit from a trial of lowering the ILE dose. Cyclic infusion has been shown to reduce serum liver enzyme and conjugated bilirubin concentrations when compared with continuous infusion. Enteral feeding should be attempted to promote enterohepatic circulation of bile acids. The protein dose does not seem to play a role in the development of cholestasis in adults.

Who is likely to develop an allergic reaction to ILE? Why?

Can occur in patients with history of egg allergy Allergic reaction is most likely a result of the egg phospholipid that is used as an emulsifier

How frequently should blood glucose be monitored in PN patients?

Capillary blood glucose should be monitored every 6 to 8 hours in patients receiving short-acting subcutaneous insulin and more frequently in critically ill patients receiving insulin infusion therapy

What is the limit for the carbohydrate administration rate in PN?

Carbohydrate administration should not exceed a rate of 4 to 5 mg/kg/min or 20 to 25 kcal/kg/d in acutely ill patients

Once macronutrient tolerance has been established what is the focus of PN management?

Centers on fluid and electrolytes

Which of the following PN modifications is recommended to help prevent and/or treat osteoporosis in a long term PN patient? A. maintain protein intake at least 2 g/kg/d B. provide more than 20 mEq calcium per day C. add injectable vitamin D to the PN formulation D. provide 20 to 40 mmol phosphorus per day

D. provide 20 to 40 mmol phosphorus per day Inadequate phosphorus dose may increase urinary calcium excretion. ASPEN recommends that phosphorus doses of 20 to 40 mmol/d be added to the PN formulation. Patients receiving PN are vulnerable to a negative calcium balance, calcium supplementation in the PN formulation is limited by calcium's physical compatibility with phosphorus, higher calcium doses are offset by higher urinary losses. ASPEN recommends that calcium gluconate 10 to 15 mEq/d be added to the PN formulation. High protein doses (2 g/kg/d versus 1 g/kg/d) in PN formulations have been associated with increased urinary calcium excretion in adult patients. Excessive vitamin D doses can be detrimental to the bone because they can suppress parathyroid hormone PTH and promote bone resorption, individual forms of parenteral ergocalciferol or cholecalciferol are not available.

How frequently should weight be monitored in PN patients? long term therapy?

Daily Long term therapy daily

How frequently should total fluid intake/output be monitored in PN patients? long term therapy?

Daily until stable, then as needed Long term therapy As needed basis

How frequently should BMP, phosphorus and magnesium be monitored in PN patients? long term therapy?

Daily until the patient is advanced to PN goal and stable then 1-2 times/wk Long term therapy Weekly, then decrease frequency in stable patients

When should the dextrose dose of the PN formulation be advanced?

Dextrose dose in the PN formulation should not be advanced until the patient's blood glucose concentrations are controlled. Insulin dose should be proportionally increased and decreased with respect to the PN dextrose dose.

How should the dose of ILE be adjusted for patients on propofol? Why?

Dose of ILE should be reduced or discontinued in mechanically ventilated patients receiving propofol for sedation because propofol is supplied as a 10% ILE

How quickly can EFAD occur with ILE-free PN?

EFAD can occur within 1 to 3 weeks in adults receiving ILE-free PN

How frequently should capillary glucose be monitored in PN patients? long term therapy?

Every 6 hours until patient is advanced to PN goal and as needed to maintain glucose level of 140-180 mg/dL Long term therapy Not routine, done as needed basis to coordinate with PN infusion cycle

What is the mechanism for LCFAs immunosuppression?

Evidence suggest that certain LCFA may impair immune function by interfering with phagocytosis and chemotaxis and may increase the patient's risk of infection

What type of error is excessive administration of insulin considered?

Excessive or erroneous administration of insulin is a severe medical error

How is intolerance to the protein load observed clinically?

Exhibited by an increase in blood urea nitrogen

Why was hyperammonemia a greater risk historically?

Hyperammonemia was a greater risk when protein hydrolysates contained excessive amounts of ammonia and insufficient arginine for urea cycle metabolism. Complication has become a rare occurrence since the advent of crystalline amino acid solutions.

What is the most common complication associated with PN administration?

Hyperglycemia is the most common complication associated with PN administration

What limits should be put on ILE administration?

ILE intake should be restricted to less than 30% of total energy or 1 g/kg/d

Should ILE be provided to a patient on PN with pancreatitis?

ILE is considered safe for use in patients with pancreatitis without hypertriglyceridemia

What can result from ILE-free PN?

ILE-free PN may result in EFAD

How long should ILE be ran for if it is a piggy-back?

If ILE is administered separately it should be provided slowly over at least 8 to 10 hours

What is the recommendation (units per gram) for adding insulin to PN?

Initial insulin regimen of 0.05 to 0.1 units per gram of dextrose in the PN solution is common, or 0.15 to 0.2 units per gram of dextrose may be used inpatients who are already hyperglycemic

Several vitamins are known to undergo substantial degradation after addition to the PN formulation, for which patient population is this an issue? What is an example of this? How can this be avoided?

Issue is not considered a significant problem in the acute care setting because of the relatively short time period between compounding and administration. Because PN formulations are compounded in batch fashion for patients in the home setting, degradation is a risk with these solutions. Vitamin A degradation was clearly demonstrated in a home PN patient who developed night blindness within 6 months of receiving PN that was prepared on a weekly basis with the vitamins added to the PN formulation by the pharmacy before delivery Substantial amounts of vitamin A were likely lost to degradation and adsorption to the plastic matrix of the bag because the vitamins were added to the PN formulation up to a week before administration To avoid this problem the patient or caregiver must perform the task of adding vitamins to the PN formulation prior to administration in the home setting

Has hyperammonemia been observed with new crystalline amino acids?

It has been observed with the new crystalline amino acid solutions in patients with urea cycle defects, such as ornithine transcarbamylase deficiency.

What is the fatal consequence of Uncontrolled hyperglycemia?

May result in hyperosmolar hyperglycemia, nonketotic dehydration, coma and death secondary to osmotic diuresis

Are metabolic complications more common with EN or PN?

Metabolic complications are more commonly associated with PN rather than enteral nutrition

Are trace element deficiencies common in PN?

No, trace element deficiencies are relatively uncommon in patients receiving PN

How frequently should iron studies be monitored in PN patients? long term therapy?

Not routine Long term therapy Baseline than every 3-6 months

How frequently should vitamin D be monitored in PN patients? long term therapy?

Not routine Long term therapy Baseline than every 3-6 months

How frequently should zinc, copper, selenium and manganese be monitored in PN patients? long term therapy?

Not routine Long term therapy Baseline then every 6 months

What type of insulin should be added to the PN?

Only regular insulin should be added to the PN formulation

Why does PN associated hypoglycemia usually occur?

PN associated hypoglycemia can occur from excess insulin administration (via PN solution, IV infusion or subcutaneous injection

What amount of carbohydrate should be provided in PN initially (first 24 hours)? When would lower dextrose be warranted?

PN should be initiated at half of the estimated energy needs or about 150 to 200 g dextrose for the first 24 hours Delivery of less dextrose (approximately 100 g) may be warranted if the patient has a low BMI or poor glucose control

Does ILE cause pancreatitis?

Pancreatitis due to ILE induced hyperlipidemia is rare unless serum triglyceride concentrations exceed 1000 mg/dL

When urea clearance is impaired what may be needed?

Patients may require dialysis

What patients have a higher risk for rebound hypoglycemia?

Patients requiring large doses of insulin have a greater propensity for rebound hypoglycemia

What patients are most prone to azotemia? Why?

Patients with hepatic or renal disease are prone to developing azotemia Because their ability to metabolize and eliminate urea is impaired

Is it possible to predict which patients will experience rebound hypoglycemia?

Predicting which patients will experience rebound hypoglycemia is difficult

What may be necessary in patients who have hyperglycemia limiting their PN dextrose dose?

Proportional increase in fat content or frequency may be necessary to increase energy from PN

Should protein restriction be prescribed for patients with liver failure and hyperammonemia with encephalopathy? Should high BCAA formulas be prescribed?

Protein restriction in patients in liver failure with hyperammonemia and encephalopathy has not been demonstrated to improve outcomes, discouraged. Patients with hepatic failure and hepatic encephalopathy, the use of high branched chain, low aromatic amino acid formulations has provided inconsistent results and is not recommended.

Should protein be restricted in critically ill patients with AKI?

Protein should not be restricted in critically ill patients with AKI receiving CRRT or iHD especially in the setting of malnutrition

What is a rare complication of hyperglycemia? What does it result in? What may be necessary to correct it?

Rarely, hyperglycemia may be related to chromium deficiency Insulin is less effective in patients with chromium deficiency Increasing the chromium dose in the PN formula beyond the standard amount in commercially prepared multiple trace element injections may be necessary

What may help minimize the effects of ILE on hypertriglyceridemia?

Reducing the dose and/or lengthening the infusion time of ILE will help minimize these effects

What blood glucose concentration range does SCCM recommend for the general ICU population?

SCCM recommends blood glucose concentrations be maintained between 150 to 180 mg/dL for the general ICU population

When should serum triglycerides be checked with PN therapy initiation?

Serum triglyceride concentrations should be checked prior to ILE administration in any patient with a known history of hyperlipidemia or risk of hypertriglyceridemia

What vitamin deficiency is associated with lactic acidosis?

Several cases of lactic acidosis due to thiamine deficiency, including 3 deaths, were reported in patients receiving PN without thiamin during a period of parenteral multivitamin shortage

Why does stress-associated hyperglycemia develop?

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

Abrupt discontinuation of PN solutions has been associated with rebound hypoglycemia, what do studies show?

Studies have not reported symptomatic hypoglycemia after abruptly stopping PN infusions given over 16 to 24 hours, some patients had asymptomatic hypoglycemia

What treatment has been recommended in patients with a history of prolonged poor dietary intake?

Supplemental thiamin (50 to 100 mg/d) and folic acid (1 mg/d) beyond what is provided in the parenteral multivitamin preparation for the initial 5 to 7 days of PN therapy

Patients with a history of prolonged poor dietary intake or alcohol abuse are at risk for developing what vitamin deficiency?

Thiamin deficiency, especially with initiation of carbohydrate

How much linoleic and linolenic acid needs to be provided to prevent EFAD? What does this translate to in ILE delivery? What about with newer generation ILEs?

To prevent EFAD 1% to 2% of daily energy requirements should be derived from linoleic acid and 0.5% of energy from linolenic acid Goal translates to approximately 250 mL of 20% or 500 mL of 10% soy based ILE administered over 8 to 10 hours twice a week. Alternatively 500 mL of a 20% soy based ILE can be given once a week When using an alternative oil-based ILE, such as those containing MCT, olive oil and fish oil a greater amount of ILE is required to meet EFA requirements because these non soy based products contain lower quantities of linoleic and linolenic acid

How can the risk for rebound hypoglycemia be reduced?

To reduce the risk of rebound hypoglycemia in susceptible patients a 1 to 2 hour taper down of the infusion, or half the infusion rate, may be necessary

What is the treatment for fluid and electrolyte complications?

Treatment involves replacing the lost fluids with IV fluid of similar electrolyte composition

What biochemical indices is diagnostic of EFAD?

Triene:tetraene ratio of more than 0.2 indicates EFAD

What vitamin toxicity has been reported in patients with chronic renal failure receiving PN? What have clinicians suggested to combat this? Is this feasible?

Vitamin A toxicity some clinicians have recommended reducing the frequency of fat-soluble vitamin administration to twice per week in these patients There are no injectable multivitamin preparations available without fat soluble vitamins, water soluble vitamin deficiency is a risk with restricted dosing Some water-soluble vitamins may be lost with hemodialysis, provision of water-soluble vitamins to patients receiving dialysis has been recommended Oral vitamin B complex supplement or individual parenteral B supplementation can be used to address this recommendation.

What vitamin toxicity is a potential complication of PN?

Vitamin toxicity, particularly of the fat-soluble vitamins, is a potential complication of PN

What needs to be accounted for when using repeated doses of insulin?

When administering repeat doses of insulin, take into account the duration of action of the insulin formulation previously provided before administering the next dose. Giving the subsequent dose too soon is referred to as "stacking" insulin and can result in hypoglycemia.

Supplemental short acting or rapid acting insulin may be administered subcutaneously if needed, using a sliding scale in PN patients, if this is being done how can it be used to adjust insulin in the PN solution?

⅔ of the total amount of sliding scale insulin required over 24 hours may then be added to the next day's PN formulation